Podcasts about ecg

Archana Dubey, MD, the Chief Clinical Officer at AliveCor, has worked as a primary care physician, on the enterprise side at HP, and in startups as a founder herself. AliveCor has been a pioneer in the med tech device market for a decade, introducing the world's first single-lead ECG built for consumers. Our conversation centers on AliveCor's lessons learned in clinical validation, consumer marketing, and tech integrations. --- Entrepreneurs: How to get investment from StartUp Health startuphealth.com Investors: How to invest in StartUp Health Moonshots healthmoonshots.com Want more content like this? You can subscribe to the podcast as well as other health innovation updates at startuphealth.com/content. Sign up for StartUp Health Insider™ to get funding insights, news, and special updates delivered to your inbox.

It's time to review some recent cardiac arrest literature. Both of today's articles come from Resuscitation and address predictors of OHCA survival. Should we take a third attempt at intubating an OHCA patient, should we intubate OHCA at all? What about PEA arrest, can ETCO2 help identify pseudo-PEA? Listen to get some hot off the press OHCA literature updates. REFERENCES 1. Murphy DL et al. Fewer tracheal intubation attempts are associated with improved neurologically intact survival following out-of-hospital cardiac arrest. Resuscitation. 2021 Oct;167:289-296. 2. Crickmer M, et al. The association between end-tidal CO2 and return of spontaneous circulation after out-of-hospital cardiac arrest with pulseless electrical activity. Resuscitation. 2021 Oct;167:76-81. 3. Bergum D, et al. ECG patterns in early pulseless electrical activity-Associations with aetiology and survival of in-hospital cardiac arrest. Resuscitation. 2016 Jul;104:34-9.

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Please join author George Dangas and Associate Editor Brendan Everett as they discuss the article “Colchicine in Cardiovascular Disease.” Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: Welcome, everyone, to 2022. I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Carolyn, oh, we're starting off the year with a twist on the feature article. It's a review article on colchicine and cardiovascular disease. But before we get to that, how about we grab a cup of coffee and jump into some of the other articles in the issue? Dr. Carolyn Lam: Absolutely. The new year is starting off with a bonanza issue. This first topic is so important. We know that various non-invasive, intermittent rhythm monitoring strategies have been used to assess arrhythmia recurrences in atrial fibrillation ablation trials. But the question is, what is the frequency and duration of non-invasive rhythm monitoring that accurately detects arrhythmia recurrences and approximates the atrial fibrillation burden derived from continuous monitoring using the gold standard, implantable cardiac monitor? Now to answer this question, investigators Jason Andrade and colleagues from the Montreal Heart Institute, who looked at the rhythm history in 346 patients enrolled in the CIRCA-DOSE trial. They reconstructed the rhythm history using computer simulations and evaluated event-free survivals, sensitivity, negative predictive value, and AF burden in a range of non-invasive monitoring strategies including those used in contemporary AF ablation trials. Dr. Greg Hundley: Ah, very interesting, Carolyn. So what did they find? Dr. Carolyn Lam: Detection of arrhythmia recurrence following ablation was highly sensitive to the monitoring strategy employed between trial discrepancies and outcomes, in fact, may reflect these different monitoring protocols. Binary efficacy outcomes, such as time to AF recurrence, appeared to underestimate the true impact of catheter ablation on the burden of atrial arrhythmia. The most commonly performed intermittent rhythm monitoring techniques, like short duration 24- or 48-hour ambulatory Holter, they do miss a substantial proportion of arrhythmia recurrences and significantly overestimate the true AF burden in patients with recurrences. So based on measures of agreement, serial long-term, that is four seven-day or two 14-day intermittent monitors accumulating at least 28 days of annual monitoring provide estimates of AF burden that are comparable with the implantable cardiac monitor. However, implantable cardiac monitors outperform intermittent monitoring for arrhythmias and should be considered the gold standard for clinical trials. Dr. Greg Hundley: Very nice, Carolyn. It sounds like a lot of clarification on monitoring of AF burden. Well, my first paper comes to us from Dr. Prabhakara Nagareddy from The Ohio State University, The Wexner Medical Center. Carolyn, acute myocardial infarction results in an overzealous production and infiltration of neutrophils in the ischemic heart, and this is mediated in part by granulopoiesis induced by the S100A8/A9 NLRP3, IL-1 beta signaling axis in injury-exposed neutrophils. In this study, Carolyn, the investigators evaluated a hypothesis as to whether IL-1 beta is released locally within the bone marrow by inflammasome prime and reverse migrating neutrophils. Dr. Carolyn Lam: Ah, okay. So what did they find, Greg? Dr. Greg Hundley: Okay, Carolyn. In response to myocardial infarction, the NLRP3 inflammasome prime neutrophils upregulated CXCR4 and reverse migrated to the bone marrow, where they adhered to adhesion molecules like P-selectin on the bone marrow endothelial cells. Second, Carolyn, in the bone marrow, the inflammasome prime neutrophils released IL-1 beta through gasdermin-dependent conduit pores without undergoing the mandatory pyroptosis. Third, genetic and/or pharmacological strategies aimed at limiting reverse migration of inflammasome prime neutrophils to the bone marrow or release of IL-1 beta, both suppressed granulopoiesis and improved cardiac function in mouse models of myocardial infarction. So Carolyn, therefore, strategies aimed at targeting specific signaling pathways within the neutrophils or reducing retention of the inflammasome prime neutrophils in the bone marrow may provide novel avenues to regulate inflammation and improve cardiac outcomes. Dr. Carolyn Lam: Wow, neat, Greg. Thanks for explaining that so nicely. Well, the next paper deals with my favorite topic, heart failure with preserved ejection fraction of HFpEF, and this time looks at mechanisms of sinoatrial node dysfunction. The investigators, led by Dr. Cingolani from Smidt Heart Institute at Cedars-Sinai Medical Center, sought to investigate the role of the intrinsic pacemaker on chronotropic incompetence in HFpEF. They performed extensive sinoatrial node phenotyping, both at baseline and after stress in the well-characterized Dahl salt-sensitive rat model of HFpEF. These rats exhibited limited chronotropic response associated with intrinsic sinoatrial node dysfunction, including impaired beta-adrenergic responsiveness and an alternating leading pacemaker within the sinoatrial node. Prolonged sinoatrial node recovery time and reduced sinoatrial node sensitivity to isoproterenol were confirmed in the two hit mouse model. Adenosine challenge unmasked conduction blocks within the sinoatrial node, which were associated with structural remodeling. Finally, single-cell studies and transcriptomic profiling revealed HFpEF-related alterations in both the membrane clock or iron channels and the calcium clock of the spontaneous calcium release events. Dr. Greg Hundley: Wow, Carolyn, lot of really interesting data here. So what were the clinical implications? Dr. Carolyn Lam: Yeah, it's a really great study. Two models of HFpEF-consistent result in an important topic. Basically, here at the take-home messages. Provocative testing can be valuable to elicit functional abnormalities to facilitate HFpEF diagnosis and considering the exceptionally high clinical and epidemiologic convergence between AFib and HFpEF, sinoatrial node dysfunction may underlie the development of abnormal atrial rhythms in HFpEF. Dr. Greg Hundley: Very nice, Carolyn. More information on HFpEF, again, one of your favorite subjects. Next, we're going to turn to a paper from Dr. Jian Li from the Peking Union Medical College Hospital. Carolyn, doxycycline has previously been demonstrated in a retrospective study to be associated with greater survival in patients with light chain AL amyloidosis. Therefore, Carolyn, this group prospectively compared the efficacy of bortezomib, cyclophosphamide, dexamethasone, or cyclophosphamide B or D, and cyclophosphamide B or D combined with doxycycline for cardiac amyloidosis. Dr. Carolyn Lam: Cool. So what did they find, Greg? Dr. Greg Hundley: Carolyn, this was a multi-center, open-label, randomized controlled trial, and 140 patients underwent randomization. The primary outcome was two-year progression-free survival. Progression-free survival was defined as the time from randomization to death, hematologic progression or organ progression, and that's the heart, the kidney, or the liver. And so Carolyn, these investigators in this trial demonstrated that doxycycline combined with cyclophosphamide B or D failed to prolong progression-free survival or cardiac progression-free survival compared with cyclophosphamide B or D alone in patients with cardiac AL amyloidosis. So Carolyn, a negative study that's quite informative and a very nice editorial that accompanies this article pertaining to future directions for management of AL cardiac amyloid. Dr. Carolyn Lam: Indeed important. Thank you. And there are other important papers in today's issue. There's a Research Letter by Dr. Pfeffer on the impact of sacubitril/valsartan versus ramipril on total heart failure events in the PARADISE-MI trial. Dr. Greg Hundley: Great, Carolyn. In the nail bag, boy, I've got a big list today. First, Dr. Churchwell has an AHA update on the need for policy change to improve maternal cardiovascular health. Next, Dr. Piazza has a Perspective piece on expanding the role of coronary CT angiography in interventional cardiology. There's an ECG challenge from Dr. Yarmohammadi entitled “Dancing Bundles with Stable Sinus Rhythm.” And next, we have our own Darren McGuire who, in this issue for all of 2021, is really recognizing our outstanding reviewers. And we want to thank all the listeners and everyone that reviews for us in this journal. Such an important feature and aspect to the publication of the wonderful articles that we receive. And then finally, there are some highlights from the circulation family of journals. Well, Carolyn, how about we get on to that feature discussion and learn more about colchicine and its use in cardiovascular disease. Dr. Carolyn Lam: Let's go and a Happy New Year, again, everyone. Dr. Greg Hundley: Welcome listeners to this January 4th feature discussion. This week, we're deviating a little bit because we are going to have an author discuss one of our in-depth reviews. As you know, we select those occasionally where they're is a topic that's very relevant in cardiovascular medicine and an investigator or team of investigators or authors will put together a very nice review of a topic. This week, we're going to talk about colchicine, and we have with us Dr. George Dangas from the Icahn School of Medicine at Mount Sinai and our associate editor, Dr. Brendan Everett, who manages this paper and he is from Brigham and Women's Hospital. Welcome, gentlemen. George, we'll start with you. George, why colchicine? Can you tell us a little bit about mechanism of action? Tolerability? Why would we want to use this particular agent in patients with cardiovascular disease? Dr. George Dangas: Thank you very much for the opportunity to join this interesting podcast. Colchicine is indeed an interesting drug. It's been around for centuries, in all honesty. In general, I would say it's a mild anti-inflammatory and in general, it's rather well tolerated. We'll go into those perhaps a little bit later. The precise mechanism is actually interestingly not quite defined. It may have a few ways to act by blocking perhaps the chemotaxis of the leukocytes or the adhesion of the leukocytes or the ability to release their granules, et cetera, but there isn't a specific major one that is targeting. Perhaps, it's targeting more than one mechanism in a mild way, and I think that goes into each utility, as well as the absence of the major side effect that might limit it. Dr. Greg Hundley: Very nice. So you started to mention the word utility, so maybe let's go through some clinical indications, or clinical uses perhaps rather than indications, can you tell us a little bit about its use in individuals with pericarditis? Dr. George Dangas: I think this is where it started to enter the cardiovascular field because we all recognize that pericarditis is an inflammatory disease and inflammation of the pericardium of different reasons perhaps. And anti-inflammatory drug is rather fitted to treat an inflammatory disease and besides, it's not like we had any other drug, in all honesty. Clearly, recurrent pericarditis might be treated with steroids for example, but steroids is not something any cardiologist would jump as a first line and give high doses and all that. Colchicine made its way to pericarditis like acute or recurrent pericarditis, post-cardiac cardiology syndrome, restless syndrome or the specific post-cardiac surgery, major inflammation. And indeed has a daily dosage perhaps with some loading dose or double the daily dosage or something initially and then we give it for a prolonged period of time in order to suppress. I would say this is a reasonable choice rather than jumping to the steroid. And of course, you reserve the steroid for the, I would say, more severe or more recurrent cases. I think everybody understands this type of activity. There've been quite a few clinical studies in this aspect. Again, in the absence of a competitor, I think it's a winner in this area. Dr. Greg Hundley: Very nice. And then, how about atrial fibrillation? Are there uses of this colchicine in patients with atrial fibrillation? Dr. George Dangas: Well, again, it's very interesting that a lot of atrial fibrillation, it may be in some ways inflammatory in origin. And quite frankly, we had an interesting [inaudible 00:14:50] clinical trial in American Heart Association in 2021. I'd like to point out here, the study that postoperative atrial fibrillation was mitigated when, during cardiac surgery, there was a slicing of the posterior pericardial. This allowing the inflammation in some ways that's related there. To me, that was a very interesting observation, though I related to colchicine because it validates the fact that there is something inflammatory in pericardial that related with the postoperative atrial fibrillation. So along these lines, let's go back to colchicine, Afib, and postop Afib, and post-ablation I would say patients. Again, there are risks of some inflammation and that's where the theory of a mild, rather well-tolerated, anti-inflammatory might come in. And there's been few studies, not a large definitive study, but several studies that are the, I would say, component with interesting results with colchicine in these patients. Dr. Greg Hundley: Very good. Another area of cardiovascular disease that's emerging literally with some demonstrable results using colchicine is the realm of ischemic heart disease. Can you walk us through some of the utility myocardial infarction or maybe even post-percutaneous coronary artery intervention? Dr. George Dangas: Again, the hallmark in this type of diseases, cardiovascular disease or coronary heart disease, is the hallmark of role of inflammation in this disease. And we know very well from the studies of the C-reactive protein, importance is a marker of inflammation. Very, very important in the CAD as well as in even the treatment with the antibody canakinumab a little bit earlier in the CANTOS trial a few years earlier at the very high level inhibited inflammation had a benefit and colchicine comes in maybe a milder anti-inflammatory about this agent, but at the same time with significantly less cause and significantly better recognition among the clinicians and a lot less, I would say, tolerability problems or issues are less unknowns. And I think that's where it comes in. The difficulty has been that whenever you go to cardiovascular, the cardiovascular, I would say coronary artery disease specifically, ACS and all that, the level evidence required for the doctors to believe in a therapy is very different than the areas we discussed before where there's little bit of a pericardial disease, for example, not that many drugs, all of a sudden, coronary artery disease, the bar is so high, and that's where the difficulty has been. There've been several studies. They've been interesting results with some benefits, particularly due to the decrease in inflammation and the secondary prevention, one can say. That is really the hallmark of where it aims to benefit in the secondary prevention, but there hasn't been one massive study with clearly superb results. I would say adequately powered single study that is missing in some ways. But several studies have been, again, very, very encouraging, but we learned that there's no much point if loading a lot of doses of high doses of colchicine, and it's a little bit better, again, when you aim with a daily dose towards reduced recurrences, particularly if you started early after an acute event. Dr. Greg Hundley: Very nice. Well, listeners, we're going to now turn to our associate editor, Dr. Brendan Everett, from Brigham and Women's Hospital. Brendan, you have a lot of papers come across your desk. First and foremost, what attracted you to this particular article? Dr. Brendan Everett: Well, thanks, Greg. And kudos to George and his team for putting together a really nice paper. It's great to have this kind of paper come into my inbox. That's specifically because colchicine, I think, has exploded as a really important novel therapy even though the therapy itself is perhaps hundreds of years old, as you heard George say a moment ago, but its role in treating cardiovascular diseases has really begun to emerge rapidly. I think there's a tremendous amount of enthusiasm for other ways to treat our patients who have really a recalcitrant cardiovascular disease, whether that's pericarditis, atrial fibrillation or I think, importantly, ischemic heart disease, because that's such a common disease and something where we're always looking for new ways to help patients live longer with fewer recurrent events. And so this paper I thought did a really good job of capturing the existing evidence for these conditions and some others and giving us a sense of where the strengths of that evidence lay and where the weaknesses were. I thought particular strength was in the tables where the authors laid out each of the trials and the results of the trial, their endpoints, where the benefit was potentially. And also importantly, where risks were seen because I think that's one of the really important questions that remains open with respect to colchicine therapy when we begin to talk about using it in a vast population of people with stable ischemic heart disease or post-myocardial infarction ischemic heart disease. Dr. Greg Hundley: Brendan, tell us a little bit about those risks. Dr. Brendan Everett: I'd be happy to do that. I want to emphasize before I dive in that I think the benefits that George has laid out are important, and I don't want to overshadow what the major trials have seen. But I think the thing that it is at least a little bit of the fly in the ointment, if you will, for colchicine in ischemic heart disease is that a couple of the large trials have shown an increased risk of non cardiovascular mortality or bad non-cardiovascular outcomes. And that's of concern, I think, as we saw in the CANTOS trial, which was the monoclonal antibody trial for canakinumab that George mentioned earlier, there was an increase in infection-related mortality. And so whenever you use an anti-inflammatory drug, you're worried about whether or not you're blunting other compensatory mechanisms that the body has to protect against infection and other diseases. I think it's likely that these findings are the play of chance, but we don't know for sure. For example, in the COLCOT trial, which I think is probably the largest and most interesting trial, which was designed and run in Canada, there was a slightly higher level of pneumonia in patients who got active therapy as compared to placebo. And then, two of the trials that were published more recently including LoDoCo2, which was a trial of about 5,000 patients run in the Netherlands and Australia. There was actually a marginally increased risk of non-cardiovascular mortality. That didn't reach statistical significance, but it was awfully close, and I think it gave people some concern. And then, there was also the COPS trial. Again, all these are really outlined in wonderful detail in the manuscript where there was a slight increase of total death and non-cardiovascular death. These events are few, but they're in a direction in two trials, and so they make people a little bit worried. I think the other thing that I noticed was the high prevalence of myalgia as a side effect. I think, Greg, you're always interested in the clinical implications and yesterday I was in clinic and saw a young patient who had had pericarditis. He had been prescribed colchicine by his primary care physician, and he literally couldn't stand and walk up straight because of the amount of abdominal pain he had, which was unusual. To be honest, I've given colchicine to a hundred patients at least, and none of them have had that profound of a side effect, but it's at least worth considering that some patients will not tolerate the therapy because of adverse effects. Dr. Greg Hundley: Very good. Well, in just 30 seconds or so, for each of you, first George and then Brendan. George, balancing some of the efficacy and then some of the concerns, what do you see is the next studies to be performed really in this sphere of research? Dr. George Dangas: This is a great question. And indeed, the concerns one can say or the issues, I would say, regarding this drug, are indeed real because any drug that suppresses inflammation has this risk. There are two ways one can address those. One is with term administration. You don't prescribe it as an annuity forever, but you prescribe it in a three- to six-month or one-month or try to control the time. I think this is done in clinical practice, in all honesty. I don't think that people are prescribing colchicine for life. Same way when we prescribe statins, for example. On the other hand or from investigational point of view, I think the two sets of information we need and, in all honesty, when you investigate issues regarding mortality or these are rare events, there's only one. You need a very large trial or a very large register. A very large trial preferably and colchicine being an often genetic drug, funding sources are rather limited, but we have NIH chipping in with some funding periodically and that might really be needed. So I want to outline that in the last table of our very large, I would say large table of our manuscript but were very happily outlined many ongoing trials. There are, in atrial fibrillation, three coronary artery disease. One in PCI and two in stroke. Something we didn't touch up again. But again, there's the question of inflammation in stroke. I think there's a lot of work ongoing. Perhaps you can see some meta-analysis, again, in order to get a handle of those risks, but at a rather low rate. It's just a difficult thing to come around. Dr. Greg Hundley: Very good. Brendan, anything to add? Dr. Brendan Everett: I would just add I agree a hundred percent with George just said. I think the only missing piece there is heart failure, which I think is and many have shown that there's an inflammatory component to heart failure, whether it's heart failure with reduced ejection fraction or preserved ejection fraction. And the timing of when that intervention might be, whether it might be before the development of symptoms or because there's a lot of trials out there that have struggled with this question and have unfortunately failed to show any benefit, I would just encourage the listeners of the podcast to look at this paper because it's a really marvelous compilation of the evidence for what is a really hot topic in cardiovascular medicine, a really important topic for a lot of the reasons that George mentioned. It's just very well done and comprehensive. Again, kudos to the authors for making such a great effort at putting something together that has a lot of clinical relevance, I think, and also points the way forward for research as you ask, Greg. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. George Dangas from Icahn School of Medicine in Mount Sinai and our own associate editor, Dr. Brendan Everett from Brigham and Women's Hospital for bringing us this data pertaining to colchicine benefits, as we know in acute and recurrent pericarditis, but also emerging indications related to post-procedural atrial fibrillation or coronary artery disease. And really, colchicine's targeting of cardiovascular inflammation is being helpful in those alleviating those processes. Well, on behalf of Carolyn and myself, we want to wish you a great week, and we will catch you next week on the run. Dr. Greg Hundley: This program, this copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

10 Mitos Sobre aprendizado no ECG by Cardiopapers

Precisa "levar jeito" para aprender ECG? by Cardiopapers

2021 is coming to an end and so does the ECG podcast. But believe me there are so many things to look forward to in 2022! 2021 it was definitely a great year of learnings about business, myself and my own strengths and limitations. It's also a year of growth as a human and as a woman as well and I am definitely looking forward to 2022 and going out of my comfort zone again. So I hope you enjoyed this review of the year on a personal and business note and then if you liked this episode just share little stars and share your feedback. In this episode: -Review of 2021 -Planning 2022 -Priorities of 2022 -Systems that we loved -What's coming in 2022 Enjoy! Follow me on Social! Geraldinejippe.com | Facebook | Instagram | Instagram ECG.Podcast | Twitter | Linkedin | Entrepreneurs, In Conversation With Géraldine --- Support this podcast: https://anchor.fm/geraldinejippe/support

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Sara Svensk won Ironman Cozumel 2021 in a new Ironman-branded World Record of 8.22.:40. This would be incredible enough, but, as we'll hear in the interview, she did this on less than four months of training! After contracting Covid in May, Sara had ongoing health problems, including heart problems that ECG indicated could have been related to a heart attack. Following 6 week of no training at all, and numerous medical investigations, she was given the all clear to return to gentle training, and, 4 months later, was able to produce that incredible performance in Mexico. I hope this interview gives hope to anyone struggling with a health condition that it is possible to return to full health and fitness!Sponsorshttps://www.precisionhydration.com/ - Multi-strength electrolytes that match how you sweat, and Precision Fuel 30 Gel and Drink mix to ensure enough carbohydrate to perform at your best. Get 15% off your first order With the code OXYGENADDICT15· Take the Quick Carb Calculator· Take the Free online Sweat Test· Book a free 20-minute hydration and fueling strategy video consultationLike what you heard in this interview? Join hundreds of other age group triathletes making the most of their limited training time, training with Team OxygenAddict! http://team.oxygenaddict.com - The most comprehensive triathlon coaching program for busy age groupers. To find out more, You can book a zoom, phone or skype call with Rob or the Team here Join the Oxygenaddict Triathlon Community page on facebook here: https://www.facebook.com/groups/666558563716897/Listen on Spotify: http://bit.ly/OATriPodSpotifyListen on iTunes: http://bit.ly/OATriPodiTunes

Merhabalar... Yazı dizimizin üçüncü ve son bölümü ile karşınızdayız... İyi okumalar... Akut Göğüs Ağrısında; Hasta Merkezli Algoritmalarla Doğru Yol Seçimi Aşağıdaki şekil; akut göğüs ağrısı olan hastaya, hasta merkezli algoritmayla genel bir bakış sağlar. Akut Göğüs Ağrısı ve Akut Koroner Sendrom Şüphesi Olan Hastalara Öneriler (STEMI Dahil Değil) Akut göğüs ağrısı ve şüpheli akut koroner sendrom (AKS) ile başvuran hastalarda, klinik karar algoritmaları (KKA), düzeni ve tanısal değerlendirmeyi kolaylaştırmak için hastaları düşük, orta ve yüksek riskli olarak sınıflandırmalıdır (COR I / LOE B-NR).Akut göğüs ağrısı ile başvuran ve miyokard hasarını dışlamak için seri troponinlerin endike olduğu AKS şüphesi olan hastaların değerlendirilmesinde, kontrol tetkik için alınan ilk troponin numunesinden sonra (sıfır zamanı) önerilen kontrol tetkik zaman aralıkları: High sensitive troponin (hs-cTn) için 1 ila 3. saat ve geleneksel troponin için 3 ila 6. saatte alınmalıdır (COR I / LOE B-NR).Akut göğüs ağrısı ve şüpheli AKS ile başvuran hastalarda miyokard hasarının saptanmasını ve ayırt edilmesini standart hale getirmek için kurumlar, kendi troponin tahlillerine dayalı bir protokol içeren bir klinik karar algoritmaları (KKA) uygulamalıdır (COR I / LOE C-LD).Akut göğüs ağrısı olan ve AKS şüphesi olan hastalarda, mevcut olduğunda önceki testler düşünülmeli ve KKA'lara dahil edilmelidir (COR I / LOE C-LD).Acil servise başvurmadan en az 3 saat önce başlayan akut göğüs ağrısı ile normal EKG'si olan, AKS'yi düşündüren semptomları olan hastalarda, ilk ölçümde (sıfır zamanı) normal sınırının altında olan tek bir hs-cTn konsantrasyonu, miyokard hasarını dışlamak için yeterlidir (COR IIA / LOE B-NR). Akut Göğüs Ağrısı ve Akut Koroner Sendrom Şüphesi Olan Hastalar (STEMI Dahil Değil) STEMI hariç, akut göğüs ağrısı olan ve AKS şüphesi olan hastaların; hastalık olasılığının spektrumunu ve düşük, orta veya yüksek risk gruplarına göre sınıflandırılmasını kapsar.Göğüs ağrısı risk skorları, bir hastanın AKS olasılığını veya 30 günlük majör istenmeyen kardiyovasküler olay (MACE) riskini tahmin etmek için yaş, EKG'deki ST segment değişiklikleri, semptomlar, KAH risk faktörleri ve kardiyak troponin (cTn) gibi klinik bilgileri birleştiren özetleyici bir değerlendirme sağlar.Semptomlar değişmediğinde önceki kardiyak testin güven aralık zamanı dikkate alınmalıdır. Önceki Kardiyak Test için Güven Aralık Zamanı Normal koroner anjiyogram veya KBTA' da (koroner bilgisayarlı tomografik anjiografi) anlamlı darlık yapmayan KAH veya plak gösterilmesi için güven aralık zamanı 2 yıl.Normal stres testi güven aralık zamanı 1 yıl. Göğüs Ağrısı Olan Düşük Riskli Hastalar İçin Kullanılan Tanım ADAPT, tek biyobelirteç olarak güncel troponinleri kullanan göğüs ağrısı semptomları olan hastalara erişmek için 2 saatlik hızlandırılmış tanı protokolünü belirtir.mADAPT, modifiye 2 saatlik hızlandırılmış tanı protokolü, tek biyobelirteç olarak güncel troponinleri kullanan göğüs ağrısı semptomları olan hastalara erişimEDACS (Emergency Department Acute Coronary Syndrome), acil servis akut koroner sendrom.HEART skoru (History, ECG, Age, Risk Factors, Troponin), öykü, EKG, yaş, risk faktörleri,troponin.MACE (Major Adverse Cardiovascular Events), major istenmeyen kardiyovasküler olaylar.NOTR (No Objective Testing Rule), objektif olmayan test kuralı.NPV (Negative Predictive Value), negatif prediktif değer.TIMI (Thrombolysis in Myocardial Infarction), miyokard enfarktüsünde tromboliz. Akut Göğüs Ağrısı Olan Düşük Riskli Hastalar Akut Göğüs Ağrısı Olan Düşük Riskli Hastalara Öneriler Akut göğüs ağrısı olan ve 30 günlük ölüm veya majör istenmeyen kardiyovasküler olay (MACE) riski

În acest episod este prezentat ceasul inteligent Samsung Watch 4 Classic și modul de utilizare cu cititorul de ecran Talkback. Sunt prezentate funcționalitățile ceasului, precum: activitate zilnică, pași, consum calorii, compoziție corporală, ECG, tensiune arterială, somn, diverse aplicații și altele.

Listen to a recap of the best deals and news from 9to5Toys each day at noon. 9to5Toys Daily is available on iTunes and Apple Podcasts, Google Play, or through our dedicated RSS feed. New episodes of 9to5Toys Daily are recorded every weekday. Subscribe to our podcast in iTunes/Apple Podcast or your favorite podcast player to guarantee new episodes are delivered as soon as they're available. Save on nearly all of Apple's official iPhone 12/Pro/Max/mini cases starting at $20Save up to $130 on Hue Gradient Lightstrip bundles, outdoor packages, more from $13Fitbit Charge 5 sports ECG, 7-day battery, and a $130 price tag following $50 discount Host Blair Altland  Links: Subscribe to our YouTube channel!Follow us on Twitter!Like our Facebook page!Download the 9to5Toys app!Subscribe to our newsletter!

 I wake up, (11.08.2021) lying with the back on a cold bathroom floor with a bucket over my face…Sound familiar…? (I don't take any drugs for so many years)So what, I am still alive, I feel dizzy and weak…Somehow, I make it to the bed, without dropping down…My heart is pumping blood like crazy, I am getting fiber flare-ups, sweating like crazy…And I have big tooth pain.I apply what I have learned before. Don't call the emergency or friends… Because the anxiety to be in a car going to the hospital can kill me.And that is true for Millions of heart patience!!!The last time when that happens even not so worse than now, I got Cardiac arrest (When I was in the car, racing to the hospital) and my whole body was paralyzed… Even my heart is totally healthy.OK, I am alone with God and that is good enough for repeating my Mantra…What happened before or was the cause?I got a root canal treatment for my tooth (because my teeth bridge was broken) This was the first time in my life, before I treated that with an antibiotic and later with colloidal silver…Then I got huge stress…My previous girlfriend simulated to have blood spitting and that worried me a lot…She fabricated horror stories about her condition and at the end of the day, I got her to the best hospital… My condition was, that I wanted to speak with the doctor and to see the hospital bill when she went to the best hospital.…It didn't work out and I was cheated (big money) by her. I phoned the hospital and she never had been there.Then I phoned her and said I will never help you again.Afterward, my root canal inflammation got terrible… All heavy tooth issues are related to big stress!This told me an emergency dentist working at the hospital.In the morning after the knockdown, I checked my heart ECG (you can buy such a device cheap)… by myself.  And it was so perfect, never so perfect as before… Then I touched my swollen face close to my nose and mouth, I got dizzy and saw black…I waited and then I decided to take every 4 hours 20ml of my self-made colloidal silver.For my swollen face and my inflammation, I took 2times/day ice cubes on my face and Magnetic pulse therapy…Again, it worked miraculously…The whole root canal treatment is a fraud…!The Indian Dentists treat this kind of inflammation like all the other inflammations with Antibiotics for 14 to 21 days. And it works! The most important thing is to try to calm down if we are under severe health issues…With faith, we can cure everything and fear kills everybody!What is the difference between an engineer and a medical Doctor?An engineer is doing what works and a medical Doctor is doing what makes profit most!My video: Episode 35 Knockdown…https://youtu.be/5nvFqLp0h5AMy audio: https://divinesuccess.net/wp-content/uploads/2021/Podcast1/Episode35Knockdown….mp3

A young pediatric patient is having nausea and vomiting at school and is said to not be 'staying awake very well.' You discover assessment findings such as hypotension, hypoglycemia, and maybe even peaked T waves on the ECG. You receive information indicating that the child has something called "CAH". Or, perhaps... An older patient is having dizziness upon standing, and persistent hypotension. You note a somewhat jaundiced appearance. They become unconscious in their kitchen while searching for a salty snack, and they appear rather sick. Or... A middle-aged patient has suddenly stopped taking their high-dose prednisone for their asthma and is now feeling very weak and cannot stand. We already know what this episode is about - adrenal insufficiency. However, what if those scenarios up above were in the form of a test question? Or worse yet, a real patient? Would we be aware of what's causing the signs and symptoms, and what the appropriate treatment is? Endocrinology does not get the respect it deserves in EMS, probably due to its low volume - we just do not see that many patients with endocrine emergencies outside of diabetes. Or do we, and we just don't notice?

A new study reveals the remote patient monitoring industry (RPM) is expected to grow by 12.5% in the next ten years. And another study shows that almost half of healthcare providers believe that remote patient monitoring will be as prevalent as in-person monitoring within the next five years. All this comes at a time when Apple also recently announced new heart and health monitoring features for their latest smartwatch. Waqaas Al-Siddiq, CEO and founder of Biotricity, discusses how RPM will continue to improve patient outcomes and why RPM tech is poised for rapid growth. Waqaas shares his insights on whether wearable devices such as the Apple Watch can replace other devices for patients with heart conditions. We also explore what the future holds for remote patient monitoring technology. About Biotricity Biotricity is a medical technology company committed to improving healthcare by developing solutions that aid chronic disease prevention and management. Biotricity's premier product is Bioflux, an ECG monitoring system that will be prescribed by physicians to diagnose and remotely monitor cardiac patients.  Biotricity is expanding medical-grade monitoring into the consumer market via its Biolife solution, which empowers users to self-manage chronic conditions. Biolife helps users make lifestyle changes by combining medically relevant ECG data with social media interactivity and a lifestyle log.  Biotricity's R&D continues to focus on the preventative healthcare market, with a vision of putting health management into the hands of the individual. The company aims to support the self-management of critical and chronic conditions with the use of innovative solutions to ease the growing burden on the healthcare system. 

Please join first author Cecilia Bahit and Associate Editor Graeme Hankey as they discuss the article "Predictors of Development of Atrial Fibrillation in Patients With Embolic Stroke Of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center, and Duke; National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor and Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, we're going to analyze the RE-SPECT ESUS trial. What does that pertain to? Well, you're going to have to wait and find out, but it relates to atrial fibrillation and embolic stroke. But before we get to that, how about we grab a cup of coffee and go through some of the other articles in the issue? Would you like to go first? Dr. Carolyn Lam: I sure would. Greg, we know that Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease or diabetes. The question is: What are the effects of Icosapent Ethyl across the range of kidney function in patients with established cardiovascular disease or diabetes from the REDUCE-IT trial? Dr. Greg Hundley: Ah, Carolyn, can you remind us what was the REDUCE-IT trial? What did it encompass there? Dr. Carolyn Lam: The REDUCE-IT trial was a multicenter double-blind, placebo-controlled trial that randomized statin treated patients with elevated triglycerides, who had cardiovascular disease or diabetes, and one additional risk factor, two treatment with icosapent ethyl at 4g daily versus placebo. After a median follow up period of 4.9 years, the study drug demonstrated a 25% relative risk reduction in the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina. Dr. Greg Hundley: Ah, great summary of the original paper, but now this is sort of a follow-up paper. What did this paper research? Dr. Carolyn Lam: Well first, remember they focused on renal function and the median baseline GFR was 75 ml/min with a range of 17 to 123 mL/min/1.73 m2. Treatment with Icosapent Ethyl led to consistent reduction in both primary and secondary composite endpoints across the baseline GFR categories. Patients with the GFR >60 treated with Icosapent Ethyl had the largest absolute, but similar relative risk reduction for the primary composite endpoint. And while patients with GFR >60 treated with Icosapent Ethyl had the highest numerical rates of atrial fibrillation of flutter and serious bleeding. The hazard ratios for atrial fibrillation flutter and serious bleeding were similar across GFR categories. In summary Icosapent Ethyl reduced cardiovascular events among patients with elevated triglycerides in a well-controlled LDL on statin therapy across a wide range of baseline renal function. Dr. Greg Hundley: Oh, Carolyn. Beautiful presentation. That presentation was so good that I know you are ready for a quiz. We haven't had Carolyn's quiz in a week, so we've got to get right back to that. Dr. Carolyn Lam: No, we don't (laughs). Dr. Greg Hundley: Can you describe the primary sequelae of Hutchinson-Gilford progeria syndrome? Dr. Carolyn Lam: Oh wow. Okay. So this is the syndrome where there's premature aging, there's a lot of vascular stiffening, calcification. I'm going to guess some sort of atherosclerotic consequence (laughs). Dr. Greg Hundley: Very nicely done Carolyn. Oh my goodness. I need to get you to take my ABIM recertification- Dr. Carolyn Lam: (laughing) Dr. Greg Hundley: Beautifully done. So Carolyn, this paper comes to us from Dr. Vicente Andrés from Centro Nacional De Investigaciones Cardiovasculares Carlos III, and Hutchinson-Gilford progeria syndrome is a rare disorder characterized, just like you said, Carolyn by premature aging and death, mainly due to myocardial infarction, stroke or heart failure. The disease is provoked by progerin, a variant of lamin A expressed in most differentiated cells. Carolyn, these patients look healthy at birth and symptoms typically emerge in the first or second year of life. In assessing the reversibility of progerin induced damage, and the relative contribution of specific cell types is critical to determining the potential benefits of late treatment and to developing new therapies. Dr. Carolyn Lam: Wow, you've really, really piqued my interest. So what did these investigators do and what did they find? Dr. Greg Hundley: Oh Carolyn, very clever design. So the authors use CRISPR-Cas9 technology to generate mice engineers to ubiquitously express progerin while lacking lain A and allowing progestin suppression in lain A restoration in a time and cell type specific manner upon CRE recombinase activation. They characterize the phenotype of these engineered mice and cross them with CRE transgenic lines to assess the effects of suppressing progestin and restoring lain A ubiquitously at different disease stages, as well as specifically in vascular smooth muscle cells and cardiomyocytes. So Carolyn, what did they find? Well, number one, like Hutchinson-Milford progenia syndrome patients, their engineered mice appeared healthy at birth, and progressively developed Hutchinson-Milford progenia syndrome symptoms, including failure to thrive, Lipodystrophy, vascular smooth muscle cell loss, vascular fibrosis, electric cardiographic anomalies and early death. Their median lifespan was 15 months versus 26 months in the wild types. Dr. Greg Hundley: Second, ubiquitous progestin suppression in lain A restoration significantly extended lifespan, when induced in six month old, mildly symptomatic mice, and even in severely ill animals aged 13 months, although the benefit was much more pronounced upon the early intervention. And then finally, Carolyn remarkably major vascular alterations were prevented and lifespan normalized in engineered Hutchinson-Milford progenia syndrome mice when progestin suppression and lain A restoration were restricted to: just Vascular smooth muscle cells and Cardiomyocytes. Dr. Carolyn Lam: Wow, just fascinating, but, okay. What is the clinical take home message? Dr. Greg Hundley: Right, Carolyn. So these authors findings suggest that it is never too late to treat Hutchinson-Milford progenia syndrome, although the benefit is much more pronounced when progestin is targeted early in mice with mild symptoms. Also, restricting its suppression to Vascular smooth muscle cells in Cardiomyocytes is sufficient to prevent Vascular disease and normalize lifespan in mice, and therefore these data suggest that strategies to treat Hutchinson-Milford progenia syndrome through gene therapy or RNA therapy should consider targeting Vascular smooth muscle cells and Cardiomyocytes. Dr. Carolyn Lam: Oh wow. Very, very cool. Well, my next paper is a basic science paper that's significant for both its methods and its results. Dr. Greg Hundley: Oh wow, Carolyn, I can't wait. So tell us about this novel methodology. Dr. Carolyn Lam: Well, this paper is from Dr. Chang from Westlake University in Hangzhou, China, and colleagues who use a gene editing approach to efficiently institute Exon Skipping without introducing DNA double-strand breaks. So harnessing a fusion of a nuclease defective Case protein, and a cytidine deaminase, which is, we're going to abbreviate it as Targeted AID-induced mutagenesis (TAM) or base editor three (BE3), their approach precisely edited conserved guanines at splice sites, thus abrogating Exon recognition resulting in a programmable skipping of the targeted Exons. Isn't that neat? Dr. Greg Hundley: Yeah, it really is sophisticated Carolyn, wow. So what did they do using these methods? Dr. Carolyn Lam: A novel mirroring model of Duchenne muscular dystrophy was generated, which recapitulated many cardiac defects observed in the human form of the disease, including dilated cardiomyopathy, reduced left ventricular function and extensive cardiac fibrosis. Using this model, they examined the feasibility of using a cytidine base editor to install Exon Skipping and rescue the dystrophic cardiomyopathy in vivo. A single dose administration of an Adenovirus 9EtAm, instituted over 50% targeted Exon Skipping in the Chengdu muscular dystrophy transcripts and restored up to 90% dystrophin in the heart. And as a result, early ventricular remodeling was prevented and cardiac and skeletal muscle function were improved, leading to an increased lifespan of the mice. Despite gradual decline of the Adenovirus vector and base editor expression, the dystrophin restoration and pathophysiological rescue of muscular dystrophy lasted for at least a year. And so this technique really has the potential to be applied to monogenic human diseases, to modulate Exon Skipping or inclusion. Isn't that cool? Dr. Greg Hundley: Absolutely, Carolyn. Beautifully explained. Dr. Carolyn Lam: Well, let me end by sharing what else is in today's issue. There's a Perspective piece by Dr. Alexander on “Chest Pain Redux: Updated and Patient Centered.” There is an In Depth paper by Dr. Kroemer on NAD plus metabolism in cardiac health, aging and disease. And there's a Research Letter by Dr. Shepherd on sudden death in female athletes, with insights from a large regional registry in the United Kingdom. Dr. Greg Hundley: Very good, Carolyn. What a great issue. Now, how about we get to that feature discussion? Dr. Carolyn Lam: Let's go, Greg. Dr. Greg Hundley: Welcome listeners to our feature discussion today on this November 30th. And we have with us Dr. Cecilia Bahit from Rosario, Argentina and our own associate editor, Dr. Graeme Hankey from Perth, Australia to talk to us about a paper pertaining to Atrial Fibrillation. Welcome to you both, and Cecilia, we'll start with you. Could you describe for us a little bit of the background information that went into formulating your study, and then what hypothesis did you want to address? Dr. Cecilia Bahit: Thank you for the invitation. So we all know that embolic stroke of undetermined source, which is called ESUS isn't just a subset of cryptogenic stroke, and is associated with stroke recurrence about 3-6% per year. And on the other hand, we know that continuous cardiac monitoring in this patient population shows that atrial fibrillation can be detected between 10% at six months or 30% at three years. So the underlying atrial fibrillation may be a mechanism for the recurrent thromboembolic stroke in this patient population. So we know that prior studies have identified some predictors of atrial fibrillation in these patients. And if we are able to identify which patients could benefit from cardiac monitoring and have a higher yield to detect atrial fibrillation, we could do a better job at treating them. So, that was our idea behind the paper. So using the RE-SPECT ESUS trial, which was a trial that included patient with ESUS stroke and were randomized to the bigger trend versus Aspirin, we look at predictors of atrial fibrillation unassociated regarding stroke. Dr. Greg Hundley: Very nice. And so, now was this a sub-study here and maybe define for us a little bit, your study design and specific study population. Dr. Cecilia Bahit: So this was a secondary analysis of a randomized clinical trial that as mentioned it was not a sub-study, it was a secondary analysis. We thought all along to do it because of the interest of the clinical question. We look at the total patient population was 5,390 patients. And we looked at those patients who developed atrial fibrillation during the 19 months of follow-up. And it was 7.5%, 403 patients developed atrial fibrillation. Dr. Greg Hundley: Very good. And what were your results? Dr. Cecilia Bahit: So, as I mentioned, we saw that 7.5% of our patient population developed atrial fibrillation during the follow-up. And we know those patients were older, were like, have higher morbidities, and we assessed, we did an one variable analysis and then a multi-variable analysis, trying to identify predictors for atrial fibrillation. And for our model, we identified different predictors, older age, hypertension, lack of diabetes, and higher body mass index, were independent predictors of atrial fibrillation. So the patients who have atrial fibrillation have a higher recurrence of stroke, it was 7.2 versus four, compared to those that did not have atrial fibrillation. Dr. Cecilia Bahit: So I think there's an important part, that 20% of the patient population of the overall trial, this is a little more than a thousand patients, had NT-prob measure at baseline. And when we included this biomarker into the model, only older age and NT-prob were independent predictors of atrial fibrillation. In addition, even though this was not the objective of this analysis, we look at the treatment effect of the bigger trend. And even though we saw that there was a statistical benefit of the bigger trend versus Aspirin in the higher group of these in our score, the overall treatment effect was not there. So we couldn't assess the fact that the bigger trend was better compared to Aspirin in patient with atrial fibrillation, but of course the numbers were very small. Dr. Greg Hundley: Very good. Thank you so much for that wonderful description. And Graeae, now we'll turn to you as associate editor for us at Circulation, and also the editorialist on this particular paper. What caught your attention about this particular study and the results from the many papers that really come across your desk. Dr. Graeme Hankey: Thank you, Greg. And congratulations to Cecilia and her RE-SPECT ESUS colleagues. I mean, this is a landmark study, the RE-SPECT ESUS study, and just to go back, embolic stroke of undetermined source is really common. About one in four ischemic strokes, we don't know the cause of, and it's one of the major subtypes of cryptogenic stroke is an embolic ischemic stroke in which the source could have come from the heart or the aortic arch or the carotids. And we're not really sure. And we think that some of these patients have occult atrial fibrillation, but we can't pick it up at the time. So one way is to try and monitor them with prolonged ECG monitoring. And another way is to actually treat them with anticoagulation because we know that, that's more effective in people with cardio embolic stroke. And so RE-SPECT ESUS and NAVIGATE ESUS used the latter strategy and said, let's see if treating people with ESUS with anticoagulation is more effective than antiplatelet therapy. Dr. Graeme Hankey: And both studies were not significant in terms of showing that Dabigatran or Parovarian for NAVIGATE ESUS was more effective than antiplatelet therapy. So we're left now with this default that all patients with ESUS just get Aspirin, but we have a hunch that some of them actually have cardiogenic embolism and are being undertreated with Aspirin and need anticoagulation. So it's a heterogeneous entity, but we're treating it homogeneously with a sort of weak antiplatelet. So we want to try and find out who's going to get AF or who's already got it that is occult. And this study is a really great and prospective study with 5,000 patients as Cecilia said, who of whom 7% did develop AF just through annual ECG reporting and just with symptom reporting. And that's probably an under report. You know, if they'd had monitoring, they probably would've found about 20 or 30% would've developed AF during that time of 19 months follow up. Dr. Graeme Hankey: And it's the first study to really then show that not just the AF people had a higher stroke rate, but in that group who they predicted to be at high risk of AF with older age and the NT-prob, that the high risk group had a significant reduction with Dabigatran versus Aspirin in that high risk group. It's just, when you look for hetero homogeneity or heterogeneity across the risk groups, it wasn't quite significant. And that might be because it's not significant or it might be that study was underpowered to look at those three, across those three risk subgroups. And also it might be a bit confounded because of it, the patients weren't randomized according to their risk status for AF, they were just randomized, whether they had ESUS, so it's further excited us that there might be a subgroup who needs anticoagulation. And that's why the ARCADIA trial is ongoing now, looking at where the people with ESUS who have high risk of AF benefit from a apixaban versus aspirin. Dr. Greg Hundley: Very nice. And so, with these results that we have here, maybe come back to Cecilia, what do you think would be the next series of studies that needs to be performed in this area of research? Dr. Cecilia Bahit: Well, there's one side that's ongoing as Dr. Hankie mentioned, but I think we should be able to identify which patients have a higher risk of atrial fibrillation and those patients who use cardiac monitoring for long term to identify atrial fibrillation and to treat properly. So I think that would be key in this area. Dr. Greg Hundley: Very nice. And Graeae, what are your thoughts? Dr. Graeme Hankey: Yes. Well, one way is to have our ESUS patients have prolonged ECG monitoring by implantable loop recorders, for example, and then those who develop AF randomizing them to anticoagulation versus antiplatelet therapy. Although if they declare themselves with AF they're usually just go straight onto anticoagulation therapy. So the burning question is, in these people with ESUS who haven't declared themselves as AF, but have predictors of AF like those shown in RESPECT ESUS, like older age, high blood pressure, high BMI ,prob, and perhaps echo features, like left atrial size or ECG features like lots of premature atrial contractions or P wave of abnormalities. Dr. Graeme Hankey: Are these, the subgroups or even LV dysfunction, are these subgroups who need to be more specifically targeted in a randomized trial rather than the whole group of ESUS. And also with longer follow up. NAVIGATE ESUS stopped after 11 months. The bigger RESPECT ESUS stopped after a median follow up of 16 months and the curves were diverging. Maybe with five years follow up, a lot of these people would've developed AF and would've benefited from longer term anticoagulation, but the trials were stopped early, because there wasn't a signal of benefit and there was an early risk of bleeding with anticoagulation. Dr. Greg Hundley: Very good. Well listeners, this has been a really interesting study and we want to thank Cecilia and Graeme for sharing results of the RESPECT ESUS study, highlighting that, in patients with embolic stroke of undetermined source, atrial fibrillation occurs and is a possible source of this stroke, and then also older age, and elevation of NT-prob can be associated with development of atrial fibrillation, subsequent to that stroke event. Dr. Greg Hundley: Well listeners, we want to wish you a great week. And on behalf of Carolyn and myself, look forward to catching you next week on The Run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more visit ahajournals.org.

Episode 76: Eating Disorders. The malaria vaccine is announced by Dr Parker, eating disorders such as anorexia and bulimia are briefly discussed by Sophia, Jeffrey and Dr Arreaza. Introduction: Introducing the malaria vaccine (RTS,S)Written by Hector Arreaza, MD; read by Tana Parker, MD.  Today is November 26, 2021.Malaria is a devastating disease that continues to kill thousands of people every year around the world. Since the year 2000, there have been 1.5 billion cases of malaria and 7.6 million deaths. In 2019, there were 229 million new cases, and 409,000 deaths, mostly children under 5 years of age.Effective vaccines for many protozoal diseases are available for animals (for example, the vaccine against toxoplasmosis in sheep, babesiosis in cows, and more.) However, vaccines for protozoal disease in humans had not been widely available … until now. The RTS,S is a vaccine against malaria approved by the European Medicines Agency in July 2015 for babies at risk, and it was rolled out in pilot projects in Malawi, Ghana and Kenya in 2019.  In October 2021, the World Health Organization announced the recommendation of this anti-malaria vaccine. The trade name of this vaccine is Mosquirix®. The vaccination is recommended for children in sub-Saharan Africa and other regions with moderate to high transmission of Plasmodium falciparum, which is considered the deadliest parasite in humans.  The approved vaccine has shown low to moderate efficacy, preventing about 30% of severe malaria after 4 doses in children younger than five years old. Implementation of vaccination is not free from challenges, and it should be executed not as the solution for the disease, but as part of the solution, along with other efforts such as mosquito control, effective health care, and more.RTS,S is an add-on to continue the fight against malaria worldwide. Hopefully we can lighten the heavy burden of malaria for more than 87 countries that suffer the severe consequences of poor control of this devastating disease. This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. ___________________________Eating Disorders. Written by Sophia Dhillon, MS3, Jeffrey Nguyen, MS3. Discussion with Hector Arreaza, MD.  This is not intended to be a comprehensive lecture on eating disorders. This episode is intended to give you basic information, hoping to motivate you keep learning about it. Let's start talking about eating disorders today, specifically anorexia nervosa and bulimia nervosa. What is an eating disorder? An eating disorder is a disturbance of eating that interferes with health. As a reminder, health is “a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity.” So, an eating disorder, in a wide context, is any eating pattern that is out of what is considered “normal”, and that variation in feeding causes health problems. But in general, when we talk about eating disorders in medicine, we refer to anorexia nervosa and bulimia nervosa, but it includes also avoidant/restrictive food intake disorder, binge eating disorder, night eating disorder, pica, and rumination disorder.  ANOREXIAIn general, anorexia is characterized by immoderate food restriction, inappropriate eating habits or rituals, obsession with having a thin figure or an irrational fear of weight gain as well as distorted body self-perception. There are 2 main subtypes of anorexia: restricting type vs binge-eating/purging type. Tell us the difference between anorexia restrictive type and binge eating-purging type.Anorexia, restrictive type is when weight loss is achieved by diet, fasting and/or excessive exercise, meanwhile the binge-eating/purging type entails eating binges followed by self-induced vomiting and/or using laxatives, enemas or diuretics. These patients will have intense fear of gaining weight or becoming fat. They will have a distorted perception of body weight and shape or denial of the medical seriousness of one's low body weight.Anorexia nervosa is different than avoidant/restrictive food intake disorder. In anorexia, you have an altered perception of your body (“I'm fat”), but in avoidant/restrictive food intake disorder, your perception of your body weight and shape is not abnormal. “I'm skinny, and I'm OK with that.” This is new information for me. I thought anorexia was present always when a patient refused to eat, whether you liked your body or not.Why do people develop eating disorders? There are so many reasons why people develop eating disorders. First, it can be psychological due to low self-esteem, feelings of inadequacy or failure, feeling of being out of control, response to change (i. e. puberty) or response to stress. Second, it can be due to interpersonal issues like having trouble with family and personal relationships, difficult expressing emotions or feelings, or even history of being teased based on size or weight. Lastly, it is the social and cultural norms that we grow up in. There are cultural pressures that glorify thinness and place value on obtaining the perfect body, narrow definitions of beauty that include women and men of specific body weights and shapes. Sometimes there is no reason. Some people just get obsessed with their weight and perceive themselves as “fat”. Effect of anorexia on different parts of the bodySince these patients are scared of gaining weight, how does it affect the entire body?Anorexia can affect multiple systems in our body. Just to name a few symptoms that it can manifest as: amenorrhea, infertility, constipation, dizziness, hypothermia, bradycardia, hypotension, dry skin and even hair loss. Starvation induces protein and fat catabolism that leads to loss of cellular volume and atrophy of the heart, brain, liver, intestines, kidneys, and muscles. Cardiac: It can decrease cardiac mass, decrease cardiac chamber volumes, cause myocardial fibrosis and pericardial effusion. These manifestations are reversible if the patient gains weight. Functionally, it can cause bradycardia due to increased parasympathetic activity, hypotension, decreased heart rate variability and QT prolongation on ECG. Lungs: shortness of breath due to weakened and wasting of the respiratory muscles, pneumothorax and aspiration pneumonia. GI system: it leads to gastroparesis with bloating, constipation, severe pancreatitis and mild transaminitis. Hematologic: anemia, leukopenia and thrombocytopenia. Skin manifestations include dry/scaly skin, hair loss, acne, hyperpigmentation and acrocyanosis. You can also find lanugo, which is a very thin, light colored hair on the face and body. It is thought that the lanugo is an adaptation from the body to keep it warm. Lanugo is common in patients with anorexia nervosa or other causes of malnourishment. That's why wearing coats in warm weather can be a silent sign of anorexia. Other subtle signs include social withdrawal, fidgeting (to burn calories), and always “eating” in private.  It is important to remember that all these manifestation that Jeffrey mentioned are not present with intermittent fasting because intermittent fasting is an intermittent restriction of food, the nutritional needs are met during the “feasting” periods after “fasting”. Some may argue that intermittent fasting may promote eating disorders, but I believe intermittent fasting is just an effective treatment for obesity.Treatment plan for anorexiaThere are several treatment options for these patients. We can refer them to nutritional rehabilitation where they can supervise meals. We can refer them to psychotherapy, such as cognitive behavioral therapy or motivational interviewing. There is also a drug called Olanzapine for this condition. Sometimes, patients may need admission to the hospital. I learned recently that UCLA has an Eating Disorder Program which includes inpatient services. Some centers are very specialized and include family therapy and group therapy. Listeners, you can continue to research about anorexia, it's is fascinating. The prevalence of anorexia in the US is estimated to be 0.6%[3]. BULIMIABy definition, bulimia nervosa is when a person binge eats and then uses certain behaviors to prevent weight gain. These behaviors may include self-induced vomiting, using laxatives or diuretics, exercising excessively, or fasting and having a restrictive diet. Signs and symptoms to look forA physical examination is key. On physical presentation, these people usually can have overweight or obesity. That's the main difference with anorexia. Anorexia: skinny people, bulimia: normal weight, overweight or obesity. Regardless of their weight, these patients are malnourished. They may lack some essential nutrients causing serious health consequences. That's why nutrition cannot be assessed by BMI only. Common signs they will present with will include tachycardia, hypotension (systolic blood pressure below 90), dry skin, and hair loss. If the person uses self-induced vomiting to prevent weight gain, they may have erosion of the dental enamel from all the acid that comes up when they vomit. There may also be scarring or calluses on the dorsum side of the hand from all the acid too. Their parotid glands, that are located on the side of the jaws will also be swollen, causing a sign known as chipmunk face of bulimia.From talking to this person and getting a detailed history, we will learn of the symptoms bulimia nervosa can cause. This will include lethargy and fatigue, irregular menstrual periods in a female, abdominal pain and bloating, and constipationThis disorder really does take a toll on the body. There's plenty of complications that come with it as well. Let's try to break it down by system. GI system has the most complications: esophageal tears from the vomiting called Mallory-Weiss syndrome, which will present with bloody vomits, a loss of gag reflex, esophageal dysmotility, abdominal pain and bloating, GERD, diarrhea and malabsorption of nutrients, fatty stools known as steatorrhea, colonic dysmotility leading to constipation, irritable bowel syndrome, rectal prolapse, and pancreatitis. Cardiac: serious complication is ipeac-induced myopathy, let's spend a little time on this. Ipecac is a syrup that someone with bulimia nervosa may use to make themselves vomit. If a person uses this syrup frequently or for a long amount of time, there is a component called emetine will accumulate in muscle, including cardiac muscle. If a person uses ipecac chronically, it can be detected in the urine for up to 60 days. This will damage the heart muscles or myocardium and lead to cardiomyopathy. It will present with symptoms such as chest pain, shortness of breath, hypotension, tachycardia or bradycardia, T wave abnormalities on ECG, conduction delays, arrythmias, pericardial effusions, and even congestive heart failure. Cardiomyopathy may be irreversible. Renal system: dehydration, hypokalemia, hypochloremia, hyponatremia, and metabolic alkalosis. This could happen in patient who use diuretics as a purging mechanism. Endocrine system: Electrolytes and hormones imbalance. The endocrine system primarily impacts the reproductive and skeletal systems. Among 82 women treated for bulimia nervosa, menstrual irregularities were present in 45 percent at pretreatment and in 31 percent at 12-month follow-up. These irregularities may look like spotty or very light menstrual cycles. Cycles may be very erratic or completely absent. Skeletal system: osteopenia and osteoporosis are common with bulimia nervosa. Osteopenia means weaker and more brittle bones. Osteoporosis is more serious than osteopenia and can more easily result in fractures.The diagnosis of bulimia nervosa can usually be made clinically. And after the diagnosis with bulimia nervosa, the first step in helping them is always getting a full lab work up to see what systems to the body have been impacted. Treatment options include nutritional counseling, behavioral therapy, and even medications. If a person needs help connecting with someone that can help with this disorder, there are organizations that they can contact which will connect them with proper resources in their area. Organizations include the Academy for Eating Disorders and the National Eating Disorders Association. Bulimia nervosa is more prevalent in females than males in all age groups. In the US, adult prevalence is 1.0% and adolescent prevalence is 0.9%, with the median age of onset of 18 years. After comparing different age groups, we have seen the prevalence of bulimia nervosa has increased over time. Conclusion: Anorexia nervosa and bulimia nervosa are eating disorders that can have consequences on the health of our patients. We should know the difference between these two diseases and know the resources available in our community to assist these patients. The diagnosis may be done clinically, but you will need to order labs or imaging for a full assessment. Eating disorders are an example of the direct effect a mental illness can have in the body. In the specific case, anorexia and bulimia cause malnutrition. The treatment of these diseases requires a multidisciplinary team to treat the patient and the family as well.____________________________Conclusion: Now we conclude our episode number 76 “Eating Disorders.” We started this episode with exciting news about the new malaria vaccine, a step forward on our fight against malaria. Sophia, Jeffrey, and Dr Arreaza presented an interesting overview about anorexia and bulimia. They taught us that if a patient perceives him or herself as “fat”, but they are actually underweight, they may have anorexia. Patients with bulimia tend to have normal or above normal BMI but have periods of binging and purging. Be aware of these conditions while assessing your patients' nutritional status and treat appropriately or refer as needed. Even without trying, every night you go to bed being a little wiser.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Tana Parker, Sophia Dhillon, and Jeffrey Nguyen. Audio edition: Suraj Amrutia. See you next week! _____________________References: Malaria's Impact Worldwide, Centers for Disease Control and Prevention, https://www.cdc.gov/malaria/malaria_worldwide/impact.html, accessed on November 15, 2021.  Constitution of the World Health Organization, Basic Documents, Forty-fifth edition, Supplement, October 2006, accessed on Aug 26, 2021. Accessed on November 15, 2021.  https://www.who.int/governance/eb/who_constitution_en.pdf. 12 Secret Signs of Anorexia, CBS News, August 12, 2010, https://www.cbsnews.com/pictures/12-secret-signs-of-anorexia/3/.  Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry. 2007 Feb 1;61(3):348-58. doi: 10.1016/j.biopsych.2006.03.040. Epub 2006 Jul 3. Erratum in: Biol Psychiatry. 2012 Jul 15;72(2):164. PMID: 16815322; PMCID: PMC1892232. https://pubmed.ncbi.nlm.nih.gov/16815322/.  Mitchell, James E, MD; and Christie Zunker, PhD, CPH, CHES, Bulimia nervosa and binge eating disorder in adults: Medical complications and their management, UpToDate, October 2021. https://www.uptodate.com/contents/bulimia-nervosa-and-binge-eating-disorder-in-adults-medical-complications-and-their-management?search=Bulimia%20nervosa%20and%20binge%20eating%20disorder%20in%20adults:%20Medical%20complications%20and%20their%20management&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 Yager, Joel, MD, Eating disorders: Overview of epidemiology, clinical features, and diagnosis, UpToDate, October 2021. https://www.uptodate.com/contents/eating-disorders-overview-of-epidemiology-clinical-features-and-diagnosis?search=Eating%20disorders:%20Overview%20of%20epidemiology,%20clinical%20features,%20and%20diagnosis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 Yager, Joel, MD, Eating disorders: Overview of prevention and treatment, UpToDate, October 2021. https://www.uptodate.com/contents/eating-disorders-overview-of-prevention-and-treatment?search=Eating%20disorders:%20Overview%20of%20prevention%20and%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Heart intelligence. The ancients throughout many cultures left us wisdom that suggests the heart is as powerful, if not more, than the brain. And despite how modern medicine puts the heart and brain in different categories, there's a persistent belief that the heart is the source of so much more. Howard Martin, of the Heart Math Institute, is an expert in the head and heart connection. He and co-founder, Doc Childre, have been studying the heart and developing systems to help humanity heal for thirty years. Through their scientific studies of the heart and its relationship to the brain, they've discovered powerful ways of regulating emotions, reducing stress, improving health, improving decisiveness, and improving adaptability to change. For businesses this translates in to improved return on investment as staff are more productive and healthcare costs are down. In short, the heart Math techniques improve a person's ability to carry dignity and nobility throughout their day.   Expert actions steps: Practice the quick coherence technique, 3 times a day for the next 2 weeks. Check out the free empowering resources on the heartmath.org website. Buy the emWave device to increase productivity, lower stress, improve decisiveness, improve health, and it's also known to lower blood pressure.   Also mentioned in this episode: The Heart Math Solutions Book. Marcy Shimoff's book Happy For No Reason.   Raymond Aaron has shared his vision and wisdom on radio and television programs for over 40 years. He is the author of over 100 books, including Branding Small Business For Dummies, Double Your Income Doing What You Love, Canadian best-seller Chicken Soup for the Canadian Soul, and he co-authored the New York Times best-seller Chicken Soup for the Parent's Soul. www.Aaron.com

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What degree of hyperkalemia makes you worried enough to send your patient to the ED? Are ECG changes sensitive in detecting hyperkalemia? Do you know how to advise your patient on dietary changes? What medications can you effectively use in the outpatient setting?Show notes, Transcript and References: https://www.coreimpodcast.com/2021/11/17/hyperkalemia-mind-the-gap-segment/ Get CME-MOC credit with ACP: https://www.acponline.org/cme-moc/cme/internal-medicine-podcasts/core-im Time stamps01:01 Introductions07:58 Nutrition17:13 Medications20:48 Outpatient medications26:16 RecapTags: IM Core, CoreIM, outpatient, blood work, diet, electrolytes, ECG, nephrology, chronic kidney disease, nutrition

CardioNerds (Amit Goyal and Daniel Ambinder), join CardioNerds FIT Ambassador, Dr. Natasha Cuk and her co-fellows, Dr. Lily Stern, and Dr. Paul Marano from the Cedars-Sinai Cardiology Fellowship for some late afternoon smoothies on the beach. They discuss the case of a 46-year-old woman who presented with sudden cardiac arrest and was ultimately found to have a mobile intraluminal aortic thrombus adherent to a penetrating ulcer in the ascending aorta. This mobile thrombus was ultimately thought to be the cause of transient ischemia and the patient's cardiac arrest. We discuss a differential for sudden cardiac arrest, initial management after resuscitated cardiac arrest, a differential for arterial thrombus, and review an illness script for penetrating atherosclerotic ulcers. Dr. Dominick Megna provides the provides the E-CPR for this episode. Audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship). This Case Report has been published in JACC Case Reports! Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls - Notes - References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Episode Teaching https://twitter.com/LilySternMD/status/1460811173113184263?s=20 Pearls - Cardiac Arrest due to Aortic Thrombus After cardiac arrest, the initial ECG obtained after the return of spontaneous circulation can provide important information on the etiology of the arrest. The ECG can narrow our structured differential, for which one approach would be the following breakdown: acute ischemic events, structural heart disease, arrhythmogenic syndromes with no structural abnormality, and then non-cardiac causes such as drugs, toxins, trauma, metabolic arrangementsThe risk vs benefit of emergent angiography after sudden cardiac arrest depends on balancing the potential benefit from revascularization in an acute ischemic event vs bleeding risks and potential delays in other aspects of care, particularly given that a large percentage of mortality is related to neurologic injury from the arrest, which would not be impacted by immediate angiography. The available randomized controlled trial evidence has not demonstrated a survival or neurologic outcome benefit to immediate angiography, and the decision depends on weighing the risk/benefit for each patient.Due to high flow, a thrombus in the aorta should prompt an investigation for causes focused on the other two ‘points' of Virchow's triad (aside from stasis): endothelial injury and hypercoagulability.A penetrating atherosclerotic ulcer (PAU) is a deep atherosclerotic lesion where there is a focal ulceration of the elastic lamina that extends through the medial layer of the aortic wall. These lesions are most commonly associated with extensive atherosclerosis, but can also occur related to inflammatory, infectious, or traumatic causes.A PAU is a type of acute aortic syndrome and accounts for up to 8% of total acute aortic syndromes. It may present with a spectrum of symptoms, including as an incidental finding on cardiothoracic imaging or a severe chest and back pain, like an aortic dissection. While it is a subtype of aortic syndrome, PAU can also progress to become aortic dissection and rupture. Notes - Cardiac Arrest due to Aortic Thrombus 1. How might a post-ROSC ECG help determine the etiology of a sudden cardiac arrest? During our case, we discussed a systematic approach to the differential diagnosis for sudden cardiac arrest. We broke down the causes into the buckets of: Acute ischemic eventsStructural heart diseaseArrhythmogenic syndromes with no structural heart diseaseNon-cardiac causes such as drugs, toxins, trauma, and metabolic arrangements The post-ROSC ECG can provide immediate information to help narrow our diffe...

Please join authors Babken Asatryan and Anwar Chahal, and Associate Editor Ntobeko Ntusi as they discuss the Primer article "Inflammation and Immune Response in Arrhythmogenic Cardiomyopathy: State-of-the-Art Review." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health at Richmond, Virginia. Well, Carolyn this week, our feature discussion, we're not going to go with one of our original articles, but we are going to feature a primer and a primer is a state of the art review article. The topic is going to be on arrhythmogenic cardiomyopathy and we'll be looking at the role of inflammation and the immune response in arrhythmogenic cardiomyopathy. But before we get to that feature, how about we grab a cup of coffee and talk about some of the other articles in the issue? Would you like to go first? Dr. Carolyn Lam: I would, because guess what? I'm going to be talking about prescription opioids. We know these are a major contributor to the ongoing epidemic of persistent opioid use. What do you think is the incidence after cardiac implantable electronic device procedures? Greg, let's start with a Greg Hundley quiz. I'll give you multiple choice, how about that? Do you think it is 1%, 10%, 25%. 50%? Dr. Greg Hundley: All right, Carolyn, I'm going to guess here. I'm going to go 10%. Dr. Carolyn Lam: Smart. Well, guess what? Today's paper actually gives us insight into that question, it's from Dr. Frankel from the hospital of the university of Pennsylvania and his colleagues, and these authors performed a retrospective cohort study using data from a national Administrative Claims Database from 2004 to 2018 of patients undergoing cardiac implantable electronic device procedures. Adult patients were included if they were opioid naive during the 180 day period before the procedure and did not undergo another procedure with anesthesia in the following 180 days. Dr. Carolyn Lam: Persistent opioid use, which is what we're interested in, was defined by filling an additional opioid prescription more than 30 days following the procedure. So, here's your answer. Of the more than 143,000 patients meeting these inclusion criteria, 11%, so you were right Greg, 11% filled an opioid prescription within 14 days of surgery. Among these patients, persistent opioid use occurred in 12.4% of patients, 30 to 180 days after surgery. The likelihood for developing persistent opioid use was increased for patients who had a history of drug abuse, pre-operative muscle relaxant or benzodiazepine use or opioid use in the prior five years. Also, patients who have prescribed more than 135 milligrams of oral morphine equivalence had a significantly increased risk of persistent opioid use. Dr. Carolyn Lam: Now, this is important because all physicians who perform cardiac implantable electronic device procedures and care for these patients should be aware of the risk of persistent opioid use. This is discussing in editorial by Dr. Kandil from UT Southwestern. Dr. Greg Hundley: Very interesting Carolyn, so connecting sometimes the prescription use of opioids after cardiac implantable electronic devices. Great presentation. Well, my first paper comes to us from the world of preclinical science and it's from our prior editor in chief Dr. Joseph Loscalzo from Brigham and Women's Hospital and the Harvard Medical School. So Carolyn, interferon gamma, producing CD4 positive and CD8 positive T-lymphocytes, have been identified as the predominant pathological cell subsets in human atherosclerotic plaques. Dr. Greg Hundley: While the immunological consequences of these cells have been extensively evaluated, their interferon gamma mediated metabolic effects on endothelial cells remains unknown. So Carolyn, the purpose of this study was to determine the metabolic consequences of the T-lymphocyte cytokine interferon gamma on human coronary artery endothelial cells. Dr. Carolyn Lam: Interesting. So what did Dr. Loscalzo and colleagues find? Dr. Greg Hundley: Right, Carolyn. So, the authors found that interferon gamma impairs endothelial glucose metabolism via altered tryptophan metabolism while depleting NAD plus, which results in a metabolic shift toward increased fatty acid oxidation, and therefore, Carolyn, this work suggests a novel mechanistic basis for pathologic T-lymphocyte endothelial interactions in atherosclerosis, mediated by interferon gamma, linking endothelial glucose, tryptophan, and fatty acid metabolism with NADH and ATP generation and their adverse endothelial functional consequences. Dr. Carolyn Lam: Oh, very nice, Greg. Thank you. The next paper describes a comprehensive characterization of cardiomyopathy caused by filament C truncating variance. Dr. Greg Hundley: Whoa. Okay, Carolyn. Now what is filamin-C? Dr. Carolyn Lam: I thought you may ask and I wasn't going to quiz you, see Greg? The filamin-C gene can cause a striated muscle protein that crosslinks actin and anchors cell membrane proteins to the cytoskeleton, sarcolemmal and sarcomere Z-disc. So, the co-corresponding authors of today's paper Drs. Mestroni and Taylor from University of Colorado, Denver Anschutz Medical Campus, analyzed longitudinal clinical data from an international multicenter cohort of 85 carriers of this filamin-C truncating variants. And this is what they found. Dr. Carolyn Lam: First, the cardiomyopathy associated with filimin-C truncating variants appeared to be a disease with heterogeneous phenotypic presentation, ranging from typical dilated cardiomyopathy to arrhythmogenic, right ventricular cardiomyopathy, and with frequently overlapping forms. Dr. Carolyn Lam: Number two, left ventricular ejection fraction was associated with the risk of death, either all cause or non-arrhythmic, heart transplantation, or LVAD, but not with the risk of sudden cardiac death or major ventricular arrhythmias, highlighting the need for alternative strategies of stratification of the arrhythmic risk in these patients with the filimin-C truncating variant cardiomyopathy. Dr. Carolyn Lam: And number three, this cardiomyopathy was associated with a high risk of ventricular arrhythmias with frequencies of life-threatening ventricular arrhythmias, not significantly different from things like Lamin and desmoplakin cardiomyopathy. Dr. Greg Hundley: Well, Carolyn, just fantastic. My next paper comes to us from Professor Lena Claesson-Welsh from Uppsala University and Carolyn, palmdelphin belongs to the family of paralemmin proteins implicated in cytoskeletal regulation and single nuclide polymorphisms in the palmdelphin locus that result in reduced expression are strong risk factors for development of calcific aortic valve stenosis, and predict the severity of the disease. Dr. Carolyn Lam: Wow, interesting. Palmdelphin, great. So tell us, what did they find and what are the clinical implications please? Dr. Greg Hundley: Right, Carolyn, great question. So first, calcific aortic valves stenosis patients with the single nucleotide polymorphism RS754 3130 express reduce palmdelphin levels in valve endothelial cells, which shows hallmarks of palmdelphin deficiency, such as loss of cytoplasmic RanGAP1, altered nuclear morphology and nuclear rest of P53 of P21. Carolyn, second, gene-regulatory changes affecting actin reorganization, are detected in seemingly healthy regions of calcifying bowels, in agreement with disturbed actin-dependent processes, being an early event, instigating the calcific process. And so Carolyn, the take home message is that palmdelphin is prominently expressed in endothelial cells and the presence of the palmdelphin single nucleotide polymorphism correlated both with a Barrett endothelium and calcific aortic valve stenosis suggesting that endothelial cell dysfunction is essential in development of calcific aortic valve disease. Dr. Carolyn Lam: Oh, wow, wow. Thank you for translating that into the clinical implication. Thanks Greg. Let's maybe discuss what else is in today's issue. There's a prospective piece by Dr. Kirchof entitled “In Patients With Recently Diagnosed Atrial Fibrillation, Think Anticoagulation And Rhythm Control.” There's an exchange of letters between Drs. Liao and Hakala regarding the article Cardiovascular Risk Factor Trajectory Since Childhood And Cognitive Performance In Midlife, The Cardiovascular Risk In Young Finns, study. Dr. Greg Hundley: And Carolyn, I've got a research letter from Professor Ramin entitled “Association Between Sarcomeric Variants In Hypertrophic Cardiomyopathy In Myocardial Oxygenation, Insights From A Novel Oxygen-Sensitive CMR Approach.” Well, how about now we get onto that primer feature discussion relating to arrhythmogenic cardiomyopathy? Dr. Carolyn Lam: Yay. All right, let's go, Greg. Dr. Greg Hundley: Well, listeners, we are now onto our feature discussion and this week we've got a different aspect to the feature discussions. We're going to work through a review article and what we call as a primer. It's one of our state-of-the-art family of publications, where we take a topic and perform a review on a new evolutionary concept that might be occurring in a particular field. This week, we are going to discuss arrhythmogenic cardiomyopathy and we have with us two of the authors of this primer, Dr. Babken Asatryan from Bern, Switzerland and also Dr. Anwar Chahal from Lancaster, Pennsylvania. And of course, as always, we invite one of our associate editors and we have with us this week Ntobeko Ntusi from South Africa. Welcome gentlemen and Babken, let's start with you. Can you give us just a little bit of review regarding arrhythmogenic cardiomyopathy? We hear that term as opposed to arrhythmogenic right ventricular cardiomyopathy, and then maybe also, what are the underlying fundamental histopathologic and pathophysiologic findings associated with this disease? Dr. Babken Asatryan: Thank you, Greg. It's really an absolute pressure being here and thank you for your invitation again. So arrhythmogenic cardiomyopathic is genetically-determined heart disease and the common cause of sudden cardiac death in individuals younger than 40 years of age, it's characterized pathologically by fibrosis and/or fibro fatty infiltration of the myocardium. This infiltration provides a substrate for electrical and stability and leads to ventricular arrhythmias ranging from isolated premature ventricular contractions to sustain ventricular tachycardia and ventricular fibrillation. Live ventricular arrhythmias are cardio manifestations of the orthogenic cardiomyopathy, and they typically occur at early stages of the disease, preceding pathological and functional abnormalities. We call that a concealed stage of the disease. Dr. Babken Asatryan: The typical form for arrhythmogenic cardiomyopathy, which has been previously termed as arrhythmogenic right ventricular cardiomyopathy, primarily affects the right ventricle and has been recognized for decades. Following implementation of postmortem autopsy, increased use of contrast, enhanced cardiac MRI, and improved understanding of the genotype phenotype correlations, more recently cases with more pronounced left ventricular involvement have been discovered as well as cases with biventricular involvement of the disease. Dr. Babken Asatryan: Nowadays, we believe that around 60% of cases have also left ventricular involvement, even if they're diagnosed based on the 2010 task force criteria for arrhythmogenic cardiomyopathy. Causative variants in desmosomal genes are identified in about 60% of patients with typical arrhythmogenic right ventricular cardiomyopathy. Dr. Babken Asatryan: Recently, there have been studies reporting non-desmosomal gene variants in patients with arrhythmogenic right ventricular cardiomyopathy, as well as in those left ventricular and biventricular forms of the disease. But the left ventricular form is quite new to us, so we are learning a lot every day about this disease. Dr. Babken Asatryan: The pathogenesis of this condition appears to be quite complex. We know that these pathogenic variant in desmosomal genes can initiate several pathways and these could be gene dependent. What we do know, that these eventually lead to fibrosis and fibro fatty infiltration of the myocardium, which is the hallmark feature of arrhythmogenic cardiomyopathy. Dr. Greg Hundley: And patients present generally when, in terms of lifespan? Dr. Babken Asatryan: So, patients present in between 30 to 40 years of age, there's a typical presentation for arrhythmogenic cardiomyopathies but young presentations are also common nowadays, particularly. So, programs in families, they usually present 30 to 40 years of age. But in families, we do discover patients who have typical arrhythmogenic right ventricular cardiomyopathy or left and right ventricular involvement were younger at age, but they still need the criteria. Dr. Greg Hundley: And then when we diagnose this condition, do we also need to think about, at least clinically, looking for other affected individuals within a family? Dr. Babken Asatryan: Absolutely. So most of the arrhythmogenic biventricular cardiomyopathy, arrhythmogenic left ventricular cardiomyopathy cases are autosomal dominant diseases. So, this means if an individual carries a pathogenic variant in one of the genes responsible for the condition, the likelihood that the first degree family members will carry the same variant is about 50%. The disease however, presents with reduced penetrance and variable expressivity. Some of the family members may have just arrhythmias and others may develop arrhythmias and structural heart disease. And some of the individuals who carry pathogen occurrence in desmosomal are the genes responsible for the condition may not show phenotype at all. So, that makes the decision-making in families quite challenging. Dr. Greg Hundley: Very nice. Well, thank you so much Babken and now, we're going to turn to one of your co-authors, Anwar and Anwar, in this primer, you start to present a new sort of theme, that inflammation actually may play a role in this disease, at least in terms of adverse events. Can you describe a little bit what your team was thinking here and what took you in this direction and what are some of the research that you've revered here that supports this new line of thinking?   Dr. Anwar Chahal: Thanks, Greg and Ntobeko, for first, the kind invitation to come on this podcast. I must add that I normally listen to the podcast and very much enjoy it, so it's a great honor and privilege for us. Dr. Anwar Chahal: Let me contextualize it, I think it's important to think about what are problems are when we evaluate cases, whether that's the program or the family members, and try to determine what's actually going on. There's been a number of changes over the last 15 years that really evolve around a better understanding and the availability of multimodality imaging, which has altered the way we evaluate these cases. If you look at the 2010 taskforce criteria, for example, they talk about volumetric changes and injection fractions by echo or MRI, and even ventriculogram synapse on fluoroscopy, which I don't think many people do anymore, but they don't mention gadolinium enhancement, and there is an updated version that will come out and talk about that, and the advantages of MRI and even contrast-enhanced CT, and now 18F-FDG, CT PET imaging. Dr. Anwar Chahal: So, the patient journey and the problem that we face is that actually some people present with very unusual features, chest pain, troponin rise, undergo coronary angiography, normal coronary arteries, or unobstructed coronary arteries. We put them through MRI scanners and we see a little bit of gadolinium enhancement. We follow them over the next five years or so, and it develops into taskforce criteria, positive ARVC. So, that's the sort of clinical angle where we've started to see this. Dr. Anwar Chahal: As we put people through scanners, we see the hearts lights up on PET scanners, pretty reproducibly and reliably, that tells us that there's some inflammation there. We look back into the literature and actually very, very early work that was done, autopsy-based, some of it endomyocardial biopsy-based describing lymphocytic infiltrates. Usually that's dry, as you say, or sterile, but there have been reports of even viral pathogens. Dr. Anwar Chahal: That's where it stirred this debate up for us about whether there's this signal that we're seeing there, what is it? What's actually going on? It raises a question, we recognize the other mechanisms, the fiber fatty replacement, the apoptotic pathways, that contribute to that. But there's such variable expressivity with this disease. It's a difficult disease to pin down and it raises a question. What are these other effect modifiers? Is there something else that we do not recognize? And that's really what's driven this. Dr. Anwar Chahal: Our group of co-authors are leaders in the field. Some of them are colleagues in veterinary medicine, Dr. Anna Geltser, and we work together on boxer dog patients. So, she is a practicing vet and a scientist, and has lots of boxer dogs with arrhythmogenic cardiomyopathy. We've been looking at how we could utilize that as a model to test some of the findings that we have in humans and pioneering work really by Bob Hamilton in Toronto, in this paper where they described anti-DSG2 antibodies, which were found not only in humans, whatever the underlying genotype, but also in boxer dogs with arrhythmogenic cardiomyopathy. And that's been followed up with work from Europe, describing anti-heart antibodies, anti-intercalated disk antibodies. Dr. Anwar Chahal: It doesn't really matter what the genotype is, but we're seeing these antibodies there and we're seeing these positive scans indicating inflammation. So the big question is, is this inflammation of primary insult or is it secondary? Is it that the heart in somebody with a genetic cardiomyopathy is predisposed, maybe the remodeling is affected. Bob Hamilton thinks this is probably the best explanation to explain why, whatever the genotype, that these antibodies were positive, that actually that myocardium becomes exposed. The epitope of DSG is now exposed to the immune system, which mounts an antibody response, and hence you see the rise in these antibodies, but it's possible it could it be primary as well. With COVID, and this is a bit of a stretch, so just bear with me there, with COVID we've been recognizing that there's myocardial injury. Dr. Anwar Chahal: There's not as much myocarditis as we expected, but there's been, with virus SARS-CoV-2, we know regular human coronavirus is a recognized cause of viral myocarditis. So, the question really arose are we going to see a lot more of this myocarditis? In our lab discussion, it was, "Well, do you think we're going to see something similar in that we've seen with arrhythmogenic cardiomyopathy, these genetically predisposed individuals are more likely to get invaded? Now, we haven't really seen that with COVID and I won't delve too much into it, but going back to the classical viral infections that we see with myocarditis, here's a really, really interesting biological link. Most of them invade through the desmosome, so with SARS-CoV-2, we see the ACE2 receptors as the way the virus really invades. But with these regular coxsackie virus, for example, parvovirus, a lot of them invade through the desmosome, and that's where we thought, here's a link. Dr. Greg Hundley: Very nice. Ntobeko, you see a lot of papers come across your desk. What attracted you to this group of investigators and this particular review article? Dr. Ntobeko Ntusi: Thank you very much, Greg. I want to start by congratulating Babken, and Anwar for a really fantastic submission, which as an associate editor, was an absolute pleasure to handle. There really are six things that stood out for me about this article. The first one really relates to the question that you ask Babken, which relates to the nomenclature and people have traditionally thought of this is a disease of the right ventricle. I think it's now timely to consider a clear change in nomenclature, that recognizes not only right ventricular involvement, but also left ventricular involvement. And the common finding of biventricular disease in patients with ACM. Dr. Ntobeko Ntusi: The second really important contribution for me from this primer was that we've always thought of arrhythmogenic cardiomyopathies as a genetic disorder with abnormalities in the genes, encoding components of the desmosome. Many groups recently, including our own group that described novel mutations for arrhythmogenic cardiomyopathy in adhering to poultry and other genes outside of the desmosome are showing that the genetic underpinnings are much wider. But the key contribution here is really the consideration of the centrality of inflammation to the pathogenesis of this disease. Anwar has spoken to some length about that, so I won't rehash those comments, but for me, what is key for future work in this area is really to clarify whether the inflammation, as in with many other forms of cardiovascular disease, is merely an epiphenomenon, or whether it plays a critical role in the causal pathway for the phenotypes that we see. Dr. Ntobeko Ntusi: The next important feature for me was the review of the literature and evidence in the association with myocarditis. So, we've seen lots of case reports and small case series showing young people presenting with myocarditis and meeting either the Dallas criteria histologically, or the Lake Louise criteria on imaging, and then subsequent genetic testing confirming the diagnosis of an arrhythmogenic cardiomyopathy. I thought for the first time with quite a compelling review of the link between these two. Dr. Ntobeko Ntusi: The fourth important contribution relates really to the contribution of imaging modalities, both in diagnostics, but critically in risk stratification for this clinical entity. And for me, the importance of cardiovascular magnetic resonance, either with planimetric mapping or late gadolinium enhancement to really add to our ability to predict future events. Dr. Ntobeko Ntusi: Then there's been quite a number of publications in the last five years that have clarified our understanding of the at risk patient with arrhythmogenic cardiomyopathy who's likely to suffer a sudden cardiac death event. This tends to be somebody who was young, who was male, who has a history of documented non-sustained ventricular tachycardia or a history of syncope and on ECG, quite extensive T wave inversion. So again, this is nicely reviewed, and we think about those as candidates who'll benefit from implantation of an ICD. Dr. Ntobeko Ntusi: Then I thought for me, the last really nice contribution from this piece was the review of advancing our understanding of the hot phase. So in all forms of heart muscle disease, we speak of the presentation of patients with the chest pain syndrome, with a troponin leak, but unobstructed coronaries. On further investigation, we don't really find any other evidence of an inflammatory event. We call this a hot phase. And in some case reports in small case series, endomyocardial biopsy has revealed the association of these, whether in TCM, HCM, or arrhythmogenic cardiomyopathy with lymphocytic infiltration. I thought this was all very nicely reviewed. Dr. Ntobeko Ntusi: So, the question that really left me with having read this review, was whether in the future, we may actually need to consider targeting inflammatory pathways as a therapeutic target in this heart muscle disorder. Thanks Greg. Dr. Greg Hundley: Yes. Thanks so much in Ntobeko. You've really led us to the next question that I'm going to ask both Babken and Anwar, you've discussed where do you feel this field is moving and what is the next study or series of studies we need to perform. Babken, first you, and then Anwar. Babken, what do you think is the next study to be performed in this space? Dr. Babken Asatryan: I so much agree with Ntobeko, that perhaps understanding better what can be targeted in these patients, in order to prevent development of phenotype or least to prevent cardiac events, is perhaps the most important next step. In our first figure, we have summarized this potential mechanisms, involving inflammation leading to with arrhythmogenic cardiomyopathy in these patients. We have also highlighted the potential mechanisms that perhaps in the future can be targeted. This could include both targeting the inflammatory cytokines, as well as the primary agents that cause the myocardial inflammation in patients, depending on the results that we will receive over the next years and perhaps animal models should be the next step to better understand how similar arrhythmogenic cardiomyopathy phenotype, where inflammatory contributors to the phenotype are important. And then we can understand whether this can be the same in humans as well. Dr. Greg Hundley: Very nice. And Anwar, do you have anything to add? Dr. Anwar Chahal: Yes. So, agree with that. I guess I would add what are we doing to try to help decipher this? So some of the work that we're doing, I mentioned earlier with the boxer dog patients, who have arrhythmogenic cardiomyopathy. So some of the aspects that we're actually looking at is taking swab cells to see if we can phenotype as a alternative tender myocardial biopsy. And one of the co-authors, Angeliki Asimaki, really pioneered that as a alternative tool because the desmosis are ubiquitous and this may help us phenotype patients better. But also, we want to look at using that as a tool in the pheno copies of arrhythmogenic cardiomyopathy. So we would advocate, re-phenotyping people as well as possible and trying to use some of these techniques. Dr. Anwar Chahal: The next thing we're really looking at is antibody based tools, either working with collaborators, who've already described these antibodies such as anti-DSG2, anti-heart antibody, and anti-skeletal disc to see if we can develop those and perhaps identify others in both human and ox models. And that will then hopefully open the way for us to develop therapeutics that may be able to target those and address that, and maybe use these antibodies as markers to see disease progression, or halting of disease. Dr. Greg Hundley: Very nice. Well listeners, we want to thank Dr. Babken Asatran from Bern, Switzerland, Anwar Chalal from Lancaster, Pennsylvania, and our own associate editor, Ntobeko Ntusi from South Africa, really helping us see this new scientific consideration regarding the potential role of inflammation in causal pathways of adverse manifestations of arrhythmogenic cardiomyopathy. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more visit ahajournals.org.

#636-Critérios de Vereckei no ECG. by Cardiopapers

Ever wonder what else that Apple Watch on your wrist can do? How about that ECG the patient gave you that they took from it? Let's explore what the Apple Health app and the Apple Watch can do for us in EMS in this episode of The Ready Room!

Sheeza Hussain is the Chief Commercial Officer of Biofourmis which is developing a hospital-at-home model for health systems that is even more in demand due to the stress of COVID-19 patients.  In addition to acute care, Biofourmis is also applying its remote monitoring technology to post-acute and chronic care. Sheeza explains, "When we think about hospital-at-home, we think about acute level type care-at-home. It's not about being cared for exactly as you would be in a hospital. But it's for those patients who still, for all intents and purposes, need to be monitored and need to be admitted to a hospital. But instead, they get to go home. They get monitoring equipment, they get to go to the comfort of their own bed, and they're still visited by clinicians or physicians every day in person as is a requirement for some of the reimbursement." "So when it comes to hospital-at-home, it's about in our case, a patch and we're device agnostic. We offer a patch that the patient wears on their chest, and it is continuously capturing data, things like the single-lead ECG, heart rate, respiratory rate. And that is feeding our analytics engine and allowing us to be able to establish a personalized baseline for each and every patient." @Biofourmis #HospitalatHome #RemoteCare #CareatHome #PatientMonitoring #PostAcute #ChronicCare #Hospitals Biofourmis.com Listen to the podcast here

Sheeza Hussain is the Chief Commercial Officer of Biofourmis which is developing a hospital-at-home model for health systems that is even more in demand due to the stress of COVID-19 patients.  In addition to acute care, Biofourmis is also applying its remote monitoring technology to post-acute and chronic care. Sheeza explains, "When we think about hospital-at-home, we think about acute level type care-at-home. It's not about being cared for exactly as you would be in a hospital. But it's for those patients who still, for all intents and purposes, need to be monitored and need to be admitted to a hospital. But instead, they get to go home. They get monitoring equipment, they get to go to the comfort of their own bed, and they're still visited by clinicians or physicians every day in person as is a requirement for some of the reimbursement." "So when it comes to hospital-at-home, it's about in our case, a patch and we're device agnostic. We offer a patch that the patient wears on their chest, and it is continuously capturing data, things like the single-lead ECG, heart rate, respiratory rate. And that is feeding our analytics engine and allowing us to be able to establish a personalized baseline for each and every patient." @Biofourmis #HospitalatHome #RemoteCare #CareatHome #PatientMonitoring #PostAcute #ChronicCare #Hospitals Biofourmis.com Download the transcript here

SD121 – Inteligência Artificial na Cardiologia. Neste podcast, conversamos com Antonio Luiz Pinho Ribeiro (Tom Ribeiro). Professor Titular do Departamento de Clínica Médica da Faculdade de Medicina da UFMG e Coordenador do Setor de Inovação e Pesquisa do Hospital das Clínicas da UFMG. Ele nos explicará: como a inteligência artificial (IA) tem revolucionado diversas áreas da cardiologia; como foi a sua pesquisa que gerou dois artigos na Nature; a experiência do HC-UFMG com a telemedicina aliada à IA. Errata: no Episódio, falamos que ele tinha fator H de 23 pelo ISI, 25 pelo Scopus e 32 pelo Google Scholar. Números que já eram impressionantes. Na verdade, eles são ainda maiores: fator H de 39 pelo ISI, 41 pelo Scopus e 57 pelo Google Scholar. O que conversamos neste episódio? Background do prof. Antonio Luiz Pinho Ribeiro O prof. Tom é também vice-Diretor do Centro de Inovação em Inteligência Artificial em Saúde, presidente da Sociedade Internacional de Eletrocardiologia (2019-2021), pesquisador 1A do CNPq, pesquisador visitante da Universidade de Southampton (2017-2022) e editor associado das revistas BMJ Heart e Journal of Electrocardiology. Coordena a Rede de Telessaúde de Minas Gerais e é vice-coordenador do Instituto de Avaliação de Tecnologia em Saúde (INCT-IATS).  Inteligência artificial e medicina A inteligência artificial está se colocando como uma tecnologia, um método, que vai permitir que ferramentas antigas, como a radiografia de tórax, a tomografia e o eletrocardiograma forneçam informações para muito além do que nós conhecemos hoje.  Então, conseguiremos tirar muito mais coisa de métodos já disseminados que existem em nossa base tecnológica. Eventualmente esses achados influirão em como os médicos consultam os pacientes e como eles são tratados.  Eletrocardiogramas e aprendizado de máquina No exemplo do grupo de Telessaúde da UFMG, eles tinham uma base de  2.4 milhões com dados brutos e laudos. Então, eles criaram um algoritmo de inteligência artificial. Os resultados desse estudo foram publicados na Nature e mostram como a inteligência artificial está revolucionando a tecnologia médica. Isso mostra a importância de um médico ter conhecimento profundo na sua área, mas estar aberto a novas habilidades.  A telemedicina no HC-UFMG O centro de telessaúde na UFMG, que coordena uma rede de telemedicina principalmente para a atenção primária. O prof. Antônio relata que os integrantes do grupo de pesquisa em telessaúde sabiam que os dados dos eletrocardiogramas seriam importantes eventualmente. Uma grande vantagem dessa equipe é que era multiprofissional — com médicos, estatísticos, cientistas de dados, entre outros.  Por isso, eles tiveram o cuidado de guardar todas as informações, inclusive o traçado original de cada ECG laudado pela telessaúde do HC. Nos últimos 5 anos, eles se preocuparam em organizar essa base para estudos epidemiológicos e em criar algoritmos para diagnóstico automático, sem nenhum processamento dos dados. Links para os estudos publicados na Nature e citados no podcast Deep neural network-estimated electrocardiographic age as a mortality predictor Automatic diagnosis of the 12-lead ECG using a deep neural network Participe do MEDFRIDAY DO WHITEBOOK A Black Friday do Whitebook traz uma oportunidade imperdível para as conquistas da sua carreira médica. Para ficar por dentro de todas as novidades e promoções, não deixe de acessar o link abaixo: NOVIDADES DA MEDFRIDAY! Participe do Saúde Digital Podcast Deixe-nos saber o que você achou deste episódio! Você tem alguma dica para dar ao Saúde Digital Podcast? Quer sugerir um tema? Sua participação é muito importante! Clique aqui para falar conosco. Você pode falar também diretamente com o host Lorenzo Tomé pelo Instagram, Linkedln ou Telegram no @lorenzotome Conheça os melhores canais de conteúdo para médicos SDConecta: um hub, um ponto de encontro, do médico com o conhecimento digital na medicina. Conheça nossa plataforma feita pelo time do Saúde Digital, focada na sua experiência de aprendizado. Invitation Only exclusiva para médicos com programa de incentivos e uma rica rede de networking para você. Conheça o primeiro e maior Hub de comunidades médicas da América Latina – Clique no link a seguir:  https://sdconecta.com/ Música usada no episódio https://www.youtube.com/watch?v=0he3R37nALM  

Please join author Maria Nunes and Associate Editor Ntobeko Ntusi as they discuss the article “Incidence and Predictors of Progression to Chaga Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals.” Dr. Carolyn Lam:             Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley:           And I'm Dr. Greg Hundley, Associate Editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well Carolyn, this feature this week, we're going to talk about Chagas disease and we have some really important long-term, really for the first time, observational data and a cohort that's been followed in Brazil. And it's just a wonderful discussion from a team that's been working very hard in this area over an extended period of time. But before we get to that, how about we grab a cup of coffee and get started on some of the other articles in this issue? Would you like to go first? Dr. Carolyn Lam:             I would. And with your coffee, I would like to tell you about non-combustible nicotine or tobacco products. Fancy a smoke with your coffee? Well, you know that those are novel forms of nicotine consumption composed of things like nicotine vaping products that vaporize the nicotine-containing fluids and heated tobacco products that really heat the tobacco products without combustion. Now, these have recently gained popularity because they're portrayed as being safer modes of smoking compared with the traditional combustible cigarettes. However, their associations with subsequent cardiovascular disease risks are still unclear. So Greg, here's today's quiz. Gosh, I miss our quizzes. What do you think? Are they safer or are they not? Dr. Greg Hundley:           Oh, Carolyn, you're catching me on this and I never know which way to go, but I'm going to guess not. How about you tell us? Dr. Carolyn Lam:             Well, the paper will tell us, and this is from co-corresponding authors Dr. Lee from Seoul National University Bundang Hospital and Dr. Park from Seoul National University College of Medicine and their colleagues. And they basically studied more than 5,000,000 adult men who underwent health screening examinations during both a first and second phase of health screening periods from the Korean National Health Insurance Service Database spanning 2014 to 2018. Initial combustible cigarette smokers who subsequently quit that cigarette smoking and converted to a non-combustible nicotine or tobacco product use was associated with a lower incident cardiovascular disease risk compared to those who continue the combustible cigarette use. However, compared with combustible cigarette quitting without using these non-combustible substitutes, those who ceased smoking but continued with the non-combustible products was associated with a higher cardiovascular disease risk. So the take home message is although the non-combustible nicotine or tobacco products may be associated with a lower cardiovascular disease risk compared with continued combustible cigarette smoking, those who quit without using these substitutes may benefit the most in reducing the risk of developing future cardiovascular disease events. And this is discussed in a wonderful editorial by Dr. Auer, Diethelm and Berthet. Dr. Greg Hundley:           Very nice, Carolyn. Great presentation and really new information in this space. Well, my paper comes from the world of preclinical science and it involves long noncoding RNAs. And Carolyn, they are important regulators of biological processes involved in vascular tissue homeostasis and cardiovascular disease development. And so, the current study, led by Professor Lars Maegdefessel from Karolinska Institute, assessed the functional contribution of the long noncoding RNAs myocardial infarction associated transcripts and their relationship to atherosclerosis and carotid artery disease. Dr. Carolyn Lam:             Hmm, interesting. They are the rage, these lncRNAs. So what did they find, Greg? Dr. Greg Hundley:           Right, Carolyn. So long noncoding RNAs possess key regulatory functions directly interacting and mediating expression and functionality of proteins, other RNAs, as well as DNA. Next, the long noncoding RNA myocardial infarction associated transcript plays a key role during atherosclerotic plaque development and lesion destabilization. Its expression becomes highly increased in high risk patients with vulnerable plaques. And so, Carolyn, the take home therapeutic targeting of the long noncoding RNA myocardial infarction associated transcript, using antisense oligonucleotides, well that offers novel treatment options for patients with advanced atherosclerosis in the carotid arteries that are at risk of stroke. Dr. Carolyn Lam:             Oh, very interesting. So from the preclinical world back to the clinical world with an important clinical trial. Now, we know that percutaneous closure of the left atrial appendage is an alternative to chronic oral anticoagulation to reduce stroke risk in patients with nonvalvular atrial fibrillation. The Amplatzer Amulet Left Atrial Appendage Occluder IDE trial, called the Amulet IDE trial, was designed to evaluate the safety and effectiveness of the dual seal mechanism of the Amulet left atrial appendage occluder compared with the WATCHMAN device. And here, 1,878 patients with nonvalvular atrial fibrillation at increased risk of stroke were randomly assigned to undergo percutaneous implantation of a left atrial appendage occluder with the Amulet occluder or a WATCHMAN device. And the primary end points included safety, which was a composite of procedure-related complications all cause death or major bleeding at 12 months, and effectiveness, which was a composite of ischemic stroke or systemic embolism at 18 months. They also looked at the rate of left atrial appendage occlusion at 45 days. And this paper is from Dr. Lakkireddy and colleagues from Kansas City Heart Rhythm Institute. Dr. Greg Hundley:           Well Carolyn, these devices, they are really being heavily tested in patients with atrial fibrillation. So what did they find? Dr. Carolyn Lam:             The Amulet occluder was non-inferior with respect to safety and effectiveness compared to the WATCHMAN device, and superior with respect to left atrial appendage occlusion; however, procedure-related complications were higher with the Amulet occluder, largely related, perhaps, to more frequent pericardial effusion and device embolization. And the authors noted that the procedure-related complications decreased with operator experience; however, I think all of this still needs to be further investigated. Well, those were really nice original papers, but let's also discuss what else there is in today's issue. There is an exchange of letters between Drs. Mueller and Allen regarding the article “Diagnostic Performance of High Sensitivity Cardiac Troponin T Strategies and Clinical Variables in a Multisite U.S. Cohort.” There's a perspective piece by Dr. Olson, “Toward CRISPR Therapies for Cardiomyopathies.” Dr. Greg Hundley:           And Carolyn, I've got a research letter from Professor Layland entitled “Colchicine in Patients with Acute Coronary Syndromes: Two Year Follow Up of the Australian COPS Randomized Clinical Trial.” Well, what a great set of papers that we've discussed. Now, let's get on to that feature discussion and learn a little bit more about the longitudinal history and progression of cardiovascular disease and patients with Chagas disease. Dr. Carolyn Lam:             Yay. Let's go, Greg. Dr. Greg Hundley:           Well, listeners, we are here for our feature discussion today and a very exciting one we have, pertaining to Chagas disease. And we have with us today Dr. Maria Nunes from Belo Horizonte, Brazil, and also one of our Associate Editors, Dr. Ntobeko Ntusi from Cape Town, South Africa. Welcome to you both. And Maria, we'll start with you. Could you describe for us some of the background information pertaining to your study and what was the hypothesis that you wanted to address? Dr. Maria Nunes:             Yes, thank you for these opportunities. My main hypothesis is that Chagas disease is the major cause of dilated cardiomyopathy in endemic areas. So we selected patients without cardiomyopathy at baseline to see if the Trypanosoma cruzi seropositivity is a predictor of further developing of cardiomyopathy. Dr. Greg Hundley:           Very nice. And so tell us, how did you construct this study? What was your design? And then also, maybe describe for us how you selected the participants for this study. Dr. Maria Nunes:             We selected the participants from two blood donor centers. One in Sao Paulo and one in Montes Claros, which is north of Minas Gerais State. We select blood donors because it's the way that we have Chagas disease's screening tests. And in asymptomatic patients, usually at the hospital, patients comes to us with heart failure or a kind of symptoms related to Chagas disease. Our main goals in this study is to select healthy participants based on the screen test of Trypanosoma cruzi. So the population was blood donors selected from two centers. Dr. Greg Hundley:           Very good. And then again, your study design. So did you follow these two groups of individuals longitudinally over time, and for how long? Dr. Maria Nunes:             Yes, we have different visits of this study with the patients initially was selected at first in 1996 and 2002. At this time, they don't have cardiovascular exams. And our study actually is starting 2008 to 2010, and we select all these patients with all comprehensive cardiovascular evaluation with the clinical examination, echocardiogram and electrocardiogram, and then just the baseline for our patient population. And we follow them 10 years on average until 2018, 2019. Dr. Greg Hundley:           Very nice. So it sounded like from individuals in two regions of Brazil, identified those through screening of the blood, and I guess these were blood donors, and then performed a series of cardiovascular exams 2008 to 2010 and followed them for the next 10 years. And you're going to tell us about the results that occurred 2018 to 2019. And so what were those results? Dr. Maria Nunes:             We found that Trypanosoma cruzi seropositive is a risk factor for developing cardiomyopathy. Nowadays, this is still a risk factor, seropositive without cardiomyopathy at baseline has two times higher risk of developing cardiomyopathy compared to the seronegative controls. And we have also detected that the parasite load or the level of parasite in the blood expressed by antibodies against Trypanosoma cruzi is an important risk factor for disease progression. That means some patients have Chagas disease, but the level of antibodies is not too high. These patients go well. And other hand, the patients with high level antibodies means the parasite load may be higher too. This is the high risk of disease progression to cardiomyopathy or of dying too. Dr. Greg Hundley:           Very nice. And were there any subgroups of patients where you found these relationships to be particularly more striking? So for example, the elderly, or was there a discrepancy based on sex, men versus women? Dr. Maria Nunes:             Yes, other studies has already shown that the male gender is a risk factors in Chagas disease. Usually they progress more, they have more severe clinical presentation, usually die at the age between 30 and 50 years old, the most productive years of the life. That's why Chagas is so important here in Brazil and Argentina, in Latin America countries because people die at early ages. Dr. Greg Hundley:           And your results confirmed what was previously known in that regard. Dr. Maria Nunez:             Yes, patients with developing cardiomyopathy with heart failure has a high mortality rate. And then even patients with cardiomyopathy detected by exams like based on ECG or echo, they asymptomatic, but they progress more for dying or to develop cardiomyopathy compared to seronegative with similar risk effects for cardiovascular disease, such as hypertension, diabetes, smoking. Dr. Greg Hundley:           Very good. Well Ntobeko, you see many papers come across your desk as an Associate Editor for Circulation, and what attracted you to this paper and the results that Maria has described? Dr. Ntobeko Ntusi:          Thank you, Greg. I was attracted to this paper because it's an important natural history study of Chagas disease. But secondly, it's also one of the largest contemporaneous cohorts of Chagas disease which provides important insights and advances in our knowledge with regard to this clinical entity. And for me, there were three things that stood out. The first one was an important description of the outcomes of Chagas cardiomyopathy. The second was the contemporaneous description of the epidemiology in a well-characterized cohort. And the third and novel contribution was the description of the determinants of disease progression. So I thought overall, the really important contribution to the field. Dr. Greg Hundley:           Very good. And for those that might not live in the endemic area, but might occasionally encounter someone with Chagas disease, what results from this paper can we use to help manage patients in this situation? Dr. Ntobeko Ntusi:          Thanks, Greg. So this was a study which had a number of really positives. Firstly, it's a large study, it was non acute [inaudible 00:16:42] design and it used PCR for diagnosis. And unlike many other studies, also ascertained antibody levels and had very good clinical characterization, which included electrocardiographic, echocardiographic assessment, including serum assessment of proBNP and CK-MB. And all really important take home messages are for me. The first one is understanding that the relationship of your antibody levels and baseline LV function to mortality. In other words, are finding that in those with existing LV structural abnormalities, or higher levels of antibody titers, mortality was higher. The second important contribution is a description of the incidence of Trypanosoma cruzi, and this was highest as one would expect in the seropositive donors and much lower in seronegative donors. The third important contribution relates to our improved understanding of the determinants of disease progression, which were related to the Trypanosoma cruzi antibody levels. In other words, the higher your antibody titers, the quicker you progressed to manifest the cardiomyopathic phenotype. And then lastly, the predictors of mortality, which were related to your PCR being positive, as well as your antibody titers. Important is this contribution is there are a number of important caveats. The first is that the study is limited by the huge amount of loss to follow up, which as you can imagine, adds a number of biases to our conclusions. The second is that the observations may of course be confounded by comorbidity in particular because these patients are older and had higher comorbidity. The third is that we assume that the PCR positivity and antibody titers actually correlate with parasite pattern, but in fact, we know that is not always the case. And then lastly, for people who read this paper from non-endemic parts of the world, the result may not be clearly generalizable to those parts of the world. Dr. Greg Hundley:           Very nice. Well, we've had a great discussion, listeners. From Maria and Ntobeko sort of presenting the paper and then what are some of the take home messages. So now I'd like to go back to both of them and Maria, first you and then Ntobeko. Maria, what do you think is the next study to really be performed in this sphere of research? Dr. Maria Nunes:             We may should stratify patients with Chagas disease. Those who have high antibodies titers should refer to a kind of treatment or benznidazole treatment. We should intervene in this subgroup. Dr. Greg Hundley:           Very good. And Ntobeko, anything to add? Dr. Ntobeko Ntusi:          Yes, Greg, I think that there are two important next steps. The first one is that I think we need other large designed prospective studies that will validate the observations by Dr. Nunes and colleagues. And then the second key step for me would be the design of randomized controlled trials to test therapeutic agents with antitrypanosomal activity to demonstrate their ability to retard or completely block disease progression, which would be a nice way to complete the story. Dr. Greg Hundley:           Very nice. Well listeners, we've had a great discussion today and we want to thank Maria Nunes from Brazil and Ntobeko Ntusi from South Africa for bringing these really informative results pertaining to Chagas disease, and highlighting the natural history and showing an association between these high titer values and poor cardiovascular outcomes. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on The Run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.

Episode 73: Anticoagulation in Afib. When should you start anticoagulation in atrial fibrillation? What medications are appropriate? Virginia Bustamante, Charizza Besmanos and Dr Arreaza discuss this topic.  By Charizza Besmanos, MS4; Virginia Bustamante, MS4; and Hector Arreaza, MDCharizza: Hello, welcome to today's episode of Rio Bravo qWeek Podcast. My name is Charizza Besmanos, a 4th year medical student from American University of the Caribbean and I am joined here today by Virginia Bustamante.  Virginia: I'm Virginia Bustamante, an incoming 4th year medical student from Ross University.  Arreaza: And I'll be here just to make sure that you guys behave during this episode. Charizza: Before we get started on our discussion, I have a quick patient case to share with you.  This is a 66-year-old woman who is brought to the ED with sudden onset of severe difficulty speaking and weakness while having breakfast. She has hypertension, hyperlipidemia, severe left atrial enlargement seen on previous ECHO, and is noncompliant with her medications. She is a lifetime nonsmoker and does not drink alcohol. On admission, her blood pressure is 152/90 and pulse is 124/min and irregularly irregular. She is awake and alert but has difficulty finding words while trying to speak. She has severe right lower facial droop and marked weakness and sensory loss in the right arm and mild weakness in right leg. Fingerstick glucose is at 105. ECG shows atrial fibrillation. Acute stroke management is started right away. CT shows occlusion of the left MCA. What management could have prevented this complication?  Virginia: This patient clearly has multiple risk factors for thromboembolism events but given her irregularly irregular pulse consistent with atrial fibrillation, she would've warranted long-term anticoagulation to prevent stroke, which she most likely had.  Charizza: Exactly. Today's topic is atrial fibrillation, specifically the use of anticoagulation. __________________This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. __________________ Virginia: Anticoagulation is indicated to decrease the risk of thromboembolic events such as ischemic stroke in patients with atrial fibrillation (A-fib). Not all patients receive anticoagulation. Like most things in medicine, you must decide to start anticoagulation when the benefits of decreasing the risk of stroke outweighs the risk of bleeding. So, for assessing the risk of stroke in A-fib, the American College of Cardiology along with American Heart Association and the Heart Rhythm Society published a guideline in the Journal of the American College of Cardiology in 2014 and was recently updated in 2019[1] detailing in which patients anticoagulation is recommended.  Charizza: Yes, according to the guideline, “high risk patients” are all patients with valvular A-fib, and those with nonvalvular A-fib with a CHADVASC score of >/= 2 in men or >/= 3 in women, and those with nonvalvular Afib and hypertrophic cardiomyopathy. Those with “medium risk” are patients with nonvalvular Afib with CHAD2VASc score of 1 in men or 2 in women. In these patients, anticoagulation is considered but the risk and benefits are discussed with the patient. Those with “low risk” are patients with CHAD2VASc score of 0 in men or 1 in women and anticoagulation is not routinely recommended in these patients. Can you tell us briefly what CHA2DVASc score is?  Virginia: CHA2DS2-VASc score is the stroke risk assessment tool of choice by the AHA/ACC/HRS guideline. It is great because it is a mnemonic. Each letter is assignment 1 point except for 2 criteria. C stands for congestive heart failure, H for HTN defined as >140/90, A2 is for or Age>75 which is for 2 points, D for diabetes, S2 is for stroke or TIA and it's for 2 points, V for vascular disease such as MI, A for age 65-74, S for female sex.  Charizza: That certainly makes it easy to remember. Not only that, but you can also find CHA2DS2-VASc score of MDCalc to make it even easier. Virginia: Now that we've established which patients should receive anticoagulation, how do we choose which anticoagulant?  Charizza: For this discussion today, I would like to focus on nonpregnant patients. There really are 2 main anticoagulants, DOACs (or the direct oral anticoagulants) and warfarin. DOACs are the direct thrombin INH (dabigatran) and the direct factor Xa INH (rivaroxaban, apixaban, and edoxaban). DOAC is recommended as first-line in the long-term management of nonvalvular afib as trials have shown DOACs are more successful at reducing risk of thromboembolic events and have a lower risk of bleeding than warfarin and warfarin requires INR monitoring with dose adjustments. Although, in patients with valvular Afib, warfarin is preferred. Arreaza: All of them are by mouth.  Virginia: Dosing of DOACs depends on the kidney function, so it is important to obtain the creatinine clearance. For dabigatran, the direct thrombin INH, the recommended dose for patients with CrCl >30 mL/min is 150mg PO twice daily based on the results from the RE-LY trial (2), which evaluated the efficacy and safety of dabigatran with warfarin in patients with Afib. For patients with CrCl of 15-30 mL/min, the recommended dose is 75mg PO BID. Those with CrCl 1.5, patient who is > 80years old or body weight

Please join author Ole Fröbert and Associate Editor Dharam Kumbhani as they discuss the article "Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center in Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, associate editor, director of the Poly Heart Center at VCU health in Richmond, Virginia. Well, listeners, this week we've got a really hot feature topic pertaining to flu vaccines, which are coming in the US, North America, South America, coming up soon, and their relationship to myocardial infarction. But before we get to that feature discussion, let's grab a cup of coffee and jump in to some of the other articles in this issue. Oh, wait a minute. Our first article, we've got a co-author here. Carolyn, something about the VICTORIA trial, which you were a part of. Can you tell us a little bit about this? Dr. Carolyn Lam: I would love to, and first of all, I'm doing this on behalf of a big team, and I want to really, really call up first Dr. Paul Armstrong who's the senior author from University of Alberta. But let me tell you first about the VICTORIA study. VICTORIA evaluated vericiguat, a soluble guanylate cyclase stimulator, compared to placebo, in patients with heart failure with reduced ejection fraction with a recent worsening heart failure event and the primary result was actually a significant reduction in the primary composite outcome of cardiovascular death or heart failure hospitalization with vericiguat compared to placebo. Dr. Carolyn Lam: Now, interestingly though, in VICTORIA, we found that anemia occurred more often in patients treated with vericiguat at a rate of about 7.6% compared to placebo, which was 5.7%. Now, although earlier studies of another soluble guanylate cyclase stimulator like riociguat was found to be associated with anemia. The etiology really remains unknown. In the current paper, we explored the relationship between markers of anemia and vericiguat versus placebo in VICTORIA. We further explored the changes in hemoglobin and hematocrit over the course of the trial and their relationships with the primary composite outcome. Dr. Greg Hundley: Carolyn, this is such an important new study heart failure therapy for those with reduced ejection fraction, and again, an important topic related to anemia. What did they find? Dr. Carolyn Lam: Thanks, Greg. First, approximately a third of patients in VICTORIA had anemia at randomization, and this is using the standard sex-based definitions. With a lower hemoglobin indeed predicting a higher risk for cardiovascular death, heart failure hospitalization, all-cause mortality. As I had already mentioned, we found more anemia with vericiguat than with placebo. The interesting thing though is after 16 weeks, no further decline in hemoglobin occurred over the remaining and over 96 weeks of follow up, and the ratio of hemoglobin to hematocrit remained constant. Now, overall, the adverse event of anemia occurred in 7.1% of the patients. Dr. Carolyn Lam: Importantly, the lower hemoglobin was not related to the beneficial effect of vericiguat over placebo on the primary outcome. Now, I know all of that may be more descriptive and reassuring than really understanding the mechanism by which it occurred. Further mechanistic studies are certainly warranted to better understand the basis of the anemia development, and it's of principle importance because as you said, vericiguat I think it's going to be an important new medication that we can consider in high-risk patients with recent worsening heart failure with reduced ejection fraction. Dr. Greg Hundley: Thanks so much, Carolyn, especially the perspective of being an author on this particular study. Well, Carolyn, my next study is going to come to us from Dr. Zhao Wang from University of Texas Southwestern Medical Center, and it's really about the integrated stress response, and that's an evolutionary conserved process to cope with intracellular and extracellular disturbances. Myocardial infarction is a leading cause of death worldwide. Coronary artery perfusion is the most effective means to mitigate cardiac damage resulting from myocardial infarction. However, that can cause, as we know, additional reperfusion injury. This study aim to investigate the role of the integrated stress response in myocardial ischemia reperfusion injury. Dr. Carolyn Lam: Oh, very interesting. What were the results? Dr. Greg Hundley: Right, Carolyn. The authors found that the integrated stress response is activated by ischemia reperfusion injury in the heart, and the perk branch of the integrated stress response protects the heart from ischemia reperfusion injury through inhibition of protein synthesis. Also, Carolyn, mitochondrial complex proteins are selectively suppressed and oxidative stress is reduced by the integrated stress response. Carolyn, the takeaway is that this integrated stress response is cardioprotective against cardiac ischemia reperfusion injury. Perhaps pharmacological stimulation of the integrated stress response at reperfusion, well, that may reduce heart damage and improve cardiac outcomes after ischemia reperfusion injury. Dr. Carolyn Lam: Cool. Thanks, Greg. Well, I've got one more paper, and this deals with coronary microcircuitry dysfunction and acute rejection after heart transplantation. Co-corresponding authors, Doctors Lee and Choi from Heart Vascular Stroke Institute in Samsung Medical Center sought to evaluate the prognostic implications of coronary microcircuitry dysfunction assessed by the index of microcircuitry resistance or IMR for the risk of acute cellular rejection after heart transplantation. They did this by prospectively enrolling 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment one month after transplantation.   Dr. Greg Hundley: Very interesting, Carolyn. What did they find here? Dr. Carolyn Lam: IMR measured early after heart transplantation was significantly associated with the risk of acute cellular rejection, and an IMR above or at 15 was highly predictive for the recurrence of acute cellular rejection during two years of follow up following heart transplantation. Adding IMR to the prediction model with clinical variables significantly increase discriminant and reclassification ability for the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, the implications are that early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation, and this is discussed in an editorial by Doctors Fearon and Valentine from Stanford University. Dr. Greg Hundley: Very nice, Carolyn. Dr. Carolyn Lam: Great. Greg, before we go to the exciting feature discussion, let's round it up by just a quick tour of what else there is in today's issue. There is an exchange of letters between Doctors Pappone Leor on atrial fibrillation as a cardiomyopathy, global rounds on United Kingdom by Dr. Cowie, an ECG challenge by Dr. Tsai on grouped beating following acute inferior myocardial infarction, and a research letter by Dr. Salem on electrocardiographic manifestations of immune checkpoint inhibitor myocarditis. Dr. Greg Hundley: Great, Carolyn. Well, I can't wait to get to this next feature discussion and learn a little bit more about the relationship between flu vaccines and future myocardial infarction. Dr. Carolyn Lam: Today's feature discussion was a really hot topic at the ESC 2021, and in fact, a simultaneous publication. It is about influenza vaccination after myocardial infarction, a very important topic and a very novel paper. We are so pleased to have the first and corresponding author, Dr. Ole Fröbert from Orebro University in Sweden to discuss this paper, as well as our associate editor, Dr. Dharam Kumbhani, from UT Southwestern. Welcome, gentlemen. Only if I could start with asking you to describe the rationale for why you did this study, and then perhaps quickly summarize the results. Dr. Ole Fröbert: Yeah, thank you so much, Carolyn. The background of the study was that during influenza epidemics, more people die from cardiovascular causes, and out in the literature, there are numerous observational studies suggesting a protective effect from influenza vaccination on cardiovascular events. There are also three smaller single-center randomized trials supporting these registered findings. Currently influenza vaccination carries a Class I, Level of Evidence B recommendation in both American and European secondary prevention guidelines, but uptake is low and vaccination timing is unclarified. Our aim was to determine whether influenza vaccination improves clinical outcomes in patients with a recent myocardial infarction or with high risk corona artery disease. Dr. Ole Fröbert: The study was international, multi-centers investigator initiated, double-blind randomized control trial, and we enrolled patients at 30 centers across eight countries in both the Northern and the Southern Hemisphere, Sweden, Denmark, Norway, Latvia, Scotland, Czech Republic, Bangladesh and Australia. We enrolled patients between October 2016 and March 2020. We had quite broad inclusion criteria. We included hospitalized patients with STEMI or non-STEMI, or high-risk stable patients over 75 years of age undergoing an angio or PCI. We excluded patients already vaccinated or intending to be vaccinated during the current season. We also included, of course, patients if they had allergy to X or influenza vaccine, if they had infection or if they were immunosuppressed or previously randomized in the trial. Dr. Ole Fröbert: Over these four years of inclusion, we enrolled a total of 2,571 participants. The primary outcome was a composite of all-cause death, MI and stent thrombosis. This outcome occurred in 67 participants assigned influenza vaccine and 91 assigned placebo corresponding to a reduction of the primary endpoint of 28% with a P value of 0.04. Also, rates of all-cause death and of cardiovascular death were reduced and both with a hazard ratio of 0.59 corresponding to a reduction of 41% in all-cause death and cardiovascular death. Based on these results, we think that this trial and what we know from previous smaller trials should be sufficient to establish influenza vaccination as a new standard of care as part of in-hospital treatment after an MI. Dr. Carolyn Lam: Heartfelt congratulations, Ole. What an elegant intervention in a very frankly challenging situation that the trial obviously carried on through COVID as well, multinational. May I just double check? Was it investigator-led? Because- Dr. Ole Fröbert: Yes, this was- Dr. Carolyn Lam: That's amazing. Dr. Ole Fröbert: ... an idea that just popped up, and then yeah, we did it, but it was seven years of work. Dr. Carolyn Lam: Wow. Hard work as I can just imagine. First, heartfelt congratulations. Very impactful results. Dharam, could I invite you to put those results in context and why we single this out? Dr. Dharam Kumbhani: Yeah. No, thank you, Carolyn. Ole, I want to amplify or recapitulate the amazement and wonder that Carolyn just articulated. I think this is a huge endeavor. It's a very important topic. It's "a fairly simple intervention." It's vaccination, and you've just really shown that even in the acute setting, that A, this is as feasible, B, it is safe, and three, it is effective. I think it's potentially ... Given the magnitude of influenza in the world, I think this has tremendous public health ramifications. I really want to congratulate you and your investigators for pursuing this important question and then just executing this, I'm sure despite multiple challenges over a long period of time. Dr. Ole Fröbert: Thank you very much. Dr. Dharam Kumbhani: Yeah, no. I guess you already alluded to the fact that this may influence guidelines. As you mentioned, it's a 1B. Maybe get your thoughts, I suppose this may move the needle towards becoming perhaps a little stronger on the recommendation front, both in the US and the European guidelines? Dr. Ole Fröbert: Yeah. I think what has been the challenge until now is that many places, of course, you commend patients to take a flu jab when treatment is over in the hospital. But then the responsibility is diffused. Who should take care of that? Is that up to the patient or the primary care physician? Who is in charge? One important finding of this study is, as you said, it's safe. There were no differences, adverse events between the two groups. It's safe and it could be given early. I think a take-home factor from the study is that it should be given at the hospital and it's a responsibility of the cardiologist. Dr. Dharam Kumbhani: Yeah, I really like that. Actually, I'm sure this would resonate across the board in the cardiology community. We've taken ownership for starting from statin and now SGLT-2 inhibitors, which kind of ... All of these medications have come from non-cardiology realms, so to say. But now we prescribe those medications. We know they have clear cardiovascular benefits. I suppose you could make a case to say we, the cardiology community, has to adopt this. The implementation gap that exists for a lot of these therapies, that also comes to us and for us to move that forward. It's thought provoking. I certainly felt very strongly after your study. I don't know how you feel about that. We should really be the ones driving this and help with more widespread immunization in these patients. Dr. Ole Fröbert: I think because not just this study, but also the previous studies and what we know from observational findings is that this is safe and it works. What we also saw in our study, and it has been indicated in previous meta analysis, is that the maximum effect is seen in the acute setting. It's the acute coronary syndrome patients, the patients we had in our study, that benefit the most. That's also a case for actually doing this in the hospital and not postponing it. Dr. Carolyn Lam: Wow. That's amazing. Ole, I do have one question. Just for clarification. You were careful to say that you did this during influenza seasons, right? Coming from my part of the world in Singapore where we don't really have influenza seasons, don't have any seasons, frankly, what would you think? What would you advise? Dr. Ole Fröbert: There is influenza seasons in all parts of the world, I'm sorry. Dr. Carolyn Lam: True. Dr. Ole Fröbert: For example, we had Bangladesh on board in our study. It's in the Northern Hemisphere, but influenza-wise, it's in the Southern, and their season is between May and September. But it's not as clearly defined as the Northern Hemisphere season. It's almost always in two waves during that season. One practical challenge with influenza vaccine is that it's produced for the seasons. It's difficult to say, "Yeah, we can just do it all year round," and also we didn't test that. I, of course, feel we should give it all year round, but it's not available, the vaccine. Perhaps it should be tested, but it is probably difficult to find funding for such a study. Dr. Carolyn Lam: Very fair, and thanks for the correction. It's true though. Singapore's on the Equator, so we don't have maybe weather seasons. But yeah, we do get vaccinated for both North and South. It's quite fascinating. But nonetheless, could I now switch topics a little bit and just over the next couple of minutes just ask you, could you please perhaps share with the audience what it was like to work with Circulation, to do this simultaneous publication? You see, our associate editor, Dharam Kumbhani, really leads this effort to get simultaneous a fast-track publication from major conferences, and it means a lot to us that investigators like you chose us. Could you share a bit? Dr. Ole Fröbert: Yeah, thank you very much. Overall, it was a pleasure. Of course, we were ... With every study of this size, you are under stress, you get the results late, and there's a conference coming up, and you would like your paper to come out at the same time across to maximize impact and attention. What I really like with working with Circulation was turnaround time was ultra fast, really extremely fast. Of course, we had a lot of questions to our study, but these were ... Some of them of course were quite difficult, but they were fair. In a way, they were also helpful in a way that made it easier to address the questions in a more, you could say, collaborative way. It was very smooth. No hiccups. Dr. Carolyn Lam: Thank you. Dharam, any final responses to that? Dr. Dharam Kumbhani: No, thank you, Carolyn. Yeah. Well, Ole, it was really a pleasure to work with you on this. I think we all recognize that this was an important study and wanted to make sure that we were able to accomplish the goal of simultaneous publication. Thank you for working with us on that. I just want to put a pitch in, I think this, for Joe, Dr. Hill and the rest of the editorial team, having a robust simultaneous publication program has been very, very important. We are very committed to working with investigators and authors on this. We are really blessed with our team on the backside that works seamlessly with us nights, weekends, just to get these things done. I just want to end with that to say this is very important for us, and we look forward to the opportunity to work with Ole and others on future papers as well.   Dr. Carolyn Lam: I love that. Thank you both for being on this podcast today. Today I want to especially call out David Rivera, a wonderful managing editor who really, really is part of leading this entire group that supports us, but also even this very podcast. You've been listening to Circulation on the Run. Thank you, from both Greg and I, for joining us today, and don't forget to tune in again next week. Thank you. Dr. Greg Hundley: This program is copyright of the American Heart Association 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.

Many of us wear wireless, battery-powered medical sensors on our wrists in the form of our smartwatches or fitness trackers. But someday soon, similar sensors may be woven into our very clothing. Harry's guest this week, Nanowear CEO Venk Varadan, explains that his company's microscopic nanosensors, when embedded in fabric and worn against the skin, can pick up electrical changes that reveal heart rate, heart rhythms, respiration rate, and physical activity and relay the information to doctors in real time. And that kind of technology could move us one step closer to a world where we're far more intimately connected to the medical system and doctors can catch health problems before they turn into disasters.Nanowear's leading product is a sash called SimpleSense that fits over the shoulder and around the torso. Last month the company won FDA approval for the software package that goes with the SimpleSense sash and turns it into a diagnostic and predictive device. It's currently being tested in a network of clinics as a way to monitor and manage congestive heart failure.Varadan trained in biochemistry at Duke, earned an MBA at Columbia, and spent about a decade in pharmaceutical sales and marketing and technology investment banking before co-founding Brooklyn, NY-based Nanowear in 2014. His father Vijay Varadan, MD, PhD, now an emeritus professor in the Department of Engineering Science and Mechanics at Penn State, is the other co-founder and the company's chief innovation officer. "Nanowear's technology was actually the culmination of his life's work," Venk says.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.Full TranscriptHarry Glorikian: Hello. I'm Harry Glorikian. Welcome to The Harry Glorikian Show, the interview podcast that explores how technology is changing everything we know about healthcare.Artificial intelligence. Big data. Predictive analytics. In fields like these, breakthroughs are happening way faster than most people realize. If you want to be proactive about your own health and the health of your loved ones, you'll need to learn everything you can about how medicine is changing and how you can take advantage of all the new options.Explaining this approaching world is the mission of my new book, The Future You. And it's also our theme here on the show, where we bring you conversations with the innovators, caregivers, and patient advocateswho are transforming the healthcare system and working to push it in positive directions.Everyone's used to the idea that if they're being treated in a hospital, they'll probably get wired up to sensors that track their heart rate or respiration rate or blood oxygen level.We've talked on the show before about a new generation of portable medical sensors for everyday life, like continuous glucose monitors for people with diabetes.And some people even wear medical sensors on their wrists in the form of their Fitbit or Apple Watch. Some of these devices can go beyond fitness monitoring to alert wearers to problems like cardiac arrhythmia.But what if medical sensors were woven into your very clothing? My guest this week is Venk Varadan, and he's the CEO and co-founder of a company called Nanowear that's taken a big step in that direction. Nanowear has developed a way to put microscopic nanosensors inside clothes .If that cloth is worn against the skin, it can pick up electrical changes that reveal heart rate, heart rhythms, respiration rate, and physical activity and relay the information to doctors in real time. Nanowear's leading product is a sash called SimpleSense that fits over the shoulder and around the torso. And last month the company won FDA approval for the software package that goes with the SimpleSense sash and turns it into a diagnostic and predictive device.But Varadan says that in the future the nanosensors and the software could be put into even more places, like headbands, conventional clothing, or bed sheets. That's just one example of the explosion in mobile health technology that's putting more power into the hands of patients. And it's also one of the topics in my book The Future You, which is available now in Kindle ebook format. You can get your copy by going to Amazon.com and searching for "The Future You," by Harry Glorikian. The book grows partly out of conversations like the ones I have here on the podcast with medical researchers and entrepreneurs. But it goes even deeper into the impact of wearable sensors, AI, and so many other technologies that have the potential to help us live longer, healthier lives. So I hope you'll check it out.And now on to my conversation with Venk Varadan.Harry Glorikian: Venk, welcome to the show.Venk Varadan: Thank you, Harry.Harry Glorikian: So, look, we all know that with with technology startups, there's always this sort of chicken and the egg question what what came first in the mind of the inventors: the market need or the product that needs to address it. You know, ideally they come together simultaneously and there's a back and forth dialogue between founders and potential customers. And you end up with what the startup community calls--what is it?--product-market fit, if I talk to my, you know, my Silicon Valley nephew of mine. So in the case of Nanowear, you know, did you start to think about the problem and how to solve it? Or did you start out with the technology? Which in your case involves a way to embed these tiny nano-pillar sensors into cloth and then look at ways to make it sellable. So which one was it for you?Venk Varadan: Great question, Harry, and again, thanks for having me on the podcast. We were squarely the latter and I think most entrepreneurs are the former. But we had this great advanced material, a cloth based nanotechnology that could pick up really, really high fidelity clinical grade biomarker data off the body. And we didn't really know what to do with it. Do we start as a consumer company? Work on fitness, B2B, sports? Do we think about industrial safety, military use cases? They've been trying to figure out smart textiles forever. Or do we go into health care? And I think stubbornly so, and a little bit of altruism, we chose the harder route, which was health care. But I think it was probably more premised on that we believed in the quality of the sensor. It was doing something from a quality and quantity standpoint that no other on body sensor or non-invasive sensor out there could do, whether it was consumer grade off the shelf or health care based electrodes. So all we really knew when we started is that we wanted to be a health care company, but we didn't know the right application to start with.Harry Glorikian: Yeah, I was going to say, let's, let's pick the hardest one and see if we can get over that hill. So let's back up here and talk about like the medical need you're trying to address. I mean, at a high level, why is portable diagnostic sensing so important for people's health?Venk Varadan: I think it was always important because of an access issue, right? Not everybody can go see a physician or can do high cost diagnostic tests that require a facility or diagnostic tools in person. And there's a cost even to running a blood pressure cuff or checking your heart with a stethoscope or running a hemodynamic monitor, all the way up to more expensive tests like sleep studies and sleep labs. So I think it started, remote diagnostic needs started with an access issue, and it's not like we haven't had telemedicine in the past. But even that was sort of limited due to access issues. You needed a broadband network, you needed particular devices, you needed smartphones, and there were a lot of industry, I guess, pressures holding this sort of need to sort of push health care out into the more wide stream for those that have access issues. And we all said that this was going to happen one day. Virtual care, telemedicine, remote monitoring at home, replacing offices at home. And it was a nice sound bite. And COVID kind of forced the issue and I think completely accelerated that 10 year frame on the need, right? Because folks were still sick. Folks still have chronic disease. Folks still needed acute procedures. But you weren't really able to do a lot before, during and after, if you had to have these people camped out in the hospital or in outpatient clinics or acute surgical centers. So that's when while everybody thought it was cool and one day I'll employ these digital technologies, it really took COVID to shut their business down or they didn't have any patients, to force them to adopt. So I think a lot of our, companies like us, we were all doing the right thing. And we also are the first to admit that we got fortunate that the pandemic sort of accelerated the need for our solutions.Harry Glorikian: Yeah, I mean, I remember I put together, god, it's got to be like 15 plus years ago, I put together a distributed diagnostics conference, because I was like, "This is going to happen." And, well, OK, eventually. But so let's talk about, let's step back for a minute and talk about some of the specific medical conditions where continuous, high resolution, high fidelity data is useful. Like, I know we need to probably start with congestive heart failure.Venk Varadan: Yes, so that's where we actually started before COVID. That was the sort of market need where our technology, our ability to sort of simultaneously and synchronously look at biomarkers from the heart, from the lungs, the upper vascular system in a sort of contiguous way and sort of map the trends over the same period of time as you would with a stethoscope or blood pressure cuff and electrocardiogram or hemodynamic monitor if they were all in one platform. That's really what we're replacing as part of our solution and our device-enabled platform. But the economics of heart failure and the business need were really what was pulling us there in the sense that there were penalties from CMS to avoid that next hospitalization within 30 days. And many of these patients are, one in four are being readmitted within 30 days. One in two are readmitted within six months. So this isn't a problem that we can just medicate our way out of. We have to understand when decompensation of the heart is happening before symptoms show up, because once symptom show up in fluids accumulating in their lungs, it's already too late. So I think there was a good product need for us, as well as the economic need with reimbursement and solutions for something that can be done outside the body that a patient could be be using at home.Venk Varadan: And then I think, you know, COVID hit and the market applications really just exploded beyond heart failure. Heart failure is still on our roadmap. Our clinical study to prove that ALERT algorithm of, we take all these data points, send it into the cloud, do a risk based predictive algorithm to predict worsening heart failure or decompensated heart failure weeks before fluid accumulates in the lungs. That's still firmly on our roadmap. We've just got to restart the study that was halted due to COVID. But the same product that does the same parameters with a different sort of algorithmic use cases opened up a lot of other applications that now have a business need and economic need to use us. So the two that we're starting with is pos-procedural or post-surgical follow up in an acute use case setting. And the second is outpatient cardiology longitudinal care for someone who unfortunately probably has to see a cardiologist for the rest of their life.Harry Glorikian: And if I'm not mistaken, congratulations are in order because of an FDA approval.Venk Varadan: Yes, so we actually got our third 510K just two days ago. September 21st, sorry, September 22nd, we got our third 510K. This is actually an example of our of our first digital-only clearance. So our first two clearances, our first clearance in 2016 was primarily around the advanced material, the nanotechnology, to get FDA comfortable in its safety and efficacy profile. The second was for our product, which is the SimpleSense shoulder sash, which simultaneously and synchronously captures data across the heart, lung and upper vascular system biomarkers, feeds that data through a mobile application and into the cloud. And then this clearance is sort of for an end-to-end digital infrastructure that circularly includes ingestion of our 85 biomarkers and then analytics circularly across our spectrum that continues to sort of process and then has the ability to push insights or algorithmic alerts down. So that last part is not included. But if you think about it, Harry, we kind of had a strategy before we got to the AI part. Now everything we submit with FDA has nothing to do with the device, has nothing to do with software infrastructure, has nothing to do with what would be MDDS or what wouldn't be. We can simply send in statistical analysis on the AI algorithms based on the inputs that we've already cleared and then looking retroactively on the outcomes. So it was it's a nice win for us to kind of show that we're not a device company, we're a device-enabled platform. But I think what it's really exciting the market on is that we're ready for AI diagnostics. We hope to have a first one and our fourth 510K, I guess here with FDA pretty soon in the complex chronic disease state. So really exciting times for us.Harry Glorikian: Yeah. And I mean, as an investor, I mean, I, you know, I've been in diagnostics forever and I, you know, I'm so focused on Where's the data? Show me the exponential nature of the data and then what we can do with it and really like blow that up, right? That's where I see the value in these platforms and technologies. But there are technically other methods that had been used, right, that you might say you might or might not say are competitive in some way. But one of them is called a Holter monitor, right? Which people put on their skin to monitor, you know, electrocardiogram and EKG rhythms outside the hospital. And I don't want to say the name wrong, but I think it's SimpleECG for yours and then the SimpleSense vest, [how does it] compare to that. What are the alternatives? How long do you wear it and how do you compare it to the existing status quo?Venk Varadan: Sure. So, you know, a Holter monitor has a specific use case. It's looking at your electrocardiogram rhythm to see if you have a rhythm or abnormality, right? So we one of the metrics we capture is an electrocardiograph, right, and we do multiple channels of that. So it's not a single lead. So we could certainly compete against that application and just look at rhythm abnormalities in the same way. Companies like iRhythm have that, and Apple Watch has that 30 second feature on it. We are not playing in that space. And the difference between us, even though our signal quality, we would argue, is much cleaner than a Holter monitor that's using standard electrocardiographs, with those you have to shave your chest, you have to stand the dead skin down. You have to put gel on for the electrode to get a conductive signal. We don't have to do any of that because of the nanotechnology. But what the nanotechnology also affords, in addition to a better experience and better quality, is the ability to do more than just a Holter monitor, right? So imagine if that same Holter monitor wasn't just looking at rhythm abnormalities, it was also looking at the acoustics of your heart and your lungs, the sounds of your heart in your lungs. It was looking at the flow characteristics. The blood injection times, the fluid accumulation in your lungs. It was looking at your breathing rate, your breath per minute, your lung capacity, your changes in lung capacity over time, if it was looking at your pressure related issues at the aorta, systolic and diastolic blood pressure. In addition to being a better experience in all of these and sort of kind of replacing a Holter monitor and a stethoscope and what have you, the real value is being able to do all of that at the same period of time over the same period of time. So even if I'm monitoring for, our use cases are about 30 minutes to an hour in the morning, 30 minutes or at night. And because we're getting such dense quality and quantity of data over that time period, we can actually see trends across the cardiopulmonary and upper vascular complex, which is actually the first company and platform that can do that. And that may not have been important before COVID. But COVID, I think, was revelatory in the sense that COVID may have started as a respiratory disease, but it affects the heart. It affects the upper vascular system. You can get a DVT from it. And I think it opened the world's eyes into understanding. We're not looking at all of these systems, the heart-lungs-upper-vascular system that all work together and work uniquely in each of our own bodies. We're only getting a risk based signature on just cardiac rhythm or just breaths per minute or just the sound murmurs of your heart, whereas we're doing it now.Harry Glorikian: Yeah. So for a guy like me, like, I'm like, Oh my god, how do I get one of these? I want one of these right now. I'm thinking like, Oh, I could use it right after I work out. And I'm, you know, forget the I'm sick part of it. I want to use it as a wellness monitoring and sort of to see, get a baseline. Tell me where I'm going, right, over time. That's what I'm always discussing with my my physician is we need a baseline because I don't know how it's going to change over time. If I only look at it at that point in the future, I don't know what it was. So, but the other side, I think to myself, there are physicians listening to this show that are probably all excited about this. And there are physicians going, "That's a lot of different data points. How in the hell am I going to make sense of that?" And so I'm I'm assuming what you're going to tell me is you've got this amazing software that lets you visualize, you know, and make sense of all these different parameters together.Venk Varadan: And that's exactly right. You know, we were actually stubbornly annoying to our KOLs, our clinical teams, as well as our original customers in beta rollouts, because Harry, we agreed with you. We looked at where Gen 1 and Gen 2 sort of digital health companies struggled in health care. Health and wellness is a little bit different right? I mean, to each their own, right. I mean, if you market well, you'll find that pocket of people that want to be overwhelmed with data or what have you. But we really listened to what digital health was doing for the provider and patient relationship. There were some good things there and there were other bad things, and the bad things we realized actually wasn't monolithic between clinics. Some people thought that bad things were "I'm alerted too often." Others wanted to be alerted all the time. Some were like, "This is noisy data. It's too unclean." Others were saying, "I just need, you know, 70 percent C-minus level data," right? And then we were thinking about all of those aspects which we couldn't get consensus on. How do you bring all of those aspects that gives control to the provider so the provider can say, how often are they alerted, how much data and the raw signals do I want to look at, how much do I not want to look at? And really, with the thesis of building the platform on them, spending less time than what they do before? Because I think Gen 1 and Gen 2 products unfortunately actually added more time in adjudication and frequency of the provider being notified, and also cause some anxiety for patients as well because they were looking at their screen and their data at all times.Venk Varadan: So we really tried to be sponges of all of those different devices that were tech enabled and sort of moving from hundred-year-old devices to now Gen 1, Gen 2, pushing into the cloud. And really listened on... And I'll tell you, it was mostly from staff. It wasn't necessarily from the physicians and the surgeons themselves. It was mostly from triage nurse, from health care staff, the people that are running around coordinating the follow up visits, coordinating the phone calls from patients that were doing poorly or feeling bad after feeling sick after a procedure. And I just think we just kept our ears open and didn't go in saying, we know what you need. We were asking, What do you?Harry Glorikian: All right, so let's talk about the technology itself, the  SimpleSense wearable sash. How does the cloth sensor in the garment work? I mean, on a microscopic level, what are the kind of changes that this nano pillar detects and how?Venk Varadan: Yeah, so not to get to sort of, you know, granular into the physics, although I'm happy to Harry, if you if your audience ends up sending me some questions. But think about our ability to just detect a difference in potential action potential from point A to point B. And it's an oversimplified way of describing what we do, but the reason we can do it better than anybody else with any other sensor -- and that's what really feeds the cleanliness and the quality of our data and allows us to derive so many biomarkers that other others can't, which obviously feeds the ability for AI -- is because we've got these billions of vertically standing nano sensors per centimeter of surface area. The differential or the potential difference that we can find because our signal quality so clean is so narrow. Whereas other sensors that might be treated as noise, we can consistently see deltas from point A to point B and know exactly what caused those deltas, right? And that's unique to us and our vector orientation. And it's probably a little too wonky here, but if you have a vector across the largest slice of the heart, across the largest slice of the lungs, across the upper vascular system in its entirety, with that finite ability to get really microscopic level changes in potential, irrespective of what signal you're looking at. Because once you we know what signal we're looking for, we just set the frequency bands for those, right? Right. And that's really, in a nutshell, how it works across the multiple parameters that we can capture from a biomarker standpoint.Harry Glorikian: So you said 85 biomarkers, right? We're not going to go through all of them because we'll be at the end of the show. But what are the kinds of, let's say, physiological data that you're pulling in and that you're differentiating on?Venk Varadan: Sure. So I probably summarize it into several different buckets that each have maybe 20 or 30 derivatives under it. But, you know, cardiopulmonary biomarkers. So the coupling between the cardio and pulmonary complexes, impedance cardiography, thoracic impedance and then looking at not only the means and the median trends across those metrics, but the standard deviation. So one of our board members famously said, Nadim Yared, the CEO of CVRx, You will learn so much more from the standard deviations than you will from the trends. Don't just look at the sort of the trend. So that's an example. Cardiopulmonary: We look at the electrical signals of the cardio complex and electrocardiographs. We look at a combinatorial methodology of cardiographs, acoustics, BMI, height and weight. And then we tie activity, posture, movement. What is your sleep orientation? Are you sleeping on your left side? Are you sleeping on your right side? All of these sort of things together actually enable some really interesting insights from a machine learning standpoint. And again, the beauty of our ability to sort of understand them and see more biomarkers. Eighty-five is where what we know right now, what we've validated. There's probably a lot more that we will discover under certain disease states. But what we're able to sort of mesh together from all of those are really cool aspects like blood ejection times. That's not a physical, raw metric we're getting. That's a derived metric and combining a lot of these aspects cardiac output, stroke volume, you know, these are things that could only have previously been done with an arterial line in your body and in a hospital system. So I don't know if that answers your question.Harry Glorikian: Well, no. I mean, listen, I mean, this is why I invest in this space because, you know, theoretically, as I get older, I may be a patient and you know, the better these technologies get, the better off I'm going to be. But so let's talk about for a second, where did where did this originate from? And I think your dad, your father had something to do with this, if my research is correct.Venk Varadan: He sure did. This may be a little bit of a long winded answer, Harry. But but for your audience, I'll tell the story because it's important for dad to be happy at all times, even though I'm 40 years old. So, Dr. Vijay Vardhan is our co-founder and Chief Innovation Officer. My father, 40 plus year academic researcher in the fields of materials, research and biomedical engineering and this was actually, Nanowear's core technology was actually a culmination of his life's work. Back in the 80s and the 90s when I was still a young pup and he was convincing me to go be a doctor, he was doing research in this field, and it wasn't even called nanotechnology back then. There wasn't a term for it, but he was doing defense related projects in the ability to detect very minute signals at very, very, very, very difficult detect detection environment. So an example is submarine coating, right? Submarines when they're below water are picking up their external environment information through sonar. The deeper they get in the ocean, the harder that sonar frequency is to be able to differentiate. Is that a a school of plankton? Is that a whale? Is that a thermal geyser that's sending me the signal? Or is it a Russian sub, right? And his thesis was, if I have a really big footprint of sensors and exponentially higher surface area of sensors and not just one sensor or two or one hundred but billions across the hull, I can start to differentiate over time the nuanced differences between the sonar a whale emits, the sonar a thermal geyser emits, or oh, by the way, what are our friends in the USSR emitting, right? And that's an example in really, really hard to detect environments. He did the same with observatory jets and missile defense systems at 75,000 feet, you know, the opposite, very high frequencies at very high speeds. So that original thesis, the human body is also a very complex environment and hard to detect environment as well, right? So long story short, he kind of took that same thesis over many years of playing around in the lab and publishing papers and doing great work for our government and our Department of Defense, but also with an eye to the future on what could this do in the human body one day?Harry Glorikian: Right. Well, that's great. I mean, it's I'm sure he's very happy that you two are working together to bring this to market.Venk Varadan: He's not as disappointed in me about not going to med school anymore. Let's put it that way.Harry Glorikian: Yeah. Keeping parents happy is is a is a difficult thing. I know many people are like, Are you going to be a doctor or are you going to be a lawyer? You know, I know the I know the joke. So you've got FDA approval for a number of, as you said, you're building on top of, this layering that you've been doing from an FDA approval standpoint. What did it take to get them to sign off? What sort of evidence did they need to see?Venk Varadan: Yeah, it's a great question. I think that we kind of had to create our own playbook with them. I'm sure if they're listening, they don't want to hear this because you're not supposed to sort of commend and compliment the agency. They're just supposed to be there as sort of the gatekeepers. But we used to hear just a lot of horror stories like, "Oh man, you know, working with the agency, it's really tough. You know, they're really tough on this." I mean, we always looked at them as our partners, you know, we were bringing a novel technology to the world. We chose to go into a regulated environment because we believed in the promise of saving patients. We were not taking a sort of anti-regulation attitude that I can fix this, government get out of my way. I'm a patient first. I like living in a country with FDA where something is scrutinized that I have to take when I'm sick. And I think that attitude and going into it from us as a product and R&D team, first of all, helped in clarifying our understanding of FDA's processes because it's a lot, and you really need to dig through the guidance in that. But I would say this is really hats off, Harry, to our founding engineers. I mean, they went from being engineers to really understanding process, and that's really what FDA is. Our first clients we met with, we went down to Washington 11 times in person to demo to ask questions continuously. And "Hey, we read this part of the guidance. Does this make sense for us?" And we shut up and listened when we didn't agree with them. We said, "But what do you think about this? Doesn't this solve it?" We weren't trying to go around them, and so we were trying to develop sort of new understandings of it.Venk Varadan: And I think collaboratively we put together a good playbook with FDA to clear a material that they had never seen before. Right? It would be one thing if we use the standard electrode like all Holter monitors do and combined it with something, and did different things on the software side. That would be somewhat straightforward because they know the data that's being generated is often the standard electrode. But for us, we had to do a lot of different and in many cases, much more rigorous testing, which that was painful. Don't get me wrong, but totally worth it, right? I mean, our sort of boundaries and our understanding of what FDA put us through, it turned out to be a boon in disguise. I mean, our whole team can sort of run through the needs now of FDA and we feel very experienced and very well equipped on how they think. And now that they're comfortable with the sort of data we capture, all the great things we can do on the AI side, which is still scary to a lot of people. You just say I've got a black box and I'm combing electronic medical records, and here's what the unsupervised learning tells me. I was a regulator. I'd be like, Wow, I'm not touching that with a 10-foot pole, you know? So it's different with us, right? I mean, we can define everything that's coming in and we can define the outputs. Yes, the AI in the middle is the magic, but we're not sort of defining everything until the outcomes, right, which is where I see a lot of companies got into trouble. So I think it was worth it with the FDA.Harry Glorikian: Well it's funny because, I mean, I always say to people, I'm like, Listen, they're not the enemy, actually. They can make your life easier because and I say, people tell me, "Well, I'm not going to go until I'm absolutely done." I'm like, If you wait that long and they tell you you're wrong, you just spent a whole lot of money for "and you're wrong." Right? So you should look at them as your partner. Right. And I'm assuming you went to, you worked with the digital health group at the FDA.Venk Varadan: We worked predominantly, consistently we work with CDRH [the Center for Devices and Radiological Health] and now actually as a as a board member on Advamed, sitting on the executive leadership group for digital health, Advamed is a trade association that helps with FDA and with CMS on on industry innovation. CDRH does have its own sort of digital health group within it that's focused on a lot of these issues that we're talking about A.I., data privacy, cybersecurity, which in this sort of next decade, I think is going to be the main sort of frontier for the industry government relationship that we all sort of signed up for when we decided to go into health care, because even the most sleepy widgets right that we use consistently, they're all tech enabled now. Everything is digital, you know?Harry Glorikian: So yeah, and I mean, they're they've been creating that from the ground up. I remember talking to the the gentleman that runs it and he's like, I feel like I'm running a startup because, right, most of the stuff that we're, you know, we need to figure out has never been done before at the regulatory agency. And so we're sort of creating it from scratch, right? So I mean, in a way that that's good because he understands the pains that the companies are having to go through in creating something that hasn't been done before.[musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's to make it easier for other listeners discover the show by leaving a rating and a review on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing us a huge favor.And one more thing. If you like the interviews we do here on the show I know you'll   like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in Kindle format. Just go to Amazon and search for "The Future You" by Harry Glorikian.And now, back to the show.[musical interlude]Harry Glorikian: So let's go back for a second to, you know, 2020 in the first wave of coronavirus pandemic, right? You partnered with some medical centers in New York and New Jersey to start using it to monitor patients. And what did you learn from those studies and how did the device help improve treatment?Venk Varadan: There were two things I think. One, it was all anybody was talking about, and there were so many unknowns about it that we recognized that this was a, you know, a virus that was affecting the cardiopulmonary complex. Those that were getting sick and we're going to the E.R. had issues there, and that's what we were doing. And so in the same way that we're looking at potential use cases with the ultimate goal of assessing someone's risk, right, which is really what we're what we're doing as a remote diagnostic company or a remote hospital at home patient monitoring company, we went into COVID with that same thesis in doing so. And obviously in our backyard in New York, we got punched in the mouth first in the USA. With that, pretty much everybody I know was infected in March. We were all riding the subway together, you know, up until the last day as sardines. So it was not escapable here. And we're a dense city, right? We all sort of live on top of each other and our hospitals almost in a week. There were patients in the cafeteria. They were we were making tent villages for additional beds in Crown Heights, Brooklyn. It was completely overwhelming. And so we really feel it felt like we wanted to do something about it now. We would have gotten on patients right away, but. We did have to go through the IRB processes, which would take time, unfortunately, but we learned a couple of things and the two things actually that we learned are is that we're not necessarily super helpful in a acute virus that hits you really fast.Venk Varadan: The patients that this is sending to the ICU, it's doing so very quickly. It's rare that someone is sick for three or four weeks. They progress so badly that then they go to the ICU. They have a drop pretty quickly when it happens. So what we found was, our study was really to go on patients while they were in the general ward, and the endpoint would be when they were transferred to the ICU because they had gotten so sick a morbidity event or they were discharged. And I think we were unable, to be candid, we were unable to find the lead up to that point because we just simply didn't know what patients were coming in. I would have loved data on them from 48 hours beforehand. Right? We could have learned so much, even very basic functions that Fitbit and the Apple Watch are trying to market. "I saw a spike in heart rate from the all patients that got infected with COVID 48 hours before." That is the premise of where I would have loved to go with our granular data, but we're not the type of device that somebody just wears at all times, whether they're sick or not, right? So I think that was a learning experience for us that if there's an unknown of when something's going to hit, it'll be challenging. Venk Varadan: For infectious disease that becomes chronic disease, I think we're going to be in much better shape, and I think we could definitely do a longitudinal study for the long hauler community, right> You know, the folks that have been infected with COVID and have literally seen symptoms for a year or two, I think there's a lot we can learn longitudinally from there. And that's really where I think our study with our with our great partners at Maimonides Medical Center in Brooklyn and Hackensack, New Jersey and others across the country would, we would be more than happy to to participate in some of those longitudinal studies because, you know, we don't know what the long hauler is going to look like in five to 10 years, right? Or even people that have been infected before the vaccines now. That's still a let's figure it out type thing. So it's not you have to balance sort of running a sales product business versus a research part, but with the right resources and the right partners we would love to continue that work in COVID because it's not going anywhere as you know.Harry Glorikian: Well, listen, I actually want you to put it into a T-shirt and send me one so that I can wear it and monitor myself. But let's talk about where this technology is going in the future, right? The SimpleSense sash looks, you know, comfortable, convenient, way more comfortable than, say, a Holter monitor. But you'll correct me if I'm wrong, but it's still a specialty device. It isn't made from off the shelf materials, et cetera. But do you think there's like we're moving to a day where you can sort of embed these sensors in, as I said, a T-shirt, familiar cloth items. I'm looking at digital health and saying it has the ability to monitor me and sort of help identify problems before they come up so I can get ahead of them. And so that's how I'm thinking about this technology, because those sensors look pretty small and thin, at least from what I could see visually in the picture.Harry Glorikian: We're the first to say we don't know when we don't know, Harry. I know the market wants you to always have an answer for everything. A lot is going to depend on the additional aspects that we all use in technology stack. Where does 5G take us? Where does increased broadband take us? You know, 10 years ago, we didn't realize everyone in the world would have a smartphone, right? Villages in India and Africa, they have these now, you know what I mean? They may not have running water, but they've got, you know, a Samsung device, right? And so we may have never thought that monitoring in remote places like that because we couldn't find an economic model to sell shirts or bed sheets for a dollar out there. But maybe with the volume and with the right partners, that's where we could go. We certainly built our our stack with that sort of dream in mind. We filed IP and got patents awarded to embed in clothing and bed sheets and upholstery on cars and seatbelts and on the steering wheel and. You know, this could be in the gloves of a pilot one day. You know, this could replace your sort of neurological monitoring. We've got a prototype of a headband that's calculating all your EEG and EOG signals could replace an 18 lead one day. I think when you throw in real good advances in automated supply chain and 3D printing, there's a lot that can be done in this space and it's going to be done through partnership. We're not going to do it all on our own.Harry Glorikian:  No way. I was going to say Venk, get to work, man! What are you doing? Like, you're using this in a in a medical application, but I really want to understand: so especially if, you must have believed in it because you filed the patents, but do you think that this sort of sensor technology could just be a normal part of preventative health care in healthy patients?Venk Varadan: I think that was always the goal, Harry. What can we do to really help a physician provider and ultimately a payer understand someone's risk without them coming in to a hospital or doing a visit? Because really the only people you should be seeing in person are people that need to be seen, not me, for an annual physical. Not you for an annual physical. Not, you know, somebody in the villages in Africa who really just needs to understand why they have a fever, whether there's something really wrong inside them. That's where I think this should go. It always was that case. We never knew what the right problem was to start to build a business around it. But this should replace your your annual physical, your annual checkup for healthy people. This should replace the follow up visit for your post-surgical, whether you get a knee replacement and angioplasty or a stent in your heart and should replace your chronic disease visits. If you have sleep disorder or heart failure where you know, do you really have to go get a $10,000 test every three months to see if you're regressing, improving or if you're staying the same? I think that this can democratize all of that in some way, and it's cloth. We all wear clothes every day, right? So yeah.Harry Glorikian: I mean, I look at I've looked at all these technological advances and I look at them as deflationary in a sense right. We're allowing people to get higher quality care from these technologies because of the information that comes off of it and then utilizing AI and machine learning and, you know, different forms of data analytics to sort of highlight trends and problems or hopefully, no problems, and then if one comes up, it sort of sticks out like a sore thumb, but it gives you a longitudinal view on that patient. And that's where I see all of this going, I mean, COVID has just pulled everything forward a lot faster than. You know, anybody could have guessed, and I agree with you, if you look at 5G and all these things coming together, it's just it's going to take it one more leap forward that much faster. I mean, I can imagine a partner for you would be Apple or Google thinking about, you know, clothing. Or Lululemon, for that matter, I guess. But somebody that that can incorporate this into their into their materials and make it more available. Because I got to believe that there's a consumer application that somebody could take advantage of rather than just a hardcore medical need, if that makes sense.Venk Varadan: No, you're absolutely right, and again, this sort of went through our strategic thinking when we were thinking about what we wanted to be when we grew up. And we think that the our unique cloth nanosensor technology, which good luck trying to replicate and copy that for anybody who's interested, I mean that again, this was 40 years of work that sort of how to create it and we're bulletproof, protected from a from a patent standpoint. But we think this can enable all of those markets. Our thesis was always, Harry, if we could start in health care we'd have the need-to-have population. The people that don't have a choice, right? I mean, I can go out for a jog or I don't need to go out for a jog, right? I can run with a monitor but I don't need to. But there's a good percentage of the population that doesn't have a choice. They must be monitored. If we could start with that, need to have population and prove it, prove that it works, that it's changing outcomes. Why would the nice-to-have market use something that you know, is already working for for sick people, right? And that was kind of always our thesis. We don't really have a timeline on when we're going into the consumer market, but because, you know, there are different aspects that are involved there from a business standpoint, customer acquisition marketing are the obvious ones, but sexiness, fit, we did not focus on "Do we look cool?" We were focusing on, you know, design is important on everything, don't get me wrong, but we first started with "make it work." We didn't start with "It has to be this big" and then figure it out, right? We started the other way around.Harry Glorikian: Well, and if you think about all the existing wearable technologies, they incorporate a sensor that everybody understands very well, right? There's no question that temperature monitoring, there's no question that, you know, if you can have a CGM on you, you can sort of understand what foods affect you positively or negatively. You're right. We need the scientific publication to prove that the technology that you built does what it needs to do, and it's probably all the time going to give you new information. You're going to be like, I didn't know we could figure that out, right? Which is the beauty of having 85 biomarkers. You're going to find something new all the time, but you could easily see that certain applications would then become accepted and then make its way into mainstream.Harry Glorikian: Yeah, absolutely. And I think the more that folks are using and the cool thing or not, maybe not cool, maybe it bothers some people, I'm sure, but technology goes one way. It does not go backwards, right? And COVID sort of shifting virtual care into the forefront, which is what technophiles did before. "Oh, I just talked to my doctor on the phone." I would have laughed. I was like, What can they do with that right before I started Nanowear, right? But that's not going back right. If you don't have to go see your position in person and you've got an alternative now that replaces it, why wouldn't you do that right? So. Yeah, I think as people get more accustomed with devices, they'll understand how to differentiate from them. You know, I'm not taking shots at our friends in Cupertino, but there's only so much you can do on the wrist, righHarry Glorikian: Absolutely.Venk Varadan: If you're not going across the heart, across the lungs, across the brain, you're going to be limited in what you can do if you just have an armband device that's picking up your pulse rate and your skin temperature, you're limited in what you can do, right? So I think what we're excited about, maybe not just on this form factor in this product, but understanding its application around the body. You can't put a smartwatch around your body, but you can put a cloth around your body. You can put a sheet around your body, right? I think that hopefully the understanding is going to come that there is a delineation between something that's great for the consumer and something that's great for, you know, the health care population. And where does that nexus come together? I think that's going to be driven by patients. I don't think it's going to be driven by us. I don't think it's going to be driven by the provider or the payer. I think the patients are going to demand, you know, as they are doing now, right? I mean, the reason providers are buying our solution right now is because the patients are demanding it right. The payers are kind of demanding it. To some extent, cardiologists would love to see 40 patients a day in their office again. They were really used to that, right?Harry Glorikian: Yeah. This is a longer debate over a beer at some point.Venk Varadan: It is Friday!Harry Glorikian: Listen, it was great to talk to you. Healthy congratulations on the on the latest approval and look forward to seeing other approvals as as you're taking this thing forward. And you know, I can only wish you great success. I mean, obviously since I'm an investor, I have a soft spot in my heart for every entrepreneur out there.Venk Varadan: Thank you, Harry, and thank you for the opportunity to spend some time with you and and your audience. Hopefully, it's the first of many and I can come back and give an update in a year or so. And hopefully by then, it's not just about FDA approvals, but I'm showing we really built sales here because I know investors care about that. Just selling our product in the enterprise for the first time this month in September, and early numbers are great. So it's a really exciting time. I think six and a half years into the journey and being able to do it starting with dad has been pretty special. So so thanks for having us and appreciate you following our progress going forward. Harry Glorikian: Excellent.Thanks for participating.Venk Varadan: Thanks, Harry.Harry Glorikian: That's it for this week's episode. You can find past episodes of The Harry Glorikian Show and MoneyBall Medicine at my website, glorikian.com, under the tab Podcasts.Don't forget to go to Apple Podcasts to leave a rating and review for the show.You can find me on Twitter at hglorikian. And we always love it when listeners post about the show there, or on other social media. Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview. 

Please join author Jonathan Newman and Associate Editor Sandeep Das as they discuss the article "Outcomes of Participants With Diabetes in the ISCHEMIA Trials." Dr. Carolyn Lam: Welcome to circulation on the run, your weekly podcast, summary, and backstage pass to the journal and its editors. We're your co-hosts; I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU health in Richmond, Virginia. Well, Carolyn, this week's feature, a couple of weeks ago, we had that feature forum on the ischemia trial. Now we're going to explore some of the outcomes in patients with diabetes, from the ischemia trial in the feature discussion today. But, before we get to that, let's grab a cup of coffee and start in on some of the other articles in this issue. So, how about if I go first, this time? This particular paper, Carolyn, we're going to start on one of your topics. I know you're a fan of diet related interventions. So high intake of added sugar is linked to weight gain and cardio-metabolic risk. And in 2018, the U S National Salt and Sugar Reduction Initiative proposed government supported voluntary national sugar reduction targets. Dr. Greg Hundley: This intervention's potential health and equity impacts and cost effectiveness are unclear. And so Carolyn, these authors, led by Dr. Renata Micha from Tufts University, incorporated a validated micro-simulation model - CVD Predict coded in C++, and used it to estimate incremental changes in type two diabetes, cardiovascular disease, quality adjusted life years, cost and cost effectiveness of this national policy. The model was run at the individual level and the model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across three cycles spanning from 2011 to 2016, added sugar related diseases from meta-analysis and policy costs and health-related costs from established sources and a simulated nationally representative us population was created and followed until age 100 years or death with 2019 as the year of intervention start and findings were evaluated over 10 years and a lifetime from healthcare and societal perspectives. Dr. Carolyn Lam: Ooooh, You so got my attention, Greg, a very important topic and so, what did they find? Dr. Greg Hundley: Right, Carolyn. So achieving the NSRI sugar reduction targets could prevent 2.48 million cardiovascular death related events, 0.5 million cardiovascular disease deaths, and three quarters of a million diabetes cases, gain 6.7 million quality adjusted life years, and save $160.8 billion in net cost from a societal perspective over a lifetime. The policy became cost-effective, defined as less than $150,000 for quality adjusted life years at six years and highly cost-effective at seven years with a cost savings noted at nine years. And therefore, Carolyn, implementing and achieving the NSSRI sugar reformation targets could generate substantial health gains, equity gains, and cost savings. Dr. Carolyn Lam: Wow, thanks Greg. So, moving from a very publicly health focused paper to this paper that really focuses on hypoplastic left heart syndrome with very, very scientifically significant findings. Now, first, we know hypoplastic left heart syndrome is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis is unknown, but hemodynamic disturbances are assumed to play a prominent role. Authors led by Doctors Moretti and Laugwitz from Technical University of Munich in Germany, as well as Dr. Gruber from Yale University School of Medicine, and their colleagues combined whole exome sequencing of parent offspring, trios, transcriptome profiling of cardiomyocytes from ventricular biopsies and immuno-pluripotent stem cell derived cardiac progenator or cardiomyocyte models of 2D and 3D cardiogenesis, as well as single cell gene expression analysis to decode the cellular and molecular principles of hypoplastic left heart syndrome phenotypes. Dr. Greg Hundley: Wow, Carolyn, there is a lot of data, very complex preclinical science here. So what did they find? Dr. Carolyn Lam: Indeed, Greg. As I said, scientifically incredible and rigorous, and they found that initial aberrations in the cell cycle unfolded protein response, autophagy hub led to disrupted cardiac progenator lineage commitment, consequently, impaired maturation of ventricular cardiomyocytes limited their ability to respond to growth cues. Resulting in premature cell cycle exit and increase apoptosis under biomechanical stress in 3D heart structures. Together, these studies provide evidence that the hypoplastic left heart syndrome pathogenesis is not exclusively of hemodynamic origin, and they revealed novel potential nodes for rational design of therapeutic intervention. Dr. Greg Hundley: Wow, Carolyn, we really need research in this topic and this is great preclinical science that we're getting here in our journal. Congratulations to the authors and what a great presentation of that by you. Well, Carolyn and my next paper there remain major uncertainties regarding disease activity within the Retain Native Aortic Valve, as well as bioprosthetic valve durability, following transcatheter aortic valve implantation. And these authors led by Doctor Jacek Kwiecinski, from the Institute of Cardiology, aimed in a multi-center cross-sectional observational cohort study to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison to subjects with bioprosthetic surgical aortic valve replacement or SAVR. Dr. Carolyn Lam: Oh, very interesting. And what were the results? Dr. Greg Hundley: An interesting comparison, Carolyn. So in patients with TAVI, native aortic valves demonstrated 18 F sodium fluoride uptake around the outside of the bioprosthesis that showed a modest correlation with the time from TAVI. Next, 18 sodium fluoride uptake in the bias prosthetic leaflets was comparable between SAVR and TAVI groups. Next, the frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echo cardiography 6 and 8% respectively, CT, 15 and 14% respectively, and with PET scanning. Next, baseline 18 F sodium fluoride uptake was associated with subsequent change in peak aortic velocity for both TAVI and SAVR. And on multi-variable analysis, the 18 F sodium fluoride uptake was the only predictor of peak velocity progression. And so Carolyn, therefore, in patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease and across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR suggesting comparable midterm durability. Dr. Carolyn Lam: Very nice, important stuff. Dr. Carolyn Lam: Well, thanks, Greg. Let's tell everyone about the other papers in today's issue. There's an exchange of letters between Doctors Baillon and Blaha regarding the article very high coronary artery, calcium and association with cardiovascular disease events, non-cardiovascular outcomes and mortality from MESA. There's an ECG challenge from Dr. Bell Belhassen on a left bundle branch block, tachycardia following transcatheter aortic valve replacement. And On My Mind paper by Dr. Neeland on cardiovascular outcomes trials for weight loss interventions, another tool for cardiovascular prevention, another Research Letter by Dr. Nakamura on clinical outcomes of Rivaroxaban Mono therapy in heart failure, patients with atrial fibrillation and stable coronary artery disease. So insights from the AFIRE trial, and finally, a Research Letter from Dr. Kumoro three-dimensional visualization of hypoxia induced, pulmonary vascular remodeling in mice. Dr. Greg Hundley: Great, Carolyn, and I've got an in-depth piece from Professor Jia Sani entitled breadth of life, heart disease, linked to developmental hypoxia. Dr. Greg Hundley: Well, Carolyn, how about we get onto that feature discussion and learn more about results from the ischemia trial? Dr. Carolyn Lam: Let's go Greg. Dr. Carolyn Lam: Well, we all know how important diabetes is as a risk factor for atherosclerotic coronary disease. And we know it's a very common comorbidity among patients with chronic coronary disease, but the question is do patients with diabetes and chronic coronary disease on top of guideline directed medical therapy and lifestyle interventions, of course, do they derive incremental benefit from an invasive management strategy of their coronary disease? Well, we are going to try to answer that question today in our feature discussion. Thank you so much for joining us today. The first author and corresponding author of today's feature paper, which tells us about results from the ischemia trials. And that's Dr. Jonathan Newman from New York university Grossman School of Medicine. We also have associate editor Sandeep Das from UT Southwestern. So welcome both of you. And if I could please start with Jonathan reminding us, perhaps, what were the ischemia trials and then what you tried to answer and do in today's paper, Dr. Jonathan Newman: Of course, Carolyn, and thank you so much for having me and for the discussion with Sandeep. It's a pleasure to be here. So sure has a little bit of background, as you indicated, the ischemia trials basically enrolled and for the purposes of this discussion and this analysis, I'm referring to both the main ischemia trial and the ischemia chronic kidney disease trials. So ischemia CKD under the umbrella of the ischemia trials. Ischemia stands for the international study of comparative health effectiveness with medical and invasive approaches. And the purpose of the trial was to test to see whether a routine invasive approach on a background of intensive guideline directed medical therapy for high risk patients with chronic coronary disease and at least moderate ischemia and obstructive coronary disease documented on a blinded CCTA or computed coronary tomography angiography prior to randomization was associated with benefits for a cardiovascular composite. And we looked in this analysis at whether or not there was appreciable heterogeneity of treatment effect or a difference in treatment effect for patients compared without diabetes in the ischemia trials, in ischemia and ischemia CKD. Dr. Carolyn Lam: Great, thanks for lining that up so nicely. So what, Dr. Jonathan Newman: So the results of our analysis really highlighted a couple of things that I think you touched upon initially, the first thing that I would highlight is that diabetes was very common in this high risk cohort with chronic coronary disease, over 40% of participants in the ischemia trials, 43% with obstructive coronary disease and moderate to severe, you may have had diabetes. Perhaps not surprisingly patients with diabetes had higher rates of death or MI than those without diabetes. And the rates were highest among those patients that required insulin, had insulin treated diabetes, but using really robust methods to assess for heterogeneity using a Bassen assessment of heterogeneity of treatment effect accounting for violation of proportional hazards. The fact that there was an upfront hazard and a late benefit, we really saw no difference in death or MI, between the invasive or conservative strategies for patients with, or without diabetes over about three years of follow-up. Dr. Jonathan Newman: And the results importantly were consistent for ischemia and ischemia CKD and provided the rationale for us when we started by looking to see if the distribution of risk and characteristics allowed the trials to be combined. The study really confirms this higher risk of death or a MI for chronic coronary disease patients who have diabetes extends these findings for those patients with moderate or severe ischemia. And I think really notably also adds information about chronic coronary disease patients with diabetes and CKD. That's sort of the overall findings. And I'm happy to talk in more detail about that. Dr. Carolyn Lam: I love the way you explain that Jonathan and especially, going into detail on what was so different about the paper and the really important statistical methods that made these findings robust, very important and impactful findings. If I could ask Sandeep to share your thoughts. Dr. Sandeep Das: Thanks, Carolyn. You know, I am just a big fan of everything that's come out of the ischemia group. One of the things that I really most enjoy as a consumer of the literature is when well done studies give me results that are unexpected. And I know it's become fashionable now to say that everybody knew that all along that this is what going to be the result. But honestly, I think we all sort of are many of us thought that there's going to be a subgroup somewhere that's really going to benefit from an invasive approach in terms of preventing heart outcomes. I think the key here that really jumped out at me was that this is identifying what we typically think of is a very high risk subgroup. You know, patients with diabetes patients with multi-vessel coronary disease patients with insulin dependent diabetes. Dr. Sandeep Das: And we did see the association with mortality across the increased disease severity and the increased severity of diabetes as expected. But really we didn't see a signal that revascularization, routinely revascularizing patients, even the higher risk patients led to clinically relevant heart outcome benefits. So I thought that that was a really interesting top line finding and really that's kind of. I mean, it would have been interesting if it was the other way too, but it was, it really was kind of the hook that got me into the paper. Dr. Sandeep Das: I actually have a question for Jonathan, one of the things that I think we spend a lot of time as an editorial group thinking about and talking about, and we bounce back and forth with the authors a few times was the idea that relatively few of these patients with multi-vessel CAD ended up having CABG. So, you would typically think of diabetes multi-vessel CAD as being a pretty strong signal for patients that may benefit in terms of mortality from having bypass surgery. And here it was a relatively small group about a third, or maybe even less than a third. And I realized up front, they excluded the left main and the patients that had angina had a CTA, et cetera. But what I'd be curious as to your thoughts about, the benefits of bypass surgery and diabetes, which have been established in other trials. Dr. Jonathan Newman: It's a great question. And I think we really appreciated the questions from you and from the editors to try and get at some of the nuance with this issue. As you indicated in the ischemia and ischemia CKD trials overall, and the patients in the invasive treatment arm, it was about 25% or so 26% and 15% were revascularized with CABG. Part of the issue here is that it gets a little tricky with the use of CCTA of pre randomization CTA to define coronary artery severity, which was not required in the CKD population due to impaired renal function. But what we can say is among the patients with diabetes and multi-vessel coronary disease, 29% were revascularized surgically in their combined analysis, which is comparable to the 30% in Bery 2d that were revascularized via bypass surgery, as we've discussed. And as you know, the decision for surgical versus percutaneous revascularization in ischemia, as in Barry 2d was non-randomized though we might want to, we really tried to be very, very cautious in terms of comparing revascularization strategies on outcomes for patients with diabetes and multi-vessel CAD, which has you suggested. Dr. Jonathan Newman: And as we pointed out, the proportion with multi-vessel CAD was more common amongst in patients with diabetes compared with those patients without diabetes. The other thing I would sort of say in the framework of, the revascularization and strategies for revascularization, comparing, let's say ischemia to Barry 2d or to freedom. Basically we have very little data about revascularization approaches for those patients with creatinine with impaired renal function and, patients with the crediting greater than two were excluded from Barry 2d. So while we had about 15% or so that had severe CKD. So in the GFR, less than 30 are on dialysis. And we know that's an extremely high risk group of patients with diabetes and chronic coronary disease. And we don't have great evidence on which strategy for revascularization if at all provides additional benefit. So I think it's a really a tough question to answer, and we tried to be as judicious as possible in our comments about revascularization approaches, given the nature of the trial design. Dr. Carolyn Lam: Gee, thanks so much, Jonathan, for explaining that. So, well, I actually have a related question now, referring to the medical therapy. Can I, sort of ask you about the fact that, these days that the rage is all about GLP one receptor agonist, for example, that are known to reduce the risk of atherosclerotic cardiovascular disease and diabetes. So these ischemic trials, I assume, did not have a high usage of these medications. And what do you think would be the impact, if anything, I suppose even more for guideline directed medical therapy. Huh? Dr. Jonathan Newman: Yeah. So it's a great question, Carolyn. As you know, in strategy trials and clinical trials in general, that take a while it's always a real challenge to keep the trial contemporary with current clinical practice, whether it's revascularization strategies or changes in medical therapy. And as you indicated, the real revolution and glucose lowering therapies with profound cardiovascular benefit for patients with diabetes, we worked hard to try and stay up to date and encourage sites around the world with the use of best SGLT2 inhibitors and GLP ones. The rates were very, very low and we don't actually given the fact that the ischemia trials were conducted a real multinational and is really an international trial is over 330 sites worldwide. So we really had to balance the data that we could get from sites with the reality of collecting and running this trial across the whole world. Dr. Jonathan Newman: So we don't actually know. We know insulin use or non-use or oral medication use or non-use or no medication use or non-use, but not much more than that. From what, as, you know, unfortunately, even after now, six going on seven years of impressive data for the benefit of these agents, uptake remains low for patients with diabetes, whether it's with coronary disease or heart failure. And there was certainly the case with the trial, which started back in 2015, or sorry, before 2015, even before the results of EMPA-REG. So the rates of those agents were low. I would expect as you indicated that if we did have greater use of these beneficial therapies. Medical therapy may have performed even better and potentially given an added boost potentially for our high risk, even higher risk subgroups that we'd looked at that were available in these trials. Dr. Carolyn Lam: Oh, thanks again. I wish we could go on forever, but we've got just a little bit of time left. So I'd like to ask you both for your quick take home messages for the audience. Could I start with Sandeep and then Jonathan? Dr. Sandeep Das: Yeah. You know, I think a key take home from this is that, although it may be naively intuitive that a very aggressive invasive strategy would be superior, especially in high risk patients. You know, the data are very, very convincing that it's not. And so therefore I think in an absolute minimum, you have plenty of time and ability to think about these patients carefully, to select who, if anybody would be a great candidate for revascularization, more aggressive therapy and more invasive therapy, but the most patients will do well with conservative management. Dr. Sandeep Das: And I think that that's the, that's a real key take home here. And I think that the points that Jonathan raised about, you know, poor uptake of GLP one RAs and SGLT 2 inhibitors in the community as they're so far are key, right? So we have great medicines that we just under used, and that to me is the other sort of clarion call here is that if in the context of a nice trial, that you can see similar result for invasive conservative approaches, then lets, let's get our medical therapy where it needs to be to provide our patients the best outcomes we can Speaker 3: Love it, Jonathan. Dr. Jonathan Newman: Yeah. So I'm really glad that Sandeep brought up the issue of medical therapy in the trial. And maybe I can take a minute to sort of frame what San kind of build off of what Sandeep just said, you know, we, in the context of this clinical trial, you know, Dr. Judy Hawkman, the study chair and Dr. David Marin, the co-chair and I, we worked very hard with optimizing medical therapy across the trials, for all participants. So really getting patients on the maximum tolerated doses of high-intensity statins, lowering patient's LDL as aggressively as possible evolving our systolic blood pressure targets. And it was extremely challenging. And at the end of the day, we see that patients with diabetes were more likely than those without to get to our LDL goal. We used a threshold problematic concept that that still may be to some extent, but they were less likely to achieve their systolic blood pressure goals. Dr. Jonathan Newman: And I think Sandeep was exactly right. We have a way to go with implementing existing therapies, existing medical therapy. There may be a benefit for as demonstrated in Dr. S. for patients that remain highly symptomatic to derive symptom benefit with revascularization. The other context I would sort of add with the medical therapy issue is that despite really aggressive medical therapy, and we really did as much as we could, patients with diabetes still had, a 40, 50% greater risk of death or MI than those without diabetes. So there's still this idea of kind of residual risk. And these were patients with diabetes that were very well managed from a medical and glycemic control perspective. So we still have a lot of work to do. And I think understanding ways we can benefit our patients is really that challenge. Speaker 3: Thanks so much, Jonathan, and thank you Sandeep for joining us today. Speaker 3: And thank you audience for listening from Greg and I. This has been "Circulation On The Run", please tune in again. Next week. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association for more visit AHJjournals.org.

It's the JournalFeed Podcast for the week of October 18-22, 2021. We cover intubating angioedema patients, inhaled steroids for COVID-19, non-operative management of appendicitis, part-time physician outcomes, and ECG diagnosis of wide complex tachycardia.

How do you handle stressful situations? Everyone's built a little different — some people can take their hits on the chin and come out smiling. But not everyone can take those hits. The pandemic has taken its mental toll on so many people. Others might still be struggling with past traumas and dealing with anxiety. Their situation keeps them in a state of constant worry and hypervigilance. That state of mind doesn't only harm their mental and emotional health — it can make them sick and more prone to physical diseases. More than ever, it's time to begin mental healing from past traumas, so we can better cope with our daily stresses.  Dr Don Wood joins us again in this episode to talk about the TIPP program and how it facilitates mental healing. He explains how our minds are affected by traumas and how these can affect our health and performance. If we want to become more relaxed, we need to learn how to go into the alpha brainwave state. Since mental healing is not an immediate process, Dr Don also shares some coping strategies we can use in our daily lives.  If you want to know more about how neuroscience can help you achieve mental healing, then this episode is for you.    Here are three reasons why you should listen to the full episode: Learn how trauma can put you in a constant state of survival and affect your performance and daily life.  Understand that it's not your fault. Achieving mental healing will require you to learn how to go into an alpha brainwave state.  Discover healthy habits that will keep you from entering survival mode.   Resources Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron!  A new program, BOOSTCAMP, is coming this September at Peak Wellness! Listen to other Pushing the Limits episodes:  #183: Sirtuin and NAD Supplements for Longevity with Dr Elena Seranova #189: Understanding Autophagy and Increasing Your Longevity with Dr Elena Seranova  #199: How Unresolved Trauma Prevents You from Having a Healthy Life With Dr Don Wood Check out Dr Don Wood's books:  Emotional Concussions: Understanding How Our Nervous System is Affected By Events and Experiences Throughout Our Life You Must Be Out Of Your Mind: We All Need A Reboot   Connect with Dr Don Wood: Inspired Performance Institute I Facebook I LinkedIn     Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to  https://www.lisatamati.com/page/epigenetics-and-health-coaching/.   Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer  Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5-km or run a 100-miler? ​​Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle?  Go to www.runninghotcoaching.com for our online run training coaching.   Health Optimisation and Life Coaching If you are struggling with a health issue and need people who look outside the square and are connected to some of the greatest science and health minds in the world, then reach out to us at support@lisatamati.com, we can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity, or want to take your performance to the next level and learn how to increase your mental toughness, emotional resilience, foundational health, and more, then contact us at support@lisatamati.com.   Order My Books My latest book Relentless chronicles the inspiring journey about how my mother and I defied the odds after an aneurysm left my mum Isobel with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions all around the world, go to https://shop.lisatamati.com/collections/books.   Lisa's Anti-Ageing and Longevity Supplements  NMN: Nicotinamide Mononucleotide, an NAD+ precursor Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health so you can live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and rigorously tested by an independent, third party lab. 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Manufactured in an ISO9001 certified facility Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health  Metabolic Health   My  ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection.   Episode Highlights [06:05] The Pandemic-Induced Mental Health Crisis The pandemic forced many people into a state of freeze mode, not the typical fight or flight response.  As people get out of freeze mode, there will be a rise in mental health issues.  Teenagers are robbed of the opportunity to develop social and communication skills during this time.  [08:24] How Dr Don Wood Started Studying Traumas Dr Don's wife grew up in a household with an angry father who instilled fear. He used to think that she would be less anxious when they started to live together, but she struggled with mental healing.  She had an inherent belief that misfortune always follows good things. Her traumas and fears also led to a lot of health issues.  She also was hyper-vigilant, which she used as a protective mechanism. However, this prevented her from being relaxed and happy. A person's environment can dictate whether they go into this hyper-vigilant state, but genetics can also play a factor.  [15:42] How Trauma Affects the Brain Trauma is caused by a dysregulation of the subconscious. If your brain is in survival mode, it will access data from the past and create physiological responses to them. These emotions demand action, even when it is no longer possible or necessary. This dysregulation prevents you from living in the present and initiating mental healing.  In this state, people can be triggered constantly, which interferes with their day-to-day life.  [21:07] The Role of the Subconscious Your conscious mind only takes up around 5%, while the subconscious takes up 95%. Your subconscious mind cannot tell the difference between real and imagined.  In survival mode, people will keep replaying the past and think about different scenarios and decisions.  You're left stuck because the subconscious mind only lives in the now. It does not have a concept of time.  This process is the brain trying to protect you. [25:04] What Happens When You're Always in Survival Mode Being in survival mode will take a physical toll since it's constantly activating the nervous system, increasing cortisol and adrenaline. When you're in this state, your body and mind cannot work on maintenance and recovery. It is more focused on escaping or fixing perceived threats. Over time, this will affect your immune system and make you sick.  To truly achieve mental healing, you need to get to the root cause of your problems.  However, you also have to develop coping strategies to manage your day-to-day activities.  [30:18] Changing Your Brainwave State Traumatic events are usually stored in a beta brainwave state. Changing your response to traumatic events starts with going into an alpha brainwave state.  The beta state is usually from 15 - 30 hertz, while the alpha is lower at 7 - 14 hertz. Anything below that is the delta state, usually when you're in deep meditation or sleep. People who have trouble sleeping are usually in that beta state, which keeps processing information.  It's only in the delta state that your mind and body start the maintenance phase. This phase helps not only with mental healing but also physical recovery.  Learn more about Lisa and Dr Don's personal experiences with these brainwave states in the full episode!  [34:30] Mental Healing and Physical Recovery Starts with the Brain Recovery is about genetics and the environment. In sleep, your mind will always want to deal with the threats first. It can only get to the delta state once it finishes processing these dangers. Your risk for developing sickness and depression rises if your brain can't do maintenance. Living in the beta state will make it difficult to focus.  [41:40] It's Not Your Fault If you have a lot of trauma, you are predisposed to respond in a certain way. It's not your fault.  There's nothing wrong with your mind; you just experienced different things from others.  Dr Don likened this situation to two phones having a different number of applications running.  Predictably, the device that runs more applications will have its battery drained faster.  [44:05] Change How You Respond Working on traumas requires changing the associative and repetitive memory, which repeats responses to threats. You cannot change a pattern and get mental healing immediately—it will take time.  That's the reason why Dr Don's program has a 30-day recovery phase dedicated to changing your response pattern.  Patterns form because the subconscious mind sees them as a beneficial way of coping with traumas.  This function of your subconscious is how addictions form.  [47:04] Why We Can Be Irrational The subconscious lives only in the present. It does not see the future nor the past.  It will want to take actions that will stop the pain, even if the actions are not rational.  At its core, addiction is all about trying to stop the pain or other traumatic experiences.  Survival mode always overrides reason and logic because its priority is to protect you. [50:57] What to Do When You're in Survival State In this survival state, we're prone to movement or shutting down completely.  The brain can stop calling for emotions to protect you, and this is how depression develops.  When in a depressed state, start moving to initiate mental healing. Exercise helps burn through cortisol and adrenaline.  Once your mind realises there's no action required for the perceived threats, the depression will lift.   [53:24] Simple Actions Can Help There's nothing wrong with you.  Don't just treat the symptom; go straight to the issue.  Don't blame genetics or hormonal imbalances for finding it hard to get mental healing. Find out why.  Also, seek things that will balance out your hormones. These can be as simple as walking in nature, taking a break, and self-care.  [56:04] How to Find a Calming Symbol Find a symbol that will help you go back into the alpha brainwave state.  Lisa shares that her symbol is the sunset or sunrise, and this helps her calm down. Meanwhile, Dr Don's are his home and the hawk.  Having a symbol communicates to all parts of your brain that you're safe.  [59:58] The Power of Breathing  Stress may lead to irregular breathing patterns and increase your cortisol levels and blood sugar. Breathing exercises, like box breathing, can also help you calm down because the brain will take higher oxygen levels as a state of safety.  If you're running out of oxygen, your brain will think you're still in danger.  Make sure that you're breathing well. It's also better to do nasal breathing.    7 Powerful Quotes ‘The purpose of an emotion is a call for an action. So the purpose of fear is to run.' ‘People who have a lot of trauma have trouble sleeping. Because not only is their mind processing what it experienced during the day, it's also taking some of those old files saying “Well, okay, let's fix that now. Right. Let's get that.”' ‘I was getting maximum restorative sleep. So an injury that I would have that could heal in two or three days, my teammates would two or three weeks. Because they were living in these, which I didn't know, a lot of my friends were dealing with trauma: physical, emotional, sexual abuse.' ‘There's nothing wrong with anybody's mind. Everybody's mind is fine except you are experiencing something different than I experienced so your mind kept responding to it, and mine didn't have that.' ‘That dysregulation of the nervous system. That's what we want to stop because that is what is going to affect health, enjoyment of life, and everything else.' ‘I talked about addiction as a code. I don't believe it's a disease. Your mind has found a resource to stop pains and your subconscious mind is literal. It doesn't see things as good or bad, or right or wrong.' ‘If there's a survival threat, survival will always override reason and logic because it's designed to protect you.'   About Dr Don Dr Don Wood, PhD, is the CEO of The Inspired Performance Institute. Fueled by his family's experiences, he developed the cutting-edge neuroscience approach, TIPP. The program has produced impressive results and benefited individuals all over the world.  Dr Wood has helped trauma survivors achieve mental healing from the Boston Marathon bombing attack and the Las Vegas shooting. He has also helped highly successful executives and world-class athletes. Marko Cheseto, a double amputee marathon runner, broke the world record after completing TIPP. Meanwhile, Chris Nikic worked with Dr Wood and made world news by becoming the first person with Down Syndrome to finish an Ironman competition. Interested in Dr Don's work? Check out The Inspired Performance Institute. You can also reach him on Facebook and LinkedIn.    Enjoyed This Podcast? If you did, be sure to subscribe and share it with your friends! Post a review and share it! If you enjoyed tuning in, then leave us a review. You can also share this with your family and friends so they can learn steps to mental healing. Have any questions? You can contact me through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa   Transcript Of Podcast Welcome to Pushing the Limits, the show that helps you reach your full potential with your host Lisa Tamati, brought to you by lisatamati.com.  Lisa Tamati: Hi, everyone and welcome back to Pushing the Limits. Today, I have Dr Don Wood who, you may recognise that name if you listen to the podcast regularly. He was on the show maybe a couple of months ago, and he is the CEO and founder of The Inspired Performance Institute. He's a neuroscience guy, and he knows everything there is to know about dealing with trauma and how to get the mind back on track when you've been through big, horrible life events or some such thing. Now, when we talked last time, he shared with me his methodology, the work that he's done, how he can help people with things like addictions as well and depression, and just dealing with the stresses of life, whether they be small stressors or big stressors.  We got to talking about my situation and the stuff that I've been through in the last few years, which many of you listeners know, has been pretty traumatic. From losing babies, to losing my dad, to mom's journey. So I was very privileged and lucky to have Dr Don Wood actually invite me to do his program with him. We share today my stories, how I went with that, and he explains a little bit more in-depth the neuroscience behind it all and how it all works. So if you're someone who's dealing with stress, anxiety, PTSD, depression, if you want to understand how the brain works and how you can help yourself to deal with these sorts of things, then you must listen to the show. He's an absolutely lovely, wonderful person.  Now, before we get over to the show, I just love you all to do a couple of things for me. If you wouldn't mind doing a rating and review of the show on Apple, iTunes or wherever you listen to this, that would be fantastic. It helps the show get found. We also have a patron program, just a reminder if you want to check that out. Come and join the mission that we're on to bring this wonderful information to reach to people.  Also, we have our BOOSTCAMP program starting on the first of September 2021. If you listen to this later, we will be holding these on a regular basis so make sure you check it out. This is an eight-week live webinar series that my business partner, my best buddy, and longtime coach Neil Wagstaff and I will be running. It's more about upgrading your life and helping you perform better, helping you be your best that you can be, helping you understand your own biology, your own neuroscience, how your brain works, how your biology works. Lots of good information that's going to help you upgrade your life, live longer, be happier, reduce stress, and be able to deal with things when life is stressful. God knows we're all dealing with that. So I'd love you to come and check that out. You can go to peakwellness.co.nz/boostcamp.  I also want to remind you to check us out on Instagram. I'm quite active on Instagram. I have a couple of accounts there. We have one for the podcast that we've just started. We need a few more followers please on there. Go to @pushingthelimits for that one on Instagram, and then my main account is @lisatamati, if you want to check that one out. If you are a running fan, check us out on Instagram @runninghotcoaching and we're on Facebook under all of those as well. So @lisatamati, @pushingthelimits, and @runninghotcoaching.  The last thing before we go over to Dr Don Wood, reminder check out, too, our longevity and anti-aging supplement. We've joined forces with Dr Elena Seranova and have NMN which is nicotinamide mononucleotide, and this is really some of that cooler stuff in the anti-aging, and longevity space. If you want to check out the science behind that, we have a couple of podcasts with her. Check those out and also head on over to nmnbio.nz. Right. Over to the show with Dr Don Wood.  Hi, everyone and welcome back to Pushing the Limits. Today, I have a dear, dear friend again who's back on the show as a repeat offender, Dr Don Wood. Dr Don Wood: I didn't know I was a repeat offender. Oh, I'm in trouble. That's great.  Lisa: Repeat offender on the show. Dr Don, for those who don't know, was on the show. Dr Don is a trauma expert and a neuroscientist, and someone who understands how the brain works, and why we struggle with anxiety, and depression, and post-traumatic stress disorder. We did a deep dive last time, didn't we, into the program that you've developed. Since then, everyone, I have been through Dr Don's pro program. He kindly took me through it. Today, I want to unpack a little bit of my experiences on the other side, s the client, so to speak. Talk about what I went through.  Dr Don, so firstly, welcome to the show again. How's it all over in your neck of the woods? Dr Don: Well, it's awesome over here in Florida. COVID is basically non-existent. Oh, yeah. Well, in terms of the way people are treating it, that's for sure. Very few people you see in masks now, everything is pretty much wide open. You can't even get reservations at restaurants. It's unbelievable. The economy is exploding here. There's so much going on. Yeah, I know the rest of the country, a lot of different places are still struggling with whether they're going to put mask mandates back on and all this kind of stuff but Florida seems to be doing very well.  Lisa: Well, I'm very glad to hear that because any bit of good news in this scenario is good because this keeps coming and biting everybody in the bum.  Dr Don: I know. Especially down there. You guys are really experiencing quite severe lockdowns and things, right? Lisa: Yeah and Australia, more so. Australia has gone back into lockdown. I've got cousins in Sydney who are experiencing really hard times in Melbourne and we've stopped the trans-Tasman bubble at the moment. Trans-Tasman was open for business, so to speak, with Australians being able to come to New Zealand without quarantine, but it's been shut down again. So yeah, we're still struggling with it, and the economy is still struggling with it but actually, in our country, we've been very lucky that we've managed to keep it out because they've had such tight controls on the borders. But yes, it's a rocky road for everybody, and it's not over yet, I think. Dr Don: Looks like it's going to continue, and that's creating a lot of stress.  Lisa: Oh, yeah, perfect.  Dr Don: This is what I've said. I think we're coming up to a tsunami of mental health issues because a lot of people have gone into freeze mode as opposed to fight or flight. Some people are in fight or flight. You're hearing about that on airlines: people just losing it, and getting mad, and fighting with flight attendants and passengers, and you see a lot of that. But I think that's obviously not the majority. I think most people are in that mode of just get through this, do what they ask, don't cause any waves, and just get this over with. So that's a freeze mode, and I think when people come out of freeze, you're going to start to see some of these mental health issues.  Lisa: Yes, I totally agree and I'm very concerned about the young people. I think that being hit very hard especially in the places that have the hardest lockdowns. If you're going through puberty, or you're going through teenagehood, or even the younger kids, I think, they're going to be affected massively by this because it's going to be a big before and after sort of situation for them.  Dr Don: And just the social. When we were teenagers, social was everything, I suppose. Learning how to communicate, and talk, and get along with other people, and good and bad. There were always struggles in school with learning how to get along with everybody but that is just sort of squashed. It's going to be fascinating to see when they do a study on the real true results of this pandemic. It's going to be a lot different than many people think.  Lisa: Yes, and I think the longer you ignore stuff, is we're going to see it's not just the people are unfortunately dying and being very sick from the actual COVID, but the actual effects on society are going to be big. That's why talking about the topic that we're talking about today, dealing with anxiety, and dealing with stress, and being able to actually fix the problem instead of just managing the problem, which I know you're big on.  So let's dive in there, and let's recap a little bit. Just briefly go back over your story, how you got to here, and what your method sort of entails in a helicopter perspective. Dr Don: Yeah, basically how I developed this was really because of the life that my wife led first and my daughter. My wife grew up in a very traumatic household with a very angry father that created tremendous fear. So everybody was... Just constant tension in that household. When I met her, I just realised how this was so different than my life. My life was in the complete opposite: very nurturing, loving. So I didn't experience that. I thought when she started moving in and we got married at 19, we were very young, that this would all stop for her. Because now, she's living in my world, my environment, and it didn't.  She just kept continuing to feel this fear that something was going to go wrong and nothing is going to go right. She struggled with enjoying things that were going well. I would say to her, 'We've got three beautiful children. We've got a beautiful home. Everything's going pretty good; nothing's perfect. You have your ups and downs, but it's generally a pretty good life.' She couldn't enjoy that because as a child, whenever things were going okay, it would quickly end and it would end, sometimes violently. So the way she was protecting herself is don't get too excited when things are going well because you'll get this huge drop. So that was what she was doing to protect herself. I just had a lady come in here a couple months ago, who very famous athlete is her husband: millionaires, got fame, fortune, everything you want, but she had a lot of health issues because of trauma from her childhood. When I explained that to her, she said, 'That's me. Your wife is me. I should be enjoying this, and I can't get there. I want to. My husband can't understand it.' But that's really what was going on for her too. Lisa: So it's a protective mechanism, isn't it? To basically not get too relaxed and happy because you've got to be hyper-vigilant, and this is something that I've definitely struggled with my entire life. Not because I had a horrible childhood. I had a wonderful childhood but I was super sensitive. So from a genetic perspective, I'm super sensitive. I have a lot of adrenaline that makes me code for, for want of a better description, I'm very emotionally empathetic but it also makes me swung by emotional stimuli very much. So someone in my environment is unhappy, I am unhappy. I'm often anxious and upset. My mum telling me she took me to Bambi. You know the movie Bambi? From Disneyland? She had to take me out of theatre. I was in distraught.  That's basically me. Because Bambi's mother got killed, right? I couldn't handle that as a four-year-old, and I still can't handle things. Things like the news and stuff, I protect myself from that because I take everything on. It's even a problem and in our business service situations because I want to save the world. I very much take on my clients' issues. I'm still learning to shut gates afterwards, so to speak, when you're done working with someone so that you're not constantly... So there's a genetic component to this as well.  Dr Don: Absolutely. So yours was coming from a genetic side but that's very, very common amongst people who have had a traumatic childhood. They're super sensitive.  Lisa: Yes. Hyper-vigilant.  Dr Don: Hyper-vigilant. That was my wife. She was constantly looking for danger. We'd come out of the storage and go: 'Can you believe how rude that clerk was?' 'What do you mean she was rude? How was she rude?' ‘You see the way she answered that question when I asked that, and then the way she stuffed the clothes in the bag?' And I'm like, 'Wow.' I never saw her like that. She was looking for it because that's how she protected herself because she had to recognise when danger was coming. So it was protection, and I hadn't experienced that so that made no sense to me; it made perfect sense to her.  Lisa: Yeah, and if someone was rude to you, you would be just like, 'Well, that's their problem, not my problem, and I'm not taking it on.' Whereas for someone your wife and for me... I did have a dad who was  a real hard, tough man, like old-school tough. We were very much on tenterhooks so when they came home, whether he was in a good mood today or not in a good mood. He was a wonderful, loving father but there was that tension of wanting to please dad. Mum was very calm and stable, but Dad was sort of more volatile and just up and down. It was wonderful and fun and other times, you'd be gauging all of that before he even walked in the door. That just makes you very much hyper-vigilant to everything as well.  Then, you put on, on top of that, the genetic component. You've got things like your serotonin and your adrenaline. So I've got the problem with the adrenaline and a lack of dopamine. So I don't have dopamine receptors that stops me feeling satisfaction and... Well, not stops me but it limits my feeling of, 'Oh, I've done a good job today. I can relax.' Or of reward. And other people have problems, I don't have this one, but with a serotonin gene, which is they have dysregulation of their serotonin and that calm, and that sense of well-being and mood regulation is also up and down. While it's not a predisposition that you'll definitely going to have troubles because you can learn the tools to manage those neurotransmitters and things like nutrition and gut health and all that aspect. Because it's all a piece of that puzzle, but it's really just interesting, and it makes you much more understanding of people's differences.  Why does one person get completely overwhelmed in a very trivial situation versus someone else who could go into war and come back and they're fine? What is it that makes one person? Then you got the whole actual neuroscience circuitry stuff, which I find fascinating, what you do. Can you explain a little bit what goes on? Say let's just pick a traumatic experience: Someone's gone through some big major trauma. What is actually going on in the brain again? Can we explain this a little bit?  Dr Don: Yeah, this is one of the things that... When I did my research, I realised this is what's causing the dysregulation: is your subconscious your survival brain is fully present in the moment all the time. So everything in that part of our brain is operating in the present. which is what is supposed to be, right? They say that that's the key, that success and happiness is live in the present. Well, your survival brain does that. The problem comes in is that only humans store explicit details about events and experiences. So everything you've seen, heard, smelled, and touched in your lifetime has been recorded and stored in this tremendous memory system. Explicit memory.  Animals have procedural memory or associative memory. We have that memory system too. So we have both. They only have procedural, associative. So they learn through repetition, and they learn to associate you with safety and love, but they don't store the details about it. But we store all the details about these events and experiences. So this is where this glitch is coming in. If you've got the survival brain, which is 95% of everything that's going on, operating in the present, accessing data from something that happened 10 years ago because something looks like, sounds like, smells like it again, it's creating a response to something that's not happening. It's looking at old data and creating a physiological response to it, and the purpose of an emotion is a call for an action. So the purpose of fear is to run, to escape a threat. But there's no threat. It's just information about the threat. That disrupts your nervous system and then that creates a cascade of chemical reactions in your body because your mind thinks there's an action required. Lisa: This is at the crux of the whole system really, isn't it? This is this call for action to fix a problem that is in the past that cannot be fixed in the now. So if we can dive a little bit into my story, and I'm quite open on the show. I'm sharing the good, the bad, and the ugly. When I was working with Dr Don, I've been through a very, very traumatic few years really. Lost my dad, first and foremost, last July, which was the biggest trauma of my life. And it was a very difficult process that we went through before he died as well. And there's a lift, as you can imagine, my brain in a state of every night nightmares, fighting for his life, he's dying over, and over, and over, and over again.  Those memories are intruding into my daily life, whereas in anything and at any time, I could be triggered and be in a bawling state in the middle of the car park or the supermarket. Because something's triggered me that Dad liked to to buy or Dad, whatever the case was, and this was becoming... It's now a year after the event but everything was triggering me constantly. Of course, this is draining the life out of you and interfering with your ability to give focus to your business, to your family, to your friends, every other part of your life. I'd also been through the trauma of bringing Mum back from that mess of aneurysm that everyone knows about. The constant vigilance that is associated with bringing someone back and who is that far gone to where she is now, and the constant fear of her slipping backwards, and me missing something, especially in light of what I'd been through with my father. So I'd missed some things, obviously. That's why he ended up in that position and through his own choices as well.  But this load, and then losing a baby as well in the middle, baby Joseph. There was just a hell of a lot to deal with in the last five years. Then, put on top of it, this genetic combination of a hot mess you got sitting before you and you've got a whole lot of trauma to get through. So when we did the process, and I was very, super excited to do this process because it was so intrusive into my life, and I realised that I was slowly killing myself because I wasn't able to stop that process from taking over my life. I could function. I was highly functional. No one would know in a daily setting, but only because I've got enough tools to keep my shit together. so to speak. But behind closed doors, there's a lot of trauma going on.  So can you sort of, just in a high level, we don't want to go into the details. This is a four-hour program that I went through with Dr Don. What was going on there. and what did you actually help me with?  Dr Don: So when you're describing those things that were happening to you, what was actually happening to your mind is it was not okay with any of that. It wanted it to be different, right? So it was trying to get you into a state of action to stop your father from dying: Do it differently. Because it kept reviewing the data. It was almost looking at game tape from a game and saying 'Oh, had we maybe run the play that way, we would have avoided the tackle here.' So what your mind was saying 'Okay, run that way.' Well, you can't run that way. This is game tape. Right? But your mind doesn't see it as game tape. It sees it as real now, so it's run that way. So it keeps calling you into an action.  And especially with your dad because you were thinking about, 'Why didn't I do this?' Or 'Had I just done this, maybe this would have happened.' What your mind was saying is, 'Okay, let's do it. Let's do that.' What you just thought about. But you can't do that. It doesn't exist. It's information about something that happened but your mind sees it as real. That's why Hollywood have made trillions of dollars because they can convince you something on the screen is actually happening. That's why we cry in a movie or that's why we get scared in a movie. Because your mind, your subconscious mind cannot tell the difference between real or imagined. So that's actually happening.  You were just talking about the movie with Bambi, right? When you were little. 'Why is nobody stopping this from happening?' So your mind was not okay with a lot of these things that were happening, and it kept calling you to make a difference. That's what I never understood my wife doing. That before I really researched this, my wife would always be saying, 'Don't you wish this hadn't have happened?' Or 'Don't you wish we hadn't done this?' What I didn't understand at the time, because I used to just get like, 'Okay, whatever.' She'd go, 'Yeah, but wouldn't it have been better?' She wanted to get me into this play with her, this exercise. Lisa: This is going on in her head. Dr Don: Because it's going on in her head, and she's trying to feel better. So she's creating these scenarios that would make her feel like, 'Well, if I had just done that, gosh that would have been nice, thinking about that life.' And her mind seeing that going, 'Oh, that would be nice. Well, let's do that. Yes.' So she was what if-ing her life. And it was something that she did very early as a child because that's how she just experienced something traumatic with her father. In her mind, she'd be going, 'Well, what if I had to just left 10 minutes earlier, and I had have escaped that?' Or 'What if I hadn't done this?' So that's what she was doing. It made no sense to me because I hadn't experienced her life, but that's what she was doing. Her mind was trying to fix something. It's never tried to hurt you. It was never, at any point, trying to make you feel bad. It was trying to protect you. Lisa: Its job is to protect you from danger and it sees everything as you sit in the now so it's happening now. I love that analogy of these... What was it? Two-thirds of the car or something and... Dr Don: So goat and snowflake? Lisa: Goat and snowflake. And they're going off to a meeting and they're late. And what does the goat says to snowflake or the other way around? Dr Don: So snowflake, which is your conscious mind, your logical reasonable part of your mind, there's only 5, says the goat 95%, which is your subconscious mind. Who runs into a traffic jam says, 'Oh, we're going to be late. We should have left 15 minutes earlier.' To which goat replies 'Okay, let's do it. Let's leave 15 minutes earlier because that would solve the problem.'  Lisa: That analogy is stuck in my head because you just cannot... It doesn't know that it's too late and you can't hop into the past because it only lives in the now. This is 95% of how our brain operates. That's why we can do things like, I was walking, I was at a strategy meeting in Auckland with my business partner two days ago. We were walking along the road and he suddenly tripped and fell onto the road, right? My subconscious reacted so fast, I grabbed him right, and punched him in the guts. I didn't mean to do that but my subconscious recognised in a millimeter of a second, millionth of a second, that he was falling and I had to stop him. So this is a good side of the survival network: stopping and falling into the traffic or onto the ground.  But the downside of it is that brain is operating only in the now and it can't... Like with my father, it was going 'Save him. Save him. Save him. Why are you not saving him?' Then that's calling for an action, and then my body is agitated. The cortisol level's up. The adrenaline is up, and I'm trying to do something that's impossible to fix. That can drive you to absolute insanity when that's happening every hour, every day. Dr Don: Then that's taking a physical toll on your body because it's activating your nervous system, which is now, the cortisol levels are going up, adrenaline, right? So when your mind is in that constant state, it does very little on maintenance. It is not worried about fixing anything; it's worried about escaping or fixing the threat, because that's the number one priority.  Lisa: It doesn't know that it's not happening. I ended up with shingles for two months. I've only just gotten over it a few weeks ago. That's a definite sign of my body's, my immune system is down. Why is it down? Why can that virus that's been sitting dormant in my body for 40-something years suddenly decide now to come out? Because it's just becoming too much. I've spent too long in the fight or flight state and then your immune system is down. This is how we end up really ill.  Dr Don: We get sick. I was just actually having lunch today with a young lady and she's got some immune system issues. And I said, 'Think about it like the US Army, US military is the biggest, strongest military in the world. But if you took that military and you spread it out amongst 50 countries around the world fighting battles, and then somebody attacks the United States, I don't care how big and strong that system was, that military system was. It's going to be weakened when it gets an attack at the homefront.' So that's what was happening. So all of a sudden, now that virus that it could fight and keep dormant, it lets it pass by because it's like, 'Well, we can let that go. We'll catch that later. Right now, we got to go on the offensive and attack something else.' Lisa: Yeah, and this is where autoimmune, like your daughter experienced... Dr Don: About the Crohn's? Yep.  Lisa: Yep. She experienced that at 13 or something ridiculous? Dr Don: 14, she got it. Then she also got idiopathic pulmonary hemosiderosis which is another lung autoimmune disorder where the iron in the blood would just cause the lungs to release the blood. So her lungs just starts filling up with blood. They had no idea what caused it, that's the idiopathic part of it, and they just basically said, ‘There's no cure. She just needs to live close to a hospital because she'll bleed out if she has another attack.' Only 1 in 1.2 million people ever get that. So it's very rare so there's no research being done for it. They just basically say, ‘If you get it, live close to a hospital.' That's the strategy. Lisa: That's the way of fixing it.  Dr Don: And so both of those are autoimmune, and ever since we've gone to the program, she's hasn't had a flare-up of either one of those. Because I think our system is directly now able to address those things.  Lisa: Yeah, and can calm down. I think even people who haven't got post-traumatic stress like I've had or whatever, they've still got the day to day grind of life, and the struggle with finances, and the mortgage to be paid, and the kids to feed, and whatever dramas we're all going through. Like we talked about with COVID and this constant change that society is undergoing, and that's going to get faster and more. So this is something that we all need to be wary of: That we're not in this. I've taught and learned a lot about the coping and managing strategies, the breathing techniques, and meditation, the things, and that's what's kept me, probably, going. Dr Don: Those are great because they're... Again, that's managing it but it's good to have that because you've got to get to the root of it, which is what we were working on. But at the same time, if you don't have any coping, managing skills, life gets very difficult. Lisa: Yeah, and this is in-the-moment, everyday things that I can do to help manage the stress levels, and this is definitely something you want to talk about as well. So with me, we went through this process, and we did... For starters, you had to get my brain into a relaxed state, and it took quite a long time to get my brainwaves into a different place. So what were we doing there? How does that work with the brainwave stuff?  Dr Don: Well, when we have a traumatic event or memory, that has been stored in a very high-resolution state. So in a beta brainwave state because all your senses are heightened: sight, smell, hearing. So it's recording that and storing it in memory in a very intense state. So if I sat down with you and said, 'Okay, let's get this fixed.' And I just started trying to work directly on that memory, you're still going to be in a very high agitated state because we're going to be starting to talk about this memory. So you're going to be in a beta brainwave state trying to recalibrate a beta stored memory. That's going to be very difficult to do.  So what we do is, and that's why I use the four hours because within that first an hour and a half to two hours, we're basically communicating with the subconscious part of the brain by telling stories, symbols with metaphors, goat and snowflake, all the stories, all the metaphors that are built-in because then your brain moves into an alpha state. When it's in alpha, that's where it does restoration. So it's very prepared to start restoring. And then, if you remember, by the time we got to a couple of the traumatic memories, we only work on them for two or three minutes. Because you're in alpha, and so you've got this higher state of beta, and it recalibrates it into the same state that it's in. So if it's in alpha, it can take a beta memory, reprocess it in alpha, takes all the intensity out of it.  Lisa: So these brain waves, these beta states, just to briefly let people know, so this is speed, and correct me if I'm wrong, but it's the speed at which the brain waves are coming out. So in beta, like you'd see on ECG or something, it's sort of really fast. I think there's a 40 day... Dr Don: It's 15 to 30 hertz. Lisa: 15 to 30 hertz and then if you're in alpha, it's a lot lower than that? Dr Don: 7 to 14. Lisa: 7 to 14, and then below that is sort of when you're going into the sleep phase, either deep meditative or asleep. Dr Don: You're dreaming. Because what it's doing in dreaming is processing. So you're between 4 and 7 hertz. That's why people who have a lot of trauma have trouble sleeping. Because not only is their mind processing what it experienced during the day, it's also taking some of those old files saying, 'Well, okay, let's fix that now. Right. Let's get that.' That's where your nightmares are coming from. It was trying to get you into a processing to fix that. but it couldn't fix it. So it continues, and then when you go below 4 hertz, you go into delta. Delta is dreamless sleep and that's where the maintenance is getting done.  Lisa: That's the physical maintenance side more than the... Dr Don: Physical maintenance. Yeah, because that's not processing what it experienced anymore. What it's really now doing is saying, 'Okay, what are the issues that need to be dealt with?' So if you're very relaxed and you've had a very... Like me, right? I played hockey, so I had six concussions, 60 stitches, and never missed a hockey game. The only reason now that I understand I could do that is because I'm getting two or three times more Delta sleep than my teammates were. Lisa: Physical recuperative sleep.  Dr Don: Yeah, I was getting maximum restorative sleep. So an injury that I would have that could heal in two or three days, my teammates would two or three weeks. Because they were living in these, which I didn't know, a lot of my friends were dealing with trauma: physical, emotional, sexual abuse. I didn't know that was going on with my friends. Nobody talked about it. I didn't see it in their homes, but they were all dealing with that.  Lisa: So they are not able to get... So look, I've noticed since I've been through the program. My sleep is much better, and sometimes I still occasionally dream about Dad. But the positive dreams, if that makes sense. They're more Dad as he as he was in life and I actually think Dad's come to visit me and say, ‘Hi, give me a hug' rather than the traumatic last days and hours of his life, which was the ones that were coming in before and calling for that action and stopping me from having that restorative sleep.  I just did a podcast with Dr Kirk Parsley who's a sleep expert, ex-Navy SEAL and a sleep expert that's coming out shortly. Or I think by this time, it will be out, and understanding the importance, the super importance of both the delta and... What is the other one? The theta wave of sleep patterns, and what they do, and why you need both, and what parts of night do what, and just realising...Crikey, anybody who is going through trauma isn't experiencing sleep is actually this vicious cycle downwards. Because then, you've got more of the beta brainwave state, and you've got more of the stresses, and you're much less resilient when you can't sleep. You're going to... have health issues, and brain issues, and memory, and everything's going to go down south, basically.  Dr Don: That's why I didn't understand at the time. They just said 'Well, you're just super healthy. You heal really fast.' They had no other explanation for it. Now, I know exactly why. But it had nothing to do with my genetics. It had to do with my environment. Lisa: Just interrupting the program briefly to let you know that we have a new patron program for the podcast. Now, if you enjoy Pushing the Limits if you get great value out of it, we would love you to come and join our patron membership program. We've been doing this now for five and a half years and we need your help to keep it on here. It's been a public service free for everybody, and we want to keep it that way but to do that, we need like-minded souls who are on this mission with us to help us out. So if you're interested in becoming a patron for Pushing the Limits podcast, then check out everything on patron.lisatamati.com. That's patron.lisatamati.com.  We have two patron levels to choose from. You can do it for as little as 7 dollars a month, New Zealand or 15 dollars a month if you really want to support us. So we are grateful if you do. There are so many membership benefits you're going to get if you join us. Everything from workbooks for all the podcasts, the strength guide for runners, the power to vote on future episodes, webinars that we're going to be holding, all of my documentaries, and much, much more. So check out all the details: patron.lisatamati.com, and thanks very much for joining us.  Dr Don: That's, at the time, we just thought it was all, must have been genetics. But I realised now that it was environment as well. So maybe a genetic component to it as well, but then you take that and put that into this very beautiful, nurturing environment, I'm going to sleep processing in beta what I experienced that day and then my mind basically, at that point, is 'What do we need to work on? Not much. Let's go. Let's start now doing some maintenance.' Because it wants to address the top of item stuff first. What is it needs to be taken care of right now? Right? Those are the threats.  Once it gets the threats processed, then it can then start working on the things that are going to be the more long-term maintenance. So then it'll do that. But if it never gets out of that threat mode, it gets out for very little time. Then, if you're getting 30 minutes of delta sleep at night and I'm getting two hours, it's a no-brainer to figure out why I would heal faster.  Lisa: Absolutely, and this is independent of age and things because you've got all that that comes into it as well. Your whole chemistry changes as you get older and all this. There's other compounding issues as it gets more and more important that you get these pieces of the puzzle right.  Do you think that this is what leads to a lot of disease, cancers, and things like that as well? There's probably not one reason. There's a multitude of reasons, but it's definitely one that we can influence. So it's worth looking at it if you've got trauma in your life. People were saying to me 'Oh my God, you don't look good.' When you start hearing that from your friends, your people coming up to you and going, 'I can feel that you're not right.' People that are sensitive to you and know you very well, and you start hearing that over and over, and you start to think, 'Shit, something's got real. Maybe I need to start looking at this.'  Because it's just taking all your energy your way, isn't it, on so many levels. The restorative side and the ability to function in your life, and your work, and all of that, and that, of course, leads into depressive thoughts and that hyper-vigilant state constantly. That's really tiresome rather than being just chill, relax, enjoying life, and being able to... Like one of the things I love in my life is this podcast because I just get into such a flow state when I'm learning from such brilliant... Dr Don: You're in alpha. Lisa: I am. I am on it because this is, 'Oh. That's how that works.' And I just get into this lovely learning in an alpha state with people because I'm just so excited and curious. This is what I need to be doing more of. And less of the, if you'd see me half an hour ago trying to work out the technology. That's definitely not an alpha state for me. Dr Don: That's where they said Albert Einstein lived. Albert Einstein lived in alpha brainwave state. That's why information just float for him because there was no stress. He could then pull information very easily to float into. But if you're in a high beta brainwave state, there's too much activity. It has trouble focusing on anything because it's multiple threats on multiple fronts. So when we have a traumatic event, that's how it's being recorded. If you remember, what we talked about was there's a 400 of a millionth of a second gap in between your subconscious mind seeing the information and it going to your consciousness. So in 400 millionths of a second, your subconscious mind has already started a response into an action even though your conscious mind is not even aware of it yet.  Lisa: Yeah. Exactly what I did with rescuing my partner with the glass falling off the thing. I hadn't reached that logically. Dr Don: It's funny because that's one of the things that I talked about ,which is sort of, give us all a little bit of grace. Because if you've had a lot of trauma, you're going to respond a certain way. How could you not? If your mind's filtering into all of that, of course you're going to respond with that kind of a response because your mind is prone to go into that action very, very quickly. So we can give ourselves a little bit of grace in understanding that of course, you're going to do that, right? And not beat ourselves up.  Because you know what I talked about with everybody, there's nothing wrong with anybody. There's nothing wrong with anybody's mind. Everybody's mind is fine except you are experiencing something different than I experienced so your mind kept responding to it, and mine didn't have that. So you had multiple... Think about we have a hundred percent of our energy on our phone when we wake up in the morning, right? Fully powered up. You fire the phone up and eight programs open up, right? And mine has one.  Lisa: Yeah. You're just focusing on what you need to. Dr Don: Then noon comes, and you're having to plug your phone back in because you're out of energy.  Lisa: That's a perfect analogy. You're just burning the battery. My all is a hundred windows open in the back of my brain that is just processing all these things and so now, I can start to heal. So having gone through this process with you, like you said, we worked on a number of traumatic experiences, and I went through them in my mind. And then you did certain things, made me follow with my eyes and track here, and my eyes did this, and then, we pulled my attention out in the middle of the story and things. That helped me stay in that alpha state, brainwave state as I probably now understand while I'm still reliving the experience. That's sort of taking the colour out of it so that it's now sort of in a black and white folder. Now, it can still be shared, and it hasn't taken away the sadness of... Dr Don: Because it is sad that these things happen but that's not the response for an action which is that fear or anger, right? That dysregulation of the nervous system. That's what we want to stop, because that is what is going to affect health, enjoyment of life and everything else.  Lisa: Wow, this is so powerful. Yeah, and it's been very, very beneficial for me and helped me deal. For me, it also unfolded. Because after the four hour period with you, I had audiotapes and things that are meditations to do every day for the next 30 days. What were we doing in that phase of the recovery? What were you targeting in those sort of sessions?  Dr Don: So if you remember what we talked about, we have two memory systems. The explicit memory is what we worked on on that four hours. That's detail, events, and experiences. Once we get the mind processing through that, then we have to work on the same memory animals have, which is that associative repetitive memory. So you've built a series of codes on how to respond to threats, and that has come in over repetition and associations. So the audios are designed to start getting you now to build some new neural pathways, some new ways to respond because your mind won't switch a pattern instantly. It can switch a memory instantly, but a pattern is something that got built over a period of time. So it's like a computer. If I'm coding on my computer, I can't take one key to stop that code. I have to write a new code. Yeah, so what we're doing over the 30 days is writing new code. Lisa: Helping me make new routines and new habits around new neural pathways, basically.  Dr Don: You don't have that explicit memory interfering with the pathways. Because now, it's not constantly pulling you out, going back into an action call. It's basically now able to look at this information and these codes that got built and say, 'Okay, what's a better way? So do we have a better way of doing it?' Or 'Show me that code. Write that code.' If that code looks safer, then your mind will adopt that new code. Lisa: This is why, I think for me, there was an initial, there was definitely... Like the nightmares stopped, the intrusive every minute, hour triggering stopped, but the process over the time and the next... And I'm still doing a lot of the things and the meditations. It's reinforcing new habit building. This is where... Like for people dealing with addictions, this is the path for them as well, isn't it?  Dr Don: Yeah. Because I talked about addiction as a code. I don't believe it's a disease. Your mind has found a resource to stop pains, and your subconscious mind is literal. It doesn't see things as good or bad, or right or wrong. It's literal. 'Did that stop the pain? Let's do that.' Because it's trying to protect you. So if you've now repeated it over and over, not only have you stopped the pain, but you've built an association with a substance that is seen as beneficial. Lisa: Because your brain sees it as medicine when you're taking, I don't know, cocaine or something. It sees it as essential to your life even though you, on a logical level, know that, ‘This is destroying me and it's a bad thing for me.' Your subconscious goes, 'No, this is a good thing and I need it right now.' Dr Don: Because it's in the present, when does it want the pain to stop? Now. So it has no ability to see a future or a past. Your subconscious is in the moment. So if you take cocaine, the logical part of your brain goes, 'Oh, this is going to create problems for me. I'm going to become addicted.' Right? Your subconscious goes, ‘Well, the pain stopped. We don't see that as a bad thing.' I always use the analogy: Why did people jump out of the buildings at 911? They weren't jumping to die. They were jumping to live because when would they die? Now, if they jump, would they die? No. They stopped the death. So even jumping, which logically makes no sense, right? But to the subconscious mind, it was going to stop the pain now.  Lisa: Yeah, and even if it was two seconds in the future that they would die, your brain is going...  Dr Don: It doesn't even know what two seconds are.  Lisa: No. It has no time. Isn't it fascinating that we don't have a time memory or understanding in that part of the brain that runs 95% of the ship?  Dr Don: It's like what Albert Einstein said, ‘There's no such thing as time.' So it's like an animal. If an animal could communicate and you say, 'What time is it?' That would make no sense to an animal. 'What do you mean? It's now.' 'What time is it now?' 'Now. Exactly.' Lisa: It's a construct that we've made to... Dr Don: Just to explain a lot of stuff, right? When something happens.  Lisa: Yeah, and this is quite freeing when you think of it. But it does make a heck of a lot of sense. So people are not being destructive when they become drug addicts or addicted to nicotine, or coffee, or chocolate. They're actually trying to stop the pain that they're experiencing in some other place and fix things now. Even though the logical brain... Because the logical brain is such a tiny... Like this is the last part of our evolution, and it's not as fully...  We can do incredible things with it at 5%. We've made the world that we live in, and we're sitting here on Zoom, and we've got incredible powers. But it's all about the imagination, being able to think into the future, into the past, and to make correlations, and to recognise patterns. That's where all our creativity and everything, or not just creativity, but our ability to analyse and put forth stuff into the world is happening. But in actual, we're still like the animals and the rest of it. We're still running at 95%, and that's where we can run into the problems with these two.  Dr Don: Because you got two systems. You got a very advanced system operating within a very primitive system, and it hasn't integrated. It's still integrating, right? So if there's a survival threat, survival will always override reason and logic, because it's designed to protect you. So there's no reason and logic that will come in if there's a survival threat. It's just going to respond the way it knows, does this Google search, 'What do we know about this threat? How do we know to protect ourselves, and we'll go instantly into survival mode.' Again, there's the reason and logic. Why would you jump out of a building, right? If you applied reason and logic, you wouldn't have jumped, right? People will say, 'Well, but they still jumped.' Yes, because reason and logic didn't even come into the process. It was all about survival.  Lisa: Yeah. When the fire is coming in it was either... Dr Don: 'Am I going to die out now or I'm going to move and not die now?'  Lisa: Yeah, and we're also prone to movement when we're in agitation and in an agitated state, aren't we? Basically, all of the blood and the muscles saying, 'Run, fight, do something. Take action.' Dr Don: That's why when people get into depression, it's the absence of those emotions.  Lisa: Yeah, and people feel exhaustion.  Dr Don: Yeah. The mind kept calling for an action using anger, for example, but you can't do the action because it's not happening, so it shuts down to protect you and stops calling for any emotion, and that's depression. So the key to get out of depression is actions. It's to get something happening. So in a lot of people who are depressed, what do I tell them to do? 'Start moving. Start exercising. Get out. Start doing things.' Right?  Lisa: So I run ultras. Dr Don: Exactly. Perfect example, right?  Lisa: Yeah, because I was. I was dealing with a lot of shit in my life at the time when I started doing ultra-marathons. To run was to quiet the pain and to run was to be able to cope and to have that meditative space in order to work through the stuff that was going on in my life. And I know even in my husband's life, when he went through a difficult time, that's when he started running. So running can be a very powerful therapeutic, because there is a movement, and you're actually burning through the cortisol and the adrenaline that's pouring around in your body. Therefore, sitting still and that sort of things was just not an option for me. I had to move. And it explains what, really. It's calling the movement. Like it was a movement because I couldn't fix the other thing.  Dr Don: That's what they'll tell you to do. To get out of depression is to move. What I say is the way to get out of depression is to get your mind to resolve what it's been asking for. Lisa: It's going a little deeper.  Dr Don: Yeah. So it's going down and saying, 'Okay, why has it been getting you angry and now, it shut down from the anger?' Because it's been trying to get you in your situation. 'Don't let Dad die. Don't let this happen.' Right? So because you couldn't do it, it just shuts down. Makes perfect sense but when we get to the resolution that there is no action required, there's no need for the depression anymore. The depression will lift because there's no more call for an action.  Lisa: I can feel that in me, that call. Anytime that anything does still pop up, I sort of acknowledge the feeling and say, 'There is no call for action here. This is in the past. This is a memory.' So I do remind myself that when things do still pop up from time to time now, as opposed to hourly. I go, 'Hey, come back into the now. This is the now. That was the then that's calling for an action. This is why you're doing thing.' Even that understanding

In this month's EM Quick Hits podcast, Anand Swaminathan on tips and tricks in polytrauma, Rohit Mohindra on diagnosis and management of toxic megacolon, Jesse McLaren on ECG in pulmonary embolism, Victoria Myers on approach to the patch call for cardiac arrest, Brit Long on when to do a CT head before LP, Salim Rezaie on nebulized ketamine - the ketaBAN study... The post EM Quick Hits 33 Polytrauma Tips & Tricks, Toxic Megacolon, ECG in PE, Patch Calls, CT Before LP, Nebulized Ketamine appeared first on Emergency Medicine Cases.

Medicare Advantage star ratings released; Security firm raises FIN12 ransomware attack concerns. Plus: Withings receivesan FDA clearance for Scan Watch's ECG and SpO2 monitoring features .Links to the stories:See the rankings: More than 70 health plans earned 5 stars in Medicare Advantage star ratingsCyber experts warn of 'aggressive' threat actor targeting healthcareWithings scores FDA clearance for smartwatch ECG and SpO2 monitoring

Please join author Milton Packer and Associate Editor Justin Ezekowitz as they discuss the Perspective "Heart Failure and a Preserved Ejection Fraction: A Side-by-Side Examination of the PARAGON-HF and EMPEROR-Preserved Trials." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, it really is so great to be back with you chatting about the papers here in the Journal. Thank you for going solo and for just being the greatest partner on earth. Thank you for that. For everyone listening in, we are back with some gusto and especially with this feature discussion today. You are not going to want to miss it. We are talking to Dr. Milton Packer as well as Dr. Justin Ezekowitz. We are going to compare PARAGON and EMPEROR-Preserved trials in heart failure with preserved ejection fraction. A really interesting discussion you're not going to want to miss, but now let's start with some papers in today's issue. I'd like to start, please. Dr. Greg Hundley: You bet. Dr. Carolyn Lam: Greg, you know the optimal duration of antiplatelet therapy in patients with high bleeding risk with or without oral anticoagulation after coronary stenting? Well, that still remains a question. Today's paper is a pre-specified subgroup analysis of the MASTER DAPT trial and reports on the outcomes of patients with or without an oral anticoagulation indication in this study. Dr. Greg Hundley: Right, Carolyn. Remind us. What was the MASTER DAPT trial? What did it test? Dr. Carolyn Lam: Ah. MASTER DAPT investigated an abbreviated or one-month versus a non-abbreviated or three to 12-month dual antiplatelet therapy and a stopping of antiplatelet therapy at six months strategy after coronary stenting in an all-comer population at high bleeding risk. Dr. Greg Hundley: Carolyn, what did this subgroup analysis of outcomes in patients with and without oral anticoagulation show? Dr. Carolyn Lam: At 12 months of follow-up, ischemic and net risk did not differ with abbreviated versus non-abbreviated anti-platelet regimens in both subgroups, although significantly fewer clinically relevant bleeding events occurred in the group without an oral anticoagulation indication. Whereas only numerically fewer bleeding events occurred in the group with an oral anticoagulation indication that did not reach statistical significance. This subgroup analysis from the MASTER DAPT trial really adds additional evidence that dual antiplatelet therapy beyond one month in patients with or without an indication for oral anticoagulation really has no benefit and only increases bleeding risk. Dr. Greg Hundley: Oh, very important finding, Carolyn. Great research. Well, Carolyn, how the extracellular matrix microenvironment modulates the contractile phenotype of vascular smooth muscle cells and confers vascular homeostasis really remains elusive. Thus, these investigators led by Professor Wei Kong at Peking University applied protein-protein interaction network analysis to explore novel extracellular matrix proteins associated with the vascular smooth muscle cell phenotype. Dr. Carolyn Lam: Huh. Interesting. What did they find, Greg? Dr. Greg Hundley: Right, Carolyn. By combining an in-vitro and an in-vivo genetic mice vascular injury model, they identified nidogen-2, a basement membrane glycoprotein, as a key extracellular matrix protein for maintenance of vascular smooth muscle cell identity. Nidogen-2 exerted its protective function via direct interaction and modulation of Jagged1-Notch3 signaling. Dr. Carolyn Lam: Wow! Nidogen-2 and Jagged1-Notch3. I always learn so much. What are the clinical implications, Greg? Dr. Greg Hundley: Right, Carolyn. Perhaps targeting nidogen-2 to precisely modulate Jagged1-Notch3 signaling, well, that may provide novel therapeutic strategy for atherosclerosis and post-injury restenosis. Dr. Carolyn Lam: Very nice. Well, in the next paper, we discuss inflammation in heart failure. We know that inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Interesting, huh? Well, these authors, Dr. Wollert and colleagues from Hannover Medical School in Germany, identified an adaptive crosstalk between inflammatory cells and cardiomyocytes that protects against persistent afterload stress-induced heart failure in mice. Monocytes and macrophages produced myeloid-derived growth factor in the pressure overloaded myocardium to augment SERCA2a expression in cardiomyocyte's calcium cycling and contractility. Myeloid-derived growth factor plasma concentrations were also found to be elevated in patients with aortic stenosis and to decline after aortic valve implantation indicating that pressure overload also triggers myeloid-derived growth factor release in humans. Dr. Greg Hundley: Carolyn, really informative preclinical science, but what are the clinical implications? Dr. Carolyn Lam: Ah. These observations molecularly defined a feature of the inflammatory response to hemodynamic overload that protects against heart failure development. Inflammation's beneficial trade therefore need to be considered when developing inflammation as a therapeutic target in heart failure. All of this is really discussed in a lovely editorial entitled Inflammation and Heart Failure: Friend or Foe? That's by Drs. Hajjar and Leopold. Dr. Greg Hundley: Great job, Carolyn. Well, my next paper focuses on resistant hypertension. Carolyn, although lifestyle modifications generally are effective in lowering blood pressure among patients with unmedicated hypertension or those treated with one to two antihypertensive agents, the value of exercise and diet for lowering blood pressure in patients with resistant hypertension is unknown. To address this, Professor James Blumenthal and co-authors at Duke University Medical Center enrolled 140 patients with resistant hypertension with an average age of 63 years, 48% women, 59% black, 31% diabetes, and 21% with chronic kidney disease and randomly assigned them to A, a four-month cardiac rehab center-based program of lifestyle modification. We're going to call that C-LIFE, consisting of dietary counseling, behavior and weight management, and exercise. Or number 2 or the B, a single counseling session providing standardized education and physician advice. We'll call that SEPA. Dr. Greg Hundley: The primary endpoint was clinic measured systolic blood pressure. Secondary endpoints included 24-hour ambulatory blood pressure and selective cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of baroreflex on heart rate; high-frequency heart rate variability to assess vagally-mediated modulation of heart rate; flow-mediated dilation to evaluate endothelial function; and pulse wave velocity to assess arterial stiffness; and then finally left ventricular mass to characterize left ventricular structure and remodeling. Dr. Carolyn Lam: Wow! That is a very, first of all, important clinical question. Then also, just very intricate methodology in assessing this. What did they find? Dr. Greg Hundley: Right, Carolyn. Between-group comparisons revealed that the reduction in clinic systolic blood pressure was greater in C-LIFE compared with SEPA. Next, 24-hour ambulatory systolic blood pressure also was reduced in C-LIFE with no change in SEPA. Then next, compared with SEPA, C-LIFE resulted in greater improvements in baroreflex sensitivity, high-frequency heart rate variability, and flow-mediated dilation. There was no between-group differences in pulse wave velocity or LV mass. Dr. Greg Hundley: Carolyn, diet and exercise can lower blood pressure in patients with resistant hypertension. When delivered in a cardiac rehabilitation setting, a four-month program of diet and exercise as adjunctive therapy, results in a significant reduction in clinic and ambulatory blood pressure, and improvement in selected cardiovascular disease biomarkers. Dr. Carolyn Lam: Wow! Really nice, Greg. Okay. Well, looks like we're all going to round up already with what else there is in today's issue. Let me start. There's an exchange of letters between Drs. Fang and Vinceti regarding the article Blood Pressure Effects on Sodium Reduction: Dose-Response Meta-analysis of Experimental Studies. Dr. Greg Hundley: Right, Carolyn. I've got a few things in the mail bag. First, Professor Anker has a Research Letter regarding the Kidney Function After Initiation and Discontinuation of Empagliflozin in Heart Failure Patients With and Without Type 2 Diabetes: Insights From the EMPERIAL Trials. Dr. Gerstenfeld has an ECG challenge entitled Atrioventricular Block with Narrow and Wide QRS: The Pause That Refreshes. Then lastly, Dr. Donald Lloyd-Jones has an AHA update regarding the American Heart Association's focus on primordial prevention. Well, Carolyn, I can't wait to hear this fantastic feature discussion with you and Dr. Packer. How about we jump to that? Dr. Carolyn Lam: Great. Let's go, Greg. Dr. Carolyn Lam: Because side-by-side exam of PARAGON and EMPEROR is like side-by-side of... Dr. Justin Ezekowitz: You can compare our new and our old prime minister much like your paper did. Dr. Milton Packer: Yeah, yeah. Dr. Justin Ezekowitz: There are [crosstalk] and it could be viewed until they perform in the broader world how it goes. You don't quite know. Dr. Milton Packer: The only problem is you can't do a head-to-head comparison of the old prime minister and the new prime minister. Dr. Justin Ezekowitz: That is true except that the head-to-head comparison includes excellent care by both the new and the old. I think that comparison's going to be pretty equal. I think we can case-control that one. Dr. Carolyn Lam: I really liked that that was politically correct because we are recording. Everybody, welcome to the feature discussion. I am here with Dr. Milton Packer from Baylor and he really needs no introduction. We're discussing heart failure with preserved ejection fraction. As well as our associate editor, Dr. Justin Ezekowitz from University of Alberta. Hence, in case anybody's wondering, we were talking about the Canadian elections. Let's just launch straight into it, a side-by-side comparison of PARAGON and EMPEROR-Preserved. Dr. Packer... Milton, if I may, what in the world drove you to do this? Dr. Milton Packer: My God. Oh, my God. Yes. Dr. Carolyn Lam: Tell us about what drove you to do this and please, if you could just summarize the results. Dr. Milton Packer: Well, let me just say from the outset that this was a commentary, not an original research article. Dr. Carolyn Lam: Yes. Dr. Milton Packer: The commentary was motivated by two very straightforward observations. We had two large scale outcome trials of two different drugs in heart failure with a preserved ejection fraction. I was privileged to serve as you were, Carolyn, on the leadership committees of both trials. It's not as if we have involvement in only one trial. We have involvement in both trials and we are very proud of that involvement. Dr. Milton Packer: One trial came in with a effect size of about 13% on its primary endpoint with a borderline P-value. A second trial, EMPEROR-Preserved, came in with a 21% reduction and its primary endpoint with a really small and persuasive P-value. The two patient populations in the two trials were really amazingly similar. We wanted to understand why it was 21% in one trial and persuasively so and why it appeared to be smaller in the PARAGON trial with sacubitril/valsartan. We thought, well, maybe that difference was related to how endpoints were defined or maybe that difference was related to the influence of ejection fraction. The reason we got excited about that was that as almost everyone knows, PARAGON found an influence of ejection fraction on the effect of sacubitril/valsartan in patients with HFpEF. We found an influence of ejection fraction on the effect of empagliflozin in HFpEF in EMPEROR-Preserved. We wanted to understand whether that influence was similar in the two trials. Dr. Milton Packer: Just to make life simple, PARAGON had created certain cut points for ejection fraction. They had presented and previously published in Circulation endpoints based on those cut points of ejection fraction. All we did was we used their endpoints and their cut points, and we put the two trials side by side. We did not do a statistical comparison of the effect size. There're actually no P-values in the whole commentary. But what we wanted to see was: Was the shape of the ejection fraction influence relationship similar or different in the two trials? Well, very simple. In PARAGON, as has been reported, there was a linear relationship: as ejection fraction increased, the effect of sacubitril/valsartan got smaller. In EMPEROR-Preserved, there was also an attenuation at a highest ejection fraction, but the relationship wasn't linear. It was like a hockey stick. It was flat and then went up at an ejection fraction over 62.5, which was the cut point that PARAGON used. Dr. Milton Packer: When we compared patients between the low 40s and the low 60s, the effect size in empagliflozin appeared to be larger than the effect size of sacubitril/valsartan in that ejection fraction group using the same endpoints. In fact, for hospitalizations for heart failure, which is really what SGLT2 inhibitors do, it was twice as great with empagliflozin in EMPEROR-Preserved than with sacubitril/valsartan in PARAGON-HF. We thought this was really interesting. We put the pictures up side by side. We wrote a commentary and Circulation was so kind to accept it. Dr. Carolyn Lam: Oh, but Milton, you were very, honestly as always, very clever to have done this analysis. But if I could reiterate a few things for the audience, which is very important. First of all, as you rightly first pointed out, it's a perspective piece. It is not a head-on comparison with P-values. It could not be. Let's just also give the audience a bit of background in that PARAGON included patients with an ejection fraction of 45% and above. EMPEROR-Preserved was above 40. PARAGON looked at total heart failure hospitalizations and cardiovascular death as a primary outcome. EMPEROR looked at first cardiovascular death or heart failure hospitalization. Dr. Carolyn Lam: Let's just remember the designs were different. Of course in the comparison, PARAGON compared sacubitril/valsartan versus valsartan. I like the way you very carefully wrote in your study that it was more a study of neprilysin inhibition since it's sacubitril/valsartan against valsartan and it was empagliflozin versus placebo. We know that it's important to state that as a basis. Then really important to say to everybody out there, pick up our journal. You must look at this bigger. I myself have already cited it at least twice already, Milton, because people will just naturally ask that. "Are the results different because of ejection fraction or different endpoints?" What you did there in that beautiful figure is that you tried as best as you can to match it up in terms of ejection fraction bins and match it up in terms of hospitalizations. There. I just wanted to state those few things, but I'm really- Dr. Milton Packer: Oh, no. No. Carolyn, you're 100% right. That's why there are couple of things. I just want to underscore what you said because I think your points were spot on. First of all, we really lined up the endpoints and the ejection fraction. We tried our best to compare apples and apples. It would not have been a useful exercise for us to compare different endpoints and different ejection fraction subgroups. But I just want to make sure that everyone understands: I'm a big fan of sacubitril/valsartan and I'm a big fan of neprilysin inhibition. As you know, both PARADIGM-HF and PARAGON-HF weren't really tests of sacubitril/valsartan; they were tests of neprilysin inhibition. They were great tests at that. PARAGON in particular was a great test of that. We're comparing neprilysin inhibition and SGLT2 inhibition. Dr. Milton Packer: But here's my most important point: we do not want people to choose one over the other. That was not the intent. We think that there are data in patients with certain ejection fractions, let's say between 40 and 60, I'm just creating a range, where both interventions are appropriate. Now I understand there are cost considerations and I don't want to minimize that, but we are not suggesting that anyone prefer one drug over the other. All we wanted to do was we wanted to ask the question: Since the effect size in one trial seemed to be different than the effect size in the other trial, what were the ejection fraction subgroups that represented that difference? We found that the patients with ejection fractions greater than 60, 65% did not contribute to that difference. It was the patients with lower ejection fractions that contributed to the difference. I hope that's helpful. Dr. Carolyn Lam: Ah. That's wonderful. Justin, have you recovered from the talk about the Canadian elections? Dr. Justin Ezekowitz: Oh. I have indeed. Dr. Carolyn Lam: I'm on swinging. Dr. Justin Ezekowitz: I have indeed. Thanks for recognizing that Canada just had a major election we carried out in six weeks. But, Milton, I really enjoyed reading this. Maybe I can just ask you about two elements within this perspective piece, which is number 1, what's incredibly concordant is a lack of difference across cardiovascular death for both agents in both trials regardless of the trial differences and the potential differences in patient populations recruited; that's number 1. It's incredibly flat for cardiovascular death. Dr. Justin Ezekowitz: But number 2 is there is a danger in comparing trials even non-statistically. That's often a pitfall we get into, but we have to put some frame of reference on that. What is the one or two key things you think differ between PARAGON and EMPEROR-Preserved that you say, "You really need to look at these trials differently"? Those two questions came to mind when looking at this great figure that you produced. Dr. Milton Packer: Okay. The first question is so much easier and that is that these drugs don't reduce cardiovascular deaths. Full stop. It's really interesting because sacubitril/valsartan reduces cardiovascular death in people with ejection fractions of 40% or less, but not in patients with ejection fraction greater than that. The primary effect is heart failure hospitalizations. Empagliflozin didn't reduce cardiovascular death even in patients with the ejection fraction less than 40% or greater than 40%. What we're really, really talking about two drugs where the major effect is a reduction in heart failure hospitalizations. That comes out whether you do the analysis as time-to-first-event or total heart failure hospitalizations. Dr. Milton Packer: Of course, we're looking forward to the DELIVER trial with dapagliflozin. My own personal expectation is they're going to come out with a very striking effect on heart failure hospitalizations and not on cardiovascular deaths. Cardiovascular deaths in patients with HFpEF is really... It's a hard goal because only half of the deaths are cardiovascular. These patients have so many comorbidities that influence prognosis. The other thing, which is really important, is that heart failure hospitalizations only represented 18% of all hospitalizations in these patients; it's really small. I think of empagliflozin as being a treatment of the heart failure of HFpEF, not a treatment for HFpEF. I hope that makes sense. Justin, what was your second question? Dr. Justin Ezekowitz: Absolutely. Dr. Milton Packer: Oh, the differences between- Dr. Justin Ezekowitz: Yeah. Thank you, Milton. Dr. Milton Packer: Okay. There's always differences between two trials. As I said before, Carol and I were involved in both trials. They were done slightly at different times. They didn't overlap. Remember that the cut points in the two trials, one was 40%, one was 45%, really didn't matter to our analysis because we corrected for that in our ejection fraction subgroups. I was actually really much more impressed by the similarities than by the differences, but here's the catch. HFpEF is an incredibly heterogeneous disease. When we look at baseline characteristics, we're looking at means, medians, percentages. We're not picking up on any heterogeneity and there's a lot of heterogeneity. I actually think that HFrEF is a reasonably homogeneous disease. I think HFpEF is an incredibly diverse disease with a whole host of different disorders. What I'm amazed by is that we actually got an effect size that was greater than 20% in an all-comers HFpEF analysis. Dr. Milton Packer: But in all honesty, Justin, it wasn't really all-comers. We excluded people with BMIs over 45. There are a lot of patients who are obese and had BMIs greater than 45 who have HFpEF. By the way, especially in Texas. I didn't say that. We didn't enroll those patients. In all honesty, if I had to do it all over again, I would have. By the way, PARAGON didn't enroll them either. Dr. Carolyn Lam: Well, this is an incredible conversation. I know that we could just do a whole hour of chatting about what this implies for the higher ejection fraction, what this implies for how we should be treating heart failure. I don't even dare to ask for some last words maybe from both Justin and Milton, but recognizing that the time is short, anything else to add? Dr. Milton Packer: I think Justin should do last words. Dr. Justin Ezekowitz: Well, let me summarize by saying there is a hockey stick. We love hockey sticks in Canada. A simple and an excellent comparison. I think people should really look at that figure to understand it, but do not undertreat your patients with HFpEF and look at these with a grain of salt. Thanks for joining us, Milton. Thanks, Carolyn. Dr. Milton Packer: Thank you so much. Dr. Carolyn Lam: On behalf of Greg and I, you've been listening to Circulation on the Run. Thank you so much for joining us today and don't forget to tune in again next week. Dr. Greg Hundley: This program is copyright of the American Heart Association 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors, or of the American Heart Association. For more, visit ahajournals.org.

The Electricity Company of Ghana (ECG) has assured consumers it will not embark on any load shedding as speculated in the media.The power distributor is embarking on a plan maintenance work that will be carried out by the Ghana Grid Company (GRIDCo) The Managing Director of ECG, Kwame Agyemang- Budu speaking at a press conference in Accra assured the public of enough power to stabilise its network during the maintenance work.

Welcome to October's papers of the month! Should patients who gain a ROSC following an out of hospital cardiac arrest go for an immediate angiogram if their ECG does not show an STEMI or Left Bundle Branch Block? We've looked at this before with the COACT trial which only looked at those patients with a shockable rhythm but this months paper looks at all ROSCs from all rhythms. Next up we take a look at a paper that investigates senior paramedics decision making in cessation of cardiac arrests and think further about the decision making that goes into these complex decisions. Finally we take a look at a huge trial assessing the use of balanced fluids versus Normal Saline in critically ill patients and gain more information about the strategy we should employ. Once again we'd love to hear any thoughts or feedback either on the website or via twitter @TheResusRoom. Enjoy! Simon & Rob

In this session we will examine the varied pathology of Transient Loss of Consciousness (TLOC), the definition, the causes, the sequalae, and the management. I wanted to also examine some of the key aspects of TLOC that are red flags and should be examined further within clinical practice. To do this I have Consultant Cardiologist and Honorary Senior Lecturer, Dr Nicholas Gall with me. In the episode we look at an established definition of TLOC, Nick's efforts to start a blackout pathway, the fundamental problem of TLOC in unpacking why undifferentiated TLOC can be a clinical minefield. We then examine the aetiology of TLOC and the diagnostic tools with which to differentiate the pathology (USS and ECG nuances). We then look at red flags warning signs and subtle information cues with TLOC, treatment of TLOC patients (broad take home messages) and clinical examples from practice. I hope you enjoy this episode with a fascinating and insightful guest.

In this second episode on vascular access, the team from the Australian Vascular Access Society (AVAS) discuss vessel assessment with RaCeVa and RaPeVa as well as the use of Micropuncture and establishing optimal catheter tip position.  Before puncturing a vessel for vascular access it is important to: Trace the anatomy of the vascular pathway for aberrancy Ensure that the vessel calibre is suitable for the chosen catheter Ensure no obstruction with thrombus or occlusion Moreover, it is vital that the catheter doesn't occupy more than one-third of the diameter of the vessel. This will significantly reduce venous blood flow and increase the risk of catheter-related thrombosis. For PICC line insertion the arm can be divided into three zones to select an optimal vessel puncture site. The brachial fossa region is a "Red - no Go" zone, the mid-arm is the "Green - Optimal" zone and the proximal third of the arm is a "Yellow - Axillary" zone. When inserting a line, the catheter tip should be at the cavoatrial junction approximately 3-5cm below the carina on a chest X-ray. The use of a navigation system like catheter tip ECG (intracavitary ECG) is extremely accurate. It is often still useful in patients in atrial fibrillation but more difficult for patients' with paced rhythms. For more like this, head to codachange.org/podcasts/ 

This week's episode features special Guest Host Victoria Delgado, as she interviews author Qiang Zhang and Greg (who was the editorialist and handling editor) as they discuss the article "Towards Replacing Late Gadolinium Enhancement with Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your cohost. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. And Carolyn, this week's feature actually is a magnetic resonance imaging paper, which you know, of course, I'm very fond of. And these authors have come up with a new methodology to get information equivalent to a late gadolinium-enhanced exam without administering gadolinium. But before we get to that feature discussion, how about we start in with some of the other articles in this issue? Dr. Carolyn Lam: Yep. Dr. Greg Hundley: Well, how about if I go first? So Carolyn, the first paper I'm going to discuss is from Dr. Paul Welsh from the University of Glasgow, and it pertains to abdominal aortic aneurysms, which you know can occur in patients who are ineligible for routine ultrasound screening. A simple abdominal aortic aneurysm risk score was derived and compared to current guidelines used for ultrasound screening of abdominal aortic aneurysms. Dr. Greg Hundley: And so, this study comes to us from the UK Biobank, and they examined participants without previous, and let's just abbreviate this as AAA or AAA. So without previous AAA, we're split into a derivation cohort of 401,820 individuals, and a validation cohort of 83,000 individuals. An incident AAA was defined as a first hospital, inpatient diagnosis of AAA, death from AAA, or a AAA-related surgical procedure. And, of course, they used multivariable Cox models to develop the derivation cohort, and then apply that to the validation cohort. Dr. Carolyn Lam: Wow, Greg, that is a large number of people, the power of the UK Biobank, huh? So, what did they find? Dr. Greg Hundley: Right. So, Carolyn, components of the AAA risk score were age, stratified by smoking status, weight, stratified by smoking status, any hypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and then diabetes. Dr. Greg Hundley: So, Carolyn, in the validation cohort, over 10 years of follow-up, the C index, for the model for the USPSTF guidelines, was 0.705, whereas, the C index of the risk score as a continuous variable was 0.856. And in the validation cohort, the USPSTF model yielded a sensitivity of 63%, and a specificity of 71%. Dr. Carolyn Lam: Okay, Greg, but what's a take-home message? Dr. Greg Hundley: Right, Carolyn. So the take-home message is that in an asymptomatic general population, a risk score based on patient age, height, weight, and a medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. And also, these results highlight that further development and validation of risk scores to detect asymptomatic AAA are needed. Dr. Carolyn Lam: Wow, and that was a great summary with a lot more data in the article, huh? Let's refer the readers to it. But for my paper, it highlights the key role of histidine triad nucleotide-binding protein 1, or HINT 1, in the pathogenesis of cardiac hypertrophy. Dr. Greg Hundley: Wow. Carolyn, so tell me a little bit more about HINT 1. Dr. Carolyn Lam: I thought you may ask. HINT 1 is a highly-conserved 14 kilodalton protein that belongs to the histidine triad super family. It was previously shown to play a role in diverse neuropsychiatric diseases. Loss of HINT 1 increased susceptibility to carcinogenesis in mice, suggesting, as well, a tumor suppressor role. So recently, HINT 1 has emerged as a tumor suppressor with multiple molecular mechanisms, involving regulation of apoptosis, gene transcription, and cell cycle control. Dr. Carolyn Lam: Now, with that as a background, today's paper from co-corresponding authors Drs. Ji, Xie and Han, from Nanjing Medical University, used animal models and cell models of hypertrophic growth, and found that HINT 1 deficiency aggravated overload-induced cardiac hypertrophy and fibrosis and deteriorated cardiac dysfunction in mice, whereas, cardiac-specific HINT 1 over-expression attenuated cardiac hypertrophy, and rescued cardiac dysfunction. Dr. Carolyn Lam: Furthermore, the more the authors uncovered Homeobox A5, or Hox A5, as a HINT 1 target gene, which contributed to hypertrophy through activating the TGF beta signal pathway. Combined, these findings demonstrate HINT 1 may be a prognostic biomarker, and this may establish a foundation for future investigation of its potential as a therapeutic target for cardiac hypertrophy and heart failure. Greg Hundley: Great, Carolyn. So, we get a hint for future cardiac hypertrophy. Dr. Carolyn Lam: Hahaha. Dr. Greg Hundley: Couldn't resist. Dr. Carolyn Lam: Bravo. Dr. Greg Hundley: Couldn't resist. So, Carolyn, my next paper comes to us from Dr. Mark Gladwin from the University of Pittsburgh. And, as you know, many patients with one of your faves, heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension. Now, increases in pulmonary vascular resistance, in patients with HFpEF portend a poor prognosis. This phenotype is referred to as combined pre- and post-capillary pulmonary hypertension. Dr. Greg Hundley: And therapeutic trials of exercise-induced pulmonary hypertension, and pre- and post-capillary pulmonary hypertension, have been disappointing, suggesting the need for strategies that target upstream mechanisms of the disease. And so, this work reports novel rat exercise-induced pulmonary hypertension models and mechanisms of pulmonary vascular dysfunction, centered around the transcriptional repression of the soluble guanylate cyclase enzyme in pulmonary artery smooth muscle cells. Dr. Carolyn Lam: Ooh, so much of this is of interest to me, from HFpEF to soluble guanylate cyclase. Ah, all right, so what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So, in the HFpEF and in the pre- and post-capillary pulmonary hypertension models, metabolic syndrome contributed to pulmonary vascular dysfunction and exercise-induced pulmonary hypertension through enhanced reactive oxygen species and MIR193B expression, which downregulates NFYA-dependent soluble guanylate cyclase beta-1 expression, and adenovirus mediated NFYA over-expression and SGLT-2 inhibition restored NFYA soluble guanylate cyclase beta-1 cyclic GMP signaling, and ameliorated exercise-induced pulmonary hypertension. Dr. Greg Hundley: So Carolyn, after all of that, these results uncover a molecular explanation for the unsolved clinical associations linking metabolic syndrome with exercise-induced pulmonary hypertension in patients with pre- and post-capillary pulmonary hypertension, as well as HFpEF. Dr. Carolyn Lam: Wow. That is super, Greg. Thanks. Now, other articles in today's issue include a research letter by Dr. Schunkert on identification of a functional PDE5A variant at the chromosome 4q27 coronary artery disease locus in an extended myocardial infarction family. Dr. Carolyn Lam: There is a policy front paper by Dr. Lackey on applying decision analysis to inform FDA's benefit risk assessment of ticagrelor for primary prevention of myocardial infarction or stroke, based on the THEMIS trial. There's an exchange of letters between Drs. Olson and Reiffel regarding the article emulating randomized controlled trials with non-randomized real-world evidence studies, the first results of the RCT Duplicate Initiative. Dr. Greg Hundley: Great. Carolyn. Well, I've got two other papers. There's an ECG challenge from Professor Macherey entitled, Wide QRS complex bradycardia in a hemodynamically unstable young woman. And then, finally, one of our nice perspective pieces from Dr. Armstrong entitled, Extending the product label for ticagrelor: Looking under the FDA hood. Well, Carolyn, now we're going to learn a little bit more about that non-contrast method of MRI to get, maybe, the equivalent to late gadolinium enhancement in patients with hypertrophic cardiomyopathy. Dr. Carolyn Lam: And all by AI. Very, very cool. All right, let's go. Dr. Victoria Delgado: Hello, I'm Victoria Delgado, associate editor of Circulation, and working at the University Medical Center, and I have the privilege to welcome Dr. Zhang from the University of Oxford, division of cardiovascular medicine, and first author of the article published in Circulation, which presents a new technology that has the potential to change our clinical practice, and how do we assess myocardial tissue characteristics, particularly fibrosis with cardiac magnetic resonance. Dr. Victoria Delgado: With us, we have also Dr. Greg Hundley from VCU Pauley Heart Center, associate editor of Circulation, and host of Circulation on the Run and editorialist of this article. And Greg has handled this article in the review process and guided Dr. Zhang and coworkers to finally get a very impactful, in my opinion, and novel paper that has the potential to change clinical practice. He will help us to put in perspective the main message of this article. But first, Dr. Zhang, why don't you tell us briefly, what is this new technology for myocardial tissue characterization with cardiovascular magnetic resonance, and why did you develop it? Dr. Qiang Zhang: Well, first, I want to say thank you very much for the invitation. Well, as we know, CMR late-gadolinium enhancement, or LGE, has been the imaging gold standard for micro tissue catheterization. However, LGE requires the injection of a contrast agent, which prolongs the scan, increase the cost, and is cautioned in some patient groups. It is therefore desirable to develop a contrast-free technique to replace LGE. A native or pre-contrast CMR such as cine imaging, T1-mapping and the T2-mapping are alternative means for myocardial tissue characterization without the need for contrast. Dr. Qiang Zhang: And notably, T1-mapping can detect a wider range of pathology, but its clinical application is hindered by confounding factors and a lack of clear interpretation. So we thought that since MRI is inherently multimodal and multiparametric, with different modalities reflecting complimentary information about micro tissue, therefore can we use the ones of an AI  method to combine the enhanced pre-contrast and modalities to produce a virtual LGE image without the need for contrast, and this leads to our concept of CMR virtual native enhancement. Dr. Victoria Delgado: Excellent. And in which population did you evaluate this technology? Why did you choose? So, can you tell us a little bit the characteristics of the population where you choose to assess the performance of this new technology? Dr. Qiang Zhang: Yes, so we validated this concept first on the hypertrophic cardiomyopathy patients using the image data from HCMR study, which is a larger multinational study. We trained the new network models on about 2,700 images, and then we tested independently on 124 patient materials. Dr. Victoria Delgado: And what were the results? Can you summarize them for us to understand what you found, how you evaluated the performance of this new technology compared to classical late gadolinium enhancement? Dr. Qiang Zhang: Yeah. So, we found that first, the VNE image had significantly better image quality than the traditional LGE, and the secondly, the VNE revealed characteristic HCM lesions in hypertrophic segment and added the anterior and the inferior right ventricular insertion point, and those VNE lesions were in high visual spatial agreement with the lesions detected by LGE. And thirdly, VNE correlated strongly with LGE in quantifying hyperintensity, micro lesions, but also more subtle intermediate-intensity lesions as often observed in the HCM patients. Dr. Victoria Delgado: Exciting. And now I would like to turn to Greg. You are a renowned expert on CMR. What did this article attract you? What were the main findings that you found interesting in this article? Dr. Greg Hundley: Yes. Thank you so much, Victoria. And just first, before I get started, I wanted to thank Zhang for sending us this work, and his entire team really spanning several institutions around the globe. Victoria, I want to thank you for leading this discussion. And Victoria, we work as a team looking at imaging, and what's very impressive is this caught multiple of us on the imaging team, but also the editorial board. So want to thank you Victoria. And then, finally, I want to thank Dr. Charlotte Manisty and Jennifer Jordan who helped with the editorial. Dr. Greg Hundley: So, just to take a little bit of a step back in the year 2000, Dr. Ray Kim, Dr. Bob Bono, Dr. Bob Judd at Northwestern University, in Chicago, administered gadolinium contrast. It's an extra cellular agent and they were examining myocardial perfusion, and then they noticed if they took images 10 or so minutes after that administration, they appreciated this late enhancement of the myocardial tissue that was associated with two things, one myocardial injury, and then, also, scar formation. Dr. Greg Hundley: And for the last 21 years, that technique has been very valuable in assessing infarct size in those with ischemic cardiomyopathy, and then also recognizing extracellular fibrosis or forms of myocardial injury in a variety of non-ischemic cardiomyopathy processes. And one of those is hypertrophic cardiomyopathy. And so, Zhang and his group have been working on a technique that did not utilize gadolinium anymore. And they based this on, really, had two important features. Dr. Greg Hundley: One is, some examination of the T1 relaxation that's available when you acquire magnetic resonance images, and then also applying artificial intelligence to analysis of these images. Those two factors allowed this investigative team to produce images that are very similar to what we appreciate with gadolinium enhancement in patients with hypertrophic cardiomyopathy. And why is that significant? So administration of gadolinium, we think about two things, again, that are an issue with that. Dr. Greg Hundley: Well, one, we've got to give the contrast agent, and some patients are not well-suited. If you have renal dysfunction, you can develop nephrogenic systemic fibrosis, a scleroderma-like syndrome when the gadolinium is not cleared, and it's stays in your body a long time. The other thing we tend to worry about much more recently was accumulation of gadolinium in the brain stem. We don't know that that has an adverse effect, but we're certainly aware of it. Dr. Greg Hundley: And finally, I guess there is a third point. There are a few patients, one in 20 to 40,000 that have allergic reactions. So, for all those patients that really can't get gadolinium, this is another potential opportunity moving forward. The second point is time. So during an MRI scan time, or process, we administer the gadolinium. And remember what I said, we've got to wait about 10 minutes to then collect these images. Well, if you can have a technique where you don't have to administer gadolinium, you get the same administration and you don't have to wait that 10 minutes, we might be able to save a large amount of time. And you say, well, 10 minutes, what does that mean? Dr. Greg Hundley: But if you're doing many patients during the day, that really could equate to a big time-savings. So what attracted us to this article? A technical innovation that perhaps may obviate the need for the administration of gadolinium in many cases, and here in these patients with hypertrophic cardiomyopathy, I think the images were quite stunning in that they appreciated the extent of the fibrosis and scar in patients with hypertrophic cardiomyopathy to the same degree, and maybe even with higher image quality than we had in the gadolinium-enhanced comparitors. Dr. Victoria Delgado: Yeah. I agree with all those comments, indeed. For these 20 years, there have been other developments, in terms of assessing diffuse fibrosis with T1-mapping techniques after administration of gadolinium, but also before administration of gadolinium. And this technology Dr. Zhang and co-workers have shown actually reduces the time of acquisition because you only need 15 minutes to acquire the cine images and the T1 images. And the analysis is not very long in terms of post-processing, because it's also very short. As seen the paper was indicated. Dr. Victoria Delgado: And as you said, the administration of gadolinium enhancement is not free of potential risks. And in these patients, for example, we have hypertrophic cardiomyopathy that can undergo repetitive evaluations during follow-up. The use of this imaging technique can help to reduce the exposure to gadolinium enhancement. Dr. Victoria Delgado: Now, the question for you, Qiang, will be, what are the next steps for you and your team to further develop this technique, to further convince the community to implement this technique in clinical practice, and that can have an impact in our management of these patients with hypertrophic cardiomyopathy, or with other patients on whom we also evaluate the presence of myocardial fibrosis? Dr. Qiang Zhang: Thank you, Victoria. And thank you Greg, for the very insightful comments. So we think that the immediate future work would be to validate the VNE HCMR study clinical outcomes as a potential new contrast-free biomarker for HCM patients. And in the meantime, we are working on extending the method to other pathologies, particularly myocardial infarction, for viability assessment. Dr. Qiang Zhang: And we also think that the concept of AI virtual contrast agent maybe apply it to other post-contrast images, such as early gadolinium enhancement and extracellular volume refraction mapping, or even, maybe, first perfusion. And also in collaboration with MR vendors, we plan to implement VNE as inline sequence on the scanner to display lesions immediately after the pre-contrast cine and the T1-mapping acquisitions. Dr. Victoria Delgado: Very interesting. And Greg, another group of patients, for example, that I'm thinking of where this technology can be very helpful, and you have expertise on this, are patients undergoing treatment with chemotherapy, what we need to address, for example, or to evaluate the presence of cardiac toxicity. Would you see in this population the value of this technique, or how do you see the future of these technique in clinical practice? Dr. Greg Hundley: Yeah. Great questions, Victoria. I think probably five things and many of those Qiang has already just brought up. One, with the current study, it's going to be great to follow these patients over time and look at the outcomes. What did amount, presence, location of the findings with this new technique, how did they equate to outcomes in patients with hypertrophic cardiomyopathy? So we're going to anxiously await that. Dr. Greg Hundley: I think once we move out of the current study, thinking about other vendors, using this and acquiring images from General Electric and Phillips, and multiple vendors around the world and multiple field strengths, how do we going to understand the findings there? I think another particular issue will be different diseases as Qiang ha said, ischemic cardiomyopathy. Well, what about amyloid? Victoria, you've mentioned using the other possibility here is, can this technique help us produce something similar to extracellular volume fraction measures? And could that be used to identify interstitial disease processes? Dr. Greg Hundley: And, for example, as you mentioned, the fibrosis that's associated with the administration of certain chemotherapeutic agents or radiation therapy. I think another thing is, Qiang, can we go back and use retrospectively-collected data? Can your technique be modified so that many of the studies that have been performed in the past, large population studies, like Mesa or a Framingham or Jackson heart study, and could we use that to develop forecasting and algorithms moving forward? Dr. Greg Hundley: And then, lastly, I think as you mentioned, the artificial intelligence component of what you've described and how's that can compare when Victoria and I look at the images, and could we get into combining reads from one institution, reads from another, reads from another, tracking outcomes? And so, when a patient comes in and has a study performed, your artificial intelligence, not only does it read that study and highlights the increased signal in the myocardium, but then goes and looks at outcomes across multiple sites, and what would that mean for a given patient with a different condition? So, oh my goodness, the horizon is just so expansive here. The future is very bright. And just to congratulate you on, I really think this could be another landmark technical innovation, so fantastic work. Dr. Victoria Delgado: Indeed. Thank you very much, Greg, for all these insightful comments and these perspectives that we have in the future, particularly with the use of this technique in retrospective studies in large cities, that where we can develop these algorithms. And I would like also to thank Qiang for submitting your article to Circulation, for giving us the opportunity to present this new technology and make this article, like the landmark article, where there will be many other articles to follow. We hope that you also choose us. Dr. Victoria Delgado: But with this, I would like to thank both of you, Greg and Qiang, for the excellent discussion that we have had in this new technology, based on artificial intelligence, that can identify myocardial fibrosis without the use of gadolinium enhancement, that maybe by now will be obsolete in the future, and that can impact on how we do our clinical practice. Many thanks to all of you and happy to discuss in the future other articles. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, I want to thank our speakers, and then also, wish everyone a great week. And we will catch you next week On the Run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.  

During this presentation, logical steps to rhythm strip analysis will be recalled and applied to a rapid review of sinus, atrial, junctional and ventricular rhythms. The significance of each rhythm will be examined and potential interventions considered. The target audience includes nurses or health care providers seeking to refresh prior learning or increase confidence with ECG rhythm interpretation.

AirTags screen protectors, Fitbit Luxe, Donda Stem player This is what Apple's AirPods look like on the inside The AudioStick is the easiest way to connect AirPods to your Switch Netflix Now Offers Spatial Audio Support for iPhone and iPad Someone's inexplicably gone and made AirTags 'screen protectors' Leviton's second-generation Decora Dimmer review: Wi-Fi connected HomeKit switches Why the app store model won't work for Alexa skill discovery The New Oculus Quest feature can automatically sync VR photos and video clips to your phone Google Nest Doorbell (2021) Review: Cheaper, but Not Better Google Nest Doorbell (Battery) Review: Smart And Chunky Google Shuts Down Android Auto Smartphone App Google Health division dissolved as the company restructures Fitbit adds ECG and stress-level scanning to its Charge fitness tracker Fitbit Luxe review: Not as luxurious as the name suggests Offline playback on Spotify's Wear OS app is rolling out now YouTube Music Wear OS app finally released A tour of Jason's smart home The usefulness of Family Bell on Google Assistant Kanye West's Donda Stem player Samsung Galaxy Watch 4 Classic Hosts: Matthew Cassinelli and Jason Howell Download or subscribe to this show at https://twit.tv/shows/smart-tech-today Get episodes ad-free with Club TWiT at https://twit.tv/clubtwit Show notes and links for this episode are available at: https://twit.tv/shows/smart-tech-today/episodes/93 Sponsor: casper.com/stt promo code STT

AirTags screen protectors, Fitbit Luxe, Donda Stem player This is what Apple's AirPods look like on the inside The AudioStick is the easiest way to connect AirPods to your Switch Netflix Now Offers Spatial Audio Support for iPhone and iPad Someone's inexplicably gone and made AirTags 'screen protectors' Leviton's second-generation Decora Dimmer review: Wi-Fi connected HomeKit switches Why the app store model won't work for Alexa skill discovery The New Oculus Quest feature can automatically sync VR photos and video clips to your phone Google Nest Doorbell (2021) Review: Cheaper, but Not Better Google Nest Doorbell (Battery) Review: Smart And Chunky Google Shuts Down Android Auto Smartphone App Google Health division dissolved as the company restructures Fitbit adds ECG and stress-level scanning to its Charge fitness tracker Fitbit Luxe review: Not as luxurious as the name suggests Offline playback on Spotify's Wear OS app is rolling out now YouTube Music Wear OS app finally released A tour of Jason's smart home The usefulness of Family Bell on Google Assistant Kanye West's Donda Stem player Samsung Galaxy Watch 4 Classic Hosts: Matthew Cassinelli and Jason Howell Download or subscribe to this show at https://twit.tv/shows/smart-tech-today Get episodes ad-free with Club TWiT at https://twit.tv/clubtwit Show notes and links for this episode are available at: https://twit.tv/shows/smart-tech-today/episodes/93 Sponsor: casper.com/stt promo code STT

AirTags screen protectors, Fitbit Luxe, Donda Stem player This is what Apple's AirPods look like on the inside The AudioStick is the easiest way to connect AirPods to your Switch Netflix Now Offers Spatial Audio Support for iPhone and iPad Someone's inexplicably gone and made AirTags 'screen protectors' Leviton's second-generation Decora Dimmer review: Wi-Fi connected HomeKit switches Why the app store model won't work for Alexa skill discovery The New Oculus Quest feature can automatically sync VR photos and video clips to your phone Google Nest Doorbell (2021) Review: Cheaper, but Not Better Google Nest Doorbell (Battery) Review: Smart And Chunky Google Shuts Down Android Auto Smartphone App Google Health division dissolved as the company restructures Fitbit adds ECG and stress-level scanning to its Charge fitness tracker Fitbit Luxe review: Not as luxurious as the name suggests Offline playback on Spotify's Wear OS app is rolling out now YouTube Music Wear OS app finally released A tour of Jason's smart home The usefulness of Family Bell on Google Assistant Kanye West's Donda Stem player Samsung Galaxy Watch 4 Classic Hosts: Matthew Cassinelli and Jason Howell Download or subscribe to this show at https://twit.tv/shows/smart-tech-today Get episodes ad-free with Club TWiT at https://twit.tv/clubtwit Show notes and links for this episode are available at: https://twit.tv/shows/smart-tech-today/episodes/93 Sponsor: casper.com/stt promo code STT

AirTags screen protectors, Fitbit Luxe, Donda Stem player This is what Apple's AirPods look like on the inside The AudioStick is the easiest way to connect AirPods to your Switch Netflix Now Offers Spatial Audio Support for iPhone and iPad Someone's inexplicably gone and made AirTags 'screen protectors' Leviton's second-generation Decora Dimmer review: Wi-Fi connected HomeKit switches Why the app store model won't work for Alexa skill discovery The New Oculus Quest feature can automatically sync VR photos and video clips to your phone Google Nest Doorbell (2021) Review: Cheaper, but Not Better Google Nest Doorbell (Battery) Review: Smart And Chunky Google Shuts Down Android Auto Smartphone App Google Health division dissolved as the company restructures Fitbit adds ECG and stress-level scanning to its Charge fitness tracker Fitbit Luxe review: Not as luxurious as the name suggests Offline playback on Spotify's Wear OS app is rolling out now YouTube Music Wear OS app finally released A tour of Jason's smart home The usefulness of Family Bell on Google Assistant Kanye West's Donda Stem player Samsung Galaxy Watch 4 Classic Hosts: Matthew Cassinelli and Jason Howell Download or subscribe to this show at https://twit.tv/shows/smart-tech-today Get episodes ad-free with Club TWiT at https://twit.tv/clubtwit Show notes and links for this episode are available at: https://twit.tv/shows/smart-tech-today/episodes/93 Sponsor: casper.com/stt promo code STT

This week's episode features special Guest Host Victoria Delgado, as she interviews author Qiang Zhang and Greg (who was the editorialist and handling editor) as they discuss the article "Towards Replacing Late Gadolinium Enhancement with Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your cohost. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. And Carolyn, this week's feature actually is a magnetic resonance imaging paper, which you know, of course, I'm very fond of. And these authors have come up with a new methodology to get information equivalent to a late gadolinium-enhanced exam without administering gadolinium. But before we get to that feature discussion, how about we start in with some of the other articles in this issue? Dr. Carolyn Lam: Yep. Dr. Greg Hundley: Well, how about if I go first? So Carolyn, the first paper I'm going to discuss is from Dr. Paul Welsh from the University of Glasgow, and it pertains to abdominal aortic aneurysms, which you know can occur in patients who are ineligible for routine ultrasound screening. A simple abdominal aortic aneurysm risk score was derived and compared to current guidelines used for ultrasound screening of abdominal aortic aneurysms. Dr. Greg Hundley: And so, this study comes to us from the UK Biobank, and they examined participants without previous, and let's just abbreviate this as AAA or AAA. So without previous AAA, we're split into a derivation cohort of 401,820 individuals, and a validation cohort of 83,000 individuals. An incident AAA was defined as a first hospital, inpatient diagnosis of AAA, death from AAA, or a AAA-related surgical procedure. And, of course, they used multivariable Cox models to develop the derivation cohort, and then apply that to the validation cohort. Dr. Carolyn Lam: Wow, Greg, that is a large number of people, the power of the UK Biobank, huh? So, what did they find? Dr. Greg Hundley: Right. So, Carolyn, components of the AAA risk score were age, stratified by smoking status, weight, stratified by smoking status, any hypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and then diabetes. Dr. Greg Hundley: So, Carolyn, in the validation cohort, over 10 years of follow-up, the C index, for the model for the USPSTF guidelines, was 0.705, whereas, the C index of the risk score as a continuous variable was 0.856. And in the validation cohort, the USPSTF model yielded a sensitivity of 63%, and a specificity of 71%. Dr. Carolyn Lam: Okay, Greg, but what's a take-home message? Dr. Greg Hundley: Right, Carolyn. So the take-home message is that in an asymptomatic general population, a risk score based on patient age, height, weight, and a medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. And also, these results highlight that further development and validation of risk scores to detect asymptomatic AAA are needed. Dr. Carolyn Lam: Wow, and that was a great summary with a lot more data in the article, huh? Let's refer the readers to it. But for my paper, it highlights the key role of histidine triad nucleotide-binding protein 1, or HINT 1, in the pathogenesis of cardiac hypertrophy. Dr. Greg Hundley: Wow. Carolyn, so tell me a little bit more about HINT 1. Dr. Carolyn Lam: I thought you may ask. HINT 1 is a highly-conserved 14 kilodalton protein that belongs to the histidine triad super family. It was previously shown to play a role in diverse neuropsychiatric diseases. Loss of HINT 1 increased susceptibility to carcinogenesis in mice, suggesting, as well, a tumor suppressor role. So recently, HINT 1 has emerged as a tumor suppressor with multiple molecular mechanisms, involving regulation of apoptosis, gene transcription, and cell cycle control. Dr. Carolyn Lam: Now, with that as a background, today's paper from co-corresponding authors Drs. Ji, Xie and Han, from Nanjing Medical University, used animal models and cell models of hypertrophic growth, and found that HINT 1 deficiency aggravated overload-induced cardiac hypertrophy and fibrosis and deteriorated cardiac dysfunction in mice, whereas, cardiac-specific HINT 1 over-expression attenuated cardiac hypertrophy, and rescued cardiac dysfunction. Dr. Carolyn Lam: Furthermore, the more the authors uncovered Homeobox A5, or Hox A5, as a HINT 1 target gene, which contributed to hypertrophy through activating the TGF beta signal pathway. Combined, these findings demonstrate HINT 1 may be a prognostic biomarker, and this may establish a foundation for future investigation of its potential as a therapeutic target for cardiac hypertrophy and heart failure. Greg Hundley: Great, Carolyn. So, we get a hint for future cardiac hypertrophy. Dr. Carolyn Lam: Hahaha. Dr. Greg Hundley: Couldn't resist. Dr. Carolyn Lam: Bravo. Dr. Greg Hundley: Couldn't resist. So, Carolyn, my next paper comes to us from Dr. Mark Gladwin from the University of Pittsburgh. And, as you know, many patients with one of your faves, heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension. Now, increases in pulmonary vascular resistance, in patients with HFpEF portend a poor prognosis. This phenotype is referred to as combined pre- and post-capillary pulmonary hypertension. Dr. Greg Hundley: And therapeutic trials of exercise-induced pulmonary hypertension, and pre- and post-capillary pulmonary hypertension, have been disappointing, suggesting the need for strategies that target upstream mechanisms of the disease. And so, this work reports novel rat exercise-induced pulmonary hypertension models and mechanisms of pulmonary vascular dysfunction, centered around the transcriptional repression of the soluble guanylate cyclase enzyme in pulmonary artery smooth muscle cells. Dr. Carolyn Lam: Ooh, so much of this is of interest to me, from HFpEF to soluble guanylate cyclase. Ah, all right, so what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So, in the HFpEF and in the pre- and post-capillary pulmonary hypertension models, metabolic syndrome contributed to pulmonary vascular dysfunction and exercise-induced pulmonary hypertension through enhanced reactive oxygen species and MIR193B expression, which downregulates NFYA-dependent soluble guanylate cyclase beta-1 expression, and adenovirus mediated NFYA over-expression and SGLT-2 inhibition restored NFYA soluble guanylate cyclase beta-1 cyclic GMP signaling, and ameliorated exercise-induced pulmonary hypertension. Dr. Greg Hundley: So Carolyn, after all of that, these results uncover a molecular explanation for the unsolved clinical associations linking metabolic syndrome with exercise-induced pulmonary hypertension in patients with pre- and post-capillary pulmonary hypertension, as well as HFpEF. Dr. Carolyn Lam: Wow. That is super, Greg. Thanks. Now, other articles in today's issue include a research letter by Dr. Schunkert on identification of a functional PDE5A variant at the chromosome 4q27 coronary artery disease locus in an extended myocardial infarction family. Dr. Carolyn Lam: There is a policy front paper by Dr. Lackey on applying decision analysis to inform FDA's benefit risk assessment of ticagrelor for primary prevention of myocardial infarction or stroke, based on the THEMIS trial. There's an exchange of letters between Drs. Olson and Reiffel regarding the article emulating randomized controlled trials with non-randomized real-world evidence studies, the first results of the RCT Duplicate Initiative. Dr. Greg Hundley: Great. Carolyn. Well, I've got two other papers. There's an ECG challenge from Professor Macherey entitled, Wide QRS complex bradycardia in a hemodynamically unstable young woman. And then, finally, one of our nice perspective pieces from Dr. Armstrong entitled, Extending the product label for ticagrelor: Looking under the FDA hood. Well, Carolyn, now we're going to learn a little bit more about that non-contrast method of MRI to get, maybe, the equivalent to late gadolinium enhancement in patients with hypertrophic cardiomyopathy. Dr. Carolyn Lam: And all by AI. Very, very cool. All right, let's go. Dr. Victoria Delgado: Hello, I'm Victoria Delgado, associate editor of Circulation, and working at the University Medical Center, and I have the privilege to welcome Dr. Zhang from the University of Oxford, division of cardiovascular medicine, and first author of the article published in Circulation, which presents a new technology that has the potential to change our clinical practice, and how do we assess myocardial tissue characteristics, particularly fibrosis with cardiac magnetic resonance. Dr. Victoria Delgado: With us, we have also Dr. Greg Hundley from VCU Pauley Heart Center, associate editor of Circulation, and host of Circulation on the Run and editorialist of this article. And Greg has handled this article in the review process and guided Dr. Zhang and coworkers to finally get a very impactful, in my opinion, and novel paper that has the potential to change clinical practice. He will help us to put in perspective the main message of this article. But first, Dr. Zhang, why don't you tell us briefly, what is this new technology for myocardial tissue characterization with cardiovascular magnetic resonance, and why did you develop it? Dr. Qiang Zhang: Well, first, I want to say thank you very much for the invitation. Well, as we know, CMR late-gadolinium enhancement, or LGE, has been the imaging gold standard for micro tissue catheterization. However, LGE requires the injection of a contrast agent, which prolongs the scan, increase the cost, and is cautioned in some patient groups. It is therefore desirable to develop a contrast-free technique to replace LGE. A native or pre-contrast CMR such as cine imaging, T1-mapping and the T2-mapping are alternative means for myocardial tissue characterization without the need for contrast. Dr. Qiang Zhang: And notably, T1-mapping can detect a wider range of pathology, but its clinical application is hindered by confounding factors and a lack of clear interpretation. So we thought that since MRI is inherently multimodal and multiparametric, with different modalities reflecting complimentary information about micro tissue, therefore can we use the ones of an AI  method to combine the enhanced pre-contrast and modalities to produce a virtual LGE image without the need for contrast, and this leads to our concept of CMR virtual native enhancement. Dr. Victoria Delgado: Excellent. And in which population did you evaluate this technology? Why did you choose? So, can you tell us a little bit the characteristics of the population where you choose to assess the performance of this new technology? Dr. Qiang Zhang: Yes, so we validated this concept first on the hypertrophic cardiomyopathy patients using the image data from HCMR study, which is a larger multinational study. We trained the new network models on about 2,700 images, and then we tested independently on 124 patient materials. Dr. Victoria Delgado: And what were the results? Can you summarize them for us to understand what you found, how you evaluated the performance of this new technology compared to classical late gadolinium enhancement? Dr. Qiang Zhang: Yeah. So, we found that first, the VNE image had significantly better image quality than the traditional LGE, and the secondly, the VNE revealed characteristic HCM lesions in hypertrophic segment and added the anterior and the inferior right ventricular insertion point, and those VNE lesions were in high visual spatial agreement with the lesions detected by LGE. And thirdly, VNE correlated strongly with LGE in quantifying hyperintensity, micro lesions, but also more subtle intermediate-intensity lesions as often observed in the HCM patients. Dr. Victoria Delgado: Exciting. And now I would like to turn to Greg. You are a renowned expert on CMR. What did this article attract you? What were the main findings that you found interesting in this article? Dr. Greg Hundley: Yes. Thank you so much, Victoria. And just first, before I get started, I wanted to thank Zhang for sending us this work, and his entire team really spanning several institutions around the globe. Victoria, I want to thank you for leading this discussion. And Victoria, we work as a team looking at imaging, and what's very impressive is this caught multiple of us on the imaging team, but also the editorial board. So want to thank you Victoria. And then, finally, I want to thank Dr. Charlotte Manisty and Jennifer Jordan who helped with the editorial. Dr. Greg Hundley: So, just to take a little bit of a step back in the year 2000, Dr. Ray Kim, Dr. Bob Bono, Dr. Bob Judd at Northwestern University, in Chicago, administered gadolinium contrast. It's an extra cellular agent and they were examining myocardial perfusion, and then they noticed if they took images 10 or so minutes after that administration, they appreciated this late enhancement of the myocardial tissue that was associated with two things, one myocardial injury, and then, also, scar formation. Dr. Greg Hundley: And for the last 21 years, that technique has been very valuable in assessing infarct size in those with ischemic cardiomyopathy, and then also recognizing extracellular fibrosis or forms of myocardial injury in a variety of non-ischemic cardiomyopathy processes. And one of those is hypertrophic cardiomyopathy. And so, Zhang and his group have been working on a technique that did not utilize gadolinium anymore. And they based this on, really, had two important features. Dr. Greg Hundley: One is, some examination of the T1 relaxation that's available when you acquire magnetic resonance images, and then also applying artificial intelligence to analysis of these images. Those two factors allowed this investigative team to produce images that are very similar to what we appreciate with gadolinium enhancement in patients with hypertrophic cardiomyopathy. And why is that significant? So administration of gadolinium, we think about two things, again, that are an issue with that. Dr. Greg Hundley: Well, one, we've got to give the contrast agent, and some patients are not well-suited. If you have renal dysfunction, you can develop nephrogenic systemic fibrosis, a scleroderma-like syndrome when the gadolinium is not cleared, and it's stays in your body a long time. The other thing we tend to worry about much more recently was accumulation of gadolinium in the brain stem. We don't know that that has an adverse effect, but we're certainly aware of it. Dr. Greg Hundley: And finally, I guess there is a third point. There are a few patients, one in 20 to 40,000 that have allergic reactions. So, for all those patients that really can't get gadolinium, this is another potential opportunity moving forward. The second point is time. So during an MRI scan time, or process, we administer the gadolinium. And remember what I said, we've got to wait about 10 minutes to then collect these images. Well, if you can have a technique where you don't have to administer gadolinium, you get the same administration and you don't have to wait that 10 minutes, we might be able to save a large amount of time. And you say, well, 10 minutes, what does that mean? Dr. Greg Hundley: But if you're doing many patients during the day, that really could equate to a big time-savings. So what attracted us to this article? A technical innovation that perhaps may obviate the need for the administration of gadolinium in many cases, and here in these patients with hypertrophic cardiomyopathy, I think the images were quite stunning in that they appreciated the extent of the fibrosis and scar in patients with hypertrophic cardiomyopathy to the same degree, and maybe even with higher image quality than we had in the gadolinium-enhanced comparitors. Dr. Victoria Delgado: Yeah. I agree with all those comments, indeed. For these 20 years, there have been other developments, in terms of assessing diffuse fibrosis with T1-mapping techniques after administration of gadolinium, but also before administration of gadolinium. And this technology Dr. Zhang and co-workers have shown actually reduces the time of acquisition because you only need 15 minutes to acquire the cine images and the T1 images. And the analysis is not very long in terms of post-processing, because it's also very short. As seen the paper was indicated. Dr. Victoria Delgado: And as you said, the administration of gadolinium enhancement is not free of potential risks. And in these patients, for example, we have hypertrophic cardiomyopathy that can undergo repetitive evaluations during follow-up. The use of this imaging technique can help to reduce the exposure to gadolinium enhancement. Dr. Victoria Delgado: Now, the question for you, Qiang, will be, what are the next steps for you and your team to further develop this technique, to further convince the community to implement this technique in clinical practice, and that can have an impact in our management of these patients with hypertrophic cardiomyopathy, or with other patients on whom we also evaluate the presence of myocardial fibrosis? Dr. Qiang Zhang: Thank you, Victoria. And thank you Greg, for the very insightful comments. So we think that the immediate future work would be to validate the VNE HCMR study clinical outcomes as a potential new contrast-free biomarker for HCM patients. And in the meantime, we are working on extending the method to other pathologies, particularly myocardial infarction, for viability assessment. Dr. Qiang Zhang: And we also think that the concept of AI virtual contrast agent maybe apply it to other post-contrast images, such as early gadolinium enhancement and extracellular volume refraction mapping, or even, maybe, first perfusion. And also in collaboration with MR vendors, we plan to implement VNE as inline sequence on the scanner to display lesions immediately after the pre-contrast cine and the T1-mapping acquisitions. Dr. Victoria Delgado: Very interesting. And Greg, another group of patients, for example, that I'm thinking of where this technology can be very helpful, and you have expertise on this, are patients undergoing treatment with chemotherapy, what we need to address, for example, or to evaluate the presence of cardiac toxicity. Would you see in this population the value of this technique, or how do you see the future of these technique in clinical practice? Dr. Greg Hundley: Yeah. Great questions, Victoria. I think probably five things and many of those Qiang has already just brought up. One, with the current study, it's going to be great to follow these patients over time and look at the outcomes. What did amount, presence, location of the findings with this new technique, how did they equate to outcomes in patients with hypertrophic cardiomyopathy? So we're going to anxiously await that. Dr. Greg Hundley: I think once we move out of the current study, thinking about other vendors, using this and acquiring images from General Electric and Phillips, and multiple vendors around the world and multiple field strengths, how do we going to understand the findings there? I think another particular issue will be different diseases as Qiang ha said, ischemic cardiomyopathy. Well, what about amyloid? Victoria, you've mentioned using the other possibility here is, can this technique help us produce something similar to extracellular volume fraction measures? And could that be used to identify interstitial disease processes? Dr. Greg Hundley: And, for example, as you mentioned, the fibrosis that's associated with the administration of certain chemotherapeutic agents or radiation therapy. I think another thing is, Qiang, can we go back and use retrospectively-collected data? Can your technique be modified so that many of the studies that have been performed in the past, large population studies, like Mesa or a Framingham or Jackson heart study, and could we use that to develop forecasting and algorithms moving forward? Dr. Greg Hundley: And then, lastly, I think as you mentioned, the artificial intelligence component of what you've described and how's that can compare when Victoria and I look at the images, and could we get into combining reads from one institution, reads from another, reads from another, tracking outcomes? And so, when a patient comes in and has a study performed, your artificial intelligence, not only does it read that study and highlights the increased signal in the myocardium, but then goes and looks at outcomes across multiple sites, and what would that mean for a given patient with a different condition? So, oh my goodness, the horizon is just so expansive here. The future is very bright. And just to congratulate you on, I really think this could be another landmark technical innovation, so fantastic work. Dr. Victoria Delgado: Indeed. Thank you very much, Greg, for all these insightful comments and these perspectives that we have in the future, particularly with the use of this technique in retrospective studies in large cities, that where we can develop these algorithms. And I would like also to thank Qiang for submitting your article to Circulation, for giving us the opportunity to present this new technology and make this article, like the landmark article, where there will be many other articles to follow. We hope that you also choose us. Dr. Victoria Delgado: But with this, I would like to thank both of you, Greg and Qiang, for the excellent discussion that we have had in this new technology, based on artificial intelligence, that can identify myocardial fibrosis without the use of gadolinium enhancement, that maybe by now will be obsolete in the future, and that can impact on how we do our clinical practice. Many thanks to all of you and happy to discuss in the future other articles. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, I want to thank our speakers, and then also, wish everyone a great week. And we will catch you next week On the Run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.  

It's the JournalFeed Podcast for the week of August 2-6, 2021. We cover GRACE-1, communicating stats better, managing seizures after initial control, POCUS for intussusception, and reading STEMI on ECG with a paced rhythm.

Valve's Steam Deck, Google updates, Amazon's Alexa developer conference The Steam Deck aims to kill the console once and for all I'm Begging You to Use a VPN at Hotels It's time for Alexa, Google Assistant, and Siri to swear Google Workspace users can now use Assistant on Nest Hub Google TV update adds an option to manually clear out the 'Continue watching' row Google Maps Timeline adds new monthly 'Insights' tab Volley's Magic Word is a voice-based puzzle game on Google Assistant New iOS 14.7, tvOS 14.7, and watchOS 7.6 updates expand ECG support and more iOS 15 & watchOS 8 now let you install them with almost no available space Amazon's Alexa voice options now include Shaq and Melissa McCarthy Amazon will let devs compete for your Echo Show's screen and everything else Alexa just added Amazon promises most Echo speakers will get upgraded to Matter Amazon aims to inject new life into Alexa with the release of developer tools and features Picks of the week Matthew & Mikah: MagSafe Battery Pack Hosts: Mikah Sargent and Matthew Cassinelli Download or subscribe to this show at https://twit.tv/shows/smart-tech-today Get episodes ad-free with Club TWiT at https://twit.tv/clubtwit Show notes and links for this episode are available at: https://twit.tv/shows/smart-tech-today/episodes/88 Sponsor: Molekule.com promo code STT120