Podcasts about has bled

Revoyez en 20 minutes avec Dr Jérôme Schwartz, cardiologue-rythmologue à Nancy, l'essentiel à savoir sur la fibrillation atriale et les nouvelles recommandations de l'European Society of Cardiology d'Août 2024. Au terme de ce podcast, vous aurez revu :  ✅ Qui anticoaguler ? Nouveau score CHA2DS2-VA

Deepthy Varghese, MSN, ACNP, FNP, Northside Hospital, is joined by Gregory Lip, MD., University of Liverpool, and Elaine Y. Wan, MD, FHRS Columbia University, Cardiology to discuss the limitations of current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) taking direct-acting oral anticoagulants (DOACs). Conducted as a secondary analysis of the RE-LY trial and validated in multiple cohorts, the study introduces the DOAC Score as a personalized risk assessment tool. The DOAC Score incorporates various covariates such as age, creatinine clearance, underweight status, medical history, and medication use to estimate the comparative risk for major bleeding. The risk prediction model demonstrated robust performance, outperforming the HAS-BLED score in terms of predictive accuracy. Internal and external validation in diverse cohorts, including the GARFIELD-AF registry, COMBINE-AF pooled clinical trial cohort, and administrative databases, confirmed the score's reliability in stratifying bleeding risk among individuals on different DOACs. The DOAC Score represents a significant advancement in tailoring risk assessments for bleeding in AF patients receiving DOAC therapy, contributing to more informed clinical decision-making.  https://www.hrsonline.org/education/TheLead https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064556 Host Disclosure(s): D. Varghese: No relevant financial relationships with ineligible companies to disclose. Contributor Disclosure(s): G. Lip: Honoraria, Speaking, and Consulting: Bristol-Myers Squibb, Pfizer, Inc., Daiichi  E. Wan: Honoraria, Speaking, and Consulting: Medtronic, National Institutes for Health, Sanofi, Boston Scientific, Research: Zoll Medical Corp. This episode has .25 ACE credits associated with it. If you want credit for listening to this episode, please visit the episode page on HRS365     https://www.heartrhythm365.org/URL/TheLeadEpisode54

Découvrez en 15 minutes avec Pr Popovic, cardiologue au CHRU de Nancy, l'essentiel à savoir concernant l'utilisation des anticoagulants oraux directs (AOD = NACO) en MG. ✅ Quelles sont les différences entre les 2 classes d'AOD ? ✅ Quelles sont les indications actuelles des AOD ? ✅ Quelles sont les différences de maniement par rapport aux AVK ? ✅ Quelles sont les posologies recommandées ? ✅ Quels sont les 3 points essentiels à surveiller dans la prescription des AOD ? ✅ Que faire quand un patient a une indication d'AOD et d'antiagrégants plaquettaires ? Marre de perdre du temps dans vos formations DPC ? Abonnez-vous ici

I am thrilled to introduce you to Midge Bowers.Not only is Midge a Clinical Professor and Director of the cardiovascular specialty at Duke University School of Nursing, she practices as a nurse practitioner in a Heart Failure Access Clinic.She's an expert in cardiology, a seasoned healthcare educator, and shares so much incredible knowledge in this jam-packed episode.In this episode, we covered:The importance of looking beyond creatinine levelsHow to focus on practical aspects of echosDemystifying anticoagulation choicesPractical tips on adjusting Warfarin dosagesReversal agents and safety measuresThis barely scratches the surface of the wealth of information Midge provides.0:00 - 3:35 - Introduction and Overview3:36 - 8:39 - Importance of Monitoring Creatinine and GFR 8:40 - 15:06 - Impact of New Medications on Kidney Function15:07 - 20:30 - Understanding Echo Results: Akinesia, Hypokinesia, and EF20:31 - 25:01 - Interpreting Trends in Echo Reports25:02 - 31:17 - Anticoagulation Choices: Warfarin vs. DOACs 31:18 - 38:15 - Adjusting Warfarin Dosages and INR Monitoring38:16 - 42:42 - Assessing Bleeding Risks with CHADS-VASc and HAS-BLED 42:43 - 46:03 - Reversal Agents and Safety in Anticoagulation46:04 - 53:41 - Managing DOACs in Different Clinical Scenarios Read the full blog here.______________________________Please note: This episode is intended only for medical providers and students learning to be medical providers. Hosted on Acast. See acast.com/privacy for more information.

CardioNerds (Amit Goyal), Dr. Colin Blumenthal (CardioNerds Academy House Faculty Leader and FIT at the University of Pennsylvania), and Dr. Anjali Wagle (CardioNerds Ambassador and FIT at Johns Hopkins University), discuss the baseline assessment of stroke and bleeding risk in patients with atrial fibrillation (AF) with Dr. Elaine Hylek. Dr. Hylek is a professor of medicine at the Boston University School of Medicine and is the Director of the Thrombosis and Anticoagulation Service at Boston Medical Center. Stroke is a potentially devastating and preventable complication of AF. Understanding the balance between stroke and bleeding risk is crucial in determining who should be on anticoagulation. Join us to discuss this topic! In the next episode of the series, we will discuss situational risk assessment in the context of peri-cardioversion, peri-procedural status, triggered atrial fibrillation, and more. Audio editing by CardioNerds Academy Intern, Pace Wetstein. This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal. This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. We have collaborated with VCU Health to provide CME. Claim free CME here! Disclosures: None Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Atrial Fibrillation PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Atrial Fibrillation: Assessment of Stroke & Bleeding Risk The CHA2DS2-VASc should be used to determine stroke risk in all patients. It was updated from the CHADS2 score to better separate patients into high and low risk and a score of 0 has a very low risk of a stroke.Understanding a given model's derivation is key to application for any risk model. Understanding who was and was not included when a risk score was derived helps determine how to clinically use it. For example, mechanical valves, hypertrophic cardiomyopathy, cardiac amyloidosis, and moderate to severe MS were all excluded or poorly represented and should receive AC in AF regardless of CV.The HAS-BLED score should be used to identify modifiable risk factors for bleeding and address them. It is less useful to determine when we should stop AC. Factors that go into the score are dynamic and the intention was to alert the provider of potentially modifiable factors that could be addressed to lower bleeding risk (such as better BP control).Fear the clot. Patients should be on AC unless there is a serious contraindication as embolic strokes can be devastating with a high mortality (~24% mortality at 30 days)“What am I saying by not writing the prescription... I am saying that it's OK to have an ischemic stroke.” Survey data shows that patients are willing to experience 3.5 GI bleeds on average before 1 stroke, so favoring AC is often a patient centered approach Notes - Atrial Fibrillation: Assessment of Stroke & Bleeding Risk Notes drafted by Dr. Anjali Wagle 1. Why do strokes happen in atrial fibrillation? Why is reducing stroke risk so important? Atrial fibrillation is associated with a significantly increased risk of stroke. The mortality of strokes related to AF have been estimated to be around 25% at 30 days in early studies which included either persistent or permanent AF, though of note, these studied were biased towards larger strokes since the diagnosis was based on physical exam and not high resolution imaging. AF promotes thrombogenesis through Virchow's triad which includes:

This podcast is the second in a series of three featuring insights from expert cardiology pharmacists on nonvalvular atrial fibrillation (NVAF). In this episode, cardiology pharmacist Stephanie Dwyer Kaluzna, PharmD, BCCP, reviews key literature and guideline recommendations for stroke prevention in patients with NVAF. Dr Dwyer Kaluzna discusses the most recent evidence for prescribing, dosing, and monitoring direct oral anticoagulants (DOACs); using the risk-screening tools HAS-BLED and CHA2DS2-VASc to design patient-specific pharmacotherapy plans; and the use of DOACs in special patient populations, including older patients, patients with end-stage renal disease, and patients with low or high body weights.Presenter:Stephanie Dwyer Kaluzna, PharmD, BCCP  Clinical Assistant ProfessorDepartment of Pharmacy PracticeUniversity of Illinois Chicago College of PharmacyCardiovascular Clinical PharmacistUniversity of Illinois Hospital and Health Science SystemChicago, IllinoisContent is based on an online CE program supported by an educational grant from the Bristol Myers Squibb Pfizer Alliance.This podcast series was first delivered as live webinars, which are now available as on-demand, CE-certified microlearning modules with downloadable slidesets. The program also features a ClinicalThought commentary and a downloadable infographic reference guide. To access the full program, go tohttps://bit.ly/3OMazV8

Dica de Prova: Como interpretar o Has Bled? by Cardiopapers

Dica de prova: Conhece o escore HAS-BLED? by Cardiopapers

This week is a Double Feature Circulation on the Run. Please join authors Alexander Benz and Lars Wallentin as they discuss their article "Biomarker-Based Risk Prediction With The ABC-AF Scores in Patients With Atrial Fibrillation Not Receiving Oral Anticoagulation." Then, please join author Timothy McKinsey, editorialist Thomas Gillette and Associate Editor Sergio Lavandero as they discuss the article "HDAC Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling" and the editorial "HDAC Inhibition in the Heart: Erasing Hidden Fibrosis." TRANSCRIPT BELOW 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: I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, I cannot get enough of our double features, and this one's really nice because it's a clinical feature and a preclinical feature, and both are just phenomenally interesting. The first is about the ABC-AF scores. In case you don't recognize it, well, then you just have to listen. Very, very important information on biomarker-based risk prediction in patients with atrial fibrillation, not receiving oral anticoagulation. Then we've got a really interesting paper talking about HDAC inhibition and diastolic dysfunction. Interested? Well, listen up. Dr. Carolyn Lam: First, let's talk about some of the papers in today's issue, shall we? I want to start, Greg. You grab your coffee. I need to talk about this first one, which really provides the first extensive genetic and phenotypic landscape of a very important condition, peripartum cardiomyopathy. This is from Dr. Arany and colleagues from Perlman School of Medicine, University of Pennsylvania. What they did is studied 469 women with peripartum cardiomyopathy, who were identified from several US and international academic centers. They acquired clinical information and DNA samples. Next-generation sequencing was performed on 67 genes and evaluated for the burden of truncating and missense variance. Dr. Carolyn Lam: What they found was that women with peripartum cardiomyopathy bear a significantly high burden of loss of function variants in a number of genes, including familiar ones like TTN, FLNC, DSP, and BAG3. The identity and relative abundance of these variants were remarkably similar to that seen in idiopathic dilated cardiomyopathy, indicating that the genetic predisposition to peripartum cardiomyopathy and dilated cardiomyopathy may be one in the same. Now, while peripartum cardiomyopathy patients with the TTN truncating variants presented with lower ejection fraction. No significant differences in the rates of recovery were seen. Dr. Greg Hundley: Really interesting, Carolyn. Clinically, what are the implications today as we see these patients? Dr. Carolyn Lam: Well, I think the most important one is that genetic counseling and testing should, perhaps, be considered for women with peripartum cardiomyopathy, following the guidelines for dilated cardiomyopathy. What about you, Greg? Dr. Greg Hundley: Very nice, Carolyn. Well, my paper evaluates the role of inflammation and outcomes in patients that sustain out-of-hospital cardiac arrest. It comes to us from Dr. Martin Meyer from Rigshospitalet. Carolyn, out-of-hospital cardiac arrest patients who remain comatose after initial resuscitation are at high risk of morbidity and mortality due to the ensuing post-cardiac arrest syndrome. Now, systemic inflammation constitutes a major component of the post-cardiac arrest syndrome and interleukin 6 levels are associated with this severity. The IL-6 receptor antagonists tocilizumab could potentially dampen inflammation after post-cardiac arrest. The objective of the present trial was to determine the efficacy of tocilizumab to reduce systemic inflammation after out-of-hospital cardiac arrest, A presumed cardiac cause, and thereby potentially mitigate organ injury. Dr. Carolyn Lam: Oh, wow. Interesting, Greg. what did they find? Dr. Greg Hundley: Carolyn, they had 80 comatose out-of-hospital cardiac arrest patients and they were randomized 1:1 in a double-blind, placebo-controlled trial to a single infusion of tocilizumab or placebo, in addition to standard of care, including targeted temperature management. The primary endpoint of the study was reduction of CRP response. This was achieved by tocilizumab, as there was a significant treatment-by-time interaction. Systemic inflammation was reduced by treatment with tocilizumab, as both CRP and leukocyte levels were markedly reduced. Now, myocardial injury was also reduced, documented by reductions in CK-MB and troponin T. However, there were no differences, Carolyn, in survival or neurological outcome. So Carolyn, it looks like for those that survive an out-of-hospital cardiac arrest and do experience neurological recovery, there could be cardiac benefits. Dr. Carolyn Lam: Wow, very interesting. I cannot imagine how difficult it must've been to perform such a trial. Thanks, Greg. Well, the next paper demonstrates a new mechanism underlying diastolic dysfunction, and provides theoretical and experimental evidence to explain, perhaps, the ineffectiveness of conventional nitric oxide enhancement trials for HFpEF. And you know, that's my favorite topic. Dr. Greg Hundley: Wow, Carolyn, really interesting. Can you summarize it for us? Dr. Carolyn Lam: Sure. Well, first of all, this comes from Doctors Eom and Kook from Chonnam National University Biomedical Research Center in Korea. These authors used two animal models of diastolic dysfunction, the salty drinking water, unilateral nephrectomy with aldosterone, or SAUNA, model, and a mild transverse aortic constriction model. They also looked at human heart samples from patients with left ventricular hypertrophy. Dr. Carolyn Lam: Together, in very, very elegant experiments, they showed that neuronal nitric oxide synthase was upregulated in diastolic dysfunction, which increases S-nitrosylation and cardiomyocytes, and its pharmacologic inhibition, as well as genetic ablation, alleviated diastolic dysfunction. Now, specifically, protein S-nitrosylation of histone deacetylase 2, or HDAC2, played a critical role in the development of diastolic dysfunction and nitric oxide reduction and the following protein denitrosylation may provide a novel therapeutic strategy for HFpEF. Dr. Greg Hundley: Very nice, Carolyn. Well, my next paper comes from Dr. William Pu from Boston Children's Hospital and looks at reactive oxygen species-mediated CaM kinase 2 activation, and how that contributes to calcium handling abnormalities and impaired contraction in the Barth syndrome. Carolyn, mutations in tafazzin, a gene required for biogenesis of cardiolipin, the signature phospholipid of the inner mitochondrial membrane, causes Barth syndrome. Carolyn, remember that Barth syndrome occurs primarily in males, is associated with cardiomyopathy, a low white count, and recurrent infections, and also skeletal muscle myopathy and short stature. Cardiomyopathy and the risk of sudden cardiac death are prominent features of the Barth syndrome, but the mechanisms by which impaired cardiolipin biogenesis causes cardiac muscle weakness and these arrhythmias are poorly understood. Dr. Carolyn Lam: Oh, Greg, thanks so much for not quizzing me on that one. I was trying to remember what Barth syndrome is, and thanks for the review. Okay, so what did they find? Dr. Greg Hundley: Right, Carolyn. The investigators identified a molecular pathway that links tafazzin mutation to abnormal calcium handling and decreased cardiomyocyte contractility. This pathway may offer therapeutic opportunities to treat Barth syndrome, and potentially other diseases with elevated mitochondrial reactive oxygen species production. Dr. Carolyn Lam: Thanks, Greg. Nicely summarized. Well, let's go through what else there is in today's issue. There is a Perspective piece by Dr. Singh, entitled The Morbidly Obese Patients with Symptomatic Atrial Fibrillation: Why are we Holding Back on Bariatric Surgery? There's an On My Mind piece by Dr. Wenger on the incremental change versus disruptive transformation: COVID-19 and the cardiovascular community. There's also a research letter by Dr. Phillip on cardiovascular evaluation after COVID-19 in 137 collegiate athletes, and it's the results of an algorithm-guided screening. A very interesting piece. Dr. Greg Hundley: Very nice, Carolyn. Well, Carolyn, in the mailbag, I've got an exchange of letters regarding the article Anti-Inflammatory Actions of Soluble Ninjurin-1 and the Amelioration of Atherosclerosis with Dr. Zheng, Jianmin, and Oh. Then finally, Dr. Rob Califf has an On My Mind piece, entitled Avoiding the Coming Tsunami of Common Chronic Disease: What the Lessons of the COVID-19 Pandemic Can Teach Us. Well, Carolyn, I'm really excited. Another double feature Tuesday. How about we turn our attention and move toward those articles? Dr. Carolyn Lam: Yep. Something for everyone in this one. Let's go. Today's feature discussion will sound somewhat familiar if we're talking about the ABC scores. Now, remember that stands for age, biomarkers, clinical history scores, and they're the scores that we use in patients with atrial fibrillation receiving oral anticoagulation, or at least that's the data we have so far. But, what are the utilities of these ABC scores in patients not receiving oral anticoagulation? Dr. Carolyn Lam: Well, guess what? That's what today's feature paper is all about. I'm so pleased to have with us today, the first author, Dr. Alexander Benz, from Population Health Research Institute, McMaster University in Canada, as well as Dr. Lars Wallentin, he's a senior author from Uppsala University in Sweden. Welcome, gentlemen. Alex, if I could start with you, please. A very interesting question and not so easy to answer, could you please tell us a little bit about the background to your study, what you did, and what you found? Dr. Alexander Benz: Sure. Thanks for the opportunity to speak here. The ABC scores have now been shown to outperform clinical risk scores in the setting of patients with AFib receiving oral anticoagulant therapy. But so far, nobody has ever looked at the performance of these scores in patients who are not treated with oral anticoagulant therapy. So here we validated the ABC stroke, bleeding, and death scores in patients with AFib who were not receiving oral anticoagulant therapy. We chose the ACTIVE A and AVERROES trials, where patients were randomized to receive antiplatelet therapy, so aspirin or aspirin plus clopidogrel, for the validation study. We ended up studying the scores and over 4,300 patients who were receiving either aspirin, which were over 3,195 patients, or aspirin plus clopidogrel in about 1100 patients, in these studies. Dr. Alexander Benz: Now, we found that the ABC stroke score was superior to the CHA2DS2–VASc score, yielding a C-index of 0.7. The ABC bleeding score was also better than the currently recommended HAS-BLED score for the assessment of the risk of bleeding, yielding an overall C-index of 0.73. And finally, the ABC-AF death score yielded a C-index of 0.78, which I think is remarkable. Dr. Alexander Benz: Now, as these scores were derived from patients receiving oral anticoagulant therapy, we're not surprised to see that the ABC stroke score underestimated the risk of stroke in this population. And very similarly, the ABC bleeding score overestimated the risk of bleeding in these patients receiving antiplatelet therapy. So these scores, the ABC stroke and bleeding scores, were recalibrated for our prediction of absolute event rates in the absence of oral anticoagulant therapy. Dr. Carolyn Lam: Thanks, Alex. That was a beautiful summary. Now, Lars, if I could ask you, please, could you really highlight to all of us, what is the key thing about validating these scores in patients with atrial fibrillation, but not receiving oral anticoagulation? Dr. Lars Wallentin: I think what people like to have is an estimate of the risk of stroke and the risk of bleeding. If you start them on oral anticoagulation and that has been difficult, we only knew this based on the risk scores on patients that were on treatment. But if we now are using this score, which are also well-calibrated, we can really estimate the absolute risk of a stroke. Let's say, 3% without oral anticoagulation, then how much is it lowered by oral anticoagulation down to 1%? And we can do this on an individual level, because there is a variability between patients and we can identify the risk for an individual patient without treatment, and the risk on treatment, and that can be balanced then against the risk for bleeding on treatment and without the treatment. And thereby, you can get the precise estimate on the risk-benefit ratio for the individual patients. Dr. Lars Wallentin: This is a precision medicine approach, which we think will provide a better treatment with better outcomes for the patients than we have had before. Also, death can be, of course, involved at the final net benefit, with and without treatment. Therefore, we think this is a great step forward, and this cannot be implemented in the real life because we have used biomarkers that now can be available in the routine laboratories. These are NTproBNP and troponin, which are available in all hospitals, and a new marker, GDF-15, a marker that's related to the bleeding risk and that is currently launched by Roche Diagnostics as a new tool. So I think this is a realistic future to improve treatments. Dr. Carolyn Lam: Dr. Lars, I have to tell you, all us editors fully agreed as well, that this is a great contribution, filling an important gap in the literature so far in a very clinically important question when we face the patient who hasn't started anticoagulation. So really, again, thank you both for this study and for publishing with us. A couple of questions, though. It does require these extra biomarkers that come with some, what can I say, cost of needing to measure them if they're not already measured. Could you give us some idea of how much the scores add to what we're used to, the CHA2DS2–VASc and the HAS-BLED score? I don't know, maybe Alex? Dr. Alexander Benz: Sure. I think one downside of the widely-accepted and also often useD clinical scores is that they rely on Arbitrary categorization and dichotomization of clinical variables, and with biomarkers, we have the great advantage of having a continuous tool to assess the risk of outcomes here. And as Lars mentioned, these are mainly the cardiac biomarkers NTproBNP and cardiac troponin, as well as the GDF-15, or growth differentiation factor 15. We think that biomarkers reflect a powerful tool to also reflect underlying subclinical disease, which is very important, I think, in this stratification, and this is probably where much of the superiority of the biomarker-based tool stems from. Dr. Carolyn Lam: Right, thanks. Back to what Lars had said about more precision, which is exactly what the whole of cardiology is, I think, moving towards as well, but it was very, very clever to look for the studies ACTIVE and AVERROES. Hard to think of the population in which you tested this. But weren't the blood samples in these studies very old? Did you then have to remeasure those biomarkers? Were they reliable? Dr. Lars Wallentin: Yes. These were old samples that were taken at entry into the ACTIVE and AVERROES trial. The investigators in Canada were really very clever to save the sample, but the samples have been saved for a decade or more since then. But fortunately, these assays are very stable over time, so all of them, and therefore the results are reliable. The levels are very similar to the ones we get in the real-life setting for samples as the one we have in ARISTOTLE and RE-LY, where the scores were derived. So this seems to be, I think, also an advantage that this can be used for stored samples, and fresh samples. Dr. Carolyn Lam: Thank you for addressing that so nicely. We're running out of time sadly, but I would love to hear, maybe as final remarks, what you think are the overall clinical implications and perhaps the next steps for important studies that need to be done. Maybe I could ask Alex to start first and then Lars can finish? Dr. Alexander Benz: Well, I think the next steps in the ABC score program will depend on potential integration or a combination of scores, which then may guide physicians in whom to treat or even whom not to treat. Withholding anti-platelet therapy in certain very low-risk patients, that's what comes to mind. I know that Lars and his colleagues are performing a randomized controlled trial in Sweden where they're testing the ABC scores in clinical practice against the usual care with the clinical scores. Maybe, Lars, you want to elaborate on this. Dr. Lars Wallentin: Yeah, I think the final step is, of course, a prospective randomized trial showing which are the real benefits. We are randomizing 6,000 patients to conventional care versus precision medicine-based care using the ABC risk scores. Outcomes are death and stroke and bleeding. I hope that we will find usefulness of this also in a prospective trial, which will be the final piece of evidence, of course. Dr. Carolyn Lam: Wow, Lars, that is amazing. Thank you so much for sharing that with us. First time on Circulation on the Run. Well, audience, I'm sure you enjoyed that. Thank you so much, Lars and Alex. Now, hold on tight, we're going on to our next feature discussion. Dr. Carolyn Lam: Oh, I can't wait to get onto this feature discussion. You see, it's actually going to reveal a potential new way to target diastolic dysfunction. My absolute favorite topic. It's a basic science paper. It is incredible. You're going to hear all about its clinical translational potential and significance, and from none other than the corresponding author, Dr. Timothy McKinsey from University of Colorado School of Medicine, and editorialist of a beautiful accompanying editorial, Dr. Thomas Gillette from UT Southwestern, and Dr. Sergio Lavandero, our Associate Editor from University of Chile, San Diego. Thank you so much for being here. Tim, could I get you started off? Recognizing there are a lot of clinicians listening out there, this is an incredible paper. HDAC, I think for some, it will be the first time you've been hearing such a word. Please, please, could you break it down for us what you did and what you found? Dr. Timothy McKinsey: Sure. Thanks, Carolyn, and thanks for inviting me to do this. It's really a pleasure. HDAC, that stands for a class of enzymes called histone deacetylases, and those are also known as erasers of acetyl marks on chromatin. So they're really famous for the regulation of epigenetics or gene expression. But we found that HDACs do a lot of other things in the heart too, by deacetylating both histone and non-histone proteins, and we're just really interested in the therapeutic potential of inhibiting HDAC enzymes for the treatment of heart failure. And, in so doing, we assess their ability to reverse existing diastolic dysfunction in a mouse model of kidney disease and hypertension. Dr. Carolyn Lam: You know what, Tim, I really liked the way you very carefully said that. A mouse model of diastolic dysfunction with preserved ejection fraction, that I think, previously, a lot of people with just very loosely used the word HFpEF for such a model, but I really, really appreciate how carefully you worded that. Could you tell us a little bit about the model and what you found? Dr. Timothy McKinsey: Sure. Yeah, we've been really careful not to call it a model of HFpEF, because it isn't a model of heart failure. It really is a model of isolated diastolic dysfunction and preserved ejection fraction. It's a model that's been used in the literature in the past, where you perform a uninephrectomy in mice, so remove one kidney, and then implant something called DOCA, which is an aldosterone memetic. And over time, these animals develop systemic hypertension that results in cardiac hypertrophy and diastolic dysfunction. Dr. Timothy McKinsey: We were perplexed because we couldn't see any fibrosis in the model. But when we did a deep dive into fibrosis using more sensitive methods than are traditionally used, we did uncover what we're calling hidden fibrosis. We believe that HDAC inhibitors, our data suggests that HDAC inhibitors, can actually block the formation of hidden fibrosis that leads to diastolic dysfunction. Dr. Carolyn Lam: Very nice. If you could just give us a one-line on how will you find this hidden fibrosis? Dr. Timothy McKinsey: We got stuck on that for years, because we did all the traditional assays to measure cardiac fibrosis, mainly picrosirius red stain, and we didn't see anything. But we were fortunate to team up with some really talented collaborators, including Maggie Lam here at the University of Colorado, who is an expert at using mass spectrometry to study cardiac remodeling, and also Luisa Mestroni and Brisa Peña who use atomic force microscopy to look at tissue stiffness. When we teamed up with those investigators, first with Maggie we found that, sure enough, when we used her sensitive mass spec assay to look at extracellular matrix protein expression in the heart, there was really a profound increase in ECM protein expression in this mouse model, even though the staining for fibrosis was negative. That told us that there was this underlying hidden fibrosis. Dr. Carolyn Lam: Oh, that is really interesting. And so it is that form of fibrosis that was actually reversed, perhaps, by the HDAC inhibition, and that's what you showed. Would that be accurate to say? Dr. Timothy McKinsey: Yeah. So the HDAC inhibitor really had this profound ability to block that ECM remodeling, the hidden fibrosis, to the point where initially we thought it was an artifact. We thought maybe there was a mix-up of samples. It wasn't a mix up. It's just that the compound, this inhibitor of HDAC enzymatic activity, really has this amazing ability to block the formation of hidden fibrosis. Dr. Carolyn Lam: Oh, wow. Wow, Tom, I really, really loved your editorial where you put all of this in context and talked a little bit about the translational and clinical potential. Could you maybe share your thoughts here? I love the title by the way, Erasing Hidden Fibrosis. Dr. Thomas Gillette: Thanks. Thanks for that. Yeah, first of all, Tim, it was a really great piece of work, and it's actually really exciting because when we think of this diastolic dysfunction, and really it's the development of HFpEF, I think, that a lot of people are... It's the single most critical unmet need in cardiovascular medicine, is the treatment for HFpEF. That diastolic dysfunction, it's really that stiffness that Tim was measuring with his atomic force microscopy and those changes in ECM that really seemed to be critical, at least in that model. Dr. Thomas Gillette: And we know from other models as well that these underlying changes in fibrosis and stiffness, perhaps in the ECM, play a really important role, not only in the diastolic dysfunction, but also if you think about in strain as well, because I know in our models of HFpEF and this mouse model of HFpEF, we have the two-hit model published that Gabrielle, a Allie developed with Dr. Hale in Nature. It's that strain that we could measure that really seems to correlate well with the heart failure phenotype. And so it begs the question, has he caught a very early change in the ECM that's really critical to the development of this pathology? And is there a way that we could detect it early on in patients? Is there a way we could measure that in patients and really get a sense of who's progressing and how they're progressing? Dr. Thomas Gillette: Then there's a second point, and I mentioned a little bit in the editorial, I didn't go into it too deeply, and that is, it's really intriguing what this might mean for the development of the disease, because the matrix not only is involved in stiffness, but it's also a reservoir for growth factors, it helps recruit inflammatory cells, and inflammation plays a huge role in HFpEF. And so it begs the question, how many of those changes may proceed a lot of that pathology as well? Dr. Carolyn Lam: Wow, Tom, I really couldn't agree more. I made a big deal earlier about agreeing with Tim, calling this a diastolic dysfunction model rather than HFpEF, but I completely agree with you that the implications are for the development of HFpEF, and it needed the begs, the question of how many patients actually have this hidden fibrosis? And we know that in patients with HFpEF, there is a stage of advanced fibrosis where we feel patients don't respond to treatment as well. So have we caught an early phase that may be clinically applicable? I really loved the way you worded that. But finally, with Sergio, could you put it all together and what the editors thought of this paper? Why you invited Tom to write this editorial? And perhaps what next steps are? Dr. Sergio Lavandero: Okay, Tim, this is really a fascinating work. I have a long road, because in Italy, you develop the most important new concept. The new concept, the hidden fibrosis. The second important, originally, most of the HDAC inhibitors were developed for other diseases, originally for cancer. So now we have more data that, probably, this compound can apply to other diseases like cardiovascular disease. It was difficult to convince at the beginning some reviewers about the concept of hidden fibrosis, because it's not traditional. But finally, we asked to another expert to, "Okay, why don't you explain, please, this new technique?" For the future, Tim, what do you think? How can we evaluate hidden fibrosis in patients? Dr. Timothy McKinsey: Ideally, and you would have a non-invasive approach to assessing hidden fibrosis in patients. Obviously I know myocardial biopsies could be analyzed using the mass spec approach and atomic force microscopy, but not everyone is going to want to get a myocardial biopsy. So ultimately, we would like to correlate data that we obtain with biopsies, with circulating factors to see if there is a non-invasive surrogate circulating factor that correlates with the existence of hidden fibrosis. I think that would be very powerful clinically. Dr. Sergio Lavandero: What do you think the specificity of this research, because maybe it's too broad? What do you think? Dr. Timothy McKinsey: Yeah, that's a great point. There's a negative impression of general HDAC inhibition, because people just can't believe that you could inhibit a large number of HDAC enzymes throughout the body and not kill someone. But you can. And in our models you can use pretty low doses of these HDAC inhibitors and see efficacy. But obviously, the holy grail in this field would be to identify specific HDAC isoforms that regulate specific disease processes. So we have an active area of investigation where we're trying to tease apart the roles of different HDACs in the heart, with the ultimate goal of finding the HDAC or a subset of HDACs that regulate in fibrosis. Then you could selectively inhibit those and perhaps have a safer drug than a general HDAC inhibitor. Dr. Carolyn Lam: Thank you, once again. This is an amazing discussion and really, really an example of just the kind of papers we love publishing at Circulation. So novel and with such translational potential. Thank you, Tim, again, and Tom and Sergio. Thank you, audience, for joining us today. From Greg and I, you've been listening to Circulation on the Run. 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 ABCs of Atrial Fibrillation   The Nurse Practitioner • Vol. 45, No. 8 By Mohamed Toufic El Hussein, PhD, NP and Lauren Kilfoil What is atrial fibrillation? Atrial fibrillation is an irregular and often rapid heart rate that occurs when the two upper chambers of your heart experience chaotic electrical signals. The result is a fast and irregular heart rhythm. The heart rate in atrial fibrillation may range from 100 to 175 beats a minute (Mayo Clinic, 2019) The article can be found at: https://nursing.ceconnection.com/default Find the article. Take the test and earn your CEU credit.  This one is Free for all. Also FREE: Bully Prevention for Nurses:  A Real Solution Podcast Outro New Artist - Patek: 1Way Kenzo https://www.kkbox.com/sg/en/album/IW0im0005rJ2j0F43hrn009H-index.html CHA2DS2-VASc & HAS-BLED tool for clinicians Sharing knowledge and educating those in the community for a healthier stronger safer community. MOTTO: GUMBO We'll teach your Grandma, Uncles, Mama, Brothers, and Others (GUMBO) The book is complete.  It was written to help raise money for the Non-profit. "Casey and the Crawfish" will be sold starting in January 2019. Everyone can purchase from  https://www.etsy.com/ie/listing/931849433/casey-and-the-crawfish Or try the Kindle Edition from Amazon https://www.amazon.com/dp/B08DLB473N    

Bu yazıda, Avrupa Kardiyoloji Derneği (ESC) ve Avrupa Kardiyo-Torasik Cerrahi Derneği (EACTS) işbirliğiyle geliştirilen atriyal fibrilasyonun tanı ve yönetimi 2020 kılavuzunda​1​ yer alan güncel noktaları paylaşmak ve kılavuzda acil pratiğimizi etkileyen maddeleri vurgulamak istedim. Bu yazı kılavuzun tamamını içermemektedir, acil servis yaklaşımı ön planda tutulmuştur.  Kılavuzun tamamına buradan ulaşabilirsiniz. 2016 kılavuzunda yer alan bilgiler içinse Ş. Kerem Çorbacıoğlu’nun ilgili yazısına buradan ulaşabilirsiniz. Atriyal Fibrilasyon Tanımı ve Klinik Özellikleri Atriyal fibrilasyon, koordine olmayan atriyal elektriksel aktivasyon ve inefektif atriyal kontraksiyon sonucu meydana gelen bir supraventriküler taşiaritmidir. EKG bulguları şu şekildedir: Düzensiz R-R aralıkları  (atriyoventiküler iletimin bozulmadığı durumlarda)Belirgin tekrarlayan P dalgalarının olmamasıDüzensiz atriyal aktivasyon Klinik olarak AF; EKG ile gösterilmiş, semptomatik veya asemptomatik AF durumudur.  Tanı koymak için gereken izleme süresi en az 30 saniye veya 12 derivasyonlu EKG’nin tamamıdır. Atriyal yüksek hızlı epizod/subklinik AF tablosu ise AF semptomu olmayan, klinik AF'nin daha önce tespit edilmediği kişilerde kardiyak implante edilebilir ya da giyilebilir cihazlarla tespit edilmiş, atriyal fibrilasyon, atriyal flutter ya da atriyal taşikardi ataklarıdır. Semptomatik AF hastalarda senkop, baş dönmesi, göğüste sıkışma/ağrı, palpitasyon, nefes darlığı, egzersiz kapasitesinde azalma gibi şikayetlere neden olabilir. Senkop, semptomatik hipotansiyon, akut kalp yetmezliği/pulmoner ödem, devam eden miyokardiyal iskemi ve kardiyojenik şok durumu varsa hemodinamik anstabilite söz konusudur.  AF’ye bağlı komorbiditeler nedeniyle ölüm riski 1.5 ila 3.5 kat artar. Başlıca komorbiditeler arasında inme (iskemik inmelerin %20-30’u AF nedenlidir), sol ventrikül disfonksiyonu ve kalp yetmezliği ve bunlara bağlı gelişen klinik tablolar yer almaktadır. AF Sınıflaması İlk tanı: Semptom varlığı/ağırlığı ve süreye bakılmaksızın AF’nin ilk defa saptanmasıParoksismal AF: Kendiliğinden ya da başlangıçtan sonraki 7 günde sona eren AF atağıSürekli (persistent) AF: 7 günden fazla süren, devamlı ve sürekli AF atağı (ilaç veya elektriksel kardiyoversiyonla 7 gün sonra sonlanan epizotlar dahil)Uzun süreli ve sürekli AF: Ritim kontrol stratejisi belirlenen 12 ay ve üzerinde AFKalıcı (permanent) AF: Ritim kontrolü için müdahale yapılmayan 12 ay ve üzerinde AF Antikoagülasyon/İnmeyi Önleme Genel olarak AF, inme riskini beş kat artırır. Sık rastlanan inme risk faktörleri, kliniğe dayalı CHA2DS2-VASc skorunda özetlenmiştir. Bu skor riskli hastalarda tromboembolik olayları öngörmede ve buna yönelik tedaviyi belirlemede kullanılır. CHA2DS2-VAScSkorKonjestif kalp yetmezliği1Hipertansiyon1Yaş ≥ 752Diyabetes mellitus1İnme/GİA/Tromboemboli2Damar hastalığı(geçirilmiş MI, PAH ya da aortik plak)1Yaş 65-741Kadın cinsiyet1 Antitrombotik tedaviye başlarken, potansiyel kanama riskinin de değerlendirilmesi gerekir. Bu riskin öngörülmesi adına çeşitli skorlar mevcuttur ancak yüksek risk gruplarını (HAS-BLED skoru > 3) tanımada genel olarak HAS-BLED skoru daha başarılıdır. HAS-BLED skoruPuanHipertansiyon1Böbrek veya karaciğer hastalığı (her biri için 1 puan)1 veya 2İnme1Kanama öyküsü veya yatkınlık1Labil INR1Yaş > 651İlaç veya alkol kullanımı (her biri için 1 puan)1 veya 2 Akut Hız Kontrolü Hız kontrolü, AF yönetiminin ayrılmaz bir parçasıdır ancak AF’de optimal kalp hızı hedefi kesinleşmiş değildir. Farmakolojik hız kontrolü beta blokerler, digoksin, diltiazem ve verapamil veya bu ilaçların kombinasyonu ile sağlanabilir. Hız kontrol ilaçlarının seçimi semptomlara, komorbiditelere ve olası yan etkilere bağlı değişir. Akut hız kontrolünde enfeksiyon veya anemi gibi altta yatan nedenler her zaman değerlendirmelidir. İlacın seçimi ve hedef kalp hızı hasta özelliklerine, semptomlara, LVEF değerine ve hemodinamiye bağlı yapılır.

Bu yazıda, Avrupa Kardiyoloji Derneği (ESC) ve Avrupa Kardiyo-Torasik Cerrahi Derneği (EACTS) işbirliğiyle geliştirilen atriyal fibrilasyonun tanı ve yönetimi 2020 kılavuzunda​1​ yer alan güncel noktaları paylaşmak ve kılavuzda acil pratiğimizi etkileyen maddeleri vurgulamak istedim. Bu yazı kılavuzun tamamını içermemektedir, acil servis yaklaşımı ön planda tutulmuştur.  Kılavuzun tamamına buradan ulaşabilirsiniz. 2016 kılavuzunda yer alan bilgiler içinse Ş. Kerem Çorbacıoğlu’nun ilgili yazısına buradan ulaşabilirsiniz. Atriyal Fibrilasyon Tanımı ve Klinik Özellikleri Atriyal fibrilasyon, koordine olmayan atriyal elektriksel aktivasyon ve inefektif atriyal kontraksiyon sonucu meydana gelen bir supraventriküler taşiaritmidir. EKG bulguları şu şekildedir: Düzensiz R-R aralıkları  (atriyoventiküler iletimin bozulmadığı durumlarda)Belirgin tekrarlayan P dalgalarının olmamasıDüzensiz atriyal aktivasyon Klinik olarak AF; EKG ile gösterilmiş, semptomatik veya asemptomatik AF durumudur.  Tanı koymak için gereken izleme süresi en az 30 saniye veya 12 derivasyonlu EKG’nin tamamıdır. Atriyal yüksek hızlı epizod/subklinik AF tablosu ise AF semptomu olmayan, klinik AF'nin daha önce tespit edilmediği kişilerde kardiyak implante edilebilir ya da giyilebilir cihazlarla tespit edilmiş, atriyal fibrilasyon, atriyal flutter ya da atriyal taşikardi ataklarıdır. Semptomatik AF hastalarda senkop, baş dönmesi, göğüste sıkışma/ağrı, palpitasyon, nefes darlığı, egzersiz kapasitesinde azalma gibi şikayetlere neden olabilir. Senkop, semptomatik hipotansiyon, akut kalp yetmezliği/pulmoner ödem, devam eden miyokardiyal iskemi ve kardiyojenik şok durumu varsa hemodinamik anstabilite söz konusudur.  AF’ye bağlı komorbiditeler nedeniyle ölüm riski 1.5 ila 3.5 kat artar. Başlıca komorbiditeler arasında inme (iskemik inmelerin %20-30’u AF nedenlidir), sol ventrikül disfonksiyonu ve kalp yetmezliği ve bunlara bağlı gelişen klinik tablolar yer almaktadır. AF Sınıflaması İlk tanı: Semptom varlığı/ağırlığı ve süreye bakılmaksızın AF’nin ilk defa saptanmasıParoksismal AF: Kendiliğinden ya da başlangıçtan sonraki 7 günde sona eren AF atağıSürekli (persistent) AF: 7 günden fazla süren, devamlı ve sürekli AF atağı (ilaç veya elektriksel kardiyoversiyonla 7 gün sonra sonlanan epizotlar dahil)Uzun süreli ve sürekli AF: Ritim kontrol stratejisi belirlenen 12 ay ve üzerinde AFKalıcı (permanent) AF: Ritim kontrolü için müdahale yapılmayan 12 ay ve üzerinde AF Antikoagülasyon/İnmeyi Önleme Genel olarak AF, inme riskini beş kat artırır. Sık rastlanan inme risk faktörleri, kliniğe dayalı CHA2DS2-VASc skorunda özetlenmiştir. Bu skor riskli hastalarda tromboembolik olayları öngörmede ve buna yönelik tedaviyi belirlemede kullanılır. CHA2DS2-VAScSkorKonjestif kalp yetmezliği1Hipertansiyon1Yaş ≥ 752Diyabetes mellitus1İnme/GİA/Tromboemboli2Damar hastalığı(geçirilmiş MI, PAH ya da aortik plak)1Yaş 65-741Kadın cinsiyet1 Antitrombotik tedaviye başlarken, potansiyel kanama riskinin de değerlendirilmesi gerekir. Bu riskin öngörülmesi adına çeşitli skorlar mevcuttur ancak yüksek risk gruplarını (HAS-BLED skoru > 3) tanımada genel olarak HAS-BLED skoru daha başarılıdır. HAS-BLED skoruPuanHipertansiyon1Böbrek veya karaciğer hastalığı (her biri için 1 puan)1 veya 2İnme1Kanama öyküsü veya yatkınlık1Labil INR1Yaş > 651İlaç veya alkol kullanımı (her biri için 1 puan)1 veya 2 Akut Hız Kontrolü Hız kontrolü, AF yönetiminin ayrılmaz bir parçasıdır ancak AF’de optimal kalp hızı hedefi kesinleşmiş değildir. Farmakolojik hız kontrolü beta blokerler, digoksin, diltiazem ve verapamil veya bu ilaçların kombinasyonu ile sağlanabilir. Hız kontrol ilaçlarının seçimi semptomlara, komorbiditelere ve olası yan etkilere bağlı değişir. Akut hız kontrolünde enfeksiyon veya anemi gibi altta yatan nedenler her zaman değerlendirmelidir. İlacın seçimi ve hedef kalp hızı hasta özelliklerine, semptomlara, LVEF değerine ve hemodinamiye bağlı yapılır.

#172 - HAS-BLED alto contraindica anticoagulação? by Cardiopapers

#54 - HAS-BLED: como usar na prática? by Cardiopapers

Show Notes Jeff: Welcome back to EMplify the podcast corollary to EB Medicine’s Emergency medicine Practice. I’m Jeff Nusbaum and I’m back with Nachi Gupta. This month, we are tackling a topic for which the literature continues to rapidly change - we’re talking about the ED management of patients taking direct oral anticoagulants or DOACs, previously called novel oral anticoagulants or NOACs. Nachi: Specifically, we’ll be focusing on the use of DOACs for the indications of stroke prevention in atrial fibrillation and the treatment and prevention of recurrent venous thromboembolisms. Jeff: This month’s article was authored by Dr. Patrick Maher and Dr. Emily Taub of the Icahn School of Medicine at Mount Sinai, and it was peer reviewed by Dr. Dowin Boatright from Yale, Dr. Natalie Kreitzer from the University of Cincinnati, and Dr. Isaac Tawil from the University of New Mexico. Nachi: In their quest to update the last Emergency Medicine Practice issue on this topic which was published in 2013, they reviewed over 200 articles from 2000 to present in addition to 5 systematic reviews in the cochrane database, as well as guidelines from the American Heart Association, European society of cardiology, and the american college of cardiology. Jeff: Thanks to a strong literature base, Dr’s Maher and Taub found good quality evidence regarding safety and efficacy of the DOACs in relation to warfarin and the heparin-based anticoagulants. Nachi: But do note that the literature directly comparing the DOACs is far more limited and mostly of poor quality. Show More v Jeff: Fair enough, we’ll take what we can get. Nachi: Well, I’m sure more of those studies are still coming. Jeff: Agree. Let’s get started with some basics. Not surprisingly, DOACs now account for a similar proportion of office visits for anticoagulant use as warfarin. Nachi: With huge benefits including reduced need for monitoring and a potential for reduced bleeding complications, this certainly isn’t surprising. Jeff: Though those benefits are not without challenges - most notably the lack of an effective reversal agent and the risk of unintentional overdose in patients with altered drug metabolism. Nachi: Like all things in medicine, it’s about balancing and finding an acceptable risk/benefit profile. Jeff: True. Let’s talk pathophysiology for a minute - the control of coagulation in the human body is a balance between hemorrhage and thrombosis, mediated by an extensive number of procoagulant and anticoagulant proteins. Nachi: Before the development of the DOACs, vitamin K antagonists controlled the brunt of the market. As their name suggests, they work by inhibiting the action of vitamin K, and thus reducing the production of clotting factors 2, 7, 9, and 10, and the anticoagulant proteins C and S. Jeff: Unfortunately, these agents have a narrow therapeutic window and many drug-drug interactions, and they require frequent monitoring - making them less desirable to many. Nachi: However, in 2010, the FDA approved the first DOAC, a real game-changer. The DOACs currently on the market work by one of two mechanisms - direct thrombin inhibition or factor Xa inhibition. Jeff: DOACs are currently approved for stroke prevention in nonvalvular afib, treatment of VTE, VTE prophylaxis, and reduction of major cardiovascular events in stable cardiovascular disease. Studies are underway to test their safety and efficacy in arterial and venous thromboembolism, prevention of embolic stroke in afib, ACS, cancer-associated thrombosis, upper extremity DVT, and mesenteric thrombosis. Nachi: Direct thrombin inhibitors like Dabigatran, tradename Pradaxa, was the first FDA approved DOAC. It works by directly inhibiting thrombin, or factor IIa, which is a serine protease that converts soluble fibrinogen into fibrin for clot formation. Jeff: Dabigatran comes in doses of 75 and 150 mg. The dose depends on your renal function, and, with a half-life of 12-15 hours, is taken twice daily. Note the drastically reduced half-life as compared to warfarin, which has a half-life of up to 60 hours. Nachi: The RE-LY trial for afib found that taking 150 mg of Dabigatran BID had a lower rate of stroke and systemic embolism than warfarin with a similar rate of major hemorrhage. Dabigatran also had lower rates of fatal and traumatic intracerebral hemorrhage than warfarin. Jeff: A separate RCT found similar efficacy in treating acute VTE and preventing recurrence compared with warfarin, with reduced rates of hemorrhage! Nachi: Less monitoring, less hemorrhage, similar efficacy, I’m sold!!! Jeff: Slow down, there’s lots of other great agents out there, let’s get through them all first... Nachi: Ok, so next up we have the Factor Xa inhibitors, Rivaroxaban, apixaban, edoxaban, and betrixaban.As the name suggests, these medications work by directly inhibiting the clotting of factor Xa, which works in the clotting cascade to convert prothrombin to thrombin. Jeff: Rivaroxaban, trade name Xarelto, the second FDA approved DOAC, is used for stroke prevention in those with nonvalvular afib and VTE treatment. After taking 15 mg BID for the first 21 days, rivaroxaban is typically dosed at 20 mg daily with adjustments for reduced renal function. Nachi: The Rocket AF trial found that rivaroxaban is noninferior to warfarin for stroke and systemic embolism prevention without a significant difference in risk of major bleeding. Interestingly, GI bleeding may be higher in the rivaroxaban group, though the overall incidence was very low in both groups at about 0.4% of patients per year. Jeff: In the Einstein trial, patients with VTE were randomized to rivaroxaban or standard therapy. In the end, they reported similar rates of recurrence and bleeding outcomes for acute treatment. Continuing therapy beyond the acute period resulted in similar rates of VTE recurrence and bleeding episodes to treatment with aspirin alone. Nachi: Next we have apixaban, tradename Eliquis. Apixaban is approved for afib and the treatment of venous thromboembolism. It’s typically dosed as 10 mg BID for 7 days followed by 5 mg BID with dose reductions for the elderly and those with renal failure. Jeff: In the Aristotle trial, when compared to warfarin, apixaban was superior in preventing stroke and systemic embolism with lower mortality and bleeding. Rates of major hemorrhage-related mortality were also nearly cut in half at 30 days when compared to warfarin. Nachi: For the treatment of venous thromboembolism, the literature shows that apixaban has a similar efficacy to warfarin in preventing recurrence with less bleeding complications. Jeff: Unfortunately, with polypharmacy, there is increased risk of thromboembolic and hemorrhage risks, but this risk is similar to what is seen with warfarin. Nachi: And as compared to low molecular weight heparin, apixaban had higher bleeding rates without reducing venous thromboembolism events when used for thromboprophylaxis. It’s also been studied in acute ACS, with increased bleeding and no decrease in ischemic events. Jeff: Edoxaban is up next, approved by the FDA in 2015 for similar indications as the other Factor Xa inhibitors. It’s recommended that edoxaban be given parenterally for 5-10 days prior to starting oral treatment for VTE, which is actually similar to dabigatran. It has similar levels of VTE recurrence with fewer major bleeding episodes compared to warfarin. It has also been used with similar effects and less major bleeding for stroke prevention in afib. In the setting of cancer related DVTs specifically, as compared to low molecular weight heparin, one RCT showed lower rates of VTE but higher rates of major bleeding when compared to dalteparin. Nachi: Next we have Betrixaban, the latest Factor Xa inhibitor to be approved, back in 2017. Because it’s utility is limited to venous thromboembolism prophylaxis in mostly medically ill inpatients, it’s unlikely to be encountered by emergency physicians very frequently. Jeff: As a one sentence FYI though - note that in recent trials, betrixaban reduced the rate of VTE with equivalent rates of bleeding and reduced the rate of stroke with an increased rate of major and clinically relevant non-major bleeding as compared to enoxaparin. Nachi: Well that was a ton of information and background on the DOACs. Let’s move on to your favorite section - prehospital medicine. Jeff: Not a ton to add here this month. Perhaps, most importantly, prehospital providers should specifically ask about DOAC usage, especially in trauma, given increased rates of complications and potential need for surgery. This can help with destination selection when relevant. Interestingly, one retrospective study found limited agreement between EMS records and hospital documentation on current DOAC usage. Nachi: Extremely important to identify DOAC use early. Once the patient arrives in the ED, you can begin your focused history and physical. Make sure to get the name, dose, and time of last administration of any DOAC. Pay particular attention to the med list and the presence of CKD which could point to altered DOAC metabolism. Jeff: In terms of the physical and initial work up - let the sites of bleeding or potential sites of bleeding guide your work up. And don’t forget about the rectal exam, which potentially has some added value here - since DOACs increase the risk of GI bleeding. Nachi: Pretty straight forward history and physical, let’s talk diagnostic studies. Jeff: First up is CT. There are no clear cut guidelines here, so Drs. Maher and Taub had to rely on observational studies and expert opinion. Remember, most standard guidelines and tools, like the canadian and nexus criteria, are less accurate in anticoagulated patients, so they shouldn’t be applied. Instead, most studies recommend a low threshold for head imaging, even with minor trauma, in the setting of DOAC use. Nachi: That is so important that it’s worth repeating. Definitely have a low threshold to CT the head for even minor head trauma patients on DOACs. Basically, if you’re on anticoagulation, and you made it to the ED for anything remotely related to your head, you probably win a spin. Jeff: I suspect you are not alone with that stance... There is, however, much more debate about the utility of follow up imaging and admission after a NEGATIVE scan. Nachi: Wait, is that a thing I should routinely be doing? Jeff: Well there’s not great data here, but in one observational study of 1180 patients on either antiplatelet or anticoagulant therapy, a half a percent of them had positive findings 12 hours later, and importantly none required surgical intervention. Nachi: Certainly reassuring. And for those with positive initial imaging, the authors recommend repeat imaging within 4-6 hours in consultation with neurosurgical services or even earlier in cases of unexpected clinical decline. Jeff: Interestingly, though only a small retrospective study of 156 patients, one study found markedly reduced mortality, 4.9% vs 20.8% in those on DOACs vs warfarin with traumatic intracranial hemorrhage. Nachi: Hmm that actually surprises me a bit with the ease of reversibility of warfarin. Jeff: And we’ll get to that in a few minutes. But next we should talk about ultrasound. As always with trauma, guidelines recommend a FAST exam in the setting of blunt abdominal trauma. The only thing to be aware of here is that you should have an increased index of suspicion for bleeding, especially in hidden sites like the retroperitoneum. Nachi: And just as with traumatic head bleeds, a small observational study of those with blunt abdominal trauma found 8% vs 30% mortality for those on DOACs vs warfarin, respectively. Jeff: That is simply shocking! Let’s also talk lab studies. Hemoglobin and platelet counts should be obtained as part of the standard trauma work up. Assessing renal function via creatinine is also important, especially for those on agents which are renally excreted. Nachi: Though you can, in theory, test for plasma DOAC concentrations, such tests are not routinely indicated as levels don’t correspond to bleeding outcomes. DOAC levels may be indicated in certain specific situations, such as while treating life-threatening bleeding, development of venous thromboembolism despite compliance with DOAC therapy, and treating patients at risk for bleeding because of an overdose. Jeff: In terms of those who require surgery while on a DOAC - if urgent or emergent, the DOAC will need to be empirically reversed. For all others, the recommendation is to wait a half life or even multiple half-lives, if possible, in lieu of level testing. Nachi: Coagulation tests are up next. Routine PT and PTT levels do not help assess DOACs, as abnormalities on either test can suggest the presence of a DOAC, but the values should not be interpreted as reliable measures of either therapeutic or supratherapeutic clinical anticoagulant effect. Jeff: Dabigatran may cause prolongation of both the PT and the PTT, but the overall correlation is poor. In addition, FXa inhibitors may elevate PT in a weakly concentration dependent manner, but this may only be helpful if anti-fXa levels are unavailable. Nachi: Which is a perfect segway into our next test - anti-factor Xa level activity. Direct measurements of the anti-Fxa effect demonstrates a strong linear correlation with plasma concentrations of these agents, but the anticoagulant effect does not necessarily follow the same linear fashion. Jeff: Some labs may even have an anti-FXa effect measurement calibrated specifically to the factor 10a inhibitors. Nachi: While measuring thrombin time is not routinely recommended, the result of thrombin time or dilute thrombin time does correlate well with dabigatran concentrations across normal ranges. Jeff: And lastly, we have the Ecarin clotting time. Ecarin is an enzyme that cleaves prothrombin to an active intermediate that can be inhibited by dabigatran in the same way as thrombin. The ECT is useful for measuring dabigatran concentration - it’s not useful for testing for FXa inhibitors. A normal ECT value could be used to exclude the presence of dabigatran. Nachi: So I think that rounds out testing. Let’s move into the treatment section. Jeff: For all agents, regardless of the DOAC, the initial resuscitation follows the standard principles of hemorrhage control and trauma resuscitation. Tourniquet application, direct pressure, endoscopy for GI bleeds, etc... should all be used as needed. And most importantly, for airway bleeding, pericardial bleeding, CNS bleeding, and those with hemodynamic instability or overt bleeding, those with a 2 point drop in their hemoglobin, and those requiring 2 or more units of pRBC - they all should be considered to have serious, life threatening bleeds. This patient population definitely requires reversal agents, which we’re getting to in a minute. Nachi: A type and screen should also be sent with the plan to follow standard transfusion guidelines, with the goal of a hemoglobin level of 7, understanding that in the setting of an active bleed, the hemoglobin level will not truly be representative. Jeff: Interestingly, in the overdose literature that’s out there, bleeding episodes appear to be rare - occurring in just 5% of DOAC overdose cases. Nachi: Finally, onto the section we’ve all been waiting for. Let’s talk specific reversal agents. Praxbind is up first. Jeff: Idarucizumab or Praxbind, is the reversal agent of choice for dabigatran (which is also called pradaxa). According to data from the RE-LY trial, it reverses dabigatran up to the 99th percentile of levels measured in the trial. Nachi: And praxbind should be given in two 2.5 g IV boluses 15 minutes apart to completely reverse the effects of dabigatran. Jeff: As you would expect given this data, guidelines for DOAC reversal recommend it in major life-threatening bleeding events for patients on dabigatran. Nachi: Next up is recombinant coagulation factor Xa (brand name Andexxa), which was approved in 2018 for the FXa inhibitors. This recombinant factor has a decoy receptor for the FXa agents, thus eliminating their anticoagulant effects. Jeff: Recombinant factor Xa is given in either high or low dose infusions. High dose infusions for those on rivaroxaban doses of >10 mg or apixaban doses >5 mg within the last 8 hours and for unknown doses and unknown time of administration. Low dose infusions should be used for those with smaller doses within the last 8 hours or for last doses taken beyond 8 hours. Nachi: In one trial of 352 patients, recombinant factor Xa given as an IV bolus and 2 hour infusion was highly effective at normalizing anti-FXa levels. 82% of the assessed patients at 12 hours achieved hemostasis, but there were also thrombotic events in 10% of the patients at 30 days. Jeff: And reported thrombotic events aren’t the only downside. Though the literature isn’t clear, there may be limited use of recombinant factor Xa outside of the time of the continuous infusion, and even worse, there may be rebound of anti-Fxa levels and anticoagulant effect. And lastly, the cost is SUBSTANTIAL. Nachi: Is there really a cost threshold for stopping life threatening bleeding…? Jeff: Touche, but that means we need to save it for specific times and consider other options out there. Since this has only been around for a year or so, let’s let the literature play out on this too... Nachi: And that perfectly takes us into our next topic, which is nonspecific reversal agents, starting with prothrombin complex concentrate, also called PCC. Jeff: PCC is FDA approved for rapid reversal of vitamin K antagonist-related hemorrhagic events and is now being used off label for DOAC reversal. Nachi: PCC comes in 3 and 4 factor varieties. 3-factor PCC contains factors 2, 9, 10 and trace amounts of factor 7. 4 factor PCC contains factors 2, 9 10, as well as purified factor 7 and proteins C and S. Jeff: Both also contain trace amounts of heparin so can’t be given to someone with a history of HIT. Nachi: PCC works by overwhelming the inhibitor agent by increasing the concentration of upstream clotting factors. It has been shown, in healthy volunteers, to normalize PT abnormalities and bleeding times, and to achieve effective bleeding control in patients on rivaroxaban, apixaban, and edoxaban with major bleeding events. Jeff: In small studies looking at various end points, 4 factor PCC has been shown to be superior to 3 factor PCC. Nachi: Currently it’s given via weight-based dosing, but there is interest in studying a fixed-dose to decrease both time to medication administration and cost of reversal. Jeff: Guidelines currently recommend 4F PCC over 3F PCC, if available, for the management of factor Xa inhibitor induced bleeding, with studies showing an effectiveness of nearly 70%. As a result, 4F PCC has become an agent of choice for rapid reversal of FXa inhibitors during major bleeding events. Nachi: Next we have activated PCC (trade name FEIBA). This is essentially 4Factor PCC with a modified factor 7. Though traditionally saved for bleeding reversal in hemophiliacs, aPCC is now being studied in DOAC induced bleeding. Though early studies are promising, aPCC should not be used over 4factor PCC routinely as of now but may be used if 4Factor PCC is not available. Jeff: Next we have recombinant factor 7a (trade name novoseven). This works by activating factors 9 and 10 resulting in rapid increase in thrombin. Studies have shown that it may reverse the effect of dabigatran, at the expense of increased risk of thrombosis. As such, it should not be used as long as other agents are available. Nachi: Fresh Frozen Plasma is the last agent to discuss in this section. Not a lot to say here - FFP is not recommended for reversal of any of the DOACs. It may be given as a part of of a balanced massive transfusion resuscitation, but otherwise, at this time, there doesn’t seem to be a clear role. Jeff: Let’s move on to adjunct therapies, of which we have 3 to discuss. Nachi: First is activated charcoal. Only weak evidence exists here - but, according to expert recommendations, there may be a role for DOAC ingestions within 2 hours of presentations. Jeff: Perhaps more useful than charcoal is our next adjunct - tranexamic acid or TXA. TXA is a synthetic lysine analogue with antifibrinolytic activity through reversible binding of plasmin. CRASH-2 is the main trial to know here. CRASH-2 demonstrated reduced mortality if given within 3 hours in trauma patients. There is very limited data with respect to TXA and DOACs specifically, so continue to administer TXA as part of your standard trauma protocol without modification if the patient is on a DOAC, as it’s likely helpful based on what data we have. Nachi: Next is vitamin K - there is no data to support routine use of vitamin K in those taking DOACs - save that for those on vitamin K antagonists. Jeff: Also, worth mentioning here is the importance of hematology input in developing hospital-wide protocols for reversal agents, especially if availability of certain agents is limited. Nachi: Let’s talk about some special circumstances and populations as they relate to DOACs. Patients with mechanical heart valves were excluded from the major DOAC trials. And of note, a trial of dabigatran in mechanical valve patients was stopped early because of bleeding and thromboembolic events. As such, the American College of Cardiology state that DOACs are reasonable for afib with native valve disease. Jeff: DOACs should be used with caution for pregnant, breastfeeding, and pediatric patients. A case series of 233 pregnancies that occurred among patients on a DOAC reported high rates of miscarriage. Nachi: Patients with renal impairment are particularly concerning as all DOACs are dependent to some degree on renal elimination. Current guidelines from the Anticoagulation Forum recommend avoiding dabigatran and rivaroxaban for patients with CrCL < 30 and avoiding edoxaban and betrixaban for patients with CrCl < 15. Jeff: A 2017 Cochrane review noted similar efficacy without increased risk of major bleeding when using DOACs in those with egfr > 30 (that’s ckd3b or better) when compared to patients with normal renal function and limited evidence for safety below this estimated GFR. Nachi: Of course, dosing with renal impairment will be different. We won’t go into the details of that here as you will probably discuss this directly with your pharmacist. Jeff: We should mention, however, that reversal of the anticoagulant in the setting of renal impairment for your major bleeding patient is exactly the same as we already outlined. Nachi: Let’s move on to some controversies and cutting-edge topics. The first one is a pretty big topic and that is treatment for ischemic stroke patients taking DOACs. Jeff: Safety and efficacy of tPA or endovascular therapy for patients on DOACs continues to be debated. Current guidelines do not recommend tPA if the last DOAC dose was within the past 48 hours, unless lab testing specific to these agents shows normal results. Nachi: Specifically, the American Heart Association suggests that INR and PTT be normal in all cases. ECT and TT should be tested for dabigatran. And calibrated anti-FXa level testing be normal for FXa inhibitors. Jeff: The AHA registry actually included 251 patients who received tpa while on DOACs, which along with cohort analysis of 26 ROCKET-AF trial patients, suggest the risk of intracranial hemorrhage is similar to patients on warfarin with INR < 1.7 and to patients not on any anticoagulation who received tpa. However, given the retrospective nature of this data, we cannot exclude the possibility of increased risk of adverse events with tpa given to patients on DOACs. Nachi: Endovascular thrombectomy also has not been studied in large numbers for patients on DOACs. Current recommendations are to discuss with your stroke team. IV lysis or endovascular thrombectomy may be considered for select patients on DOACs. Always include the patient and family in shared decision making here. Jeff: There are also some scoring systems for bleeding risk to discuss briefly. The HAS-BLED has been used to determine bleeding risk in afib patients taking warfarin. The ORBIT score was validated in a cohort that included patients on DOACs and is similarly easy to use, and notably does not require INR values. Nachi: There is also the ABC score which has demonstrated slightly better prediction characteristics for bleeding risk, but it requires high-sensitivity troponin, limiting its practical use. Jeff: We won’t say more about the scoring tools here, but would recommend that you head over to MD Calc, where you can find them and use them in your practice. Nachi: Let’s also comment on the practicality of hemodialysis for removal of the DOACs. Multiple small case series have shown successful removal of dabigatran, given its small size and low protein binding. On the other hand, the FXa inhibitors are less amenable to removal in this way because of their higher protein binding. Jeff: Worth mentioning here also - dialysis catheters if placed should be in compressible areas in case bleeding occurs. The role of hemodialysis for overdose may be limited now that the specific reversal agent, praxbind, exists. Nachi: In terms of cutting-edge tests, we have viscoelastic testing like thromboelastography and rotational thromboelastometry. Several studies have examined the utility of viscoelastic testing to detect presence of DOACs with varying results. Prolongation of clotting times here does appear to correlate with concentration, but these tests haven’t emerged as a gold standard yet. Jeff: Also, for cutting edge, we should mention ciraparantag. And if you’ve been listening patiently and just thinking to yourself why can’t there be one reversal agent to reverse everything, this may be the solution. Ciraparantag (or aripazine) is a universal anticoagulant reversal agent that may have a role in all DOACs and heparins. It binds and inactivates all of these agents and it doesn’t appear to have a procoagulant effect. Nachi: Clinical trials for ciraparantag have shown rapid and durable reversal of edoxaban, but further trials and FDA approval are still needed. Jeff: We’ve covered a ton of material so far. As we near the end of this episode, let’s talk disposition. Nachi: First, we have those already on DOACs - I think it goes without saying that any patient who receives pharmacological reversal of coagulopathy for major bleeding needs to be admitted, likely to the ICU. Jeff: Next we have those that we are considering starting a DOAC, for example in someone with newly diagnosed VTE, or patients with an appropriate CHADS-VASC with newly diagnosed non-valvular afib. Nachi: With respect to venous thromboembolism, both dabigatran and edoxaban require a 5 day bridge with heparin, whereas apixaban and rivaroxaban do not. The latter is not only easier on the patient but also offers potential cost savings with low risk of hemorrhagic complications. Jeff: For patients with newly diagnosed DVT / PE, both the American and British Thoracic Society, as well as ACEP, recommend using either the pulmonary embolism severity index, aka PESI, or the simplified PESI or the Hestia criteria to risk stratify patients with PE. The low risk group is potentially appropriate for discharge home on anticoagulation. This strategy reduces hospital days and costs with otherwise similar outcomes - total win all around. Nachi: Definitely a great opportunity for some shared decision making since data here is fairly sparse. This is also a great place to have institutional policies, which could support this practice and also ensure rapid outpatient follow up. Jeff: If you are going to consider ED discharge after starting a DOAC - there isn’t great data supporting one over another. You’ll have to consider patient insurance, cost, dosing schedules, and patient / caregiver preferences. Vitamin K antagonists should also be discussed as there is lots of data to support their safety outcomes, not to mention that they are often far cheaper…. As an interesting aside - I recently diagnosed a DVT/PE in an Amish gentleman who came to the ED by horse - that was some complicated decision making with respect to balancing the potentially prohibitive cost of DOACs with the massive inconvenience of frequently checking INRs after a 5 mile horseback ride into town... Nachi: Nice opportunity for shared decision making… Jeff: Lastly, we have those patients who are higher risk for bleeding. Though I’d personally be quite uneasy in this population, if you are to start a DOAC, consider apixaban or edoxaban, which likely have lower risk of major bleeding. Nachi: So that’s it for the new material for this month’s issue. Certainly, an important topic as the frequency of DOAC use continues to rise given their clear advantages for both patients and providers. However, despite their outpatient ease of use, it definitely complicates our lives in the ED with no easy way to evaluate their anticoagulant effect and costly reversal options. Hopefully all our hospitals have developed or will soon develop guidelines for both managing ongoing bleeding with reversal agents and for collaborative discharges with appropriate follow up resources for those we send home on a DOAC. Jeff: Absolutely. Let’s wrap up with some the highest yield points and clinical pearls Nachi: Dabigatran works by direct thrombin inhibition, whereas rivaroxaban, apixaban, edoxaban, and betrixaban all work by Factor Xa inhibition. Jeff: The DOACs have a much shorter half-life than warfarin. Nachi: Prehospital care providers should ask all patients about their use of anticoagulants. Jeff: Have a low threshold to order a head CT in patients with mild head trauma if they are on DOACs. Nachi: For positive head CT findings or high suspicion of significant injury, order a repeat head CT in 4 to 6 hours and discuss with neurosurgery. Jeff: Have a lower threshold to conduct a FAST exam for blunt abdominal trauma patients on DOACs. Nachi: Assessment of renal function is important with regards to all DOACs. Jeff: While actual plasma concentrations of DOACs can be measured, these do not correspond to bleeding outcomes and should not be ordered routinely. Nachi: The DOACs may cause mild prolongation of PT and PTT. Jeff: Idarucizumab (Praxbind®) is an antibody to dabigatran. For dabigatran reversal, administer two 2.5g IV boluses 15 minutes apart. Reversal is rapid and does not cause prothrombotic effects. Nachi: Recombinant FXa can be used to reverse the FXa inhibitors. This works as a decoy receptor for the FXa agents. Jeff: Vitamin K and FFP are not recommended for reversal of DOACs. Nachi: Consider activated charcoal to remove DOACs ingested within the last two hours in the setting of life-threatening hemorrhages in patient’s on DOACs. Jeff: Hemodialysis can effectively remove dabigatran, but this is not true for the FXa inhibitors. Nachi: 4F-PCC has been shown to be effective in reversing the effects of the FXa inhibitors. This is thought to be due to overwhelming the inhibitor agent by increased concentrations of upstream clotting factors. Jeff: tPA is contraindicated in acute ischemic stroke if a DOAC dose was administered within the last 48 hours, unless certain laboratory testing criteria are met. Nachi: Emergency clinicians should consider initiating DOACs in the ED for patients with new onset nonvalvular atrial fibrillation, DVT, or PE that is in a low-risk group. Jeff: So that wraps up Episode 31! Nachi: As always, additional materials are available on our website for Emergency Medicine Practice subscribers. If you’re not a subscriber, consider joining today. You can find out more at ebmedicine.net/subscribe. Subscribers get in-depth articles on hundreds of emergency medicine topics, concise summaries of the articles, calculators and risk scores, and CME credit. You’ll also get enhanced access to the podcast, including any images and tables mentioned. PA’s and NP’s - make sure to use the code APP4 at checkout to save 50%. Jeff: And the address for this month’s cme credit is www.ebmedicine.net/E0819, so head over there to get your CME credit. As always, the [DING SOUND] you heard throughout the episode corresponds to the answers to the CME questions. Lastly, be sure to find us on iTunes and rate us or leave comments there. You can also email us directly at EMplify@ebmedicine.net with any comments or suggestions. Talk to you next month!

Dr Paul Wang:                   Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor in Chief, with some of the key highlights from this month's issue.                                                 In our first paper Lucas Boersma and associates examined the final two-year outcome data from 47 centers, in 1,020 patients receiving the left atrial appendage occlusion watchman devices. Their study population had a mean age of 73.4 years, with 311 having prior ischemic stroke or TIA, 153 having prior hemorrhagic stroke, and 318 having prior major bleeding. 49% had a CHAS II vast score of 5 or greater, and 40% had a HAS-BLED score of three or greater. Oral anticoagulation was contraindicated in 72%. During follow up, 161 patients, or 16.4% died, 22 strokes were observed or 1.3 per 100 patient years representing an 83% reduction versus historic data. And 47 major non-procedural bleeding events were observed, or 2.7 per 100 patient years representing a 46% reduction versus historic data.                                                 Device thrombus was observed in 34 patients or 4.1%, and was not correlated to the drug regimen during follow up. P=0.28.                                                 In our next paper, Anish Amin and Associates examined whether high voltage impedance and subcutaneous or SICD system implant position are associated with ventricular fibrillation or VF conversion success with a sub-maximal joule shock. In the SICD investigational device exemption study, a successful conversion test required two consecutive VF conversions at 65 joules in either shock vector. Sub-optimal device position was defined as an inferior electrode or pulse generator, or electrode coil depth of greater than three mm anterior to the sternum, based on chest radiograph. Of 314 patients who underwent SICD implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 joules. 62 conversion failures, or 9.7%, occurred in 42 or 14.9% of patients.                                                 Lower body mass index or BMI, and lower shock impedance, were associated with higher conversion success rate. Whereas white race was associated with lower conversion success rate. Sub-optimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high BMI.                                                 In our next paper, Je-Wook Park and associates examined the left atrial pressure after repeat radiofrequency catheter ablation procedures. Among 1,848 patients who underwent atrial fibrillation or AF catheter ablation, the authors measured the left atrial pressure, LAP, immediately following the transseptal puncture in sinus rhythm in 1,687 patients before De novo ablation, median age 59 years, 72.4% male and 72.8% paroxysmal AF, and in 142 with second procedures. In the same 142 patients, the degree of left atrial stiffness, reflected by LAPP, the difference between LAP peak and LAP nater, was significantly higher in the second procedure than in the De novo procedure. P

Dr Paul Wang:                   Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue.                                                 In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction.                                                 Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure.                                                 In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose.                                                 Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping.                                                 In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P > 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P > 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures.                                                 In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0.                                                 In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries.                                                 In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs.                                                 The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern.                                                 In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice.                                                 Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk.                                                 In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress.                                                 In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score.                                                 In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array.                                                 That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time.                                                 This program is copyright American Heart Association 2019.

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, from National Heart Center and Duke National University of Singapore. Dr Greg Hundley:             And I'm Greg Hundley, associate editor for circulation from VCU Health Systems in Richmond, Virginia. Dr Carolyn Lam:                What does cardiac autoimmunity, glycemic control, and cardiovascular disease risk and Type I diabetes have in common? Well, you've got to wait for our feature discussion. This one's such a hot one, don't you agree, Greg? We could hardly finish talking. Dr Greg Hundley:             Absolutely, and Myra, you're just going to love listening to her. Dr Carolyn Lam:                Yep, but stay tuned. First, we're going to discuss a couple of papers each. Greg. Dr Greg Hundley:             Thanks Carolyn. So, the first paper I've got is from Professor Van Rein at Leiden University Medical Center. And basically he's getting at the issue of bleeding in patients with atrial fibrillation. So this is a retrospective cohort that evaluates different anticoagulation strategies for atrial fibrillation. They examined 272,315 patients that had a median age of 75 years and followed them longitudinally over time. These individuals experience 31,459 major bleeding events, and what he did is he evaluated whether they were not taking anticoagulant therapy, whether they were on a vitamin K antagonist, a DOAC, antiplatelet therapies, and then all combinations of the above, including single, double and triple therapy.                                                 What he observed is relative to taking a vitamin K antagonist alone. The hazard ratios range from 1.13 to 3.73 in those that were receiving dual antiplatelet therapy of vitamin K antagonist plus antiplatelet therapy, a DOAC plus antiplatelet therapy, and then of course triple therapy, which had that highest hazard ratio. Dr Carolyn Lam:                But were there particular combinations within these groups that had particularly high bleeding risk? Dr Greg Hundley:             Well, yeah, Carolyn. As we might expect, triple therapy was the worst, but those that were receiving triple therapy, there were two subgroups that were particularly susceptible to having a bleeding episode. First, those that were greater than 90 years of age, and second, those that had CHADS-VASc 2 scores greater than six. Of course, these are very complicated patients, often particularly that latter group. So there are clinical implications. I mean, clearly, this isn't a randomized trial, but what we should take away from this is that if we have one of those two patient groups, age greater than 90, CHADS-VASc score greater than six, that we ought to minimize the time that those individuals are on that triple therapy. Dr Carolyn Lam:                Talk about and bleeding, I've got a paper, and it's on the performance of the ABC scores for assessing the risk of stroke and systemic embolism or bleeding in patients with atrial fibrillation. This is a study that actually looked at the performance of these scores in an external cohort, which actually hasn't really been done. Now, as a reminder, the ABC score is actually the age biomarker clinical history stroke score, which helps to estimate the risk of stroke or systemic embolism. The ABC bleeding risk score incorporates biomarkers along with the clinical variables to estimate the risk of bleeding.                                                 All of these were tested in the ENGAGE AF-TIMI 48 trial, which was that multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS-VASc 2 score of two and above. Now, this was from Dr Morrow and the TIMI study group in the Brigham and Women's Hospital, Harvard Medical School in Boston, Massachusetts. Basically what they found was that the ABC stroke and ABC bleeding risk scores performed well in stratifying the risk for stroke or systemic embolic events or major bleeding in this multinational trial.                                                 Compared to the CHADS-VASc score, the ABC stroke score provided both correct upward and downward reclassification of the stroke systemic embolism risk. Compared with the HAS-BLED score, the ABC bleeding score resulted in a predominantly correct downward reclassification of the bleeding risk. Dr Greg Hundley:             So, this new ABC score, do we integrate it with HAS-BLED? Do we integrate it with CHADS-VASc 2? How do we use this clinically? Dr Carolyn Lam:                So first of all, there are some important remaining unanswered questions, and this was really nicely discussed in an accompanying editorial by Dr Hylek from Boston University School of Medicine. Among this, first of all, the ABC scores need to be validated in patients outside of a clinical trial. Remember, this was a clinical trial cohort. Then there are questions about the timing of measurements of the score, the different settings, hospital and otherwise. Do these scores perform equally well across different vascular beds and in diverse patient populations at the same thresholds used?                                                 So, all these things still need to be addressed. And really, in Dr Hylek's words, the work has just begun. Dr Greg Hundley:             This is an issue with the theme that might be bleeding, and I'm going to talk about a study from Professor Huisman from Leiden University again, and this is the RE-VERSE AD study. Again, patients that are receiving dabigatran and that may have a GI bleed or patients that are on this therapy and unexpectedly need an emergent surgical procedure, this investigative team evaluated the utility of idarucizumab on reversing that anticoagulant dabigatran. So what did they do? They administered 2.5 milligrams of idarucizumab twice separated by 15 minutes.                                                 And again, the study population was uncontrolled GI bleeding or those in need of an emergent procedure. The types of GI bleeds that were involved in this study, a third were upper GI bleeds, a third lower, and then a third, it was either unknown, or there was a mixture of both upper GI or lower GI bleeding. So how do we know that dabigatran is effective? We use a DTT time, and 98% of those with an elevated diluted thrombin time had that reduced after receiving these two twin 2.5 milligram doses at a time point of four hours after administration. Dr Carolyn Lam:                Okay, but were there any complications? Dr Greg Hundley:             Yeah, there were. So first of all, something to think about is that this is a high-risk group. In this study, 14.6% of the cohort actually later died either from the bleeding or what have you. Then another thing we need to be thinking about is when we reversed this anticoagulant, do patients experience thrombotic events? So what this group reported is 4.4% did within 30 days. What were those? Myocardial infarction, deep venous thrombosis, and subsequent PE. Then also at the 30-day time point, one patient experienced an ischemic event.                                                 Another question is once you've administered this, you've gone through the procedure. You stopped the GI bleeding, or you've had the surgery. In this particular study, 66% of those individuals had restarted their DOAC. Those events occurred on top of that. So, interesting information. Looking at administration of idarucizumab, and we'll be using this I think frequently as DOACs are used more frequently in the population, particularly dabigatran, so some important data in guiding us on what we might expect when we administer this therapy. Dr Carolyn Lam:                I think going back to atrial fibrillation though, this is my other selected paper, and it's actually results from the GARFIELD-AF Registry. It's from Dr Bassand from University of Besançon in France, and colleagues, and basically, they looked at the early risks of death, stroke, systemic embolism and major bleeding in patients with newly diagnosed atrial fibrillation in the GARFIELD-AF Registry. They basically found that the rates of all three major clinical events was significantly higher during the first month than in the subsequent period set following up to 12 months.                                                 The leading causes of early death were heart failure, sudden death, acute coronary syndromes, infection or sepsis, and respiratory failure. Dr Greg Hundley:             So, what's the take-home message here? Dr Carolyn Lam:                This is observational, so the key thing to understand here, it's a registry. It's observational. We can't really tell chicken from egg with regards to its newly diagnosed AF verses events, which comes first, which causes what. But nonetheless, the increased hazards of an early event and especially cardiovascular mortality in these newly diagnosed AF patients really point to the importance of comprehensive care for such patients and really should alert physicians to detect warning signs of possible early mortality in these newly diagnosed patients. Dr Greg Hundley:             Very good, Carolyn. Dr Carolyn Lam:                I think that wraps it up. Let's hop to our feature discussion, shall we? I'm so super excited about today's feature paper because it may explain that strong link between hyperglycemia and cardiovascular disease in type one diabetes and all by revealing a potential novel pathway that may have been hiding in plain sight. And yes, I'm stealing the words of editorialists and our associate editor, Dr Naveed Sattar from University of Glasgow, and we're all so pleased to have with us the corresponding author of today's feature paper, Dr Myra Lipes from Joslin Diabetes Center in Boston, Massachusetts. Myra, start us off by telling us a little bit about your study please. Dr Myra Lipes:                   Sure. So we were interested in examining the role of whether chronic hyperglycemia could trigger cardiac autoimmunity in type one diabetes, because chronic hyperglycemia is associated with subclinical myocardial damage, and we had actually previously observed just unexpectedly in a young adult cohort that ... Actually from Italy, where unexpectedly, we noticed that patients with the poorest glycemic control expressed cardiac antibodies. There's a lot of interesting people who are autoimmune-proned may overreact to injury of certain tissues.                                                 So, type one diabetes, it's a classical autoimmune disorder. So we examined, really tested this hypothesis, in stored samples from the DCCT/EDIC study, and this is a very landmark study where patients were randomized to tight glycemic control, intensive glycemic control. Then another group had just conventional control, and this was done over an average of six and a half years. So during this time, the samples were stored. Every year samples were stored from participants, and this was quite a rich data set that is publicly available. So we studied the development of autoimmunity in two groups that had very distinct separations of the A1C level.                                                 We specifically excluded people who developed kidney disease or cardiovascular disease events during the study. So this is a cohort that had relatively recent onset type one diabetes. They're relatively healthy, and again, groups were matched with cardiovascular risk factors at the beginning and the end of this DCCT period. And of course with our studies, we've also looked genetically because your HLA immune response genes can influence susceptibility to autoimmunity.                                                 These patients were actually matched in HLA genotypes. So what we found was that patients with poor glycemic control, there was expression over time. You could see a time course relationship between expression of antibodies over time on the levels of the antibodies that were different in the two A1C groups. The number of antibodies were different in that with the high group expressing more antibodies, more different types of antibodies. These are antibodies ... might say antibodies as like proteins in the blood, and they're actually directed against parts of the myocytes, the myofibrillar complex, and a major target is cardiac myosin heavy chain.                                                 We saw the different parts of the myosin heavy chain retarded, and the presence of two or more antibodies, different types of antibodies, different regions of the myosin to different isoforms. Also, we saw antibodies, the troponin, troponin I. So the number of antibodies with different ... with almost a complete absence of antibodies in a tightly controlled group. I might mention the A1C average was 6.5%, so this is a very tightly controlled group whereas the poorly controlled group is at the opposite extreme, the average A1C during DCCT. The mean updated A1C was about 10%.                                                 So, it was a very clean group, two different groups, and we could see that the number of the types, the number over time, very different in the two groups. In fact the profiles of these antibodies were almost very similar to patients with Chagas cardiomyopathy. That was our positive control group. Chagas cardiomyopathy is possibility to be a form of chronic myocarditis directed against cardiac myosin. So the profiles are almost indistinguishable. So on one hand, you have relatively healthy patients with type one before glycemic control, and that was very unexpected that this would look pretty similar.                                                 But very interestingly, and I might say unexpectedly, we saw ... It was very clear that the people with the highest titers of antibody and the most different types of antibodies, particularly two or more, were subsequently ... We noticed that those patients were at high risk for developing CVD events. And that's while the number of events was slow, we noticed that all the patients, some 60%, had two or more antibodies and developed cardiovascular events. Perhaps one more striking example is a single patient in the study could die of cardiovascular death, had a positivity for all five antibodies at highest titer.                                                 Then we looked at coronary calcification just to measure subclinical atherosclerosis. We noticed that the same numbers, two or more, and also the same antibody specificities that were the highest predictors of CVD events were also predictive of coronary ... had detectable coronary calcification. In addition, we looked at the levels trying to find mechanistically what could explain the link between cardiac autoimmunity and an increased risk for atherosclerosis. We looked at CRP, high sensitivity CRP levels.                                                 Again, these were measured about a decade after the antibody samples were obtained, and we saw that the positivity for multiple antibodies was also associated with markedly elevated ... subsequently elevated high sensitivity CRP levels with levels of six versus something like 1.4 in a group with one or less antibody. So these were very intriguing findings, suggesting a role for autoimmune pathways as a susceptibility to cardiovascular disease in type one diabetes. Dr Greg Hundley:             Myra, that was absolutely incredible description of the study and all the particulars of the findings. I wonder if I could ask both you and Naveed, where do you see the next steps moving forward with this research in the future? Number one. And number two, is this in any way can be used to segregate patients that may need, for example, really aggressive glucose control with an insulin pump or something of that nature? Naveed Sattar:                  I think we left this study as beautifully described as you see by Dr Lipes. I think the context ... We looked at this from editorial perspective ... is that most people don't realize if you have a middle-aged person with type one, their hazard ratio for cardiovascular risk is about somewhere between four to six fold for men and women respectively, which is much higher than type two. It's often thought that it's the area under the curve for hyperglycemia. But what this paper throws up is actually maybe there's another pathway, which we just didn't understand that this wasn't a permanent autoimmunity closing subclinical myocardial disease and inflammations.                                                 But potentially, for me though, there's a saying in British that one swallow does not make a summer. So, it would be nice for other groups to replicate this. I think the findings are, as they stand in isolation, fantastically well done. But it would be lovely if other groups had accessible samples, and I knew of several groups that have up towards tens of thousands of samples, maybe even not 10,000. Certainly 10,000 or so plus or minus samples for type and prospective outcomes to potentially validate the findings and extend them.                                                 And really, if the antibodies do help protect people at higher risk in a meaningful way and improve beyond what we can already do, then you're right. Absolutely. If we can pick up early people who are going to have substantially higher risk, you would want to potentially improve glycemic control, potentially pumps, CGM, closed-loop systems or more intensive statins or lower blood pressure targets or other types of antihyperglycemic agents, which seem to be being tested in type one as well. So that's really one example.                                                 And for me, the other thing would be really nice is to pull up any inflammation. Is this high systemic inflammation? Is it IL-6 level? Is it something else? What about troponin and BNP levels, et cetera. I'd be interested to hear what Dr Lipes thinks and how do you think to take it forward as well. Dr Myra Lipes:                   So, this is something Dr Sattar said and I completely agree. Actually, right now, we're looking at the DCCT cohort as a whole for already. It's relatively small compared to the population-based studies. But there's 1,400 patients, and the subjects had CMR studies that were published in Circulation. So we're going to actually study next whether we see CMR evidence of systolic dysfunction and looking at the broader DCCT cohort. So, those studies are underway. But of course the ultimate test would be looking at if there were samples available from the Swedish NDRs, Scottish registry.                                                 I think it's something that's not often done prospectively. So that would be incredibly exciting, and that's the important thing. I'd say with type one diabetes, for screening for type one diabetes, the use of autoantibodies and particularly two or more different types of islet autoantibodies, and this is just putting things in a broader context, is the entry criteria for type one diabetes prevention trials and something cardiologists wouldn't be aware of but this particular thing. So in decades, people, researchers, in the field has spent decades optimizing islet antibody assays.                                                 So by analogy, it would be really important to standardize assays so that they can be done in Sweden and Scotland and so that other groups could confirm this, and I'm confident that this could be done, since the setting up of our assays was really built on the experience of people of developing standardized assays and rigorous cutoff points for antibody positivity. So it would be really important to work internationally to try to tap into this. Dr Carolyn Lam:                Oh, my goodness. Myra, Naveed, these are such insightful comments. I think as Greg said earlier, I think we could go on forever discussing this paper, but I'm so sorry. Our time is up. Before we go though, I must point all readers to look at figure five of this marvelous paper. It puts together the whole schema of how autoantibodies can play a role both in myocardial and atherosclerotic cardiovascular disease and type one diabetes.                                                 Thank you so much. Greg and I loved having you. Listeners, don't forget to tune in again next week.                                                 This program is copyright American Heart Association 2019.  

The CHADS2 and HAS-BLED predictive index are useful in assessing a patient’s thromboembolic risk and in predicting which antithrombotic therapy is most suitable; and that is either aspirin, clopidogrel, or anticoagulants. The 3 new anticoagulants may be simpler to use and may have less intracranial hemorrhage side effect than warfarin, there has been longer clinical […] The post A Fib 2: CCS 2012 Treatment Guidelines appeared first on Family Pharm Podcast.