Podcasts about emperor preserved

Tirzepatide vs semaglutide in obesity; GLP1a use is complicated; HF outcomes; the misuse of meta-analyses in HF; and a breakthrough in HF care are the topics John Mandrola, MD, covers this week. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. SURMOUNT 5 Clinicaltrials.gov https://clinicaltrials.gov/study/NCT05822830 Press Release   II. Access to GLP-1 Agonist Drugs CMS statement https://www.cms.gov/newsroom/press-releases/biden-harris-administration-announces-medicare-advantage-and-medicare-part-d-prescription-drug III. SUMMIT TRIAL commentary Has Tirzepatide Scaled the HFpEF/Obesity SUMMIT? https://www.medscape.com/viewarticle/has-tirzepatide-scaled-hfpef-obesity-summit-2024a1000m2h IV. Blank Spot in HF Evidence – All cause hospitalizations   Sayed and colleagues What Is Success in HF Trials? https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2827168 EMPEROR-Preserved https://www.nejm.org/doi/full/10.1056/NEJMoa2107038 Mayo Observational Study 10.1016/j.mayocp.2016.11.009 DIG Trial https://jamanetwork.com/journals/jama/fullarticle/195990 V. Misuse of Meta-analysis by HF Community Lu and colleagues PARAGON/PARADIGM Meta-analysis https://jamanetwork.com/journals/jamacardiology/fullarticle/2823259 Desai 2004 https://jamanetwork.com/journals/jama/fullarticle/199995 PARADIGM HF https://www.nejm.org/doi/full/10.1056/NEJMoa1409077 PARAGON HF https://www.nejm.org/doi/full/10.1056/NEJMoa1908655 VI Integration of Palliative Care Into HF Care Chuzi and colleagues Palliative Care in HF 10.1016/j.cardfail.2024.10.435 Kotecha and colleagues Beta-blocker Metaanalysis 10.1016/S0140-6736(14)61373-8 You may also like: The Bob Harrington Show with the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

CardioNerds Drs. Jason Feinman, Gurleen Kaur, and Rick Ferraro discuss the implementation of SGLT inhibitors in clinical practice with Dr. Alison Bailey. Notes were drafted by Dr. Jason Feinman. In this episode, we discuss the implementation of SGLTi in clinical practice scenarios, including for individuals with heart failure regardless of ejection fraction, those with chronic kidney disease, and those with diabetes mellitus. The group also discusses important side effects to monitor for, as well as how to counsel patients when prescribing these medications. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - Clinical Implementation of SGLT Inhibitors For patients with heart failure with reduced ejection fraction, SGLT inhibitors reduce the composite outcome of cardiovascular death or heart failure hospitalization by 25%. SGLT inhibitors can be safely started in patients with an eGFR as low as 20. There are ongoing trials investigating the safety of these medications in individuals with eGFR lower than 20 or those who are receiving dialysis. An eGFR decrease of 3-5 ml/min on average is expected after starting an SGLTi, but this will stabilize over time and provides protective effects of renal dysfunction in the long run. Early data that suggested an association between SGLTi and bacterial UTI development hasn't panned out in the long run, but there is an association between SGLTi and the development of either genital mycotic infections or yeast infections. Perineal hygiene is important to prevent the development of either. A patient-centered, shared decision-making approach should guide the choice of agents for individuals with type 2 diabetes mellitus. In certain patients, it may be reasonable to choose an SGLTi as the first-line agent. Show notes - Clinical Implementation of SGLT Inhibitors What is the data supporting the use of SGLTi in HFpEF? The EMPEROR-Preserved and DELIVER trials investigated the impact of empagliflozin and dapagliflozin, respectively, on cardiovascular outcomes in patients with mildly reduced or preserved ejection fraction. The SOLOIST-WHF trial investigated a combined SGLT1/2 inhibitor, sotagliflozin, in patients with recently worsening heart failure, irrespective of ejection.SGLTi have been demonstrated to reduce the risk of cardiovascular death or worsening heart failure, including heart failure hospitalization, in these individuals. A meta-analysis of the EMPEROR-Preserved and DELIVER trials demonstrated a hazard ratio of 0.80 for cardiovascular death or first hospitalization for heart failure for empagliflozin or dapagliflozin over placebo in the setting of HFpEF. What is the data supporting the use of SGLTi in HFrEF? In addition to the SOLOIST-WHF trial that was previously discussed, the EMPEROR-HF and DAPA-HF investigated the impact of SGLTi medications in patients with HFrEF. In patients with HFrEF, SGLTi medications have been demonstrated to reduce the risk of either cardiovascular death or heart failure hospitalization. Dapagliflozin and empagliflozin had a pooled risk reduction of all-cause death of 13%, a pooled risk reduction of cardiovascular death of 14%, and a 26% reduction in the combination of CV death or first hospitalization for heart failure. What is the expected impact of SGLTi on renal function? Dapagliflozin, empagliflozin, sotagliflozin, ertugliflozin, and canagliflozin have all been studied for their impact on renal dysfunction in individuals both with and without diabetes. In the CANVAS trial,

Welcome to Olink Proteomics in Proximity Podcast!  Below are some useful resources from this episode:  Highlighted publication:Girerd N, et al. Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study. Circ Heart Fail. 2023 May;16(5):e009694. doi: 10.1161/CIRCHEARTFAILURE.122.009694 https://pubmed.ncbi.nlm.nih.gov/37192292/ Large-scale cardiovascular studies:·         Heart “OMics” in AGEing (HOMAGE), a European-based consortium investigating biomarkers to predict heart failure and as drug targets for prevention: https://www.homage-hf.eu/·         Atherosclerosis Risk in Communities (ARIC) consortium, a prospective epidemiologic study to investigate the causes of atherosclerosis and its clinical outcomes: https://sites.cscc.unc.edu/cscc/projects/ARIC·         Framingham Heart Study, a study identifying common factors or characteristics that contribute to cardiovascular disease across three generations: https://www.framinghamheartstudy.org/'·         EMPEROR-Preserved trial, a cohort of patients who had chronic heart failure and a left ventricular ejection fraction of more than 40% : https://www.wikijournalclub.org/wiki/EMPEROR-Preserved High-throughput platforms mentioned during the podcast or used in this study that measure tens to thousands of proteins simultaneously: ·         Olink® Target 96: https://olink.com/products-services/target/ ·         Olink® Explore 3072: https://olink.com/products-services/explore/·         Olink® Explore HT: https://olink.com/products-services/exploreht/ Podcast mentioned during this podcast:Cooper, Peter M, host. Easter Island – Where Giants Walked. Fall of Civilizations, Episode 6, July 2019, https://fallofcivilizationspodcast.com/ Books mentioned during the podcast:·         Attia, Peter. Outlive: the science & art of longevity. New York: Harmony, 2023. https://www.goodreads.com/en/book/show/61153739·         Hood, Leroy and Price, Nathan. The Age of Scientific Wellness: Why the Future of Medicine Is Personalized, Predictive, Data-Rich, and in Your Hands. Cambridge, MA and London, England: Harvard University Press, 2023. https://doi.org/10.4159/9780674293465 Would you like to subscribe to the podcast on your favorite player or app? You can do so here:  Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...  Amazon Music: https://music.amazon.com/podcasts/d97...  Podcast Addict: https://podcastaddict.com/podcast/409...  Deezer: https://www.deezer.com/show/5178787  Player FM: https://player.fm/series/series-3396598   In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY  For any questions regarding information Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/ WHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Dale Yuzuki, Cindy Lawley and Sarantis Chlamydas.

The following question refers to Section 7.6 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.  The question is asked by premedical student and CardioNerds Intern Pacey Wetstein, answered first by Baylor College of Medicine Cardiology Fellow and CardioNerds Ambassador Dr. Jamal Mahar, and then by expert faculty Dr. Nancy Sweitzer. Dr. Sweitzer is Professor of Medicine, Vice Chair of Clinical Research for the Department of Medicine, and Director of Clinical Research for the Division of Cardiology at Washington University School of Medicine. She is the editor-in-chief of Circulation: Heart Failure. Dr. Sweitzer is a faculty mentor for this Decipher the HF Guidelines series. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #9 Mr. Flo Zin is a 64-year-old man who comes to discuss persistent lower extremity edema and dyspnea with mild exertion. He takes amlodipine for hypertension but has no other known comorbidities. In the clinic, his heart rate is 52 bpm and blood pressure is 120/70 mmHg. Physical exam reveals mildly elevated jugular venous pulsations and 1+ bilateral lower extremity edema. Labs show an unremarkable CBC, normal renal function and electrolytes, a Hb A1c of 6.1%, and an NT-proBNP of 750 (no prior baseline available). On echocardiogram, his LVEF is 44% and nuclear stress testing was negative for inducible ischemia. What is the best next step in management? A Add furosemide BID and daily metolazone B Start empagliflozin and furosemide as needed C Start metoprolol succinate D No change to medical therapy Answer #9 Explanation The correct answer is B – start empagliflozin and furosemide as needed. The patient described here has heart failure with mildly reduced EF (HFmrEF), given LVEF in the range of 41-49%. In patients with HF who have fluid retention, diuretics are recommended to relieve congestion, improve symptoms, and prevent worsening HF (Class 1, LOE B-NR). For patients with HF and congestive symptoms, addition of a thiazide (eg, metolazone) to treatment with a loop diuretic should be reserved for patients who do not respond to moderate or high-dose loop diuretics to minimize electrolyte abnormalities (Class 1, LOE B-NR). Therefore, option A is not correct as he is only mildly congested on examination, and likely would not require such aggressive decongestive therapy, particularly with normal renal function. Adding a thiazide diuretic without first optimizing loop diuretic dosing would be premature. The EMPEROR-Preserved trial showed a significant benefit of the SGLT2i, empagliflozin, in patients with symptomatic HF, with LVEF >40% and elevated natriuretic peptides. The 21% reduction in the primary composite endpoint of time to HF hospitalization or cardiovascular death was driven mostly by a significant 29% reduction in time to HF hospitalization, with no benefit on all-cause mortality. Empagliflozin also resulted in a significant reduction in total HF hospitalizations, decrease in the slope of the eGFR decline, and a modest improvement in QOL at 52 weeks. Of note, the benefit was similar irrespective of the presence or absence of diabetes at baseline. In a subgroup of 1983 patients with LVEF 41% to 49% in EMPEROR-Preserved, empagliflozin, an SGLT2i, reduced the risk of the primary composite endpoint of cardiovascular death or hospitalization f...

This week, please join authors Jonas Oldgren and Signild Åsberg as they discuss the article "Early Versus Delayed Non–Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study." Dr. Carolyn Lam: Welcome to Circulation on The Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Poly Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Today's featured paper is a very important discussion, and in fact, the first study to compare early versus delayed NOACs after acute ischemic stroke in patients with atrial fibrillation. The timing study. You're not going to want to miss this, but you're going to have to wait for it, because we're going to discuss all the papers in today's issue. Can I start, Greg? Because I want to start, or is it too early to start with a Greg quiz? With the quiz question being, what is cell-free DNA? Dr. Greg Hundley: Oh, thank you Dr. Lam. I really appreciate your wonderment into the world of preclinical science. So something maybe short DNA fragments, but I'm not sure. Dr. Carolyn Lam: Aw, you're absolutely right. It's circulating DNA fragments predominantly from mononuclear zones that represent cell injury and/or turnover. So what we know is elevated total cell-free DNA concentration has been associated with worse prognosis in a variety of conditions such as sepsis, trauma, malignancy. In addition, and this may be where a lot of us have heard of cell-free DNA, it's become clinically relevant as a noninvasive marker of solid organ transplant rejection as well as a tool for genotyping and surveillance in oncology. However, in today's paper, given the parallels in the pathogenesis of pulmonary artery hypertension, two of the diseases I've talked about before that are characterized by increased cell proliferation and turnover, like the cancers and inflammatory mediated tissue injury. Now this particular study sought to determine if plasma cell-free DNA concentrations were elevated in pulmonary artery hypertension, and if those levels would correlate with disease severity or predict outcomes. Dr. Greg Hundley: Oh wow, Carolyn, this sounds really informative. So what did they find? Dr. Carolyn Lam: Well, this study from corresponding authors, Dr. Solomon from NIH Clinical Center and Dr. Agbor-Enoh from NHLBI in Bethesda and their team found that circulating cell-free DNA is elevated in patients with pulmonary arterial hypertension compared to healthy controls. In two independent PAH patient cohorts, cell-free DNA concentrations increased with severity of disease and predicted transplant free survival in the larger of the two cohorts. Interestingly, methylation patterns revealed increased cell-free DNA originating from biologically plausible sites including erythrocyte progenator and myeloid lineage inflammatory cells, vascular endothelium, and cardiac myocytes. So the implications are that in pulmonary arterial hypertension, cell-free DNA concentrations could serve as a non-invasive biomarker of underlying disease activity, may add prognostic value to currently use risk scores, and may provide a unique noninvasive window into its pathogenesis. Dr. Greg Hundley: Wow, Carolyn. So another interesting technique and pathophysiologic study highlighting the utility of circulating cell-free DNA. Wow. Well, Carolyn, how about I start in with my first study and it comes to us from the world of clinical science and refers to the paradise MI echocardiographic substudy. So Carolyn, the prospective RNE versus ACE inhibitor trial to determine superiority in reducing heart failure events after myocardial infarction. So the Paradise MI echo study tested the effect of Sacubitril/Valsartan compared to Ramipril on LV function and adverse remodeling following high risk acute myocardial infarction. So this substudy included 544 Paradise MI participants that underwent echocardiography at randomization, and then again later at eight months. Patients were randomized within a half to seven days of their presentation with their index, myocardial infarction, to receive a target dose of Sacubitril/Valsartan of 200 milligrams or Ramipril five milligrams twice daily. Dr. Carolyn Lam: All right. So the Paradise MI echo substudy, what did they find? Dr. Greg Hundley: Right Carolyn, so treatment with Sacubitril/Valsartan compared to Ramipril following acute myocardial infarction did not result in changes in left ventricular ejection fraction or left atrial volume at eight months. Patients randomized to Sacubitril/Valsartan had less LV enlargement and greater improvement in filling pressure, and thus there are new insights here in that treatment with Sacubitril/Valsartan compared to Ramipril early following acute myocardial infarction may beneficially impact LV size and diastolic properties possibly due to reductions in LV filling pressure. Dr. Carolyn Lam: Oh, very nice, Greg. Thank you. Another clinical study here, and this time a paper aimed to evaluate the influence of sex on the effects of empagliflozin in patients with HFpEF enrolled in the Emperor Preserved trial. Dr. Greg Hundley: Ah, Carolyn, two of your favorite things, sex differences and SGLT2 inhibitors. So Carolyn, remind us, what did Emperor Preserved show us? Dr. Carolyn Lam: Ah, so Emperor Preserved studied the sodium glucose cotransporter 2 or SGLT2 inhibitor empagliflozin in patients with HFpEF, which is an ejection fraction above 40%, and showed a significant reduction in the risk of cardiovascular death or heart failure hospitalization. In the current paper, corresponding author Dr. Javed Butler from University of Mississippi Medical Center and colleagues found that empagliflozin reduced the risk of the primary outcome of cardiovascular death or hospitalization for heart failure to a similar degree in both women and men with HFpEF irrespective of baseline left ventricular ejection fraction. Empagliflozin produced comparable benefits for the pre-specified secondary outcomes of total heart failure hospitalizations, cardiovascular death, and all-cause mortality, as well as physiologic measures and health status. The pattern of the effects of empagliflozin and HFpEF in both sexes in EMPEROR- Preserved stands in contrast to the influence of sex on the response to neprilysin inhibition. So very interesting paper. I encourage everyone to pick it up, of course, because it's two of my favorite topics. Dr. Greg Hundley: Very nice, Carolyn. Well, my next paper comes to us from the world of pre-clinical science, and it's from Dr. Chunyu Zeng from Diping Hospital, the third military medical university. Carolyn, adverse environmental exposure during the prenatal period can lead to diseases in offspring, including hypertension. Now whether or not the hypertensive phenotype can be trans-generationally transmitted is really not new. Dr. Carolyn Lam: Wow, that's interesting. So what did this paper find? Dr. Greg Hundley: Carolyn, this was really interesting. So these authors in a rat model, they found that prenatal lipopolysaccharide exposure can impair the ability to excrete a salt load and induce hypertension from the first to the third generations, with the fourth and fifth generations inducing salt-sensitive hypertension. And Carolyn, really interestingly, and based on these findings, they treated lipopolysaccharide exposed pregnant rats with the reactive oxygen species scavenger temple, which successfully prevented hypertension in the first-generation offspring and the transgenerational inheritance of hypertension. So Carolyn, these findings show that adverse prenatal exposure induces transgenerational hypertension through an epigenetic regulated mechanism. And these findings identify potentially preventive and therapeutic strategies for this form of generationally transmitted hypertension. Really interesting. Dr. Carolyn Lam: Wow, that sounds wild. Very, very interesting. Well, let's go through the other things that are in today's issue. There's a research letter by Dr. Moayedi on anteroposterior pacer pad position is more likely to capture than anterolateral for transcutaneous cardiac pacing. Dr. Greg Hundley: Great, Carolyn. And I've got a research letter from Professor Porrello entitled, “Defining the Fetal Gene Program at Single Cell Resolution in Pediatric Dilated Cardiomyopathy.” And then lastly, there's an ECG Challenge from Dr. Chen entitled, “A Shark Thin Electric Cardiogram in the Intensive Care Unit.” Well Carolyn, how about we get onto that featured discussion and learn more about non-vitamin K antagonists after acute ischemic stroke? Dr. Carolyn Lam: Yep. In patients with EF, here we go. Today's feature discussion is all about atrial fibrillation, how it's a risk factor for stroke, but also about how we've never known really how soon after an acute stroke can we start oral anticoagulation to prevent recurrent strokes? Today we're going to talk about the timing study. It's the first randomized controlled study to evaluate the efficacy and safety of initiation of treatment with NOACs within 10 days of acute ischemic stroke in patients with atrial fibrillation. Wow. What an exciting study, and also how exciting that we have two co-first authors. We have Dr. Jonas Oldgren and Dr. Signild Åsberg from Uppsala University in Sweden, and this represents a partnership between neurology and cardiology. I mean really unique in many aspects as well as the way this study was performed, which is truly, truly a feat in itself. May I ask you both please to tell me the story of how this study came to be in the first place? Dr. Signild Åsberg: Well, we like to mention the late Professor Gesteruen student who actually was the first to bring this question to the table. Together we talked with the cardiology department and Jonas Oldgren to see if we can collaborate to solve this important question for us that works with stroke patient, because it's on a weekly or even a daily basis, troublesome question. Dr. Jonas Oldgren: My background is as a cardiologist and professor of coagulation research. I've been very interested in anticoagulants, antithrombotic treatments, and had the pleasure and privilege to be part of the development of the novel oral anticoagulants. And in all those pivotal trials, we excluded patients with a recent stroke at least seven days from the stroke, sometimes even 30 days from the acute stroke we excluded them from the studies. So when we found the exciting results with at least as good efficacy as warfarin and at least as good safety as warfarin and the tremendous reduction in intracerebral or intracranial bleeds, that was a finding which was not evaluated in acute stroke patients with atrial fibrillation. And when Signild approached me with this idea, I said, "Well this is absolutely a very important question and why hasn't it been resolved earlier?" And the problem is, of course, that these are patients who are in a sensible setting earlier after the acute ischemic stroke, and when are we able to safely start an effective treatment? Dr. Carolyn Lam: Oh, I couldn't agree more with you about how important that is. I mean, when we have an acute stroke patient, we just don't know whether we should start the NOAC early or delay it and we definitely need that evidence gap filled. But I'm also so intrigued with the way you did it with the Swedish Stroke Register. I mean, what a powerful way to look at important questions like this. Could you tell us a bit more about the method used? Dr. Jonas Oldgren: Yeah, so in cardiology we started rather early by using our national health registries for doing randomized controlled trials. We did a lot of observational studies in our registries, both in stroke and in cardiovascular medicine, otherwise in every other area of medicine. But in the end we realized that we could at best be hypothesis generating, but we still needed to add randomized controlled studies to have the last piece of the puzzle to provide good evidence. And then we ran a lot of studies in cardiologists, especially in myocardial infarction patients, by just adding to simplify, by adding a randomization module, and then follow the patients in the registries because we know that we have high quality data in the registry. For instance, in the stroke registry. So we anyway collect every important data on each and every patient in the register. So by adding a randomization module, we can facilitate the conduct of a clinical study. Dr. Carolyn Lam: Wow. The way you say it, you make it sound so simple, but I can tell you what you have there in Sweden is like the envy of the whole world, and everybody's thinking about how to do a registry based trial like that. So maybe after you tell us the results, you could also share a little bit of how difficult and challenging it can be as well. But would either of you like to share the results? Dr. Signild Åsberg: Well, the major result from our trial is that initiating NOAC within four days is non-inferior to starting in a delayed phase of up to 10 days. So that's our key finding. But equally important is that we didn't have any patients explaining as symptomatic and terrible hemorrhage, and that is extremely good news for us who worked with these patients. Dr. Carolyn Lam: That is such an important message. The early initiation was non-inferior. Could you expand on non-inferior in terms of what primary outcome? Dr. Jonas Oldgren: Yeah, so the primary outcome was really a clinically important outcome we think, both from the cardiac perspective but also from stroke specialists. So we had a combination composite of symptomatic intracerebral hemorrhages, ischemic strokes and death. And this is what matters to patients and to doctors. We would like to avoid strokes, and it doesn't matter if it's an ischemic stroke or if it's a hemorrhagic stroke. We would like to avoid them. And of course we would not like to have an increased mortality as well. So it's a relevant endpoint. And when we designed the study, the main drug used was warfarin, and there we knew that there was a lot of hemorrhagic transformations and a lot of intracerebral hemorrhages. So we designed the trial to look at these three endpoints to prevent ischemic strokes, but to avoid hemorrhagic strokes. And that is why we choose to have a non-inferiority design, because we also have the advantage of starting early if we can make the decision to start with the stroke specialists sometimes in collaboration with the cardiologist, and then we can have the patient step down unit earlier if the treatment is already started. So that was the choice of a non-inferiority design. We of course also tested for superiority, but unfortunately we didn't meet that superiority testing endpoint. But as Signal mentioned, I think thrilling results is to have no symptomatic intracerebral hemorrhage in any of the groups. That really speaks in favor of the safety of this drug or these drugs that we used, but also the concept to start early. We can also note that we had some ... I mean there were numerically lower rates of both ischemic strokes and deaths in the early group, albeit not meeting the significance for superiority, but it's important. And as we see also the events tend to occur very early. So we really gain with treating our patients earlier with this intervention. Dr. Carolyn Lam: Oh indeed. And to all the listeners, do pick up the paper because if you look at the Kaplan-Meier curves, they're really impressive, exactly like you said, numerical differences, although the trial did demonstrate non-inferiority and could not demonstrate the superiority. But have a look at those figures. And if I could just clarify the comparator arm, notice that we've been saying NOACs, not a particular NOACs. So could you expand on that a bit? Dr. Signild Åsberg: We used all the four NOACs that we have in Sweden, so that was to the physician's discretion to choose between them. So that was not a part of the randomization. So we only randomized the timing to the early phase or the delayed phase. Dr. Carolyn Lam: I love that. And then if you could please educate the cardiologist in me, please. There are symptomatic intracerebral hemorrhages, and then there are all kinds of little things that you can pick up if you image the brain and hemorrhagic transformation and microbleeds and all these things. So I think one of the things here was their systematic imaging and does it matter? Could you teach us a little bit more about these different types of bleeds? Dr. Signild Åsberg: We did not have a systematic imaging, but in Sweden that is performed mostly by CT on admission. So that was for all patients. And then on events, the imaging was performed and reported through the registry. And yes, there were hemorrhagic transformation actually in three patients, two in the early phase, and one in the delayed phase, but only one before day 10. So all blood that was seen on imaging was reported, but we used symptomatic criteria from the stroke severity scale. Dr. Carolyn Lam: Thank you. That's a good clarification. And then the study aimed for a larger number, and here perhaps if either of you could tell us the story, the struggles, and how you ended up with these beautiful results. Dr. Signild Åsberg: Yeah, struggle is the word. It was troublesome and we had long talks. So why was this happening? Why didn't science recruit more? But I think one issue might have been that NOACs had been on the market for a while once we started, and even the stroke physicians were getting used to it and had trouble not to start. Before the timing study started, we did a observational pre-timing study just to see how we were doing in Sweden at this stage. Because we didn't really know that. We know that a lot of patients were discharged with oral anticoagulation, but we didn't really know when they started. And so by that study we could see that in median time to initiation was five days, already before the timing study. So one thought was that this was for some physicians then had to delay their start. They were getting used to start early. So that could have been one explanation. Dr. Jonas Oldgren: And of course there has been a lot of observational studies looking at the safety of NOACs or other oral anticoagulants in the early setting after acute ischemic stroke in patients with atrial fibrillation. And of course with the evidence from such studies, albeit observational doctors felt perhaps more confident starting very early despite the lack of evidence from randomized control trials. So we had the opportunity to follow those patients as well in the stroke registry. Every patient with an acute stroke in Sweden attending a stroke unit is registered. So we have in the supplement of the paper in circulation, we have observational data from the centers participating in stroke, but patients not randomized in the timing study. And we also have observational data from all stroke centers in Sweden. So we can see that many start very earlier with NOACs based on observational data, based on experiences. And perhaps we're more and more reluctant to randomize the patient in the study because as Signal says, that means there is a 50% chance of delayed treatment by randomization. And when we started this study, there were no evidence from randomized controlled trials within the first 14 days. But while running the study for a couple of years, you start to believe that there seemed to be safety because no one saw any symptomatic intracerebral hemorrhage. And we discussed that, of course, at investigative meetings that this seemed to be a very good treatment, which is bad for running a clinical study, but it's of course good for the patients. Dr. Carolyn Lam: Interesting. So echo points kind of may have shifted a little bit even during the course of the trial. So just thank you so much all the more. Thank you for seeing this to completion in the sense of a beautiful manuscript with very meaningful results. If I could ask you both to each summarize just very quickly what the take home message is for clinical practice from neurologist's point of view and cardiologist's point of view? Dr. Signild Åsberg: Yeah, what I would say, it seems both safe and reasonable to initiate NOAC earlier after an acute ischemic stroke. So I think that's the key take home message that really to consider the acute secondary prevention. Dr. Jonas Oldgren: I may bring that from another perspective. I think when there's lack of data in collaboration, we can do a lot. So in this case, we had a great collaboration in the student committee, cardiologist and stroke specialists collaborating to run such a study. And we are extremely grateful for all the sites and all the investigators at the sites participating in the study. And then of course grateful to circulation for publishing it because we are very proud of this study. Dr. Carolyn Lam: And we are proud to be publishing this. So ladies and gentlemen, you heard it right here in Circulation On The Run. Remember this is about early versus delayed initiation of NOACs in patients after an acute stroke who also have atrial fibrillation. And this is a very, very, I think, important study that fills an important evidence gap. We're so grateful to both of you for being here to discuss it, and to the audience for listening today. You've been listening to Circulation On The Run. And don't forget to tune in again next week. Dr. Greg Hundley: This program is Copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit AHAjournals.org.

This week, please join author Rod Stables and Associate Editor Nick Mills as they discuss the article "Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary and backstage pass through the journal and its editors. We're your co-hosts! I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature... Very interesting. There is a lot of information about using fractional flow reserve during contrast coronary angiography. But how does that compare to just reviewing the angiograms when managing patients with coronary artery disease? Well, we are going to hear some results from the RIPCORD 2 trial, and they may surprise you a little bit. But, before we get to that interesting feature discussion with authors and editors, how about we grab a cup of coffee and dive into some of the other articles in the issue? Dr. Carolyn Lam: Yeah, let's do that, Greg. Do you have a paper to share first? Dr. Greg Hundley: Oh, thanks Carolyn. Sure. So Carolyn, as we know, Apolipoprotein B or apoB, provides an integrated measure of atherogenic risk. But whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndromes, beyond that provided by low density, lipoprotein cholesterol, or LDLC, that's uncertain. So Carolyn this study emanates from the Odyssey Outcomes trial, which compared the Proprotein Convertase Subtilisin/Kexin Type 9 inhibitor, Evolocumab with placebo in 18,924 patients with recent ACS and elevated atherogenic lipoproteins despite optimized statin therapy. Now the primary outcome was major adverse cardiovascular events. So MACE was coronary heart disease, death, nonfatal myocardial infarction, fatal non-fatal ischemic stroke, and hospitalization for unstable angina. And associations between baseline ApoB or ApoB at four months and MACE were assessed in adjusted Cox proportional hazards and propensity score matched models over median of 2.8 years. Dr. Carolyn Lam: Oh, right. So what were the results, Greg? Dr. Greg Hundley: Right, Carolyn so impatience with recent ACS and elevated atherogenic lipoproteins, MACE increased across baseline ApoB strata, and now evolocumab reduced MACE across all strata of baseline ApoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved ApoB was associated with lower risk of MACE, even after accounting for achieved LDLC or Non-HDLC indicating that ApoB provides incremental information. And therefore, Carolyn, if it is modified achievement of an ApoB level less than or equal to 35 milligrams per deciliter may reduce lipoprotein attributable residual risk after ACS. Isn't that interesting? Dr. Carolyn Lam: Yes. Very nice, Greg. Thank you. This next paper is a pre-specified analysis of the EMPEROR-Preserved trial, looking at patients with and without diabetes. Dr. Greg Hundley: So remind us, Carolyn, what was the EMPEROR-Preserved trial and what did it show? Dr. Carolyn Lam: Well, in EMPEROR-Preserved Empagliflozin, the SGLT2 inhibitor reduced risk of the composite of cardiovascular death or heart failure hospitalization, as well as first and recurrent heart failure hospitalizations and slowed renal function decline in patients with heart failure and an ejection fraction greater than 40%. So the current paper sought to determine if effects were consistent in patients with, and without diabetes, of the almost 6,000 patients enrolled, 49% had diabetes. The risk of adverse outcomes, first of all, was higher in patients with diabetes. Now the treatment effect of Empagliflozin was however, similar in that Empagliflozin reduced the rate of the primary outcome and total heart failure hospitalization, irrespective of diabetes status. The effect of Empagliflozen falls into attenuate GFR decline, however, was also present in patients with, and without diabetes, although more pronounced in patients with diabetes. Now across all these three endpoints, the effect of Empagliflozen did not differ in patients with prediabetes or normal glycemia. And importantly, there was no increased risk of hypoglycemic events in either subgroup compared with placebo. So a very nice paper there. And that was from Dr. Gerasimos Filippatos from Athens University Hospital Attikon and colleagues. Dr. Greg Hundley: Wow, Carolyn, just really interesting information coming out of the world of SGLT2 innovation. Well, Carolyn, my next paper comes to us from the world of preclinical science and it's from Dr. Kunhua Song from the University of Colorado Anschutz Medical campus. So Carolyn, abnormalities of calcium homeostasis are closely associated with cardiac arrhythmias and heart failure and conditions that cause death of millions of people every year. Now, Carolyn Triadin physically interacts with the Ryanodine receptor 2 and plays an important role in releasing calcium from the sarcoplasmic reticulum to increase the free intracellular calcium concentration in cardiomyocytes. Now alternative splicing of a single Triadin gene produces multiple Triadin isoforms, the predominant cardiac Triadin isoform mouse Mt1 or human Trisk 32 is encoded by Triadin exons from one to eight. In humans, mutations in the Triadin gene that lead to a reduction in Trisk 32 levels in the heart cause cardiac dysfunction, cardiac arrhythmias and sudden death. Decreased levels of Trisk 32, in the heart, are also common in patients with heart failure. However, mechanisms that regulate alternative splicing of the Triadin gene to maintain levels of cardiac Triadin protein in the heart, remains somewhat elusive. Dr. Carolyn Lam: Wow. I am always learning from these cool papers. Thanks Greg. So what were the results? Dr. Greg Hundley: So Carolyn, the investigators found several things. First, the cardio MyoSite specific long non-encoding RNA or link RNA Triadin AS is essential for maintenance of cardiac function, exercise capacity and normal lifespan and Triadin AS knockout mice were found predisposed to cardiac arrhythmias in response to catecholamine challenge. And finally Carolyn, Triadin AS controls, levels, of cardiac Triadin isoforms, by regulating the splicing of the Triadin gene. Dr. Carolyn Lam: Oh, wow. All right. So could you bring it home for us, Greg? What are the clinical take home messages? Dr. Greg Hundley: Right, Carolyn. So cardiac explants from human heart failure patients as well as patients with cardiac arrhythmias, demonstrate reduced expression of Triadin AS and Triadin. And then next the mechanism of the Triadin AS and Triandin AS mediated alternative splicing of the Triadin gene to specifically control levels of cardiac isoforms of Triadin in the heart, provides a potential strategy for the treatment of cardiac arrhythmias and heart failure. Dr. Carolyn Lam: Wow. Thank you, Greg. Well, let's talk about what else is in today's issue. There's a Research Letter by Dr. Agarwal on Chlorthalidone for resistant hypertension and advanced chronic kidney disease. Dr. Greg Hundley: And Carolyn, I've got a perspective piece by Professor Cowie pertaining to atrial fibrillation entitled, “I'm Sorry, Mrs. Jones, but We Cannot Make You Feel Better Today.” Well, Carolyn, how about we get onto that feature discussion and review the utility of fractional flow reserve measurements, in patients undergoing contrast coronary angiography. Dr. Carolyn Lam: Great, let's go. Dr. Greg Hundley: Welcome listeners to this August 30th feature discussion. And we have with us this afternoon, Dr. Rod Staples from Liverpool and our own associate editor, Dr. Nick Mills from Edinburgh, Scotland. And gentlemen, welcome, Rod we'll start with you. Can you describe for us the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Rod Staples: Okay, well thanks very much for hosting today. I'm very grateful to be working circulation on this. I'm working with my co-lead investigator Professor Nick Harrison from Southampton, who's been doing an enormous amount of work on coronary physiology. He actually did the original RIPCORD study, what I suppose we'd now call RIPCORD 1, but it was called RIPCORD in the early days, an observational study that showed that systematic use of fractional flow reserve at the time of diagnostic angiography. Assessing the functional significance measured in each of the major coronary vessels, appeared in an observational study to have a dramatic effect on the subsequent management plans allocated to patients. And we decided to test this in a prospective randomized trial. Dr. Greg Hundley: Very nice. And so the exact hypothesis that you were going to test was what? Dr. Rod Staples: At the time of coronary angiography, a strategy of systematic measurement of fractional flow reserve in each and every coronary vessel, large enough to be considered for revascularization, would improve outcomes compared to a strategy based on angiographic assessments alone. Dr. Greg Hundley: Very nice. And so you mentioned a randomized trial. Can you describe further your study design and then which study population did you include? Dr. Rod Staples: Well, this is a classic multicenter randomized trial performed in the UK. We actually recruited in 17 different UK centers. We asked them to assess patients who were scheduled for invasive, currently angiography for participation against some very minimal inclusion and exclusion criteria, trying to keep the trial generalizable with good external validity. I think one important point to note is that we did allow the inclusion of both patients being assessed with elective angiography for stable symptoms, but in the end half of the population were recruited in the context of a stabilized acute coronary syndrome, a Non-ST-elevation event a day or so down the line. Dr. Greg Hundley: And just a quick breakdown, how many men, how many women? Dr. Rod Staples: Well, it's in that respect, the population is very, very typical for this type of cardiovascular trial. A 70, 30 split an age in the midsixties, a diabetic population in the high teens. So a very typical population we've seen in all this kind of trial environment. Dr. Greg Hundley: Very nice. And so about 1100 patients. And then what were your study results? Dr. Rod Staples: Well, I think there was a very good adherence to the study protocol, very, very few crossovers. And also we were pleased to see that our investigators stayed true to the protocol in that the median number of epicardial vessels assessed by FFR in that randomized arm was four. So there was a good assessment by FFR. The trial was interesting in another respect, in that we assessed an economic outcome based on all NHS hospital costs over the following year and a patient reported outcome based on quality of life using the WHOQOL, and interestingly we found no significant differences either in total subsequent hospital costs from randomization for a year, or indeed in patient reported quality of life by WHOQOL or Angina symptoms by the Canadian Cardiovascular Society classification. Dr. Greg Hundley: Very nice. And then, what about clinical events? Did you examine those as well? Dr. Rod Staples: We did. And again, just a little caveat here, the trial is again interesting in that, what is often in the UK these days called a lean efficient methodology. Whereby, rather than individually contacting individual trial participants or scouring medical records, we interrogated the central national NHS digital repository of all hospital admissions. And we examined electronically a download of every hospitalization event for every patient using algorithms based on diagnostic and procedural codes to define events. And again, we found a very credible representative rate exactly at incidents and events we would've predicted, but again, no difference between the randomized groups. Dr. Greg Hundley: Very nice, well listeners, now we're going to turn to our own Associate Editor, Dr. Nick Mills. And Nick, again, you see many papers come across your desk. What attracted you to this particular manuscript? And it's very interesting study results. Dr. Nick Mills: Thanks, Greg. Firstly, it addresses an important clinical question. Going beyond that, what appealed to me was it was investigator initiated. It was managed by independent trials unit. It recruited a target, it reported the registered outcomes and it was thoughtfully interpreted. And the fact that it didn't prove the hypothesis was irrelevant because it addresses a really important clinical question. And I think it requires some context, and that is that from the previous randomized trials The FAME series, we have been chastised as interventional cardiologists for not using FFR for relatively low use of FFR clinical practice. It's always around one in 20 patients in most series, given the evidence that FFR guided intervention improves outcomes. But actually what FFR is good at is discouraging you from stenting patients with stable Coronary Disease. And so, I think a pragmatic trial that addresses that, the fundamental question, should we be doing more FFR more broadly in both acute and stable disease to guide revascularization with a definitive message that we shouldn't, it doesn't improve quality of life. It doesn't alter costs. Clinical outcomes are similar, but there are more complications associated with routine pressure wire use, gives us a very clear steer for the future. So this is a really important trial addressing a fairly fundamental clinical question. Dr. Greg Hundley: Very interesting. Well, Rod, we're going to turn back to you with Nick's comments and how we're really seeing an evolution in thought processes regarding both diagnostic angiography, and then also the use of functional testing. What do you see is the next study, really in this sphere of research that would be performed? Dr. Rod Staples: Well, I agree with Nick in a way that this raises important philosophical points about the use of intelligence, selective employment of tests or interventions, and that perhaps we need to reflect this in the way we conduct our future studies. I think we're all aware that fractional flow reserve and other measures of functional significance are tremendously valuable in certain clinical settings. And that value's been proven in randomized trials, but in PRECORD 2, for example, if a patient randomized to angiography only was an acute coronary syndrome patient, who had inverted their T waves in their anterior leads, had an associated troponin rise, an echocardiogram had shown some Hypokinesia in the anterior territory. Then I think the potential value of PCI in the LAD does not necessarily require FFR confirmation, and hence that patient will have an equivalent outcome in the angiography group. Similarly, high quality pre-angiography preparation in the elective population with functional testing, stress testing, other forms of imaging mean that we can reserve the use of invasive fractional flow reserve, tight indices to more selective use. Dr. Greg Hundley: And Nick, turning to you, what do you think is the next research study that could be informative in this space? Dr. Nick Mills: I think our whole philosophy by how to manage stable coronary disease is changing. In part because of some other landmark trials that the Ischemia trial and some of the key secondary analyses of the Ischemia trial that tells the Pathoma burden, low attenuation plaque, other aspects of chronic disease are vitally important in predicting major events in the future. And that leaves us with the role for FFR or CT FFR, primarily to manage symptoms. And I think we're getting increasingly good evaluating patients before they get to the Cathflow, optimizing their medical treatment. And so for me, the trial that we really need to help us, is a CT FFR trial to understand the role of Ischemia testing plus anatomical testing and how they dovetail in guiding treatment decisions before they get to the cath lab. I think we need to move this before the lab, always going to be a role for intelligent FFR testing in selected patients once we get to it. But I think that the question probably needs to be addressed before they get to the cath lab. Dr. Greg Hundley: Very nice. Well listeners, we want to thank, Dr. Rod Staples from Liverpool and Dr. Nick Mills from Edinburgh, Scotland for bringing us this very interesting study, highlighting that a strategy of systematic FFR assessment, when compared to angiography alone, did not result in a significant reduction in cost or improvement in quality of life. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

In this episode, guest host Deepak Bhatt, MD, MPH, FACC, offers a preview of some of the most important and clinically transformative studies being presented at the ESC 2022 Conference, August 26-29. Day One includes: more data from the EMPEROR trial on the mechanisms and clinical benefits of SGLT2i in heart failure, the TAILOR-PCI randomized trial on genotype-guided oral P2Y12 inhibitor therapy, phase 2 data from the ENTRIGUE study on pegozafermin for the treatment of severe hypertriglyceridemia, and the results of the TIME trial on the timing of morning versus evening medication. Also on Day One, Dr. Valentine Fuster will present the results of the SECURE trial, a polypill strategy in secondary prevention. There will also be a presentation of the ASCEND study on the effects of aspirin and omega−3 fatty acid supplements on heart failure. Dr. Bhatt will present data from the REDUCE-IT trial on the significant reduction in ST-Elevation MI with icosapent ethyl. Day One will also cover the EXHAUSTION project, investigating air temperature and cardiovascular disease, as well as the ADDICT-ICCU study on carbon monoxide and acute cardiac events. Day Two will include: a presentation by Davada Perera on REVIVED, investigating percutaneous revascularization for ischemic ventricular dysfunction, ALL-HEART data on allopurinol and cardiovascular outcomes in ischemic heart disease, and a major presentation by Scott Solomon on the DELIVER trial, examining dapagliflozin in heart failure with mildly reduced and preserved ejection fraction. There will also be a number of pooled analyses on Day Two, including one looking at DAPA-HF and DELIVER, and a pre-specified meta-analysis of DELIVER and EMPEROR-Preserved. Together these studies will firmly cement the concept of the SGLT-2 inhibitors class as a heart failure medication.  Day Three opens with an important presentation on INVICTUS, exploring rivaroxaban versus VKA for rheumatic atrial fibrillation. There will also be a group of presentations on some modest but significant Phase 2 trials on factor XIa inhibitor asundexian. Additionally, Renalto Lopes will present data on the APOLLO trial exploring apixaban for prophylaxis of thromboembolic outcomes in COVID-19, and the five-year data from the MOMENTUM 3 study on LVAD Therapy will be presented.   On the fourth and final day, presentations include the clinical outcomes at 5 years of follow-up in the ISCHEMIA-CKD EXTEND trial, the review of the MASTERDAPT trial data at 15 months, the primary results of FOURIER-OLE, and data from the PANTHER Trial on P2Y12 inhibitor versus aspirin monotherapy in patients with coronary artery disease. ESC 2022 promises to be a rich and rewarding experience for those who can attend in person or participate virtually.

C. Michael Gibson and Stefan Anker discuss the effects of empagliflozin on CV death and HF hospitalizations in patients with HFpEF, with and without diabetes.

Os inibidores da SGLT2, discutindo os estudos centrais para sua análise: EMPAREG 2015, DAPA-HF (2019) e por fim o EMPEROR-REDUCED (2020) e FEP. EMPEROR PRESERVED. Dr. José Alencar, Cardiologista e Eletrofisiologista do setor de ECG e do PS do Instituto Dante Pazzanese de Cardiologia. Convidado: Dr. Daniel Araújo é cardiologista do setor de dislipidemias e diabetes do Instituto Dante Pazzanese de Cardiologia. Instagram: @josenalencar @oficialmanole

In this week's View, Dr. Eagle discusses a comparison of patients infected with Delta versus Omicron COVID-19 variants, then looks at a post-hoc analysis of the EMPEROR-Preserved trial on mineralocorticoid receptor antagonists and empagliflozin in patients with heart failure and preserved ejection fraction. Finally, Dr. Eagle explores a recent NCDR Registry paper on sex differences in management and outcomes of acute myocardial infarction patients presenting with cardiogenic shock.

This episode provides an in-depth analysis of the EMPEROR-Preserved study, including the main components of the study methodology, patient population, efficacy and safety findings, and overall clinical application. A review of SGLT2 inhibitors in HF is also covered, along with a discussion of ongoing studies. The information presented during the podcast reflects solely the opinions of the presenter. The information and materials are not, and are not intended as, a comprehensive source of drug information on this topic. The contents of the podcast have not been reviewed by ASHP, and should neither be interpreted as the official policies of ASHP, nor an endorsement of any product(s), nor should they be considered as a substitute for the professional judgment of the pharmacist or physician.

Dr. Ebell and Dr. Wilkes discuss the POEM titled ' Empagliflozin reduces hospitalization for heart failure with preserved ejection fraction (NNT = 59 per year), but not mortality outcomes (EMPEROR-Preserved) '

Join Dr. Steve Greene and Dr. Muthiah Vaduganathan for a regular news roundup of the latest evidence and clinical trial insights across cardiovascular, renal, and metabolic diseases. In the inaugural episode of Don't Miss a Beat, Drs. Greene and Vaduganathan discuss the impact of an early career mentor and provide insight into their favorite trials from 2021, including EMPEROR-Preserved and SSaSS. A video version of this podcast, which includes visual aids, can be found on PracticalCardiology.com

Please join author Mohamed Abdel-Wahab and Associate Editor Stefan James as they discuss the article "Comparison of a Pure Plug-Based Versus a Primary Suture-Based Vascular Closure Device Strategy for Transfemoral Transcatheter Aortic Valve Replacement: The CHOICE-CLOSURE Randomized Clinical Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run. Your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, a very interesting topic, looking at closure devices at the sites of access for patients that are undergoing TAVR procedures. But before we get to that, how about if we grab a cup of coffee and start with some of the other articles in the issue. Would you like to go first? Dr. Carolyn Lam: I would love to and I would like to describe not just one, but two articles from recent SGLT2 inhibitor trials. So, the first paper is an analysis of the DAPA-HF trial. Now we know that circulating high sensitivity, cardiac troponin T predominantly reflects myocardial injury. And higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction or HFrEF. But what about the prognostic significance of changes in high sensitivity troponin T over time and the effects of Dapagliflozin and on clinical outcomes in relation to baseline levels, as well as the effect of dapagliflozin on the high sensitivity troponin T levels? Well, this is what this study answers. It's a biomarker substudy of the DAPA-HF trial from Dr. Berg of the TIMI study group at Brigham women's hospital and colleagues. Dr. Greg Hundley: Wow. Carolyn, very interesting. So remind us about the DAPA heart failure trial. What was it about? Dr. Carolyn Lam: Ah, well, DAPA-HF was a randomized double blind placebo control trial of dapagliflozin in patients with symptomatic HFrEF defined by injection fraction 40% or less wherein dapagliflozin significantly reduced the primary endpoint of cardiovascular death or worsening heart failure events. And in today's biomarker substudy increases in high sensitivity, cardiac troponin T over a one year interval of time were highly predictive of subsequent risk of worsening heart failure and cardiovascular death. The effect of dapagliflozin on the primary endpoint was consistent irrespective of baseline troponin T concentration with no evidence of attenuated treatment benefit in those with very high troponin T concentrations. Dr. Greg Hundley: Very interesting Carolyn. Now you've got another study. Is this one on EMPA? Dr. Carolyn Lam: You are right. Thank you. The next paper is and analysis of the Emperor-Preserved trial. As a reminder, Emperor-preserved study the SGLT2 inhibitor empagliflozin in patients with HFpEF this time, which is a left ventricular ejection fraction above 40, and showed a significant reduction in the risk of cardiovascular death or heart failure hospitalization. The current paper evaluated the efficacy of empagliflozin on health related quality of life in patients with HFpEF and whether the clinical benefit observed with empagliflozin varied according to baseline health status. Dr. Greg Hundley: Very nice, super review Carolyn. So what were the results of this study? Dr. Carolyn Lam: In Emperor-Preserved, baseline health status and quality of life did not influence the magnitude of effect of empagliflozin on the risk of cardiovascular death or hospitalization for heart failure. Empagliflozin improved health status and quality of life as assessed by the Kansas city cardiomyopathy questionnaire across all domains and at all measured time points. Thus an effect that appeared early and was sustained for at least one year. Dr. Greg Hundley: Very nice. So two really informative papers on SGLT2 inhibitors. Well Carolyn, I'm going to turn the conversation to the world of preclinical science and talk about Titin. So Carolyn, titin truncation variants are the most common inheritable risk factor for dilated cardiomyopathy and their pathogenicity has been associated with structural localization. The A-band variants with overlapping myosin heavy chain binding domains appear more pathogenic than the I-band variants and the mechanisms for this are not well understood. So these investigators led by Dr. Hinson at the Jackson Laboratory for genomic medicine, performed a study demonstrating why A-Band variants are highly pathogenic for dilated cardiomyopathy and how they could reveal new insights into dilated cardiomyopathy pathogenesis. Titin functions and therapeutic targets were assessed. Dr. Carolyn Lam: Wow, interesting. So what did they enroll in? How did they do this? what did they find? Dr. Greg Hundley: Great Carolyn, so human Cardiomyocytes and cardiac micro tissue functional assays revealed that highly pathogenic A-Band Titin truncation mutations generate four shortened titin poisoned peptides and diminish full length, titin protein levels. While less pathogenic I-band titin mutations only diminish titin protein levels. And so Carolyn, the authors developed a one and done, genome editing therapeutic approach using CRISPR technology to repair the reading frame of Titin truncation mutations in cardiomyocytes. And therefore these genome editing therapeutics could correct the underlying genetic lesion responsible for dilated cardiomyopathy due to these Titin mutations. Dr. Carolyn Lam: Wow. Interesting. One and done genome editing. You learn something new every day with circulation. You've got another paper? Dr. Greg Hundley: Yes, Carolyn. Thank you. And so this paper comes to us from Dr. Beiyan Zhou From the Yukon health, school of medicine and again, from the world of preclinical science. So Carolyn, while several interventions can effectively lower lipid levels and people at risk for atherosclerotic cardiovascular disease, cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to this cardiovascular event risk. Now monocytes and macrophages play central roles in atherosclerosis, but previous work has yet to provide a detailed view of macrophage populations involved in increased atherosclerotic cardiovascular disease risk. Dr. Carolyn Lam: Huh? Okay. Well, I'm super excited to hear what these investigators did Greg. Dr. Greg Hundley: Right, Carolyn. Well these authors developed a novel computational program. They call AtheroSpectrum, which identified a specific gene expression profile associated with inflammatory macrophage foam cells. And additionally, a subset of 30 genes expressed in circulating monocytes jointly contributed to the prediction of symptomatic atherosclerotic vascular disease. So therefore Carolyn, in the future, perhaps incorporating this new pathogenic foaming gene set with known risk factors may significantly strengthen the power to predict atherosclerotic cardiovascular disease risk. Dr. Carolyn Lam: Wow. Super interesting and well summarized. Thank you, Greg. Well also in today's issue, there's a Perspective by Dr. Kirtane on “The Long-Awaited Revascularization Guidelines are Out. What's In Them?” A Research Letter by Dr. Laffin on rise in blood pressure observed among us adults during the COVID 19 pandemic. Dr. Greg Hundley: Very Nice Carolyn. Well in our Cardiovascular News Segment, there's a piece on metabolic risk factors and how they drive the burden of Ischemic heart disease. Well, what a great issue here and now, how about we get onto that feature discussion? Dr. Carolyn Lam: Very Cool. Closure devices after TAVR. Here we go. Dr. Greg Hundley: Well, listeners welcome today to our feature discussion and we have with us Dr. Mohamed Abdel Wahab from Leipzig Germany. And we are going to discuss some issues pertaining to transcatheter aortic valve replacement, in terms of access to the arteries in the lower extremity. Welcome Mohamed. And can you start with, what was some of the background that led you to perform your study and what was the hypothesis that you wanted to address? Dr. Mohamed Abdel-Wahab: Thank you, Greg. And thank you for having me here. So as you mentioned, there are several cardiovascular procedures that currently require large-bore arterial access. The most common of these procedures is transcatheter aortic valve replacement. But there are other procedures as well, like endovascular aortic repair, mechanical circulatory devices. All of these require large-bore arterial access and of course, closure afterwards. And what we were interested in looking at was whether different types of vascular access site closure devices or strategies behave differently in the setting. Particularly in the setting of transcatheter aortic valve replacement. The reason behind this is that for many years, we only had one technique, to percutaneously close arterial access sites after these procedures. And these were mainly based on suture based devices or suture based techniques. Very recently, alternative techniques based on collagen plugs have been introduced. Dr. Mohamed Abdel-Wahab: And we know these types of devices or closure techniques from usual coronary intervention procedures for smaller access sites or for smaller sheath size. But they have been developed a step further for these large-bore procedures. These newer devices, particularly what we call the MANTA device, which is based on the collagen plug has been shown in initial visibility studies and also in registry based analysis to be very safe and effective. It leads to a very rapid hemostasis. And data from observational studies have suggested that it may be even superior to the suture based techniques, largely based on what we call the ProGlide device or the [inaudible 00:10:56]. And this is actually what we were aiming to look at. To compare these two different strategies based on two different devices. The suture based, the classical suture based technique using two ProGlides compared to the newer plug based technique using the MANTA in a population treated with TAVR. Dr. Greg Hundley: Very nice. And describe for us, your study design. And then also maybe explain a little bit more about the study population. Who did you include in this study? Dr. Mohamed Abdel-Wahab: So the design was more or less, very inclusive. So we designed the trial to more or less represent real word population. More or less [inaudible 00:11:40] population receiving transcatheter aortic valve replacement. So we included patients, of course where the procedure is being thought to be indicated and feasible by a multidisciplinary heart team. And also where the heart team thought that the transfemoral access route, which is the main route for the majority of patients, is obtainable and use of a percutaneous closure device is also possible. Dr. Mohamed Abdel-Wahab: Of course we had some exclusions. For example, patients where the use of a surgical access technique was necessary. They couldn't be naturally included in the trial. Patient that already had complications related, for example, to previous coronary angiogram PCI at the access site, they couldn't be included. But we were more or less, very inclusive in this trial. The trial population reflects the patients that are currently being treated with TAVR, so more or less an elderly population. More or less equally split-by males and females, which is very particular, again to the TAVR population. So this is a little bit different than the population that receives PCI, where we usually have a predominantly male population. This is not the case here. So these are the broad lines. Also reflecting current practice, the population that has been included in the trial is more or less overall, an intermediate risk population, when you look at the surgical scores. Dr. Greg Hundley: Very nice. So this was multicenter and then also patients were randomized to each of the two therapies, I believe. And was that a one to one randomization? Dr. Mohamed Abdel-Wahab: Exactly. So it was a multicenter trial. Patients were randomized between these two techniques. We mentioned the ProGlide based and the MANTA based in 1:1 fashion. And steering committee of course was more or less dominated by interventional cardiologists. Of course, in the context of this particular trial setting, the trial was only performed in Germany and it was an investigative initiated trial, not sponsored by the industry. Dr. Greg Hundley: Very nice. And can you describe for us, Mohamed, your results? Dr. Mohamed Abdel-Wahab: Yes. We actually hypothesized based on the observational data we have, that we will have less vascular complications with the MANTA based technique or the collagen based technique. At the end of the day, what we observed is completely the opposite. So the primary endpoint of the trial, which was what we call major and minor vascular complications defined according to the standardized criteria provided by the valve academic research consortium. These events occurred significantly more common in patients that were randomized to the MANTA based technique, as opposed to the ProGlide based technique, which was statistically significant. Dr. Greg Hundley: And did you observe those results across both the men and the women? And also, were there any differences in the results related to participants' age? Dr. Mohamed Abdel-Wahab: Yeah. So there were no interactions with various subgroups, both the predefined ones, including age and sex, as you mentioned. But also we looked at some post hoc subgroups, including for example, whether this is being affected by the size of the access vessels or by the presence and location of calcification, for example. But there were no interactions in all subgroups we looked at, with one exception which was chronic renal insufficiency. But all other subgroups showed actually no significant interaction, favoring the suture based, ProGlide based technique in all subgroups. Dr. Greg Hundley: Very good. And so can you describe in terms of, for individuals performing TAVR procedures and obtaining access, how do we use the results of your study to inform how we might move forward with closure of the artery in the future? Dr. Mohamed Abdel-Wahab: I mean, the first thing I would like to stress is the importance of doing randomized trials in general. Because I think this is not the first time we see opposite results when we are comparing randomized evidence with the evidence from observation studies, with the known limitations of observational comparative analysis. The second thing I think is really reassuring that the suture based technique that we know and that we have been using for many years now is safe and appears to be even more effective than the newly developed plug based technique. So this is one important information I think from this trial. The third piece of information is that the recently developed plug based technique, although being inferior in the study, it still may have some advantages in selected patients. And this is what we probably need to look at in a little bit more details in the future. Dr. Mohamed Abdel-Wahab: For example, what we realized from the study is that it could be a good option as a bailout device. So in some cases where the suture based technique has failed in the study, the crossover to the MANTA device was successful in the majority of cases. And may lead or help avoid complex endovascular interventions and implanting for example, stents or covered stents or even doing surgery. So this is something that is a nice observation from the dataset we have, but of course needs validation in larger studies. Dr. Greg Hundley: Very nice. And so really you've answered, kind of one of our key questions is, your thoughts on the next study that you see needs to be performed really in this area of research? Dr. Mohamed Abdel-Wahab: Yeah, so I think there are several things. One thing is, again, to look at potential patient subgroups that may benefit from the plug based device from the beginning. So probably it's not something that we should be using as a default strategy based on the results of this trial. But there could be certain subgroups we need maybe to dig a little bit more into the details or subgroups, if you wish to say so. Look a little bit more granularly at some patient groups that could benefit. But as mentioned, I think that the bailout indication is a very interesting one and needs to be looked at. Dr. Mohamed Abdel-Wahab: Not only in the TAVR setting, but also in the setting of other procedures. Such as for example, the use of mechanical circulatory assist device or ECMOs, where it may be difficult to apply these sutures post hoc. So the sutures that we apply during a TAVR procedure and what we use in this trial, this is the so-called preclosure technique. So you apply the sutures after gaining access. Then you insert your large-bore sheaths through the procedure. And then the sutures are already there and you can close the access site, usually without problems. Which is difficult, if you obtain access, for example, with an ECMO or an Impella. And then after a couple of days, you need to close it. So the sutures are not yet in place. In this particular scenario, it may be beneficial to use a plug afterwards. Or as a bailout device as previously Mentioned. Dr. Greg Hundley: Very nice well listeners. We want to thank Dr. Mohamed Abdel Wahab from Leipzig Germany for bringing us this study indicating that among patients treated with transfemoral TAVR, this pure plug based vascular closure technique using the MANTA VCD was associated with a higher rate of access site or access related vascular complications. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American heart association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American heart association. For more, please visit AHA journals dot org.

In the second part of Parallax's review of 2021, Dr Sukh Nijjer, Interventional Cardiologist from Imperial College London, and Dr Ankur Kalra discuss key advances in the field of heart failure and cardiac surgery. SGLT2 inhibitors are proving to be the blockbuster drug of this decade: Sukh summarises and compares the learnings from DAPA-HF, Emperor-Reduced, and Emperor-Preserved. Next, Sukh highlights the data from SOLOIST-WHF that showed sotagliflozin to have beneficial effects on CV outcomes among patients with type 2 diabetes and HF. Additionally, they discuss how findings on finerenone (FIGARO-DKD) will shape the field. Sukh talks about the semaglutide and the STEP studies, an injectable medication that further expends cardiologist knowledge beyond their speciality. Ankur and Sukh reflect on how the advancement of this field shaped their own practices. 2021 was a busy year for cardiac surgery trials: Sukh and Ankur review the most pertinent data from the AVATAR randomised study presented at AHA 2021. Sukh interprets the outcomes and asks Ankur about his clinical experiences. Finally, they review the investigator led LAAOS III study that showed patients with atrial fibrillation undergoing cardiac surgery, left atrial appendage occlusion was superior to no occlusion. What were the top practice informing heart failure trials of 2021? What does the latest data say on current cardiac surgery practices? How will these findings inform patient care? Questions and comments can be sent to “podcast@radciffe-group.com” and may be answered by Ankur in the next episode. Guest @SukhNijjer, hosted by @AnkurKalraMD. Produced by @RadcliffeCARDIO. Brought to you by Edwards: www.edwardstavr.com

Although guideline-directed medical therapy substantially improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), treatments that clearly improve outcomes in those with HF and an EF >40% remain elusive. Unfortunately, the incidence and prevalence of HF are expected to substantially increase in the coming decades.  More evidence and effective treatments for those with HF with preserved ejection fraction are clearly needed.  Enter the EMPEROR-Preserved trial. Guest Authors:  Gabrielle Givens, PharmD, BCPS and Robert Parker, PharmD Music by Good Talk

Can SGLT2 inhibitor Empagliflozin impact on true normal LVEF and heart failure?

On Health Suites, Claressa Monteiro speaks to Associate Professor David Sim from National Heart Centre Singapore to learn more about a chronic heart condition known as heart failure with preserved ejection fraction (HFpEF) and the results of the ground-breaking recent EMPEROR-Preserved clinical trial.See omnystudio.com/listener for privacy information.

On this episode, we are joined by Dr. Spencer Carter, MD and Dr. Kyle Fischer, PharmD, to discuss preserved ejection fraction heart failure. Dr. Carter is a cardiologist finishing his fellowship that is focused on heart failure and cardiac transplant.  Dr. Fischer is currently a PGY1 general clinical pharmacy resident. We begin by discussing some background information including pathophysiology and the clinical differences of HFpEF compared to HFrEF. We then review the medications often utilized in HFpEF. We finish with a deep dive into the new data surrounding sacubitril/valsartan in chronic heart failure (PARAGON HF) and the SGLT-2 inhibitors (EMPEROR-Preserved, DELIVER).  Follow Dr. Carter on Twitter: @spencercarter55 Follow Dr. Fischer on Twitter and Instagram: @Kfischer_10 and @kgfischerx Thanks for listening! If you want to support the podcast, check out our Patreon account. Subscribers will have access to all previous and new pharmacotherapy lectures as well as downloadable Power Point slides for each lecture. You can find our account at the website below:  www.patreon.com/corconsultrx If you have any questions for Cole or me, reach out to us on any of the following: Text - 415-943-6116 Mike - mcorvino@corconsultrx.com Cole - cswanson@corconsultrx.com Instagram and other social media platforms - @corconsultrx This podcast reviews current evidence-based medicine and pharmacy treatment options. This podcast is intended to be used for educational purposes only and is intended for healthcare professionals and students. This podcast is not for patients and not intended as advice or treatment.  

Drs. Deepak Bhatt, Payal Kohli, and Kim Eagle discuss highlights from the hottest clinical trials presented during Day 2 of the 2021 AHA Annual Scientific Session, including trials EMPULSE (0:28), EMPEROR-Preserved (2:21), CHIEF-HF (4:05), and PALACS (7:43).     Subscribe to Eagle's Eye View

Este fin de semana se celebra la AHA Scientific Sessions 2021 (13 al 15 de noviembre). Entre los resultados más esperados de la cita americana se cuenta el subestudio del EMPEROR- Preserved, que analiza el efecto de la empagliflozina en pacientes con insuficiencia cardiaca (IC) con fracción de eyección (FEVI) preservada ≥50%. David González Calle, Domingo Marzal y Alberto Esteban apuntan las claves más importantes antes de conocer los siguientes resultados. https://secardiologia.es/publicaciones/podcast/13076-emperor-preserved-punto-de-partida-con-empagliflozina-en-insuficiencia-cardiaca-preservada

#EMPEROR PRESERVED trial was recently published in #NEJM in 2021. It was also presented at #ESC2021. Heart Failure with Preserved Ejection Fraction (#HFpEF) is responsible of more than half of the cases of heart failure. It is a difficult to diagnose and difficult to treat condition. #Emplagliflozin and #dapagloflozin are 2 #SGLT2inhibitors have been found to be useful drugs in the management of #heart failure with reduced ejection fraction. The EMPEROR REDUCED and DAPA-HF trials have proven the efficacy of both these drugs in #heartfailure with reduced ejection (HFrEF). The #EMPEROR PRESERVED trial tested that whether #emplagliflozin can be useful in the management of Heart Failure with Preserved Ejection Fraction (#HFpEF).

Dr. Alex Goncharenko and CardioScripts co-host, Dr. Elisabeth Wang, discuss the EMPEROR-Preserved Trial. 

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

Dans cette 43e baladodiffusion, les Dr Charles Dussault et Luc Lanthier de l'efficacité de l'empagliflozine (Jardiance®), un inhibiteur des SGLT2, chez les sujets avec insuffisance cardiaque à fraction d'éjection préservée avec l'étude EMPEROR-Preserved, en plus de réviser la littérature médicale de juin, juillet et aout 2021.   Quiz clinique (3 min 41), étude principale (4 … Continuer la lecture de « BC 043 – Efficacité de l'empagliflozine chez les sujets avec insuffisance cardiaque à fraction d'éjection préservée (étude EMPEROR-Preserved) »

CardioNerds (Amit Goyal, Daniel Ambinder) and Dr. Mark Belkin, (CardioNerds Correspondent) and Dr. Shirlene Obuobi (CardioNerds Ambassador) from University of Chicago are honored to bring to you the Dr. Milton Packer perspective on the evolution of the neurohormonal hypothesis as part of The CardioNerds Heart Success Series. In part 4, Dr. Packer shares his perspective on the revolutionary SGLT2 inhibors. We discuss the mechanisms of action and the data regarding their role in the care of heart failure patients. This episode is particularly historic in that Dr. Packer shares his thoughts about the EMPEROR-PRESERVED trial well before the data was available. Also see Dr. Mark Belkin's DocWire News article EMPEROR's New Groove? Empagliflozin Provides Long-Awaited Treatment for HFpEF where Dr. Packer is quoted as saying “we are pleased to have the first trial in patients with HFpEF that shows an unequivocally positive and clinically important result. We are looking forward to many secondary papers that will provide detailed information about what we have found, and what it means for patients.” Check out the CardioNerds Heart Failure Success Series Page for more heart success episodes and content! This is a non CME episode. Disclosures: Milton Packer reports receiving consulting fees from Abbvie, Actavis, Amgen, Amarin, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Casana, CSL Behring, Cytokinetics, Johnson & Johnson Health Care Systems Inc., Eli Lilly and Company, Moderna, Novartis, ParatusRx, Pfizer, Relypsa, Salamandra, Synthetic Biologics, Teva Pharmaceuticals USA Inc. and Theravance Biopharma Inc. CardioNerds Heart Failure Success Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! This CardioNerds Heart Failure Success Series was created in memory of Dr. David Taylor. We thank our partners at the Heart Failure Society of America which is a multidisciplinary organization working to improve and expand heart failure care through collaboration, education, research, innovation, and advocacy. Its members include physicians, scientists, nurses, nurse practitioners, and pharmacists. Learn more at hfsa.org.

In this interview, Jeroen Bax, PhD, MD, FACC; Stefan Anker, MD, PhD; and Sherry-Ann Brown, MD, PhD, FACC, discuss the ESC Congress 2021 late breaker EMPEROR-Preserved, which evaluates the effect of empagliflozin for risk of cardiovascular death and hospitalisation for patients with heart failure and a preserved fraction with and without diabetes. Like what you hear? Get 20 episodes a month with CME/MOC credit at www.acc.org/ACCEL.

#597Discussão Emperor-Preserved Com Jefferson Viera e Fernando Figuinha! by Cardiopapers

Será que encontramos “A” droga para o tratamento da IcFep?Fala galera! Nesse episódio Pâmela Valelongo conversa com Carlos Aurélio, especialista em Insuficiência Cardíaca e Transplante Cardíaco pelo Instituto do Coração (InCor), sobre o polêmico trabalho apresentado no ESC 2021 - EMPEROR-PRESERVED TRIAL.Além do aspecto técnico do trabalho e respondendo à pergunta da nossa tag o time do Clube conversa sobre os aspectos clínicos da emblemática Insufiência Cardíaca com Fração de Ejeção Preservada. Convidado: Carlos Aurélio S. Aragão - Cardiologista pelo Instituto Dante Pazzanese de Cardiologia (IDPC), mestre pela USP/IDPC e especialista em Insuficiência Cardíaca e Transplante Cardíaco pelo Incor - HCFMUSP.Host: Dra. Pâmela O. ValelongoMédica pela Faculdade de Medicina do ABC. Residência médica em Clínica Médica (FMABC). Residência médica em Cardiologia Clínica pelo Instituto Dante Pazzanese de Cardiologia (IDPC). Ecocardiografista pelo Hospital Israelita Albert Einstein e médica do setor de Ecocardiografia do HIAE. Título de Cardiologia pela SBC e de Ecocardiografia pelo DIC. Plantonista da Unidade Coronariana e de Cuidados Pós-Operatórios de Cirurgia Cardíaca do IDPC.  Professora da Disciplina de Emergência da Faculdade de Medicina do ABC.A emergência é desafiadora, exige essas habilidades em um pacote só, e o nosso paciente, diversas vezes, não tem tempo, ele precisa de todos esse anos de conhecimento agora. O Clube da Cardio convida você a continuar se preparando SEMPRE para esse momento. “Como?” Com o SAFER, o método de ensino de emergências cardiovasculares do Clube da Cardio. Transforme seu conhecimento e sua prática com o SAFER e seja referência. Seja excelente! Torne-se EXCELENTE AGORA

Join us this week for another congress highlights episode covering the recent European Society of Cardiology congress, held virtually from 27-30 August 2021. Listen for commentary on the key highlights, including: - Professor Subodh Verma on EMPEROR-Preserved, EMPEROR-Pooled, and a post hoc analysis of SUSTAIN 6 and PIONEER 6 - Professor Darren McGuire on FIGARO-DKD, and new guidelines for heart failure and cardiovascular disease prevention Disclosures: Prof. Darren McGuire declares the following: Clinical trial leadership: AstraZeneca, Boehringer Ingelheim, Eisai Esperion, GlaxoSmithKline, Janssen, Lexicon, Merck & Co. Inc, Novo Nordisk, Sanofi, CSL Behring, Lilly Consultancy: Affimune, Applied Therapeautics, AstraZeneca, Boehringer Ingelheim, Lilly, Merck & Co. Inc, Pfizer Inc, Novo Nordisk, Metavant, Sanofi, Bayer Prof. Subodh Verma declares the following: Research Grants: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk Speaker Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Sanofi, Sun Pharma Consultancy: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk All conflicts of interest have been mitigated prior to this activity. Funding statement: This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education. References Packer M, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMoa2107038. Online ahead of print. [EMPEROR-Preserved] Packer M, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. [EMPEROR-Reduced] Packer M, et al. Empagliflozin and Major Renal Outcomes in Heart Failure. N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411. Online ahead of print. [EMPEROR-Pooled] Verma S, et al. Neutrophil-to-lymphocyte ratio predicts cardiovascular events in patients with type 2 diabetes: post hoc analysis of SUSTAIN 6 and PIONEER 6. Eur Heart J 2021. In press Pitt B, et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med. 2021 Aug 28. doi: 10.1056/NEJMoa2110956. Epub ahead of print. [FIGARO-DKD] Bakris GL, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. [FIDELIO-DKD] FIDELITY analysis: Presented by Dr. Gerasimos Filippatos at the European Society of Cardiology Virtual Congress, August 28, 2021. McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Aug 27:ehab368. doi: 10.1093/eurheartj/ehab368. Epub ahead of print.

An interview with lead investigator on full results from EMPEROR-Preserved Trial, which affirm that empagliflozin lowers the risk of CVD for heart failure in patients with HFpEF.Welcome to this episode of Physician's Weekly Podcast. My name is Dr Rachel Giles, from Medicom Medical Publishers, in collaboration with Physician's Weekly.  This week I am recording this episode in the Italian alps, while attending the European Association of Urology Guidelines Panel meeting for Renal cell carcinoma, but we have 2 great in-depth  interviews for you this week.  Later in this episode, Physician's Weekly's Editorial Director Chris Cole interviews Dr. J. Stacey Klutts, a medical microbiologist at Rush University, about his op-ed in the Tampa Bay Times comparing the Delta variant of SARS-CoV-2 to Gorilla Glue, which went viral. And yes, the pun was intended. Dr Klutts also tells us about exactly how the vaccine was developed and how the Delta variant is detected in patients. Did you know there are currently 13 subtypes of the Delta variant? But first, we speak with the presenter at the European Society of Cardiology Annual Congress HOTLINE plenary talk, prof. Stefan Anker at the Charité Hospital in Berlin, Germany, about the full results of the EMPEROR-Preserved trial, which affirm that empagliflozin lowers the risk of cardiovascular death/hospitalization for heart failure in patients with heart failure and preserved ejection fraction (HFpEF), leading one expert to say this is “a big day for patients living with HFpEF, a big day for heart failure clinicians.”The primary endpoint—a composite of CV death and hospitalization for heart failure—was reduced by a relative 21% in patients treated with the sodium-glucose cotransporter 2 (SGLT2) inhibitor emagliflozin.Published simultaneously online in the New England Journal of Medicine, these results represent the first trial to show unequivocal benefit of any drug on major heart failure outcomes in patients with heart failure and a preserved ejection fraction. Anker SD, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Aug 27.  Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

In this week's episode Dr Ankur Kalra's guest is Dr. Purvi Parwani, Director of Women's Cardiovascular Disease Clinic and Assistant Professor at Loma Linda University Medical Center. In this special ESC 2021 edition of Parallax, Ankur asks Purvi to review the highlights of the congress. Purvi summarises the design and findings of the trials and their importance in the treatment of patients. Ankur and Purvi discuss how the novel data presented at ESC will inform their practice. Trials covered in detail include • SSaSS: Effect of Salt Substitution on Cardiovascular Events and Death, • STEP: Intensive vs. standard blood pressure control among older hypertensive patients • EMPEROR-Preserved and Pooled: Effect of empagliflozin on cardiovascular death and heart failure hospitalisations in patients with heart failure with a preserved ejection fraction, with and without diabetes, • LOOP: Screening for AF with an implantable loop recorder to prevent stroke compared with results of the STROKESTOP trial, • IAMI: Influenza Vaccination after Myocardial Infarction randomised trial. What are the take-home messages of ESC 21? How can we utilise the findings in our practice? What are the questions that need further investigation? Questions and comments can be sent to “podcast@radcliffe-group.com” and may be answered by Ankur in the next episode. Guest @purviparwani, hosted by @AnkurKalraMD. Produced by @RadcliffeCARDIO. Brought to you by Edwards: www.edwardstavr.com

EMPEROR-Preserved, the LOOP study, ablate-and-pace for AF, and salt substitute and stroke: John Mandrola, MD provides a first of two ESC reviews. To read a partial transcript or to comment, visit: https://www.medscape.com/twic 1 - HFpEF - EMPEROR-Preserved: Empagliflozin Scores HFpEF Breakthrough https://www.medscape.com/viewarticle/957405 - Empagliflozin in Heart Failure with a Preserved Ejection Fraction https://www.nejm.org/doi/full/10.1056/NEJMoa2107038 - Empagliflozin and Major Renal Outcomes in Heart Failure https://www.nejm.org/doi/full/10.1056/NEJMc2112411 - Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure https://www.nejm.org/doi/full/10.1056/NEJMoa2022190 2 - AF Screening - LOOP Trial Undercuts Value of Long-term Continuous ECG Screening for Atrial Fibrillation https://www.medscape.com/viewarticle/957473 - Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01698-6/fulltext - Subclinical Atrial Fibrillation and the Risk of Stroke https://www.nejm.org/doi/full/10.1056/nejmoa1105575 3 - Ablate and Pace for AF and HF - APAF-CRT: 'Ablate and Pace' Cuts Mortality in Narrow-QRS HF, Permanent AF https://www.medscape.com/viewarticle/957467 - A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS https://academic.oup.com/eurheartj/article/39/45/3999/5078460 - AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial https://doi.org/10.1093/eurheartj/ehab569 4 - Salt Substitute and Stroke - Salt Substitute Shows Clear Reduction in Stroke, CV Events, and Death https://www.medscape.com/viewarticle/957472 - Effect of Salt Substitution on Cardiovascular Events and Death https://www.nejm.org/doi/full/10.1056/NEJMoa2105675 Features: - Incremental, Not Monumental, Win for Empagliflozin in Heart Failure With Preserved Ejection Fraction https://www.medscape.com/viewarticle/957465 - Empagliflozin in HFpEF: Putting EMPEROR-Preserved in Context https://www.medscape.com/viewarticle/957388 - Lessons on AF Screening From the LOOP Study https://www.medscape.com/viewarticle/957512 - Ablate-and-Pace Delivers a Huge Win for Those Sick With AF https://www.medscape.com/viewarticle/958033 - Will the Positive Findings From the SSaSS Trial on Salt Substitution Silence the Salt Skeptics? https://www.medscape.com/viewarticle/957510 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In this special episode of Eagle's Eye View, Dr. Deepak Bhatt, Dr. Gabriel Steg, and Dr. Carolyn Lam discuss highlights from Day 1 of ESC Congress 2021, including EMPEROR-Preserved, EMPEROR-Pooled, GUIDE-HF, and the ESC guidelines for the diagnosis and treatment of acute and chronic heart failure.

COVID-19, NEJM vaccine safety paper, full-dose anticoagulation in COVID-19, AF and Exercise, and early results on EMPEROR-Preserved are the studies John Mandrola, MD, discusses in this week's podcast. https://www.medscape.com/twic 1 - COVID-19 - Heart Inflammation More Common After COVID Than After Vaccination https://www.medscape.com/viewarticle/957343 - Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting https://www.nejm.org/doi/full/10.1056/NEJMoa2110475 2 - Full dose AC in COVID-19 - Heparin's COVID-19 Benefit Greatest in Moderately Ill Patients https://www.medscape.com/viewarticle/956630 - Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19 https://www.nejm.org/doi/full/10.1056/NEJMoa2105911 - Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19 https://www.nejm.org/doi/full/10.1056/NEJMoa2103417 3 - AF and Exercise - Aerobic Exercise Can Reduce AF Frequency, Severity: ACTIVE-AF https://www.medscape.com/viewarticle/957322 4 - EMPEROR AF - EMPEROR-Preserved: Empagliflozin Scores HFpEF Breakthrough https://www.medscape.com/viewarticle/957405 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In this week's View, guest host Deepak Bhatt, MD, MPH, FACC, offers a preview of some of the hottest trials at the European Society of Cardiology Congress 2021, taking place virtually August 27-30, including IAMI, EMPEROR-Preserved, EMPEROR-Pooled, MASTER DAPT, ENVISAGE-TAVI AF, FIGARO-DKD, FIDELITY, Colchicine in Patients Hospitalized with COVID-19, PREPARE-IT, The Michelle trial, GUIDE-HF, QUARTET, TWILIGHT-HBR, PRONOUNCE, and Amulet IDE.