Don't Miss a Beat

This episode of Don't Miss a Beat centers on the evolving treatment landscape for transthyretin amyloid cardiomyopathy (ATTR-CM) with special guest Ahmad Masri, MD. Hosts Muthiah Vaduganathan, MD, MPH, a cardiologist and codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women's Hospital, and Steve Greene, MD, an advanced heart failure specialist at Duke University School of Medicine, are joined by Masri, who serves as the director of the HCM and Amyloid Program at Oregon Health & Science University, to discuss the rapid therapeutic advances in ATTR-CM and the emerging questions shaping real-world clinical practice. Masri reviews the progression from a previously untreatable disease to one now managed with three US Food and Drug Administration (FDA)-approved disease-modifying agents: tafamidis (VYNDAMAX), acoramidis (Attruby), and vutrisiran (AMVUTTRA). He highlights the tafamidis approval in 2019 as a landmark in the field, showing a substantial survival benefit in the ATTR-ACT trial, followed by similar results from acoramidis, which received approval in late 2024, in ATTRibute-CM. Vutrisiran, a TTR gene silencer approved by the FDA in March 2025, represents a mechanistically distinct approach validated in the HELIOS-B trial. Despite these advances, Masri notes that patients with late-stage disease derive limited symptomatic benefit and that residual risk remains high, even with treatment. The conversation explores whether stabilizers and silencers can or should be combined, with Masri urging caution, citing the absence of clinical data demonstrating additive benefit and warning against assumptions of harmony without clinical evidence. Masri indicated ongoing trials, such as CARDIO-TTRansform, may offer clarity on this issue. Without direct comparisons between therapies, treatment selection often hinges on patient preference, delivery method, pill burden, and payer coverage. In practice, clinicians rely on pharmacodynamic markers, like changes in TTR levels, to assess treatment effect and adjust therapy accordingly. Masri emphasizes that while ATTR-CM trials may not show improvements in quality-of-life scores, slowing disease progression remains a critical and meaningful endpoint in this severe, high-mortality condition. Looking ahead, the panel discusses the next wave of therapeutic innovation. Multiple trials are now testing agents that aim to clear amyloid from the myocardium, including NI006 (ALXN2220), PRX004, and AT-02. These immune-modulating treatments are designed for long-term use and may complement stabilizers or silencers in patients with established amyloid burden. The episode closes with a discussion on prevention. For patients with asymptomatic cardiac involvement, current therapies halt disease progression entirely in many cases. For those with pathogenic TTR variants but no overt disease, surveillance is the current standard. However, Masri introduces the ACT Early trial, which will test whether early treatment with acoramidis can prevent the onset of clinical disease in high-risk individuals, potentially reshaping the paradigm of ATTR-CM care. Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Key Episode Timestamps 00:00:00 Introduction and Guest Introduction 00:00:52 Current State of Amyloid Therapeutics 00:03:41 Introduction of New Stabilizers and Silencers 00:06:05 Combination Therapy and Clinical Data 00:10:36 Choosing Therapy for Patients 00:16:40 Disease Progression and Clinical Trials 00:20:28 Pipeline and Future Therapies 00:23:51 Preventative Therapy and Asymptomatic Patients 00:27:19 Conclusion and Future Directions

This episode of Don't Miss a Beat, recorded at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, explores the evolving landscape of heart failure with preserved ejection fraction (HFpEF) treatment, focusing on the implementation of combination therapies. Hosts Steve Greene, MD, and Muthiah Vaduganathan, MD, MPH, discuss the transition from a previously limited treatment landscape to a new era with multiple proven therapeutic options. To open the episode, Greene argues in favor of rapid-sequence implementation of HFpEF therapies, drawing parallels to the established 4-pillar guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). He highlights 3 key classes of medications—SGLT2 inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and incretin-based therapies—as the foundation of HFpEF treatment. He emphasizes the importance of early and aggressive therapy initiation to maximize clinical benefits and reduce the risk of delayed or missed treatment opportunities among this population. Vaduganathan acknowledges the strength of the data supporting combination therapy but suggests a more risk-based approach, considering the broad clinical variability among HFpEF patients. He advocates for prioritizing rapid implementation in high-risk patients, such as those recently hospitalized, while allowing a more measured approach for lower-risk individuals. The discussion also touches on the role of phenotyping in tailoring treatment decisions, with GLP-1 receptor agonists being particularly relevant for patients with obesity and ARNi potentially benefiting those with mildly reduced ejection fraction. Looking ahead, the hosts preview upcoming trials, including CONFIDENCE and CONFIRMATION, which will evaluate combination therapy strategies in chronic kidney disease and HFpEF populations. They also discuss the potential of fixed-dose combination therapies to simplify implementation and improve adherence. The episode closes with both experts agreeing on the need for a structured, evidence-based approach to HFpEF treatment while emphasizing the importance of translating trial data into real-world practice. Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Chapters 00:00-Intro 02:30-Argument for Rapid Sequencing 05:32-Argument Against Rapid Sequencing 10:00-Argument for Risk-Based Sequencing 14:25-Pillars of GDMT in HFpEF

In this on-site episode of Don't Miss a Beat from the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, hosts Muthiah Vaduganathan, MD, MPH, and Steve Greene, MD, break down a pair of trials from the meeting: STRIDE and SOUL. STRIDE Trial The STRIDE trial, funded by Novo Nordisk, was a double-blind, randomized, placebo-controlled study initiated in 2020 to evaluate the effects of semaglutide 1.0 mg (Ozempic) on walking distance in patients with type 2 diabetes (T2D) and peripheral artery disease (PAD). Conducted across 112 sites in 20 countries, the trial enrolled 792 patients, who were randomized 1:1 to receive semaglutide or placebo for 52 weeks. Participants assigned to semaglutide received an escalating dose regimen (0.25 mg to 1.0 mg). The primary endpoint, the ratio from baseline in maximum walking distance at 52 weeks, favored semaglutide (1.21 [interquartile range, 0.95–1.55] vs 1.08 [0.86–1.36]), with an estimated treatment ratio (ETR) of 1.13 (95% CI, 1.06–1.21; P = .0004). Secondary outcomes further supported semaglutide's benefit. At week 57, the improvement in walking distance was greater with semaglutide (ETR, 1.08; P = .038). Quality-of-life scores (VascuQoL-6) at week 52 were significantly higher in the semaglutide group (median difference, 1.00; P = .011). Pain-free walking distance also improved more with semaglutide than with placebo (ETR, 1.11; P = .0046). SOUL Trial The SOUL trial was a double-blind, placebo-controlled, event-driven study designed to assess the cardiovascular effects of oral semaglutide (Rybelsus) in patients with T2D and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). The trial enrolled 9650 patients aged ≥50 years and was conducted across 450 centers in 44 countries. Participants were randomized 1:1 to receive semaglutide or placebo, with a mean follow-up of 47.5 months. Primary outcome events occurred in 12.0% of participants receiving semaglutide (3.1 events per 100 person-years) compared with 13.8% in the placebo group (3.7 events per 100 person-years), resulting in a hazard ratio (HR) of 0.86 (95% CI, 0.77–0.96; P = .006). The primary driver of benefit was a 26% reduction in nonfatal myocardial infarction, with additional reductions in nonfatal stroke (12%) and cardiovascular death (7%). No significant improvements in kidney function were observed. Serious adverse events occurred slightly less frequently in the semaglutide group compared with placebo (47.9% vs 50.3%; P = .02). However, gastrointestinal adverse events, including nausea, diarrhea, constipation, and flatulence, were more common in the semaglutide group (5.0% vs 4.4%). Benefits were consistent across subgroups, including participants receiving sodium-glucose cotransporter-2 inhibitors. Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Chapters 00:00 - Intro 00:50 - STRIDE Background 02:50 - STRIDE Results 08:19 - SOUL Background 10:40 - SOUL Results

In this episode of Don't Miss a Beat, hosts Muthiah Vaduganathan, MD, MPH, and Steve Greene, MD, are joined by Taher Modarressi, MD, to explore the practicalities of implementing cardiometabolic therapies in clinical practice. Modarressi shares his experiences establishing a cardiometabolic clinic and offers invaluable advice on overcoming barriers like insurance coverage and cost issues. The discussion provides real-world strategies for integrating advanced treatments for conditions such as obesity, diabetes, and cardiovascular disease, while ensuring patient access to these therapies. Chapters Introduction - 00:00 Acquiring Expertise in Cardiometabolic Health - 02:29 Advice for Aspiring Cardiometabolic Health Specialists - 04:09 Practical Aspects of Running a Cardiometabolic Practice - 07:30 Navigating Insurance and Cost Barriers - 08:43 Practical Tips for Implementing Cardiometabolic Therapies - 20:21 Conclusion and Final Thoughts - 22:54

Live from ESC Congress 2024! In this edition of Don't Miss a Beat, Stephen Greene, MD, an advanced heart failure specialist at Duke University School of Medicine, discusses the prospect of finerenone in treatment algorithms for heart failure with Muthiah Vaduganathan, MD, MPH, codirector of the Center for Cardiometabolic Implementation Science of Brigham and Women's Hospital, based on data from the meeting, including FINEARTS-HF, FINE-HEART, and an analysis on MRA use in heart failure. Chapters 00:00 - Welcome and Introduction 01:18 - FINEARTS-HF Study Design and Patient Population 03:04 - Inclusion of Hospitalized Patients 04:43 - Primary and Secondary Endpoints 05:56 - Challenges in Achieving Statistical Significance 07:39 - Health Status Improvement and Additional Analyses 10:01 - Combination Therapy and Future Trials 12:20 - Hyperkalemia and Steroidal vs. Non-Steroidal MRAs 15:30 - Conclusion and Acknowledgments

Brendon Neuen, MBBS, PhD, joins hosts to discuss the landmark FLOW trial and its implications on the future of chronic kidney disease management as well as other compelling data surrounding semaglutide from the 61st European Renal Association Congress. Key Highlights: 00:00 - Intro 01:12 - ERA Recap  03:06 - FLOW Background 05:20 - FLOW Results 06:56 - FLOW Reaction (Neuen) 09:13 - Semaglutide Mortality Benefit 12:43 - Semaglutide 2.4 in CKD 17:30 - Implementation Science 22:30 - Management Approach

In this episode of Don't Miss a Beat, Javed Butler, MD, joins hosts Muthiah Vaduganthan, MD, MPH, and Steve Greene, MD, for a breakdown of the EMPACT-MI trial, including primary results, secondary findings, how data from DAPA-MI and EMPACT-MI complement each other, and what is next for the SGLT2 inhibitor class.  Key Highlights: 00:00 - Intro 01:57 - Trial Design and Results 07:00 - Inclusion Criteria and Patient Characteristics 10:53 - Primary Results of EMPACT-MI 14:34 - Subgroup Analyses 15:27 - Implications for Post-MI Patient Population  19:53 - Takehome Messages for Care 23:39 - Kidney Outcomes in Post-MI Patient Population

In this episode, hosts sit down between sessions at AHA 2023 to discuss the landmark SELECT trial, their interpretation of the data, and its implications for care moving forward. Later in the episode, hosts give an overview of the DAPA-MI trial. 

On the floor from HFSA 2023! Hosts Muthiah Vaduganathan, MD, MPH, and Steve Greene, MD, are joined by Marat Fudim, MD, MHS, of Duke, to discuss the REBALANCE-HF trial, which examined endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction

In this episode of Don't Miss a Beat, hosts offer a breakdown of 3 trials of note from the upcoming ESC Congress 2023 and provide context around the recent announcement of topline results from the SELECT trial.

In this episode of Don't Miss a Beat, hosts sit down at ESC HFA to discuss key takeaways from the ACC's expert clinical decision pathway and preview HFpEF data scheduled to be presented during the meeting.

Hosts are joined by Tor Biering-Sørenson, MD, MSc, MPH, PhD, to discuss the NUDGE FLU trial and how the lessons learned can inform implementation strategies for various other types of therapies.

Don't Miss a Beat hosts are joined by Alexandre Mebazaa, MD, PhD, lead investigator of the STRONG-HF trial, to discuss the inspiration for the trial, its design, and important takeaways for those looking to implement a similar strategy of rapid, in-hospital uptitration of GDMT in heart failure at their own practice. Video Version

Muthiah Vaduganathan, MD, MPH, of Brigham and Women's Hospital, and Stephen Greene, MD, of the Duke University School of Medicine, are bringing you insights from the floor at the American Heart Association 2022 Scientific Sessions in Chicago, Il. In the episode, which was recorded on day 2 of the 3-day meeting, our hosts offer listeners perspective on the EMPA-KIDNEY and the TRANSFORM-HF trial, the latter of which Greene served on as an investigator.

In this special edition episode of Don't Miss a Beat, which was filmed on-site at the HFSA 2022 annual scientific meeting, hosts Muthiah Vaduganathan, MD, MPH, codirector of Center for Cardiometabolic Implementation Science at Brigham and Women's Hospital, and Stephen Greene, MD, assistant professor of medicine at Duke University School of Medicine, take the audience on a deep dive into implementation science at the meeting, the potential for a polypill in heart failure, and other highlights from HFSA 2022.

In this episode of Don't Miss a Beat, hosts Stephen Greene, MD, and Muthiah Vaduganathan, MD, MPH, provide a recap of the European Society of Cardiology Congress 2022. This recap begins with a discussion on the results of the phase 3 DELIVER trial, in which Vaduganathan served as an investigator, the ADVOR trial, and REVIVED. 

In the latest edition of Don't Miss a Beat, Drs. Greene and Vaduganathan are joined by special guest Brendon Neuen, MBBS, MSc, of the George Institute of Global Health. A trialist currently contributing to the FIND-CKD trial, Neuen takes Vaduganathan and Greene on a deep dive into the use of eGFR slope as an end point in clinical trials and as a tool in clinical practice. 

A first-in-class allosteric and reversible inhibitor selective for cardiac myosin approved based on the results of the EXPLORER-HCM trial, mavacamten was approved for the treatment of adults with symptomatic NYHA class 2-3 obstructive hypertrophic cardiomyopathy after their phase 3 data indicated use was with improved exercise capacity, LVOT obstruction, NYHA functional class, and health status patients with oHCM.  In the latest edition of Don't Miss a Beat, hosts Stephen Greene, MD, and Muthiah Vaduganathan, MD, MPH, are joined by special guest Anjali Owens, MD, of Penn Medicine. An assistant professor of medicine in the Division of Cardiology and medical director of the Center for Inherited Cardiac Disease at the Perelman School of Medicine, Owens is a leading researcher in oHCM with real-world clinical experience treating the disease. During the episode, Owens takes our hosts on a deep dive into the disease state from her perspective. 

In this episode of Don't Miss a Beat, hosts Drs. Greene and Vaduganathan break down the new ACC/AHA/HFSA heart failure guidelines debuted at ACC.22 and compare the recommendations against those made in the European Society of Cardiology's 2021 heart failure guidelines.

Headed to ACC.22 this weekend or following along virtually? Get the weekend started with our special ACC.22 preview edition of Don't Miss a Beat. Hear from co-hosts Drs. Vaduganathan and Greene on their top picks from the late-breaking sessions at the upcoming American College of Cardiology meeting and offer their thoughts on the recent EMPA-KIDNEY announcement. 

Dr. Eugene Braunwald joins Don't Miss a Beat hosts Dr. Greene and Dr. Vaduganathan to provide perspective on founding the TIMI study group, how trials have evolved, and advice he would give to young professionals interested in becoming trialists.

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

Based on a study she presented at ACC.21, Laxmi Mehta, MD, discusses COVID-19 and burnout among cardiology professionals with Practical Cardiology senior editor Patrick Campbell.  This conversation has been edited for time and clarity.

In this episode, Dr. Stephen Greene, of the Duke Clinical Research Institute, breaks down a recent study he led comparing the sensitivity of NYHA class versus patient-reported outcomes for capturing changes in disease state among patients with HFrEF.

In this special National Wear Red Day edition of Inside Cardiology, we speak with Jennifer Majersik, MD, about a special edition of the Stroke journal highlighting disparities in stroke care for women. 

Prof. Kausik Ray discusses inclisiran data from the ORION program presented at ESC Congress 2020 and examines whether clinicians should feel comfortable prescribing the agents based on clinical trial data.

This episode features Robert L. Page II, PharmD, a professor of clinical pharmacy at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences and co-author of a recent scientific statement from the American Heart Association (AHA) describing the current state of understanding regarding marijuana and its effect on cardiovascular health.  

For this episode, you will be hearing from Dr. Deepak Bhatt. Dr. Bhatt is the lead author of a recent article published in the Journal of the American Heart Association examining the impact of the ongoing COVID-19 pandemic.  A leading trialist, Dr. Bhatt offers perspective on data and from personal experience on how the pandemic has, is, and will continue to effect clinical trials, with the ripple causing disruptions in treatment pipelines and the treatment of patients. 

Hear fromDr. Hyung Chun, associate professor of medicine and pathology at Yale School of Medicine and director of Translational Research in the Yale Pulmonary Vascular Disease Program.  Dr. Chun recently led a study examining one of the most pressing issues in the treatment of COVID-19 patients: Blood clots. In the interview, we discuss the potential mechanism behind blood clots in COVID-19 patients as well as the overall impact this has on treatment course.