HCPLive Cardiology Podcasts

In this episode of Don’t Miss a Beat, hosts Stephen Greene, MD, and Muthiah Vaduganathan, MD, MPH, sit down with Darren McGuire, MD, to explore the groundbreaking results of the SURPASS-CVOT trial. This cardiovascular outcome study is the first to directly compare two incretin-based therapies—tirzepatide, a dual GIP/GLP-1 receptor agonist, and dulaglutide, a GLP-1 receptor agonist—among patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD). Unlike the placebo-controlled GLP-1 programs of the past decade, SURPASS-CVOT represents a pivotal move toward active comparator trials in cardiometabolic medicine.

00:00:00 Intro
00:01:35 Behind the trial
00:04:35 What is imputed placebo?
00:08:32 The size and scope of SURPASS-CVOT
00:11:01 Results of SURPASS-CVOT
00:14:20 How to select comparators among obesity medicines
00:17:37 Future trials
00:18:56 Interpreting these new kinds of comparisons
00:20:50 Active comparators are the future
00:24:01 Closing

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