Ahmad Masri, MD, MS, is the director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University. 

Ahmad Masri, MD, MS

ATTRibute-CM: Acoramidis Reduces Cardiovascular Mortality and Hospitalization with Ahmad Masri, MD

Acoramidis significantly reduced cumulative cardiovascular mortality (CVM) and recurrent cardiovascular-related hospitalization (CVH) over 30 months in patients with 

transthyretin amyloid cardiomyopathy (ATTR-CM)

, based on an exploratory analysis of ATTRibute-CM.

Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025

 by Ahmad Masri, MD, director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, this analysis also revealed surprisingly rapid changes in both endpoints, reaching significance after the first month.

 sat down with Masri to discuss the exploratory analysis, its findings, and the implications for treating the underserved ATTR-CM patient population.

“One important point that emerged – and these are all exploratory analyses – is the timing when you start to see those events accruing in the acoramidis arm versus placebo,” Masri told 

. “We usually think of this disease as needing some time to confer some benefit to patients on the drug. However, what we’ve seen here is that once you start acoramidis, within a few months, even as early as the first month, you start to accrue fewer events than placebo.”

ATTRibute-CM, a phase 3, double-blind clinical trial, saw investigators randomly assign patients with ATTR-CM in a 2:1 ratio to either acoramidis 800 mg twice daily or matching placebo. The trial lasted 30 months, with a 4-step primary hierarchical analysis endpoint consisting of all-cause mortality, CVH, change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and change from baseline in 6-minute walk distance.

Patients were eligible if they had an established diagnosis of ATTR-CM and clinical 

 with ≥1 previous hospitalization for heart failure, volume overload, or heart failure resulting in diuretic treatment. Patients also had to have a 6-minute walk distance of ≥150 m on ≥2 tests performed between 24 hours and 3 weeks apart, a level of NT-proBNP of ≥300 pg/mL, and a left ventricular wall thickness of ≥12 mm on a previous imaging study.

Ultimately, 632 patients underwent randomization, with 421 assigned to acoramidis and 211 to placebo. Mean age was 77 +/- 6.6 years, 90.2% of participants were men, and 90.3% of patients had wild-type TTR. Most patients also had either New York Heart Association class II (72%) or III (17.2%) symptoms.

Investigators found that acoramidis outperformed placebo by a win rate of 1.8 (95% CI, 1.4-2.2) based on the 4-step hierarchical analysis. CVM and CVH contributed over half of the wins and losses to the win ratio, while NT-proBNP pairwise comparisons showed the highest ratio of wins to losses.

Masri and colleagues’ exploratory analysis found that CVM and CV-related hospitalization occurred in 33.3% (136) of participants in the acoramidis arm versus 98 (48.5%) in the placebo group. Acoramidis also substantially reduced the risk of cumulative CVM or recurrent CVH compared to placebo (hazard ratio [HR], 0.51; 95% CI, 0.43-0.62; 

 <.0001). Masri and colleagues observed treatment effects beginning at Day 16, which continued to improve through month 30. Difference in mean cumulative events reached 53 per 100 participants (95% CI, 29-79; 

“I think this is the most important takeaway of what we have presented,” Masri said of the early cumulative event change. “Usually, there is no urgency on average for getting a diagnosis of transthyretin amyloidosis. People in general think of it as more of a chronic disease, and that 6 months’ delay is not going to make a huge difference for initiating therapy. I think this analysis actually challenges that.”

Editor's Note: Masri reports disclosures with Pfizer, Attralus, Eidos, Ionis, Cytokinetics, BioMarin, and others.

Masri A, Judge D, Ruberg F, et al. Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis from ATTRibute-CM. Presented at the Heart Failure Society of America Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

Razvi Y, Judge DP, Martinez-Naharro A, et al. Effect of Acoramidis on Myocardial Structure and Function in Transthyretin Amyloid Cardiomyopathy: Insights From the ATTRibute-CM Cardiac Magnetic Resonance (CMR) Substudy. Circ Heart Fail. 2024;17(12):e012135. 

Videos

An exploratory analysis of the ATTRibute-CM trial spotlighted acoramidis’s superior efficacy in lowering CVD-related risks versus placebo.

ATTRibute-CM: Acoramidis Reduces Cardiovascular Mortality and Hospitalization, With Ahmad Masri, MD

Expert Perspectives: Top News in Heart Failure from HFSA Annual Scientific Meeting 2025

The Heart Failure Society of America Annual Scientific Meeting 2025,

 incorporating over 50 scientific sessions and hundreds of abstract presentations from leading researchers, saw a slew of exciting trial updates and insights from some of the best minds in cardiology.

During the conference, the editorial team at 

 sat down with several of these experts, collecting their thoughts on the most significant developments in 

’s approval of finerenone, the upcoming decision on aficamten, and the recent VICTOR, SUMMIT, and MAPLE- and ODYSSEY-HCM trials were highlighted.

The clinicians included in this summary are:

Ronald Witteles, MD, professor of cardiovascular medicine at Stanford University and co-director of the Stanford Amyloid Center and the Stanford Multidisciplinary Sarcoidosis Program

Barry Borlaug, MD, professor of cardiology at Mayo Clinic

Justin Ezekowitz, MD, professor of medicine at University of Alberta and cardiologist at the University of Alberta Hospital and Mazankowski Alberta Heart Institute

Ahmad Masri, MD, director of the Oregon Health & Science University Hypertrophic Cardiomyopathy Center and Knight Cardiovascular Institute Cardiac Amyloidosis Program

Javed Butler, MD, MPH, professor and chair of the department of medicine and Patrick H. Lehan Chair of Cardiovascular Research at the University of Mississippi Medical Center

Benjamin Hansen, MD, postdoctoral research fellow at the Department of Intensive Care at Copenhagen University Hospital - Rigshospitalet

Henri Roukoz, MD, associate professor of medicine, cardiovascular division, and section chief of electrophysiology, director of complex and congenital ablation at the University of Minnesota

Petra Mamic, MD, instructor of cardiovascular medicine at Stanford University Medicine

Stephen Greene, MD, cardiovascular disease fellow at Duke University Medical Center

Viet Le, DMSc, PA-C, associate professor of research at Intermountain Health

Milind Desai, MD, director of the center for hypertrophic cardiomyopathy and vice chair of education of the Heart Vascular Thoracic Institute at the Cleveland Clinic

I may be biased, but to me, ATTR amyloidosis is still the biggest story in heart failure. You’re talking about a disease that, a decade ago, most people hadn’t heard of. Maybe there would be one session every few years at the meetings, which was sparsely attended, but there was little interest, it was wildly underdiagnosed, and there were no therapies for it. Now we’re in an era where we realize this disease is not that rare, that if you look at the right patient populations, particularly older men with heart failure, thick hearts, and atrial fibrillation, you will pick up a lot of this. And it’s easy to diagnose; most patients can be diagnosed non-invasively. And now we have 3 FDA-approved treatments for ATTR 

, we have multiple other treatments approved for ATTR polyneuropathy, and multiple other agents in phase 3 trials. It is a super dynamic area, and it’s one that I think is particularly gratifying because it went from a fundamental understanding of the pathophysiology of the disease that led directly to the therapies. In the world of ATTR amyloidosis, the therapies have been designed to do exactly what they do, and in a rare thing in medicine, they pretty much all work.


The SUMMIT trial is probably the biggest news. It wasn’t a lot of events, it wasn’t a big trial, but it was a statistically significant improvement with a drug that was developed for weight loss, and it’s really ushering in a new era. HFpEF is a disease that’s driven by adiposity and everything that comes with that, such as visceral adiposity, pro-inflammatory and profibrotic effects, and many others. It’s opening the door for a lot of different drugs and potentially even devices that can target this cardiometabolic axis.


 2025 has been a pretty banner year for some trials: the VICTOR trial, being the largest recent clinical trial, has been quite important; the completion of DAPA-ACT, being the last real SGLT2 trial, showing that, when in combination with the meta-analysis, there is an advantage to starting those drugs early on. I think seeing the secondary analysis from some trials, such as the SUMMIT trial and the MRI of adipose tissue, is really interesting because it shows there’s a change in the structure and function of the myocardium that really is interesting. We’ve had so many great smaller trials as well, though, so it’s hard to pick one. There’s so much good stuff going on.


 Focusing on hypertrophic cardiomyopathy specifically, I think the 2 recent trials that were published, MAPLE-HCM and ODYSSEY-HCM, are really important findings in this space. MAPLE-HCM showed that beta blockers, as represented by metoprolol, are detrimental to patients with obstructive hypertrophic cardiomyopathy. This challenges a practice of 60-plus years of using beta blockers as first-line therapy. You don’t see reversals in approach frequently, because you don’t see these first-time agents challenged frequently. ODYSSEY-HCM, on the other hand, while it wasn’t a positive trial, showed that you have to be careful in your evaluation of patients with hypertrophic cardiomyopathy. You have to be mindful that you can’t just use 1 trial in a specific population and expand the drug treatment to other populations without investigation. This is a drug that was successful in obstructive hypertrophic cardiomyopathy with some safety issues that were managed and dealt with that wasn’t successful in non-obstructive HCM, and the safety signal was much worse. The trial wasn’t positive, but it reminded us that we have to be really careful when applying an extension of the current use of drugs, and we have to strive to stay with evidence-based medicine as much as we can with our newer therapies.


 The biggest story so far is that the field continues to move forward. We had a lot of positive data that has come out of either smaller primary studies or secondary analyses of larger studies with the obesity trials. That is becoming the solid, certified data that evidence generation needs, which has led to a lot of ongoing studies. The other is smaller studies that have shown that aldosterone modulation in ways other than MRA, like aldosterone synthase inhibitors, may be very helpful. And third, there’s a lot of compelling data that has come out about prevention of heart failure in high-risk populations.


 If I were to call out just one big news, it’s the role of vericiguat. I think that’s something of a hot topic right now, so I guess that’s something we really need to look further into to see its role in this population of well-treated outpatients with difficult-to-treat or advanced heart failure.


I would say how widely the SGLT2 inhibitors are being used and the increase in the indication to cover HFpEF patients. The second part is rhythm control and afib in heart failure, which is still a dominant thing from the EP standpoint.


This past year, we’ve had incredible studies published about gut microbiome in the context of heart failure, which have really put certain gut microbial metabolites on the map for their roles in heart failure. I think where we have come from 2024 to 2025 has really informed my research in a huge way.


There’s some things to pick from, but one thing that’s very notable is the FDA approval of finerenone as an evidence-based treatment for HFpEF, not just diabetic kidney disease anymore. The FINEARTS trial was presented last year, but FDA approval now really solidifies this in my mind that we have another pillar for HFpEF. SGLT2 inhibitors were the first definitively proven therapy for patients with HFpEF, and despite making up more than half of our heart failure population, we had no evidence-based therapy, no disease-modifying therapy to offer them. Now we have another therapy that I would argue strongly is definitively proven for improving hard clinical outcomes. I think we need to embrace that.

I’d also like to encourage people to think that it’s not an either-or when we talk about the “pillars of therapy,” and I don’t want to make the same mistakes that we made in HFrEF. We have multiple evidence-based therapies; you need to be willing to initiate them simultaneously and not get distracted with this specific medication sequence. People need both for prognosis comparable to cancer, not either-or.


GLP-1s are one of these unifying therapies across multiple diseases, and I think as we think back to 2025, we’re just having this confluence of heart failure from the diabetic space. Everyone is reporting clinical data trending towards benefit with GLP-1s. I think this is such a great jump-off point. So many different industry partners are looking into this, and before 2025, they were thinking about it. But now I think the community is much more aware. I look forward to seeing where those fit in the space of heart failure, but also in cardiovascular, kidney, and metabolic health.


I think the continued evolution of high-quality randomized controlled trial data in the context of cardiomyopathy, not just hypertrophic obstructive cardiomyopathy. Gene therapy is rapidly evolving, and you’re going to hear a lot about it. The other important thing is the utilization of novel artificial intelligence techniques to make early and precise diagnoses in these spaces. A rising tide lifts all boats, so they say; there’s a major tide that is lifting a lot of boats right now.

The quotes contained in this video summary were edited for clarity.

Editor's Note: Le reports disclosures with Pfizer, Novartis, Janssen, Idorsia, Amarin, and Lexicon. Greene reports disclosures with Amgen, Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Corcept, and others. Butler reports disclosures with Abbott Laboratories, Amgen, Bristol-Myers Squibb, Cytokinetics, Medtronic, Merck, and others. Masri reports disclosures with Pfizer, Ionis Pharmaceuticals, AstraZeneca, Cytokinetics, BioMarin, Akros, and others. Desai reports disclosures with Bristol-Myers Squibb, Medtronic, Cytokinetics, Edgewise, Viz-Al, and Tenaya Therapeutics. Borlaug reports disclosures with Amgen, Novo Nordisk, Eli Lilly, Edwards LifeSciences, Boehringer Ingelheim, AstraZeneca, and others. Witteles reports disclosures with Pfizer, Alnylam Pharmaceuticals, Bridge Bio, Janssen, AstraZeneca, and Alexian Pharmaceuticals. Roukoz, Hansen, Mamic, and Ezekowitz report no disclosures.

US FDA Approves KERENDIA (finerenone) to Treat Patients with Heart Failure with Left Ventricular Ejection Fraction ≥40% Following Priority Review. Bayer. July 14, 2025. Accessed October 3, 2025. 

https://www.bayer.com/en/us/news-stories/fda-approves-kerendia

Reddy YNV, Butler J, Anstrom KJ, et al. Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial. Eur J Heart Fail. 2025;27(2):209-218. 

Packer M, Zile MR, Kramer CM, et al. Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial. J Am Coll Cardiol. 2025;85(18):1721-1735. 

Hegde SM, Wang X, Garcia-Pavia P, et al. Effect of Aficamten Compared With Metoprolol on Echocardiographic Measures in Symptomatic Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM. J Am Coll Cardiol. Published online August 27, 2025. 

Desai MY, Olivotto I, Abraham T, et al. Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy: Insights From the ODYSSEY-HCM Trial. J Am Coll Cardiol. Published online August 25, 2025. 

This set of interviews collects perspectives from 11 leading clinicians in the heart failure field, cataloguing the biggest news from 2025.

A Look Into the Future of ATTR-CM Clinical Trials

Summary for Physicians: Designing Future Trials in ATTR-CM

 (transthyretin amyloid cardiomyopathy) should focus not only on evaluating the efficacy of 

, including amyloid depleters, but also on enhancing our understanding of the mechanisms driving 

 to current treatments. Key considerations for trial design include:

 Trials should incorporate biomarkers (eg, NT-proBNP, troponin, TTR, amyloid-related markers) to assess how therapies impact both amyloid burden and cardiac dysfunction. This will help define the relationship between amyloid deposition and heart failure progression.

 mutations) and advanced techniques such as 

 could help identify specific molecular mechanisms underlying disease progression, particularly in wild-type ATTR-CM and in nonresponders.

 with advanced imaging techniques could provide insights into amyloid infiltration, inflammation, and fibrosis, allowing for a deeper understanding of the pathological changes in the heart.

 Trials should stratify patients into distinct groups (eg, wild-type vs hereditary ATTR, responders vs nonresponders) to assess differential responses to therapies. This approach can identify factors that contribute to lack of response in certain patients and guide more personalized treatment strategies.

 Include long-term follow-up data to capture how treatments impact disease progression over time, particularly for patients with wild-type disease, who may have a slower progression.

 In addition to traditional clinical outcomes such as mortality or hospitalization, surrogate end points (eg, improvement in biomarkers, cardiac imaging findings, or exercise capacity) should be included to more quickly evaluate therapeutic effects.

 should be incorporated to assess the broader impact of therapy on daily functioning and patient well-being.

Trials should explicitly include patients who have shown little to no benefit from current therapies (eg, tafamidis, diflunisal) to better understand the reasons behind therapy resistance. This can help identify potential new therapeutic targets or biomarkers associated with nonresponsiveness.

 Investigating combination therapies, including amyloid depleters and other novel agents targeting different pathways involved in cardiac dysfunction (eg, inflammation, fibrosis), may provide insights into better treatment strategies for nonresponders.

 collection and collaboration across centers to enhance the diversity of the patient population and improve generalizability. Multicenter collaborations, including registries and biobanks, could facilitate a deeper understanding of disease variability and therapeutic outcomes.

In conclusion, future clinical trials for ATTR-CM should integrate 

 to better understand and address the underlying causes of cardiac dysfunction, leading to more effective, personalized treatment strategies.

Panelists discuss how future clinical trials in transthyretin amyloid cardiomyopathy (ATTR-CM) should focus on incorporating mechanistic research, patient stratification, and diverse end points, while also including nonresponders to current therapies to better understand cardiac dysfunction and develop more personalized treatment strategies.

Prognostic Indicators of Disease Progression in ATTR-CM

Summary for Physicians: Prognostic Indicators and Detection of Progression in ATTR-CM

 (transthyretin amyloid cardiomyopathy), identifying and monitoring progression is crucial for optimal patient management. Several 

 and methods for detecting progression include:

 Increasing shortness of breath, fatigue, and edema suggest cardiac deterioration.

 New-onset atrial fibrillation, sustained ventricular arrhythmias, or worsening arrhythmias signal disease progression.

 A reduction in exercise tolerance or worsening ability to perform daily activities.

 Progression can be indicated by worsening left ventricular ejection fraction, increased wall thickness, or diastolic dysfunction.

 Increased gadolinium retention (suggesting amyloid deposition) or worsening myocardial edema may indicate progression.

 In patients with bone tracer uptake, an increase in uptake may reflect more extensive amyloid deposition.

 An increase in NT-proBNP levels indicates worsening heart failure and may suggest progression.

 Continuous or rising levels of cardiac troponin reflect myocardial injury and may signal disease progression.

 Changes in these biomarkers may indicate disease progression or response to treatment.

 A decline in the distance walked may reflect worsening functional status.

 Tools assessing functional capacity and patient-reported symptoms, such as the Kansas City Cardiomyopathy Questionnaire, can provide insight into disease progression.

 Lack of response or disease stabilization despite treatment may signal progression.

 Worsening symptoms of other organ involvement (eg, neuropathy, carpal tunnel syndrome) may also be indicative of disease progression.

 in ATTR-CM is defined by a combination of clinical, imaging, biomarker, and functional assessments. Monitoring these factors regularly helps physicians detect progression early, enabling timely interventions to manage the disease effectively.

Panelists discuss how monitoring clinical indicators, cardiac imaging, biomarkers, and functional assessments—such as NT-proBNP, troponin, and the 6-minute walk test—helps detect progression in transthyretin amyloid cardiomyopathy (ATTR-CM), allowing for early intervention and optimal disease management.

Ahmad Masri, MD, MS

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