Milind Desai, MD, MBA

The Evolution of Hypertrophic Cardiomyopathy Care With Milind Desai, MD

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

, Milind Desai, MD, director of clinical operations of the Tomsich Department of Cardiovascular Medicine at Cleveland Clinic, discussed recent advancements in the diagnosis and treatment of 

 sat down with Desai to discuss the disease, recent clinical and medicinal advancements, and where the pipeline may lead in 2026. Desai mentioned several current and ongoing studies investigating medical therapies, spotlighting aficamten’s progress in the pipeline and mavacamten’s reaffirmed efficacy.

“In the last few years since 2018, we’ve had a plethora of phase 3 randomized control trials using cardiac myosin inhibitors,” Desai told 

. “Mavacamten being one of the first in line, and aficamten is currently undergoing review by the [

]. And between these two, I can count about 6 randomized controlled trials across the world, all of which have shown that this class of drug, compared to placebo, improves symptoms, exercise capacity, need for septal reduction therapy, biomarkers, favorable cardiac remodeling, etc.”

Desai mentions the recent SEQUOIA-HCM trial, which investigated the efficacy of aficamten compared to placebo in patients with symptomatic obstructive HCM. The 24-week trial enrolled 182 patients; the 142 randomly assigned to aficamten saw a significant improvement in limiting symptoms (71% vs 42%; 

Additionally, patients receiving aficamten were more likely to have complete hemodynamic response (68% vs 7%), demonstrate enhance exercise capacity (47% vs 24%), and show a decrease in N-terminal pro-B type natriuretic peptide (84% vs 8%; 

 ≤.002 for all). An improvement in ≥1 of these measures was achieved in 97% of patients receiving aficamten versus 59% in the placebo cohort.

Mavacamten, meanwhile, had its efficacy reaffirmed during the EXPLORER-HCM trial, which enrolled 251 patients and randomly assigned them to receive either mavacamten or placebo. Investigators measured exercise performance parameters including carbon dioxide output, minute ventilation, ventilatory efficiency, peak respiratory exchange ratio, ventilatory power and threshold, and peak exercise time, among others. Investigators saw significantly greater improvements among the mavacamten cohort across every parameter during the trial.

Desai also highlighted invasive therapies and surgeries, explaining newer and more efficient techniques coming out of various countries in recent months.

“There’s a lot of surgical myectomy which traditionally has been done through the trans-aortic route. Now there’s emerging data, a lot of it coming out of China, where they’re doing beating heart myectomy, which is where the heart continues to beat and there’s a small incision in the apex, through which the surgeon does a myectomy,” Desai said. “There’s also something called SESAME, which tries to mimic a myectomy through an interventional, catheter-based technique.”

Finally, Desai gave his advice to clinicians dealing with HCM, noting the critical importance of determining the specific type of HCM prior to treatment. In addition, Desai pushed for shared decision-making conversations if first-line background therapy fails, warning clinicians not to approach further treatment as mutually exclusive.

“I always say the following: it is not this 

this,” Desai said. “If you go on a pathway of cardiac myosin inhibitors, it doesn’t mean that myectomy is no longer going to be an option.”

Editor’s Note: Desai reports disclosures with Bristol Myers Squibb, Cytokinetics, Tenaya, viz.AI, Edgewise, and others.

Maron MS, Masri A, Nassif ME, et al. Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Coll Cardiol. 2024;84(19):1821-1831. 

Wheeler MT, Olivotto I, Elliott PM, et al. Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol. 2023;8(3):240-247. 

Videos

Desai details recent advancements in medicine and invasive treatments while reminding clinicians of what can still be done to protect patients.

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.

Milind Desai, MD: Real-World Data Supports Mavacamten’s Safety for oHCM

Real-world results from the Risk Evaluation and Mitigation Strategy (REMS) program confirmed mavacamten, a cardiac myosin inhibitor for 

obstructive hypertrophic cardiomyopathy (oHCM)

, maintained a favorable safety profile in more than 6,000 real-world patients.

American Heart Association (AHA) Scientific Sessions 2024

, data collected between April 2022 and February 2024 revealed that temporary treatment interruption due to reduced left ventricular ejection fraction (LVEF <50%) was rare, occurring in only 4.6% of patients, while HF requiring hospitalization (HFH) was even less frequent (1.3%).

“Overall, all the REMS objectives with regards to the mavacamten program were achieved based on the current report,” presenting investigator Milind Y. Desai, MD, MBA, a professor of medicine at the Cleveland Clinic Lerner College of Medicine, told 

. “Of course, REMS is not a clinical trial, we don’t have extensive data, but that is not what this program was designed [to do]. Every patient in the United States is represented here."

Among the 1,929 patients treated with mavacamten for at least 1 year, 4.04% experienced LVEF reductions to <50% and 0.21% had concurrent HFH, often linked to confounders like atrial fibrillation. Across 29,111 health status forms submitted during the study, LVEF <50% was reported in 0.9% of cases, and HFH occurred in only 0.3%. Additionally, drug interaction monitoring—part of the REMS protocol—led to dose adjustments in 0.25% of cases and discontinuation of interacting medications in 0.32%.

Overall, these findings reinforce mavacamten’s safety and tolerability for patients with symptomatic NYHA class II-III oHCM, even with prolonged use. Clinicians can be reassured by these real-world outcomes, demonstrating effective risk management under the REMS program. Further dosing analyses are expected to provide additional insights into optimizing long-term treatment strategies.

“The next programs will inevitably require a REMS program and they have a playbook they can adapt off of the mavacamten experience,” Desai told HCPLive. “I would imagine the future set of cardiologists or practicing clinicians who may have to deal with the REMS program, we have a huge contemporary lesson to learn from."

Disclosures: Desai reports relevant disclosures with Bristol Myers Squibb, Cytokinetics, Edgewise, and others.

Desai MY, Seto D, Cheung M, Coiro M, et al. Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.

Mavacamten, a cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy, demonstrated a favorable safety profile in over 6,000 patients under the REMS program. Data from April 2022 to February 2024 showed low incidences of reduced left ventricular ejection fraction and heart failure requiring hospitalization. Among patients treated for at least a year, LVEF reductions and HFH were rare. Drug interaction monitoring led to minimal dose adjustments and medication discontinuations. These findings support mavacamten's safety and tolerability, providing a model for future REMS programs in cardiology.

Milind Desai, MD describes favorable real-world safety outcomes from mavacamten use over 22 months of the Risk Evaluation and Mitigation Strategy (REMS) program.

Milind Desai, MD: Real-World Safety Data Supports Mavacamten for oHCM

 So in the last few minutes, I'm going to ask each of you as you look into the future caring for our patients with obstructive HCM [hypertrophic cardiomyopathy] and non-obstructive HCM, what other things are you excited about? We talked a little bit about the myosin inhibitors, but clearly there are other things that Milind alluded to that are coming down the pike for us. It's an exciting time to be in HCM position. What are the things that you're most looking forward to and Jim, I'll start with you.

 Yeah, thanks very much. I'll put my clinical trial hat on. We've fully enrolled a clinical trial looking at metabolic manipulation of myocardial function using a partial fatty acid oxidase inhibitor in patients with HCM. So approaching the question from a completely different angle that would be additive together with cardiac myosin inhibition, so thinking about newer pathways to address in patients with HCM to improve their symptoms. That's really exciting to me.

 So speaking as a heart failure, transplant cardiologist is what I spend most of my time doing. I think we still have so many unanswered questions in patients with non-obstructive HCM with advanced symptoms. What's the role of guideline directed medical therapy—was just traditional garden variety heart failure with preserved ejection fraction therapy like mineralocorticoid antagonists, angiotensin receptor neprilysin inhibitors, SGLT2 inhibitors. Do they work? Will they be effective in non-obstructive HCM? I think that is an unmet need in a huge space that I'm hopeful in the future we'll have more answers.

 I agree with you completely. That group of patients are perhaps the most difficult and challenging to treat in the clinic and hopefully will make some headway there. Milind, what are you looking forward to?

 I will start with what Michelle alluded to the next frontier is the non-obstructive HCM. So I am not a heart failure transplant doctor, but can mavacamten or CMIs [cardiac myosin inhibitors] work in this space because it's not all about the LVOT [left ventricular outflow tract] obstruction. There are structural changes that are happening, and we are answering this question in an ongoing randomized clinical trial, RCHCM, and there is another one with aficamten, that is being planned coming down the pike. That will help us clear some of that air. Of course, we need to understand the other drugs like SGLT. Could that work? But the bigger picture I think is the genetic space, the gene therapies, the adenovirus-based therapies that can help modulate the deficient protein in the heart of MYBPC3 so that space is active and brewing the business of gene editing CRISPR, etcetera. All these things obviously, I often joke as long as it does not create mutant Ninja Turtles down the road, meaning the uncertain offshoot effects, I think the future is bright. Honestly, I just told this to one of my patients a couple of days ago is that I can excitedly look forward to having a potential cure for this disease before I hang my boots into retirement. So I'm looking forward to all and plus the PROs [patient reported outcomes] and the shared-decision making. The other thing is the HCMR trial, hypertrophic cardiomyopathy registry from NIH which I am also part of, so I have to plug it in. That is going to start reading out in the next year or so that will help understand the risk stratification space a lot more.

 What's left? They've taken all the low hanging fruit And even the high hanging fruit from the tree. No fruit left on the tree.

 You're climbing all the way up the tree to the top.

 No fruit left on the tree. So I would echo what Jim said. I think that the potential for positive remodeling of the left ventricle not only pathologically with hypertrophy, but maybe reducing the progression of fibrosis would be a major advancement. If we can show that a therapy reduces progressive fibrosis that we can see on late gadolinium enhancement, we know its association with worsening progressive heart failure as well as ventricular arrhythmias, that would be a huge benefit. As Milind said that fibrosis is also shown with severe diastolic dysfunction as well, and many of our patients have some symptoms with outflow tract relief from diastolic dysfunction. So I think that is another unmet need. The last thing I would say is you know how normal can we make patients feel? With obstructive hypertrophic cardiomyopathy, will they be safe to be highly competitive, vigorous athletes, even with this condition? Can we really get close to normalizing what they really can do and feel like they can do and want to do?

 Yeah, that's what's a wonderful goal. It is a lofty goal, but one that we may meet. So with that, I'd like to thank you all for joining our panel today. This has been a very rich, informative and lively discussion and thank you audience for watching our HCPLive Peer Exchange®. You can subscribe to the enewsletter and receive other great content right in your inbox. Thanks again everyone.

Transcript is AI-generated and edited for clarity and readability.

Andrew Wang, MD; James Januzzi, MD; Michelle M. Kittleson, MD, PhD; and Milind Desai, MD, MBA, share a look into the future of oHCM treatment.

Milind Desai, MD, MBA

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