Matthew Martinez, MD

Mavacamten Safety and Real-World Data Emerging at ACC.26, With Matthew Martinez, MD

Real-world evidence continues to refine the clinical profile of mavacamten in 

obstructive hypertrophic cardiomyopathy (HCM)

, with new data from both the MARVEL-HCM cohort and a large US Risk Evaluation and Mitigation Strategy (REMS) registry analysis reinforcing its effectiveness and safety in routine practice.

, Matthew Martinez, MD, associate professor of medicine, director of sports cardiology, and director of the Hypertrophic Cardiomyopathy program at Morristown Medical Center/Atlantic Health System, discussed the emerging data from the MARVEL-HCM trial, presented at the 

American College of Cardiology (ACC) Scientific Sessions 2026

“Most often, patients will ask, ‘How long have you been using this drug?’ So, the value of long-term safety data continues to be helpful,” Martinez told 

. “When I’m educating patients about options, I don’t determine what therapy we’re going to use. I give them the option of what’s best for them, and then we can decide together which therapeutic option is the next best step. Ongoing, long-term data continues to be helpful in that discussion.”

In MARVEL-HCM, a multicenter study of 239 patients, women presented at an older age than men (68.5 vs 59.3 years) and with more advanced disease, including higher rates of New York Heart Association (NYHA) class III symptoms and more severe diastolic dysfunction. Over 48 weeks of treatment, patients experienced significant reductions in resting and Valsalva left ventricular outflow tract (LVOT) gradients, improved functional status, and decreased severity of mitral regurgitation. Left ventricular mass index declined in both groups, supporting a role for reverse remodeling, while left ventricular ejection fraction (LVEF) remained stable, and no new safety signals were observed.

These findings are complemented by data from a large REMS-based analysis including more than 6000 patients treated with mavacamten in the United States. In this real-world cohort, 60% of patients were women and nearly two-thirds were older than 60 years, reflecting a population similar to that seen in clinical practice. Over a follow-up period of up to 22 months, reductions in LVOT obstruction were observed, with 70.3% of patients achieving a post-Valsalva gradient <30 mm Hg at 6 months.

Among more than 5,500 patients in the REMS study with monitoring data, 4.6% experienced a reduction in LVEF to <50%, and only 1.3% required hospitalization for heart failure. At the level of individual assessments, these events were infrequent, occurring in <1% of evaluations. Most patients remained on low-dose therapy, with approximately three-quarters maintained on 5 or 10 mg daily.

Taken together, these datasets highlight several clinically relevant themes. First, mavacamten demonstrates consistent effectiveness across diverse patient populations, including those with more advanced disease at baseline. Second, the drug appears to exert favorable effects on cardiac structure and hemodynamics beyond symptom relief. Third, real-world safety outcomes - particularly the low incidence of systolic dysfunction and heart failure - support the feasibility of REMS-guided monitoring in routine care.

The MARVEL-HCM findings also underscore persistent sex-based disparities in disease recognition and severity at treatment initiation. Earlier diagnosis and referral, particularly among women, may further enhance the clinical benefits observed with mavacamten in obstructive HCM.

“I think the real-world data is going to be critical,” Martinez said. “You’re already seeing the ability to be a little more granular with some of the real-world data, such as MARVEL and COLLIGO, because it allows us to ask other questions that may not have been specifically addressed during the clinical trials that led to mavacamten’s approval. All of these real-world studies allow us just a glimpse into what’s happening outside of large academic centers.”

Editors’ Note: Martinez reports disclosures with Bristol Myers Squibb, Cytokinetics, Major League Soccer, and the NHL Combine.

1: Martinez M, Wheeler M, Mehra V, et al. Real-World Evidence from the MARVEL-HCM Multicenter Study of Mavacamten – A Sex-Based Analysis of Baseline Characteristics and Cardiac Structural and Functional Changes. Abstract presented at the American College of Cardiology Scientific Sessions 2026, New Orleans, LA. March 28-30, 2026.

2: Desai MY, Seto D, Cheung M, et al. Mavacamten: Real-world experience from 22 months of the risk evaluation and mitigation strategy (REMS) program. 

Videos

Martinez discusses the bigger picture of mavacamten, highlighting its safety and efficacy as well as recent real-world trial data in patients with HCM.

Implementing Cardiac Myosin Inhibitors in oHCM: Workflow and Team-Based Care

Effective implementation of cardiac myosin inhibitor therapy for oHCM depends heavily on systems of care rather than on the prescribing physician alone. Mariko Harper, MD, describes a dedicated cardiac myosin inhibitor clinic in Washington State staffed by a cardiac pharmacist who functions in many ways like an advanced practice provider. This pharmacist leads initiation, titration, drug–drug interaction review, and REMS documentation, while nurse coordinators manage direct lines of communication, scheduling, and coordination of echocardiography. Advance scheduling of the first several echocardiograms at the time of therapy planning, with flexibility to adjust as needed, provides clarity for patients and staff.

Matthew Martinez, MD, highlights the role of telemedicine for interim visits, which allows efficient, geographically flexible follow-up and facilitates rapid response to clinical or imaging changes. He and Harper emphasize that experienced sonographers, nurses, advanced practice providers, and pharmacists must function as equal partners in a “team sport,” with explicit empowerment to escalate concerns such as suspected atrial fibrillation or unexpected gradient patterns. Over time, as volumes increase, team members train newer staff, transforming what initially feels like a challenging REMS-driven process into a predictable, streamlined workflow after the first several patients.

Martinez and Harper also offer granular practical advice, such as coordinating the actual start date of therapy with the timing of follow-up echocardiography and patient support. They encourage patients to contact the nurse coordinator as soon as the initial shipment is received so that day 1 dosing and subsequent imaging timelines can be aligned. Martinez often recommends initiating therapy on a Sunday evening to maximize weekday availability for early follow-up and to ensure that questions about tolerability arise during regular clinic hours. This segment provides a detailed operational blueprint for clinicians seeking to integrate cardiac myosin inhibitors into everyday oHCM practice while maintaining high safety and patient satisfaction standards.

Martinez and Harper outline practical workflows for initiating and titrating cardiac myosin inhibitors, emphasizing multidisciplinary team structure, telemedicine, and logistics around REMS and imaging.

Comprehensive oHCM Follow-up: Hub-and-Spoke Care and 4-Pillar Framework

As oHCM prevalence and recognition increase, the limited capacity of specialized centers necessitates collaborative care models. Mariko Harper, MD, advocates for a hub-and-spoke strategy in which HCM centers of excellence provide initial diagnosis, risk stratification, and treatment planning, then partner closely with community cardiologists who assume much of the ongoing imaging, rhythm monitoring, and general cardiovascular management. Virtual initial consultations allow for early education, efficient planning of on-site testing, and tailored delegation of which assessments should occur locally versus at the referral center. Patients typically value annual visits to the expert center for complex counseling, genetic and family screening updates, and information on emerging therapies and clinical trials.

Matthew Martinez, MD, introduces a four-pillar framework he uses to structure follow-up encounters. The first pillar is symptom assessment, with attention to new, progressive, or changing limitations, including patients who underreport symptoms because of uncertainty about next steps. The second pillar is arrhythmia surveillance, particularly atrial fibrillation and ventricular tachycardia, both for symptom control and sudden cardiac death risk stratification. The third pillar involves family-based care, focusing on genetic testing where appropriate, periodic imaging of first-degree relatives, and reassessment of family history as life circumstances evolve. The fourth pillar centers on lifestyle, encompassing exercise prescriptions, weight management, nutrition, and pregnancy planning when relevant.

Within this structure, Martinez and Harper discuss practical use of stress echocardiography to detect latent obstruction even in patients deemed nonobstructive for many years, as well as the growing role of natriuretic peptides such as NT-proBNP in flagging changes in hemodynamics or unveiling new processes such as diastolic dysfunction or concomitant amyloidosis. They describe MRI at 3- to 5-year intervals in many patients for fibrosis assessment and risk stratification, and yearly echocardiography in most individuals—more frequently when on titrated medical therapy. This segment illustrates how Martinez and Harper integrate advanced diagnostics, collaborative care, and structured clinical frameworks to deliver comprehensive, long-term management for patients and families affected by oHCM.

Martinez and Harper describe a hub-and-spoke model for HCM care, follow-up cadence, and a structured “4-pillar” framework for longitudinal management, including imaging, biomarkers, and family-based risk strategies.



Long-term Safety, REMS Data, and Echo Monitoring for oHCM Therapies

Real-world experience with cardiac myosin inhibitors under Risk Evaluation and Mitigation Strategy (REMS) programs provides critical insight into the safety profile of these agents outside the controlled environment of clinical trials.

Matthew Martinez, MD, discusses a large, REMS-guided analysis of more than 6000 patients that informed his understanding of the incidence, severity, and reversibility of left ventricular ejection fraction (LVEF) decline. He now quotes patients an approximate risk of LVEF reduction on the order of 4% to 7%, while acknowledging the need for further refinement of risk prediction. The same data suggest that REMS infrastructure—though unfamiliar to many cardiologists—helps standardize monitoring and maintain appropriate safety margins in routine practice.

Mariko Harper, MD, notes that, despite the boxed warning and patient concern about heart failure, REMS registry data have shown a very low rate of clinically meaningful LVEF decline with heart failure hospitalization, approximately 0.5% among more than 11,000 patients over several years when drugs are used according to protocol. This allows her to reassure informed patients who present having read the label and online resources. Both clinicians question whether current monitoring schedules are more intensive than necessary, particularly early 4-week echocardiograms and routine 6

month follow-up imaging in clinically stable patients on long-standing doses. They observe that most clinically meaningful changes correlate with recognized triggers such as infection, new medications, or atrial fibrillation rather than occurring unpredictably in otherwise stable individuals.

In this segment, Martinez and Harper propose a more risk-adapted approach to imaging-based surveillance, emphasizing symptom-triggered assessment and targeted evaluation in higher-risk periods while potentially de-emphasizing rigid time-based echocardiography in stable patients. They also describe how patient-reported symptoms usually precede concerning echocardiographic findings, suggesting that well-structured clinical follow-up and patient education may be at least as important as frequent imaging. Their discussion highlights how REMS-generated data can both reinforce the value of structured safety programs and guide thoughtful simplification of monitoring protocols over time.

Martinez and Harper review real-world REMS data on cardiac myosin inhibitors, refine approaches to safety monitoring, and question how frequently echocardiography is truly needed in stable oHCM patients.

Matthew Martinez, MD

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