Aficamten Improves Right Ventricular Strain, Systolic Pressure in oHCM

A recent analysis of the SEQUOIA-HCM trial has demonstrated aficamten’s association with mild reductions in right ventricular free wall longitudinal strain (RVFWLS) and substantial reductions in right ventricular systolic pressure (RVSP).1

These data were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 in Phoenix, Arizona, by Theodore Abraham, MD, the Meyer Friedman Distinguished Professor of Medicine and clinical chief of cardiology at the University of California at San Francisco. The study’s established purpose was to evaluate the effects of aficamten on the right ventricle, given the lack of evidence surrounding this interaction.1

“Aficamten, a next-in-class cardiac myosin inhibitor, improved left ventricular outflow tract (LVOT) gradient, exercise capacity, quality of life, and echocardiographic measures of left-sided cardiac structure and function in patients with obstructive hypertrophic cardiomyopathy (oHCM),” Abraham and colleagues wrote. “The effects of aficamten on right ventricular (RV) function and RV-pulmonary artery (PA) coupling remain incompletely characterized.”1

SEQUOIA-HCM was a phase 3, randomized, placebo-controlled, double-blind, multicenter trial evaluating aficamten’s safety and efficacy in patients with oHCM. Patients were eligible for inclusion if they had a body mass index (BMI) <35 kg/m2, were diagnosed with HCM via left ventricular (LV) hypertrophy or end-diastolic LV wall thickness and had a resting LVOT gradient ≥30 mmHg and post-Valsalva LVOT gradient ≥50 mmHg, among other criteria.2,3

Patients were randomly assigned in a 1:1 ratio to receive either aficamten or placebo – randomization was stratified based on the use of beta-blockers and cardiopulmonary exercise testing modality. The primary endpoint was change from baseline in peak oxygen uptake (pVO2) at week 24, while secondary endpoints included change from baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Symptoms Score (KCCQ-CSS) at weeks 12 and 24, as well as the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class from baseline at weeks 12 and 24.3

A total of 282 patients underwent randomization, with 142 assigned to the aficamten group and 140 to the placebo group. At baseline, mean LV ejection fraction was 74.8%, and mean resting LVOT gradient was 55.1 mmHg. By week 24, the mean change in pVO2 was 1.8 ml/kg/min in the aficamten arm (95% CI, 1.2 to 2.3) and 0 ml/kg/min in the placebo group (95% CI, -0.5 to 0.5). Additionally, aficamten treatment improved all secondary endpoints compared with placebo.2

In the present analysis, Abraham and colleagues measured RVFWLS and RV 4-chamber longitudinal strain (RV4CLS) at baseline and week 24 via speckle-tracking echocardiography. RVSP was estimated with tricuspid regurgitation velocity, and RV-PA coupling was determined through the RVFWLS/RVSP ratio. Additionally, the team used multivariable linear regression to evaluate the effects of aficamten treatment and associations between changes in clinical parameters and changes in RV strain.1

Of the 282 patients included in the study, baseline RV strain measurements were feasible in 230 patients, split evenly between the treatment and placebo arms. Mean age among these patients was 59 +/- 13 years with a mean resting LVOT gradient 56 +/- 30 mmHg. At baseline, mean absolute RVFWLS was 24.5 +/- 5.1%, and mean absolute RV4CLS was 18.4 +/- 4%. Baseline resting RVSP was estimated successfully in 138 patients, with a mean value of 25.9 +/- 6.2 mmHg.1

By week 24, aficamten was associated with modest reductions in RVFWLS compared to placebo (-1.2%; 95% CI, -2.3 to -0.1%; P = .029) but remained within normal range. RV4CLS was unchanged after treatment (-0.5%; 95% CI, -1.3 to 0.3%; P = .25). Additionally, Abraham and colleagues found that aficamten substantially reduced RVSP (-4.3 mmHg; 95% CI, -7.1 to -1.5 mmHg; P = .003), which ultimately translated to no significant change in the RVFWLS-RVSP ratio. These changes were not associated with changes in pVO2, KCCQ scores, or NYHA functional class.1

“In patients with oHCM, aficamten was associated with a mild reduction in RVFWLS that remained within the normal range, alongside a significant reduction in RVSP, leading to preserved RV-PA coupling,” Abraham and colleagues wrote. “Changes in RV strain were not associated with other clinical measures and provide reassurance regarding RV performance with aficamten treatment.”1

References

1. Hamatani Y, Manafi A, Abraham T, et al. Association of Aficamten Treatment with Right Ventricular Function and Pulmonary Coupling in Obstructive Hypertrophic Cardiomyopathy: Results from the SEQUOIA-HCM Trial. Abstract presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.

2. Maron MS, Masri A, Nassif ME, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. New England Journal of Medicine. 2024;390(20):1849-1861. doi:10.1056/nejmoa2401424

3. Cytokinetics. Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM (SEQUOIA-HCM). ClinicalTrials.gov Identifier: NCT05186818. Updated March 3, 2026. Accessed October 11, 2026. https://clinicaltrials.gov/study/NCT05186818?term=NCT05186818&rank=1