Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial.

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro-B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown.
Objectives: The aim of this study was to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial.
Methods: VALOR-HCM included 112 symptomatic patients with obstructive HCM (mean age 60 years; 51% male). Patients assigned to receive mavacamten at baseline (n = 56) continued therapy for 56 weeks and those assigned to placebo transitioned to mavacamten (n = 52) from week 16 to week 56. Echocardiographic LA strain (reservoir, conduit, and contraction) was measured by using a vendor-neutral postprocessing software.
Results: At baseline, the mean LA volume index (LAVI) and LA strain values (conduit, contraction, and reservoir) were 41.3 ± 16.5 mL/m ² , -11.8% ± 6.5%, -8.7% ± 5.0%, and 20.5% ± 8.7%, respectively (all worse than reported normal). LAVI significantly improved by -5.6 ± 9.7 mL/m ² from baseline to week 56 (P < 0.001). There was a significant (P < 0.05) improvement in absolute LA strain values from baseline to week 56 (conduit [-1.7% ± 6%], contraction [-1.2% ± 4.5%], and reservoir [2.8% ± 7.7%]). Patients originally receiving placebo had no differences in LA measurements up to week 16. There was no significant improvement in LA strain values (conduit [-0.9% ± 3.8%], contraction [-0.4% ± 3.4%], and reservoir [1.4% ± 6.1%]; all; P = NS) from baseline to week 56 in patients with history of atrial fibrillation.
Conclusions: In VALOR-HCM, mavacamten resulted in an improvement in LAVI and LA strain at week 56, suggesting sustained favorable LA remodeling and improved function, except in the atrial fibrillation subgroup. Whether the advantageous LA remodeling associated with long-term treatment with mavacamten results in a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM remains to be proven. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072).
Competing Interests: Funding Support and Disclosures Bristol Myers Squibb policy on data sharing is provided at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html. The VALOR-HCM study was funded by Bristol Myers Squibb. Dr Desai has received consulting fees from Bristol Myers Squibb, Cytokinetics, Tenaya, Edgewise, and Viz.AI; and has done research support to Cleveland Clinic from Bristol Myers Squibb, Cytokinetics, and Tenaya. Drs Wolski and Nissen work for the Cleveland Clinic Coordinating Center for Clinical Research and are employees of the Cleveland Clinic, which received payments for the current research from Bristol Myers Squibb. Dr Geske has received consulting fees from Bristol Myers Squibb. Dr Owens has received consulting fees from Bristol Myers Squibb, Cytokinetics, Pfizer, BioMarin, Tenaya, Lexicon, Stealth, Edgewise, Renovacor; and has received grant support for research from Bristol Myers Squibb. Dr Saberi has received consulting fees from Bristol Myers Squibb and Cytokinetics. Dr Wang has received research grants (to institution) from Bristol Myers Squibb, Cytokinetics, and Abbott Vascular; has been on the consulting/advisory board from Bristol Myers Squibb; has held steering committee roles for Bristol Myers Squibb and Cytokinetics; and has received speaker fees from Bristol Myers Squibb. Dr Lakdawala has received consulting fees from Bristol Myers Squibb, Pfizer, Tenaya, Cytokinetics, and Akros; and has received research support from Bristol Myers Squibb and Pfizer. Drs Sherrid, Tower-Rader, and Naidu have received consulting fees from Bristol Myers Squibb and Cytokinetics. Dr Fermin has received consulting and speaker fees from Bristol Myers-Squibb and BridgeBio; and has received consulting fees from Pfizer. Drs Lampl and Sehnert are employed and have stock ownership at Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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