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

Milind Y Desai; Yuichiro Okushi; Kathy Wolski; Jeffrey B Geske; Anjali Owens; Sara Saberi; Andrew Wang; Paul C Cremer; Mark Sherrid; Neal K Lakdawala; Albree Tower-Rader; David Fermin; Srihari S Naidu; Kathy L Lampl; Amy J Sehnert; Steven E Nissen; Zoran B Popovic; VALOR-HCM Investigators

doi:10.1016/j.jcmg.2024.08.005

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

JACC Cardiovasc Imaging. 2024 Sep 2:S1936-878X(24)00345-0. doi: 10.1016/j.jcmg.2024.08.005. Online ahead of print.

Authors

Milind Y Desai¹, Yuichiro Okushi², Kathy Wolski³, Jeffrey B Geske⁴, Anjali Owens⁵, Sara Saberi⁶, Andrew Wang⁷, Paul C Cremer³, Mark Sherrid⁸, Neal K Lakdawala⁹, Albree Tower-Rader⁹, David Fermin¹⁰, Srihari S Naidu¹¹, Kathy L Lampl¹², Amy J Sehnert¹², Steven E Nissen¹³, Zoran B Popovic¹⁴; VALOR-HCM Investigators

Collaborators

VALOR-HCM Investigators:
M Desai, J Geske, M Sherrid, A T Owens, S Saberi, A Wang, A Tower-Rader, D Fermin, N Lakdawala, A Masri, M Zenker, J Stendahl, M Wheeler, R Bach, J Orford, S Naidu, F Rader, P Bajona

Affiliations

¹ Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address: desaim2@ccf.org.
² Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
³ Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁴ Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Department of Cardiology, Duke University, Durham, North Carolina, USA.
⁸ Department of Cardiology, New York University, New York, New York, USA.
⁹ Division of Cardiology, Mass General Brigham, Boston, Massachusetts, USA.
¹⁰ Department of Cardiology, Corewell Health, Grand Rapids, Michigan, USA.
¹¹ Department of Cardiology, Westchester Medical Center, Valhalla, New York, USA.
¹² Bristol Myers Squibb, Princeton, New Jersey, USA.
¹³ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁴ Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.

PMID: 39254622
DOI: 10.1016/j.jcmg.2024.08.005

Abstract

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/m², -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/m² 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).

Keywords: left atrial strain; mavacamten; obstructive HCM.

Associated data

ClinicalTrials.gov/NCT04349072