Mitral regurgitation in obstructive hypertrophic cardiomyopathy: assessing the impact of mavacamten
Authors: Kasolo Y , Ali H , Culshaw C , Conway N , Fairbairn T , Cooper R 
Published: January 2025

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac condition that leads to a hypercontractile state. This, as well as other features of HCM, such as abnormal mitral valve morphology and septal protrusion can lead to left ventricular outflow tract (LVOT) obstruction. Mitral regurgitation (MR) is a frequent finding in patients with hypertrophic cardiomyopathy (HCM), usually due to systolic anterior motion (SAM) of the mitral valve. Patients with outflow obstruction can present with a myriad of symptoms. With the introduction of myosin inhibitors such as mavacamten, reductions in the LVOT gradient and improvement in symptoms has been well documented. However, the impact on SAM and SAM-mediated MR has not been well explored.

Objectives
We aimed to evaluate whether mavacamten resulted in a change in SAM and subsequently a change in mitral regurgitation, in patients with obstructive HCM from baseline following a period of established mavacamten pharmacotherapy.

Methods
Transthoracic echocardiography (TTE), which is used to facilitate the safe prescription and monitoring of mavacamten therapy, was retrospectively analysed. Severity of mitral regurgitation (graded as 0-4 to delineate trivial, mild, moderate, moderate to severe and severe disease), grade of SAM (0-3) and LVOT gradients were documented, with baseline studies compared to the most recent follow up scan for the patient in question. MR severity was based on the visual impression of the reporting sonographer, and was reviewed by an imaging cardiologist. Patients had undergone between 4 and 24 weeks of mavacamten pharmacotherapy depending on their time of enrolment into the mavacamten clinic. Concurrent changes in NT-pro BNP were also evaluated.

Results
24 patients (female n=4; male n = 20) in the mavacamten clinic underwent retrospective analysis of their echocardiographic parameters. Improvement in the severity of MR occurred in 75% of patients (n=18; p&lt;0.001). In 39% of these patients, severity improved by 2 grades or more. Systolic anterior motion of the mitral valve was downgraded in 75% of patients (n=18; p&lt;0.001), with an improvement by 2 grades or more in 42% of individuals. Mavacamten therapy resulted in a reduction in LVOT gradient at rest (-28.96± 5.124mmHg P=&lt;0.0001) and with Valsalva (-60.95± 7.551mmHg P=&lt;0.0001). Furthermore, a significant reduction in serum NT-proBNP levels was demonstrated from baseline (-975.2± 7.551ng/L P=&lt;0.0001). 1 patient had to discontinue therapy at 4 weeks primarily due to a drop in left ventricular ejection fraction.

Conclusion
In patients with obstructive HCM, mavacamten resulted in a significant reduction in SAM-mediated mitral regurgitation, with corresponding falls in LVOT gradients. Cardiac myosin inhibitor scanning protocols should include detailed mitral valve assessment, to allow accurate evaluation of both SAM-dependent and SAM-independent MR mechanisms.
Severity of mitral regurgitation.
Change in grade of SAM.