Mavacamten Improves Cardiac Structure And Function In HCM: S
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Mavacamten improved left ventricular hypertrophy, decreased measures of heart stiffness and restored normal mitral valve motion in patients with obstructive hypertrophic cardiomyopathy, according to an analysis of the EXPLORER-HCM trial.

Mavacamten (MyoKardia) is an oral, allosteric modulator of cardiac myosin. This therapy was developed to target the underlying cause of hypertrophic cardiomyopathy.

The new analysis “builds on our previous observations that treatment with mavacamten led to significant improvement in symptoms, exercise capacity, health status and left ventricular outflow tract gradients,” said researcher. “Together, these results support the theory that mavacamten, as a first-in-class myosin inhibitor, impacts key pathophysiologic features of hypertrophic cardiomyopathy. This would represent a significant advance in therapy in this population.”

Researchers reported additional echocardiographic analyses to examine the effect of mavacamten on measures of cardiac structure and function. In total, 244 patients with obstructive cardiomyopathy (mean age, 59 years, 41% women) were randomly assigned to daily mavacamten 2.5 mg to 15 mg or placebo for 30 weeks, with echocardiograms performed every 2 to 4 weeks.

At 30 weeks, patients assigned mavacamten experienced significant reductions compared with placebo in left atrial volume (–7.5 ml/m2), lateral E/e' (–3.8 cm/s), septal E/e' (–3.4 cm/s) and LV mass index (–15.5 g/m2), according to the results.

In addition, compared with placebo, more patients assigned mavacamten achieved resolution of mitral valve systolic anterior motion and mitral regurgitation.

The ongoing, long-term extension study, MAVA-LTE, will follow participants of EXPLORER-HCM to evaluate long-term safety and efficacy, according to author. Serial echocardiographic data in this population will provide further insight into the long-term impact of mavacamten on cardiac structure and function, she said.

“There is an ongoing long-term extension study, MAVA-LTE, following the subjects who participated in EXPLORER-HCM to evaluate long-term safety and efficacy, and serial echocardiographic data in this population will provide further insight on the long-term impact on cardiac structure and function,” author said. “Furthermore, the VALOR-HCM study is enrolling patients with obstructive hypertrophic cardiomyopathy and severe symptoms who are eligible for septal reduction therapy to further investigate the ability of mavacamten to reduce the need for surgical or percutaneous procedures.”

The results were consistent with another imaging study presented at the AHA Scientific Sessions and published in Circulation. In that study of 30 patients from EXPLORER-HCM, those assigned mavacamten had a greater reduction in LV mass index at 30 weeks compared with those assigned placebo. The same was true for LV mass.

Source: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052359
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