(CCSP065) EARLY REAL-WORLD EXPERIENCE WITH THE NEW CARDIAC MYOSIN INHIBITOR MAVACAMTEN FOR SYMPTOMATIC HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY IN A SINGLE CANADIAN TERTIARY CARE CENTER

Background: Hypercontractility is fundamental to the pathophysiology of hypertrophic cardiomyopathy, and an essential contributor of dynamic left ventricular outflow tract obstruction. Standard pharmacological options for hypertrophic cardiomyopathy do not provide adequate relief of symptoms in a significant proportion of patients. Mavacamten, a first-in-class cardiac myosin inhibitor, recently became available in Canada. We aimed at evaluating clinical characteristics and clinical response of patients with obstructive hypertrophic cardiomyopathy treated with mavacamten within the Cardiovascular Genetics Clinic at the Montreal Heart Institute.

METHODS AND RESULTS: We evaluated consecutive patients treated with mavacamten at the Cardiovascular Genetics Clinic of the Montreal Heart Institute (n=24; 8 women and 16 men). Key characteristics of the patient population are: 1) mean age: 56 years, 2) mean heart rate at baseline: 62 beats/min, 3) baseline ejection fraction: 60%, 3) average baseline LVOT gradients: 55 mmHg at rest and 92 mmHg with Valsalva, 4) interventricular septum thickness: 19mm, 5) mitral insufficiency severity: 1.6/4, 6) baseline Nt-proBNP: 1564. Concomitant medications were beta blocker in 23/24; disopyramide in 2/24 and calcium channel blocker in 7/24. Mean follow up gradients: 1) 28 days: 31 mmHg at rest and 57 mmHg with Valsalva, 2) 8 weeks: 27 mmHg at rest and 47 mmHg with Valsalva. Mean left ventricular ejection fraction at follow up: 1) 59% at 28 days and 59% at 8 weeks. Patient reported clinical evolution: 8/11 and 5/6 reported improvement at 28 days and 8 weeks, respectively; 1/11 and 0/6 reported deterioration at 28 days and 8 weeks, respectively.

Conclusion: The early real-world experience tended to confirm findings from randomized clinical trials. Mavacamten was generally well tolerated and resulted in a significant and progressive reduction in the left-ventricular outflow tract gradient. Meaningful decrease in left ventricular ejection fraction occurred in one of 24 patients without clinical symptoms, highlighting the need for serial imaging studies. A majority of patients reported meaningful improvements in their functional class, suggesting that cardiac myosin inhibitors could play an important role in the management of symptoms of obstructive hypertrophic cardiomyopathy. These very early and single tertiary care center results will need confirmation in larger multi centric real-world registries.