Initial clinical experience with mavacamten in symptomatic oHCM patients

Background – Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disease characterised by left ventricular hypertrophy and obstruction of the left ventricular outflow tract (LVOT) which strongly influences patients’ symptoms and outcome. Until recently, standard medication with ß-blockers, calcium antagonist or surgical myectomy or alcohol septal ablation were the only treatment options. Mavacamten is the first approved and available direct myosin inhibitor for treatment of symptomatic patients with oHCM. Here we present the initial clinical experience with mavacamten in 20 patients.

Methods – From our ongoing, prospective single-centre HCM registry we enrolled 20 oHCM patients that received mavacamten and completed three months follow up. Echocardiographic measurements included left ventricular ejection fraction, LVOT gradient at rest and under valsalva maneuver. Furthermore, we assessed troponin, NTproBNP and clinical status (NYHA classification and KCCQ score). Comparison between baseline and 3-months-follow up was done using the t-test and ordinal variables were tested with Wilcoxon test.

Results – Patients were 61.1 ± 13.1 years old (range 35 to 89 years), and all had normal CYP2C19 metabolic status. LVEF was 67.1 ± 4.2 at baseline and decreased mildly but statistically significant to 62.4 ± 4.1 (p < 0.01). However, none of the patients experienced a drop of LVEF <50%. LVOT gradient at rest was 59.5 ± 34.6 mmHg and provoked LVOT gradient 112.6 ± 26.5 at baseline and decreased to 24.7 ± 25.3 mmHg (p < 0.01) and 54.3 ± 30.9 mmHg (p < 0.01) respectively. NTproBNP and troponin decreased significantly from 2081.4 ± 3334.9 to 538.5 ± 704.4 (p < 0.01) and 43.3 ± 88.6 to 14.2 ± 7.9 (p = 0.08). Clinically patients improved significantly as well, with improvement in NYHA class (from 2.45 ± 0.5 at baseline to 1.4 ± 0.5 after 3 months; p < 0.01) and increase in KCCQ score (from 73.9 ± 15.6 at baseline to 95.4 ± 16.9 after 3 months, p < 0.01). Mavacamten was well tolerated, only one patient was converted to alcohol septal ablation due to QT interval prolongation. Dose adjustments were necessary in more than 50% of cases. The specific adjustments were as follows: 8 patients required an increase to 10 mg; 3 patients required a decrease to 2.5 mg mavacamten per day. 9 patients could remain on 5 mg mavacamten daily.

Conclusion – After a few months of commercial availability of mavacamten we can conclude from this data that its use is safe and effective in the initiating phase of three months. However, data on long-term safety and efficacy is necessary to determine its place in the treatment cascade of oHCM.