https://doi.org/10.1007/s00392-025-02625-4
1Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland
Background – Mavacamten is the first approved and available direct myosin inhibitor in Europe for treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Obstruction of the left ventricular outflow tract (LVOT) 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. Here we present the initial clinical experience with mavacamten in 36 patients with focus on the determination of mavacamten maintenance dose.
Methods – From our ongoing, prospective single-centre HCM registry we enrolled 36 oHCM patients that received mavacamten and completed the initiating phase with reaching their maintenance dose. 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 60.6 ± 12.1 years old (range 36 to 88 years), and all had normal CYP2C19 metabolic status with mavacamten starting dose of 5 mg per day. LVEF was 67 ± 6 at baseline and decreased mildly but statistically significant to 62 ± 6 (p = 0.0004). However, none of the patients experienced a drop of LVEF <50%. LVOT gradient at rest was 67 ± 37 mmHg and provoked LVOT gradient 112 ± 37 at baseline and decreased to 26 ± 30 mmHg (p < 0.001) and 55 ± 35 mmHg (p < 0.001), respectively. NTproBNP and troponin decreased significantly from 1707 ± 2660 to 558 ± 737 (p = 0.0005) and 31 ± 66 to 13 ± 7 (p < 0.0001). Clinically patients improved significantly as well, with improvement in NYHA class and increase in KCCQ score (from 76 ± 17 at baseline to 94 ± 16 after 3 months, p < 0.0001). Mean time to reach maintenance dose was 14 weeks (range between 8 to 20 weeks), with necessity of dose adjustments in more than 50% of cases. The initial dose of 5 mg could be maintained in 17 patients (42.7%). In three patients, the medication was discontinued: in one due to QT prolongation and in two due to lack of response.
Conclusion – After more than one year of commercial availability of mavacamten we can conclude from this data that its use is safe and effective in the initiating phase. Individual dose adjustment is necessary for patient safety. However, data on long-term safety and efficacy is necessary to determine its place in the treatment cascade of oHCM.