1LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland
Introduction:
Hypertrophic (HCM) and hypertrophic obstructive cardiomyopathies (HOCM) are progressive myocardial disorders leading to thickening of the heart muscle, diastolic dysfunction, and – in cases of HOCM – obstruction of the left ventricular outflow tract (LVOT). Established treatment options for symptomatic patients with HOCM include medical treatment and invasive septal reduction therapy. Lately, the cardiac myosin inhibitor Mavacamten has emerged as a new therapy option for patients with HOCM. With this analysis, we give early insight into our experience treating HOCM patients with Mavacamten during the 12-week titration period.
Material and Method:
14 patients (50% female, 50% male, mean age 60.9+/-15.5 years) with HOCM were started on Mavacamten between March and November 2023. Cardiac imaging, ECG and laboratory work-up were available on site. In order to evaluate clinical outcome, the New York Heart Association (NYHA) Classification and Kansas City Cardiomyopathy-12 (KCCQ-12) Scores were assessed during visits. Initial dosing of Mavacamten was adapted to the cytochrome CYP2C19 status, and treatment was discontinued in cases of reduced left ventricular ejection fraction (LVEF) <50%. Data was available after 4, 8, and 12 weeks after therapy start in 10, 8, and 7 patients, respectively. In four patients, only first-visit data was available yet. Further visits are planned at 3, 6 and 12 months with comprehensive clinical evaluations, imaging and serum studies.
Results:
Mean post-exercise peak LVOT gradient prior to therapy initiation was 106.3+/-39.2 mmHg, mean NT-proBNP level was 1462.8+/-2418.6 pg/ml. Elevated Troponin T values were measured in 2 patients. Mean KCCQ-12 score prior to therapy initiation was 53.2+/-22.9 and all patients were symptomatic with NYHA class II or higher. 12 patients received a starting dose of 5 mg; 2 patients received a lower dose of 2.5 mg due to homozygous CYP2C19 metabolism.
Within 4 weeks of treatment, the mean LVOT gradients and NT-proBNP was significantly reduced to 23.4+/-19.7 mmHg (p<0.01) and 339.8+/-481.9 pg/ml (p=0.04), respectively. The subgroup analyses of 7 patients with a follow-up of 12 weeks revealed a persistent reduction of peak LVOT gradients (30.7+/-28.7, p<0.01) and NT-proBNP values (245.2+/-251.6 pg/µl, p=0.01). Clinical evaluation after 12 weeks revealed improvement in NYHA classification in 6 out of 7 patients (NYHA class II or III to I in 3 patients and NYHA class III to II in 3 patients); one patient remained NYHA class III. In this early phase, there was only a minor improvement in KCCQ-12 scores. Dosing adaptation to a lower Mavacamten dose was needed in 6 out of 10 patients. Treatment was temporarily discontinued in 2 patients due to reduced LVEF <50%, reevaluation of LVEF is yet pending.
Conclusion:
With this early analysis of a small cohort (n=14) treated with Mavacamten, we give first insight into the clinical usage in HOCM patients. Analyses revealed a significant and persistent reduction of LVOT gradients and NT-proBNP values, which is in line with published findings. There are signs of improvement in clinical symptoms in this early phase. Still, the need for dose correction and temporary discontinuation due to reduced LVEF highlights the need for close clinical, echocardiographic, and laboratory follow-up of all patients.