Mavacamten real-world experience: insights from the Dutch HCM Network

Abstract Background Mavacamten is the first cardiac myosin inhibitor approved for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy (oHCM). In the Netherlands, mavacamten is prescribed since 2024 by hospitals that are part of the Dutch HCM Network. Purpose Generate real-world knowledge on the efficacy and safety of mavacamten for oHCM. Methods All patients prescribed mavacamten provided informed consent and were included for analysis. Clinical and genetic data (including CYP2C19 genotype), biomarkers and echocardiography data were recorded from all patients. Adverse events (left ventricular ejection fraction (LVEF) 50%, atrial fibrillation (AF)), dose decreases, drug interactions and discontinuation of mavacamten were recorded. Timepoints of interest were 12 weeks after initiation and the maintenance phase, when the target dose was reached. Response was defined based on improvement in NYHA class, reduction of left ventricular outflow tract gradient (30mmHg) and biomarkers (50% ProBNP reduction). Results 119 patients were included (mean age 61±14, of which 57% male), of which 78 patients had at least 12 weeks follow-up and 48 patients reached their maintenance phase. For baseline characteristics see Table 1. Average NYHA class decreased with mavacamten use from 2.4 to 1.7(12w) and 1.5 (maintenance) on average (Figure 1A), with a concomitant significant decrease in LVOT gradients at rest (55±39 mmHg to 23±20 (12w) and 12±13 mmHg (maintenance), p0.001), with Valsalva (92±38 mmHg to 43±30 (12w) and 19±14 mmHg (maintenance), p0.001) (Figure 1B). Patients showed a a significant NT-proBNP decrease (median 540pg/ml to 220 pg/ml (12w) and 114pg/ml (maintenance) (p0.001)) (Figure 1C). LVEF showed a significant, yet unrelevant decrease from 62±5.5% to 59±6.0% (12w) and 58±5.3% (p=0.005) (Figure 1D). LVEF 50% occurred in 3(2.5%) patients. AF occurred in 6(5%) patients. Mavacamten was stopped in 3(2.5%) patients. CYP2C19 genotype varied (see Table 1), with only 2(1.8%) slow metabolisers in our cohort. Slow metabolisers did not experience any adverse events and both were uptitrated to 5mg during their follow-up. Reached doses were similar for the intermediate/normal/fast/ultrafast metabolisers. Hemodynamic response was achieved in 42% at 12w and 88% in maintenance for Valsalva gradients, and for 66% at 12w and 75% in maintenance for NT-ProBNP. Subjective response based on NYHA class was achieved in 57% at 12w and 70% in maintenance for all treated oHCM patients. Conclusion Mavacamten is an effective and safe therapy for oHCM in the real-world setting. CYP2C19 genotype did not influence adverse events or other effects.Table 1.Baseline Table. Figure 1.Mavacamten for oHCM