https://doi.org/10.1007/s00392-025-02625-4
1Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; 2Uniklinik Köln Radiologie Köln, Deutschland
Background:
Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but detailed clinical real-world data are lacking.
Methods:
In this prospective study, patients who were uptitrated to their maximum tolerable, available or hemodynamically necessary mavacamten dose were included and a follow up 12 weeks after final dose achievement was conducted. Patients with no NYHA improvement from baseline were classified as symptomatic non-responders, patients with remaining left-ventricular outflow (LVOT) gradient >50mmHg as incomplete hemodynamic responder. Detailed data on the clinical course, echocardiographic parameters, and biomarkers were collected and analysed.
Results:
40 HOCM patients (56.4 ± 11.9 years, 77.5% male) were included in this study. The LVOT gradient (Rest: -24.7 [-34.9 to -14.4] mmHg, p < 0.001, Valsalva: -73.2 [-92.7 to -53.7] mmHg, p < 0.001) and NT-proBNP (-785.8 [-1144.7 to -426.8] ng/l, p < 0.001) significantly decreased to the mean follow up of 184 ± 83 days. 21/40 (52%) patients had a final dose of 5mg, 18/40 (48%) patients 10mg or 15mg. The higher final dose significantly correlated with a higher gradient at baseline (Valsava: 77.9 ± 42.7 mmHg vs 113.0 ± 61.0 mmHg, p=0.048). 9/40 (22.5%) patients were symptomatic non-responders and 3/40 (7.5%) incomplete hemodynamic responders. In both patient groups, we found similar treatment effects regarding the reduction of LVOT gradients and lowering left ventricular function as in patients with clinical or complete hemodynamic response. Patients with no improvement in NYHA class had a lower E´ lat. (8.52 ± 2.7 cm/s vs 6.4 ± 1.8 cm/s, p= 0.034) at baseline but no difference in baseline LVOT gradients or LV-mass. In incomplete hemodynamic responders, a significant higher baseline septum thickness (IVSD 26.3 ± 4.9 mm vs 18.9 ± 3.3mm, p<0.001) and higher LV-mass (195 ± 71.9 vs 137.5 ± 36.7 mL/m², p= 0.019) compared to complete hemodynamic responders was found.
Conclusion:
The absolute hemodynamic improvement of the myosin inhibitor mavacamten was consistent across all patients, regardless of clinical or hemodynamic response. Our findings suggest that incomplete hemodynamic response does not signify treatment failure but may reflect advanced disease, pointing out the importance of early intervention and the potential need for higher doses in selected patients.