Background
Hypertrophic obstructive cardiomyopathy (HOCM) is associated with a high burden of heart failure. Myosin-inhibitor therapy directly targets the underlying pathophysiology of hypercontractility in HOCM, offering the potential of causal treatment and enhance clinical outcomes, although comprehensive large real-world data on HOCM management remain limited.
Methods
The multicenter German REDUCE-Registry (Registry for Patients with Diagnosed Hypertrophic Obstructive Cardiomyopathy Evaluated for Myosin-Inhibitor Therapy) involves eight tertiary cardiomyopathy referral centers across Germany. Patients diagnosed with HOCM who presented since May 2023 were included. Data from the baseline visit, defined as the first visit under established background therapy with beta-blockers or calcium channel blockers, were collected, along with subsequent six-monthly follow-ups. For patients initiating myosin-inhibitor therapy, additional clinical data (NYHA class, LVOT gradient, and biomarkers) and adverse events were gathered during four-weekly follow-ups.
Results
A total of 443 patients were enrolled (mean age 59.9 ± 13.7 years, 46.4% female). The mean disease duration was 4.5 ± 6.1 years, and mean BMI 28.8 ± 5.2 kg/m². Most patients (93.7%) had LVOT obstruction, while 5.4% had midventricular and 0.9% apical obstruction. Genetic testing was performed in 33.5%, with 10.3% positive for sarcomeric variants (predominantly MYBPC3). Arterial hypertension (63.7%) was the most frequent comorbidity. At baseline, 73.5% of patients received beta-blockers, 21.5% calcium channel blockers, and 1.1% disopyramide.
Among all patients, 330 (74%) were additionally started on mavacamten treatment, 19 (4%) were referred for TASH or myectomy, and 94 (21%) remained on baseline medical therapy. Patients in the mavacamten group had higher LVOT Valsalva gradients (90.6 ± 49.7 mmHg vs. 46.6 ± 34.7 mmHg, p < 0.001) and greater septal thickness (19.4 ± 4.0 mm vs. 17.7 ± 4.8 mm, p = 0.011) than the background therapy group at baseline. Functional limitation was more pronounced, with 48.0% of mavacamten patients reporting NYHA III symptoms versus 28.9% in the baseline therapy group (p < 0.001).
In the mavacamten cohort, LVOT gradients decreased significantly after 4 weeks, with further reduction over 20 weeks of treatment (p<0.001). Moreover, functional class improved progressively: the percentage of patients in NYHA I/II increased from 54.8% to 88.9% (p<0.001).
During the first 20 weeks, 36 adverse events were reported with 11 cases (3.3%) of LVEF < 50%, 22 (6.7%) of dizziness, and 3 (0.9%) of syncope. Mavacamten was temporarily paused in all patients with reduced LVEF, with one case leading to permanent discontinuation.
Conclusion
The German REDUCE Registry demonstrates successful real-world implementation of myosin-inhibitor therapy, with three of four HOCM patients initiated on mavacamten. Consistent with pivotal trials, mavacamten led to substantial reductions in LVOT gradients and marked improvement in NYHA class within 20 weeks, confirming its efficacy and safety profile in routine clinical care.
