Correlation of electrocardiographic reverse remodelling with treatment response to mavacamten in hypertrophic obstructive cardiomyopathy
M Menhem, N Donhauser, V Bytyqi, J Altstidl, T Kilian, M Marwan, S Achenbach, M TroebsAbstract
Background
Mavacamten, a selective cardiac myosin inhibitor, reduces left ventricular outflow tract (LVOT) obstruction and improves symptoms in hypertrophic obstructive cardiomyopathy (HOCM). While haemodynamic and biomarker responses are well established, the evolution and clinical relevance of electrocardiographic (ECG) reverse remodelling during therapy remain insufficiently characterised.
Purpose
This study aimed to characterise ECG changes during the first year of mavacamten therapy in patients with HOCM and to assess their association with haemodynamic and biomarker response, as well as potential proarrhythmic effects.
Methods
In this single-centre retrospective study, 40 consecutive patients with symptomatic HOCM treated with mavacamten were included. Clinical, laboratory, echocardiographic, and ECG parameters were assessed at baseline and at 3, 6, 12, and 24 months.
Results
Mavacamten therapy resulted in significant improvement in New York Heart Association (NYHA) functional class at 3, 6, and 12 months (all p < 0.001). NT-proBNP declined from 810 ± 740 pg/mL at baseline to 502 ± 665, 236 ± 276, and 214 ± 224 pg/mL at 3, 6, and 12 months, respectively (p = 0.024, p < 0.001, p < 0.001). Resting LVOT gradient decreased from 44 ± 30 mmHg at baseline to 20 ± 32, 11 ± 8, and 10 ± 8 mmHg at 3, 6, and 12 months, respectively (p = 0.0073, p < 0.0001, and p = 0.0002). Provoked LVOT gradient during Valsalva declined from 108 ± 49 mmHg at baseline to 53 ± 40, 24 ± 20, and 15 ± 16 mmHg at 3, 6, and 12 months, respectively (all p < 0.0001). Complete response, defined as NYHA I and LVOT gradient <30 mmHg at rest and during provocation, was achieved in 20%, 46%, and 78% of patients at 3, 6, and 12 months, respectively, and was maintained up to 24 months in longitudinal follow-up. The Sokolow–Lyon index decreased from 3.24 ± 1.20 mV at baseline to 2.85 ± 0.91, 2.47 ± 0.78, and 2.30 ± 0.85 mV at 3, 6, and 12 months, reaching significance at 6 and 12 months (p = 0.003, p = 0.001). ECG T-wave inversion burden decreased from 3.3 ± 2.0 leads at baseline to 2.2 ± 1.8 and 2.0 ± 0.95 leads at 6 and 12 months (p = 0.020, p = 0.013). Sokolow–Lyon index reduction predicted NT-proBNP normalisation <50 pg/mL (AUC 0.650) and correlated with Valsalva gradient reduction in patients with baseline Sokolow–Lyon index ≥3.5 mV (r = 0.473, p = 0.003). PQ, QT, and QTc remained stable, with no new cases of atrial fibrillation.
Conclusion
In patients with HOCM, mavacamten therapy was associated with substantial clinical and haemodynamic improvement accompanied by sustained cardiac remodelling and progressive electrocardiographic reverse remodelling. These findings suggest that serial ECG assessment may provide a practical and complementary tool for monitoring treatment response during mavacamten therapy.