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Background Mavacamten has revolutionised the treatment of hypertrophic obstructive cardiomyopathy (HOCM) but requires frequent follow-up. Routine ECG may offer an accessible tool to indicate response to therapy. This study evaluates ECG-based indices of left ventricular hypertrophy (LVH) in patients with HOCM receiving mavacamten therapy.Methods In this retrospective study, after screening of 62 consecutive patients with HOCM treated at a German tertiary referral centre from August 2023 to February 2025, 31 patients (42% female, mean age 61±12 years) were included. During the first 12 weeks of myosin inhibitor treatment, echocardiographic parameters, laboratory values, symptoms and ECG LVH indices were assessed.Results Mavacamten reduced the mean left ventricular outflow tract obstruction (LVOTO) during Valsalva from 103 mm Hg (73–145) to 32 mm Hg (19–60), (p<0.001). All ECG LVH indices significantly decreased with treatment (Sokolow-Lyon Index: 2.56±0.97 mm vs 2.04±0.75 mm, p<0.001; Cornell criteria: 1.23 mm (0.92–2.21) vs 0.92 mm (0.75–1.75), p=0.001; Peguero-Lo Presti criteria: 2.39 mm (1.62–3.22) vs 1.61 mm (1.12–2.01), p<0.001; all pre vs post mavacamten). Notably, an increase in the Sokolow-Lyon Index and Peguero-Lo Presti criteria correlated with worsening LVOTO (area under the curve 0.72 and 0.88, respectively). Sensitivity and specificity of ECG LVH indices for detecting LVOTO progression during therapy were 100% and 88.6%, respectively.Conclusion A combinatory ECG-based approach using the Sokolow-Lyon Index and Peguero-Lo Presti criteria may serve as an accessible tool for monitoring LVOTO progression in patients with HOCM on mavacamten. Prospective validation is warranted.