Echocardiographic drag effect index and its association with response to mavacamten in obstructive hypertrophic cardiomyopathy

AIMS: Despite mavacamten's effect on left ventricular outflow tract (LVOT) obstruction, clinical response is heterogeneous. Considering the central role of systolic anterior motion (SAM) in obstruction, we examined whether mitral geometry and SAM-related echocardiographic indices correlate with this variability in obstructive hypertrophic cardiomyopathy (HCM) patients. METHODS AND RESULTS: A total of 128 patients with obstructive HCM were included in this multi-centre observational study. The SAM-related echocardiographic parameters-including anterior and posterior leaflet lengths, residual leaflet length (RL), protrusion height, and aortomitral angle (α)-were measured. A drag effect index was quantified by sin(α) × RL. Clinical response was defined as achieving a lowest observed Valsalva-induced LVOT gradient of less than 30 mmHg at any point during the 12-week follow-up period. Among the 128 patients, 33 (25.8%) were non-responders. Non-responders had a smaller α (115.3 ± 8.3° vs. 125.7 ± 9.9°; P < 0.001), longer RL (1.1 ± 0.2 vs. 0.8 ± 0.3, P < 0.001), and higher drag effect index values (sin(α) × RL; 1.0 ± 0.2 vs. 0.7 ± 0.3; P < 0.001). Multivariable logistic regression identified resting LVOT gradient, α, and drag effect index as independent factors associated with non-response. Receiver operating characteristic analysis demonstrated moderate discriminative ability for α [area under the curve (AUC) 0.787], RL (AUC 0.754), and strong discriminatory ability for the drag effect index (AUC 0.825), with the drag effect index providing the highest overall accuracy (73%). CONCLUSION: Drag-based echocardiographic indices offered high discriminatory performance for mavacamten response. Integrating these patient-specific metrics into routine assessment provides valuable pathophysiological insights into SAM mechanisms in obstructive HCM.