Role of provocation and exercise imaging for the identification of candidates for myosin inhibitors
J Erzeel, S Dhont, M Van Es, P Bertrand, W Mullens, P MartensAbstract
Background
Left ventricular outflow tract obstruction (LVOTO) drives symptoms and functional limitation in obstructive hypertrophic cardiomyopathy (oHCM). Some patients probably only show treatment-qualifying obstruction during exercise stress echocardiography, yet their clinical profile and response to cardiac myosin inhibition remain insufficiently characterized.
Purpose
To evaluate the prevalence, characteristics, and treatment response of patients requiring exercise stress echocardiography to establish eligibility for mavacamten, compared with those meeting criteria at rest or during Valsalva manoeuvre.
Methods
This single-center retrospective study included 56 consecutive adults with symptomatic oHCM who initiated mavacamten between January 2024 and November 2025. Baseline transthoracic echocardiography assessed LVOTO at rest and during Valsalva manoeuvre. Exercise stress echocardiography using a semi-supine bicycle protocol was performed when resting gradients were <50 mmHg. Patients were classified as "exercise LVOTO" or "non-exercise LVOTO" based on where a treatment-qualifying gradient (≥50 mmHg) was first documented. Mavacamten was initiated at 2.5 mg once daily with protocol-driven dose titration based on left ventricular ejection fraction and LVOT gradient. Hemodynamic response was evaluated by Valsalva-provoked LVOT gradients at 12 and 24 weeks, and symptomatic response by change in NYHA class. Group comparisons used t-tests or Mann–Whitney U tests for continuous variables and chi-square or Fisher’s exact tests for categorical variables. Follow-up gradients were analyzed using ANCOVA adjusted for baseline, and longitudinal NYHA changes using generalized estimating equations.
Results
Twenty-four patients (42.9%) met treatment eligibility for mavacamten exclusively during exercise stress echocardiography. Resting and Valsalva gradients were lower by definition in the exercise LVOTO group (16.3±10.1 vs. 39.2±19.5 and 34.8±11.4 vs. 78.6±28.2, respectively; p <0.001 for both). Baseline NYHA class and structural echocardiographic parameters were comparable. Exercise capacity was similarly impaired, with comparable peak VO₂ (17.9±7.4 vs. 16.8±5.5 mL/kg/min; p = 0.550) and ventilatory efficiency (Ve/VCO₂ slope 31.3±6.4 vs. 30.9±5.9; p = 0.819). By 24 weeks, most patients in both groups achieved non-obstructive gradients (<30 mmHg; 92.3% vs. 100.0%; p=0.371) and NYHA class improvement (77.3% vs. 92.3%; p=0.377), with longitudinal analysis demonstrating progressive symptomatic improvement over time without between-group differences.
Conclusion
Patients requiring exercise stress echocardiography to document LVOTO do not appear to represent a milder phenotype and show treatment benefits from mavacamten comparable to those with resting or Valsalva-provoked obstruction. Stress echocardiography identifies additional eligible patients beyond resting assessment and should be used to guide candidacy and management in dynamic LVOTO.Valsalva LVOT gradient during mavacamtemFor image description, please refer to the figure legend and surrounding text.NYHA functional class during mavacamtemFor image description, please refer to the figure legend and surrounding text.