Role of provocation and exercise imaging for the identification of candidates for cardiac myosin inhibitors.

AIMS: Left ventricular outflow tract obstruction (LVOTO) drives symptoms and functional limitation in obstructive hypertrophic cardiomyopathy (oHCM). Some patients may only show treatment-qualifying obstruction during exercise echocardiography, yet their clinical profile and response to cardiac myosin inhibition are not well defined. This study compared the characteristics and therapeutic response of patients requiring exercise echocardiography to establish eligibility for mavacamten versus those meeting criteria at rest or during Valsalva.

METHODS AND

RESULTS

A single-centre retrospective cohort of 56 symptomatic oHCM patients treated with mavacamten was evaluated. LVOTO was assessed at rest, with Valsalva, and during exercise; patients were classified as 'exercise' or 'non-exercise' LVOTO based on the provocation manoeuvre eliciting a qualifying gradient (≥50 mmHg). Haemodynamic (Valsalva LVOT gradient) and symptomatic (NYHA class) response were assessed at 12 and 24 weeks. A total of 42.9% qualified for mavacamten exclusively during exercise echocardiography. Although resting and Valsalva gradients were lower by definition, these patients showed similar baseline functional limitation and exercise capacity (pVO2; 17.9 ± 7.4 vs. 16.8 ± 5.5 mL/kg/min, P = .550). By 24 weeks, most patients in both groups achieved non-obstructive gradients (<30 mmHg; 93.3% vs. 96.4%, P = .646) and NYHA class improvement (75.0% vs. 93.3%, P = .266), without significant between-group differences.

CONCLUSION

Patients requiring exercise echocardiography to document treatment-qualifying LVOTO do not exhibit a milder disease phenotype and derive similar treatment benefits from mavacamten compared to those with resting or Valsalva-provoked obstruction. Exercise echocardiography identifies a substantial proportion of symptomatic HCM patients with significant LVOTO missed by resting assessment and is essential for guiding treatment eligibility.