Severe LVOT obstruction in HCM: effects on exercise capacity and outcomes from cardiopulmonary exercise testing combined with stress echocardiography.

Aims: Hypertrophic cardiomyopathy (HCM) is a complex disease in which left ventricular outflow tract (LVOT) obstruction influences both functional capacity and clinical outcomes. However, the clinical relevance of varying obstruction severity remains debated. To evaluate the relationship between LVOT gradient severity and both exercise performance and long-term prognosis in HCM using combined cardiopulmonary exercise testing and stress echocardiography (TTE-CPET).

Methods and results: We retrospectively analysed 388 HCM patients undergoing TTE-CPET, stratified into four groups based on peak LVOT gradient: <30 mmHg, 30-49 mmHg, 50-79 mmHg, and ≥80 mmHg. Clinical, echocardiographic, and CPET data were compared. The primary outcome was a composite of NYHA class worsening, heart failure hospitalization, new-onset atrial fibrillation, or progression to end-stage HCM, assessed over a median follow-up of 7.4 years. Only patients with severe obstruction (≥80 mmHg, n = 82) showed significantly lower peak VO2 (15.9 vs. 19.7 mL/kg/min, P = 0.003), higher pulmonary pressures, more advanced diastolic dysfunction, and greater symptom burden. They also had a higher incidence of adverse events (50.0% vs. 31.6%, P = 0.011) and worse event-free survival (log-rank P = 0.011). A peak gradient ≥80 mmHg independently predicted adverse outcomes (HR: 1.87; P = 0.009), even after adjustment. Patients with intermediate gradients (30-79 mmHg) had generally preserved outcomes, though some exhibited early structural or functional changes.

Conclusion: Severe dynamic LVOT obstruction identifies a high-risk HCM subgroup with impaired exercise capacity and poor prognosis. Intermediate gradients may still warrant close monitoring. TTE-CPET offers critical insight for risk stratification and early intervention.