Factors Influencing Long-term Heart Failure Mortality in Patients with Obstructive Hypertrophic Cardiomyopathy in Western Sweden: Probable Dose-related Protection from Beta-blocker Therapy

Objective: In order to avoid effects of referral bias, we assessed risk factors for disease-related mortality in a geographical cohort of patients with hypertrophic obstructive cardiomyopathy (HOCM), and any therapy effect on survival.

Methods: Diagnostic databases in 10 hospitals in the West Götaland Region yielded 251 adult patients with HOCM (128 male, 123 female). Case notes were reviewed for clinical data and ECG and ultrasound findings. Beta-blockers were used in 71.3% of patients from diagnosis (median metoprolol-equivalent dose of 125 mg/day), and at latest follow-up in 86.1%; 121 patients had medical therapy alone, 88 short atrioventricular delay pacing and 42 surgical myectomy. Mean follow-up was 14.4±8.9 (mean±SD) years. Primary endpoint was disease-related death, and secondary endpoint heart failure deaths.

Results: There were 65 primary endpoint events. Independent risk factors for disease-related death on multivariate Cox hazard regression were: female sex (p=0.005), age at diagnosis (p<0.001), outflow gradient ≥50 mm Hg at diagnosis (p=0.036) and at follow-up (p=0.001). Heart failure caused 62% of deaths, and sudden cardiac death 17%. Late independent predictors of heart failure death were: female sex (p=0.003), outflow gradient ≥50 mm Hg at latest follow-up (p=0.032), verapamil/diltiazem therapy (p=0.012) and coexisting hypertension (p=0.031), but not other comorbidities. Neither myectomy nor pacing modified survival, but early and maintained beta-blocker therapy was associated with dose-dependent reduction in disease-related mortality in the multivariate model (p=0.028), and final dose was also associated with reduced heart failure mortality (p=0.008). Kaplan-Meier survival curves analysed in initial dose bands of 0-74, 75-149 and ≥150 mg metoprolol/day showed 10-year freedom from disease-related deaths of 83.1%, 90.7% and 97.0%, respectively (p=0.00008). Even after successful relief of outflow obstruction by intervention, there was survival benefit of metoprolol doses ≥100 mg/day (p=0.01).

Conclusions: In population-based HOCM cohorts heart failure is a dominant cause of death and on multivariate analysis beta-blocker therapy was associated with a dose-dependent cardioprotective effect on total, disease-related as well as heart failure-related mortality.