β Blockers for prevention of exercise-induced left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy

Whether treatment with β blockers (BBs) is of benefit to patients with hypertrophic cardiomyopathy (HC) and provocable outflow obstruction (with none or with only mild heart failure symptoms) is largely unresolved. Thus, we prospectively studied 27 patients with HC (age 36 ± 15 years; 81% men) with New York Heart Association class I or II, without obstruction at rest, but with exercise-induced left ventricular outflow tract (LVOT) gradient of ≥ 30 mm Hg. Patients underwent exercise echocardiography at baseline and after treatment with nadolol (n = 18; 40 to 80 mg/day) or bisoprolol (n = 9; 5 to 10 mg/day), according to a prespecified protocol. Without the BBs, the postexercise LVOT gradient was 87 ± 29 mm Hg and >50 mm Hg in 25 patients (93%). After a 12 ± 4-month period of BB treatment, the postexercise LVOT gradient had decreased to 36 ± 22 mm Hg (p <0.001) and was virtually abolished (to 0 or <30 mm Hg) in 14 patients (52%), substantially blunted (≥ 20 mm Hg reduction) in 9 (33%), and unchanged in only 4 (15%). Severe postexercise obstruction (range 58 to 80 mm Hg) persisted in 6 patients (22% compared to 93% without BBs; p <0.001). Nonresponders (residual postexercise gradient of ≥ 30 mm Hg with BBs) were characterized by an increased body mass index (hazard ratio 2.03/1 kg/m(2), 95% confidence interval 1.2 to 3.4; p <0.05). In conclusion, in patients with HC with mild or no symptoms, treatment with BBs can prevent the development of LVOT obstruction triggered by physiologic exercise. These findings provide a rationale for the novel strategy of early prophylactic pharmacologic treatment with standard, well-tolerated doses of BBs in physically active patients with provocable gradients, aimed at effective prevention of the hemodynamic burden associated with dynamic obstruction.