Abstract Body (Do not enter title and authors here): Introduction
Beta blockers (BB) and calcium channel blockers (CCB) are recommended in non-obstructive hypertrophic cardiomyopathy (HCM) based on limited documentation.
Hypothesis
BB and CCB enhance the cardiovascular response to exercise in patients with non-obstructive HCM.
Methods
In this randomized, double-blind, placebo-controlled triple-crossover trial, patients with non-obstructive HCM (Left ventricular wall thickness ≥15 mm and left ventricular outflow tract gradient <30 mmHg), and ≥1 marker of disease severity: NYHA class ≥II, NT-proBNP >300 ng/L, or non-sustained ventricular tachycardi were included. Each patient underwent three treatment periods with daily target doses of bisoprolol 7.5 mg, verapamil 360 mg and placebo. The main outcomes, compared to placebo, were oxygen consumption (VO₂), heart rate (HR), blood pressure (BP), anaerobic threshold (AT), ventilatory volume/carbon dioxide output (VE/VCO₂) slope, as marker of ventilatory efficiency, rate-pressure product (RPP), as marker of myocardial work and O₂-pulse, as marker of stroke volume. Outcomes were evaluated by a cardiopulmonary exercise test after two weeks of steady state treatment.
Results
Thirty-two patients aged 54 years were included. At peak exercise, bisoprolol reduced VO₂ to 25.7±8.7 mL/kg/min (-2.5 mL/kg/min, p=0.002) compared to placebo. Bisoprolol further reduced HR (-37 min^-1, p<0.001), diastolic BP (-16 mmHg, p=0.007), RPP (-7234 min^-1× mmHg, p<0.001), and increased O₂-pulse (+3.30 mL/beat, p<0.001). At peak exercise, verapamil reduced VO₂ to 28.2±8.6 mL/kg/min (-0.7 mL/kg/min, p=0.990) compared to placebo. Verapamil further reduced HR (-17 min^-1, p<0.001) and increased O₂-pulse (+1.58 mL/beat, p=0.001) at peak exercise, but RPP, systolic and diastolic BP were unchanged. The VO₂ at AT and the VE/VCO₂ slope were unchanged for both bisoprolol and verapamil compared to placebo. At rest, bisoprolol reduced HR (-13 min^-1, p<0.001), systolic BP (-8 mmHg, p=0.002), diastolic BP (-7 mmHg, p<0.001), RPP (-3005 min^-1× mmHg, p<0.001), and increased O₂-pulse, (+2.73 mL/beat, p<0.001). Resting VO₂ was unchanged. Verapamil reduced resting HR (-6 min^-1, p<0.001), diastolic BP (-5 mmHg, p=0.010), RPP (-1212 min^-1× mmHg, p<0.001), but resting systolic BP, VO₂ and O₂-pulse were unchanged.
Conclusion
Bisoprolol significantly reduced oxygen consumption and estimates of myocardial work at peak exercise compared to placebo, while verapamil did not affect these markers significantly compared to placebo.