Abstract 4359743: Exercise Response to Bisoprolol and Verapamil treatment in Non-Obstructive Hypertrophic Cardiomyopathy

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 (VO 2 ), heart rate (HR), blood pressure (BP), anaerobic threshold (AT), ventilatory volume/carbon dioxide output (VE/VCO 2 ) slope, as marker of ventilatory efficiency, rate-pressure product (RPP), as marker of myocardial work and O 2 -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 VO 2 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 O 2 -pulse (+3.30 mL/beat, p<0.001). At peak exercise, verapamil reduced VO 2 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 O 2 -pulse (+1.58 mL/beat, p=0.001) at peak exercise, but RPP, systolic and diastolic BP were unchanged. The VO 2 at AT and the VE/VCO 2 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 O 2 -pulse, (+2.73 mL/beat, p<0.001). Resting VO 2 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, VO 2 and O 2 -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.