Clinical effects of metoprolol in obstructive hypertrophic cardiomyopathy (TEMPO). A randomized, double-blinded, placebo-controlled crossover trial

Abstract

Abstract Background Treatment with beta blockers (BB) has been used for symptomatic relief in patients with obstructive hypertrophic cardiomyopathy (HCM) for decades. Even so, the guideline recommendation for the use of BB rests on expert opinions and observational cohort studies. Providing comprehensive high-quality data on the effects of BB in obstructive HCM is essential, especially in the context of newly developed pharmacological treatment strategies specifically targeting this disease (1). Purpose The study aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM. Methods This double-blinded, placebo-controlled, randomized crossover trial enrolled 30 patients with obstructive HCM and New York Heart Association (NYHA) class ≥ II symptoms from 1 May 2018 to 1 September 2020. Patients received metoprolol or placebo for two consecutive two-week periods in random order. The effect parameters were LVOT gradients, NYHA class, Canadian Cardiovascular Society (CCS) grading angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing. Results Compared with placebo, the LVOT gradient during metoprolol was lower at rest (25 [15–58] mmHg versus 72 [28–87] mmHg; p=0.007), at peak exercise (28 [18–40] mmHg versus 62 [31–113] mmHg; p<0.001), and post-exercise (45 [24–100] mmHg versus 115 [55–171] mmHg; p<0.0001) (figure 1). During metoprolol treatment, 14% of patients were in NYHA class III compared with 38% on placebo (p<0.01). Likewise, no patients were in CCS class ≥ III during metoprolol compared with 10% during placebo (p<0.01). These findings were confirmed by a higher KCCQ-OSS score during metoprolol (76.2 (16.2) versus 73.8 (19.5), p=0.039) (figure 2). Peak oxygen consumption did not differ between study arms. Conclusion Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. However, exercise capacity remained unchanged. Findings from the present study support the guideline recommendations that BB should be the first drug of choice in patients with obstructive HCM who develop symptoms. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo nordic foundation, Skibsreder Per Henriksen, R. og hustrus Foundation