Metoprolol improves symptoms, quality of life in obstructive hypertrophic cardiomyopathy
Two weeks of metoprolol improved left ventricular outflow tract gradients, symptoms and quality of life compared with placebo in patients with obstructive hypertrophic cardiomyopathy, according to results of the TEMPO trial.
According to data published in the Journal of the American College of Cardiology, N-terminal pro-B-type natriuretic peptide and measures of exercise capacity such as peak oxygen consumption and duration were unchanged during metoprolol use compared with placebo.
“The inotropic effects of catecholamine stimulation produced an increase in left ventricular outflow tract gradients, and this knowledge sparked an attempt to treat the condition with (beta-blockers),” Anne M. Dybro, MD, of the department of cardiology at Aarhus University Hospital, Denmark, and colleagues wrote. “The effects of (beta-blockers) are mediated by sympathetic modulation with a reduction in heart rate and ventricular contractility, thus leading to prolonged ventricular relaxation and diastolic filling that reduce left ventricular outflow tract obstruction. For decades, the mainstay of medical treatment in the management of patients with symptomatic left ventricular outflow tract obstruction has been nonvasodilating (beta-blockers) titrated to maximum tolerated dose. Even so, randomized, double-blind, placebo-controlled trials assessing the effects of (beta-blockers) are limited.”
For the randomized crossover TEMPO trial, researchers enrolled 29 patients with obstructive hypertrophic cardiomyopathy (HCM) of NYHA class II or more and randomly assigned them to metoprolol or placebo for two consecutive 2-week periods. Metoprolol effect parameters included LV outflow tract (LVOT) gradients, NYHA class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) and cardiopulmonary exercise testing.
Researchers reported that LVOT gradient was lower at rest (25 vs. 72 mm Hg; P = .007), peak exercise (28 vs. 62 mm Hg; P < .001) and postexercise (45 vs. 115 mm Hg; P < .0001) during weeks of metoprolol use compared with placebo.
According to the study, fewer patients were assessed as NYHA class III or higher during metoprolol weeks compared with placebo (14% vs. 38%; P < .01).
No patients were CCS class III or higher during metoprolol treatment compared with 10% during placebo use (P < .01).
Similarly, mean KCCQ-OSS was higher during metoprolol weeks compared with placebo weeks (76.2 vs. 73.8; P = .039).
“The study demonstrated that treatment with metoprolol is associated with a substantial, clinically relevant reduction in LVOT obstruction at rest, during exercise, and postexercise together with an improvement in symptoms and quality of life,” Dybro and colleagues wrote. “Analyses of cardiac function revealed that metoprolol treatment improves the longitudinal function of the left ventricle and reduces the degree of myocardial injury.”
Biomarker and exercise measures
According to the study, exercise capacity (P = .7), peak VO2 (P = .27) and NT-proBNP (P = .82) did not differ between metoprolol and placebo.
“One possible explanation may be that the heart rate substantially adds to cardiac output. In the present study, heart rate was reduced by 25%,” Dybro and colleagues wrote. “This decline may not have been fully compensated by an increase in stroke volume, even with prolonged diastolic filling.”
Implications for metoprolol use
In a related editorial, Ahmad Masri, MD, MS, cardiologist at the Oregon Health and Science University Center for Hypertrophic Cardiomyopathy and Amyloidosis, discussed the implications of the study on guiding the use of metoprolol in obstructive HCM.
“The trial provides important data to guide the use of metoprolol in the era of novel therapeutics in obstructive HCM, leaving us wondering whether: 1) the lack of improvement in exercise time, peak VO2 and NT-proBNP are related to the short, 2-week duration of the study vs. the inability of metoprolol to induce positive remodeling; and 2) metoprolol provides hemodynamic benefit by reducing LVOT gradients but possibly masks ongoing negative remodeling and progressive interstitial fibrosis as reflected by lack of improvement in left ventricular hypertrophy, diastolic function and NT-proBNP,” Masri wrote.
Reference:
Collapse