José Luis Winter1, Pablo F Castro2, Juan Carlos Quintana1, Rodrigo Altamirano1, Andres Enriquez1, Hugo E Verdejo1, Jorge E Jalil3, Rosemarie Mellado4, Roberto Concepción5, Pablo Sepúlveda6, Victor Rossel7, Luis Sepúlveda8, Mario Chiong9, Lorena García9, Sergio Lavandero10. 1. Advanced Center for Chonic Diseases, Universidad de Chile and Pontificia Universidad Católica de Chile, Santiago, Chile; División de Enfermedades Cardiovasculares and Departamento de Medicina Nuclear, Facultad Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. 2. Advanced Center for Chonic Diseases, Universidad de Chile and Pontificia Universidad Católica de Chile, Santiago, Chile; División de Enfermedades Cardiovasculares and Departamento de Medicina Nuclear, Facultad Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: pcastro@med.puc.cl. 3. División de Enfermedades Cardiovasculares and Departamento de Medicina Nuclear, Facultad Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. 4. Facultad Química, Pontificia Universidad Católica de Chile, Santiago, Chile. 5. Hospital Dipreca, Santiago, Chile. 6. Hospital San Juan de Dios, Facultad Medicina, Santiago, Chile. 7. Hospital Salvador, Facultad Medicina, Santiago, Chile. 8. Hospital Clínico, Facultad Medicina, Santiago, Chile. 9. Advanced Center for Chonic Diseases, Universidad de Chile and Pontificia Universidad Católica de Chile, Santiago, Chile; Centro Estudios Moleculares de la Célula, Facultad Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago, Chile. 10. Advanced Center for Chonic Diseases, Universidad de Chile and Pontificia Universidad Católica de Chile, Santiago, Chile; Centro Estudios Moleculares de la Célula, Facultad Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago, Chile; Cardiology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Abstract
OBJECTIVES: Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. METHODS AND RESULTS:Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, andquality of life were assessed at baseline and after TMZ treatment. Leftventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro-B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg(-1) min(-1) vs 23.0 ± 7.2 mL kg(-1) min(-1); P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with (18)FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). CONCLUSIONS: In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life.
RCT Entities:
OBJECTIVES:Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. METHODS AND RESULTS: Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro-B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg(-1) min(-1) vs 23.0 ± 7.2 mL kg(-1) min(-1); P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with (18)FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). CONCLUSIONS: In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life.
Authors: Rong Tian; Wilson S. Colucci; Zoltan Arany; Markus M. Bachschmid; Scott W. Ballinger; Sihem Boudina; James E. Bruce; David W. Busija; Sergey Dikalov; Gerald W. Dorn; Zorina S. Galis; Roberta A. Gottlieb; Daniel P. Kelly; Richard N. Kitsis; Mark J. Kohr; Daniel Levy; E. Douglas Lewandowski; Joseph M. McClung; Daria Mochly-Rosen; Kevin D. O'Brien; Brian O'Rourke; Joon-Young Park; Peipei Ping; Michael N. Sack; Shey-Shing Sheu; Yang Shi; Sruti Shiva; Douglas C. Wallace; Robert G. Weiss; Hilary J. Vernon; Renee Wong; Lisa Schwartz Longacre Journal: Circulation Date: 2019-10-01 Impact factor: 29.690