The effect of NEPRIlysin (LCZ696) on EXercise TOLerance, muscle vasodilatation, muscle strength and body composition in patients with Heart Failure - NEPRIExTol-HF Trial

• Grant number: 16/24306-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2017
• End date: July 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Antonio Carlos Pereira-Barretto
• Grantee: Marcelo Rodrigues dos Santos
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 19/14938-7 - A 28-day study to evaluate the physiologic effects of beta-nicotinamide mononucleotide on hepatic fat, insulin sensitivity, muscle bioenergetics and performance, and other NAD+-dependent physiologic processes in middle-aged and older men and women, BE.EP.PD

Abstract

Heart failure (HF) with reduced ventricular ejection fraction is a disease that affects around 5.7 million people in the United States, with a mortality rate of approximately 50% within 5 years. HF is characterized by an exacerbation of the renin-angiotensin-aldosterone system (RAAS), which leads to an increase in sympathetic nerve outflow, peripheral vasoconstriction, and reduced functional capacity. Moreover, many clinical trials have been developed for the treatment of HF patients focused on inhibition of RAAS, such as enalapril. Nevertheless, hospitalization and mortality rates in this population are excessive. However, studies with new drugs, such as the combination of valsartan/sacubitril, also known as LCZ696, have demonstrated important clinical impact on the morbidity and mortality outcomes in HF population. However, the effect of LCZ696 on the pathophysiological mechanisms of HF such as exercise tolerance (peak VO2) and peripheral muscle blood flow is not known. Since LCZ696 is a new drug with promising effects on the treatment of HF, the objective of the present study will be to evaluate the effect of LCZ696 in patients with HF on: 1) peak VO2, 2) 6-minute walk test, 3) peripheral muscle blood flow, 4) muscle strength, and 5) body composition.

Scientific publications

(12)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, MARCELO RODRIGUES; PEIXOTO DA FONSECA, GUILHERME WESLEY; SHERVENINAS, LETICIA PIRONATO; DE SOUZA, FRANCIS RIBEIRO; BATTAGLIA FILHO, ANTONIO CARLOS; NOVAES, CAIO EDUARDO; RODRIGUES PEREIRA, ROSA MARIA; NEGRAO, CARLOS EDUARDO; PEREIRA BARRETTO, ANTONIO CARLOS; DE NAZARE NUNES ALVES, MARIA-JANIEIRE. Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure. ESC HEART FAILURE, v. 7, n. 3, MAR 2020. (15/22814-5, 16/24833-0, 16/24306-0)

DE SOUZA, FRANCIS RIBEIRO; DOS SANTOS, MARCELO RODRIGUES; PORELLO, RAFAEL ARMANI; PEIXOTO DA FONSECA, GUILHERME WESLEY; CARRARI SAYEGH, ANA LUIZA; LIMA, THAIS PINHEIRO; FERREIRA, FABIANA DIAS; DE OLIVEIRA, TIAGO FRANCO; YONAMINE, MAURICIO; TAKAYAMA, LILIAM; et al. Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users. ATHEROSCLEROSIS, v. 283, p. 100-105, APR 2019. (12/10527-3, 16/24306-0)

PEIXOTO DA FONSECA, GUILHERME WESLEY; DOS SANTOS, MARCELO RODRIGUES; DE SOUZA, FRANCIS RIBEIRO; DA COSTA, MARCEL JOSE A.; VON HAEHLING, STEPHAN; TAKAYAMA, LILIAM; PEREIRA, ROSA MARIA R.; NEGRAO, CARLOS EDUARDO; ANKER, STEFAN D.; DE NAZARE NUNES ALVES, MARIA JANIEIRE. Desequilíbrio Simpático-Vagal está Associado com Sarcopenia em Pacientes do Sexo Masculino com Insuficiência Cardíaca. Arquivos Brasileiros de Cardiologia, v. 112, n. 6, p. 739-746, JUN 2019. (16/24306-0, 15/22814-5)

DOS SANTOS, MARCELO RODRIGUES; NUNES ALVES, MARIA-JANIEIRE DE NAZARE; JORDAO, CAMILA PAIXAO; NOVAES PINTO, CAIO EDUARDO; SOUZA CORREA, KELLY THAYANE; DE SOUZA, FRANCIS RIBEIRO; PEIXOTO DA FONSECA, GUILHERME WESLEY; TOMAZ FILHO, JOAQUIM; COSTA, MARCEL; RODRIGUES PEREIRA, ROSA MARIA; et al. Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study. AMERICAN HEART JOURNAL, v. 239, p. 1-10, SEP 2021. (16/24833-0, 16/24306-0, 19/14938-7)

PEIXOTO DA FONSECA, GUILHERME WESLEY; MACEDO, TANIA GARFIAS; EBNER, NICOLE; DOS SANTOS, MARCELO RODRIGUES; DE SOUZA, FRANCIS RIBEIRO; MADY, CHARLES; TAKAYAMA, LILIAM; RODRIGUES PEREIRA, ROSA MARIA; DOEHNER, WOLFRAM; ANKER, STEFAN D.; et al. Ms, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies. ESC HEART FAILURE, AUG 2020. (15/22814-5, 16/24306-0)

DOS SANTOS, M. R.; FONSECA, G. W. P.; SHERVENINAS, L.; SOUZA, F. R.; BATTAGLIA FILHO, A. C.; PEREIRA, R. M. R.; NEGRAO, C. E.; ALVES, M. J. N. N.; BARRETTO, A. C. P.. Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure. EUROPEAN HEART JOURNAL, v. 40, p. 1-pg., 2019-10-01. (16/24306-0, 16/24833-0)

DE SOUZA, FRANCIS RIBEIRO; MOTTA-SANTOS, DAISY; SOARES, DOUGLAS DOS SANTOS; DE LIMA, JULIANA BEUST; CARDOZO, GUSTAVO GONCALVES; PINTO GUIMARAES, LUCIANO SANTOS; NEGRAO, CARLOS EDUARDO; DOS SANTOS, MARCELO RODRIGUES. ssociation of physical activity levels and the prevalence of COVID-19-associated hospitalizatio. JOURNAL OF SCIENCE AND MEDICINE IN SPORT, v. 24, n. 9, p. 913-918, SEP 2021. (16/24306-0, 19/14938-7)

FONSECA, G. W. P. D.; DOS SANTOS, MARCELO RODRIGUES; DE SOUZA, FRANCIS RIBEIRO; TAKAYAMA, LILIAM; RODRIGUES PEREIRA, ROSA MARIA; NEGRAO, CARLOS EDUARDO; NUNES ALVES, MARIA-JANIEIRE DE NAZARE. Discriminating sarcopenia in overweight/obese male patients with heart failure: the influence of body mass index. ESC HEART FAILURE, v. 7, n. 1, DEC 2019. (15/22814-5, 16/24306-0)

BISPO, HENRIQUE NUNES; RONDON, EDUARDO; DOS SANTOS, MARCELO RODRIGUES; DE SOUZA, FRANCIS RIBEIRO; DA COSTA, MARCEL JOSE ANDRADE; PEREIRA, ROSA MARIA RODRIGUES; NEGRAO, CARLOS EDUARDO; CARSON, BRIAN P.; ALVES, MARIA-JANIEIRE DE NAZARE NUNES; DA FONSECA, GUILHERME WESLEY PEIXOTO. Association of Sarcopenia and Oxygen Uptake Efficiency Slope in Male Patients With Heart Failure. Journal of Cardiopulmonary Rehabilitation and Prevention, v. 44, n. 4, p. 7-pg., 2024-07-01. (16/24306-0)

DOS SANTOS, M. R.; FONSECA, G. W. P.; SOUZA, F. R.; CASTRO, V. M.; TAKAYAMA, L.; PEREIRA, R. M. R.; NEGRAO, C. E.; ALVES, M. J. N. N.. Discriminating sarcopenia in male patients with heart failure: the influence of body mass index. EUROPEAN HEART JOURNAL, v. 39, p. 1-pg., 2018-08-01. (16/24306-0)

PEIXOTO DA FONSECA, GUILHERME WESLEY; MACEDO, TANIA GARFIAS; EBNER, NICOLE; DOS SANTOS, MARCELO RODRIGUES; DE SOUZA, FRANCIS RIBEIRO; MADY, CHARLES; TAKAYAMA, LILIAM; RODRIGUES PEREIRA, ROSA MARIA; DOEHNER, WOLFRAM; ANKER, STEFAN D.; et al. Ms, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies. ESC HEART FAILURE, v. 7, n. 5, p. 9-pg., 2020-08-28. (15/22814-5, 16/24306-0)

PORELLO, RAFAEL ARMANI; DOS SANTOS, MARCELO RODRIGUES; DE SOUZA, FRANCIS RIBEIRO; PEIXOTO DA FONSECA, GUILHERME WESLEY; CARRARI SAYEGH, ANA LUIZA; DE OLIVEIRA, TIAGO FRANCO; AKIHO, CESAR ABREU; YONAMINE, MAURICIO; RODRIGUES PEREIRA, ROSA MARIA; NEGRAO, CARLOS EDUARDO; et al. Neurovascular Response during Exercise and Mental Stress in Anabolic Steroid Users. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 50, n. 3, p. 596-602, MAR 2018. (12/10527-3, 16/24306-0)