Characterization of interstitial fibrosis and cardiomyocyte hypertrophy by cardiac MRI: implication on early remodeling and on the transition to heart failure

• Grant number: 15/15402-2
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: October 01, 2016
• End date: September 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Otávio Rizzi Coelho-Filho
• Grantee: Otávio Rizzi Coelho-Filho
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Andrei Carvalho Sposito ; Cesar Higa Nomura ; José Roberto Matos Souza ; Lígia de Moraes Antunes Corrêa ; Michael Jerosch-Herold ; Otávio Rizzi Coelho ; Ravi Shah ; Rodrigo Antunes de Vasconcelos ; Wilson Nadruz Junior
• Associated research grant(s): 16/26209-1 - Multi-user equipament approved in grat 2015/15402-2: cardiorespiratory diagnostic system, AP.EMU; 17/03708-5 - Multi-user equipament approved in the grant 2015/15402-2: ecocardiograma, AP.EMU

Abstract

Cardiac hypertrophy is one of the earliest manifestations of myocardial disease, representing a modifiable, prognostic response to hemodynamic stimuli across physiologic (e.g., exercise) and pathologic states (e.g., hypertension, aortic stenosis). The extent of myocardial hypertrophy is determined by a combination of cardiomyocyte size and extracellular volume (ECV) expansion/interstitial fibrosis: while physiologic (exercise-induced) hypertrophy reflects mostly reversible cardiomyocyte hypertrophy, pathologic hypertrophy (e.g., in heart failure) is a combination of both interstitial fibrosis (potentially irreversible) and cardiomyocyte hypertro-phy (reversible). Current methods to delineate the potential for LV reverse remodeling (e.g., natriuretic peptides and echocardiographic or clinical markers) detect primarily advanced disease, missing a critical opportunity to intervene and follow patients at an early disease phase where myocardial pathology may be reversible. Therefore, establishing novel, quantitative metrics of myocardial tissue phenotype that define a transition from hypertrophy to fibrosis, and then to irreversible LV remodeling/dysfunction may facilitate targeting therapies at a modifiable stage of disease in HF. Our group has recently extended cardiac T1 mapping MRI techniques to quantify the intracellular lifetime of water (Äic) serially as an index of cardiomyocyte diameter, validating this technique histologically in mouse models of pressure overload. The central hypothesis of this application is that these novel MRI metrics will define the role of fibrosis and cardiomyocyte size in the development of LV remodeling/HF and will be associated with prognostically important indices in HF development. (AU)

Scientific publications

(11)

(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)

PEZEL, THEO; SILVA, LUIS MIGUEL; BAU, ADRIANA APARECIA; TEIXIERA, ADHERBAL; JEROSCH-HEROLD, MICHAEL; COELHO-FILHO, OTAVIO R.. What Is the Clinical Impact of Stress CMR After the ISCHEMIA Trial?. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 8, JUN 4 2021. (16/26209-1, 15/15402-2, 17/03708-5)

JEROSCH-HEROLD, MICHAEL; RICKERS, CARSTEN; PETERSEN, STEFFEN E. E.; COELHO-FILHO, OTAVIO R.. Myocardial Tissue Characterization in Cardiac Magnetic Resonance Studies of Patients Recovering From COVID-19: A Meta-Analysis. JOURNAL OF THE AMERICAN HEART ASSOCIATION, v. 12, n. 6, p. 22-pg., 2023-03-21. (17/03708-5, 16/26209-1, 15/15402-2)

TAKAZAKI, KAREN A. G.; QUINAGLIA, THIAGO; VENANCIO, THIAGO D.; MARTINEZ, ALBERTO R. M.; SHAH, RAVI V.; NEILAN, TOMAS G.; JEROSCH-HEROLD, MICHAEL; COELHO-FILHO, OTAVIO R.; FRANCA, JR., MARCONDES C.. Pre-clinical left ventricular myocardial remodeling in patients with Friedreich's ataxia: A cardiac MRI study. PLoS One, v. 16, n. 3, MAR 26 2021. (15/15402-2, 13/01766-7, 16/26209-1, 17/03708-5)

DE SOUZA, THIAGO FERREIRA; SILVA, THIAGO QUINAGLIA A. C.; COSTA, FELIPE OSORIO; SHAH, RAVI; NEILAN, TOMAS G.; VELLOSO, LICIO; NADRUZ, WILSON; BRENELLI, FABRICIO; SPOSITO, ANDREI CARVALHO; MATOS-SOUZA, JOSE ROBERTO; et al. Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease. JACC-CARDIOVASCULAR IMAGING, v. 11, n. 8, p. 1044-1055, AUG 2018. (15/15402-2)

DE SOUZA, THIAGO FERREIRA; QUINAGLIA, THIAGO; NEILAN, TOMAS G.; COELHO-FILHO, OTAVIO R.. Assessment of Cardiotoxicity of Cancer Chemotherapy The Value of Cardiac MR Imaging. MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA, v. 27, n. 3, p. 533+, AUG 2019. (15/15402-2)

CARDOSO, FERNANDO BIANCHINI; ANTUNES-CORREA, LIGIA M.; SILVA, THIAGO QUINAGLIA A. C.; SILVA, LUIS MIGUEL; TOLEDO, CAMILLA; RIBEIRO, VINICIUS CITELLI; PAIM, LAYDE R.; NEILAN, TOMAS G.; VELLOSO, LICIO; NADRUZ, WILSON; et al. Noninvasive imaging assessment of rehabilitation therapy in heart failure with preserved and reduced left ventricular ejection fraction (IMAGING-REHAB-HF): design and rationale. THERAPEUTIC ADVANCES IN CHRONIC DISEASE, v. 10, AUG 2019. (15/15402-2)

DE SOUZA, THIAGO FERREIRA; SILVA, THIAGO QUINAGLIA; ANTUNES-CORREA, LIGIA; DROBNI, ZSOFIA D.; COSTA, FELIPE OSORIO; DERTKIGIL, SERGIO SAN JUAN; NADRUZ, WILSON; BRENELLI, FACRICIO; SPOSITO, ANDREI C.; MATOS-SOUZA JR, JOSE ROBERTO; et al. Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy. SCIENTIFIC REPORTS, v. 11, n. 1, AUG 24 2021. (16/26209-1, 15/15402-2, 17/03708-5)

COY-CANGUCU, ANDREA; ANTUNES-CORREA, LIGIA M.; MAZZALI, MARILDA; ABRAO, PAULA; RONCO, FERNANDA; TEIXEIRA, CINTHIA MONTENEGRO; VIANA, KARYNNA PIMENTEL; CORDEIRO, GUILHERME; LONGATO, MAURICIO; COELHO, OTAVIO RIZZI; et al. Prognostic role of renal replacement therapy among hospitalized patients with heart failure in the Brazilian national public health system. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 10, p. 12-pg., 2023-08-23. (15/15402-2)

GEMME, CRISTIANE NARDI; SILVA, THIAGO QUINAGLIA A. C.; MARTINS, LUIZ C.; DA SILVA, LUIS MIGUEL; PAIM, LAYDE ROSANE; SPOSITO, ANDREI; NADRUZ, WILSON; FERNANDES, FABIO; DERTKIGIL, SERGIO SAN JUAN; WANDERLEY, JAMIRO DA SILVA; et al. Diffuse Myocardial Fibrosis and Cardiomyocyte Diameter Are Associated With Heart Failure Symptoms in Chagas Cardiomyopathy. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 9, p. 12-pg., 2022-06-17. (15/15402-2, 16/26209-1, 17/03708-5)

SILVA, THIAGO QUINAGLIA A. C.; PEZEL, THEO; JEROSCH-HEROLD, MICHAEL; COELHO-FILHO, OTAVIO R.. The Role and Advantages of Cardiac Magnetic Resonance in the Diagnosis of Myocardial Ischemia. JOURNAL OF THORACIC IMAGING, v. 38, n. 4, p. 12-pg., 2023-07-01. (15/15402-2)

TOLEDO, CAMILA CRISTIANE; VELLOSA SCHWARTZMANN, PEDRO; MIGUEL SILVA, LUIS; DA SILVA FERREIRA, GABRIEL; BIANCHINI CARDOSO, FERNANDO; CITELLI RIBEIRO, VINICIUS; PAIM, LAYDE ROSANE; ANTUNES-CORREA, LIGIA M.; CARVALHO SPOSITO, ANDREI; MATOS SOUZA, JOSE ROBERTO; et al. Serum potassium levels provide prognostic information in symptomatic heart failure beyond traditional clinical variables. ESC HEART FAILURE, MAR 2021. (17/03708-5, 15/15402-2, 16/26209-1)