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

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)

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Scientific publications (7)
(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)
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; COELHO, OTAVIO RIZZI; NEILAN, TOMAS G.; JEROSCH-HEROLD, MICHAEL; COELHO-FILHO, OTAVIO RIZZI. Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy. SCIENTIFIC REPORTS, v. 11, n. 1 AUG 24 2021. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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; MODOLO, RODRIGO; NADRUZ, WILSON; FERNANDES DE CARVALHO, LUIS SERGIO; COELHO-FILHO, OTAVIO R. Serum potassium levels provide prognostic information in symptomatic heart failure beyond traditional clinical variables. ESC HEART FAILURE, MAR 2021. Web of Science Citations: 0.
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; RAMOS, CELSO DARIO; DERTKIGIL, SERGIO S.; SCHREIBER, ROBERTO; SPOSITO, ANDREI; MATOS-SOUZA, JOSE ROBERTO; BERWANGER, OTAVIO; JEROSCH-HEROLD, MICHAEL; COELHO-FILHO, OTAVIO RIZZI. 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. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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; CENDES, FERNANDO; COELHO, OTAVIO RIZZI; JEROSCH-HEROLD, MICHAEL; COELHO-FILHO, OTAVIO RIZZI. 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. Web of Science Citations: 13.

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