AUTHOR=Nardi Gemme Cristiane , Silva Thiago Quinaglia A. C. , Martins Luiz C. , da Silva Luis Miguel , Paim Layde Rosane , Sposito Andrei , Nadruz Wilson , Fernandes Fabio , San Juan Dertkigil Sergio , da Silva Wanderley Jamiro , de Almeida Eros A. , Metze Konradin , Neilan Tomas G. , Jerosch-Herold Michael , Coelho-Filho Otávio R. 

TITLE=Diffuse Myocardial Fibrosis and Cardiomyocyte Diameter Are Associated With Heart Failure Symptoms in Chagas Cardiomyopathy

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.880151

DOI=10.3389/fcvm.2022.880151

ISSN=2297-055X

ABSTRACT=Background: Chronic Chagas Cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR). 
Methods: We performed a prospective observational cohort of consecutive CCC patients with a CMR protocol including ventricular function, myocardial T1, and late-gadolinium-enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CVdeath. 
Results: Thirty-seven patients with intermediate to high risk CCC were enrolled (Chagas Rassi score ≥7, mean LV ejection fraction (EF) 32±16%). Myocardial ECV (0.40±0.07) correlated with Rassi score (r=0.43; P=0.009), higher NYHA class, and LVEF (r=-0.51; P=0.0015). τic, decreased linearly with NYHA class (P=0.007 for non-parametric test of linear trend) and showed a positive association with LVEF (r=0.47; P=0.004). Over a median follow-up of 734 days (range: 6-2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (HR=1.3; 95 % CI=[1.0, 1.8]; P=0.028) and ECV (HR=3.4 for 0.1 change, 95% CI=[1.1, 11.0], P=0.039) were simultaneously associated with CV death. 
Conclusion: In patients with intermediate to high risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and heart failure severity. Exploratory analysis indicates that ECV may have prognostic value to identify CCC patients at higher risk for cardiovascular events.