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

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

doi:10.3389/fcvm.2022.880151

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

Front Cardiovasc Med. 2022 Jun 17:9:880151. doi: 10.3389/fcvm.2022.880151. eCollection 2022.

Authors

Cristiane Nardi Gemme¹, Thiago Quinaglia A C Silva^{1

2}, Luiz C Martins¹, Luis Miguel da Silva¹, Layde Rosane Paim¹, Andrei Sposito¹, Wilson Nadruz¹, Fabio Fernandes³, Sergio San Juan Dertkigil¹, Jamiro da Silva Wanderley¹, Eros A de Almeida¹, Konradin Metze¹, Tomas G Neilan², Michael Jerosch-Herold⁴, Otávio R Coelho-Filho¹

Affiliations

¹ Faculdade de Ciências Médicas, Universidade Estadual de Campinas, São Paulo, Brazil.
² Division of Cardiology, Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
³ Cardiomyopathy Unit, Heart Institute, University of São Paulo, São Paulo, Brazil.
⁴ Non-invasive Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.

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 patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τ_ic, 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 τ_ic with CV death.

Results: A total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = -0.51; P = 0.0015). τ_ic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (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 (heart rate [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 HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.

Keywords: Chagas disease; cardiac magnetic resonance; cardiomyocyte diameter; heart failure; interstitial fibrosis.

Grants and funding

K24 HL150238/HL/NHLBI NIH HHS/United States