Reverse remodelling and clinical outcomes in patients with chagas cardiomyopathy with reduced ejection fraction
Authors: Sampaio De Sousa Lira M , Silas Furquim S F , Daniel Catto De Marchi D C M , Pamela Camara Maciel P C M , Rafael Dantas R D , Fabio Fernandes F F , Barbara Maria Ianni B M I , Silvia Moreira Ayub Ferreira S M A F , Eduardo Gomes Lima E G L , Edimar Alcides Bocchi E A B 
Published: October 2024

Abstract

Introduction
Chagas disease affects around 8 million individuals globally and about 30% develop cardiac manifestations and, in time, heart failure with reduced ejection fraction (HFrEF). Chagas cardiomyopathy (CC) patients often have a poorer prognosis compared to other causes of HFrEF, owing to a higher rate of ventricular arrhythmias and thromboembolic conditions. Reverse remodelling (RR) has been linked to enhanced mortality and morbidity outcomes in HFrEF due to non-Chagas causes, but the effect of RR on CC prognosis is still unclear.

Methods
This retrospective study assessed 1043 patients diagnosed with CC via positive serology for Trypanosoma cruzi infection coupled with cardiopathy and ventricular dysfunction [left ventricular ejection fraction (LVEF) &lt; 40%] during the follow-up period from January 2006 to September 2021. The primary outcome measured included overall mortality and heart transplantation in relation to RR status. Propensity score matching was utilised to adjust for confounding factors. Positive reverse remodelling (PRR) was characterised as patients displaying improved LVEF, and negative reverse remodelling (NRR) as those with persistent ventricular dysfunction during follow-up.

Results
Initially, 221 (21.2%) were categorised as PRR and 822 (78.8%) as NRR. Participants in the PRR group were predominantly female (51.6% versus 41.4%; p &lt; 0.001), older [59 years (53 – 66) versus 56 years (47 – 64); p = 0.007], more prone to hypertension (43.4% versus 35.8%; p = 0.036), and presented with higher initial heart rates [70 bpm (60 – 80) versus 65 bpm (60 – 75); p = 0.002], systolic blood pressure [120 mmHg (110 – 130) versus 110 mmHg (100 – 120); p &lt; 0.001], diastolic blood pressure [80 mmHg (69 – 82) versus 70 mmHg (60 – 80); p &lt; 0.001], and LVEF [30.0% (26.0 – 35.0) versus 29% (25.0 – 34.0); p &lt; 0.001] compared to the NRR group. Moreover, the PRR group had a lower intake of beta-blockers (BB) (76.6% versus 87.0%; p = 0.004), spironolactone (38.5% versus 59.5%; p &lt; 0.001), and triple therapy (30.9% versus 50.4%; p &lt; 0.001). Following propensity score matching, 200 patients remained for the final analysis, with 100 in each group. Cox proportional hazards model analysis revealed PRR as an independent predictor [hazard ratio (HR): 0.367; 95% confidence interval (CI) 0.218 – 0.616; p &lt; 0.001] of mortality from all causes or heart transplantation. The PRR group exhibited a longer event-free survival duration than the NRR group (10.332 years; 95% CI 9.557 – 11.107 versus 7.348 years; 95% CI 6.606 – 8.089; p &lt; 0.001).

Discussion
This study suggests a positive association between the PRR and increased survival in patients with CHD and HFrEF. Previously published studies didn’t demonstrate this association, possibly due to the small number of patients included.

Conclusion
PRR predicts a better long-term survival free from all-cause mortality and cardiac transplantation in Chagas cardiomyopathy with LVEF &lt; 40%.Kaplan-Meier event-free survival curve