Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance

Abstract

Background: Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR).

Methods and results: Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003).

Conclusions: We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.

Keywords: Chagas’ heart disease; Gender differences; Myocardial dysfunction; Myocardial fibrosis.

Fig. 1

LGE frequency in male and female patients with Chagas’ heart disease. “n” illustrates the total of analyzed segments

Fig. 2

Examples of CMR, invasive and CT angiography in two representative patients with Chagas’ heart disease. First patient (top row): a and b CMR reveals transmural LGE pattern in the LV lateral wall (yellow arrow) with concomitant septal midwall LGE (white arrow) and, by invasive angiography, (c and d) normal coronary arteries. Second patient (bottom row): (e) cine-CMR image reveals a classical Chagas’ heart disease finding, the vorticle aneurysm (red arrow), (f and g) LGE reveals subendocardial pattern in the lateral wall (yellow arrow) and, by CT angiography, (h and i) normal coronary arteries. Blue arrow (f and g) indicating the region of interest (ROI) for calculating the mean signal intensity (SI) of the reference normal myocardium

Fig. 3

LGE patterns in male and female patients with Chagas’ heart disease. “n” illustrates the absolute frequency of the LGE pattern divided by the total of analyzed segments

Fig. 4

Sex-specific correlations between MF and LVEF

Fig. 5

a Unadjusted effect of gender on MF and b effects of gender and MF (10-unit increase) on LVEF. Model 1 demonstrates unadjusted effects of gender and MF on LVEF. Model 2 demonstrates the effect of gender on LVEF when adjusted to MF. Model 3 demonstrates the Model 2 additionally adjusted for CAD risk factors (age, diabetes mellitus, hypertension, hypercholesterolemia, body mass index, active smoking). Natural logarithm transformation was used to improve normality and/or homoscedasticity of residuals. The effect was calculated from exponential linear regression coefficients (100 × [e ^β − 1]). LVEF was defined as left ventricular ejection fraction, and MF myocardial fibrosis (%LV Mass)

Fig. 6

Mediation model illustrating indirect effect (through MF) and direct effect of gender on LVEF. β-coefficients of log-level linear regressions of Sobel-Goodman mediation tests. LVEF was defined as left ventricular ejection fraction, and MF myocardial fibrosis (%LV Mass)