Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas dosease

Background: Autoimmunity and dysautonomia are established features of Chagas disease (ChD) that could be related to its pathogenesis. Our objective was to assess heart rate variability (HRV) and levels of anti-M2 receptors autoantibodies in ChD patients with and without left ventricular (LV) dysfunction, in order to establish if these abnormalities occur early and concomitantly in the course of the illness. Methods: ChD patients (n = 75) and healthy controls (n = 14) underwent a standardized protocol including Doppler echocardiogram, Holter monitoring, HRV analysis, and measurement of anti-M2 receptors autoantibodies (ELISA). ChD patients were divided accordingly by the absence (group 1, n = 45) or presence (group 2, n = 30) of LV dysfunction, defined as reduced LV ejection fraction (< 55%) or regional wall motion abnormalities (including ventricular aneurysm). Results: Both ChD groups displayed increased optical density values of anti-M2 cholinergic autoantibodies (Median (IQR): control = 1.98(0.51); ChD 1 = 2.76(0.97); ChD 2 = 2.72(1.34), p < .001) and reduced HF power of spectral analysis of HRV when compared to controls (Median (IQR) in ms2: control = 1087(2284); ChD 1 = 286(763); ChD 2 = 285(763), p < .001). M2 levels were significantly correlated with HF power values (r = - 0.32, p = 0.023), but not with LV ejection fraction. Conclusions: Anti-muscarinic autoantibodies and abnormal vagal modulation occur early in ChD patients, independently of the presence of LV dysfunction. Levels of antibodies against M2 muscarinic receptors were significantly and negatively correlated with HRV index HF power, suggesting an inhibitory effect of autoantibodies in vagal function.