Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

Abstract

There is ample experimental and clinical evidence of functional and structural microvascular abnormalities occurring in patients with Chagas cardiomyopathy, possibly due to the infl ammatory process and/or autonomic disturbances caused by Trypanosoma cruzi infection. Those microvascular derangements are likely to constitute at least an ancillary factor that potentiates and amplifi es the chronic infl ammation in myocardial tissue. It is possible to devise appropriate therapeutic interventions aimed at reverting or slowing the progression of the microvascular abnormalities to positively affect the natural history of Chagas cardiomyopathy.

Regional Myocardial Perfusion Disturbance in Experimental Chronic Chagas Cardiomyopathy

“…In fact, autopsy observations in humans (29) and experimental studies in CCC (14,30) have demonstrated structural and functional abnormalities of the coronary microcirculation that appear to be caused by the inflammatory infiltration into surrounding tissue (8,31) and appear to be associated with the production of vasoactive substances (32,33). These changes, including arteriolar spasm and intima proliferation leading to luminal obstruction (30), formation of occlusive platelet plugs (14), and vascular rarefaction (16), would lead to regional myocardial ischemia.…”

“…Although most affected individuals never show clinical symptoms, approximately 30% progress to chronic clinical disease, of which heart involvement is the most severe condition, frequently manifesting as dilated cardiomyopathy with heart failure syndrome, cardiac arrhythmia, thromboembolic events, and sudden death (4). Additionally, 30%-40% of patients have anginalike chest pain associated with ischemic electrocardiographic changes (5), segmental wall motion impairment (6), and reversible myocardial perfusion defects (MPDs) (7), which may lead to ischemic cardiomyopathy (8). However, coronary angiograms reveal normal subepicardial coronary arteries (9,10), suggesting coronary microvascular dysfunction (7,11,12).…”

Renal denervation in patients with heart failure secondary to Chagas' disease: A pilot randomized controlled trial

“…In Chagas' disease, abundant experimental and clinical evidences suggest the existence of microvascular abnormalities, possibly due to inflammatory and/or autonomic disturbances related to T. cruzi infection. Differently from other forms of cardiac disease, a direct and localized ischemic injury to the myocardial tissue appears to be an important modulator of the natural history of Chagas cardiomyopathy . In swines with left ventricle dysfunction, renal denervation appears to improve endothelial‐dependent and endothelial‐independent vasodilatory responses of large coronaries, which may contribute to improved left ventricular function during outcomes .…”

Organometallic gold(III) [Au(Hdamp)(L14)]Cl (L1 =SNS-donating thiosemicarbazone) complex protects mice against acuteT. cruziinfection

“…T. cruzi shows preferential tropism for the muscle tissue. Locally, the presence of parasites recruits inflammatory cells to control and eliminate parasitaemia and tissue parasitism, but eventually, this event leads to death caused by T. cruzi -induced myocarditis (38). Within the first 15 days of treatment, the reduction of both parasitaemia and cardiac parasitism (Fig.…”