Chagas Heart Disease: Beyond a Single Complication, from Asymptomatic Disease to Heart Failure

Abstract

Chagas cardiomyopathy (CC), caused by the protozoan Trypanosoma cruzi, is an important cause of cardiovascular morbidity and mortality in developing countries. It is estimated that 6 to 7 million people worldwide are infected, and it is predicted that it will be responsible for 200,000 deaths by 2025. The World Health Organization (WHO) considers Chagas disease (CD) as a Neglected Tropical Disease (NTD), which must be acknowledged and detected in time, as it remains a clinical and diagnostic challenge in both endemic and non-endemic regions and at different levels of care. The literature on CC was analyzed by searching different databases (Medline, Cochrane Central, EMBASE, PubMed, Google Scholar, EBSCO) from 1968 until October 2022. Multicenter and bioinformatics trials, systematic and bibliographic reviews, international guidelines, and clinical cases were included. The reference lists of the included papers were checked. No linguistic restrictions or study designs were applied. This review is intended to address the current incidence and prevalence of CD and to identify the main pathogenic mechanisms, clinical presentation, and diagnosis of CC.

Keywords: Chagas cardiomyopathy (CC); Chagas disease; chronic Chagas cardiomyopathy (CCC); heart failure; myocarditis.

Figure 1

Flow diagram of selection process of eligible studies.

Figure 2

Global distribution of Chagas disease, based on official estimates, 2018 [11].

Figure 3

Life cycle of Trypanosoma cruzi. (A) Triatomines present two forms of the parasite: epimastigotes and metacyclic trypomastigotes. Epimastigotes will initiate their transformation to metacyclic trypomastigotes in the digestive tract of the triatomine (hindgut) after 8 to 10 days post-feeding. Trypomastigotes will gather in the rectal ampulla; during or shortly after blood ingestion, the kissing bug will defecate on the skin or near the mucous membranes (conjunctivae) of the vertebrate. (B) Entry of metacyclic trypomastigotes into the bloodstream, with subsequent infection of surrounding cells. Within the cells, they will transform into intracellular amastigotes, multiplying by binary fission. The amastigotes are able to lyse the cell and infect new ones or undergo differentiation into blood trypomastigotes and cause cell membrane rupture to disperse to other tissues. This cycle can be perpetuated, and the parasites can reinfect different host cells, with a predominance of muscle (myocardium) and neuronal cells [2,8,12,29,30,37,38,39,40].

Figure 4

Correlation of pathophysiological mechanisms with the clinical manifestations of CD. RBBB: right bundle branch block, VT: ventricular tachycardia, AF: atrial fibrillation, PVC: premature ventricular contractions, AFB: anterior fascicular block, CVE: cerebrovascular event, TR: tricuspid regurgitation, MI: mitral insufficiency, RV: right ventricle, biV: biventricular.

Figure 5

Clinical presentation and classification of heart failure secondary to T. cruzi infection are divided into four stages. * Annual mortality: a review of observational studies on predictors of mortality in chronic Chagas Disease [83]. Stages A, B (B1, B2), C, D are described in Table 1, according to the Latin American Guidelines for Diagnosis and Treatment of Chagas disease [82].

Figure 6

67-year-old woman was admitted to the emergency department for stable VT. (A,B) cardiac magnetic resonance shows LV lateral wall aneurysm in basal and middle thirds with late enhancement. (C,D) TTE(delate:-)–2DST shows the lateral aneurysm and the LV deformation. CD was confirmed by anti-Trypanosoma cruzi antibodies. Source: images taken at the Instituto Nacional de Cardiología, Ignacio Chávez (INCICh).

Figure 7

Coronary angiography and TTE study in a 74-year-old man with recurrent syncope and VT events who was diagnosed with CD due to the detection of anti-Trypanosoma cruzi antibodies and implanted with an automatic defibrillator. (A,B) Coronary angiography without evidence of lesions. (C,D) TTE with an apical aneurysm and another one in the lateral region of the LV in basal segments. Source: images taken at the Instituto Nacional de Cardiología, Ignacio Chávez (INCICh).

Figure 8

Cardiac magnetic resonance. Images in four chambers (upper row), two chambers (middle row), and short axis middle third (lower row). In the first column (a,d,g), images in diastole, the middle column (b,e,h) in systole, and the right column is inversion recovery sequence (c,f,i). Apical aneurysm (arrow), inferolateral thinning, and akinesia (arrowhead), with late transmural enhancement at this level, as well as a mid-wall septal late enhancement (dashed arrow), are shown. Source: images taken at the Instituto Nacional de Cardiología, Ignacio Chávez (INCICh).

Figure 9

Cardiac tomography in a 66-year-old man diagnosed with CD by detection of anti-Trypanosoma cruzi antibodies. (A) Perfusion study by nuclear cardiology (using ^99m Technetium-methoxyisobutylisonitrile- ^99m Tc-MIBI-) shows non-transmural infarction of the anterolateral and inferolateral wall in its basal thirds without residual ischemia: (a) upper line stress phase and (b) lower line resting phase. (B) Coronary tomography angiography study without evidence of coronary lesions, with 0 Agatston units and basal inferolateral LV aneurysm (arrow). Artifice by implantable automatic defibrillator cable in the right ventricle is observed. Source: images taken at the Instituto Nacional de Cardiología, Ignacio Chávez (INCICh).