Chagas Cardiomyopathy: From Romaña Sign to Heart Failure and Sudden Cardiac Death

Abstract

Despite nearly a century of research and accounting for the highest disease burden of any parasitic disease in the Western Hemisphere, Chagas disease (CD) is still a challenging diagnosis, primarily due to its poor recognition outside of Latin America. Although initially considered endemic to Central and South America, globalization, urbanization, and increased migration have spread the disease worldwide in the last few years, making it a significant public health threat. The international medical community’s apparent lack of interest in this disease that was previously thought to be geographically restricted has delayed research on the complex host–parasite relationship that determines myocardial involvement and its differential behavior from other forms of cardiomyopathy, particularly regarding treatment strategies. Multiple cellular and molecular mechanisms that contribute to degenerative, inflammatory, and fibrotic myocardial responses have been identified and warrant further research to expand the therapeutic arsenal and impact the high burden attributed to CD. Altogether, cardiac dysautonomia, microvascular disturbances, parasite-mediated myocardial damage, and chronic immune-mediated injury are responsible for the disease’s clinical manifestations, ranging from asymptomatic disease to severe cardiac and gastrointestinal involvement. It is crucial for healthcare workers to better understand CD transmission and disease dynamics, including its behavior on both its acute and chronic phases, to make adequate and evidence-based decisions regarding the disease. This review aims to summarize the most recent information on the epidemiology, pathogenesis, clinical presentation, diagnosis, screening, and treatment of CD, emphasizing on Chagasic cardiomyopathy’s (Ch-CMP) clinical presentation and pathobiological mechanisms leading to sudden cardiac death.

Molecular and Clinical Aspects of Chronic Manifestations in Chagas Disease: A State-of-the-Art Review

“…Several pathophysiological processes have been identified to impact the development of Ch-CMP. However, four cornerstone mechanisms play a crucial role: cardiac autonomic dysfunction, microvascular disturbances, parasite-dependent myocardial damage, and T. cruzi immune-mediated cardiac tissue injury (Figure 4) [113,114].…”

“…Cardiac autonomic dysfunction, the first of the pathophysiological mechanisms, impairs the parasympathetic nervous system's ability to keep a fine-tuned control of the heart rate and rhythm [113,114]. This process is mainly caused by direct damage to intramural neurons and ganglionic damage to neuronal somas and peripheral axonal projections; moreover, parasite-induced autoimmune damage caused through CD4+ and CD8+ Tcells also contributes to the autonomic abnormalities seen in Ch-CMP [115,116].…”

“…Given that these phenomena occur at the microcirculation, the most affected areas are distal or "watershed" perfusion areas, in particular, localized at the apex and at the basal inferolateral wall. These segments are the most commonly affected with focal fibrosis and aneurysm formation [113,119,120].…”

“…This imaging modality has proven to assess with high precision and accuracy the systolic function of the both ventricles in patients with Ch-CMP with equal or even superior results compared to TTE [154,155]. Moreover, recent studies conducted in tertiary care centers have shown that late gadolinium enhancement analysis (LGE) can be used for optimal assessment of disease severity and can also act as a surrogate for prognosis in patients with overt Ch-CMP depending on the amount of scar found [113,[156][157][158][159][160]. For over 20 years, tissular edema identified both by traditional black blood imaging sequencing and more recently using T1 and T2 mapping, has also been described in Ch-CMP although its clinical application is still to be determined [161][162][163][164].…”

Trypanosoma cruzi in Nonischemic Cardiomyopathy Patients, Houston, Texas, USA

“…This process can lead to progressive heart failure years later for some patients. Chagas cardiomyopathy patients can seek treatment for malignant ventricular arrhythmias, aneurysms, thromboembolism, or sudden cardiac death ( 2 ). Despite advances in our understanding of the pathogenic pathways, why some patients have onset of progressive cardiac disease whereas others remain in a persistent subclinical indeterminate disease remain unknown.…”