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.

Keywords: Ch-CMP/Chagas cardiomyopathy; Chagas disease; heart failure; sudden cardiac death; trypanosoma.

Figure 1

Romaña sign. CDC/Dr. Mae Melvin Image - PHIL. https://phil.cdc.gov/Details.aspx?pid=15814 (accessed on 20 April 2021) https://www.cdc.gov/parasites/chagas/gen_info/vectors/index.html#list (accessed on 16 February 2021).

Figure 2

Life cycle of Trypanosoma cruzi. 1. In the triatomine’s midgut, trypomastigotes differentiate into epimastigotes, the main invertebrate replicating form, which multiplies by binary fission. Epimastigotes then migrate into the vector’s hindgut, differentiating into trypomastigotes in the vector’s feces. 2. Trypomastigotes excreted in feces enter the host through bite wounds or mucosal surfaces such as the conjunctiva. 3. Trypomastigotes enter the circulation and infect many types of nucleated cells. 4. Inside nucleated cells, trypomastigotes transform into amastigotes and multiply by binary fission, then once again convert to trypomastigotes and cause cell rupture. Trypomastigotes are released into the host’s circulation and can infect other cells to begin a new replicating cycle. 5. When a triatomine vector ingests a blood meal from an infected mammalian host, it becomes infected, completing the parasite’s cycle. 6. Infected triatomine vectors then host Trypanosoma cruzi, which proceeds to replicate inside the vector’s gut.

Figure 3

Commonly affected segments and terminal circulation segments.

Figure 4

Apical and basal inferolateral aneurysm with the corresponding scar at the same location. (A–C): CMR cine end-diastolic frame in apical 2, 3, and 4 chamber views, (D–F): CMR cine end-systolic frame in apical 2, 3, and 4 chamber views, (G–I): CMR-LGE in apical 2, 3, and 4 chamber views.