Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi –Seropositive Individuals

Abstract

Background: There are few contemporary cohorts of Trypanosoma cruzi -seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi -seropositive blood donors. T. cruzi -seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, electrocardiogram, and echocardiogram at enrollment (2008 to 2010) and at follow-up (2018 to 2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% and/or QRS complex duration ≥ 120 ms. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. Results: We enrolled 499 T. cruzi -seropositive donors (age 48 ± 10 years, 52% male), 488 T. cruzi -seronegative donors (age 49 ± 10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48 ± 8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000py (17/114, 15%) in T. cruzi -seropositives with cardiomyopathy at baseline. Among T. cruzi -seropositive donors without cardiomyopathy at baseline mortality was 3.7 events/1000py (15/385, 4%), which was no different from T. cruzi -seronegative donors with 3.6 deaths/1000py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi -seropositive donors was 13.8 (95% CI 9.5-19.6) events/1000py (32/262, 12%) compared with 4.6 (95% CI 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI 3.6 - 15.0) events/1000py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted OR of 1.4, 95% CI 1.1-1.8). Conclusions: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti- T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.

Global, Regional, and National Trends of Chagas Disease from 1990 to 2019: Comprehensive Analysis of the Global Burden of Disease Study

“…At first, prevalence differences can be explained by biological, sociocultural, and behavioral factors, such as the exposure to the vector as a result of occupational activities, as there is evidence that suggests a potentially relevant role of vector transmission in working areas [ 26 27 ]. Moreover, male sex has been identified as an independent risk factor for progression from the indeterminate form of the disease to chronic Chagas cardiomyopathy, which may promote the diagnosis due to the onset of HF symptoms [ 28 ]. Regarding the burden of the disease, several studies have observed a higher risk of morbimortality in males due to cardiac complications of CD [ 29 ].…”

Estatística Cardiovascular – Brasil 2021

“…139 A incidência diferencial de cardiomiopatia atribuível à infecção por T. cruzi foi 1,85 por 100 pessoas-ano. 140…”

“…T. cruzi antibody level in the second visit was associated with development of cardiomyopathy (adjusted OR of 1.4, 95% CI 1.1-1.8) in the last visit. 140 …”

Anti-Trypanosoma cruzi antibody profiling in patients with Chagas disease treated with benznidazole assessed by genome phage display

“…The chronic phase is often asymptomatic and the majority of infected people will eventually die of natural causes or other illnesses. Only a fraction of them (approximately 30%) will develop, over the course of decades, the characteristic heart or gastrointestinal Chagas disease (estimated at 9.2 events/1,000 infected person-years) [ 5 ].…”