Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort

Buss, Lewis; Bes, Taniela Marli; Pereira, Alexandre C.; Natany, Larissa; Oliveira, Cláudia Di Lorenzo; Ribeiro, Antônio Luiz Pinho; Sabino, Éster Cerdeira

doi:10.1590/s1678-9946202163031

Cited by 4 publications

(6 citation statements)

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“…Cardiomyopathy among T. cruzi –seropositive and –seronegative blood donors was defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms. 18 All patients with established cardiomyopathy recruited from the outpatient service had left ventricular systolic dysfunction.…”

Section: Methodsmentioning

confidence: 99%

“…New-onset cardiomyopathy was defined as the presence of left ventricular systolic dysfunction (left ventricular ejection fraction <50%) or QRS complex duration ≥120 ms in participants undergoing cardiovascular assessment at the follow-up visit, but in whom cardiomyopathy was absent at the baseline visit. 18 Using this definition, our study design is at risk of a survivorship bias, whereby participants with new-onset cardiomyopathy were more likely to die and thus not attend the follow-up visit. This would lead to an underestimate of the true incidence of cardiomyopathy because of differential loss to follow-up.…”

Section: Outcome Definition and Analytic Groupsmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Outcome Definition and Analytic Groupsmentioning

confidence: 99%

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

et al. 2021

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“…The independent variables were sociodemographic (age, income, number of people in the household, sex, skin color, knowledge of how to read and write, and education), behavioral (smoking, physical activity, and alcoholic beverage consumption), and clinical (presence of comorbidities, ECG changes, and echocardiogram changes) characteristics. The clinical variable, presence of cardiomyopathy, was classified using the following criteria: left ventricular ejection fraction <50% and/or QRS interval ≥120 ms 24 , 26 .…”

Section: Methodsmentioning

confidence: 99%

Chagas disease and perceived quality of life: a cross-sectional study

Baldoni,

Quintino,

Oliveira

et al. 2023

Rev. Soc. Bras. Med. Trop.

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Background: Chagas disease (ChD) is a neglected tropical disease that is caused by the protozoan parasite Trypanosoma cruzi and can negatively impact quality of life (QoL). This study aimed to assess and compare QoL between individuals with and without ChD. Methods: This cross-sectional study was performed within a concurrent cohort study (REDS). The participants were derived from two blood donation centers: São Paulo capital and Montes Claros, Minas Gerais, Brazil. Participants with ChD were identified in blood donations by serological diagnosis between 2008 and 2010, and those without ChD were donors with negative serology identified during the same period. QoL was assessed using the World Health Organization Quality of Life-BREF questionnaire. Logistic regression was used to compare sociodemographic and clinical characteristics between the groups, and mean, standard deviation, and beta regression were used to compare QoL. Results: In total, 611 individuals participated in the study (328 with ChD and 283 without ChD). Participants with ChD had lower QoL in the physical (p=0.02) and psychological (p<0.01) domains than did individuals without CD. Conclusions: Individuals with ChD had worse QoL perceptions. These results provide a comprehensive understanding of the impact of ChD on individuals' QoL, while also highlighting potential opportunities for improving the care and treatment of those affected.

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“…We used a previously validated definition of Chagas Cardiomyopathy for the Brazilian population [ 7 ]. Briefly, we have considered all participants with major or minor typical ECG abnormalities to have CCC.…”

Section: Methodsmentioning

confidence: 99%

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature

et al. 2022

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Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/Principal findings We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10−9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302–5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. Conclusions/Significance We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.

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Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort

Abstract: This is an open-access article distributed under the terms of the Creative Commons Attribution License.

Cited by 4 publications

References 16 publications

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

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

Chagas disease and perceived quality of life: a cross-sectional study

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature

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