Mortality risk in chronic Chagas cardiomyopathy: a systematic review and meta‐analysis

Chadalawada, Sindhu; Rassi, Anis; Samara, Omar; Monzon, Anthony; Gudapati, Deepika; Barahona, Lilian Vargas; Hyson, Peter; Sillau, Stefan; Mestroni, Luisa; Taylor, Matthew R.G.; Moreira, Maria da Consolação Vieira; DeSanto, Kristen; Higuita, Nelson Iván Agudelo; Franco‐Paredes, Carlos; Henao‐Martínez, Andrés F.

doi:10.1002/ehf2.13648

Cited by 15 publications

(15 citation statements)

References 59 publications

(39 reference statements)

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“…Although both CCC and IDC are cardiomyopathies associated with high morbidity and mortality, CCC has been associated with a worse prognosis (3,18,(42)(43)(44). While these cardiomyopathies are clinically indistinguishable, the worse prognosis observed in CCC suggests that distinct pathogenic mechanisms may be involved in the progression of these diseases.…”

Section: Discussionmentioning

confidence: 99%

T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

Neves

Koh

Silva

et al. 2022

Front. Cardiovasc. Med.

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Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.

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Section: Discussionmentioning

confidence: 99%

T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

Neves

Koh

Silva

et al. 2022

Front. Cardiovasc. Med.

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“…Comparing CC to ischemic cardiomyopathy reveals that LVEF is a strong predictor of mortality in patients with heart disease [25,26]. However, GLS in CC is more accurate than LVEF in quantifying ventricular function and predicting VA risk [3,5].…”

Section: Discussionmentioning

confidence: 99%

Late Gadolinium Enhancement by Cardiac Magnetic Resonance and Speckle Tracking Echocardiography in the Evaluation of Cardiac Complications in Chagas Cardiomyopathy: A Systematic Review

Acero¹,

Ardila²,

Nanna³

et al. 2022

Rev. Cardiovasc. Med.

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Background: Chagas cardiomyopathy (CC) increases cardiovascular mortality associated with congestive heart failure (CHF), ventricular arrhythmias (VA), and sudden cardiac death (SCD). Different imaging techniques have been tested to assess disease progression and cardiac risk in individuals with Chagas disease (ChD). In this systematic review, we evaluated the accuracy in detecting cardiac complications in CC patients using cardiac magnetic resonance (CMR) and speckle tracking echocardiography (STE). Methods: A search was done on PubMed, Cochrane, and Embase for studies in humans over 18 years of age with ChD. Demographic data, research methodology, imaging parameters, and cardiac outcomes were extracted, and study quality was assessed, resulting in a narrative description. Results: Twelve studies with 1124 patients were analyzed. One study discovered a contractility pattern by STE. Four studies assessed the identification of Early Cardiac Impairment (ECI) and VA risk, respectively, while three studies evaluated the risk of SCD. Global Longitudinal Strain (GLS) identified patients with ECI (-18.5 ± 3.4% non-fibrosis vs -14.0 ± 5.8% fibrosis, p = 0.006 and -18 ± 2% non-fibrosis vs -15 ± 2% fibrosis, p = 0.004). The amount of fibrosis >11.78% or in two or more contiguous transmural segments were markers for VA risk. GLS and the amount of fibrosis were found to be predictors of SCD. Conclusions: STE may be considered a screening technique for identifying the subclinical status of CHF. CMR using Late Gadolinium Enhancement (LGE) is considered a relevant parameter for stratifying patients with ChD who are at risk of SCD. Fibrosis and GLS can be used as markers to categorize patients at risk for arrhythmias.

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“…Providing interventions that can prevent Chronic Chagas Cardiomyopathy (CCC), a disease with an annual mortality rate of 7.9%, to existing infected populations is also a moral imperative [15]. Such interventions have improved patients' quality of life [16][17][18]. At present, there are only two nitroimidazole derivatives, BZN and nifurtimox, both of which have similar efficacy, adverse effects (AEs) and cost characteristics [19].…”

Section: Introductionmentioning

confidence: 99%

Direct evidence gap on fixed versus adjusted‐dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta‐analysis

Ciapponi

Barreira²,

Perelli

et al. 2022

Tropical Med Int Health

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Objectives To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted‐dose for Trypanosoma cruzi‐seropositive adults without cardiomyopathy. Methods We conducted a systematic review and individual participant data (IPD) meta‐analysis following Cochrane methods, and the PRISMA‐IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi‐seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random‐effects IPD meta‐analysis using the one‐stage strategy, or, if that was impossible, the two‐stage strategy. Results Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A) was 8.83 (95% CI 1.02–76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40–52.51), probably indicating at least non‐inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14–1.38), probably indicating no worse tolerance of fixed doses. Conclusions We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight‐adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta‐analysis, through indirect comparisons, may well provide the best possible answers in the near future. Registration The study protocol was registered in PROSPERO (CRD42019120905).

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Mortality risk in chronic Chagas cardiomyopathy: a systematic review and meta‐analysis

Cited by 15 publications

References 59 publications

T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

Late Gadolinium Enhancement by Cardiac Magnetic Resonance and Speckle Tracking Echocardiography in the Evaluation of Cardiac Complications in Chagas Cardiomyopathy: A Systematic Review

Direct evidence gap on fixed versus adjusted‐dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta‐analysis

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