• Chagas heart disease
• Implantable cardiac defibrillator
• Sudden death

• Humans
• Chagas Cardiomyopathy/therapy
• Chagas Cardiomyopathy/mortality
• Chagas Cardiomyopathy/diagnosis
• Female
• Male
• Defibrillators, Implantable/trends
• Middle Aged
• Treatment Outcome
• Follow-Up Studies
• Cardiomyopathies/therapy
• Cardiomyopathies/mortality
• Cardiomyopathies/diagnosis
• Retrospective Studies
• Aged
• Adult
• Time Factors
• Death, Sudden, Cardiac/prevention & control
• Death, Sudden, Cardiac/epidemiology
• Tachycardia, Ventricular/mortality
• Tachycardia, Ventricular/therapy

• Humans
• Defibrillators, Implantable
• Male
• Middle Aged
• Female
• Chagas Cardiomyopathy/mortality
• Chagas Cardiomyopathy/therapy
• Chagas Cardiomyopathy/complications
• Chagas Cardiomyopathy/physiopathology
• Death, Sudden, Cardiac/prevention & control
• Death, Sudden, Cardiac/etiology
• Prospective Studies
• Chronic Disease
• Risk Factors
• Aged
• Secondary Prevention/methods
• Time Factors
• Primary Prevention
• Treatment Outcome

• Chagas disease
• Trypanosoma cruzi
• clinical trial
• etiological treatment
• pathophysiological treatment

• Humans
• Stroke Volume
• Ventricular Function, Left
• Heart/diagnostic imaging
• Cardiomyopathies
• Ventricular Dysfunction, Left/diagnostic imaging

• Chagas cardiomyopathy
• Chagas disease
• Exercise testing
• Prognosis

• Humans
• Chagas Disease/complications
• Chagas Disease/diagnosis
• Chagas Disease/therapy
• Cardiomyopathies/diagnosis
• Cardiomyopathies/therapy
• Chagas Cardiomyopathy/diagnosis
• Chagas Cardiomyopathy/therapy

• R01 AI138230 NIAID NIH HHS

• Humans
• Brazil
• Pacemaker, Artificial
• Defibrillators, Implantable
• Heart
• Cardiac Resynchronization Therapy Devices

• Cardiac rehabilitation
• Chagas disease
• cardiomyopathy
• cardiopulmonary exercise test
• exercise

The identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD.

This retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality.

There were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25–75% 8.0–27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00–1.03 per mmHg) and change (HR 1.03; 95% CI 1.01–1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14–13.74), during exercise (HR 2.73; 95% CI 1.44–5.20), and recovery (HR 2.60; 95% CI 1.14–5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33–3.21).

Our findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD.

• Chagas cardiomyopathy
• G-CSF therapy
• NYHA functional class
• cardiac functional analysis
• safety study

• Fundação Oswaldo Cruz

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients’ myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

• chronic Chagas disease cardiomyopathy
• energy metabolism
• idiopathic dilated cardiomyopathy
• interferon-gamma
• ischemic cardiomyopathy
• mitochondria
• proteomics
• two-dimensional electrophoresis with fluorescent labeling

This study aimed to estimate the annual mortality risk and its determinants in chronic Chagas cardiomyopathy.

We conducted a systematic search in MEDLINE, Web of Science Core Collection, Embase, Cochrane Library, and LILACS. Longitudinal studies published between 1 January 1946 and 24 October 2018 were included. A random‐effects meta‐analysis using the death rate over the mean follow‐up period in years was used to obtain pooled estimated annual mortality rates. Main outcomes were defined as all‐cause mortality, including cardiovascular, non‐cardiovascular, heart failure, stroke, and sudden cardiac deaths. A total of 5005 studies were screened for eligibility. A total of 52 longitudinal studies for chronic Chagas cardiomyopathy including 9569 patients and 2250 deaths were selected. The meta‐analysis revealed an annual all‐cause mortality rate of 7.9% [95% confidence interval (CI): 6.3–10.1; I² = 97.74%; T² = 0.70] among patients with chronic Chagas cardiomyopathy. The pooled estimated annual cardiovascular death rate was 6.3% (95% CI: 4.9–8.0; I² = 96.32%; T² = 0.52). The annual mortality rates for heart failure, sudden death, and stroke were 3.5%, 2.6%, and 0.4%, respectively. Meta‐regression showed that low left ventricular ejection fraction (coefficient = −0.04; 95% CI: −0.07, −0.02; P = 0.001) was associated with an increased mortality risk. Subgroup analysis based on American Heart Association (AHA) classification revealed pooled estimate rates of 4.8%, 8.7%, 13.9%, and 22.4% (P < 0.001) for B1/B2, B2/C, C, and C/D stages of cardiomyopathy, respectively.

The annual mortality risk in chronic Chagas cardiomyopathy is substantial and primarily attributable to cardiovascular causes. This risk significantly increases in patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D.

• Cardiomyopathy
• Chagas
• Mortality

• Chagas disease
• Decompensated heart failure
• Heart failure
• Prognosis
• Risk

Chagas disease is an important public health problem in Latin America. However, migration and globalisation have resulted in the increased presence of Chagas disease worldwide. Sudden cardiac death is the leading cause of death in people with Chagas disease, most often due to ventricular fibrillation. Although more common in patients with documented ventricular arrhythmias, sudden cardiac death can also be the first manifestation of Chagas disease in patients with no previous symptoms or known heart failure. Major predictors of sudden cardiac death include cardiac arrest, sustained and non-sustained ventricular tachycardia, left ventricular dysfunction, syncope and bradycardia. The authors review the predictors and risk stratification score developed by Rassi et al. for death in Chagas heart disease. They also discuss the evidence for anti-arrhythmic drugs, catheter ablation, ICDs and pacemakers for the prevention of sudden cardiac death in these patients. Given the widespread global burden, understanding the risk stratification and prevention of sudden cardiac death in Chagas disease is of timely concern.

• Chagas cardiomyopathy
• Chagas disease
• prevention
• review
• risk stratification
• sudden cardiac death

• Chagas cardiomyopathy
• Chagas disease
• cardiac rehabilitation
• exercise
• heart failure
• survival analysis

• Doppler tissue imaging
• cardiomyopathy
• chronic Chagas disease
• echocardiography
• predictors of cardiovascular events
• systolic and diastolic LV myocardial dysfunction

• chagas disease
• chagas cardiomyopathy
• exercise test
• exercise tolerance
• evaluation
• prognosis

• Chagas Cardiomyopathy/physiopathology
• Echocardiography
• Exercise Test/methods
• Exercise Tolerance/physiology
• Heart Failure/physiopathology
• Humans
• Prognosis
• Ventricular Function, Left/physiology
• Ventricular Function, Right/physiology

• chagas disease
• ace i/d polymorphism
• cardiomyopathy
• heart failure

• Adult
• Angiotensin-Converting Enzyme Inhibitors
• Brazil
• Case-Control Studies
• Chagas Disease/genetics
• Chagas Disease/physiopathology
• Cohort Studies
• Disease Progression
• Female
• Genotype
• Heart Failure/genetics
• Heart Failure/physiopathology
• Humans
• Male
• Middle Aged
• Peptidyl-Dipeptidase A/genetics
• Polymorphism, Genetic/genetics

• Adult
• Bradykinin/metabolism
• Calcium/metabolism
• Cell Membrane Permeability
• Chagas Cardiomyopathy/metabolism
• Endothelins/metabolism
• Female
• Humans
• Inositol 1,4,5-Trisphosphate/metabolism
• Inositol 1,4,5-Trisphosphate Receptors/metabolism
• Macrocyclic Compounds/metabolism
• Male
• Middle Aged
• Myocytes, Cardiac/metabolism
• Oxazoles/metabolism
• Quality of Life
• Sarcoplasmic Reticulum/metabolism
• Sodium/metabolism

• Florida Heart Foundation

Risk stratification of Chagas disease patients in the limited‐resource setting would be helpful in crafting management strategies. We developed a score to predict 2‐year mortality in patients with Chagas cardiomyopathy from remote endemic areas.

This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi‐Trop cohort (The São Paulo‐Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all‐cause mortality. The patients were classified into 3 risk categories at baseline (low, <2%; intermediate, ≥2% to 10%; high, ≥10%). External validation was performed by applying the score to an independent population with Chagas disease. After 2 years of follow‐up, 110 patients died, with an overall mortality rate of 3.505 deaths per 100 person‐years. Based on the nomogram, the independent predictors of mortality were assigned points: age (10 points per decade), New York Heart Association functional class higher than I (15 points), heart rate ≥80 beats/min (20 points), QRS duration ≥150 ms (15 points), and abnormal NT‐proBNP adjusted by age (55 points). The observed mortality rates in the low‐, intermediate‐, and high‐risk groups were 0%, 3.6%, and 32.7%, respectively, in the derivation cohort and 3.2%, 8.7%, and 19.1%, respectively, in the validation cohort. The discrimination of the score was good in the development cohort (C statistic: 0.82), and validation cohort (C statistic: 0.71).

In a large population of patients with Chagas cardiomyopathy, a combination of risk factors accurately predicted early mortality. This helpful simple score could be used in remote areas with limited technological resources.

• Chagas cardiomyopathy
• Chagas disease
• mortality
• risk prediction
• risk score

• Cardiomyopathy, Dilated/parasitology
• Cardiomyopathy, Dilated/physiopathology
• Chagas Cardiomyopathy/physiopathology
• Humans
• Ventricular Function, Right/physiology

• Chagas cardiomyopathy
• Chagas heart disease
• heart failure
• radiofrequency ablation
• renal denervation

• Chagas disease
• ROC curve
• daily activities
• evaluation
• oxygen uptake
• patient-reported outcomes

• Chagas disease
• late enhancement
• nonsustained ventricular tachycardia and sustained ventricular tachycardia
• ventricular tachycardia

Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC.

Forty-nine patients with ChC (50 ± 7 years, New York Heart Association “NYHA” I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression.

After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval (CI) 1.1-1.4; p = 0.001), peak oxygen uptake (HR 1.2, 95% CI 1.0-1.3; p = 0.009), and left ventricular ejection fraction (HR 0.8, 95% CI 0.7-0.9; p = 0.001) were the independent predictors of survival. The combination of low serum BDNF levels and reduced left ventricular ejection fraction were highly predictive of death (HR 5.6, 95% CI: 1.2-9.7; p = 0.026).

In patients with ChC, reduced serum BDNF levels, especially if associated with systolic function, may provide useful prognostic information.

• B-cell epitope mapping
• Chagas’ disease
• Immunodiagnosis
• Immunoinformatics
• Peptides
• Trypanosoma cruzi

• Acute death
• Chagas
• Disease complications
• Mixed infection
• Reinfection
• Trypanosoma cruzi

• Animals
• Chagas Disease/mortality
• Chagas Disease/veterinary
• Coinfection/parasitology
• Disease Progression
• Humans
• Male
• Mice
• Trypanosoma cruzi/genetics
• Trypanosoma cruzi/isolation & purification

• Trypanosoma cruzi
• heart failure
• heart transplantation
• prognosis
• sudden death

Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score.

This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score.

Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76).

CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD.