Circulating Trypanosoma cruzi load and major cardiovascular outcomes in patients with chronic Chagas cardiomyopathy: a prospective cohort study.

OBJECTIVES: To analyse the effect of parasite load assessed by quantitative reverse transcription PCR (RT-qPCR) in serum on the prognosis of patients with chronic Chagas cardiomyopathy (CCM) after a 2-year follow-up. METHODS: Prospective cohort study conducted between 2015 and 2017. One hundred patients with CCM were included. Basal parasitaemia levels of Trypanosoma cruzi (T. cruzi) were measured using a quantitative polymerase chain reaction (qPCR) test. The primary composite outcome (CO) was all-cause mortality, cardiac transplantation and implantation of a left ventricular assist device. Secondary outcomes were the baseline levels of serum biomarkers and echocardiographic variables. RESULTS: After a 2 years of follow-up, the primary CO rate was 16%. A positive qPCR was not associated with a higher risk of the CO. However, when parasitaemia was evaluated by comparing tertiles (tertile 1: undetectable parasitaemia, tertile 2: low parasitaemia and tertile 3: high parasitaemia), a higher risk of the CO (HR 3.66; 95% CI 1.11-12.21) was evidenced in tertile 2. Moreover, patients in tertile 2 had significantly higher levels of high-sensitivity troponin T and cystatin C and more frequently exhibited an ejection fraction <50%. CONCLUSION: Low parasitaemia was associated with severity markers of myocardial injury and a higher risk of the composite outcome when compared with undetectable parasitaemia. This finding could be hypothetically explained by a more vigorous immune response in patients with low parasitaemia that could decrease T. cruzi load more efficiently, but be associated with increased myocardial damage. Additional studies with a larger number of patients and cytokine measurement are required to support this hypothesis.

OBJECTIFS: Analyser l'effet de la charge parasitaire évaluée par PCR quantitative de transcription inverse (RT-qPCR) dans le sérum sur le pronostic des patients atteints de cardiomyopathie chronique de Chagas (CCM) après un suivi de deux ans. MÉTHODES: Etude de cohorte prospective menée entre 2015 et 2017. Une centaine de patients atteints de CCM ont été inclus. Les niveaux de parasitémie basale de Trypanosoma cruzi (T. cruzi) ont été mesurés en utilisant un test de réaction en chaîne de la polymérase quantitative (qPCR). Le principal résultat composite (RC) était la mortalité toutes causes, la transplantation cardiaque et l'implantation d'un dispositif d'assistance ventriculaire gauche. Les critères secondaires étaient les niveaux de base des biomarqueurs sériques et des variables échocardiographiques. RÉSULTATS: Après 2 ans de suivi, le taux de RC primaire était de 16%. Une qPCR positive n'était pas associée à un risque plus élevé de RC. Cependant, lorsque la parasitémie était évaluée en comparant les tertiles (tertile 1: parasitémie indétectable, tertile 2: parasitémie faible et tertile 3: parasitémie élevée), un risque plus élevé de RC (HR: 3,66; IC95%: 1,11-12,21) a été mis en évidence dans le tertile 2. De plus, les patients du tertile 2 avaient des niveaux significativement plus élevés de troponine T et de cystatine-C à haute sensibilité et présentaient plus fréquemment une fraction d'éjection <50%. CONCLUSION: Une faible parasitémie était associée à des marqueurs de sévérité des lésions myocardiques et à un risque plus élevé de résultat composite par rapport à une parasitémie indétectable. Cette découverte pourrait être hypothétiquement expliquée par une réponse immunitaire plus vigoureuse chez les patients présentant une faible parasitémie qui pourrait diminuer la charge de T. cruzi plus efficacement mais être associée à une augmentation des lésions myocardiques. Des études supplémentaires avec un plus grand nombre de patients et une mesure des cytokines sont nécessaires pour étayer cette hypothèse.

Chagas disease in Virgem da Lapa, Minas Gerais, Brazil: left ventricle aneurysm and the risk of death in the 24-year interval.

BACKGROUND: Left ventricular aneurysm (LVA) is indicator of high morbidity in Chagas' disease. A cross-sectional study performed identified LVA in 18.8% of the chronic chagasic patients (CCP). OBJECTIVE: Determine the risk of death of patients with chronic chagasic cardiopathy (CCC) and LVA in 24-year interval. MATERIAL AND METHODS: In 1995 a cohort of 298 CCP was evaluated by anamnesis, physical examination, EKG and ECHO and classified in groups: G0 = 86 without cardiopathy; G1 = 156 with cardiopathy without LVA and G2 = 56 with cardiopathy and LVA. 38 patients of G0 and G1 used benznidazole. Information about the deaths was obtained in the notary, death certificates, hospital records and family members. FINDINGS: Were registered 113 deaths (37.9%): 107 (35.9%) attributed to cardiopathy and 6 (2.0%) to other causes (p < 0.05). Amongst these 107 deaths, 10 (11.6%) occurred in G0; 49 (31.4%) occurred in G1 and 48 (85.7%) occurred in G2 (p < 0.05). The risk of death was 2.7 and 7.4 times significantly higher in G2, than in G1 and G0, respectively. CONCLUSION: Chronic chagasic patients with LVA and ejection fraction < 45% have a higher risk of death than those without.

Chagas disease is associated with a worse prognosis at 1-year follow-up after implantable cardioverter-defibrillator for secondary prevention in heart failure patients.

INTRODUCTION: There are conflicting data regarding the efficacy of implantable cardioverter-defibrillator (ICD) in Chagas disease (CD) patients. This study aims to evaluate the short-term outcome after ICD for secondary prevention, in a population where CD is a prevalent cause of heart failure (HF). METHODS AND RESULTS: Consecutive patients with HF and reduced left ventricular ejection fraction (LVEF), who underwent ICD implantation for secondary prevention of SCD. Clinical and demographic data were collected to investigate mortality predictors at 1 year. During the study period, 117 patients underwent ICD implantation, of which 108 were included. The most frequent causes of HF was CD: 52 (48.1%) and ischemic cardiomyopathy: 20 (18.5%). Chagas and non-Chagas patients were well balanced-male: 32 (61.5%) vs 38 (67.9%), P = .548; age: 59.2 (±10.9) vs 56.8 (±13.4), P = .681; and LVEF: 34.1 (±0.2) vs 31.3 (±8.7), P = .064, respectively. At the mean follow-up of 15.7 months, overall mortality occurred in 14 (12.9%) patients, with a higher incidence in patients with CD cardiomyopathy, 11 (21.2%) vs 3 (5.4%), P = .021 (log-rank). In the multivariate analysis, CD remained as an independent predictor for death (hazard ratio: 4.62, confidence interval [95% CI]: 1.27-16.81, P = .021). CONCLUSION: CD was associated with a poor short-term outcome in patients with HF submitted to ICD implantation for secondary prevention when compared with other HF etiologies. In this specific HF population, ICD indication should be individualized, considering the worst prognosis of these patients.

Renal denervation in patients with heart failure secondary to Chagas' disease: A pilot randomized controlled trial.

INTRODUCTION: Chagas disease is one of the most relevant endemic parasitic diseases in Latin America, affecting approximately 6 million people. Overt Chagas heart disease is an ominous condition, occurring in 20-30% of infected individuals, which has besides the persistent myocarditis a peculiar intracardiac ganglionic neuronal depletion and dysautonomy. This study aims to evaluate the safety and feasibility of renal denervation for patients with advanced symptomatic Chagas cardiomyopathy. METHODS: Open-label prospective pilot study that randomized patients with Chagas heart disease to either renal denervation or conservative treatment (2:1 ratio). The primary endpoint was the incidence of major adverse events at 9 months, defined as a composite of all-cause death, myocardial infarction, stroke, need for renal artery invasive treatment, or worsening renal function. RESULTS: A total of 17 patients were allocated for renal denervation (n = 11) or conservative treatment (n = 6). Included patients had severe symptomatic heart disease, with markedly depressed left ventricular function (average ejection fraction 26.7 ± 4.9%). For patients randomized to renal denervation, the procedure was performed successfully and uneventfully. After 9 months, the primary endpoint occurred in 36.4% of patients in the renal denervation group and 50.0% in the control arm (p = .6). After 9 months, clinical, laboratory, functional, echocardiographic, and quality of life parameters were similar between groups. CONCLUSIONS: This pilot study suggests that renal denervation is safe and feasible in patients with Chagas cardiomyopathy, warranting future studies to better evaluate the clinical efficacy of the interventional strategy in improving the prognosis of this high-risk population.

Predictors of mortality and heart transplantation in patients with Chagas' cardiomyopathy and ventricular tachycardia treated with implantable cardioverter-defibrillators.

AIMS: Data on long-term follow-up of patients with Chagas' heart disease (ChHD) receiving a secondary prevention implantable cardioverter-defibrillator (ICD) are limited and its benefit is controversial. The aim of this study was to evaluate the long-term outcomes of ChHD patients who received a secondary prevention ICD. METHODS AND RESULTS: We assessed the outcomes of consecutive ChHD patients referred to our Institution from 2006 to 2014 for a secondary prevention ICD [89 patients; 58 men; mean age 56 ± 11 years; left ventricular ejection fraction (LVEF), 42 ± 12%]. The primary outcome included a composite of death from any cause or heart transplantation. After a mean follow-up of 59 ± 27 months, the primary outcome occurred in 23 patients (5.3% per year). Multivariate analysis showed that LVEF < 35% [hazard ratio (HR) 4.64; P < 0.01] and age ≥ 65 years (HR 3.19; P < 0.01) were independent predictors of the primary outcome. Using these two risk factors, a risk score was developed, and lower- (no risk factors), intermediate- (one risk factor), and higher-risk (two risk factors) groups were recognized with an annual rate of primary outcome of 1.4%, 7.4%, and 20.4%, respectively. A high burden of appropriate ICD therapies (16% per year) and electrical storms were documented, however, ICD interventions did not impact on the primary outcome. CONCLUSION: Among ChHD patients receiving a secondary prevention ICD, older age (≥65 years) and left ventricular dysfunction (LVEF < 35%) portend a poor outcome and were associated with increased risk of death or heart transplantation. Most patients received appropriate ICD therapies, however, ICD interventions did not impact on the primary outcome.

Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy.

BACKGROUND: The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven. METHODS: We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event. RESULTS: The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction). CONCLUSIONS: Trypanocidal therapy with benznidazole in patients with established Chagas' cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.).

A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy.

Aims: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results: This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. Conclusion: This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.

Dysautonomy in different death risk groups (Rassi score) in patients with Chagas heart disease.

BACKGROUND: It has been difficult to prove that "catecholamine-induced cardiomyopathy" contributes to the mechanism of sudden cardiac death in Chagas heart disease. Also, it is almost impossible to rule out the possibility that it is not involved in the process. More importantly, the vagal-cholinergic pathway in the ventricle plays a direct role in the prevention of the initiation of complex ventricular arrhythmias, including nonsustained ventricular tachycardia, ventricular fibrillation responsible for sudden death. OBJECTIVE: To determine frequency of parasympathetic autonomic indices among the different groups of risk of cardiovascular death when stratified by Rassi score. METHODS: Patients with Chagas heart disease were selected and divided into three risk groups by Rassi score. A fourth group, non-Chagas group, was of similar age and gender. All were subjected to analysis of heart rate variability during controlled breathing (RSA) and tilt table passive test (tilt test). High frequency and low frequency/high frequency ratio were calculated and presented by box-plot. Also, t-test was used to compare the two groups. RESULTS: It was observed that the parasympathetic and sympathetic component were affected, when the risk group increased the response was worsened to the stimulus (RSA or Tilt). Also, the low-risk group was jeopardized, when compared to the non-Chagas group. CONCLUSION: The loss of parasympathetic modulation was present in all Rassi risk groups, including the low risk, indicating that a morphological change of the myocardium represents a detectable neurofunctional change.

Long-term follow-up of Chagas heart disease patients receiving an implantable cardioverter-defibrillator for secondary prevention.

BACKGROUND: Chagas heart disease (CHD) is a dilated cardiomyopathy characterized by malignant ventricular arrhythmias and increased risk of sudden cardiac death (SCD). Much controversy exists concerning the efficacy of implantable cardioverter-defibrillator (ICDs) in CHD because of mixed results observed. We report our long-term experience with ICDs for secondary prevention in CHD, with the specific aim of assessing the results in groups with preserved or depressed global left ventricular function. METHODS: 111 patients (75 males; 60 ± 12 years) were followed for 1,948 ± 1,275 days after ICD. Time to death was the primary outcome; LVEF ≤ 45% the exposure; and age, gender, and ICD therapy delivery the potential confounders. We used time-to-event methods and Cox proportional models for analysis, censoring observations at time of death or at 5-year follow-up in survivors. RESULTS: Seventy-two percent of the patients presented at least one sustained ventricular arrhythmia requiring appropriate therapy, and only three patients received inappropriate therapy. Death occurred in 50 (45%) patients, with an annual mortality rate of 8.4%, mostly due to refractory heart failure or noncardiac causes. Unadjusted survival rates were significantly distinct between patients with left ventricular ejection fraction (LVEF) ≤ 45% (26 deaths), 50.5% (95% confidence interval [CI]: 36.2%-63.2%) when compared to patients with LVEF > 45% (10 deaths), 77.6% (95% CI: 62.3%-87.3%, P < 0.01). After adjusting for confounders, low LVEF (hazard ratio [HR]: 5.2, 95% CI: 2.3-11.6), age (HR: 1.04, 95% CI: 1.01-1.07), and female gender (HR: 3.97, 95% CI: 1.85-8.54) were independently associated with the outcome. CONCLUSIONS: ICDs successfully aborted life-threatening arrhythmias in CHD patients. Impaired left ventricular function predicted higher mortality in CHD patients with an ICD for secondary prevention of SCD.

Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy.

Current treatments for chronic Chagas cardiomyopathy, a disease with high mortality rates and caused by the protozoan Trypanosoma cruzi, are unsatisfactory. Myocardial inflammation, including endothelial activation, is responsible for the structural and functional damage seen in the chronic phase. The clinical efficacy of benznidazole could be improved by decreasing chronic inflammation. Statins, which have anti-inflammatory properties, may improve the action of benznidazole. Here, the action of simvastatin in a murine model of chronic Chagas cardiomyopathy and the link with the production of the proresolving eicosanoid 15-epi-lipoxin A4, produced by 5-lipoxygenase, are evaluated. Simvastatin decreased the expression of the adhesion molecules E-selectin, intracellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1) in T. cruzi-infected mice. However, when this drug was administered to 5-lipoxygenase-deficient mice, the anti-inflammatory effect was not observed unless exogenous 15-epi-lipoxin A4 was administered. Thus, in chronic Chagas disease, 5-epi-lipoxin A4 induced by simvastatin treatment could improve the pathophysiological condition of patients by increasing the trypanocidal action of benznidazole.

Seven years of use of implantable cardioverter-defibrillator therapies: a nationwide population-based assessment of their effectiveness in real clinical settings.

BACKGROUND: The efficacy of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) therapy has already been established in clinical trials but their effectiveness in several clinical settings remains undetermined. This study aimed to assess the effectiveness of ICD and CRT-D therapies within the Brazilian National Health System (SUS). METHODS: All patients who underwent ICD or CRT-D implantation within the SUS from 2001 to 2007 were included in the study. We compared estimated Kaplan-Meier survival curves using the Peto's test. Prognostic factors were selected using Cox's models. RESULTS: There were included 3,295 patients in the ICD group and 681 patients in the CRT-D group. Cardiac causes accounted for 79% of all deaths in both groups and Chagas' heart disease accounted for 31% of these deaths. In the CRT-D group, survival significantly decreased around the fourth year of follow-up, with a decrease from 59.5% to 38.3% in 5.5 months. Transvenous implantation technique was used in 62% of CRT-D patients. In-hospital case-fatality rates were higher in those undergoing surgical implantation (5.3%) than those undergoing transvenous implantation (1.6%) (p = 0.02). CONCLUSIONS: The results show that short-term, medium-term and long-term effectiveness of ICD therapy appears to be similar to that evidenced in clinical trials. In the CRT-D group, in-hospital case-fatality and 30-day case-fatality were higher than those reported in other studies. Surgical epicardial implantation technique was performed in this group at a higher frequency than that reported in the literature and was associated with poorer short-term prognosis.

Long-term follow-up of patients with chronic chagas disease and implantable cardioverter-defibrillator.

BACKGROUND/OBJECTIVES: Chronic Chagas heart disease (ChHD) is associated with ventricular tachyarrhythmias and an increased risk of sudden cardiac death. Little is known about the effectiveness of implantable cardioverter-defibrillator (ICD) therapy in this population. The objective of this study was to evaluate the efficacy of ICD in patients with ChHD and to identify predictors of mortality and appropriate ICD shocks. METHODS: The cohort study included 65 patients with ChHD and ICD for primary and secondary prevention of sudden death. The Cox model was applied to evaluate the predictors of mortality, and survival was assessed by Kaplan-Meier analysis. RESULTS: The median age was 56 ± 11.9 years. The median follow-up was 40 ± 26.8 months. Among the patients 23 (36.5%) had appropriate shocks. A total of 13 (20%) patients died (6.1% of annual mortality rate), and there was no sudden death. In univariate Cox model, functional class IV (hazard ratio [HR] = 1.99; 95% confidence interval [CI], 1.05-3.76; P = 0.034), primary prevention (HR = 0.29; 95% CI, 0.09-0.99; P = 0.048), lower education (HR = 2.51; 95% CI, 1.05-5.99; P = 0.038), and ejection fraction <30% (HR = 2.80; 95% CI, 1.09-7.18; P = 0.032) were predictors of worse prognosis (death). In the multivariate Cox model, an ejection fraction <30% and the low education remained predictors of poor prognosis. Predictors of appropriate shocks were not found. CONCLUSIONS: The ICD was effective for the prevention of sudden cardiac death in patients with chronic ChHD. An ejection fraction <30% and low education were predictors of poor prognosis.

Mortality risk score for patients with Chagas cardiomyopathy and pacemaker.

BACKGROUND: Prognosis of Chronic Chagasic Cardiomyopathy (CCC) patients depends on functional and clinical factors. Bradyarrhythmia requiring pacemaker is a common complication. Prognosis of these patients is poorly studied, and mortality risk factors are unknown. We aimed to identify predictors of death and to define a risk score for mortality in a large cohort of CCC patients with pacemaker. METHODS: It was an observational, unicentric and prospective study. The endpoint was all-cause mortality. Cox regression was used to identify predictors of death and to define a risk score. Bootstrapping method was used to internal score validation. RESULTS: We included 555 patients and after a mean follow-up of 3.7±1.5 years, 100 (18%) deaths occurred. Predictors of death were: right ventricular dysfunction (HR [hazard ratio] 2.24; 95%CI 1.41-3.53; P = 0.001); heart failure class III or IV (HR 2.16; 95% confidence interval [95%CI] 1.16-4.00; P = 0.014); renal disease (HR 2.14; 95%CI 1.24-3.68; P = 0.006); left ventricular end-systolic diameter > 44mm (HR 1.97; 95%CI 1.26-3.05; P = 0.003); atrial fibrillation (HR 1.94; 95%CI 1.25-2.99; P = 0.003) and cardiomegaly on X-ray (HR 1.87; 95%CI 1.10-3.17; P = 0.020). The score identified patients with: low (0-20 points), intermediate (21-30 points) and high risk (>31points). The optimism-corrected C-statistic of the predictive model was 0.751 (95% CI 0.696-0.806). Internal validation with bootstrapping revealed a calibration slope of 0.946 (95% CI 0.920-0.961), reflecting a small degree of over-optimism and C-statistic of 0.746 (95% CI 0.692-0.785). CONCLUSIONS: This study identified predictors of mortality in CCC patients with pacemaker defining a simple, validated and specific risk score.

A systematic review and meta-analysis of mortality in chronic Chagas cardiomyopathy versus other cardiomyopathies: higher risk or fiction?

INTRODUCTION AND OBJECTIVES: Although multiple studies suggest that chronic Chagas cardiomyopathy (CCC) has higher mortality than other cardiomyopathies, the absence of meta-analyses supporting this perspective limits the possibility of generating robust conclusions. The aim of this study was to systematically evaluate the current evidence on mortality risk in CCC compared with that of other cardiomyopathies. METHODS: PubMed/Medline and EMBASE were searched for studies comparing mortality risk between patients with CCC and those with other cardiomyopathies, including in the latter nonischemic cardiomyopathy (NICM), ischemic cardiomyopathy, and non-Chagas cardiomyopathy (nonCC). A random-effects meta-analysis was performed to combine the effects of the evaluated studies. RESULTS: A total of 37 studies evaluating 17 949 patients were included. Patients with CCC had a significantly higher mortality risk compared with patients with NICM (HR, 2.04; 95%CI, 1.60-2.60; I2, 47%; 8 studies) and non-CC (HR, 2.26; 95%CI, 1.65-3.10; I2, 71%; 11 studies), while no significant association was observed compared with patients with ischemic cardiomyopathy (HR, 1.72; 95%CI, 0.80-3.66; I2, 69%; 4 studies) in the adjusted-measures meta-analysis. CONCLUSIONS: Patients with CCC have an almost 2-fold increased mortality risk compared with individuals with heart failure secondary to other etiologies. This finding highlights the need for effective public policies and targeted research initiatives to optimally address the challenges of CCC.

Predictors of Appropriate Therapies and Death in Patients with Implantable Cardioverter-Defibrillator and Chronic Chagas Heart Disease. / Preditores de Terapias Apropriadas e Óbito em Pacientes com Cardiodesfibrilador Implantável e Cardiopatia Chagásica Crônica.

BACKGROUND: There are few retrospective and prospective studies on implantable cardioverter-defibrillators (ICD) in primary and secondary prevention of sudden death in chronic Chagas heart disease (CCHD). OBJECTIVES: To describe the long-term evolution of patients with CCHD and ICD and to identify and analyze predictors of mortality and appropriate device therapy in this population. METHODS: This was a historical prospective study with 117 patients with ICD and CCHD. Devices were implanted from January 2003 to December 2021. Predictors of appropriate therapies and long-term mortality were identified and analyzed. The level of statistical significance was p < 0.05. RESULTS: Patients (n = 117) had a median follow-up of 61 months (25 to 121 months); they were predominantly male (74%), with a median age of 55 years (48 to 64 years). There were 43.6% appropriate shocks, 26.5% antitachycardia pacing (ATP), and 51% appropriate therapies. During follow-up, 46 patients (39.7%) died. Mortality was 6.2% person-years (95% confidence interval [CI]: 4.6 to 8.3), with 2 sudden deaths during follow-up. Secondary prevention (hazard ratio [HR] 2.1; 95% CI: 1.1 to 4.3; p = 0.029) and ejection fraction less than 30% (HR 1.8; 95% CI: 1.1 to 3.1; p < 0.05) were predictors of appropriate therapies. Intermediate Rassi score showed a strong association with the occurrence of ATP alone (p = 0.015). Functional class IV (p = 0.007), left ventricular ejection fraction < 30 (p = 0.010), and age above 75 years (p = 0.042) were predictors of total mortality. CONCLUSION: ICDs in CCHD showed a high incidence of appropriate activation, especially in patients with secondary prevention, low left ventricular ejection fraction, and intermediate Rassi score. Patients with congestive heart failure, elevated functional class, and age over 75 years showed elevated mortality. Survival function of patients with implantable cardioverter-defibrillators and chronic Chagas heart disease. A - According to New York Heart Association functional class; B - According to left ventricular ejection fraction; C - According to Rassi score. D - According to age. CCHD: chronic Chagas heart disease; HR: hazard ratio; ICD: implantable cardioverter-defibrillator.

Efficacy and safety of implantable cardioverter-defibrillators in patients with Chagas disease.

AIMS: Implantable cardioverter-defibrillators (ICDs) are now a first-line option for prevention of sudden death in Chagas disease (ChD). However, efficacy and safety of ICD treatment in ChD remains controversial. The aim of our study was to compare clinical outcome after ICD implantation in ChD and non-ChD patients. METHODS AND RESULTS: The study population consists of patients who received ICD implantation in a tertiary Reference Center for ChD in Brazil. The primary endpoint of the study was appropriate therapy (appropriate shocks or anti-tachycardia pacing); the secondary endpoint was the event-free survival defined as absence of death or appropriate therapy. One hundred and thirty-five [corrected] patients were followed for the median time of 266 days. Sixty-five patients had ChD. Appropriate ICD therapy occurred in 32 (49.2%) ChD and in 19 (27.1%) non-ChD patients (P=0.005). Ventricular tachycardia occurred in 27 (42%) ChD and in 16 (23%) non-ChD (P = 0.01) patients. There was a statistically significant difference in event-free survival between the group of patients with and without ChD (P=0.004). The median event-free survival was 230 days (95% confidence interval, CI: 113-347) in patients with ChD and 549 days (95% CI: 412-687) in non-ChD patients. Chagas disease double the risk of the patient to have appropriate therapy (hazard ratio, HR = 2.2, 95% CI = 1.2-4.3, P = 0.02) and appropriate therapy or death (HR = 2.2, 95% CI = 1.2-4.2, P = 0.01) in multivariate analysis. There were 16 deaths (11.8%) with 8 deaths in each group and five inappropriate shocks (3.7%) with one in ChD patients (1.6%). CONCLUSION: The higher frequency of appropriate ICD therapy and the shorter event-free survival in ChD patients are consistent with the presence of an arrhythmogenic substrate that characterizes this cardiomyopathy.

T-wave amplitude variability and the risk of death in Chagas disease.

INTRODUCTION: Measurement of beat-to-beat T-wave amplitude variability (TWV) has been described as a promising new technique for the stratification of arrhythmic risk in postmyocardial infarction and dilated cardiomyopathy patients. Chagas disease (ChD) can lead to a potentially lethal cardiopathy that can present with ventricular arrhythmias, heart blocks, heart failure, and sudden death. The aim of the study was to evaluate the prognostic value of TWV in ChD patients in addition to traditional prognostic predictors. METHODS AND RESULTS: The study enrolled 113 ambulatory ChD patients (62 men; age: 42 ± 9 years) in sinus rhythm and without other systemic diseases, evaluated by a standard clinical protocol. We computed TWV in 10-minute ECG recordings obtained in controlled resting conditions. TWV was defined as the median values among 8 consecutive 50-ms T-wave segments and dichotomized as either ≤ or > 30 µV(2). The association of TWV and death was evaluated by Cox proportional-hazards analysis, considering other established predictors. During mean follow-up time of 106 ± 28 months, 14 patients died. A value of median TWV > 30 µV(2) predicts increased risk of death in a multivariate analysis (HR = 5.76, 95% CI 1.31-25.23, P = 0.014), in addition to depressed left ventricular function, presence of nonsustained ventricular tachycardia and QRS duration >133 ms. CONCLUSION: Repolarization variability, evaluated by TWV, is independently related to the risk of death in ChD. This noninvasive methodology could facilitate the identification of patients who may benefit from more aggressive therapeutic strategies.

Predictors of all-cause 1-year mortality in implantable cardioverter defibrillator patients with chronic Chagas' cardiomyopathy.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) have been used in the treatment of either sustained ventricular tachycardia or ventricular fibrillation in patients with Chagas' cardiomyopathy. This study aimed at determining mortality rate and risk factors of all-cause 1-year mortality in primary and secondary ICD patients with Chagas' cardiomyopathy. METHODS: One hundred and forty-eight Chagas' patients with ICDs were included from the Medtronic ICD Registry Latin America. All patients were followed for 1 year. RESULTS: At implant, mean age was 60.1 ± 9.4 years and 72.9% were male. Mean left ventricular ejection fraction (LVEF) was 40.1 ± 11%. Mean follow-up was 12 ± 7 months. During the follow-up, 15 patients died (10.2%). Patients who died were older (64 ±10.8 years vs 59 ± 9.1; P = 0.04), had more atrial fibrillation (13.3% vs 3.8%; P = 0.02), had lower LVEF (33.4%± 9.8 vs 40.9%± 11.3; P = 0.01), and worse functional class (III/IV 40% vs 21.8%; P = 0.03). The multivariate analysis showed that two independent predictors of all-cause 1-year mortality remained statistically significant: age more than 65 (hazard ratio [HR] = 2.85, 95% confidence interval [CI] 1.77-3.92; P = 0.03) and LVEF less than 30% (HR = 2.68, 95% CI 1.57-3.79; P = 0.04). CONCLUSION: This analysis showed that patients older than 65 years of age and with LVEF less than 30% were independent predictors of all-cause 1-year mortality in patients with chronic Chagas' cardiomyopathy.

Predictors of mortality in patients with Chagas' cardiomyopathy and ventricular tachycardia not treated with implantable cardioverter-defibrillators.

BACKGROUND: The natural history of the arrhythmogenic form of Chagas' heart disease is not fully understood. METHODS: We assessed the outcome of 56 patients with Chagas' cardiomyopathy ([31 men]; mean age of 55 years; mean left ventricular ejection fraction [LVEF] 42%) presenting with either sustained ventricular tachycardia (VT) or nonsustained VT (NSVT), before therapy with implantable cardioverter-defibrillator was available at our center. RESULTS: Over a mean follow-up of 38 ± 16 months (range, 1-61 months), 16 patients (29%) died, 11 due to sudden cardiac death (SCD), and five from progressive heart failure. Survivors and nonsurvivors had comparable baseline characteristics, except for a lower LVEF (46 ± 7% vs 31 ± 9%, P < 0.001) and a higher New York Heart Association class (P = 0.003) in those who died during follow-up. Receiver-operator characteristic curve analysis showed that an LVEF cutoff value of 38% had the best accuracy for predicting all-cause mortality and an LVEF cutoff value of 40% had the best accuracy for prediction of SCD. Using the multivariate Cox regression analysis, LVEF < 40% was the only predictor of all-cause mortality (hazard ratio [HR] 12.22, 95% confidence interval [CI] 3.46-43.17, P = 0.0001) and SCD (HR 6.58, 95% CI 1.74-24.88, P = 0.005). CONCLUSIONS: Patients with Chagas' cardiomyopathy presenting with either sustained VT or NSVT run a major risk for mortality when had concomitant severe or even moderate LV systolic dysfunction.

Transplantation for Chagas' disease: an overview of immunosuppression and reactivation in the last two decades.

Over the last 20 yr, the immunosuppression protocols in chagasic heart-transplanted patients have gone through three phases, and we have identified several changes and discoveries about Chagas' disease reactivation, mortality, and neoplasia development. The first phase was especially important because until that time, Chagas' disease was an absolute contraindication for transplantation. The second phase started when an adjustment was made to the immunosuppression protocol, a lower dosage being adopted to avoid adverse effects, especially neoplasias and reactivation episodes. Currently, strategies to change the immunosuppression, especially replacement of mycophenolate mofetil by azathioprine or low doses of mycophenolate in this special situation, have been shown to be effective in reducing Chagas' disease reactivation. Cardiac transplantation for Chagas' disease is a reality. Although patients with Chagas' disease may experience particular complications when undergoing transplantation compared with transplantation for other etiologies, these difficulties are well known, and treatment and preventive strategies are also better established. In other organs and tissues, transplantation in patients with Chagas' disease also has good outcomes. Blood monitoring for parasitemias is mandatory as is the institution of therapy in the case of a reactivation diagnosis. Acute Chagas' disease may occur in patients who received organs from donors with Chagas' disease.