Exercise Training Reduces Inflammation and Fibrosis and Preserves Myocardial Function and Perfusion in a Model of Chronic Chagas Cardiomyopathy. / Treinamento Físico Reduz a Inflamação e a Fibrose e Preserva a Função e a Perfusão Miocárdica em um Modelo de Cardiomiopatia Chagásica Crônica.

BACKGROUND: Chronic Chagas cardiomyopathy (CCC) is caused by an inflammatory process induced by Trypanosoma cruzi, which leads to myocarditis with reactive and reparative fibrosis. CCC progresses with myocardial perfusion abnormalities and histopathological events that affect cardiorespiratory fitness (CRF). OBJECTIVES: We evaluated the effects of aerobic physical training (APT) on myocardial perfusion and on morphological and functional impairments related with inflammation and fibrosis in Syrian hamsters with CCC. As a secondary objective, we analyzed the cross-sectional areas of the skeletal muscle. METHODS: Hamsters with CCC and their respective controls were divided into four groups: CCC sedentary, CCC-APT, sedentary control and APT control. Seven months after infection, the animals underwent echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. Moderate-intensity APT was performed for fifty minutes, five times a week, for eight weeks. Subsequently, the animals were reassessed. Histopathological analysis was conducted after the above-mentioned procedures. The level of significance was set at 5% in all analyses (p<0.05). RESULTS: CCC sedentary animals presented worse myocardial perfusion defects (MPD) over time, reduced left ventricle ejection fraction (LVEF) and showed more inflammation and fibrosis when compared to other groups (mixed ANOVA analysis). Conversely, APT was able to mitigate the progression of MPD, ameliorate inflammation and fibrosis and improve CRF efficiency in CCC-APT animals. CONCLUSIONS: Our study demonstrated that APT ameliorated cardiac dysfunction, MPD, and reduced inflammation and fibrosis in CCC hamster models. Additionally, CCC-SED animals presented skeletal muscle atrophy while CCC-APT animals showed preserved skeletal muscle CSA. Understanding APT's effects on CCC's pathophysiological dimensions is crucial for future research and therapeutic interventions.

FUNDAMENTO: A Cardiomiopatia Chagásica Crônica (CCC) é causada por um processo inflamatório induzido pelo Trypanosoma cruzi, que leva à miocardite com fibrose reativa e reparativa. A CCC progride com alterações de perfusão miocárdica e eventos histopatológicos que afetam a Aptidão Cardiorrespiratória (ACR). OBJETIVOS: Avaliamos os efeitos do Treinamento Físico Aeróbico (TFA) na perfusão miocárdica e nos comprometimentos morfológicos e funcionais relacionados à inflamação e fibrose em hamsters sírios com CCC. Como objetivo secundário, analisamos as áreas de secção transversa do músculo esquelético. MÉTODOS: Hamsters com CCC e seus respectivos controles foram divididos em quatro grupos: CCC sedentário, CCC-TFA, controle sedentário e controle TFA. Sete meses após a infecção, os animais foram submetidos à ecocardiografia, à cintilografia de perfusão miocárdica e ao teste de esforço cardiopulmonar. TFA de intensidade moderada foi realizado durante cinquenta minutos, cinco vezes por semana, por oito semanas. Posteriormente, os animais foram reavaliados. A análise histopatológica foi realizada após os procedimentos acima mencionados. O nível de significância foi estabelecido em 5% em todas as análises (p<0,05). RESULTADOS: Animais com CCC sedentários apresentaram piores Defeitos de Perfusão Miocárdica (DPM) ao longo do tempo, Fração de Ejeção do Ventrículo Esquerdo (FEVE) reduzida, e apresentaram mais inflamação e fibrose quando comparados aos demais grupos (análise ANOVA mista). Por outro lado, o TFA foi capaz de mitigar a progressão do DPM, atenuar a inflamação e a fibrose e melhorar a eficiência da ACR em animais CCC-TFA. CONCLUSÃO: Nosso estudo demonstrou que o TFA melhorou a disfunção cardíaca, DPM e reduziu a inflamação e a fibrose em modelos de hamster com CCC. Além disso, os animais CCC-SED apresentaram atrofia do músculo esquelético, enquanto os animais CCC-TFA apresentaram a AST do músculo esquelético preservada. Compreender os efeitos da TFA nas dimensões fisiopatológicas da CCC é crucial para futuras pesquisas e intervenções terapêuticas.

Enhancing risk assessment in Chagas cardiomyopathy: Electrophysiology study stratified by Rassi score.

BACKGROUND: Chagas cardiomyopathy (CCM) is increasingly prevalent in developed countries due to migration from endemic areas. Accurate risk stratification is crucial due to the variable clinical course of CCM. OBJECTIVE: To analyze the association between Rassi score progression and electrophysiology study (EPS) changes in CCM patients. METHODS: This prospective, observational cohort study involved CCM patients from two tertiary hospitals. Patients were classified as low, intermediate, or high risk based on the Rassi score. Data collected included demographics, clinical history, and diagnostic tests. EPS assessed AH, HH, and HV intervals, and inducibility of ventricular arrhythmias. Follow-ups were at 30 days and six-month intervals, with individualized discussions for cardiac implantable electric devices (CIED) based on EPS results. RESULTS: Of 67 screened CCM patients, 59 underwent EPS. The mean Rassi score was 8.7 ± 4.5 points, with 33.8 % low, 38.9 % intermediate, and 27.1 % high risk. EPS abnormalities were found in 57.6 % of patients, mainly VT/VF (52.5 %). Most induced ventricular arrhythmias were monomorphic VT (80.7 %). A significant association was found between Rassi score risk classification and EPS changes (OR = 1.88 95 %CI: 1.15-3.06 p = 0.02). Higher Rassi scores correlated with VT presence on EPS (p = 0.0036). Syncope/pre-syncope had an OR 2.45 95 %CI:1.21-4.94; p = 0.012, independent of Rassi risk. Decreased ejection fraction was linked to EPS changes (p = 0.04). CONCLUSION: EPS changes among CCM was associated with progression of the Rassi score, indicating its utility as a stratification tool. Factors such as the presence of syncope/pre-syncope, decreased LVEF and wall motion abnormalities emerged as independent predictors within Rassi scores for changes in EPS.

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.

Impact of cardiac structure and function on exercise intolerance in Chagas cardiomyopathy: Insights from CPET and echocardiography.

INTRODUCTION: Chronic Chagas cardiomyopathy (CCC), the most severe clinical condition of Chagas disease, often leads to a reduction in functional capacity and the appearance of symptoms such as fatigue and dyspnea on exertion. However, its determinant factors remain unclear. We aimed to evaluate the peak oxygen consumption (VO2peak) in patients with CCC and identify its determining factors. METHODS: An observational study with 97 CCC patients was conducted. Patients underwent clinical examination, cardiopulmonary exercise test (CPET), and echocardiography as part of the standard clinical evaluation. Multivariate linear regression was used to identify independent clinical and echocardiographic predictors of VO2peak and percentage of predicted VO2. RESULTS: Mean age of study patients was 55.9 ± 13.4 years, median left ventricle ejection fraction (LVEF) was 40 (26-61.5) % and median VO2peak was 16.1 (12.1-20.8) ml/Kg/min. 36 patients presented preserved LVEF and 61 presented reduced LVEF. There were significant differences in almost all CPET variables (p < 0.05) between these two groups. VO2peak was associated with age, male sex, NYHA functional class, LVEF, left atrium diameter, LV diastolic diameter, E wave, LV mass index, and pulmonary artery systolic pressure (PASP). Age, male sex, LVEF, and E wave remained independently associated with VO2peak in the multivariate analysis (R2 = 0.69), furthermore, only LVEF and E wave were associated with the predicted VO2 percentage (R2 = 0.53). CONCLUSION: In patients with CCC, disease severity, male sex, LV systolic and diastolic function influence the functional capacity.

Chagas Cardiomyopathy and Myocardial Sympathetic Denervation.

PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

Association of Anti-β 1 and Anti-M2 Antibodies with Autonomic Nervous System Modulation in Patients with Chronic Chagas Cardiomyopathy

Abstract Background: Different immune mechanisms of myocardial damage involved in the pathophysiology of Chagas disease coexist with high titers of autoantibodies induced by T. cruzi . There are few studies in the literature about the adaptive role of anti-β1 and anti-M2 antibodies in chronic Chagas cardiomyopathy (CCC). Objectives: To evaluate the association between anti-β1 and anti-M2 antibodies with heart rate variability (HRV) parameters on 24h Holter monitoring and the rate-pressure product (RPP) on cardiopulmonary exercise testing (CPET). Methods: Anti-β1 and anti-M2 antibody titers were measured by enzyme-linked immunosorbent assay (ELISA) in 64 patients affected by CCC. Analysis of HRV was performed through the time-domain indices NNs, mean NN, SDNN, SDANN, SDNN index, NNNs, RMSSD, and pNN50. Spearman's correlation coefficient was used to assess the association between antibody titers and numerical variables. The Mann-Whitney test was used for comparison between two groups. Multiple linear regression was used to identify independent variables capable of explaining anti-β1 and anti-M2 antibody titers at the 5% significance level. Results: On 24h Holter, during the period of greatest parasympathetic activation (2:00-6:00 a.m.), an inverse association was found between anti-β1 titers and SDNN (rs=-0.13, p =0.041, n=43), as well as a direct association between anti-M2 titers and SDANN ( r s=0.317, p =0.039, n=43). Regarding CPET variables, anti-β1 titers were directly associated with RPP (rs=0.371, p =0.005, n=56). The subgroup of patients with a normal chronotropic response showed higher anti-β1 titers than the subgroup with an impaired response (p=0.023). RPP was an independent explanatory variable for anti-β1 titers, although with a low coefficient of determination (R2=0.147). Conclusion: The findings of this study suggest that, in patients with CCC, anti-β1 and anti-M2 antibodies may affect HRV parameters. RPP was directly associated with higher anti-β1 titers.

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

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.

Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy.

Infection by the protozoan Trypanosoma cruzi causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction. As IFN-γ and TNF-α have been described to affect mitochondrial function, we hypothesized that IFN-γ and TNF-α are involved in the myocardial mitochondrial dysfunction observed in CCC patients. In this study, we quantified markers of mitochondrial dysfunction and nitro-oxidative stress in CCC heart tissue and in IFN-γ/TNF-α-stimulated AC-16 human cardiomyocytes. We found that CCC myocardium displayed increased levels of nitro-oxidative stress and reduced mitochondrial DNA as compared with myocardial tissue from patients with dilated cardiomyopathy (DCM). IFN-γ/TNF-α treatment of AC-16 cardiomyocytes induced increased nitro-oxidative stress and decreased the mitochondrial membrane potential (ΔΨm). We found that the STAT1/NF-κB/NOS2 axis is involved in the IFN-γ/TNF-α-induced decrease of ΔΨm in AC-16 cardiomyocytes. Furthermore, treatment with mitochondria-sparing agonists of AMPK, NRF2 and SIRT1 rescues ΔΨm in IFN-γ/TNF-α-stimulated cells. Proteomic and gene expression analyses revealed that IFN-γ/TNF-α-treated cells corroborate mitochondrial dysfunction, transmembrane potential of mitochondria, altered fatty acid metabolism and cardiac necrosis/cell death. Functional assays conducted on Seahorse respirometer showed that cytokine-stimulated cells display decreased glycolytic and mitochondrial ATP production, dependency of fatty acid oxidation as well as increased proton leak and non-mitochondrial oxygen consumption. Together, our results suggest that IFN-γ and TNF-α cause direct damage to cardiomyocytes' mitochondria by promoting oxidative and nitrosative stress and impairing energy production pathways. We hypothesize that treatment with agonists of AMPK, NRF2 and SIRT1 might be an approach to ameliorate the progression of Chagas disease cardiomyopathy.

Accuracy and reliability of focused echocardiography in patients with Chagas disease from endemic areas: SaMi-Trop cohort study.

BACKGROUND: Chagas disease remains a major cause of cardiovascular death in endemic areas. Focused echocardiography (FoCUS) is a point-of-care means of assessing cardiac function which can be useful for the diagnosis of cardiac involvement. OBJECTIVE: This study aims evaluating the characteristics of validity and reliability of FoCUS applied on Chagas disease patients. METHODS: Patients with Chagas disease coming from an endemic area were selected from a large cohort (SaMi-Trop). A simplified echocardiogram with only three images was extracted from the conventional echocardiogram performed in this cohort. The images were evaluated by an observer who was blinded to the clinical and echocardiographic data, to determine the accuracy and reliability of FoCUS for cardiac assessment. The analysis constituted of 5 prespecified variables, dichotomized in absence or presence: left ventricular (LV) size and systolic function, right ventricular (RV) size and systolic function, and LV aneurysm. RESULTS: We included 725 patients with a mean age of 63.4 ± 12.3 years, 483 (67%) female. Abnormal electrocardiogram was observed in 81.5% of the patients. Left and right ventricular dysfunctions were found in 103 (14%) and 49 (7%) of the patients, respectively. Sensitivity, specificity, positive predictive value and negative predictive value were 84%, 94%, 70% and 97% for LV enlargement and 81%, 93%, 68% and 97% for LV systolic dysfunction, respectively, and 46%, 99%, 60% and 98% for RV dilatation, and 37%, 100%, 100% and 96% for RV dysfunction, respectively. Inter and intraobserver agreement were 61% and 87% for LV enlargement and 63% and 92% for LV dysfunction, respectively, and 50% and 49% for RV size and 46% and 79% for RV dysfunction, respectively. LV apical aneurysm was found in 45 patients (6.2%) with the lowest sensitivity of FoCUS study (11%; 95% CI 2-28%). CONCLUSIONS: FoCUS showed satisfactory values of validity and reliability for assessment of cardiac chambers in patients with Chagas disease, except for apical aneurysm. This tool can identify heart disease with potential impact on patient management in the limited-resource setting.

Accuracy of health-related quality of life in identifying systolic dysfunction in patients with Chagas cardiomyopathy.

OBJECTIVE: Systolic dysfunction is a well-established marker of mortality in patients with Chagas cardiomyopathy (CC). However, its diagnosis is expensive and useful tools for screening these patients are required. The evaluation of the health-related quality of life (HRQoL) detects the patient's perception of the disease's impact. However, its accuracy in identifying patients with CC and systolic dysfunction is unknown. The study aimed to verify the sensitivity, specificity and predictive values of the physical and mental components related to HRQoL in identifying patients with CC and systolic dysfunction. METHODS: 75 patients with CC, aged 49 (95% confidence interval: 47-51) years, were evaluated by echocardiography and Short-Form of Health Survey (SF-36) questionnaire. Systolic dysfunction was defined by left ventricular ejection fraction <52% for men and <54% for women and left ventricular diastolic diameter >55 mm. RESULTS: Most patients (73%) had systolic dysfunction, with lower HRQoL values in the physical functioning, physical role functioning and general health perceptions domains and in the physical component summary. The accuracy of identifying patients with systolic dysfunction by the scores of physical components was 73% and 62% of mental components. The optimal cut-off point was 46 for physical and 54 for mental components, with respective positive predictive values of 91% and 80%. CONCLUSION: The evaluation of the HRQoL by the SF-36, a low-cost instrument, can be useful in identifying patients with systolic dysfunction, assisting in the screening and risk stratification of patients.

Exercise training improves microvascular function in patients with Chagas heart disease: Data from the PEACH study.

BACKGROUND: Chagas heart disease (CHD) impairs the systemic microvascular function. We investigated the effects of exercise training on cutaneous microvascular function among patients with CHD. METHODS: Patients from the PEACH study were randomly assigned to a supervised exercise training 3 times/week for 6 months (Trained; n = 10) or a control group (Untrained; n = 8). Both groups underwent evaluation of microvascular function before, and at 3- and 6-months of follow-up. Cutaneous vascular conductance (CVC) was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh), sodium nitroprusside (SNP) and during post-occlusive reactive hyperemia (PORH). RESULTS: At 3-months of follow-up, no difference was detected between groups in CVC responses to ACh (p = 0.50), SNP (p = 0.26) and HRPO (p = 0.65). However, at 6-months of follow-up, trained vs. untrained patients improved CVC induced by SNP-iontophoresis (0.19 ± 0.10 vs. 0.14 ± 0.15 APU.mmHg-1; p = 0.05) and PORH (0.63 ± 0.15 vs. 0.48 ± 0.18 APU.mmHg-1; p = 0.05). CVC response to ACh-iontophoresis was similar between groups (0.19 ± 0.11 vs. 0.22 ± 0.17 APU.mmHg-1; p = 0.38). CONCLUSION: Exercise training performed during 6 months improved the cutaneous microvascular function of CHD patients. Further studies evaluating the mechanism involved in this response are warranted.

Comparação entre classificação funcional e fração de ejeção em pacientes com insuficiência cardíaca na Doença de Chagas / Functional classification versus ejection fraction in patients with heart failure and Chagas Disease

Introdução: A doença de Chagas é uma infecção causada pelo protozoário Trypanosoma cruzi. É considerada um importante problema de saúde do mundo, tendo como manifestações a dilatação cardíaca, arritmias e morte. A insuficiência cardíaca é uma síndrome complexa e de elevada morbimortalidade, que evolui com complicações semelhantes. Para categorizar a gravidade da insuficiência cardíaca, utilizamos a classificação funcional da New York Heart Association, para estratificar risco e terapias para cardiopatias. Além disso, a reduzida fração de ejeção do ventrículo esquerdo, medida pelo ecocardiograma, tem relação direta com mau prognóstico. Objetivo: Comparar a relação entre a classificação funcional pela New York Heart Association e a medida da fração de ejeção do ventrículo esquerdo em pacientes ambulatoriais chagásicos e não chagásicos. Metódos: Estudo de corte transversal na coorte, composto de pacientes acompanhados em ambulatório de insuficiência cardíaca. Foram realizadas avaliação de prontuários, entrevista clínica e verificação da classificação funcional e da fração de ejeção do ventrículo esquerdo pelo ecocardiograma. Os dados foram arquivados em banco de dados e analisados pelo Statistical Package for the Social Sciences. Resultados: No período de agosto de 2018 a julho de 2019, foram selecionados 127 indivíduos com insuficiência cardíaca. Destes, 34 (26,8%) eram portadores da doença de Chagas e 93 (73,3%) eram não Chagas. Observou-se predominância do sexo masculino (53,5%) e de idade >60 anos (61,4%). Houve predomínio da classe funcional II nos grupos. Em relação à fração de ejeção dos pacientes chagásicos e não chagas, observou-se que, respectivamente, 71% contra 93% dos pacientes tinham fração de ejeção reduzida, 21% versus 6% tinham fração de ejeção intermediária e 8% versus 1% fração de ejeção preservada. Conclusão: Houve associação entre classe funcional avançada e reduzida fração de ejeção do ventrículo esquerdo principalmente em chagásicos, podendo ser usada para acompanhamento evolutivo ambulatorial. (AU)

Introduction: Chagas disease, an infection caused by the protozoan Trypanosoma cruzi, is an important health problem worldwide that causes cardiac dilation, arrhythmias, and death. Heart failure is a complex syndrome with high morbidity and mortality rates that progresses with similar complications. The New York Heart Association functional classification is used to categorize heart failure severity and stratify heart disease risks and therapies. A reduced left ventricular ejection fraction measured by echocardiography is directly related to a poor prognosis. Objective: To compare the relationship between New York Heart Association functional classification and left ventricular ejection fraction in Chagas versus no Chagas disease outpatients. Methods: Cross-sectional study in a cohort of patients followed at a heart failure clinic. Medical records, clinical interviews, functional classification, and left ventricular ejection fraction by echocardiography were analyzed. The data were filed in a database and analyzed using SPSS software. Results: A total of 127 patients with heart failure were selected from August 2018 to July 2019. Of them, 34 (26.8%) had Chagas disease and 93 (73.3%) had no Chagas disease. There was a predominance of men (53.5%) and patients aged > 60 years (61.4%). There was also a predominance of functional class II. Of the Chagas and no Chagas disease patients, 71% versus 93% had a reduced ejection fraction, 21% versus 6% had a mid-range ejection fraction, and 8% versus 1% had a preserved ejection fraction, respectively. Conclusion: There was an association between advanced functional class and reduced left ventricular ejection fraction, especially in Chagas patients, information that can be used for outpatient follow-up. (AU)

Deformação miocárdica (strain) e fibrose miocárdica na forma cardíaca leve da Doença de Chagas / Myocardial deformation (strain) and myocardial fibrosis in mild cardiac Chagas Disease

Fundamento: A identificação precoce do dano miocárdico parece ser importante na abordagem do paciente com doença de Chagas. A ecocardiografia com strain obtida por speckle tracking e a avaliação da fibrose miocárdica por meio da ressonância magnética cardíaca podem ser métodos diagnósticos promissores nesse sentido. Objetivo: Avaliar o acometimento miocárdico especificamente na forma crônica cardíaca leve da doença de Chagas por meio do strain por speckle tracking e da fibrose miocárdica pela ressonância magnética cardíaca, além de suas correlações. Método: Estudo de corte transversal que analisou portadores da forma cardíaca crônica leve da doença de Chagas (fração de ejeção preservada) submetidos à ecocardiografia com strain por speckle tracking e à ressonância magnética cardíaca. Resultados: Foram incluídos 21 participantes (mulheres: 62%; idade: 54 ± 5 anos). A prevalência de fibrose miocárdica por meio do realce tardio miocárdico foi de 50%. O strain longitudinal global encontrava-se diminuído em 17 pacientes (81%), com mediana de 14,1% (intervalo interquartil de 12,1 a 16,3). Os valores do mapa T1 encontravam-se, em média, elevados nos portadores de doença de Chagas (993 ± 163 ms). O mapa T1 foi significativamente correlacionado com o strain longitudinal global (r= 0,634; p = 0,015). Além disso, o índice de dispersão mecânica, obtido por strain, estava aumentado (> 55 ms) em 84%, com a maior área sob a curva Característica de Operação do Receptor (área sob a curva de 0,696; intervalo de confiança de 95% de 0,412-0,981) para discriminação de fibrose pelo realce tardio miocárdico. Conclusão: O strain miocárdico e o mapa T1 se comportam como marcadores precoces do dano miocárdico na cardiopatia chagásica crônica leve. O índice de dispersão mecânica estava elevado e foi o parâmetro que melhor se correlacionou com o realce tardio miocárdico. (AU)

Background: The early identification of myocardial damage seems important in the management of patients with Chagas disease. However, it is unknown whether speckle tracking echocardiography strain and cardiac magnetic resonance imaging are promising methods for assessing myocardial involvement and fibrosis, respectively. Objective: To evaluate myocardial involvement in the mild chronic cardiac form of Chagas disease using speckle tracking strain and myocardial fibrosis by cardiac magnetic resonance and assess their correlations. Method: This cross-sectional study analyzed patients with the mild chronic cardiac form of Chagas disease (preserved ejection fraction) using speckle tracking echocardiography and cardiac magnetic resonance. Results: The study included 21 participants (women: 62%; age: 54 ± 5 years). The prevalence of myocardial fibrosis was 50% on delayed myocardial enhancement. The median global longitudinal strain was decreased (14.1%; interquartile range, 12.1­16.3%) in 17 patients (81%). The mean T1 mapping value was high in patients with Chagas disease (993 ± 163 ms). The T1 map was significantly correlated with the global longitudinal strain (r = 0.634; p = 0.015). In addition, the mechanical dispersion index obtained by strain was increased (>55 ms) by 84%, with the largest area under the receiver operating characteristic curve (area under the curve, 0.696; 95% confidence interval, 0.412­0.981) for fibrosis discrimination by delayed myocardial enhancement. Conclusion: Myocardial strain and T1 mapping are early markers of myocardial damage in mild chronic Chagas heart disease. The mechanical dispersion index was high and the most closely correlated with delayed myocardial enhancement. (AU)

Nuclear Medicine Methods for Assessment of Chronic Chagas Heart Disease

Abstract Several different imaging methods can be used to evaluate patients with Chagas heart disease (CHD) for diagnostic and prognostic purposes, including plain chest radiography; echocardiography; myocardial perfusion scintigraphy, for detection of ischemia and fibrosis; radionuclide gated-angiography, for evaluation of biventricular function; 123I-MIBG labeling of sympathetic myocardial innervation; MRI, for detection and quantitation of myocardial fibrosis; and coronary angiography. This study aims to review the contributions of these nuclear medicine methods to understanding of the pathophysiology of chronic Chagas cardiomyopathy (CCC). Careful analysis and integration of findings provided by these imaging methods in patients with CCC at different stages has contributed significantly to improving understanding of several peculiarities of the disease. Clinical and experimental studies in animal models show that perfusion abnormalities detected in association with dysfunctional but viable myocardium are a common finding in CCC patients and correspond to areas of cardiac sympathetic denervation, as assessed by 123I-MIBG imaging. Furthermore, recent reports have demonstrated a close relationship between coronary microvascular disturbances and myocardial inflammation. Thus, ongoing research, mainly focused on refinements of 18F-FDF -PET techniques and further exploration of nuclear methods, such as SPECT, have the potential to contribute to detection and monitoring of early subclinical myocardial damage thereby enabling evaluation of therapeutic strategies targeting inflammation and microvascular ischemia that could result in better prognostic stratification of patients with CHD.

Cardiac magnetic resonance imaging in Chagas' disease: a parallel with electrophysiologic studies.

Chagas' disease (CD), caused by the parasite Trypanosoma cruzi, is the leading cause of cardiac disability from infectious diseases in Central and South America. The disease progresses through an extended, asymptomatic form characterized by latency without clinical manifestations into a symptomatic form with cardiac and gastro-intestinal manifestations. In the terminal phase, chronic Chagas' myocarditis results in extensive myocardial fibrosis, chamber enlargement with aneurysms and ventricular tachycardia (VT). Cardiac magnetic resonance imaging (CMR) has proven useful in characterizing myocardial fibrosis (MF). Sub-epicardial and mid-wall fibrosis are less common patterns of MF in CHD than transmural scar, which resembles myocardial infarction. Commonly involved areas of MF include the left ventricular apex and basal infero-lateral wall, suggesting a role for watershed ischemia in the pathophysiology of MF. Electrophysiology studies have helped refine the relationship between MF and VT in this setting. This article reviews the patterns of MF in CHD and correlate these patterns with electrogram patterns to predict risk of ventricular arrhythmias and sudden death.