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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 (VO 2peak ) 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 VO 2peak and percentage of predicted VO 2 ., 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 VO 2peak 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. VO 2peak 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 VO 2peak in the multivariate analysis (R 2  = 0.69), furthermore, only LVEF and E wave were associated with the predicted VO 2 percentage (R 2  = 0.53)., Conclusion: In patients with CCC, disease severity, male sex, LV systolic and diastolic function influence the functional capacity., Competing Interests: Declaration of competing interest All authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters., Methods and Results: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm 2 ), as compared to CH + SLN (515.1 ± 133.0 cell/mm 2 ), but larger than CO (193.0 ± 25.7 cell/mm 2 ). The fibrosis and TNF-α expression was higher in both infected groups., Conclusions: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Sudden cardiac death (SCD) can be the first clinical event of Chagas heart disease (CHD). However, current guidelines contain no clear recommendation for early cardioverter-defibrillator implantation. Using imaging modalities, we evaluated associations among autonomic denervation, myocardial hypoperfusion, fibrosis and ventricular arrhythmia in CHD., Methods and Results: Twenty-nine patients with CHD and preserved left ventricular function underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy, 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion and cardiac magnetic resonance imaging (MRI). They were divided into arrhythmic (≥ 6 ventricular premature complexes/h and/or non-sustained ventricular tachycardia on 24-hour Holter, n = 15) and non-arrhythmic (< 6 ventricular premature complexes/h and no ventricular tachycardia; n = 14) groups. The arrhythmic group had higher denervation scores from MIBG imaging (23.2 ± 18.7 vs 5.6 ± 4.9; P < .01), hypoperfusion scores from MIBI SPECT (4.7 ± 6.8 vs 0.29 ± 0.6: P = .02), innervation/perfusion mismatch scores (18.5 ± 17.5 vs 5.4 ± 4.8; P = .01) and fibrosis by late gadolinium enhancement on MRI (14.3% ± 13.5% vs 4.0% ± 2.9%; P = .04) than the non-arrhythmic group., Conclusion: These imaging parameters were associated with ventricular arrhythmia in early CHD and may enable risk stratification and the implementation of primary preventive strategies for SCD., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Chagas disease (ChD) represents a significant health burden in endemic regions of Latin America and is increasingly being recognized as a global health issue. The cardiac involvement in ChD, known as Chagas cardiomyopathy (ChCM), is the most severe manifestation and a leading cause of heart failure and mortality in affected individuals. Echocardiography, a non-invasive imaging modality, plays a crucial role in the diagnosis, monitoring, and risk stratification of ChCM. This consensus recommendation aims to provide guidance on the appropriate use of echocardiography in ChD. An international panel of experts, including cardiologists, infectious disease specialists, and echocardiography specialists, convened to review the available evidence and provide practical recommendations based on their collective expertise. The consensus addresses key aspects related to echocardiography in ChD, including its role in the initial evaluation, serial monitoring, and risk assessment of patients. It emphasizes the importance of standardized echocardiographic protocols, including the assessment of left ventricular function, chamber dimensions, wall motion abnormalities, valvular involvement, and the presence of ventricular aneurysm. Additionally, the consensus discusses the utility of advanced echocardiographic techniques, such as strain imaging and 3D echocardiography, in assessing myocardial mechanics and ventricular remodeling., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Background: Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas' cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction OBJECTIVE: To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC., Methods: 18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123 Iodo-metaiodobenzylguanidine and 99m Tc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities., Results: In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001)., Conclusion: Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Although Chagas cardiomyopathy is related to thromboembolic stroke, data on risk factors for cerebrovascular events in Chagas disease is limited. Thus, we assessed the relationship between left ventricular (LV) impairment and cerebrovascular events and sources of thromboembolism in patients with Chagas cardiomyopathy., Methods: This retrospective cohort included patients with chronic Chagas cardiomyopathy who underwent cardiovascular magnetic resonance (CMR). CMR was performed with a 1.5 T scanner to provide LV volumes, mass, ejection fraction (LVEF), and myocardial fibrosis. The primary outcome was a composite of incident ischemic cerebrovascular events (stroke or transient ischemic attack-TIA) and potential thromboembolic sources (atrial fibrillation (AF), atrial flutter, or intracavitary thrombus) during the follow-up., Results: A total of 113 patients were included. Median age was 56 years (IQR: 45-67), and 58 (51%) were women. The median LVEF was 53% (IQR: 41-62). LV aneurysms and LV fibrosis were present in 38 (34%) and 76 (67%) individuals, respectively. The median follow-up time was 6.9 years, with 29 events: 11 cerebrovascular events, 16 had AF or atrial flutter, and two had LV apical thrombosis. In the multivariable model, only lower LVEF remained significantly associated with the outcomes (HR: 0.96, 95% CI: 0.93-0.99). Patients with reduced LVEF lower than 40% had a much higher risk of cerebrovascular events and thromboembolic sources (HR: 3.16 95% CI: 1.38-7.25) than those with normal LVEF. The combined incidence rate of the combined events in chronic Chagas cardiomyopathy patients with reduced LVEF was 13.9 new cases per 100 persons-year., Conclusions: LV systolic dysfunction is an independent predictor of adverse cerebrovascular events and potential sources of thromboembolism in patients with chronic Chagas cardiomyopathy., (© 2022. The Author(s).)

Chagas disease (CD) is a neglected infectious disease associated with early mortality and substantial disability. Three-dimensional speckle tracking (3D STE) may play a role in the evaluation of CD. We aim to characterize new echocardiographic variables in patients with CD and to assess the hypothesis that 3D STE may predict outcomes. Seventy-two patients with CD were included. Clinical and conventional 2D and 3D STE analysis were performed. Patients were followed up for 60 months. Clinical events were defined as hospitalization for heart failure, complex ventricular arrhythmias, heart transplant and all-cause death. Seventy-two patients were recruited and enrolled in three groups: left ventricular ejection fraction (LVEF) < 0.40 (N = 22; reduced LVEF or rLVEF); 0.40 ≤ LVEF ≤ 0.50 (N = 10; mildly reduced LVEF or mrLVEF) and LVEF > 0.50 (N = 30; preserved LVEF or pLVEF). After a Cox model analysis, the top predictors of composite endpoints were 2D LV global longitudinal strain (GLS) ≤ - 11.3% (AUC = 0.87), 2D LV global circumferential strain (GCS) ≤  - 10.1% (AUC = 0.79), 3D LV GLS ≤ - 13% (AUC = 0.82), 3D LV area strain ≤ - 16% (AUC = 0.81) and right ventricle (RV) GLS ≤ - 17.2% (AUC = 0.78). Patients with CD and mrLVEF were morphologically similar to the rLVEF patients despite the benign evolution as the pLVEF group. RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain are strong predictors of 60 months outcomes in patients with CD., (© 2022. The Author(s).)

Background Chagas disease is a neglected tropical disease that is still considered a global health emergency. In the Amazon region, most of the reports are of acute cases that are associated with oral transmission. This study aimed to evaluate myocardial injury in patients with acute Chagas disease before and after treatment. Methods and Results We evaluated 23 patients with acute Chagas disease in 3 different stages of progression. Group 1 had 12 patients evaluated during the acute phase, at the time of diagnosis, and 1 year after treatment, and Group 2 had 11 patients in the late postacute phase who were evaluated 5.2 years on average after diagnosis and treatment. ECGs with the Selvester score, 24-hour Holter exam, and cardiovascular magnetic resonance imaging were performed. The mean age of the 23 patients was 44.3±18.9 years, and they were mostly men (15/65.24%) from Amazonas state (22/95.6%). In 69.6% (n=16) of the patients, some ECG alterations were found, the most frequent being left anterior fascicular block and ventricular repolarization. In Group 1, the 24-hour Holter exam showed atrial tachycardia in 3 (25%) patients and ventricular extrasystoles in 2 (16.7%) patients. In Group 2, 1 patient had ventricular extrasystoles. Myocardial injury was observed in 7 patients (58.3%) at the acute phase and in 5 (50%) patients at the 1-year follow-up in Group 1 and in 2 (18.2%) patients in Group 2. Conclusions This article describes, for the first time, myocardial injury shown by cardiovascular magnetic resonance imaging in a group of patients with acute Chagas disease and reveals the importance of early detection and follow-up of the cardiac impairment in these patients.

Background: Three-dimensional echocardiography (3D ECHO) allows the generation of a volume-time curve representative of changes in the left ventricular (LV) volume throughout the entire cardiac cycle., Objective: This study aims to demonstrate the hemodynamic adaptations present in Chagas cardiomyopathy (CC) by means of the volume and flow measurements obtained by the volume-time curve by 3D ECHO., Methods: Twenty patients with CC and 15 healthy subjects were prospectively enrolled in a cross-sectional design study. 3D ECHO was performed in all subjects and the volume over time curves of the LV was generated. The flow was obtained by the first derivative of the volume-time curve using the software MATLAB. Statistical significance was set at p<0.05., Results: Although CC patients had lower LV ejection fraction compared to the control group (29.8±7.5 vs. 57.7±6.1, p<0.001), stroke volume (61.5±25.2 vs. 53.8±21.0, p=0.364) and maximum ejection flow during systole (-360.3±147.5 vs. -305.6±126.0, p=0.231) were similar between the groups. Likewise, the maximum flow in the early diastolic filling phase and during atrial contraction was similar between groups. An increase in preload expressed by LV end diastolic volume (204.8±79.4 vs. 93.0±32.6), p<0.001) may maintain the flow and stroke volumes similar to the controls., Conclusion: Using a non-invasive tool, we demonstrated that an increase in LV end-diastolic volume may be the main adaptation mechanism that maintains the flow and stroke volumes in the setting of severe LV systolic dysfunction.

Electrocardiographic (ECG) abnormalities are frequently identified in Chronic Chagas cardiomyopathy (CCC) patients and advanced abnormalities are related to a worse prognosis. Cardiac Magnetic Resonance (CMR) can precisely assess ventricular systolic dysfunction and quantify myocardial fibrosis (MF), both identified as prognostic factors. We sought to investigate if ECG abnormalities in CCC patients were associated with more severe myocardial involvement as evaluated by CMR., Methods: CCC patients with 12‑lead ECG and CMR closely obtained were included. ECG analysis evaluated rhythm, presence, and type of intraventricular conduction disturbances (IVCD) and, ventricular premature beats (VPB). CMR short-axis cine and late gadolinium enhancement images were evaluated to obtain left and right ventricular ejection fractions and MF mass, respectively. Statistical significance was set in 5%., Results: 194 CCC patients (98 women, 56 ± 14 years) were evaluated, and no IVCD was detected in 71. The most common IVCD was the association of right bundle branch block and left anterior fascicular block (RBBB+LAFB) in 58 patients, followed by isolated RBBB in 34, isolated LAFB in 17, and left bundle branch block (LBBB) in 14 patients. Of patients with no IVCD, 63% had MF and the burden of fibrosis (no IVCD - 7.4 ± 8.6%; RBBB - 6.6 ± 6.5%; p = 1.00), as well as left ventricular ejection fraction (LVEF) (no IVCD - 52 ± 14%; RBBB - 55 ± 10%; p = 1.00) were similar to patients with isolated RBBB. Left conduction system impairment was associated with lower LVEF (LAFB - 39 ± 15%; RBBB+LAFB- 41 ± 15%; and LBBB - 35 ± 15%; p < 0.001) and more MF (RBBB+LAFB - 12.2 ± 10.4%; LBBB - 10.6 ± 7.5%; and LAFB - 12.0 ± 7.0%; p < 0.001). The univariable model showed that the presence of MF was related to RBBB+LAFB (OR 5.0; p = 0.001) and VPB (OR 6.3; p = 0.014). After adjustment for age, gender, and different risk factors in a multivariable model, the same findings were still significantly related to CMR myocardial fibrosis (RBBB+LAFB OR 5.0; p = 0.002 / VPB OR 6.9; p = 0.015)., Conclusions: ECG without IVCD does not exclude serious cardiac abnormalities in CCC, and isolated RBBB seems to have a benign course. The presence of VPB and left branch conduction impairment, especially LAFB associated with RBBB, indicate a more severe cardiac involvement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We aimed to identify, among Chronic Chagas Cardiomyopathy (CCC) patients with left ventricular dysfunction (LVD) and non-left bundle branch block (non-LBBB), subgroups with different functional and mechanical patterns of global longitudinal strain (GLS) and intraventricular dyssynchrony (IVD) at rest and after exercise stress test, and reclassify them using a new echocardiographic approach., Methodology: In this single-center cross-sectional study, 40 patients with CCC, left ventricular ejection fraction (LVEF) ≤ 35% and non-LBBB underwent rest echocardiography and then treadmill exercise stress echocardiography with GLS and IVD analysis. The sample was divided into four groups, based on GLS and IVD significant variation between rest and exercise: GLS + IVD+ (9 patients); GLS + IVD- (9 patients); GLS-IVD+ (10 patients); GLS-IVD- (10 patients)., Results: At rest, median LVEF was 28% (21.3%-33%) and GLS (-7% (-5%/-9.3%), were not different among groups. The average response of GLS was an increase of 0.74% over rest values, and the average response of IVD was a decrease of 6.9 ms. Group GLS-IVD+ presented more dyssynchrony at rest (p = 0.01). Left atrial (LA) volume (higher in GLS-IVD-) (p = 0.022) and TAPSE (higher in GLS + IVD+) (p = 0.015) were also different among groups at baseline. Of the 40 patients evaluated, 27 (67.5%) had very severe LVD (GLS < -8%). In addition, among these patients, 11 patients had contractile reserve after undergoing stress echocardiography., Conclusions: In patients with CCC, severe LVD and non-LBBB, the evaluation of GLS and IVD between rest and exercise was able to reclassify myocardial function and to identify subgroups with contractile reserve and significant dyssynchronopathy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The impact of left ventricular reverse remodeling (LVRR) on the prognosis of Chagas cardiomyopathy is unknown. The aim of this study was to determine whether the presence of LVRR can predict mortality in these patients., Methods: From January 2000 to December 2010, the medical charts of 159 patients were reviewed. LVRR was defined as an increase of left ventricular ejection fraction (LVEF) and a decrease of left ventricular end-diastolic diameter (LVDD) by two-dimensional echocardiography. No patient underwent cardiac resynchronization therapy or required mechanical ventricular assistance., Results: At baseline, median (25th-75th) LVDD was 64 mm (59-70), and median LVEF was 33.2% (26.4-40.1). LVRR was detected in 24.5% of patients in a 40-month (26-64) median follow-up. In the LVRR group, LVDD decreased from 64 mm (59-68) to 60 mm (56-65; p < 0.001), and LVEF increased from 31.3% (24.1-39.0) to 42.5% (32.2-47.7; p < 0.001). However, LVRR was not associated with heart failure hospitalization, cardiogenic shock, heart transplantation, or mortality (p > 0.05 for all comparisons). The Cox proportional hazard model analysis identified only cardiogenic shock (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 1.51-3.85; p < 0.001) and serum sodium level (HR: 0.91; 95% CI: 0.86-0.96; p < 0.001) as independent predictors of all-cause mortality., Conclusions: Left ventricular reverse remodeling occurs in one quarter of patients with Chagas cardiomyopathy and have no impact on the outcomes of patients with this condition.

Objectives: This study aimed to describe the electrocardiographic and echocardiographic status of chronic Chagas disease (cChD) patients treated with nifurtimox., Methods: An observational study was performed in 146 cChD patients followed over a mean of 7.9 years., Results: Of the 146 patients, 41 (28.1%) with normal electrocardiogram (ECG) at baseline maintained this condition, 34 (23.3%) with altered ECG at baseline normalised the alterations, and 46 (31.5%) with ECG abnormalities at baseline maintained this condition [23 (15.8%) with small alterations]. Finally, 25 cases (17.1%) in indeterminate phase altered the ECG. Differences before and after follow-up (P < 0.001) were found. The percentage of beneficial treatment was different than expected by chance (Z = 4.8; P < 0.001) and the annual percentage of cases that developed ECG alterations was lower than that of a historical cohort of untreated patients (P < 0.001). An echocardiogram was performed in 68 patients with baseline ECG alterations. The ejection fraction (EF) was normal in 57 (83.8%) and abnormal in 11 (16.2%). In 38 patients with ECG abnormalities that did not progress after treatment, EF and segmental motility (SM) were normal in 31 (81.6%) and 26 (68.4%), respectively. In 17 patients with ECG abnormalities, EF and SM were normal in 15 (88.2%) and 14 (82.4%) cases, respectively., Conclusion: Less progression to cardiomyopathy compared with a historical untreated cohort as well as the EF/SM results in patients with abnormal ECG that did not progress and in indeterminate cChD that altered the ECG suggests a beneficial effect of nifurtimox., Competing Interests: Competing interests None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Chagas disease is a major health concern in Latin America. Ventricular arrhythmia (VA) is a hallmark of Chagas cardiomyopathy (CCM), associated with worse prognosis. The present study aimed to verify the association between myocardial mechanical dispersion (MD) and ventricular arrhythmogenicity in CCM. In a cross-sectional study, 77 patients (55.8 ± 10.4 years) with CCM were evaluated. Global longitudinal strain (GLS) and MD were assessed by echocardiography, derived from the speckle tracking technique. Myocardial MD was measured from the onset of the Q/R wave on electrocardiogram to the peak longitudinal strain in 16 segments of the left ventricle. Frequency and complexity of ventricular extrasystoles (VES) were assessed by dynamic electrocardiography. The density and complexity of VES and the presence of non-sustained ventricular tachycardias (NSVTs) increase as MD increases. In logistic regression, MD was the only variable associated with the presence of paired VES and ventricular bigeminy. In addition, both MD and GLS were associated with the presence of NSVT (both, p < 0.01), and MD was independently associated with NSVT (OR 1.04, 95% CI 1.004-1.201, p = 0.031). In CCM, MD is associated with a higher density and complexity of VES, including NSVT., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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., (© 2021 John Wiley & Sons Ltd.)

Chagas disease (CD) mainly conveys stroke risk through structural cardiac disease. However, stroke and cognitive impairment are seen in CD independently of cardiac disease severity. Chronic inflammation may be an explanation for this association, because inflammation plays an important role in the pathogenesis of acute ischemic stroke and dementia. In the present study, we selected five candidate biomarkers for Chagas disease: interleukin-6, membrane metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP1), orosomucoid, and neprilysin. We sought to determine if mean levels of proinflammatory biomarkers are higher in patients with heart failure (HF) associated with Chagas disease when compared with other etiologies of HF. Patients were consecutively enrolled from subspecialty HF outpatient clinics at two university-based hospitals. Serum biomarker levels from blood samples were analyzed by ELISA. Severity of HF on echocardiography was worse in non-CD when compared with CD patients. No significant difference was observed in the levels of candidate biomarkers between the CD and non-CD groups. We found a significantly 2.2 ng/mL higher level of TIMP1 in CD when compared with non-CD patients with HF after adjustment for age and gender (95% confidence interval = 0.1 to 4.5, P = 0.037). In patients with heart failure, serum TIMP1 is increased in Chagas patients despite a lower myocardial disease severity on echocardiography when compared with non-Chagas patients. TIMP1 is probably one of multiple mediators of inflammatory injury.

Chagas disease is caused by infection from the protozoan parasite Trypanosoma cruzi. Although it is endemic to Latin America, global migration has led to an increased incidence of Chagas in Europe, Asia, Australia, and North America. Following acute infection, up to 30% of patients will develop chronic Chagas disease, with most patients developing Chagasic cardiomyopathy. Chronic Chagas cardiomyopathy is highly arrhythmogenic, with estimated annual rates of appropriate implantable cardioverter-defibrillator therapies and electrical storm of 25% and 9.1%, respectively. Managing arrhythmias in patients with Chagasic cardiomyopathy is a major challenge for the clinical electrophysiologist, requiring intimate knowledge of cardiac anatomy, advanced training, and expertise. Endocardial-epicardial mapping and ablation strategy is needed to treat arrhythmias in this patient population, owing to the suboptimal long-term success rate of endocardial mapping and ablation alone. We also describe innovative approaches to improve acute and long-term clinical outcomes in patients with refractory ventricular arrhythmias following catheter ablation, such as bilateral cervicothoracic sympathectomy and bilateral renal denervation, among others., Competing Interests: FUNDING SUPPORT AND AUTHOR DISCLOSURES Drs. Pisani and Scanavacca serve on the Speakers Bureau for Biosense Webster. Dr. Natale is a consultant for Boston Scientific, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic. Dr Di Biase is a consultant for Biosense Webster and Stereoataxis; and has received speaker honoraria/travel support from Biosense Webster, St. Jude Medical (now Abbott), Boston Scientific, Medtronic, Biotronik, Pfizer, and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Idiopathic dilated cardiomyopathy (DCM) is a common acquired cardiac disease in large breed dogs with a high prevalence in Doberman pinschers. It is characterized histologically by attenuated wavy fibers and fatty infiltration with degeneration. The phenotypic appearance of DCM includes ventricular dilation with systolic dysfunction and ventricular arrhythmias. These changes can be caused by other etiologies, including infectious, toxic, metabolic, and nutritional deficiencies. Chagas disease is the result of an infection with the protozoal parasite, Trypanosoma cruzi, transmitted by an insect vector. Histopathology of the myocardium is characterized by inflammation, fibrosis, and pseudocysts containing T. cruzi amastigotes. Differentiating idiopathic DCM from infectious myocarditis can be challenging when the clinical presentation and diagnostic test results are similar in affected dogs. We present thoracic radiographs, echocardiography, and post-mortem histopathology images obtained from two Doberman pinschers with similar signalment, clinical presentation, and electrocardiographic and echocardiographic appearance but with different appearing radiographs and different etiologies for their heart disease, one with idiopathic DCM and one with myocarditis attributed to Chagas disease, to highlight the value of considering alternative etiologies for DCM to guide additional clinical evaluation and owner counseling., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Chagas disease is one of the most common diseases in Latin-America, and cardiac involvement is a significant cause of death. Assessment of myocardial strain may detect early myocardial damage., Objectives: To determine differences in longitudinal strain using speckle tracking to assess regional and global left ventricular function in patients with the indeterminate form of Chagas disease, in comparison with a control group., Methods: This is a retrospective matched case-control study, conducted in a single center. We evaluated 45 adult patients with Chagas disease, diagnosed with 2 serological methods, without evidence of cardiac involvement, who were compared with 45 healthy control subjects, who were sex- and age-matched. All patients underwent Doppler echocardiography and longitudinal strain with speckle tracking., Results: Median age was 59 years, and 60% were female. Echocardiographic parameters were similar in patients with Chagas and control subjects. In patients with Chagas, global strain differed significantly from that of control subjects (-17 vs -20.3, P < .001). Segmental strain showed 7 abnormal segments in patients with Chagas (P < .05)., Conclusions: In patients with the indeterminate form of Chagas disease, global and segmental longitudinal peak systolic strain is reduced compared with healthy subjects, thus suggesting that it could be a sensitive technique to detect early myocardial damage. These findings could provide useful information regarding the pathophysiology of cardiac involvement and understand whether they might have prognostic usefulness or help develop strategies to modify the course and prognosis of patients with Chagas disease. A longitudinal prospective study would be necessary to validate our findings., (© 2020 Wiley Periodicals LLC.)

Background: Chagas disease (CD) as neglected secondary form of suspected coronary microvascular dysfunction (CMD)., Objectives: Comparison of patients with CMD related to CD (CMD-CE) versus patients with CMD caused by other etiologies (CMD-OE)., Methods: Of 1292 stable patients referred for invasive coronary angiography to elucidate the hemodynamic pattern and the cause of angina as a cardinal symptom in their medical history, 247 presented normal epicardial coronary arteries and 101 were included after strict exclusion criteria. Of those, 15 had suspected CMD-CE, and their clinical, hemodynamic, angiographic and scintigraphic characteristics were compared to those of the other 86 patients with suspected CDM-OE. Level of significance for all comparisons was p < 0.05., Results: Patients with suspected CMD-CE showed most anthropometric, clinical, angiographic hemodynamic and myocardial perfusion abnormalities that were statistically similar to those detected in the remaining 86 patients with suspected CMD-OE. LV diastolic dysfunction, expressed by elevated LV end-diastolic pressure was equally found in both groups. However, as compared to the group of CMD-OE the group with CMD-CE exhibited lower left ventricular ejection fraction (54.8 ± 15.9 vs 61.1 ± 11.9, p= 0.049) and a more severely impaired index of regional wall motion abnormalities (1.77 ± 0.35 vs 1.18 ± 0.26, p= 0.02) respectively for the CMD-OE and CMD-CE groups., Conclusion: Chronic Chagas cardiomyopathy was a secondary cause of suspected coronary microvascular disease in 15% of 101 stable patients whose cardinal symptom was anginal pain warranting coronary angiography. Although sharing several clinical, hemodynamic, and myocardial perfusion characteristics with patients whose suspected CMD was due to other etiologies, impairment of LV segmental and global systolic function was significantly more severe in the patients with suspected CMD related to Chagas cardiomyopathy. (Arq Bras Cardiol. 2020; 115(6):1094-1101).

Chagas disease (CD) will account for 200,000 cardiovascular deaths worldwide over the next 5 years. Early detection of chronic Chagas cardiomyopathy (CCC) is a challenge. We aimed to test if speckle-tracking echocardiography (STE) can detect incipient myocardial damage in CD., Methods: Among 325 individuals with positive serological tests, 25 (age 55±12yrs) were selected to compose the group with indeterminate form of Chagas disease (IFCD), based on stringent criteria of being asymptomatic and with normal EKG/X-ray studies. This group was compared with a group of 20 patients with CCC (55±11yrs) and a group of 20 non-infected matched control (NC) subjects (48±10yrs). CD patients and NC were submitted to STE and CD patients were submitted to cardiac magnetic resonance (CMR) with late gadolinium administration to detect cardiac fibrosis by the late enhancement technique. Global longitudinal strain (GLS), circumferential (GCS) and radial strain (GRS) were defined as the average of segments measured from three apical view (GLS) and short axis views (GRS and GCS). Regional left ventricular (LV) longitudinal strain (Reg LS) was measured from each of the 17 segments. Twist was measured as systolic peak difference between basal and apical rotation and indexed to LV length to express torsion., Results: STE global indices (GLS, GCS, twist and torsion) were reduced in CCC vs NC (GLS: -14±6.3% vs -19.3±1.6%, p = 0.001; GCS: -13.6±5.2% vs -17.3 ±2.8%; p = 0.008; twist: 8±7° vs 14±7°, p = 0.01 and torsion: 0.96±1°/cm vs 1.9±1°/cm, p = 0.005), but showed no differences in IFCD vs NC. RegLS was reduced in IFCD vs NC in four LV segments: basal-inferior (-16.3±3.3% vs -18.6±2.2%, p = 0.013), basal inferoseptal (-13.1±3.4 vs -15.2±2.7, p = 0.019), mid-inferoseptal (-17.7±3.2 vs -19.4±2, p = 0.032) and mid-inferolateral (-15.2±3.5 vs -17.8±2.8, p = 0.014). These abnormalities in RegLS occurred in the absence of myocardial fibrosis detectable with CMR in nearly 92% of subjects with IFCD, while myocardial fibrosis was present in 65% with CCC., Conclusion: RegLS detects early regional impairment of myocardial strain that is independent from fibrosis in IFCD subjects., Competing Interests: The authors have declared that no competing interests exist.

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.

Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease ( n = 47) and a control group ( n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF.

Chagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage before the development of symptoms. The prognosis of patients with Chagasic cardiomyopathy remains poor and life-threatening ventricular arrhythmias can occur at an early stage. Treatment of chronic Chagas cardiomyopathy is challenging with a great need for more studies in the field.

Background: The relationship between microvasculopathy, autonomic denervation, and myocardial fibrosis, in Chagas cardiomyopathy is incompletely understood. The aim of this study was to explore the relative extent and anatomic distribution of myocardial hypoperfusion, autonomic denervation, and myocardial scarring using Single-Photon Emission Computerized Tomography (SPECT) imaging and Magnetic Resonance Imaging (MRI)., Methods: Thirteen patients with Chagas disease all had Iodine-123-metaiodobenzylguanidine (MIBG) SPECT, 99m Tc-Sestamibi (MIBI) rest-stress SPECT, and gadolinium late enhancement MRI imaging within a 2-month interval. The anatomic location and extent of denervation, of stress-induced hypoperfusion and fibrosis, were assessed through image co-registration and quantification of abnormal tissue areas as a percent of total myocardium., Results: The results showed a strong general anatomic concordance between areas of hypoperfusion, denervation, and fibrosis, suggesting that the three abnormal features may be correlated. Myocardial denervation was anatomically and quantitatively closely associated areas of stress hypoperfusion., Conclusion: Combined myocardial analysis of the extent and location of autonomic denervation, hypoperfusion, and scarring may allow for better understanding of the pathophysiology of Chagas cardiomyopathy. Autonomic myocardial denervation may be a more sensitive marker of cardiac involvement in Chagas Disease than finding by other imaging modalities.

Background: Chronic Chagas cardiomyopathy (CCM) is characterized by a unique type of cardiac involvement. Few studies have characterized echocardiographic (Echo) transitions from the indeterminate Chagas disease (ChD) form to CCM. The objective of this study was to identify the best cutoffs in multiple Echo parameters, speckle tracking, and N-terminal pro B-type natriuretic peptide (NT-proBNP) to distinguish patients without CCM (stage A) vs patients with myocardial involvement (stages B, C, or D)., Methods: Cross-sectional study conducted in 273 consecutive patients with different CCM stages. Echo parameters, NT-proBNP, and other clinical variables were measured. Logistic regression models (dichotomized in stage A versus B, C, and D) adjusted for age, sex, body mass index, and NT-proBNP were performed., Results: Left ventricular global longitudinal strain (LV-GLS), mitral flow E velocity, LV mass index, and NT-proBNP identified early changes that differentiated stages A vs B, C, and D. The LV-GLS with a cutoff -20.5% showed the highest performance (AUC 92.99%; accuracy 84.56% and negative predictive value (NPV) 88.82%), which improved when it was additionally adjusted by NT-proBNP with a cutoff -20.0% (AUC 94.30%; accuracy 88.42% and NPV 93.55%)., Conclusions: Our findings suggest that Echo parameters and NT-proBNP may be used as diagnostic variables in detecting the onset of myocardial alterations in patients with the indeterminate stage of ChD. LV-GLS was the more accurate measurement regarding stage A differentiation from the stages B, C, and D. Prospective longitudinal studies are needed to validate these findings., (© 2020 Wiley Periodicals, Inc.)

Background Chronic chagasic cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, is an important public health problem attributable to progressive cardiomyopathy in patients, for which there is no cure. Chronic chagasic cardiomyopathy is characterized by myocarditis and cardiac fibrosis, which leads to life-threatening arrhythmogenic and circulatory abnormalities. This study aimed to investigate cardiac fibrosis progression in a mouse model of chronic chagasic cardiomyopathy. Methods and Results Cardiac cells infected with T cruzi produced significantly higher concentrations of transforming growth factor-β (TGF-β), connective tissue growth factor, endothelin-1, and platelet-derived growth factor-D than noninfected controls. Female Balb/c mice infected with T cruzi were compared with naïve mice. TGF-β genes and other TGF-β superfamily genes, as well as connective tissue growth factor, endothelin-1, and platelet-derived growth factor, were upregulated in infected mouse hearts. Serum concentrations of TGF-β, connective tissue growth factor, and platelet-derived growth factor-D were higher in infected mice and correlated with cardiac fibrosis. Strain analysis performed on magnetic resonance images at 111 and 140 days postinfection and echocardiography images at 212 days postinfection revealed significantly elevated left ventricular strain and cardiac fibrosis and concomitantly significantly decreased cardiac output in infected mice. Conclusions TGF-β, connective tissue growth factor and platelet-derived growth factor-D are potentially useful biomarkers of cardiac fibrosis, as they correlate with cardiac fibrosis. Strain analysis allows for use of noninvasive methods to measure fibrosis in the chronic stages of chagasic cardiomyopathy in a mouse model. These findings can be applied as noninvasive tools to study the effects of interventions and/or therapeutics on cardiac fibrosis development when using a mouse model of chronic chagasic cardiomyopathy.

Background: Myocardial perfusion defects (MPD) due to coronary microvascular dysfunction is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with development of myocardial damage. We investigated whether MPD precedes left ventricular systolic dysfunction and tested the hypothesis that prolonged use of dipyridamole (DIPY) could reduce MPD in an experimental model of CCC in hamsters., Methods and Results: We investigated female hamsters 6-months after T. cruzi infection (baseline condition) and control animals, divided into T. cruzi-infected animals treated with DIPY (CH + DIPY) or placebo (CH + PLB); and uninfected animals treated with DIPY (CO + DIPY) or placebo (CO + PLB). The animals were submitted to echocardiogram and rest SPECT-Sestamibi-Tc99m myocardial perfusion scintigraphy. Next, the animals were treated with DIPY (4 mg/kg bid, intraperitoneal) or saline for 30 days, and reevaluated with the same imaging methods. At baseline, the CH + PLB and CH + DIPY groups showed larger areas of perfusion defect (13.2 ± 13.2% and 17.3 ± 13.2%, respectively) compared with CO + PLB and CO + DIPY (3.8 ± 2.2% e 3.5 ± 2.7%, respectively), P < .05. After treatment, we observed: reduction of perfusion defects only in the CH + DIPY group (17.3 ± 13.2% to 6.8 ± 7.6%, P = .001) and reduction of LVEF in CH + DIPY and CH + PLB groups (from 65.3 ± 9.0% to 53.6 ± 6.9% and from 69.3 ± 5.0% to 54.4 ± 8.6%, respectively, P < .001). Quantitative histology revealed greater extents of inflammation and interstitial fibrosis in both Chagas groups, compared with control group (P < .001), but no difference between Chagas groups (P > .05)., Conclusions: The prolonged use of DIPY in this experimental model of CCC has reduced the rest myocardial perfusion defects, supporting the notion that those areas correspond to viable hypoperfused myocardium.

Background: The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies. Left ventricular (LV) function improvement is the most common endpoint in preclinical cardiovascular disease studies, while echocardiography is the most frequently used method to evaluate LV function. In this work, we conducted a robust echocardiographic evaluation of LV size and function in dogs chronically infected by Trypanosoma cruzi . Methods and Results: Echocardiography was performed blindly by two distinct observers in mongrel dogs before and between 6 and 9 months post infection. Parameters analyzed included end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), and fractional shortening (FS). We observed a significant LVEF and FS reduction in infected animals compared to controls, with no significant variation in volumes. However, the effect of chronic infection in systolic function was quite variable, with EF ranging from 17 to 66%. Using the cut-off value of EF ≤ 40%, established for dilated cardiomyopathy (DCM) in dogs, only 28% of the infected dogs were affected by the chronic infection. Conclusions: The canine model of CCC mimics human disease, reproducing the percentage of individuals that develop heart failure during the chronic infection. It is thus mandatory to establish inclusion criteria in the experimental design of canine preclinical studies to account for the variable effect that chronic infection has on systolic function., (Copyright © 2019 Carvalho, Ramos, Nascimento, Brasil, Mello, Oti, Sammeth, Bahia, Campos de Carvalho and Carvalho.)

Background: Ventricular tachycardia (VT) is one of the main predictors of mortality in Chagas cardiomyopathy (CC). Although the substrate of sustained and nonsustained-VT (NS-VT) seems to be the same, little is known about the distribution of late enhancement (LE). Our aim was to compare the clinical findings and the amount and patterns of LE in Chagas disease according to the presence and type of VT., Methods and Results: Magnetic resonance imaging was performed in 54 Chagas seropositive patients: 8 indeterminate and 46 with CC of whom 15 were without VT, 13 with NS-VT, and 18 with sustained-VT (S-VT). There were 31 males (57%), mean age was 55.9 ± 12.2 years. LE was found in 87% of all patients and in 50%, 80%, and 100% of the indeterminate, without VT and VT groups, respectively. The percentage of LE increased progressively in the indeterminate, CC without VT, and CC with VT groups; without a significant difference between NS-VT and S-VT (0.93%, 15.2%, 23.2%, and 21.4%, respectively). The amount of LE increased with the functional class. LE in the basal and mid lateral wall was more frequent in VT, without difference between S-VT and NS-VT. The only predictor of VT was the percentage of LE, odds ratio (OR), 6.2; (95% confidence interval [CI], 3.7-28.4; P = .01) with a cutoff of Odds Ratio 17.1%., Conclusions: The amount of LE increases in relation to the clinical stage of the disease and its functional class in Chagas seropositive patients. The amount of LE was the main predictor of VT, without difference between S-VT and NS-VT., (© 2019 Wiley Periodicals, Inc.)

The majority of global cardiovascular disease burden occurs in low- and middle-income countries (LMIC) and indigenous populations. Although common diseases, such as ischaemic heart disease, cause significant burden, there are also neglected diseases. Forgotten by many, these diseases-including rheumatic heart disease, endomyocardial fibrosis and Chagas cardiomyopathy-continue to take a tremendous toll on a large proportion of the world's population. Whilst the technology of echocardiography continues to evolve in many high-income countries, low resource countries are working out how to make this vital tool available and affordable for the most remote and poorest populations. This paper aims to highlight the neglected cardiovascular diseases and their echocardiographic features. It also highlights the latest research in relation to portable echocardiography, task shifting and disease screening. The authors make recommendations in relation to future directions, including making echocardiography an affordable and accessible tool for all., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Background: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis., Objective: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients., Methods: We enrolled 112 patients, age of 56.7 ± 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation., Results: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035)., Conclusions: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio., Competing Interests: The authors have declared that no competing interests exist.

True left ventricular aneurysms are most frequently seen after acute transmural myocardial infarction. These aneurysms are distinct from apical left ventricular pseudoaneurysms, which can also be seen in ischemia, and have a different treatment course. A major dilemma for clinicians is using echocardiographic information to make this distinction. Coronary angiography aids in this distinction; however, in the case of normal coronaries alternate etiologies must be considered. The differential for a patient with a left ventricular aneurysm and normal coronaries or no prior cardiac surgery is broad and includes traumatic, infectious and infiltrative causes. In this e-challenge, we present an unusual cause of a left ventricular apical aneurysm in a patient with normal coronary arteries residing in the United States., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Dobutamine stress echocardiography (DSE) is an important tool in the diagnosis of coronary artery disease. However, there is hesitation in clinical practice for using it in patients with Chagas disease (CD) due to the arrhythmogenic potential of this heart condition. This study aimed to evaluate the incidence and variables associated with arrhythmias during DSE in a population of patients with CD., Methods: A population of 205 consecutive patients with CD and suspected coronary heart disease was assessed through a retrospective database analysis. CD was confirmed in all patients by serological testing., Results: The mean age of the patients selected was 64 years, and 65.4% of the patients were female. Significant arrhythmias occurred as follows: nonsustained ventricular tachycardia in 7.3% of patients; supraventricular tachycardia and sustained ventricular tachycardia in 1%; and atrial fibrillation in 0.5%. Nonsignificant arrhythmias occurred as follows: premature ventricular contractions in 48% of patients and bigeminy in 4.4%. Values for the wall-motion score index at rest greater than 1.12 and 1.18 were independently correlated with the occurrence of nonsignificant arrhythmias (odds ratio [OR] = 2.90, P < 0.001) and significant arrhythmias (OR = 4.23, P = 0.044), respectively., Conclusion: DSE should be considered a safe examination in patients with CD despite the known increased risk of arrhythmias in this group of patients. The occurrence of arrhythmias was low in this study. Abnormal wall-motion score index values at rest were associated with the occurrence of significant and nonsignificant arrhythmias during the test., (© 2019 Wiley Periodicals, Inc.)

Ventricular arrhythmias (VAs) are a major cause of morbidity and mortality, especially in patients with structural heart disease. In the last decade, advanced imaging modalities, such as cardiac MR and nuclear imaging, have progressively demonstrated to play a central role in the diagnosis and management of patients presenting with VAs. PET is acquiring a growing role thanks to its capability to assess different pathophysiologic aspects of the arrhythmogenic substrate by evaluating abnormal myocardial perfusion, presence of inflammation, myocardial viability, and sympathetic innervation. This review describes the principles and main clinical applications of PET imaging in the setting of VAs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In the past two decades, a new epidemiological profile of Chagas' disease (CD) has been registered in the Brazilian Amazon where oral transmission has been indicated as responsible for the increase of acute cases. In the Amazonas state, five outbreaks of acute CD have been registered since 2004. The cardiac manifestations in these cases may be characterized by diffuse myocarditis, with alteration in the electrocardiogram (ECG) and transthoracic echocardiogram (TTE)., Objective: To perform a cardiac evaluation in autochthonous patients in the acute phase and at least one year after submitted to treatment for acute CD and evaluate the demographic variables associated with the presence of cardiac alterations., Methods: We evaluated patients diagnosed with acute CD through direct parasitological or serological (IgM) methods from 2007 to 2015. These patients were treated with benznidazole and underwent ECG and TTE before and after treatment. We assumed a confidence interval of 95% (CI 95%, p < 0.05) for all variables analyzed., Results: We observed 63 cases of an acute CD in which oral transmission corresponded to 75%. Cardiac alterations were found in 33% of the cases, with a greater frequency of ventricular repolarization alteration (13%), followed by pericardial effusion (10%) and right bundle branch block and left anterior fascicular block (2%). The follow-up occurred in 48 patients with ECG and 25 with TTE for a mean period of 15.5 ± 4.1 months after treatment. Of these, 8% presented normalization of the cardiac alterations in ECG, 62.5% remained with the normal exams. All of the patients presented normal results in TTE in the post-treatment period. As for the demographic variables, isolated cases presented more cardiac alterations than outbreaks (p = 0.044) as well as cases from Central Amazonas mesoregion (p = 0.020)., Conclusions: Although cardiac alterations have not been frequent in most of the studied population, a continuous evaluation of the clinical-epidemiological dynamics of the disease in the region is necessary in order to establish preventive measures.

Background: Myocardial fibrosis (MF) according to cardiac magnetic resonance (CMR) is a frequent finding in Chagas cardiomyopathy and has been associated with risk factors of poor outcome., Objectives: The goal of this study was to determine the prognostic value of MF in predicting combined hard events or all-cause mortality., Methods: Patients with Chagas cardiomyopathy who had a previous CMR evaluation were included, and clinical follow-up was retrospectively obtained. The primary outcome was a combination of all-cause mortality, heart transplantation, antitachycardia pacing or appropriate shock from an implantable cardioverter-defibrillator, and aborted sudden cardiac death; the secondary outcome was all-cause mortality., Results: A total of 130 patients were included; mean age was 53.6 ± 11.5 years, and 53.9% were female. The majority of patients reported no symptoms of heart failure or arrhythmia, but electrocardiographic and echocardiographic abnormalities were common. On CMR, left ventricular dilatation and dysfunction were frequent, and MF was found in 76.1%, with a mean mass of 15.2 ± 16.5 g. Over a median follow-up of 5.05 years, 58 (44.6%) patients reached the combined endpoint, and 45 (34.6%) patients died. MF was associated with the primary outcome as a continuous variable (adjusted hazard ratio: 1.031; 95% CI: 1.013 to 1.049; p = 0.001) and as a categorical variable (MF ≥12.3 g) (adjusted hazard ratio: 2.107; 95% CI: 1.111 to 3.994; p = 0.022), independently from the Rassi risk score. MF expressed as a continuous variable was also associated with all-cause mortality (adjusted hazard ratio: 1.028; 95% CI: 1.005 to 1.051; p = 0.017) independently from the Rassi risk score., Conclusions: MF is an independent predictor of adverse outcome in Chagas cardiomyopathy. Our data may support the use of CMR in better risk-stratifying this population and possibly guiding therapy., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with chronic Chagas cardiomyopathy (CCC) have pronounced myocardial fibrosis, which may predispose to sudden cardiac death, despite well-preserved global left ventricular (LV) systolic function. Cardiac magnetic resonance can assess myocardial fibrosis by late gadolinium enhancement (LGE) sequences., Objectives: This prospective study evaluated if the presence of scar by LGE predicted hard adverse outcomes in a cohort of patients with CCC., Methods: A prospective cohort of 140 patients with CCC (52.1% female; median age 57 years [interquartile range: 45 to 67 years]) were included. Cardiac magnetic resonance cine and LGE imaging were performed at enrollment with a 1.5-T scanner. The primary endpoint was the combination of cardiovascular death and sustained ventricular tachycardia. The secondary endpoint was the combination of cardiovascular death, sustained ventricular tachycardia, or cardiovascular hospitalization during follow-up., Results: After a median of 34 months (interquartile range: 24 to 49 months) of follow-up, 11 cardiovascular deaths, 3 episodes of sustained ventricular tachycardia, and 20 cardiovascular hospitalizations were recorded. LGE scar was present in 71.4% of the patients, with the lateral, inferolateral, and inferior walls most commonly affected. Patients with positive LGE had lower LV ejection fraction and higher LV end-diastolic volume and LV mass than patients without LGE. No difference in other cardiovascular risk factors was noted. Patients with scar had higher event rates compared with those without scar for the primary (p = 0.043) and the secondary (p = 0.016) endpoint. In multivariable analysis, age and LGE area were related to primary outcome; age and lower LV ejection fraction were related to the secondary outcome. The pattern of LGE myocardial fibrosis was transmural, focal, or diffuse scar in approximately one-third of patients with positive LGE, and no pattern was specifically related to outcomes., Conclusions: In patients with CCC, presence of scar by LGE is common and is strongly associated with major adverse outcomes., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD)., Methods: Differences between the maximum and minimum diameters of the coronary sinus (∆%) on echocardiography were evaluated in individuals with the indeterminate form of CD (n=14) and those without (n=16) CD. The association of the difference with abnormalities detected by echocardiography and myocardial scintigraphy was assessed., Results: The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings., Conclusions: The coronary sinus evaluation revealed no differences between the groups.

Altered myocardial perfusion is a common finding in chronic Chagas cardiomyopathy (CCC), but its underlying histologic changes have not been elucidated. We investigated the occurrence of myocardial perfusion defects (MPDs) and the correlated regional changes to histology in an experimental model of CCC in hamsters. Methods: Female Syrian hamsters ( n = 34) were infected with 3.5 × 10 4 to 10 5 trypomastigote forms of Trypanosoma cruzi, Y strain, and 6-10 mo afterward underwent in vivo imaging including resting 99m Tc-sestamibi SPECT, segmental and global left ventricular function assessment using 2-dimensional echocardiography, and 18 F-FDG PET for evaluation of myocardial viability. Histologic analysis included quantification of fibrosis, inflammatory infiltration, and the diameter and density of myocardial microcirculation. Results: MPDs were present in 17 (50%) of the infected animals. Histologic analysis revealed no transmural scar in segments with an MPD, and normal or mildly reduced 18 F-FDG uptake, indicating viable myocardium. Infected animals with an MPD, in comparison to infected animals without an MPD and control animals, showed a lower left ventricular ejection fraction ( P = 0.012), a higher wall motion score index ( P = 0.004), and a higher extent of inflammatory infiltration ( P = 0.018) but a similar extent of fibrosis ( P = 0.15) and similar microvascular diameter and density ( P > 0.05). Segments with an MPD ( n = 65), as compared with normally perfused regions in the same animal ( n = 156), showed a higher wall motion score index ( P = 0.005) but a similar extent of inflammatory infiltration, a similar extent of fibrosis, and a similar microvascular diameter and density. Conclusion: Resting MPDs are frequent in experimental CCC and are associated with myocardial inflammation but do not designate scar tissue, corresponding to regions with metabolically viable myocardium., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)