Search

Background Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy development in Chagas disease patients from different Latin American populations. Methods We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia. Samples were genotyped to conduct a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3413 Chagas disease patients. To identify the functional impact of the associated variant and its proxies, we performed an in silico analysis of this region. Results The meta-analysis revealed a novel genome-wide statistically significant association with chronic Chagas cardiomyopathy development in rs2458298 (OR = 0.90, 95%CI = 0.87–0.94, P-value  = 3.27 × 10-08), nearby the SAC3D1 gene. In addition, further in silico analyses displayed functional relationships between the associated variant and the SNX15 , BAFT2, and FERMT3 genes, related to cardiovascular traits. Conclusions Our findings support the role of the host genetic factors in the susceptibility to the development of the chronic cardiac form of this neglected disease. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is a neglected tropical disease and its main consequence is chronic chagasic cardiomyopathy (CCC). The clinical manifestations of CD can cause functional limitation and impact on the perception of quality of life (QoL). We evaluated the QoL profile of patients with CD living in remote regions, and their association with socio-demographic, behavioral, and clinical characteristics.A cross-sectional study, using the baseline of a cohort study (SaMi-Trop) was conducted in the state of Minas Gerais, Brazil, an endemic region for CD. The cohort is composed of 1959 patients with CD. The patients were interviewed, and blood collection and electrocardiogram (ECG) were performed. The WHOQOL-BREF scale was used to assess QoL. Descriptive statistics were performed and, for the QoL scale, measures of central tendency and dispersion were calculated. Inflated beta regression models constructed using the gamlss framework were used, and fitted using R software. A significance level of 5% for all analyzes was adopted.QoL was evaluated in 625 participants. The Environment (57.66) and Social Relationships (73.17) domains presented the lowest and highest QoL score respectively. There was no statistically significant difference between QoL domains in the presence of CCC. In the multivariate analysis, the factors associated with a lower QoL were in the Physical domain age increase (OR: 0.95, CI: 0.91–0.99) and using an angiotensin converting enzyme inhibitor (OR 0.89; CI: 0.80–0.99); in the Social Relations domain a history of acute myocardial infarction (OR: 0.75; CI: 0.61–0.92); and in the Environment domain age increase (OR 0.94, CI 0.91–0.97). The factor associated with higher QoL was the use of angiotensin receptor blockers (OR: 1.15; CI 1.04–1.26).The findings of this study reinforce the importance of QoL indicators for planning care and clinical management of patients from remote regions with CD. Trial registration: NCT02646943. Author summary: Chagas disease (ChD) is a neglected tropical disease, with the majority of the individuals affected living in Latin America. Functional limitation and poor perception of quality of life (QoL) may be identified. QoL indicators are important for planning and to improve patients care. However there is a gap in the literature regarding the evaluation of QoL in patients living with chronic CD, in remote regions assisted by primary health care in their territory of residence. A cross-sectional study was conducted using the baseline of a prospective cohort performed in remote towns in Minas Gerais state, Brazil. Lower QoL scores were identified in the Environment domain followed by the Physical domain. Higher scores were found in the Social Relations domain. Low QoL scores have been associated with clinical aspects such as use of angiotensin converting enzyme inhibitor (ACEI), and history of acute myocardial infarction, and socio-demographic aspects such as increasing age. QoL is positively associated with medicine use of angiotensin receptor antagonists (ARA). The subjective perception of QoL was not associated with the severity of the disease using as a marker the presence of CCC in the evaluated population. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality. Methods: The present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1β, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification. Results: Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1β and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients. Conclusion: Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients. [ABSTRACT FROM AUTHOR]

Chagas cardiomyopathy is the most severe and life-threatening manifestation of human Chagas disease--a 'neglected' tropical disease caused by the protozoan parasite Trypanosoma cruzi. The disease is endemic in all continental Latin American countries, but has become a worldwide problem because of migration of infected individuals to developed countries, mainly in Europe and North America. Chagas cardiomyopathy results from the combined effects of persistent parasitism, parasite-driven tissue inflammation, microvascular and neurogenic dysfunction, and autoimmune responses triggered by the infection. Clinical presentation varies widely according to the extent of myocardial damage, and manifests mainly as three basic syndromes that can coexist in an individual patient: heart failure, cardiac arrhythmia, and thromboembolism. NYHA functional class, left ventricular systolic function, and nonsustained ventricular tachycardia are important prognostic markers of the risk of death. Management of Chagas cardiomyopathy focuses on the treatment of the three main syndromes. The use of β-blockers in patients with Chagas disease and heart failure is safe, well tolerated, and should be encouraged. Most specialists and international institutions now recommend specific antitrypanosomal treatment of patients with chronic Chagas disease, even in the absence of evidence obtained from randomized clinical trials. Further research on the management of patients with Chagas cardiomyopathy is necessary. [ABSTRACT FROM AUTHOR]

Background: The value of signal-averaged ECG (SAECG) in the risk stratification of Chagas disease (ChD), a potentially lethal illness prevalent in Latin America, remains controversial. The aim of this prospective longitudinal study was to determine the prognostic value of SAECG in ChD, using multivariate models with other established prognostic predictors, and to develop a simple prediction risk score. Methods: The study enrolled 184 ambulatory ChD patients (107 men; age: 48 ± 12 years) in sinus rhythm and without other systemic diseases. All patients underwent comprehensive evaluation that included clinical examination, ECG, chest X-ray, 24-hour Holter monitoring, echocardiogram, stress testing, and time domain SAECG. Individual medical therapy was adjusted according to a standardized treatment regimen. The association of potential risk factors obtained by noninvasive evaluation and death was tested by Cox proportional-hazards analysis. Results: During mean follow-up time of 74 ± 17 months, 13 patients died. Three independent prognostic factors were identified: left ventricular ejection fraction <50% (HR = 5.2, P = 0.048), ventricular tachycardia at either Holter monitoring or stress testing (HR = 9.9, P = 0.036), and prolonged (>150 ms) filtered QRS complex (HR = 4.3, P = 0.035). A prognostic score developed considering the number of risk factors of each patient had an excellent performance in predicting death ( c statistic: 0.92). Conclusions: Prolonged filtered QRS duration obtained by SAECG is an independent predictor of death in ChD. A prediction score including three risk factors, depressed left ventricular ejection fraction, ventricular tachycardia and prolonged filtered QRS complex, has shown to be useful for stratifying risk categories in ChD. [ABSTRACT FROM AUTHOR]

Chagas cardiomyopathy is an endemic disease in Latin America. A significant proportion of patients develop atrial fibrillation (AF), which may result in stroke and increased morbidity or mortality. Interatrial block (IAB) has been associated with the development of AF in different clinical scenarios. The aim of our study was to determine whether IAB can predict new-onset AF in patients with Chagas cardiomyopathy and implantable cardioverterdefibrillators (ICDs). We conducted a retrospective study of patients with Chagas cardiomyopathy and ICDs from 14 centers in Latin America. Demographics, clinical, and device follow-up were collected. Surface electrocardiograms were scanned at 300 dpi and maximized 38. Semiautomatic calipers were used to determine P-wave onset and offset. Partial IAB was defined as a P wave of >120 ms and advanced IAB as a P wave of >120 ms with biphasic morphology (-) in inferior leads. AF events and ICD therapies were reviewed during follow-up by 2 independent investigators. A total of 80 patients were analyzed. Mean age was 54.6 - 10.4 years, and 52 (65%) were male. Mean left ventricular ejection fraction was 40 - 12%. IAB was detected in 15 patients (18.8%), with 8 (10.0%) partial and 7 (8.8%) advanced. During a follow-up of 33 - 20 months, 11 patients (13.8%) presented with new AF. IAB (partial D advanced) was strongly associated with new AF (p <0.0001) and inappropriate therapy by the ICD (p [ 0.014). In conclusion, IAB (partial D advanced) predicted new-onset AF in patients with Chagas cardiomyopathy and ICDs. [ABSTRACT FROM AUTHOR]

In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. Springer Nature Limited.)

Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda., Competing Interests: Dr Demacq, Dr Quijano, and Dr Geissbühler are Novartis employees and have some stocks of the company., (Copyright: © 2024 The Author(s).)