Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising.
The modern definition of Global Health has expanded its scope beyond neglected diseases and low-income and underdeveloped countries. The current initiatives focus on improvement of health, reduction of disparities and protection against global threats, seeking for interaction with health practices, policies and systems. There has been a growing interest on Global Health research, given the epidemiological transition currently underway in low and mid-income countries and the increasing epidemiological importance of cardiovascular and other non-communicable diseases, to the detriment of infectious diseases and nutritional deficiencies. Various aspects-formerly neglected-of these diseases, such as epidemiology, prevention, diagnosis and therapy, have been addressed in Global Health publications, leading to a better understanding of the importance of health as a public good, beyond borders. Scientific evidence supports broader initiatives in which governments, foundations and the civil society must share responsibilities and funding to achieve health equity, the main goal of Global Health.
Introduction:
The cardiac form is the main responsible for morbidity and mortality of Chagas disease (ChD), given its prevalence and unpredictable clinical evolution. A great part of ChD mortality occurs due to sudden ventricular arrhythmias, and the frequently observed autonomic dysfunction may be associated with unfavorable outcomes. We aimed to evaluate the predictive value of autonomic dysfunction indexes in ChD patients.
Methods:
The Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), living in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. For assessment of respiratory sinus arrhythmia (E:I ratio), patients were instructed to breathe deeply in a 10-second cycle (5 inhales and 5 exhales) while ECG was recorded. Heart rate variability indices (SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)) were calculated using a computer algorithm, supervised by an independent cardiologist blinded to clinical data. Multivariable regression was performed to access the prognostic value of autonomic dysfunction indexes, expressed as tertiles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables.
Results:
From 1,742 qualifying residents, 1,606 were enrolled, being 557 with positive ChD serology. Among these, mean age was 68 (64-74) years, and 32.5% were men. The most frequent ECG abnormality was right bundle branch block (23.2%). In 14 years, loss-to-follow-up was 7.9% and overall mortality was 51.9%. At total 321 ChD patients had valid autonomic indexes measurements. In univariate analyses, measurements of autonomic function predicted all-cause death: E:I ratio (HR: 1.20 (95% CI 1.09-1.33)), SDRR (HR: 1.26 (95% CI 1.14-1.40)) and RMSSD (HR: 1.12 (1.01-1.23)). After adjustment for sex, age and cardiovascular risk factors, none of these indexes remained as independent predictors of mortality.
Conclusions:
In a long-term cohort of elderly patients with ChD, abnormalities in autonomic function indexes were not independent predictors of 14-year mortality.
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