Prevalence and clinical course of patients with chronic heart failure secondary to chronic Chagas heart disease associated with obstructive coronary artery disease.

BACKGROUND: The prevalence and the outcomes of patients with chronic Chagas heart disease with obstructive coronary artery disease (CCHD-CAD) and chronic heart failure (CHF) with precordial chest pain are unsettled. Accordingly, the aim of this study was to determine the prevalence and clinical course of patients with CHF secondary to CCHD-CAD. METHODS: Patients with positive serology for Chagas disease and systolic CHF were included; those with precordial chest pain and at least two risk factors for CAD underwent coronary arteriogram. RESULTS: In total 262 patients were included in the investigation; 234 (89%) had CHF secondary to CCHD alone, and 28 (11%) with CHF secondary to CCHD-CAD, as observed at coronary arteriogram. The survival probability of patients with CHF secondary to CCHD alone at 12, 24, 36, 48 and 72 mo was 79%, 64%, 54%, 44% and 33%, respectively, whereas survival probability for patients with CHF secondary to CCHD-CAD at 12, 24, 36, 48 and 72 mo was 96%, 80%, 71%, 66% and 57%, respectively (p=0.04). CONCLUSIONS: In patients with CCHD with CHF, the prevalence of CAD of 11% is not neglectable in those with precordial chest pain. The outcome for patients with precordial chest pain with CHF secondary to CCHD-CAD is better than that observed in patients with CHF secondary to CCHD alone.

Resveratrol and Curcumin for Chagas Disease Treatment-A Systematic Review.

Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage-characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease's progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Resveratrol (RVT) and curcumin (CUR) are natural compounds with potent antioxidant and anti-inflammatory properties and their cardioprotective effect have been proposed to have benefits to treat CD. Such effects could decrease or block the progression of the disease's severity. The purpose of this systematic review is to analyze the effectiveness of RVT and CUR in animal and clinical research for the treatment of CD. The study was performed according to PRISMA guidelines and it was registered on PROSPERO (CDR42021293495). The results did not find any clinical study, and the animal research was analyzed according to the SYRCLES risk of bias tools and ARRIVE 2.0 guidelines. We found 9 eligible reports in this study. We also discuss the potential RVT and CUR derivatives for the treatment of CD as well.

Noninvasive prediction of late potentials in the signal-averaged ECG in patients with chronic Chagas disease.

INTRODUCTION: Considering the importance of ventricular arrhythmias in the prediction of sudden cardiac death in chronic Chagas heart disease, the aim of the present study was to associate late potentials observed in the signal-averaged electrocardiogram (SAECG) with either non-sustained ventricular tachycardia in the 24-hour Holter monitoring or reduced left ventricular ejection fraction in the 2-dimension echocardiogram. METHODS: This was a retrospective transversal study. The medical charts of 49 patients with chronic Chagas heart disease that underwent 24-hour Holter monitoring at our institution from September 2012 to December 2015 were reviewed. In the univariate analysis, variables associated with SAECG at a p value <0.05 were entered a multivariate stepwise logistic regression analysis through the model forward. A p value <0.05 was considered to have statistical significance. RESULTS: In the univariate analysis, right bundle branch block, left atrial diameter, left ventricular systolic diameter, and left ventricular ejection fraction were associated with late potential in the SAECG. In the multivariate analysis, however, right bundle branch block and left atrial diameter were retained as independent predictors of late potentials in the SAECG. CONCLUSIONS: Neither ventricular arrhythmias in the 24-Holter monitoring nor reduced left ventricular ejection fraction in the 2-D echocardiogram were associated with late potentials in the SAECG of patients with chronic Chagas heart disease.

Prognostic Significance of Chronic Kidney Disease (CKD-EPI Equation) and Anemia in Patients with Chronic Heart Failure Secondary to Chagas Cardiomyopathy.

BACKGROUND: Few studies regarding chronic kidney disease (CKD) and anemia have been conducted in patients with Chagas cardiomyopathy (CC). We evaluated the risk prediction performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and anemia in CC patients. METHODS: From 2000 to 2010, a total of 232 patients were studied in a single-center retrospective study. CKD was defined as creatinine clearance <60 mL/min/1.73 m2 according to CKD-EPI equation. Anemia was defined as hemoglobin <12 g/dL (women) and <13 g/dL (men). Cox proportional hazards models were used to establish predictors for death. RESULTS: At baseline, 98 individuals (42.2%) had criteria for CKD and 41 (17.7%) for anemia. During follow-up, 136 patients (58.6%) died. Independently, CKD and anemia were not associated with all-cause mortality. However, when they coexisted, an additional risk was attributed for these patients. Cox proportional hazard models analysis identified systolic blood pressure (hazard ratio, 0.99; 95% confidence interval (CI), 0.98 to 1.00; P=0.015), implantable cardioverter-defibrillator (hazard ratio, 0.48; 95% CI, 0.27 to 0.85; P=0.012), left anterior fascicular block (hazard ratio, 1.52; 95% CI, 1.08 to 2.13; P=0.017), left ventricular end-diastolic diameter (hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P < 0.001), and serum sodium (hazard ratio, 0.95; 95% CI, 0.92 to 0.99; P=0.020) as independent predictors for death. CONCLUSIONS: CKD and anemia are not independent predictors for long-term mortality in CC patients. However, the prognosis is poorer in individuals with both comorbidities.

The history of the evolution of the knowledge about the diagnosis and the pathogenetic aspects of heart failure: From the Egyptians to James Mackenzie.

The recognition of the syndrome of heart failure (HF) dates back to the Egyptians, although it is still a mystery how they did that because they had an erroneous notion of the blood flow. Some cardinal aspects of the clinical picture of HF were associated with cardiac disease 1600 years later. Dyspnea was associated with cardiac disease in 1000 CE by Avicenna; pedal edema was associated with cardiac disease by Pawl in 1615. Lower associated dyspnea with pedal edema in 1669, and Bonet associated ascites with cardiac disease in 1679. Lancisi associated the jugular venous distention with right ventricular dilatation in 1728. However, it was only in 1748 that Albertini associated pedal edema and dyspnea with the myocardial disease. The evolution of the understanding that myocardial contractility abnormality was the mechanism behind HF partially started with Lower in 1669, it was clearly pointed out by Albertini in 1748 and refined by Mackenzie in 1908. At that time, it was clear that the exhausted myocardial would lead to the appearance of HF. However, the full understanding of the pathogenesis of HF had to wait for the hemodynamic studies which would appear in the second decade of the 20th century, and for the neurohormonal theory of the 90's.

Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute.

Clinical predictors of inducible sustained ventricular tachycardia during electrophysiologic study in patients with chronic Chagas' heart disease.

BACKGROUND: Clinical independent predictors of inducible sustained ventricular tachycardia (VT) during electrophysiologic study (EPS) are not known in patients with chronic Chagas' heart disease. The purpose of this investigation was to fill this gap. METHODS: The medical charts of 47 patients with a positive serology for Chagas' disease who had undergone EPS between September 2006 and July 2012 at our institution were reviewed. Reasons for the EPS were the presence of unexplained syncope, non-sustained ventricular tachycardia (NSVT) on either resting ECG or 24 h-Holter monitoring as well as a LVEF < 55% and > 35% at echocardiography. A stepwise logistic regression analysis was performed to identify noninvasive predictors of inducible sustained VT/ventricular fibrillation during EPS. RESULTS: On univariate analysis, syncopal episodes (p = 0.04), amiodarone therapy (p < 0.005), diastolic blood pressure (p = 0.03), creatinine serum levels (p < 0.001), potassium serum levels (p < 0.001), and lengthening of the QRS complex (p = 0.03) were associated with inducible sustained VT during EPS. In the multivariate model, amiodarone therapy (p = 0.03; hazard ratio = 10; Wald coefficient = 4.5; 95% confidence interval 1.2 to 85.2) was the only variable retained as independent predictor of inducible sustained VT during EPS. CONCLUSION: Amiodarone therapy was the only independent variable associated with sustained VT inducibility during EPS in patients with chronic Chagas' heart disease.

When a misperception favors a tragedy: Carlos Chagas and the Nobel Prize of 1921.

Carlos Chagas, the discoverer of Chagas' disease was nominated to the Nobel Prize in 1921, but none did win the prize in that year. As a leader of a young scientist team, he discovered all aspects of the new disease from 1909 to 1920. It is still obscure why he did not win the Nobel Prize in 1921. Chagas was discarded by Gunnar Hedrèn on April 16, 1921. Hedrèn should have made a written report about the details of his evaluation to the Nobel Committee. However, such a document has not been found in the Nobel Committee Archives. No evidence of detractions made by Brazilian scientists on Chagas was found. Since Chagas nomination was consistent with the Nobel Committee requirements, as seen in the presentation letter by until now unknown Cypriano de Freitas, it become clear that Chagas did not win the Nobel Prize exclusively because the Nobel Committee did not perceive the importance of his discovery. Thus, it would be fair a posthumous Nobel Prize of 1921 to Carlos Chagas. A diploma of the Nobel Prize, as precedent with Dogmack in 1947, would recognize the merit of the scientist who made the most complete medical discovery of all times.

Dissecting slander and crying for justice: Carlos Chagas and the Nobel Prize of 1921.

Chagas disease was discovered by Carlos Chagas in 1909. Chagas worked at Oswaldo Cruz Institute, where the bases of experimental medicine were settled in Brazil, and that had no connection with the Faculty of Medicine of Rio de Janeiro. Chagas had several enemies at Oswaldo Cruz Institute mainly because of his election to Head of Service in 1910, and for the position of Oswaldo Cruz Directorship in 1917. Furthermore, Chagas gained enemies at Faculty of Medicine of Rio de Janeiro, which did not like to see the economical political autonomy of Oswaldo Cruz Institute. This allowed the Institute not only to perform top experimental research, but also to take the leadership of research in the country. Chagas was nominated to the Nobel Prize of 1921 in December, 1920. None was awarded the Nobel Prize in that year. He seems to have been evaluated by the Noble Committee of Karolinska Institute from March to May of 1921. At that time, his enemies were denying his discovery of Trypanosoma cruzi, a key point in Chagas' nomination by Karolinska Institute, and giving no epidemiological importance for the disease. By the same way, the obligation of small pox vaccination was tarnishing his public image. Having taken into account the epidemiologic importance of Chagas disease, the strong historical mistake in the process of Chagas evaluation, and the inequity behind all these facts, we insist on a posthumous Nobel Prize for the man who made the most complete medical-scientist discovery of all time.

Outcome of Chagas cardiomyopathy in comparison to ischemic cardiomyopathy.

BACKGROUND: Chagas cardiomyopathy and ischemic heart disease (IHD) are frequent causes of chronic systolic heart failure (CHF) in areas where the former is endemic. Nonetheless, a specific comparison of outcome and role of etiology of CHF failure has not been performed in patients with both conditions. METHODS: Two-hundred twenty two patients with Chagas cardiomyopathy and 79 with IHD with CHF were included in the study. A Cox proportional hazards model was used to establish independent predictors of mortality for the studied population. Survival analysis was performed with the Kaplan-Meir product limit method. RESULTS: In the multivariable model, Beta-Blocker therapy [(hazard ratio (HR)=0.36; 95% confidence interval (CI) 0.24 to 0.52; p<0.005)], Chagas etiology of CHF (HR=3.6; 95% CI 2.0 to 6.5; p<0.005), serum sodium levels (HR=0.95; 95% CI 0.91 to 0.98; p<0.005), digoxin use (HR=2.1; 95% CI 1.19 to 3.80, p=0.01), and spironolactone use (HR=1.7; 95% CI 1.10 to 2.80; p=0.02) were determined independent predictors of all-cause mortality for this cohort. Probability of survival at 12, 24, 36, 48, and 60 months was 92%, 92%, 88%, 81%, and 78%, respectively, in IHD patients, and 79%, 61%, 49%, 41%, and 35%, respectively, in Chagas cardiomyopathy patients (p<0.005). CONCLUSION: Outcome in patients with chronic systolic heart failure secondary to Chagas cardiomyopathy is poorer than that seen in those with IHD.

Device therapy in Chagas disease heart failure.

Chagas disease is the principal cause of chronic heart failure in areas where the disease is endemic. The medical treatment is the same recommended for non-Chagas disease patients. There is no evidence-based medicine support for device therapy in Chagas disease heart failure. Cardiac resynchronization therapy is recommended for Chagas disease heart failure patients with intraventricular conduction disturbances, mainly for those with left bundle branch block, and in advanced congestive heart failure refractory to targeted medical treatment, although this therapy is still polemic in Chagas disease heart failure. Implantable cardioverter-defibrillator (ICD) therapy is indicated to Chagas disease patients with left ventricular ejection fraction <30% for primary prevention of sudden cardiac death. ICD therapy is offered to patients for secondary prevention of sudden cardiac death. Patients with moderate left ventricular dysfunction and inducible arrhythmia at electrophysiological testing should receive ICD therapy.

Síndrome do QT longo congênito associado a bloqueio atrioventricular 2: 1 em lactente com síncope de repetição tratado como epilepsia / Congenital long QT syndrome associated with 2: 1 atrioventricular block in infant with repeated syncope treated as epilepsy

A Síndrome do QT longo (SQTL) congênito é uma doença dos canais iônicos cardíacos que está associada com síncope, taquiarritmias ventriculares e morte súbita cardíaca em pacientes com coração normal. Raramente, apresenta-se com Bloqueio Atrioventricular 2:1, apresentando mortalidade maior que 50% nos primeiros seis meses de vida, mesmo com tratamento adequado. O caso aqui descrito relata a evolução clínico de lactente com 6 meses de idade com SQTL congênito, síncope de repetição e BAV 2:1 inicialmente tratado como epilepsia, que após tratamento clínico adequado com mudança de estilo de vida, betabloqueadores e implante de marcapasso, não apresentou mais eventos cardíacos. No seguimento tardio (com 6 anos de vida), foi implantado Cardiodesfibrilador Implantável, sem terapias até a presente data.

Congenital long QT syndrome is a disease of cardiac ion channels that is associated withs yncope, cardiac sudden death and ventricular tachyarrhythmias in patients with normal hearts. Rarely,it presents associated with 2:1 atrioventricular block; in this case the mortality rate is higher than 50% in the first six months of life even with adequate treatment. The case described here reports on the clinical evolution of a six-month-old infant with congenital long QT syndrome, syncope of repetition and 2:1 atrioventricular block initially treated as epilepsy, that after the correct clinical treatment with changes in lifestyle, beta-blockers and pacemaker implantation, did not have further cardiac events. In the long term follow-up (six years of life), a defibrillator was implanted without the need of further therapies todate.