Augusto Cardinalli-Neto

Treatment of chronic systolic heart failure secondary to Chagas heart disease in the current era of heart failure therapy

The treatment of chronic heart failure secondary to Chagas disease has been based on extrapolation of data achieved in the treatment of non-Chagas disease heart failure. Because beta-blockers decrease the incidence of sudden cardiac death in non-Chagas disease heart failure and sudden cardiac death occurs preferentially in patients with mild Chagas disease heart failure, beta-blockers may be administered first to class I/II patients with Chagas disease heart failure. In advanced Chagas disease heart failure, angiotensin-converting enzyme inhibitor and diuretics may be given at first to compensate for congestive symptoms. After clinical status improvement, beta-blockers should be given at targeted doses, if necessary reducing angiotensin-converting enzyme inhibitor doses. Primary and secondary prevention of sudden cardiac death may be accomplished with implantable cardioverter defibrillators because of the high recurrence of life-threatening arrhythmias despite amiodarone administration. In refractory heart failure, heart transplantation is the treatment of choice.

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.

Prognosis of patients with chronic systolic heart failure: Chagas disease versus systemic arterial hypertension

Chagas disease is a major health problem in South American because it affects 11 million people; 90 million are at risk of acquiring the disease, and about 12,500 persons die of the disease yearly [1]. Furthermore, Chagas disease has become global because of international immigration. It is caused by the protozoan Trypanosoma cruzi, which is transmitted to humans through the contact of feces of blood-sucking bugs with human mucosa. Many years after infection, about 30% of patients develop chronic cardiomyopathy, whichmanifests by life-threatening ventricular arrhythmias [2], chronic systolic heart failure (CHF) [3], sudden cardiac death [4], and thromboembolism [5]. Chagas disease is the principal cause of CHF in referral centers where the disease is endemic. Prognosis for patients with CHF secondary to Chagas cardiomyopathy is very poor, with an annual mortality around 20% [6]. Overall, outcome for CHF secondary to Chagas cardiomyopathy is poor to that found in non-Chagas disease heart failure [7]. Systemic arterial hypertension (SAH)may affect about 33% of patients with chronic Chagas disease, and 8% of them develop CHF [8]. The purpose of this investigationwas to compare outcome of patients with CHF secondary to Chagas cardiomyopathywith thosewith CHF secondary to SAH in view of lack of such data in the medical literature. All patients with the diagnosis of CHF secondary to either Chagas cardiomyopathy or SAH routinely followed at our Cardiomyopathy Outpatient Service from January, 2000 to January, 2008 were initially considered for the study. Patients were entered in the study if they had 1) positive serology for Chagas disease and left ventricular systolic dysfunction or 2) SAH (systolic blood pressure N 140 × 90 mmHg) at physical examination on admission or normal systemic arterial pressure but with a history of SAH treated with antihypertensive medication at study entry associated with left ventricular systolic dysfunction, as previously reported. Details of this patients cohort have been described elsewhere [9]. All Chagas disease heart failure patients were treated as previously described [10], whereas hypertensive patients received standard treatment for CHF. The daily dose of each medication at the last follow-up visit before study close was noted. The T test for unpaired sample was used to compare continuous variables between patients with CHF secondary to Chagas cardiomyopathy and those with CHF secondary to SAH at baseline. A Cox proportional hazard models, adjusted for confounders, were used to determine independent predictors of mortality for this specific patient population. Kaplan–Meier survival curves were constructed to estimate survival probability for both groups, and the log-rank sum test was used to compare survival probability between both patient groups. Differences at the level of p b 0.05 were considered of statistical significance. Table 1 lists the comparison of relevant clinical characteristics at baseline of patients with CHF secondary to Chagas cardiomyopathy and those with CHF secondary to SAH. Of interest, mean daily dose of carvedilol (21.7 ± 17.4 mg × 34.4 ± 19.7 mg; p b 0.005) and metoprolol succinate (106.2 ± 67.6 mg × 144.3 ± 65.4 mg; p b 0.06) was lower in Chagas disease patients than in those with SAH with CHF. Onmultivariable analysis, Beta-Blocker therapy [Hazard Ratio (HR)= 0.31; 95% Confidence Interval (95%) 0.2 to 0.44; p b 0.005], Chagas etiology of heart failure (HR= 2.2; 95% CI 1.47 to 3.40; p b 0.005), need of inotropic support (HR= 1.72; 95% CI 1.19 to 2.47; p= 0.004), left ventricular diastolic diameter (HR= 1.02; 95% CI 1.19 to 2.47; p= 0.002) and serum sodium levels (HR= 0.95; 95% CI 0.91 to 0.98; p= 0.006) were independent predictors of all-cause mortality. Overall, patients were followed for 33 ± 21 months. Probability of survival for patients with CHF secondary to Chagas cardiomyopathy at 12, 24, 36, 48, and 60 months was 76%, 56%, 45%, 37%, and 29%, respectively; nonetheless, probability of survival for those with CHF secondary to SAH at 12, 24, 36, 48, and 60 months was 96%, 92%, 82%, 77%, and 73%, respectively (p b 0.05). Fig. 1 illustrates these data.

Clinical course of patients with chronic systolic heart failure due to the association of Chagas disease and systemic arterial hypertension

rosuvastatin on coronary atheroma in stable coronary artery disease: multicenter coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS). Circ J 2009;73:2110–7. [5] Smith Jr SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006;113:2363–72. [6] Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421. [7] Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227–39. [8] Deedwania P, Singh V, Davidson MH. Low high-density lipoprotein cholesterol and increased cardiovascular disease risk: an analysis of statin clinical trials. Am J Cardiol 2009;104:3E–9E. [9] Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;357:1301–10. [10] Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. Highdensity lipoprotein cholesterol and cardiovascular disease: Four prospectiveAmerican studies. Circulation 1989;79:8–15. [11] Shewan LG, Coats AJ. Ethics authorship publishing scientific articles Int J Cardiol 2010;144:1–2.

Implantable Cardioverter-Defibrillator therapy for primary prevention of sudden cardiac death in patients with severe Chagas cardiomyopathy

Sudden cardiac death (SCD) affects about half of patients who died of Chagas disease followed at a referral center, and may victim up to 20% of patients without any evidence of heart disease [1]. In the vast majority of cases, SCD is caused by either sustained ventricular tachycardia (VT) degenerating into ventricular fibrillation (VF) or direct VF [1]. In patients with non-Chagas disease dilated cardiomyopathy and left ventricular ejection fraction b35%, Implantable CardioverterDefibrillator (ICD) delivered-therapy has been recommended by international guidelines to avert SCD [2]. Conversely, the impact of ICD therapy in patients with Chagas cardiomyopathy and a left ventricular ejection fraction b35% is unknown. Accordingly, we report herein our initial experience with ICD-delivered therapy in patients with severe Chagas cardiomyopathy. From January, 2006 to December, 2009, a total of 32 patients routinely followed at the Cardiomyopathy Outpatient Service of our Institution received ICD therapy for primary prevention of SCD. The study was approved by the Local Ethical Committee (protocol 3626/ 2010). Inclusion criteria were a left ventricular ejection fraction b35% at radionuclide ventriculography, receiving standard therapy for chronic systolic heart failure, and to have a reasonable expectation of 1-year survival after device implantation [2]. All patients were on New York Heart Association class II at the time of ICD implantation and none had syncope before device implantation. Nineteen (59%) patients had a positive serology for Chagas disease and were considered to have Chagas cardiomyopathy, whereas the remaining 13 (41%) patients had non-Chagas disease dilated cardiomyopathy. Device therapy consisted of antitachycardia pacing (ATP) or shock. ATP was the initial therapy for VT. Shock was the initial therapy when heart rate was higher than 200 beats per minute (VF zone), when ATP accelerated VT heart rate, or when ATP failed to abolish VT. Baseline characteristics of the study population are given in Table 1. It is noteworthy that 87% patients were on Beta-Blocker therapy. Sustained VT was detected in 4 (21%) of 19 patients with Chagas cardiomyopathy and in 2 (15%) patients with non-Chagas cardiomyopathy (pN0.05). VF was observed in 4 Chagas cardiomyopathy (21%) patients and in 2 (15%) non-Chagas cardiomyopathy patients (pN0.05). Overall, 10 (31%) patients were shocked. In total, shock occurrence was necessary to terminate 136 out of 172 (79%) episodes of VT/VF. Inappropriate shock occurred in 4 (12%) patients; 2 (10%) in Chagas and 2 (14%) in non-Chagas cardiomyopathy patients (pN0.05). A total of 101 episodes of VFwere observed in 6 patients. Median of episodes per patient was 6.5 (3, 38). Ninety-four episodes of VF were observed in four Chagas and 7 episodes of VF in two non-Chagas cardiomyopathy patients (p=0.03). Median time to first event was 78 (34, 151) days in Chagas and 173 (71, 593) days in non-Chagas cardiomyopathy patients (pb0.005). Median time to VF was 80 (22, 147) days in Chagas cardiomyopathy patients and 151 (43, 804) days in non-Chagas cardiomyopathy patients (pb0.005). Probability of freedom from shock occurrence was similar in Chagas and non-Chagas cardiomyopathy patients (Fig. 1). Median follow upwas 292 (78, 845) days in Chagas and 654 (158, 987) days in non-Chagas cardiomyopathy patients (pb0.005). Three (9%) patients died during the study period; 2 in Chagas and 1 in non-Chagas patients (pN0.05). The frequency of shock occurrence observed in our Chagas cardiomyopathy cohort in this study was similar to that reported in patients with non-Chagas cardiomyopathy [3]. The lower mortality rate observed in our study in comparison to studies of secondary prevention of SCD [4] in Chagas disease patients may partially be explained by the lower frequency of shock occurrence. Also, the frequency of shock episodes observed in this investigation was lower than that seen in Chagas disease patients receiving ICD therapy for secondary prevention of SCD [4–6]. This can account, at least in part, for the similarity of mortality rate observed in our study in comparison to that seen in non-Chagas cardiomyopathy patients [7]. The higher frequency of VF episodes/per patient observed in Chagas cardiomyopathy patients in this study can also reflect the characteristics of the pathogenesis of Chagas disease [8]. In patients with Chagas cardiomyopathy, foci of confluent fibrosis intermingled with mononuclear cell infiltrate disseminated throughout the myocardium are frequently seen. Moreover, myocardial ischemia

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.

Did death hinder the process of justice? Carlos Chagas and the Nobel Prize of 1935

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Massive right-sided cardiac thrombosis in Chagas' heart disease without left ventricular dysfunction.

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Right ventricular pacing in Chagas heart disease

A 63-year-old woman with the diagnosis of mega-oesophagus secondary to chronic Chagas’ disease and no past cardiac history was referred for cardiac evaluation. The resting ECG showed right bundle-branch block, whereas a 2-D echocardiogram revealed marked right ventricular dilatation with hypokinesia, right atrial dilatation, normal pulmonary artery pressure, and normal left ventricular ejection fraction. A large, irregularly shaped mass, arising from the right atrium and protruding into the right ventricle through the tricuspid valve, with several diff erent bizarre forms inside the right atrium during systole and/or diastole was seen on 2-D echocardiogram. Therefore, massive right-sided thrombosis can be detected in Chagas’ disease patients with no overt right- and left-sided ventricular failure.

Letter by Bestetti and Cardinalli-Neto Regarding Article, “Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic, Trypanosoma cruzi–Seropositive Former Blood Donors”

With regard to the paper by Peixoto and colleagues [1], we would like to emphasize that our experience with pacemaker implantation in Chagas heart disease published in this Journal is somewhat different [2]. We studied 216 patients with chronic heart failure secondary to Chagas heart disease, 100 of them with a right ventricular pacemaker [2]. Our patients had a severer form of Chagas heart disease than those studied by Peixoto et al. [1] in terms of New York Heart Association Functional Classification and left ventricular ejection fraction. About 71% of patients in the study by Peixoto et al. had concomitant systemic arterial hypertension, a condition with a better survival than that of patients with Chagas disease alone [3]. Mortality was doubled in our study in comparison to that observed in the study by Peixoto et al. [1], but was similar to that observed in patients with no pacemaker.