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

Abstract

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 patient's 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.