A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America.
 Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because
 of the lack of formal trials. Hence, the objective of this study was to determine the safety
 and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas
 cardiomyopathy. This way, the investigators conducted a double-blind, placebo-controlled, and
 randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All
 patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD).
 Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol
 up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular
 ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The
 secondary end points were changes in other echocardiographic parameters, Framingham score,
 quality of life (36-item Short-Form Health Survey), New York Heart Association class,
 radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end
 points.
Chronic Chagas cardiomyopathy (CCC) is an important cause of heart failure (HF) and sudden
 death in Latin America.1 According to recent estimates, 13 million people worldwide are
 infected with Trypanosoma cruzi, of whom 3.0 to 3.3 million are symptomatic.2 The incidence
 rate is 200000 cases per year. Among those infected, 30% have clinical features of CCC and
 15% ultimately develop overt left ventricular (LV) insufficiency-the main prognostic
 determinant of the disease. In Chagas cardiomyopathy, the hemodynamic and neurohormonal
 responses do not differ from those in other cardiomyopathies. This common pathophysiology
 suggests that treatments shown to be effective by classic HF trials should be beneficial in
 CCC. However, CCC has several specific characteristics, such as early cardiac denervation,
 frequent ventricular arrhythmias, and several forms as well as grades of conduction
 disturbances, including sinus bradycardia, complete atrioventricular block, and right
 bundle-branch block. Morphologically, hypertrophy, dilatation, and severe fibrosis are
 prominent. In 20% to 40% of cases, an apical ventricular aneurysm is present.1 These
 peculiarities in combination lead to a high incidence of sudden death (60% of all deaths),
 cardiac insufficiency, and ventricular remodeling. The responses of patients to the usual
 drugs prescribed in HF could be different, and this perception has led to the suboptimal
 dosing or lack of initiation of medical treatments that are of proven efficacy in patients
 with other etiologies of HF. The underlying problem is that therapies that are effective in
 patients with HF caused by non-chagasic cardiomyopathies, such as those with
 renin-angiotensin system inhibitors (RASis) and h-blockers, have yet to be formally tested in
 CCC. There are few clinical trials and no randomized study on this subject. Consequently, the
 investigators evaluated the effects of optimizing treatment with enalapril and spironolactone
 and then undertook a randomized trial of adding a h-blocker in the treatment of patients with
 CCC.
Inclusion Criteria:

 -  Criteria for inclusion were positivity for T cruzi as confirmed by 2 or more
 serological tests (indirect immunofluorescence, ELISA, and/or indirect
 hemagglutination) and having cardiomyopathy.

 -  Cardiomyopathy was present when at least 3 of the following criteria were fulfilled:

 -  LV enddiastolic diameter (LVDD) N55 mm

 -  LVDD/body surface area > 2.7cm/m2

 -  LV ejection fraction (LVEF) < 55%

 -  QRS interval > 120 ms

 -  echocardiographic evidence of diffuse or segmental systolic wall motion
 abnormalities.

 Exclusion Criteria:

 -  Exclusion criteria were being pregnant

 -  Using any h-blocker

 -  Having additional comorbidities (eg, hypertension, diabetes mellitus, thyroid
 dysfunction, chronic obstructive pulmonary disease, asthma, and renal or hepatic
 failure).