Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

Abstract

Background: The influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood. Methods and Results: Changes in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with P-31 magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac P-31-MRS. The myocardial phosphocreatine to [beta-phosphate]adenosine triphosphate ratio (PCr/beta-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc-sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/beta-ATP was decreased in all Chagas groups (1.23 +/- 0.37) versus group C (1.88 +/- 0.08; P < .001) and was lower in group I (0.89 +/- 0.24) versus groups II (1.44 +/- 0.23) and III (1.40 +/- 0.37; P < .001). There was no stress-induced change in cardiac PCr/beta-ATP (1.88 +/- 0.08 at rest vs 1.89 +/- 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/beta-ATP was 0.89 +/- 0.24 and 0.56 +/- 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/beta-ATP was 1.44 +/- 0.23 at rest and 0.97 +/- 0.37 during exercise (33% decrease; P < .001). In group III, PCr/beta-ATP was 1.40 +/- 0.37 at rest and 0.60 +/- 0.19 during exercise (57% decrease; P < .001). Conclusions: Myocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.