César Molina

Prognostic implications of clinical, electrocardiographic and hemodynamic findings in chronic Chagas' disease.

To evaluate the prognostic importance of 19 clinical, electrocardiographic and hemodynamic variables, 556 chronic chagasic patients were submitted to an extensive protocol, including left cineventriculogram and Holter monitoring, and followed for up to 15 years. The protagonist role of the magnitude of the myocardial compromise in the evolution of chagasic patients is underscored by our results, which indicated the independent prognostic value of an ejection fraction below 0.30 (P < 0.001), a heart rate higher than 89 beats/min (P < 0.01), grade IV functional capacity (P < 0.05), end systolic stress > 120 g/cm2 (P < 0.05), and end diastolic volume index > 200 ml/m2 (P < 0.05). When only patients with an ejection fraction over 0.29 were considered, variables with independent prognostic value were: the cardio-thoracic ratio (P < 0.01), functional capacity (P < 0.05) and heart rate (P < 0.05). Survival analysis demonstrated that the presence of complex (Lown III, IV) ventricular arrhythmias increased mortality significantly (P < 0.01) only in patients with an ejection fraction over 0.29. Therefore, preservation of myocardial function is the capital measure in the treatment of chronic chagasic patients.

Left ventricular cineangiography in Chagas' disease: Detection of early myocardial damage☆

The purpose of this investigation was to identify early left ventricular (LV) cineangiographic signs of myocardial damage and to study the evolution of the characteristic lesions in 126 chronic chagasic patients, divided into three groups. Group I patients had no clinical, ECG, or radiologic evidences of heart disease; 41% of them manifested apical or anterior apical asynergy, suggestive of early subclinical myocardial damage. Group II patients had abnormal ECG findings and no clinical signs of heart failure. Extensive asynergy, LV dilatation, decreased distensibility, and depressed contractility were found in 98% of these cases. Group III patients presented with congestive heart failure, a greatly dilated, hypokinetic LV chamber, and a 40% incidence of large apical aneurysms, 20% with thromboses within the LV. The performance of a left cineventriculogram in our chagasic patients enabled us to diagnose early myocardial damage and to detect potentially resectable lesions, such as ventricular aneurysms and apical thromboses.

Clinical, histochemical, and ultrastructural correlation in septal endomyocardial biopsies from chronic chagasic patients: Detection of early myocardial damage☆

In order to recognize early signs of myocardial damage, histologic, histochemical, and ultrastructural studies were performed on septal endomyocardial biopsy tissue obtained from 79 chronic chagasic patients and from 18 patients with atypical chest pain (control group). Abnormal biopsy findings were recognized in 9 of 16 (60%) chagasic patients with no clinical evidence of myocardial damage. In cases of segmental asynergy only, biopsies were abnormal in 18 of 19 patients. When signs of advanced myocardial damage were evidenced by clinical examination or ECGs, all biopsies were abnormal. Mitochondrial, nuclear, and cell membrane irregularities were consistent findings. A peculiar dilatation and filling of the T tubule system with a glycoprotein-like substance and a remarkable increase in monoamine oxidase activity were observed early in the disease and progressed in magnitude and frequency as myocardial damage became more evident by other diagnostic methods. Septal endomyocardial biopsy is a sensitive method for detection of early myocardial damage in chronic chagasic patients. Based on these findings, a modification of the currently used classification is proposed.

Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients.

To study the relationship of complex ventricular arrhythmias to the presence and extent of myocardial damage, 556 chronic chagasic patients were submitted to an extensive protocol, including left ventricular cineangiography and Holter monitoring, and properly classified according to clinical, electrocardiographic and hemodynamic findings. Stages of the clinical-hemodynamic classification corresponded to increasing degrees of myocardial damage, age, prevalence and complexity of ventricular arrhythmias. Myocardial damage (particularly left ventricular dilatation) was the most important clinical factor linked to the presence of complex ventricular arrhythmias. A clear difference in terms of ventricular function was found only when arrhythmias were grouped into simple (Lown grades I and II) and complex (grades III and IV) forms. It is recommended that any classification for chagasic patients must be based on signs of myocardial involvement, instead of clinical or electrocardiographic findings alone. Evaluation should include accurate determination of left ventricular myocardial function, along with the search for the presence of complex ventricular arrhythmias and abnormalities of conduction.

Right ventricular function in Chagas disease

To study right ventricular function, we performed cardiac catheterization, and right and left cineventriculograms in 60 chagasic patients and 15 non-chagasic, non-heart disease patients. Chagasic patients with normal electrocardiograms and left cineventriculograms also had normal right ventricular function. Nine of 14 chagasic patients with normal Ecgs and early left ventricular damage had right ventricular dilatation and/or segmental inferior-apical asynergy. Fourteen of 19 chagasic patients with abnormal Ecgs and advanced left ventricular damage, but without signs of congestive heart failure, and all chagasic patients with congestive heart failure, had marked right ventricular dilatation, severe right contractility depression and abnormal right apical or para-apical motion. These findings indicate that Chagas disease is a diffuse cardiomyopathy in which the left ventricle seems to be affected earlier and to a greater extent than the right ventricle. Since segmental abnormalities were predominantly observed in apical and para-apical areas of the ventricles, performance of right and left cineventriculograms is recommended before implantation of cardiac pacemakers.

Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.