[Clinical, parasitological and histopathologic follow-up studies of acute Chagas patients treated with benznidazole]. / Seguimiento clínico, parasitológico e histopatológico de pacientes chagásicos agudos tratados con benznidazol.

With the purpose of studying their clinical and histopathologic evolution, 10 acute chagasic patients with myocarditis diagnosed by endomyocardial biopsy and positive sero-parasitologic methods were evaluated at 11 months (8-21 months) after treatment with oral benznidazole. Four of them were reevaluated 5 years post-treatment (58-68 months). Study protocol consisted of clinical, hemodynamic, echocardiographic, seroparasitologic and histopathologic evaluations. Results showed evidence of persisting myocarditis in 90% and 75% of patients evaluated at 11 months and 5 years respectively, along with asymptomatic, subclinical left ventricular systolic dysfunction being recognized in 75% of patients evaluated 5 years after treatment. All parasitologic studies became negative during follow-up, but serology remained positive for Trypanosoma cruzi antibodies in 80% and 75% of patients studied at 11 months and 5 years. In conclusion, myocardial damage was constantly found in our acute chagasic patients. Treatment with benznidazole eliminated symptoms and parasitemia, but it does not seem to alter favorably the histopathological evolution of the chagasic cardiac disease.

Biochemical characterization of myocardial damage in chronic Chagas' disease.

BACKGROUND: In the early asymptomatic stages of cardiomyopathy in chronic Chagas' disease, septal endomyocardial biopsies disclose multiple evidence of evolving myocardial damage. Detection of signs of an active myocardiopathic process may allow a better understanding of the evolution of this and other related dilated cardiomyopathies and provide a means for evaluation of the result of future therapeutic schemes. HYPOTHESIS: This study was designed to explore whether cellular damage caused by Chagas' disease is reflected by changes of certain serum electrolytes, enzymes, and glycoproteins associated with myocardial metabolism, especially in the coronary sinus into which the blood just metabolized by the heart is drained. METHODS: The study included 47 patients (35 men and 12 women, average age 40 years) with positive complement fixation reaction and hemagglutination test for Chagas' disease. The study protocol included medical records, electrocardiographic (ECG) recordings, routine laboratory analysis, chest x-rays, noninvasive cardiac examinations, and cardiac catheterization. RESULTS: In this study, we determined the concentration or activity of 9 electrolytes, 5 glycoprotein fractions, and 12 enzymes related to cardiac metabolism in blood from the coronary sinus, the superior vena cava, the pulmonary and femoral arteries, and found early release of inorganic phosphorus (p < 0.01) and isocitrate dehydrogenase (p < 0.01) from the heart and increased activity of serum alkaline phosphatase and aldolase (p < 0.05). Discriminant analysis suggested that the combination of the clinical picture, electrocardiographic findings, and peripheral activity of serum aldolase might be useful for the recognition of 86% of patients with Chagas' disease without segmental myocardial damage, 80% of those with early segmental abnormalities, and all patients with advanced myocardial damage or congestive heart failure. CONCLUSION: These results would make the application of more invasive techniques, such as left cineventriculography for detection of early myocardial compromise, unnecessary.

Cardiac involvement is a constant finding in acute Chagas' disease: a clinical, parasitological and histopathological study.

During the last 8 years 58 acute cases of Chagas' disease were studied. Patients from an endemic area of the state of Barinas, Venezuela, showed fever (98%) and circulating forms of T. cruzi (100%), and were treated with oral benznidazole. The recorded mortality was 8.6%. Acute myocarditis was constantly found either in myocardial biopsies or at necropsy, even in patients without any other sign of cardiac compromise (36%), which was detected by chest X-ray in 58%, by 2D echocardiography in 52%, by resting ECG in 41% and by clinical findings in 27.5% of the patients. Cardiomegaly was due to pericardial effusion rather than ventricular dilatation in most instances. Treatment eliminated parasitemia but negativized serology in only 20% of patients. It also appeared to have little influence on the ongoing myocarditic process, emphasizing the need for better therapeutic schedules, able to avoid or control the early appearance of immunologic mechanisms and microcirculatory damage involved in the future development of chronic chagasic myocarditis.

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.

[The anti-arrhythmia effect of carbamazepine in chagasic patients with advanced myocardial damage]. / Effecto antiarrítmico de la carbamazepina en pacientes chagásicos con daño miocárdico avanzado.

Oral administration of 600 mg/day of carbamazepine to 14 arrhythmic chagasic patients with advanced myocardial damage and no signs of congestive heart failure did not alter the frequency of ventricular extrasystoles, but reduced the total number of supraventricular ectopic beats in 7/14 patients and the episodes of complex ventricular arrhythmias in up to 43% of patients. This assessment was made from 24 hour continuous Holter recording during the course of this double-blind, placebo controlled, randomized crossover study. Serum levels of carbamazepine were also determined and found within therapeutic limits. Six patients complained of minor side effects. One patient presented with iatrogenic complete AV block, another case had proarrhythmic effect and one patient had to be withdrawn from the study because of gastric irritation. No instance of contractile depression was observed. Accordingly, carbamazepine is a therapeutic alternative for treatment of symptomatic complex ventricular or supraventricular arrhythmias in chronic chagasic patients without evidence of conduction system involvement or with intolerance to other antiarrhythmic drugs.

Concentration changes of electrolytes in serum of chronic chagasic myocardiopathic patients. Sodium, potassium, chloride, calcium, inorganic phosphorus and magnesium.

Sodium, potassium, chloride, calcium, inorganic phosphorus (Pi) and magnesium contents in the serum of 75 myocardiopathic chagasic patients together with that in 29 healthy controls were determined. Blood samples were taken by catheterization from the superior cava vein (SCV), coronary sinus (CS), pulmonary artery (PA) and a peripheral artery, usually the femoral (FA). The results show that the average serum sodium, potassium, chloride, calcium and PI were invariably different in most samples, except the levels of potassium in SCV and Pi levels in FA. The serum concentration of magnesium was significantly different only in the blood of CS. In general one can observe that in the chagasic patients the serum sodium, chloride and calcium tend to diminish while serum potassium, Pi and magnesium tend to increase, especially in CS blood. The coronary gradient indicates that sodium, chloride and calcium tend to deposit in heart tissues, whereas the other elements (potassium, magnesium and Pi) tend to be released from this tissue. The systemic and peripheric gradients suggest that the chemical elements under study tend either to deposit in/or be released from different tissues depending on the course of development of the chagasic myocardiopathy.

[Left ventricular mechanics in Chagas' disease and primary dilated myocardiopathies. A hemodynamic study]. / Mecánica ventricular izquierda en la enfermedad de Chagas y las miocardiopatías dilatadas primarias. Estudio hemodinámico.

The evolution of several mechanical parameters of left ventricular function was studied in 32 control subjects, 171 chronic chagasic and 60 primary dilated cardiomyopathy patients, which were submitted to an extensive invasive and non-invasive protocol. Preload and afterload (end-diastolic and end-systolic stress), contractile status (ejection fraction), the magnitude (mass/index) and adequacy of hypertrophy (mass/volume ratio) and afterload (systolic stress/volume ratio) were derived from the invasive explorations. There was an increased afterload in 25% of chronic chagasic patients without other evidence of early myocardial damage, which was accompanied by signs of inadequate hypertrophy. Both findings increased further with the progression of the disease. Systolic performance was initially preserved, but showed a progressive depression paralleling the clinical evolution. Patients with dilated cardiomyopathy showed a mechanical profile similar to chagasic patients with advanced degree of myocardial damage. The hemodynamic determination of mass index, mass/volume ratio, end-systolic and end-diastolic stress seem to be the best parameters for detection of early abnormalities in loading conditions of the heart in chronic Chagas, disease, and for indication and evaluation of the results of vasodilator therapy in both groups of patients.

[Early stress tests following an uncomplicated myocardial infarct: a comparison between symptom-limited and submaximal tests]. / Las pruebas de esfuerzo tempranas postinfarto miocárdico no complicado: comparación entre limitadas por síntomas y submaximas.

To compare the diagnostic and prognostic usefulness of symptom-limited versus load-limited submaximal stress testing, 76 patients, during the first week post acute non-complicated myocardial infarction, were submitted to a symptom-limited Naughton-modified protocol stress test. At 2 METs, 3 METs and maximal effort levels, the tests were classified as positive or negative following the currently used criteria. After a mean follow-up of 15 months, the symptom-limited protocol showed the best sensitivity (95%), specificity (78%), positive (64%) and negative (98%) predictive value, and also the highest risk ratio (27.4) for prediction of subsequent coronary events (2p less than 0.01 vs 2 METs, 3 METs and 2D-Echocardiogram results). Forward stepped multiple correlation analysis indicated independent prognostic value for the results of the symptom-limited stress test (R2: .52 p less than 0.01) and for the location of the myocardial infarction (R2: .05 p less than 0.05) only. In addition, the discriminant prognostic power of the symptom-limited protocol was significant after the fourth month of follow-up (2p less than 0.05 vs submaximal tests and 2D-Echo). Therefore, we recommend the performance of a symptom-limited stress test during the first week post acute non-complicated myocardial infarction, provided that all coronary active medication has been withheld 24 hours before the test.

Prognostic indicators of chronic chagasic cardiopathy.

After 104 patients with positive serology for Chagas' disease had been followed for a decade, a selection of 66 patients was made from this number and a total of 25 variables obtained from clinical and paraclinical findings were analyzed, with the purpose of knowing which of these variables may be of help, in time, in determining prognosis. The information was analyzed using the Cox regression model. The patients were classified into groups according to the results in the invasive and noninvasive studies: those with a normal electrocardiogram without heart disease (14 patients) or with early segmental abnormalities of the left ventricle (9 patients); those with an abnormal electrocardiogram and advanced myocardial damage but without signs of congestive heart failure (26 patients); and those with an abnormal electrocardiogram together with congestive heart failure (17 patients). Of these patients, those with electrocardiographic abnormalities correspond to stages of the disease where advanced myocardial damage is proven. There was a 42% mortality during the follow-up of these patients. According to the regression model, the value of the systolic blood pressure is a good predictor of mortality (P = 0.0380) in those with congestive heart failure. When we analyzed jointly the patients with an abnormal electrocardiogram, we found that several variables (systolic blood pressure, the presence of atrial fibrillation, the radiologic cardiothoracic index, and left ventricular end-diastolic volume obtained by the ventriculogram), were negatively correlated with regard to survival. This last model has a chi-square of 11.36 (P = 0.0228). These models allow us to predict the prognosis in this group of patients with Chagas' disease and advanced myocardial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Concentration changes of zinc, copper and iron in serum of chronic chagasic myocardiopathic patients.

Zinc, iron and copper content in serum of 75 myocardiopathic chagasic patients together with that in 29 healthy controls were determined. Blood samples were taken by catheterization from the superior cava vein, coronary sinus, pulmonary artery and a peripheral artery, usually the femoral. In general, serum zinc and iron levels tend to diminish in chagasic patients, while serum copper levels tend to increase. The coronary, systemic and peripheric gradients indicate that all these metal elements tend to deposit in heart tissue. Although zinc and iron tend to be deposited also in liver and other tissues, copper is released from them into the blood stream. Further studies should determine the requirement of these metal species in heart and other tissues of experimental animals in order to obtain more conclusive information about the cause of the serum metal impairment observed here.

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.

Life expectancy analysis in patients with Chagas' disease: prognosis after one decade (1973-1983).

We studied the evolution of chronic Chagas' disease in 107 patients with a positive Guerreiro-Machado reaction and 22 non-chagasic, non-heart disease control subjects for a follow-up period of 3 to 10 years (mean follow-up of 4.9 years). After completion of invasive and non-invasive studies, chagasic patients were classified into four groups: IA (normal ECG, without heart disease; 18 patients); IB (normal ECG, early left ventricular segmental abnormalities; 13 patients); II (abnormal ECG, advanced myocardial damage, no signs of heart failure; 42 patients); and III (abnormal ECG, end-stage, congestive heart failure; 34 patients). One out of five group IA patients re-studied with invasive methods evolved to group IB (20%); 4 group IB patients evolved to group II (33%) and 6 group II patients evolved to group III (15%). The life expectancy of patients in groups IA and IB (normal ECG) was similar to that of our control group, whereas in groups II and III it was significantly decreased (P less than 0.001). Nine group II patients (23%) and 28 group III patients (82%) died during the follow-up period. Main terminal events were refractory congestive heart failure, sudden death and systemic thromboembolism. Our findings suggest that chronic Chagas' disease follows an evolutionary course from asymptomatic, normal ECG group I stage to arrhythmic (II) and congestive (III) stages. Subjects with a positive Guerreiro-Machado reaction showed a significantly lower life expectancy than our control group, but only when clinical and/or ECG abnormalities were identified.

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 Ecg's and early left ventricular damage had right ventricular dilatation and/or segmental inferior-apical asynergy. Fourteen of 19 chagasic patients with abnormal Ecg's 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.

[High frequency electrocardiography in the early diagnosis of myocardial damage in patients with Chagas disease]. / La electrocardiografía de alta frecuencia en el diagnóstico precoz de daño miocárdico en pacientes con enfermedad de Chagas.

The present study determines the degree of usefulness provided by the qualitative analysis of the high frequency EKG with Mc Fee's triaxial system in the detection of myocardial damage during the incipient stages of Chagas disease. The results show that only the descending phase of the wave which corresponds to the vertical axis, i.e. Y, detects some kind of cardiac damage in the initial stages of disease with a high specificity, if normal values of 0-3 notches are taken, but in detriment of the sensitivity which is relatively low. This method did not prove to be useful in the longitudinal study of chagasic patients. It is a method which is very simple to perform with an inter-observer variability of 7%.

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.

[Study of sinus node function and atrioventricular conduction in patients with chagas disease (author's transl)]. / Estudio de la función del nodo sinusal y de la conducción atrioventricular en pacientes con enfermedad de chagas.

In order to detect possible abnormalities in sinus node function and atrio-ventricular conduction, one hundred and fourty three chagasic patients were subjected to electrophysiologic and pharmacologic studies. These patients were placed in four categories based on the their clinical, hemodynamic and angiographic characteristics. The chagasic patient without cardiac involvement (group IA), had no detectable abnormalities. Ten percent of those patients with early myocardial damage (group IB), had impaired sinus node automaticity. In three percent, the autonomic innervation was also altered and four percent had abnormally prolonged atrio-ventricular conduction. Among chagasic patients with abnormal EKG'S without heart failure (Group II), 45% had impaired sinus node automaticity, autonomic innervation was altered in 12%, and atrio-ventricular conduction was prolonged in 37%. Sinus node automaticity was impaired in 22% of those patients with abnormal EKG'S and heart failure (Group III). Autonomic innervation was altered in 33%, and atrio-ventricular conduction was prolonged in 47%. We conclude that over half of our patients with abnormal EKG'S will eventually require permanent pacing. Therefore, in these chagasic patients sinus node function and atrioventricular conduction should be routinely studied.

Evolution of the acid-base status in cardiac arrest.

In a study of the evolution of acid-base status in 26 patients who had cardiopulmonary arrest in the operating room, it appeared that:The determination of acid-base status within the first hour post-cardiac arrest is useful in differentiating final survivors from non-survivors. Respiratory or combined acidosis carries a poor prognosis not evidenced for metabolic acidosis. Late respiratory complications are more frequent in patients with initial combined acidosis. Treatment should be instituted on the basis of frequent determinations of acidbase status, since accurate diagnosis of degree and type of acidosis cannot be done on clinical grounds only. Recovery of consciousness is influenced by the type and severity of acidosis, less so by duration of arrest; and that high pCO(2) is associated frequently with unconsciousness after recovery of circulatory function.