Benedito Carlos Maciel

Pathogenesis of Chronic Chagas Heart Disease

Background— Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. Methods and Results— A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Conclusions— Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.

Frequency, Clinical Characteristics, and Respiratory Parameters of Hepatopulmonary Syndrome

OBJECTIVES To determine the frequency and the clinical characteristics of hepatopulmonary syndrome (HPS) in cirrhotic candidates for orthotopic liver transplantation and to identify the major respiratory parameters predictive of the presence of changes in arterial oxygenation. PATIENTS AND METHODS Patients underwent transthoracic contrast-enhanced echocardiography, pulmonary scintigraphy, pulmonary function test with diffusing capacity of lung for carbon monoxide (DLCO), and measurement of arterial blood gases. RESULTS Fifty-six patients were studied. Twenty-five patients (45%) presented with intrapulmonary vascular dilatations, but only 9 (16%) fulfilled the criteria for HPS. The clinical or demographic characteristics considered did not differ in the patients with and without HPS. The DLCO value was significantly lower in patients with HPS (P=.01). However, 32 (80%) of 40 patients with low DLCO values did not fulfill the criteria for HPS. An alveolar arterial oxygen gradient (AaPO2) of more than 20 mm Hg showed a higher diagnostic accuracy (91%) in the assessment of HPS than did the DLCO of less than 80% predicted (41%) and the AaPO2 of more than 15 mm Hg (71%). CONCLUSIONS The AaPO2 proved to be a more reliable index than PaO2 and DLCO for the determination of changes in arterial oxygenation in HPS. The DLCO does not seem to be a good marker for HPS screening. Intrapulmonary vascular dilatations were frequent, even in patients who did not fulfill the criteria for HPS.

Effects of aerobic exercise training on heart rate variability during wakefulness and sleep and cardiorespiratory responses of young and middle-aged healthy men

The purpose of the present study was to evaluate the effects of aerobic physical training (APT) on heart rate variability (HRV) and cardiorespiratory responses at peak condition and ventilatory anaerobic threshold. Ten young (Y: median = 21 years) and seven middle-aged (MA = 53 years) healthy sedentary men were studied. Dynamic exercise tests were performed on a cycloergometer using a continuous ramp protocol (12 to 20 W/min) until exhaustion. A dynamic 24-h electrocardiogram was analyzed by time (TD) (standard deviation of mean R-R intervals) and frequency domain (FD) methods. The power spectral components were expressed as absolute (a) and normalized units (nu) at low (LF) and high (HF) frequencies and as the LF/HF ratio. Control (C) condition: HRV in TD (Y: 108, MA: 96 ms; P<0.05) and FD - LFa, HFa - was significantly higher in young (1030; 2589 ms2/Hz) than in middle-aged men (357; 342 ms2/Hz) only during sleep (P<0.05); post-training effects: resting bradycardia (P<0.05) in the awake condition in both groups; VO2 increased for both groups at anaerobic threshold (P<0.05), and at peak condition only in young men; HRV in TD and FD (a and nu) was not significantly changed by training in either groups. The vagal predominance during sleep is reduced with aging. The resting bradycardia induced by short-term APT in both age groups suggests that this adaptation is much more related to intrinsic alterations in sinus node than in efferent vagal-sympathetic modulation. Furthermore, the greater alterations in VO2 than in HRV may be related to short-term APT.

Autonomic nervous control of the heart rate during isometric exercise in normal man.

The relative contribution of the efferent components of the autonomic nervous system to the regulation of tachycardia induced by isometric exercise was assessed in 23 normal males. The isometric exercise (handgrip) was performed at the maximum intensity tolerated by the individual over a period of 10 s (maximal voluntary contraction — MVC) and at levels equivalent to 75, 50 and 25% of MVC for 20, 40 and 10 s, respectively. The study was performed both under control conditions and after pharmacological blockade with atropine (12 individuals) or propranolol (11 individuals). Under control conditions, the heart rate (HR) responses to isometric effort were dependent on the intensity and duration of the exercise, showing a tendency towards progressive elevation with the maintenance of muscular contraction at the levels studied. The tachycardia evoked by this effort was of considerable magnitude and of rapid onset, especially at the more intense levels of activity. Parasympathetic blockade markedly decreased tachycardia, which manifested itself during the first 10 s of exercise at all levels of intensity, whereas sympathetic blockade markedly modified the HR response after 10 s of effort at the 75 and 50% MVC levels. A slight depression of the tachycardiac response could be observed already after 10 s of maximum effort after propranolol. The present results suggest that the autonomic regulation of these responses is based on a biphasic mechanism, with the initial phase depending on the rapid withdrawal of the parasympathetic influence, followed by a marked sympathetic contribution to the induction of tachycardia after 10 s of isometric contraction or even a little before at maximum exertion.

Effect of parasympathetic impairment on the haemodynamic response to handgrip in Chagas's heart disease.

Haemodynamic responses to sustained isometric exercise (handgrip at 30% of maximum voluntary capacity) were studied in 10 patients with Chagass cardiopathy without previous or current heart failure. Five of the patients (group 1) had profound impairment of parasympathetic control of heart rate. They had no tachycardia in response to intravenous administration of atropine and no bradycardia during phase IV of the Valsalva manoeuvre. The other five (group 2) showed normal vagal regulation of heart rate, as judged by chronotropic responses to these tests. The heart rate change (mean (SD] elicited by the handgrip test was significantly lower in group 1 (from 93.0 (14.1) to 95.0 (16.7) beats/min) than in group 2 (from 78.2 (15.8) to 92.8 (18.1) beats/min). Pressor responses to handgrip were of similar magnitude (from 91.6 (7.8) to 109.0 (8.0) mm Hg in group 1 and from 88.6 (11.9) to 106.8 (20.9) mm Hg in group 2). In both groups no significant change in stroke index was detected during handgrip. Cardiac index increased during handgrip from 4.0 (1.2) to 4.8 (1.3) 1/min/m2 in group 2, but there was no significant change in group 1 (from 4.9 (0.7) to 4.8 (1.1) 1/min/m2). Changes in calculated systemic vascular resistance were significantly higher in group 1 (from 934 (175) to 1176 (383) dyn s cm-5) than in group 2 (from 1109 (404) to 1112 (424). This study shows that parasympathetic impairment adversely influences the haemodynamic pattern of response to isometric exercise in patients with Chagass heart disease. In such conditions, the pressor response to handgrip is predominantly mediated by an increase in systemic vascular resistance rather than an increase in cardiac output.

Abnormal baroreflex control of heart rate in decompensated congestive heart failure and reversal after compensation

Congestive heart failure (CHF) causes impairment of baroreflex control of heart rate (HR). To determine if this derangement is reversible, the cardiac chronotropic control was assessed in 10 patients with class IV chronic CHF of various etiologies before and after compensation achieved by bed rest, salt restriction, diuretics and vasodilators. Mean time between the 2 studies was 15 +/- 3 days. The management was modified 3 days before the second autonomic evaluation, so as to reestablish the same diet and pharmacologic conditions of the previous study. Compensation led to significant reduction in symptom-based class, body weight, and pulmonary and systemic congestion. Mean +/- standard error of the mean HR responses (beats/min) before and after compensation were, respectively: (1) to atropine (0.04 mg/kg): 10 +/- 2 and 27 +/- 2 (p less than 0.01); (2) to handgrip (30% maximum capacity, 1 minute): 9 +/- 2 and 19 +/- 3 (p less than 0.005); (3) to headup tilt (5 minutes): 4 +/- 3 and 20 +/- 4 (p less than 0.005). Mean +/- standard error of the mean baroreflex sensitivity (ms/mm Hg) of RR responses to phenylephrine and amyl nitrate-induced changes in systolic pressure was, respectively, in each condition: phenylephrine, 0.9 +/- 0.2 and 8 +/- 2.3 (p less than 0.05); amyl nitrate, 0.3 +/- 0.2 and 4.1 +/- 1.1 (p less than 0.05). A significant correlation between improvement in HR responses to atropine and tilt and changes in body weight was obtained. These findings show a reversible component of impaired baroreflex control of HR in severe CHF, possibly due to its congestive effects.

Acute chagasic myocardiopathy after orthotopic liver transplantation with donor and recipient serologically negative for Trypanosoma cruzi: a case report.

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.

Cardiorespiratory adaptations induced by aerobic training in middle-aged men: the importance of a decrease in sympathetic stimulation for the contribution of dynamic exercise tachycardia

We investigated the effects of aerobic training on the efferent autonomic control of heart rate (HR) during dynamic exercise in middle-aged men, eight of whom underwent exercise training (T) while the other seven continued their sedentary (S) life style. The training was conducted over 10 months (three 1-h/sessions/week on a field track at 70-85% of the peak HR). The contribution of sympathetic and para-sympathetic exercise tachycardia was determined in terms of differences in the time constant effects on the HR response obtained using a discontinuous protocol (4-min tests at 25, 50, 100 and 125 watts on a cycle ergometer), and a continuous protocol (25 watts/min until exhaustion) allowed the quantification of the parameters (anaerobic threshold, VO2 AT; peak O2 uptake, VO2 peak; power peak) that reflect oxygen transport. The results obtained for the S and the T groups were: 1) a smaller resting HR in T (66 beats/min) when compared to S (84 beats/min); 2) during exercise, a small increase in the fast tachycardia (delta 0-10 s) related to vagal withdrawal (P < 0.05, only at 25 watts) was observed in T at all powers; at middle and higher powers a significant decrease (P < 0.05 at 50, 100 and 125 watts) in the slow tachycardia (delta 1-4 min) related to a sympathetic-dependent mechanism was observed in T; 3) the VO2 AT (S = 1.06 and T = 1.33 l/min) and VO2 peak (S = 1.97 and T = 2.47 l/min) were higher in T (P < 0.05). These results demonstrate that aerobic training can induce significant physiological adaptations in middle-aged men, mainly expressed as a decrease in the sympathetic effects on heart rate associated with an increase in oxygen transport during dynamic exercise.

Forma Indeterminada da Moléstia de Chagas: Proposta de Novos Critérios de Caracterização e Perspectivas de Tratamento Precoce da Cardiomiopatia

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto – USPCorrespondencia: Jose Antonio Marin-Neto – Divisao de Cardiologia, Depto. deClinica Medica - Hospital das Clinicas, FMRP-USP – Av. Bandeirantes, 390014048-900 - Ribeirao Preto, SP - E-mail: marin_neto@yahoo.comRecebido para publicacao em 26/2/02Aceito em 27/5/02

Cardiac tamponade: An unusual complication of pericardial cyst

Pericardial cysts are not common and rarely cause symptoms. We report a unique case of a 15-year-old male patient with cardiac tamponade clinically diagnosed who was referred for echocardiography. Transthoracic echocardiography revealed, in addition to a large pericardial effusion associated with echocardiographic signs of cardiac tamponade, an 8 x 5 cm echofree image suggesting a pericardial cyst adjacent to the right atrium. Immediately after pericardiocentesis, yielding a serosanguinous liquid, the patient showed striking clinical improvement and echocardiography demonstrated minimal pericardial effusion with persistence of the cystic image. At surgery a pericardial cyst containing a sanguinous fluid was found and the pathologic findings were consistent with hematic pericardial cyst. Thus echocardiography played a fundamental role for the diagnosis and treatment of the rare complication of a pericardial cyst documented in this patient.