Chronic Chagas' heart disease in children and adolescents: a clinicopathologic study

A retrospective study of the medical records filed at the University Hospital from 1965 to 1983 and of 18456 autopsies carried out in the Department of Pathology of this Institution from 1953 to 1983, referring to patients aged less than 18 years was performed in an attempt to fully characterize chronic Chagas' heart disease in children and adolescents. Only 19 of these patients fulfilled the criteria for inclusion in the present study (12 cases with only clinical information and 7 cases with clinical and pathological information). We noted that the clinical manifestations of chronic Chagas' heart disease are congestive heart failure, thromboembolism and sudden death. Radiologic, electrocardiographic and anatomo-pathological findings demonstrated serious myocardial involvement. This set of alterations is also detected in adults with chronic Chagas' heart disease. Among adolescents, however, the disease exhibits relevant peculiarities such as rapid evolution to death within a short period of time (128 days), diagnostic difficulty related to the presence of significant mitral regurgitation (61% erroneous initial diagnosis), and low frequency of right bundle branch block (11% of cases). These findings suggest that among children and adolescents, chronic Chagas' heart disease may be of a peculiar type and therefore may be useful to clarify the pathogenetic mechanism of the disease.     

Circadian profiles of heart rate and its instantaneous variability in patients with chronic Chagas' disease

INTRODUCTION AND OBJECTIVES: Impairment of the autonomous nervous system in early stages of Chagas' disease is still a matter of debate, although multiple approaches (including heart rate response to orthostatism and the Valsalva maneuver, and spontaneous variability) have been used to ascertain its occurrence. The circadian profile of heart rate and its variability have not been investigated in patients with Chagas' disease. PATIENTS AND METHOD: We analyzed the 24-hour heart rate by Holter recordings in 63 patients with and without ECG alterations, who had positive serological findings for Chagas' disease. These results were compared with those in 22 healthy subjects matched for sex and age. Mean 24-hour heart rate and its circadian amplitude were analyzed with Cusum analysis and nocturnal dip. In a subgroup of 45 subjects (30 with Chagas' disease and 15 healthy controls), heart rate instantaneous variability (24-hour pNN50 and r-MSSD) and circadian amplitude were also calculated by Cusum analysis. RESULTS: 24-hour and diurnal heart rates were lower in patients with Chagas' disease than in healthy subjects (P<.05). Circadian amplitude and dip were lower in patients, but these differences did not reach statistical significance. In the subgroup of 45 subjects, the reductions in instantaneous heart rate variability (pNN50 and r-MSSD) in Chagasic patients were small, and circadian amplitudes were preserved, when compared with healthy subjects. CONCLUSIONS: The lower heart rate in patients with Chagas' disease occurred only during diurnal activity, and instantaneous heart rate variability was preserved. These findings suggest an alteration in the sympathetic branch of the autonomous nervous system. The circadian heart rate profile, which has not been studied previously in patients with Chagas' disease, does not seem appreciably blunted in this stage of the disease.     

A clinical cardiovascular magnetic resonance service: operational considerations and the basic examination

Cardiovascular magnetic resonance (CMR) is now considered the "gold standard" for the assessment of regional and global systolic function, myocardial infarction and viability, and congenital heart disease. At specialized centers, CMR has become a clinical workhorse for the evaluation of ischemic heart disease and for heart failure and cardiomyopathies. Despite this versatility, general acceptance of CMR in cardiovascular medicine has progressed slowly. This article provides a basic understanding of important operational considerations when starting a CMR service and describes a conceptual framework of the components of a CMR examination.     

Chronic Chagas' heart disease presenting as an impending myocardial infarction: a case favoring the neurogenic pathogenesis concept

A 55-year-old Caucasian woman suddenly developed substernal chest pain at rest accompanied by pallor, diaphoresis, nausea, and vomiting. Physical examination was otherwise unremarkable. The resting ECG showed T-wave inversion in all anterior leads which returned to normal 24 h after the onset of the symptoms. The pain was eliminated promptly by sublingual isosorbide dinitrate. "Impending" acute myocardial infarction was diagnosed. Coronary arteriography, however, failed to reveal any change in any major coronary artery but an apical aneurysm of the left ventricle was detected. As the complement-fixation test for Chagas' disease was positive, the diagnosis of chronic Chagas' heart disease was then established. This unusual clinical manifestation of Chagas' disease is thought to be the consequence of a transient imbalance in the cardiac autonomic nervous system, which is considered to play a central role in the pathogenesis of chronic Chagas' heart disease. In addition, the present case may alert clinicians to the thus far neglected atypical chest pain, which is frequently seen in chagasic patients but whose etiology remains obscure.     

Distinctive impaired cardiac autonomic modulation of heart rate variability in chronic Chagas' indeterminate and heart diseases

Introduction

Cardiac autonomic dysfunction occurs in Chagas' indeterminate and heart disease, but comparison of this disturbance between both forms was not yet performed.

Methods

Time- and frequency-domain 5-minute heart rate variability in supine and standing positions were evaluated in 17 subjects with Chagas' disease with the indeterminate form, 13 with heart disease and 15 controls. Trend of variability indices across the groups was also tested.

Results

In the supine position, reduced time-domain and absolute frequency-domain indices reflecting overall autonomic modulation were observed in both Chagas' disease groups. In the standing position, the coefficient of variation and those frequency-domain indices were also reduced, and the other time-domain indices were reduced only in the cardiac group. Heart rate variability indices hypothesized to reflect relative sympathetic and parasympathetic activity showed no alteration. A significant graded reduction was observed in the altered indices in both postures, from the control to the Chagas' indeterminate and heart disease groups.

Conclusion

Cardiac autonomic dysfunction, with preserved putative measures of sympathetic and parasympathetic modulation in relative terms, was less severe or absent in the indeterminate and pronounced in cardiac form of Chagas' disease.     

Role of Cardiac Magnetic Resonance Imaging in Valvular Heart Disease: Diagnosis,Assessment, and Management

Purpose of Review

This article will review the current techniques in cardiac magnetic resonance imaging (CMR) for diagnosing and assessing primary valvular heart disease.

Recent Findings

The recent advancements in CMR have led to an increased role of this modality for qualifying and quantifying various native valve diseases. Phase-contrast velocity encoded imaging is a well-established technique that can be used to quantify aortic and pulmonic flow. This technique, combined with the improved ability for CMR to obtain accurate left and right ventricular volumetrics, has allowed for increased accuracy and reproducibility in assessing valvular dysfunction. Advancements in CMR technology also allows for improved spatial and temporal resolution imaging of various valves and their regurgitant or stenotic jets. Therefore, CMR can be a powerful tool in evaluation of native valvular heart disease.

Summary

The role of CMR in assessing valvular heart disease is growing and being recognized in recent guidelines. CMR has the ability to assess valve morphology along with qualifying and quantifying valvular disease. In addition, the ability to obtain accurate volumetric measurements may improve more precise management strategies and may lead to improvements in mortality and morbidity.

     

Trypanosoma cruzi-sensitized T-lymphocyte mediated 51CR release from human heart cells in Chagas' disease.

Cytotoxicity of T-lymphocytes from patients with Chagas' disease to parasitized and non-parasitized human heart cells labelled with 51Cr was demonstrated. The highest ratio of 51Cr released from the normal, non-parasitized heart cells was observed when the T-lymphocytes were collected from patients with acute Chagas' disease. The quantity of 51Cr released from the normal heart cells that were destroyed by T-lymphocytes collected from patients with chronic Chagas' disease was also significantly higher than the quantity of 51Cr released from normal heart cells incubated with lymphocytes from normal donors. The specific release of 51Cr from the heart cell cultures destroyed by the immune T-lymphocytes from patients with acute Chagas' disease and from patients with chronic disease was 38.1% and 25.8%, respectively, compared to the release of 51Cr observed in control studies. A small particle human heart cell antigen was shown to inhibit the migration of Trypanosoma cruzi-immune peripheral blood leukocytes. The findings appear to indicate that T-lymphocytes from patients with Chagas' disease are susceptible to activation by a cross-reactive heart cell antigen and suggest that an autoimmune mechanism can be established in some cases of acute Chagas' disease and can be perpetuated in the chronic phase of this disease by the continuous antigenic stimulation. Further, these experimental data indicate that the autoimmune destruction of heart cells in Chagas' disease is produced by delayed-type hypersensitivity mediated by T. cruzi-sensitized T-lymphocytes.     

Plasma norepinephrine in Chagas' cardioneuromyopathy: a marker of progressive dysautonomia

Chronic Chagas' disease produces pathologic changes of the cardiovascular, digestive, and autonomic nervous systems. In an attempt to elucidate the nature of the dysautonomia in patients with Chagas' disease, we measured plasma norepinephrine levels, blood pressure, and heart rate, both supine and standing in 26 patients, and compared these values of patients classified according to three clinical subsets of cardiovascular manifestations with the values of nine normal volunteers and 16 patients with nonchagasic heart failure. Results suggested (1) progressive blockade of the alpha receptor in patients with Chagas' disease who have minimal clinical symptoms (group I) and in those who have ECG alterations without congestive symptoms (group II), as reflected by normal or raised plasma norepinephrine levels without change of diastolic blood pressure during standing, which indicates absent postural reflexes; and (2) blockade associated with partial denervation in patients with Chagas' disease who have class III or IV heart failure (group III), as suggested by a lower supine plasma norepinephrine level and a fall in diastolic blood pressure in the upright position. The findings of reduced plasma norepinephrine levels are in contrast to the elevated plasma norepinephrine levels in patients without Chagas' disease with class III and IV heart failure who have sympathetic hyperactivity.     

Confirmation of Chagas' cardiomyopathy following heart transplantation

We report a case of Chagas' cardiomyopathy confirmed in a patient after heart transplantation. The patient initially presented with symptoms of congestive heart failure and was found to have positive serology for prior Trypanosoma cruzi infection. Despite optimal medical management, the patient had deterioration of his cardiac function and he underwent heart transplantation. Pathology examination of the explanted heart confirmed Chagas' cardiomyopathy. The cardiac sequelae of Chagas' disease include arrhythmias, aneurysm, thromboembolism, cardiomyopathy, and sudden death. We review the epidemiology, cardiac pathology, and evaluation of patients with Chagas' cardiac disease. We discuss the clinical features of Chagas' cardiomyopathy and available treatments including cardiac transplantation.     

Antibodies to Beta-Adrenergic Receptors Disclosing Agonist-Like Properties in Idiopathic Dilated Cardiomyopathy and Chagas' Heart Disease

Antibodies to Beta-Adrenergic Receptors. Recent studies confirm the existence of antibodies (Abs) to β adrenoceptors in patients with idiopathic dilated cardiomyopathy and Chagas' heart disease. These Abs can be shown to exert both stimulatory and inhibitory effects, which may play a role in the development of the cardiac abnormalities known to occur in these diseases, including advanced heart failure. The hypothesis is advanced that Chagas' heart disease and some forms of idiopathic dilated cardiomyopathy may represent, at least partially, a form of "adrenergic cardiomyopathy."     

Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas' cardiopathy

A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiania, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P less than 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease.     

Chagas' heart disease and myocardial infarct. Incidence and report of four necropsy cases

The authors describe the clinical-pathologic findings in four patients with myocardial infarct (MI) associated with Chagas' disease, found among 181 autopsies of chronic congestive cardiac chagasic patients. Organized thrombo-embolus was found in the epicardial portion of a coronary artery in one instance and thrombosis in the apex of the left ventricle as well as systemic infarcts were found in all cases. These data suggest thrombo-embolism, probably from the apex of the left ventricle, as a possible cause for the regional (large; transmural) MI in chronic Chagas' heart disease. The mechanism usually operative in MI, i.e. complicated atherosclerosis, was not present in the patients of this series. Moreover, our data do not support either small artery disease or heart denervation as etiologic factors for regional MI.     

Conduction Defects and Arrhythmias in Chagas' Disease:

Gap Junctions and Humoral Factors in Chagas' Disease. The protozoan parasite Trypanosoma cruzi causes Chagas' disease, a major cause of cardiac dysfunction in Latin Americans. Chagas' disease exhibits both acute and chronic phases, and each may be characterized by cardiac conduction disturbances. In acutely infected cultures of rodent heart cells, synchronized spontaneous beating becomes less regular, and coupling between cells is reduced. The basis of this decreased conduction is apparently in localization of the gap junction protein (Cx43) inside infected cells. Although total Cx43 is normal in infected cells, little is recognizable at appositional membranes. Electrophysiological properties are also altered by this infection. Action potentials are shortened, resting Ca²⁺ levels are elevated, and response to α-adrenergic agonists was altered, compared to controls. Humoral factors may contribute to the conduction defects in chronic Chagas' disease. Sera from chronically infected rabbits produced KC(J abnormalities in Langendorff-perfused rabbit hearts. These findings indicate that chagasic infection may modify ion channel function in the heart, and we suggest that these changes may be manifested in the conduction disturbances that characterize this disease.     

Decreased cardiopulmonary baroreflex sensitivity in Chagas' heart disease

No study has been performed on reflexes originating from receptors in the heart that might be involved in the pathological lesions of Chagas' heart disease. Our study was undertaken to analyze the role of cardiopulmonary reflex on cardiovascular control in Chagas' disease. We studied 14 patients with Chagas' disease without heart failure and 12 healthy matched volunteers. Central venous pressure, arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were recorded during deactivation of cardiopulmonary receptors. By reducing central venous pressure by applying -10 and -15 mm Hg of negative pressure to the lower body, we observed (a) a similar decrease of central venous pressure in both groups; (b) a marked increase in forearm vascular resistance in the control group but a blunted increase in the Chagas' group; and (c) no significant changes in blood pressure and heart rate. To analyze cardiopulmonary and arterial receptors, we applied -40 mm Hg of lower-body negative pressure. As a consequence, (a) central venous pressure decreased similarly in both groups; (b) blood pressure was maintained in the control group, whereas in patients with Chagas' disease, a decrease in systolic and mean arterial pressure occurred; (c) heart rate increased in both groups; and (d) forearm vascular resistance increased significantly and similarly in both groups. Unloading of receptors with low levels of lower-body negative pressure did not increase forearm vascular resistance in patients with Chagas' disease, which suggests that the reflex mediated by cardiopulmonary receptors is impaired in patients with Chagas' disease without heart failure. Overall control of circulation appears to be compromised because patients did not maintain blood pressure under high levels of lower-body negative pressure.     

Cardiac levels of norepinephrine, dopamine, serotonin and histamine in Chagas' disease.

Extraction and measurement of biogenic amines (norepinephrine, dopamine, serotonin and histamine) were carried out on human ventricular myocardium obtained from autopsies of individuals divided in the three following groups: chronic Chagas' heart disease (with congestive heart failure: 16 cases, and with sudden and unexpected death: 13 cases); hypertensive heart disease (12 cases); and control patients (with no heart disease: 12 cases). The myocardial samples were obtained from the free walls of left and right ventricles and from the apex. A significant depletion of norepinephrine was detected in those with congestive failure. A poorly elevated level of dopamine was also seen in right ventricular and apical myocardium from those with failure. Left ventricular and apical concentration of serotonin were significantly elevated in the presence of hypertensive heart disease. The most important findings were obtained with histamine, which is increased in both groups of Chagasic patients. We believe that the approach here reported may provide useful informations on the pathogenetic mechanisms, thus far poorly understood, of chronic Chagas' heart disease.     

Myocardiocyte apoptosis in heart failure in chronic Chagas' disease

Chagas' disease is caused by the parasite Trypanosoma cruzi. The disease affects 16-18 million patients in South America and heart involvement is the major cause of morbidity and mortality of the disease. The myocarditis observed during the chronic phase affects patients independently of the clinical manifestation, although patients with heart failure present an intense degree of myocarditis and fibrosis. To address the pathogenesis of heart failure in Chagas' disease, we investigated the role of myocardial cell loss by apoptosis in patients in the chronic phase of Chagas' disease. Apoptosis was also evaluated in inflammatory cells. Twenty-two specimens of the left ventricle were obtained during autopsies. Eleven samples from patients with heart failure and equal number from patients without heart failure. The material was analyzed by TUNEL methods to identify early apoptotic events and fibrosis was evaluated on HE-stained slides. In patients with heart failure, the extent of fibrosis and the number of apoptotic myocardial and inflammatory cells were significantly higher than in specimens obtained from patients without heart failure. These results suggest that myocardial cell loss by apoptosis and fibrosis contribute to heart failure in the chronic phase of Chagas' disease.     

Risk stratification in a Brazilian hospital-based cohort of 1220 outpatients with heart failure: role of Chagas' heart disease

BACKGROUND: Few studies evaluated prognostic factors of outpatients with heart failure of different etiologies including Chagas' heart disease. METHODS: We studied 1220 outpatients with heart failure in functional classes III and IV (NYHA) to evaluate prognostic factors. Patients aged 13-72 years (mean 45.5, standard deviation 11); 952 men (78%) and 268 women (22%) were followed up for 25.6+/-26 months from 1991 to 2000. Heart failure was attributed to idiopathic dilated cardiomyopathy in 454 (37%) patients. Etiologies were Chagas' heart disease in 242 (20%) patients, ischemic cardiomyopathy in 212 (17%), hypertensive cardiomyopathy in 170 (14%) and others in 142 (12%). Statistical analyses were performed with Kaplan-Meier and Cox proportional hazards methods, following a strategy of noninvasive model as well as in an invasive model to identify the risk of death. RESULTS: Four hundred fifteen (34%) patients died in the follow-up period, 71 (6%) patients underwent heart transplantation and 28 (2%) underwent other surgical interventions. In the noninvasive model, Chagas' heart disease (relative risk compared with other etiologies 2.26 to 2.97), left ventricular end diastolic diameter on echocardiography (relative risk 1.13) and left ventricular ejection fraction on radionuclide angiography (relative risk 0.96) were associated with higher mortality. In the invasive model, Chagas' heart disease (relative risk compared with other etiologies 2.66 to 9.13) was the most important determinant of mortality in association with the cardiac index (relative risk 0.40). CONCLUSIONS: In this cohort of patients with heart failure of different etiologies, Chagas' heart disease was the main prognostic factor for mortality.     

Assessment of diastolic function by cardiovascular magnetic resonance

Background The assessment of diastolic heart function has been hampered by multiple difficulties. Cardiovascular magnetic resonance (CMR) is a new, noninvasive technique to study cardiac function. Methods The literature on CMR for the analysis of diastolic function and its clinical applications is extensively reviewed. Results Analysis of ventricular filling velocity and volume flow, volumetric assessment of ventricular chamber volume, analysis of 3-dimensional myocardial strains, and assessment of myocardial energy content are numerous validated applications of CMR. With the advent of real-time imaging and automated analysis of myocardial strains, CMR tagging is a promising method to assess regional diastolic function. Today, many CMR techniques are leaving the experimental or developmental stage rapidly and becoming clinically available for the evaluation of diastolic function in heart disease. Conclusions CMR is emerging as a highly accurate and reproducible noninvasive 3-dimensional technique for the assessment of diastolic function. (Am Heart J 2002;144:198-205.)     

Edema and fibrosis imaging by cardiovascular magnetic resonance: How can the experience of Cardiology be best utilized in rheumatological practice?

Objectives

CMR, a non-invasive, non-radiating technique can detect myocardial oedema and fibrosis.

Method

CMR imaging, using T2-weighted and T1-weighted gadolinium enhanced images, has been successfully used in Cardiology to detect myocarditis, myocardial infarction and various cardiomyopathies.

Results

Transmitting this experience from Cardiology into Rheumatology may be of important value because: (a) heart involvement with atypical clinical presentation is common in autoimmune connective tissue diseases (CTDs). (b) CMR can reliably and reproducibly detect early myocardial tissue changes. (c) CMR can identify disease acuity and detect various patterns of heart involvement in CTDs, including myocarditis, myocardial infarction and diffuse vasculitis. (d) CMR can assess heart lesion severity and aid therapeutic decisions in CTDs.

Conclusion

The CMR experience, transferred from Cardiology into Rheumatology, may facilitate early and accurate diagnosis of heart involvement in these diseases and potentially targeted heart treatment.     

Cardiac magnetic resonance in outpatients in Germany--indications, complications and protocol suggestions from a high-volume center

BACKGROUND: Cardiac magnetic resonance (CMR) has developed into a routine examination in many centers in cardiology. However, there is little knowledge about its applicability in outpatients as a diagnostic tool for cardiovascular diseases. We report about the experiences in a high-volume cardiac imaging center and in a "mobile setting" in Germany and provide routinely used examination protocols. METHODS: 8976 patients referred for CMR from cardiologists, internal medicine practices and from general practitioners and 2200 patients examined in a "mobile" system by outpatient cardiologists were included in the study. Indications were as follows: 7672 (69%) examinations for myocardial ischemia and viability, 1313 (12%) for cardiac and pericardial inflammatory disease and cardiac mass, 976 (9%) for detection and quantification of heart valve disease and 466 (4%) for congenital heart disease. 697 (6%) were referred for other indication. Two independent readers performed image analysis of the 8976 patients in our center. RESULTS: Image quality was rated "excellent" in 90.6%, "good" in 8%, "fair" in 1.2% and "poor" in 0.2%. 0.0002% of all examinations were not assessable due to low image quality. Minor complications (temporarily, asymptomatic AV-blockade; mild chest pain and/or dyspnea; nausea) could be observed in 12% and resolved within few minutes. One patient experienced a grand mal seizure due to hyperventilation. 0.9% examinations had to be terminated untimely due to claustrophobia. CONCLUSION: CMR in outpatients is a widely used imaging modality in cardiology in Germany. A large variety of clinical questions may be answered by CMR with excellent image quality and without major complication. With user-adapted protocols, a rapid diagnosis is achieved even in outpatients in a "mobile" setting. Hence, CMR will increase its applicability as a routine imaging tool.