Nuclear Medicine Methods for Assessment of Chronic Chagas Heart Disease

Abstract Several different imaging methods can be used to evaluate patients with Chagas heart disease (CHD) for diagnostic and prognostic purposes, including plain chest radiography; echocardiography; myocardial perfusion scintigraphy, for detection of ischemia and fibrosis; radionuclide gated-angiography, for evaluation of biventricular function; 123I-MIBG labeling of sympathetic myocardial innervation; MRI, for detection and quantitation of myocardial fibrosis; and coronary angiography. This study aims to review the contributions of these nuclear medicine methods to understanding of the pathophysiology of chronic Chagas cardiomyopathy (CCC). Careful analysis and integration of findings provided by these imaging methods in patients with CCC at different stages has contributed significantly to improving understanding of several peculiarities of the disease. Clinical and experimental studies in animal models show that perfusion abnormalities detected in association with dysfunctional but viable myocardium are a common finding in CCC patients and correspond to areas of cardiac sympathetic denervation, as assessed by 123I-MIBG imaging. Furthermore, recent reports have demonstrated a close relationship between coronary microvascular disturbances and myocardial inflammation. Thus, ongoing research, mainly focused on refinements of 18F-FDF -PET techniques and further exploration of nuclear methods, such as SPECT, have the potential to contribute to detection and monitoring of early subclinical myocardial damage thereby enabling evaluation of therapeutic strategies targeting inflammation and microvascular ischemia that could result in better prognostic stratification of patients with CHD.

Echocardiography in Indigenous Populations and Resource Poor Settings.

The majority of global cardiovascular disease burden occurs in low- and middle-income countries (LMIC) and indigenous populations. Although common diseases, such as ischaemic heart disease, cause significant burden, there are also neglected diseases. Forgotten by many, these diseases-including rheumatic heart disease, endomyocardial fibrosis and Chagas cardiomyopathy-continue to take a tremendous toll on a large proportion of the world's population. Whilst the technology of echocardiography continues to evolve in many high-income countries, low resource countries are working out how to make this vital tool available and affordable for the most remote and poorest populations. This paper aims to highlight the neglected cardiovascular diseases and their echocardiographic features. It also highlights the latest research in relation to portable echocardiography, task shifting and disease screening. The authors make recommendations in relation to future directions, including making echocardiography an affordable and accessible tool for all.

Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance.

BACKGROUND: Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003). CONCLUSIONS: We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.

Assessment of cross-reactive host-pathogen antibodies in patients with different stages of chronic Chagas disease.

INTRODUCTION AND OBJECTIVES: Trypanosoma cruzi infection has been shown to induce humoral autoimmune responses against host antigens tissues. Particularly, antibodies cross-reacting with myocardial antigens may play a role in the development of the severe forms of chronic Chagas disease. The aim of this study was to determine the association between clinical stage of the disease and the presence of autoantibodies in patients with chronic Chagasic disease. METHODS: We performed a cross-sectional study in T. cruzi-seropositive patients divided into 3 groups according to the classic classification of chronic Chagas heart of Storino et al. All participants underwent complete clinical examination and their sera were used to measure autoantibody levels. RESULTS: All patients had detectable levels of anti-p2ß and anti-B13 autoantibodies but none had anti-Na-K-ATPase antibodies. No association was observed between electrocardiographic conduction disturbances and autoantibody levels. Patients with chronic Chagas disease stage III had the highest levels of anti-B13 antibodies and a high risk of mortality score, showing a clear association between disease stage and this score. CONCLUSIONS: Anti-B13 antibodies were significantly higher in chronic Chagas disease stage III patients, suggesting that these antibodies may be involved in disease progression and that they might be a useful marker of poor prognosis in terms of heart compromise. Our results also reveal an important correlation between the level of anti-B13 autoantibodies and symptomatic heart failure and/or dilated cardiomyopathy.

[Assessment of diastolic function in Chagas' disease with pulsed doppler tissue imaging]. / Utilidad del Doppler tisular pulsado en la valoración de la función diastólica en la enfermedad de Chagas.

Diastolic function is involved early during the undetermined form of Chagas' disease (Ch). Pulsed Doppler tissue imaging (DTI) is a new technique to evaluate diastolic function recording myocardial velocities in the longitudinal axis. To evaluate the relevance of DTI in patients with Ch, we studied, with Doppler and echocardiography, 49 patients (average age 49 +/- 12 years) and 20 normal subjects (average age 45 +/- 15 years) as a control group (C). Patients were divided in four groups according to the pattern of their mitral and pulmonary vein flows: Normal diastolic function (N), prolonged relaxation (PR), pseudonormal (PN) and restrictive (R). Peak velocity of the E wave of the lateral mitral annulus (Ea) was diminished in PR, PN, and R patients (0.11 +/- 0.02 m/s, 0.10 +/- 0.02 m/s and 0.12 +/- 0.06 m/s, respectively) as compared to group C (0.18 +/- 0.07 m/s, p < 0.01) but not with respect to group N (0.15 +/- 0.03 m/s, N.S.). In this latter group only peak E velocity of transmitral flow/Ea ratio was useful to detect diastolic abnormalities as compared to group C (4.92 +/- 0.98 vs 4.14 +/- 1.26, p < 0.05). DTI was useful in the assessment of diastolic function in Ch, including those patients in whom mitral and pulmonary vein flows were normal.

[Assessment of diastolic function in Chagas disease with pulsed Doppler tissue imaging]. / Evaluación de la función diastólica en la enfermedad de Chagas mediante Doppler tisular pulsado.

Diastolic function is early involved during the undetermined form of Chagas disease. Pulsed Doppler tissue imaging is a new technique to evaluate diastolic function by mean of the record of myocardial velocities in the longitudinal axis. With the purpose to evaluate diastolic function by pulsed Doppler tissue imaging in patients with Chagas disease, we studied with Doppler echocardiography 51 patients (age average 48 +/- 12 years) and 24 normal subjects (age average 47 +/- 15 years) as a control group. Patients were divided in two groups according to the pattern of mitral and pulmonary vein flow: restrictive (17 patients) and no restrictive (35 patients). Peak velocity of E wave of the lateral mitral annulus was diminished in no restrictive and restrictive patients (0.13 +/- 0.04 m/s, 0.11 +/- 0.05 m/s respectively) in regard to control group (0.18 +/- 0.07 m/s, p < 0.01). Pulsed Doppler tissue imaging was useful in the assessment of diastolic function in Chagas disease, including patients with no restrictive mitral and pulmonary vein filling pattern.

Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography.

OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.