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-p2β 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 Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease

Background

In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation.

Objective

This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects.

Methods

Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNN_T), and in AC (RMSNN_AC) and DC (RMSNN_DC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05).

Results

Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNN_T, RMSNN_AC, and RMSNN_DC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNN_AC showed significant increase as a function of MNN, whereas RMSNN_T and RMSNN_DC did not.

Conclusion

HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence.     

Left Ventricular Diastolic Function and Exercise Capacity in Patients with Chagas Cardiomyopathy

Parameters of diastolic function have been shown to correlate with exercise capacity (EC) in individuals with impaired left ventricular (LV) systolic function. However, the role of LV diastolic function in predicting EC in Chagas cardiomyopathy has not been reported. Objectives: This study aimed to determine the relationship between LV diastolic parameters assessed by echocardiography and EC in patients with Chagas cardiomyopathy. Methods: We studied 40 patients (23 men; 49 ± 8 years), with diagnosis of Chagas disease and dilated cardiomyopathy. Medical therapy was individually adjusted according to standardized guidelines. Methods of acquiring two‐dimensional Doppler, tissue Doppler imaging (TDI), and their measurements were described. Exercise testing was performed by a Bruce protocol. Brain natriuretic peptide (BNP) levels were also determined. Results: Most patients (63%) were in NYHA functional class I. Mean peak oxygen consumption estimated (peakVO₂) was 31.7 ± 10.2 mL/kg per minute, and mean left ventricular ejection fraction (LVEF) was 36.3 ± 7.8%. Univariate analysis showed that various echocardiographic parameters of diastolic function were correlated with peakVO₂. There was no correlation between BNP levels or LVEF and EC. Multivariate analysis, after adjustment for age and gender, revealed that E/E′ ratio and left atrial volume (LAV), emerged as independent predictors of EC, as demonstrated in the model: peakVO₂= 60.825 + (0.439 × LAV) ? (1.620 × E/E′ ratio) ? (0.483 × age) ? (4.821 × female gender). The R² of this model was 0.52. Conclusions: Functional capacity assessed by peakVO₂ was related to increase LV filling pressures, independently on systolic function in patients with Chagas cardiomyopathy. (Echocardiography 2010;27:519‐524)     

Chronotropic Incompetence and Abnormal Autonomic Modulation in Ambulatory Chagas Disease Patients

Background: Chagas disease (ChD) patients might present chronotropic incompetence during exercise, although its physiopathology remains uncertain. We evaluated the heart rate (HR) response to exercise testing in ChD patients in order to determine the role of autonomic modulation and left ventricular dysfunction in the physiopathology of chronotropic incompetence. Methods: ChD ambulatory patients (n = 170) and healthy controls (n = 24) underwent a standardized protocol including Doppler echocardiography, Holter monitoring, HR variability analysis, brain natriuretic peptide (BNP) measurement, and maximal exercise testing. The chronotropic response was calculated as the percentage of predicted HR achieved and the HR increment (ΔHR) during exercise. ChD patients were divided according to the absence or presence of cardiopathy and chronotropic incompetence (<85% predicted HR). Results: Chronotropic incompetence was present in 34 (20%) of all ChD patients. The group with cardiopathy displayed reduced ΔHR (91 ± 19 bpm) during exercise in comparison with ChD patients without cardiopathy (100 ± 19 bpm). Both the values observed in ChD groups were significantly different from those of controls (112 ± 13 bpm). Exercise duration, maximal oxygen consumption, and systolic blood pressure increment were significantly reduced in patients with abnormal chronotropic response. ΔHR during the exercise was significantly correlated with markers of autonomic control of sinus node, such as rest HR (r =?0.498, P ≤ 0.001), peak HR during exercise (r = 0.775, P ≤ 0.001), minimal HR during Holter recording (r =?0.231, P = 0.003), and high‐ and low‐frequency components of short‐term HR variability (r = 0.188, P = 0.042 and r = 0.203, P = 0.027). Neither left ventricular function nor BNP levels were independently related to the presence of chronotropic incompetence. Conclusions: Chronotropic incompetence may be considered an early sign of autonomic dysfunction in ChD patients.     

组织多普勒显像评价终末期肾病患者的心室功能

目的 探讨组织多普勒显像参数评价终末期肾病患者心室功能的价值.方法 健康成人和左心室射血分数正常的终末期肾病患者各31例,均行二维及组织多普勒显像检测,记录左心室射血分数、左心室舒张末期内径、左心室收缩末期内径、室间隔和左心室后壁厚度;二尖瓣和三尖瓣口舒张早期及舒张晚期峰速,计算二尖瓣和三尖瓣口舒张早期与舒张晚期峰速之比.组织多普勒显像下心尖四、两腔测定左心室后间隔、侧壁、前壁、下壁以及右心室侧壁的收缩期运动速度、舒张早期和舒张晚期运动速度,计算二尖瓣和三尖瓣口舒张早期峰速与舒张早期运动速度之比、舒张早期运动速度与舒张晚期运动速度之比.比较两组左、右心室超声参数.结果 与健康成人相比,终末期肾病患者二尖瓣和三尖瓣口舒张早期峰速与舒张晚期峰速之比、二尖瓣和三尖瓣环平均收缩期运动速度、舒张早期运动速度、舒张早期运动速度与舒张晚期运动速度之比均减低;二尖瓣舒张早期峰速与舒张早期运动速度之比增高(P<0.05).结论 终末期肾病患者左、右心室存在舒张功能障碍,收缩功能亦受损;左心室射血分数正常的终末期肾病患者收缩功能亦受损.     

Pathological Pancreatic Exocrine Function and Duct Morphology in Patients with Cholelithiasis

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.     

老年非甲状腺疾病患者甲状腺功能检测及评价

本文对老年非甲状腺疾病患者107例、健康老年人30例的血清T_3、T_4、FT_3、FT_4、γT_3、TSH水平进行测定。结果表明,老年心血管疾病、恶性肿瘤、肺部疾病、糖尿病、肝病患者T_3明显降低(P<0.05),FT_3显著降低(P<0.01),γT_3显著增高(P<0.01)。老年其他疾病(神经系疾病、胆囊炎等)T_3虽无明显变化,但FT_3仍明显降低(P<0.05)。T_4仅在肺部疾病患者明显降低(P<0.05),其余各组T_4、FT_4、TSH均无显著改变,健康老年T_3较健康成年人明显降低(P<0.05),其变化程度与疾病严重程度有一定关系,其中以FT_3更为敏感。故认为,测定甲状腺激素水平对判断老年患者病情、估计预后有重要参考价值。     

Pulmonary Function in Patients with Inflammatory Bowel Disease

Pulmonary function has been assessed in 36 outpatients with inflammatory bowel disease. The carbon monoxide transfer factor was found to be significantly reduced in patients as compared with matched controls (P less than 0.01). The reason for this reduction is not clear but it is unlikely to be due to sulfasalazine (Salazosulphapyridine).