Pattarapong Makarawate

Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand

BACKGROUND Thiopurine S-methyltransferase (TPMT) is a polymorphic enzyme associated with detoxification of azathioprine, an immunosuppressant used after renal transplantation in several Asian countries. Patients with variations of the TPMT gene may be at risk for myelosuppression after they receive a standard dosage of the drug. The frequency of TPMT*3C has been reported to be higher in the Thai population than in other Asian populations, possibly putting the Thais at higher risk for myelosuppression. OBJECTIVE The aim of this study was to assess the impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand. METHODS This study was conducted at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, and Chulalongkorn Hospital, Chulalongkorn University, Bangkok, Thailand. Eligible patients underwent kidney transplantation from deceased or living-related donors from 1984 to 2007. Electronic medical records were assessed retrospectively for the 6-month period after initiation of azathioprine treatment. TPMT genotyping and phenotyping were studied prospectively using real-time polymerase chain reaction and biochemical assay, respectively. The odds ratios (ORs), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS A total of 139 patients were enrolled (89 men, 50 women; median age, 42 years [range, 17-70 years]; mean weight, 58 kg [range, 37-87 kg]). The heterozygous TPMT*1/*3C genotype was found in 9 of the 139 patients (6.47%) (95% CI, 3.00-11.94). The TPMT activity of those patients was significantly lower than that of patients with the homozygous wild-type genotype (median, 21.37 vs 37.12 nmol 6-methylthioguanine/g . Hb/h, respectively; P < 0.001). The risk for azathioprine-induced myelosuppression in the patients with the heterozygous TPMT*1/*3C genotype was significantly higher than that in patients with the wild-type genotype (adjusted OR, 14.18 [95% CI, 3.07-65.40]; P < 0.005). The sensitivity and specificity of TPMT*3C genotyping for the prediction of azathioprine-induced myelosuppression in these kidney transplant recipients were 27% and 97%, respectively. Assuming a prevalence of azathioprine-induced myelotoxicity of 7% according to previously published data, the PPV and NPV were estimated to be 50% and 95%, respectively. CONCLUSION In these kidney transplant recipients, patients who carried the TPMT*3C allele were at a higher risk for azathioprine-induced myelosuppression than noncarriers.

SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome

Background Brugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest. SCN5A, encoding the α‐subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS. An implantable cardioverter defibrillator (ICD) is the standard treatment for secondary prevention. This study aimed to evaluate association of the SCN5A variant with this cardiac conduction disturbance and appropriate ICD shock therapy in Thai symptomatic BrS patients with ICD implants. Methods and Results Symptomatic BrS patients diagnosed at university hospital were enrolled from 2008 to 2011. The primary outcome of the study was an appropriate ICD shock defined as having non‐pacing‐associated ICD shock after the occurrence of ventricular tachycardia or ventricular fibrillation. Associations between SCN5A polymorphisms, cardiac conduction disturbance, and potential confounding factors associated with appropriate ICD shock therapy were analyzed. All 40 symptomatic BrS patients (median age, 43 years) with ICD implantations were followed for 24 months. There were 16 patients (40%) who had the appropriate ICD shock therapy after ICD treatment. An independent factor associated with appropriate ICD shock therapy was SCN5A‐R1193Q with an adjusted hazard ratio of 10.550 (95% CI, 1.631–68.232). Conclusions SCN5A‐R1193Q is associated with cardiac conduction disturbances. It may be a genetic marker associated with ventricular arrhythmia leading to appropriate ICD shock therapy in symptomatic BrS patients with ICD treatment. Because of the small sample size of study population and the appropriate ICD shock outcome, further large studies are needed to confirm the results of this study.

Malignant mesothelioma of the pericardium: a report of two different presentations.

Malignant mesothelioma of the pericardium is a rare and fatal condition that clinicians should be aware of due to its variability of clinical manifestation. The diagnosis may be delayed as a result of delayed treatment. Here, we report two cases of malignant pericardial mesothelioma with two different clinical aspects: cardiac tamponade and mimic tuberculous pericarditis. Both patients: may have indirect exposure to asbestos. Despite chemotherapy, both patients died at 2 weeks and 3 months after the diagnosis. Malignant mesothelioma of the pericardium is fatal, has a variety of presentation, and may not be related to asbestosis exposure.

Thai Yoga as an Appropriate Alternative Physical Activity for Older Adults

Thai Yoga (TY), has been recommended by the Public Health Ministry of Thailand for keeping people fit. There is little known about the physiological demand it places on those practicing it. Therefore, the purpose of this study is to determine i) the exercise intensity of TY indicating by both absolute intensity (i.e. MET) and relative intensity (i.e. percentage of maximal oxygen consumption (VO2,max) and heart rate (HRmax)) and ii) the impact it has on the cardiovascular system and energy expenditure. Fourteen healthy adults ranging in age from 50 to 65 years performed 30-minute TY and exhaustive cycling exercise (to indicate maximal oxygen consumption) sessions one week apart. Mean of MET and the percentage of mean of VO2 and HR during TY to VO2,max and HRmax were found to be 1.51±0.43 METs, 35.5+/-11.9 ml/kg/min and 50.0+/-8.6 /min, respectively. The decreased HR was observed from baseline to warm up and the peak rates of energy were found to be expended in the standing posture. Results indicate that TY may be considered a very light- to light-intensity exercise. Performing longer duration in standing posture may improve cardiovascular fitness for older adults. Moreover, the relaxation component during warm up may improve psychological well-being.

Prevalence and associated factors of early repolarization pattern in healthy young northeastern Thai men: A correlation study with Brugada electrocardiography

Early repolarization pattern (ERP) is characterized by J‐point elevation with QRS notching or slurring in the terminal portion of the QRS complex. It may be associated with sudden death. Brugada syndrome (BS) is a genetic and fatal disease commonly found in northeastern Thai men. Data on the rate and predictors of ERP in Asian populations are limited. In addition, the correlation between ERP and BS has never been studied in an endemic area of BS. This study aimed to evaluate the prevalence of ERP and its associated factors in young, healthy male Asian subjects.

Continuous positive airway pressure therapy converted atrial fibrillation in a patient with obstructive sleep apnea

Obstructive sleep apnea (OSA) is one of the possible causes of atrial fibrillation (AF). Continuous positive airway pressure (CPAP) therapy may lower the recurrence rate of AF after cardioversion to normal sinus rhythm. We report a case of AF caused by OSA and successfully converted by CPAP therapy.

Cpap Pressure by Cpap Titration or Prediction Formula

Obstructive sleep apnea (OSA) is a common disease in clinical practice and can lead to several cardiovascular complications such as death, heart failure, stroke, or atrial fibrillation [1]. The estimated prevalence is about 5-10% of general population [2]. Successful treatment with continuous positive airway pressure machine (CPAP) significantly reduces cardiovascular events [2,3]. Appropriate CPAP pressure can be determined by two methods: in hospital and home CPAP titration [4].

Value of cardiac magnetic resonance imaging in systemic sclerosis

Objectives To assess the prevalence and patterns of cardiac abnormalities as detected by cardiac magnetic resonance imaging (MRI) in systemic sclerosis. Material and methods Twenty-six consecutive patients with systemic sclerosis underwent cardiac MRI to determine morphological, functional, perfusion at rest, and delayed enhancement abnormalities. Results At least one abnormality on cardiac MRI was observed in 19/26 (73%) patients. Increased myocardial signal intensity in T2 was observed in 10 patients (38.5%), thinning of the left ventricular myocardium in 1 patient (3.5%), and pericardial effusion in 12 patients (46%). Left and right ventricular ejection fractions were altered in 10 patients (38.5%) and 11 patients (42%), respectively. Myocardial delayed contrast enhancement was found in 11 (42%) patients. No perfusion defects at rest were found. Patients with limited systemic sclerosis had similar cardiac MRI abnormalities to patients with diffuse systemic sclerosis. Four out of 11 patients (36.4%) without pulmonary arterial hypertension had right ventricular dilatation. Conclusions The present study shows that cardiac MRI is an accurate and reliable technique to diagnose cardiac involvement in systemic sclerosis and to analyze precisely its mechanisms, including inflammatory, microvascular and fibrotic components. As it is non-invasive, quantitative and highly sensitive, cardiac MRI appears to be a method of choice to determine the natural history of untreated patients or to accurately monitor the effects of treatment. Moreover, it could provide powerful prognostic factors in both groups. Compared to echocardiography, cardiac MRI appears to provide additional information by visualizing myocardial fibrosis and inflammation. Finally, the present study has shown that RV dilatation is not specific for pulmonary arterial hypertension and could correspond to a specific heart involvement in systemic sclerosis.

Reduction of radiation dose for coronary computed tomography angiography using prospective electrocardiography-triggered high-pitch acquisition in clinical routine

Purpose To evaluate the image quality, radiation exposure, and means of application in a group of patients who underwent coronary computed tomography angiography (CCTA) performed with low-dose prospective electrocardiography (ECG)-triggered acquisition in which a standard sequence was added if the low-dose sequence did not allow reliable exclusion of coronary stenosis with respect to image quality. Material and methods The present study was approved by the Ethics Committee of the Faculty of Medicine, and informed consent was obtained from all patients. The authors performed a retrospective review of 256 consecutive patients referred for CCTA using dual-source CT scanner (Definition FLASH, Siemens, Germany). CCTA was performed using prospective ECG-triggered high-pitch acquisition. In patients with higher heart rates (> 65 bpm) or in whom irregular heart rates were noted prior to the scan, a subsequent CCTA was performed immediately (double flash protocol). The effective radiation dose was calculated for each patient. All images were evaluated by two independent observers for quality on a four-point scale with 1 being non-diagnostic image quality and 4 being excellent. Results Mean effective whole-body dose of CCTA was 1.6 ± 0.4 mSv (range, 0.4-5.4) for the entire cardiac examination and 0.9 ± 0.3 mSv (range, 0.4-2.8) for individual prospective ECG-triggered high-pitch CCTAs. In 27 of these patients with higher heart rates or occasional premature ventricular contractions or atrial fibrillation, subsequent CCTAs were performed immediately. The average image quality score was good to excellent with less than 1% unevaluable coronary segments. The double flash protocol resulted in a fully diagnostic CCTA in all cases. Conclusions The prospective ECG-triggered high-pitch CCTA technique is feasible and promising in clinical routine with good to excellent image quality and minimal radiation dose. The double flash protocol might become a more robust tool in patients with higher heart rates or arrhythmia.

Autonomic and cardio-respiratory responses to exercise in Brugada Syndrome patients.

Imbalances of the autonomic nervous (ANS), the cardiovascular system, and ionics might contribute to the manifestation of The Brugada Syndrome (BrS). Thus, this study has aimed to investigate the cardio‐respiratory fitness and the responses of the ANS both at rest and during a sub‐maximal exercise stress test, in BrS patients and in gender‐matched and age‐matched healthy sedentary controls.