Optimal Strategies to Select Warfarin Dose for Thai Patients with Atrial Fibrillation.

Background: Warfarin has been the mainstay treatment for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation (AF). The optimal starting dose of warfarin remains unclear. Objective: To investigate the most optimal dosing strategies for warfarin starting dose in Thai patients with AF. Material and Methods: We enrolled consecutive AF patients who were starting on warfarin and resulting in a stable INR of 2.0-3.0 at two consecutive time points. We measured the dose of warfarin at which INR achieved the target range. The optimal dosage was defined as the difference from the actual dose within 20%. We compared strategies of warfarin dosing, including warfarin dosing formula, 2.5 mg, 3 mg and 5 mg doses. The primary endpoints were the proportions of patients in optimal, underdosing, and overdosing categories. Results: Among 1207 patients visiting the Outpatient Clinic between October 2011 and September 2021, 531 patients were identified with AF and INR in the therapeutic range of 2.0-3.0 on at least two consecutive visits. The mean age of participants was 68 ± 11 years, and men accounted for 44.4% of the population. The warfarin dosing formula resulted in optimal dosing in 37% and overdosing in 24% of cases, whereas the 2.5 mg, 3 mg and 5 mg doses resulted in optimal dosing in 36%, 39%, and 11%, and overdosing in 33%, 44% and 88% of patients, respectively (p < 0.01). Conclusions: In Thai patients with AF, the optimal warfarin starting dose may be 2.5 mg, 3 mg or a simplified warfarin dosing formula, whereas the 5 mg dose should be avoided due to the high risk of overdosing.

Predictive value of Systematic Coronary Risk Evaluation 2-Diabetes risk model and arterial stiffness for cardiovascular events in the Asian population with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Individuals with diabetes are at high risk of developing cardiovascular events. The present study investigated the predictive value of the cardio-ankle vascular index (CAVI) when added to the Systematic Coronary Risk Evaluation 2-Diabetes (SCORE2-Diabetes) risk algorithm to predict cardiovascular events in the Asian population. MATERIALS AND METHODS: The SCORE2-Diabetes risk was assessed in 1,502 patients with diabetes, aged 40-69 years. Then, we further stratified each 10-year risk category with a CAVI value of 9.0. The primary outcomes (composite of all causes of death, myocardial infarction, stroke and hospitalization for heart failure) were assessed over 5 years. RESULTS: The mean age of the population was 59.8 ± 6.4 years. The proportion of 10-year risk according to the SCORE2-Diabetes risk of low, moderate, high and very high risk identified at 7.2, 30.0, 27.2 and 35.6%, respectively. The mean CAVI value was 8.4 ± 1.4, and approximately 35.4% of the patients had CAVI ≥9.0. The SCORE2-Diabetes risk algorithm independently predicted the primary outcomes in patients with diabetes (hazard ratio 1.18, 95% confidence interval [CI] 1.13-1.22), whereas CAVI did not (hazard ratio 1.03, 95% CI 0.89-1.18). The C-index for the primary outcomes of the SCORE2-Diabetes risk algorithm alone was 0.72 (95% CI 0.67-0.77). The combination of SCORE2-Diabetes and CAVI, both in the continuous value and risk groups, did not improve discrimination (C-index 0.72, 95% CI 0.67-0.77 and 0.68, 95% CI 0.64-0.74, respectively). CONCLUSIONS: Adding the CAVI to the SCORE2-Diabetes risk algorithm did not improve individual risk stratification in patients with diabetes.

Effect of Curcuminoids on Contrast-Induced Acute Kidney Injury after Elective Coronary Angiography or Intervention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: The role of curcuminoids, a striking antioxidant, in prevention of contrast-induced acute kidney injury (CI-AKI) remains unknown. We aimed to evaluate the efficacy and safety of curcuminoids in preventing CI-AKI in patients undergoing elective coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). METHODS: We randomized 114 patients who were undergoing elective CAG and/or PCI to receive curcuminoids, 4 g/day (1 day before and 1 day after the procedure, n = 56), or placebo (n = 58). Serum creatinine was assessed at baseline, 12, 24, and 48 h after contrast exposure. The primary endpoint was development of CI-AKI defined as serum creatinine increase ≥0.3 mg/dL within 48 h after contrast exposure. The secondary endpoint was the occurrence of kidney injury defined by >30% increase in urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS: Baseline characteristics were comparable between the two groups. Seven (12.7%) in curcuminoids group and eight (14.0%) in placebo group developed CI-AKI (p = 0.84). The incidence of increased urine NGAL was comparable in the placebo and curcuminoids group (39.6% vs. 50%, respectively; p = 0.34). None in both groups had drug-related adverse events. CONCLUSION: This is a pilot study to demonstrate the safety and tolerability of curcuminoids in patients undergoing elective CAG and/or PCI. Curcuminoids have no protective effects against kidney injury after elective CAG and/or PCI.

Association of the interatrial block and left atrial fibrosis in the patients without history of atrial fibrillation.

Presence of left atrial (LA) fibrosis reflects underlying atrial cardiomyopathy. Interatrial block (IAB) is associated with LA fibrosis in patients with atrial fibrillation (AF). The association of IAB and LA fibrosis in the patients without history of AF is unknown. We examined association of IAB and LA fibrosis in the patients without AF history. This is a retrospective analysis of 229 patients undergoing cardiac magnetic resonance imaging (CMR). LA fibrosis was reported from spatial extent of late gadolinium enhancement of CMR. IAB was measured from 12-lead electrocardiography using digital caliper. Of 229 patients undergoing CMR, prevalence of IAB was 50.2%. Patients with IAB were older (56.9±13.9 years vs. 45.9±19.2 years, p<0.001) and had higher prevalence of co-morbidities. Left ventricular ejection fraction was lower in IAB group. LA volume index (LAVI) was greater in IAB group (54.6±24.9 ml/m2 vs. 43.0±21.1 ml/m2, p<0.001). Patients with IAB had higher prevalence of LA fibrosis than those without IAB (70.4% vs. 21.2%; p<0.001). After multivariable analysis, only IAB and LAVI were independent factors that predict LA fibrosis. Prevalence of IAB in patients undergoing CMR was high. IAB was highly associated with LA fibrosis and larger LA size in patients without AF history.

Effect of renin angiotensin system inhibitors on long-term major cardiovascular outcomes in patients with high atherosclerotic cardiovascular risk.

The advantage of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with preserved LV systolic function is uncertain. We aimed to investigate the effects of ACEI/ARB in high atherosclerotic risk patients without overt heart failure (HF) on long-term major cardiovascular outcomes (MACEs). The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. The patients with ejection fraction < 50% were excluded. Among 8513 recruited patients, there were 4246 patients included into final analysis after propensity score matching. At 5-years follow-up, Cox regression analysis showed that ACEI/ARB was significantly associated with reduced risk of all-cause mortality or non-fatal myocardial infarction, non-fatal stroke and HF hospitalization (HR 0.82, 95% CI 0.70-0.96, P = 0.011). The benefit was driven by the reduced all-cause mortality and HF. Subgroup analysis demonstrated that ACEI/ARB decreased risk of long-term MACEs in patients with diabetes (HR 0.77, 95% CI 0.63-0.94, P = 0.011) and patients not taking statin (HR 0.57, 95% CI 0.40-0.82, P = 0.002). We demonstrated that the use of ACEI/ARB was associated with reduced risk of long-term MACEs in a large cohort of high atherosclerotic risk patients. Reduction of all-cause mortality and HF were likely the main contributors to the benefit of ACEI/ARB.

Electromagnetic interference from automobile passive keyless entry in cardiovascular implantable electronic devices.

INTRODUCTION: The automobile passive keyless entry (PKE) system is a potential source of electromagnetic interference (EMI). We aim to determine the incidence and significance of EMI from automobile PKE system in cardiovascular implantable electronic device (CIED) patients. METHODS: This was a single-center cross-sectional study conducted at Maharaj Nakorn Chiang Mai hospital, Thailand. Patients with CIED were instructed to lock and unlock two automobiles using the PKE system. Any EMI or arrhythmias were detected by CIED interrogation and single-lead electrocardiogram event recorder. We also used a spectrum analyzer to identify the automobiles working frequency bandwidth. RESULTS: There was a total of 102 CIED patients. Device types included 48.0% defibrillators, 37.3% permanent pacemakers, and 14.7% cardiac resynchronization therapy device. Both interrogated data from device and event monitor revealed no incidence of EMI during the PKE activation. We failed to identify the working frequency bandwidth of the two studied cars due to very low signal strength, thus blended in with the background noise. CONCLUSIONS: Automobile PKE systems transmitted very low power signals. Therefore, under normal circumstances, CIED patients can use automobile PKE system safely without any EMI regardless of key fob positions in relation to the CIED pulse generator. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (https://clinicaltrials.gov), and the identification number is NCT03016390.

Aspirin for primary prevention in patients with high cardiovascular risk: insights from CORE-Thailand registry.

Aspirin may be considered for primary prevention in non-elderly patients with high cardiovascular risk. However, contemporary management aimed at aggressive cardiovascular risk factor control may alter benefit-risk ratio of aspirin. Therefore, we aimed to examine the effect of aspirin for primary prevention on the long-term MACEs in a large cohort registry. Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. Patients with established atherosclerotic cardiovascular diseases were excluded. Among 4259 patients with multiple cardiovascular risk factors, 1945 (45.7%) patients used aspirin. After propensity score matching, there were 3228 patients remained in post-matching analysis. During the median follow-up period of 58.2 months, we demonstrated that aspirin use increased risk of long-term MACEs in pre-matching cohort (unadjusted HR 1.76, 95% CI 1.43-2.17, P < 0.001) and post-matching cohort (HR 1.66 (1.31-2.10), P < 0.001). In addition, patients taking aspirin had a higher risk of bleeding than non-aspirin users in pre-matching cohort (unadjusted HR 2.28, 95% CI 1.09-4.75, P = 0.028). We demonstrated that aspirin was associated with increased risk of long-term MACEs in patients with multiple cardiovascular risk factors. Due to the non-randomized design, our results should be interpreted with caution.

Glycated hemoglobin variability and the risk of cardiovascular events in patients with prediabetes and type 2 diabetes mellitus: A post-hoc analysis of a prospective and multicenter study.

AIMS/INTRODUCTION: High glycated hemoglobin (HbA1c) variability has been reported to be linked with cardiovascular events in type 2 diabetes patients. Only a few studies have been carried out on Asian patients. This study aimed to investigate the association of prediabetes and type 2 diabetes in Asian patients by performing a post-hoc analysis of a multicenter, prospective, observational study. MATERIALS AND METHODS: Data for prediabetes and type 2 diabetes patients were retrieved from a multicenter national registry entitled "CORE-Thailand study." The primary outcome was 4P-MACE (major adverse cardiovascular events, including non-fatal myocardial infarction, heart failure hospitalization, non-fatal stroke and all-cause death). Patients were stratified according to quartiles of HbA1c standard deviation. The Cox proportional hazards regression model was used to estimate the association of HbA1c variability with incident cardiovascular disease. RESULTS: A total of 3,811 patients with prediabetes and type 2 diabetes were included. The median follow-up duration was 54 months. In the fully adjusted model, the highest quartile of HbA1c variability showed a statistically significant association with 4P-MACE (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.77-4.35), fatal and non-fatal myocardial infarction (HR 6.91, 95% CI 1.90-25.12), hospitalization for heart failure (HR 3.34, 95% CI 1.20-9.26) and all-cause death (HR 3.10, 95% CI 1.72-5.57). All these outcomes were statistically significantly different among four quartiles of HbA1c (log-rank P-value <0.05). Fatal and non-fatal stroke showed no statistically significant association with high HbA1c variability. CONCLUSION: High HbA1c variability in the highest quartile showed a statistically significant association with multiple adverse cardiovascular events in an Asian population. Minimizing HbA1c fluctuation during long-term follow up should be another important objective for type 2 diabetes patients.

Effect of Beta-Blocker on Long-Term Major Cardiovascular Events in High Atherosclerotic Risk Population.

PURPOSE: Beta-blocker is a frequently used medication in cardiovascular diseases. However, long-term benefit of beta-blocker in patients with preserved left ventricular ejection function (LVEF) on major adverse cardiovascular events (MACEs) is uncertain. METHODS: The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) was a prospective study that enrolled Thai patients with high atherosclerotic risk including multiple atherosclerotic risk factors and established atherosclerotic cardiovascular diseases. Baseline demographic data, co-morbidities and medication were recorded. Patients were followed for 5 years. Patients with LVEF<50% were excluded. Primary outcome was the effect of beta-blocker on the occurrence of MACEs including all-cause death, non-fatal myocardial infarction and non-fatal stroke (3P-MACEs). Propensity score matching was used to control confounding factors. RESULTS: There was a total of 8513 patients in the pre-matched cohort, 4418 were taking beta-blocker and 4095 were not. After adjustment of confounders, beta-blocker was an independent predictor of 3P-MACEs (adjusted HR 1.29;95% CI 1.12-1.49;p<0.001). After propensity score matching, 4686 patients remained in the post-matched cohort. Propensity score analysis showed consistent results in which patient taking beta-blocker had higher risk of 3P-MACEs (adjusted HR 1.29;95% CI 1.10-1.53;p=0.002). Subgroup analysis in patients with coronary artery disease (CAD) indicated that taking beta-blocker did not increase the incidence of 3P-MACEs (adjusted HR 0.99;95% CI 0.76-1.29) while those without CAD did (adjusted HR 1.51; 95% CI, 1.22-1.86;p-interaction=0.015). CONCLUSION: In patients with high atherosclerotic cardiovascular risk, taking beta-blockers had a higher risk of 3P-MACEs. Care should be taken when prescribing beta-blockers to patients without a clear indication. TRIAL REGISTRATION: TCTR20130520001 registered in Thai Clinical Trials Registry (TCTR) https://www.thaiclinicaltrials.org/ , date of registration 20 May 2013.

Diagnostic role of aortic valve calcium scoring in various etiologies of aortic stenosis.

Most of the studies about aortic valve calcium (AVC) score in aortic stenosis (AS) were based on degenerative or bicuspid AS but not rheumatic AS. We aimed to study the diagnostic accuracy of AVC score to determine severe AS in various etiologies. Adult patients diagnosed with mild to severe AS were enrolled. AVC score were identified from multi-detector computed tomography (MDCT) scan. The AVC score was highest in bicuspid AS (3211.9 (IQR (1100.0-4562.4) AU) compared to degenerative AS (1803.7 (IQR (1073.6-2550.6) AU)), and rheumatic AS (875.6 (IQR 453.3-1594.0) AU), p < 0.001. For the ROC curve to identify severe AS, the AVC score performed well in degenerative and bicuspid AS with the area under the ROC curve (AuROC) 0.834 (95% CI, 0.730, 0.938) in degenerative group; and 0.820 (95% CI, 0.687, 0.953) in bicuspid AS. Whereas AVC score had non-significant diagnostic accuracy with AuROC 0.667 (95% CI, 0.357, 0.976) for male and 0.60(95% CI, 0.243, 0.957) for female in rheumatic AS. The cut-off AVC score values to identify severe AS were AVCS > 2028.9AU (male) and > 1082.5AU (female) for degenerative AS, and > 2431.8AU (male) and > 1293.5AU (female) for bicuspid AS. In conclusions, AVC score is the accurate test for assessing severity in patients with degenerative and bicuspid AS but performs poorly in rheumatic AS group.

Predictive value of heart rate variability on long-term mortality in end-stage kidney disease on hemodialysis.

Autonomic disturbance is common in end-stage kidney disease (ESKD). Heart rate variability (HRV) is a useful tool to assess autonomic function. We aimed to evaluate the predictive value of HRV on all-cause mortality and explore the proper timing of HRV assessment. This prospective cohort study enrolled 163 ESKD on hemodialysis patients from April-December 2018. HRV measurements were recorded ten minutes before hemodialysis, four hours during hemodialysis, and ten minutes after hemodialysis. Clinical parameters and all-cause mortality were recorded. Cox-proportional hazard regression was used for statistical analysis. After a median follow up of 40 months, 37 (22.7%) patients died. Post-dialysis HRV parameters including higher very low frequency (VLF) (hazard ratio [HR], 0.881; 95%confidence interval [CI], 0.828-0.937; p<0.001), higher normalized low frequency (nLF) (HR, 0.950; 95%CI, 0.917-0.984; p = 0.005) and higher LF/HF ratio (HR, 0.232; 95%CI, 0.087-0.619; p = 0.004) were the independent predictors associated with lower risk for all-cause mortality. Higher post-dialysis normalized high frequency (nHF) increased risk of mortality (HR, 1.051; 95%CI, 1.015-1.089; p = 0.005). HRV parameters at pre-dialysis and during dialysis were not predictive for all-cause mortality. The area under receiver operating characteristic curve (AuROC) of VLF for survival was highest compared to other HRV parameters at post-dialysis period (AuROC 0.71; 95% CI; 0.62-0.79; p<0.001). In conclusion, post-dialysis HRV parameters predicted all-cause mortaliy in ESKD. VLF measured at post-dialysis exhibited best predictive value for survival in chronic hemodialysis patients.

Economic Evaluation of Direct Oral Anticoagulants Compared to Warfarin for Venous Thromboembolism in Thailand: A Cost-Utility Analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have been used for venous thromboembolism (VTE) in Thailand. However, they have not been listed in the National List of Essential Medicines (NLEM). A cost-effectiveness analysis is needed to aid policymakers in deciding whether DOACs should be listed in the NLEM. This study aimed to assess the cost-effectiveness of DOACs for patients with VTE in Thailand. METHODS: A cohort-based state transition model was constructed from a societal perspective with a lifetime horizon. All available DOACs, including apixaban, rivaroxaban, edoxaban, and dabigatran, were compared with warfarin. A 6-month cycle length was used to capture all costs and health outcomes. The model consisted of nine health states, including VTE on treatment, VTE off treatment, recurrent VTE, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial bleeding, post-intracranial bleeding, chronic thromboembolic pulmonary hypertension, and death. All inputs were based on a comprehensive literature review. The model outcomes included total cost and quality-adjusted life-years (QALYs) with a 3% annual discount rate. A fully incremental cost-effectiveness analysis and the incremental cost-effectiveness ratio (ICER) per QALY gained were calculated at a willingness-to-pay (WTP) of THB 160,000/QALY ($5003). The robustness of the findings was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: All DOACs were associated with a decreased risk of VTE recurrence and intracranial hemorrhage. In the base-case analysis, apixaban could increase 0.16 QALYs compared with warfarin. An ICER for apixaban was 269,809 Thai baht (THB)/QALY ($8437/QALY). Rivaroxaban had a better QALY than warfarin at 0.09 QALYs with an ICER of 757,363 THB/QALY ($23,682/QALY). Edoxaban and dabigatran could also increase by 0.10 QALYs with an ICER of 709,945 THB ($22,200) and 707,145 THB ($22,122)/QALY, respectively. Our probabilistic sensitivity analyses indicated that warfarin had a 99.8% possibility of being cost-effective, while apixaban had a 0.2% possibility of being cost-effective at the current WTP. Other DOACs had no possibility of being cost-effective. CONCLUSIONS: All DOACs were not cost-effective for VTE treatment at the current WTP in Thailand. Apixaban is likely to be the best option among DOACs.

Impact of dabigatran dose on drug levels in asian patients with atrial fibrillation or venous thromboembolism: evidence from pharmacological to clinical outcomes.

Dabigatran is commonly used in atrial fibrillation (AF) or venous thromboembolism (VTE). However, there was limited data on dabigatran levels in Asian patients. This study aimed to investigate plasma levels of dabigatran 110 mg (D110) or 150 mg (D150) twice daily and their impact on clinical outcomes in Thai patients. This was a prospective cohort study including patients who were diagnosed with AF or VTE and were prescribed either D110 or D150. Plasma dabigatran levels were measured using the diluted thrombin time method. All patients were observed for bleeding and thrombotic complications for 12 months after enrollment. Ninety patients were included in the study (45 in the D110 group and 45 in the D150 group). For the D110 group, there was no significant difference in trough and peak levels in patients with creatinine clearance (CrCl) < 50 ml/min compared to those with CrCl ≥ 50 ml/min. For the D150 group, patients with CrCl < 50 ml/min had significantly higher trough and peak levels compared to those with CrCl ≥ 50 ml/min (P = 0.016 for trough, P = 0.005 for peak). Multivariate regression analysis showed females and low CrCl were independent risk factors for high dabigatran levels. Most patients (83.33%) who experienced bleeding complications had peak levels within the expected range. D150 was associated with higher plasma dabigatran levels, especially in those with impaired renal function.

Effects of prolonged working hours on heart rate variability in internal medicine physicians.

Prior studies have utilized heart rate variability (HRV) as the assessment tools for psychological and physiological stress during 24-h shift. However, data regarding effects of prolonged working hours > 24 h on HRV are limited. We aimed to compare between pre- and post-call HRV among physicians who worked 24 plus 8 h. The study included 60 physicians in the internal medicine training. All subjects underwent Holter ECG monitoring for HRV assessment. We compared between HRV of an 8-h regular workday (8am to 4 pm) before on-call duty (pre-call HRV) and an 8-h workday after 24-h on-call duty (post-call HRV). The mean age was 26 ± 2.5 years. Mean total sleep time during on-call duty was 238.9 ± 88.3 min. In overall population, the time-domain and frequency-domain HRV parameters were not different between pre- and post-call day. However, the physicians reported their sleep time in the 1st quartile (< 180 min) had significant increase in SDNN, pNN50, high frequency (HF), and decrease in low/high frequency ratio (LF/HF). In contrast, the physicians reported their sleep time in the 4th quartile (> 307.5 min) had significant decrease in pNN50, LF, HF, and increase in heart rate. Multiple linear regression revealed total sleep time as an independent factor associated with pre- and post-call HRV alterations. More sleep during on call (> 5 h) was associated with HRV pattern suggesting both increased sympathetic activity and reduced parasympathetic activity, while less sleep (< 3 h) during on call was associated with post-call parasympathetic rebound HRV pattern.

Prognostic values of high sensitivity cardiac troponin T and I for long-term mortality in hemodialysis patients.

Previous studies using contemporary cardiac troponin (cTn) assays have shown conflicting results in predictability of mortality and major adverse cardiovascular events (MACEs) in hemodialysis patients. We aimed to evaluate the prognostic values of high-sensitivity cTnT (hs-cTnT) and hs-cTnI for long-term mortality and MACEs in asymptomatic chronic hemodialysis patients. 198 asymptomatic patients undergoing regular hemodialysis (age 62.4 ± 14.8 years) were enrolled. Pre-dialysis hs-cTnT and hs-cTnI levels were measured. The study outcomes were long-term all-cause mortality and MACEs. Median values of hs-cTnT and hs-cTnI were 61.1 ng/L (IQR 36.6-102.0) and 18.4 ng/L (IQR 9.5-36.6), respectively. During a median follow-up of 13.5 months, 30 (15.1%) patients developed MACEs, and 20 (10.1%) patients died. The patients in highest quartile of hs-cTnT level (≥ 102 ng/L) had increased risk of long-term mortality (HR 3.34; 95%CI 1.39-8.04, P = 0.005). However, hs-cTnI levels above highest quartile (≥ 36 ng/L) was not significantly associated with increased risk of all-cause mortality. Nevertheless, elevated level of hs-cTnT and hs-cTnI was associated with increased risk of MACEs. We demonstrated that higher level of hs-cTnT, but not hs-cTnI, was associated with increased risk of long-term mortality. Nevertheless, higher level of hs-cTnT and hs-cTnI both were associated with greater risk of long-term MACEs.

Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation.

Low-dose rivaroxaban has been used in Asian patients with direct oral anticoagulants (DOACs) eligible for atrial fibrillation (AF). However, there are few pharmacokinetic (PK) data in Thai patients to support precise dosing. This study aimed to develop a population PK model and determine the optimal rivaroxaban doses in Thai patients. A total of 240 Anti-Xa levels of rivaroxaban from 60 Thai patients were analyzed. A population PK model was established using the nonlinear mixed-effect modeling approach. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. Proportions of patients having rivaroxaban exposure within typical exposure ranges were determined. A one-compartment model with first-order absorption best described the data. Creatinine clearance (CrCl) and body weight significantly affected CL/F and V/F, respectively. Regardless of body weight, a higher proportion of patients with CrCl < 50 mL/min receiving the 10-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. In contrast, a higher proportion of patients with CrCl ≥ 50 mL/min receiving the 15-mg once-daily dose had rivaroxaban exposures within the typical exposure ranges. The study's findings suggested that low-dose rivaroxaban would be better suited for Thai patients and suggested adjusting the medication's dose in accordance with renal function.

Effect of particulate matter 2.5 on QT dispersion in patients with chronic respiratory disease.

PM2.5 air pollutants increased risk of ventricular arrhythmias. The prolonged corrected QT interval (QTc) and QT dispersion (QTd) is common in patients with chronic airway disease and is associated with heightened risk of ventricular tachyarrhythmia. We sought to examine the effect of PM2.5 exposure on QTc and QTd in patients with chronic airway disease. We enrolled 73 patients with chronic airway disease into the study. The 12-lead ECGs were recorded during high-exposure and low-exposure periods of PM2.5. QTc and QTd were compared between 2 periods. Mean age was 70 ± 10 years. Mean FEV1/FVC was 63 ± 14%. There was no difference in QTc between PM2.5 high-exposure and low-exposure periods. However, QTd was significantly increased during PM2.5 high-exposure compared to low-exposure periods in male patients (43.5 ± 15.0 vs. 38.2 ± 12.1 ms, P = 0.044) but no difference was found in females. We found that patients who worked mostly indoor had less QTd than those working outdoor during PM2.5 low-exposure period. In addition, those who wore face mask tended to have less QTd during low-exposure period than those who did not. High PM2.5 exposure increased QTd in male patients with chronic airway disease. Working indoors and wearing face mask were associated with less QTd.

A 34-Year-Old Thai Man Presenting with Pulmonary Stenosis and Heart Failure 24 Years After Surgical Correction with the Rastelli Procedure for Congenital Dextro-Transposition of the Great Artery, Ventricular Septal Defect, and Pulmonary Atresia.

BACKGROUND Dextro-transposition of the great arteries (D-TGA) with a ventricular septal defect (VSD) and pulmonary atresia is an uncommon congenital conotruncal abnormality. Surgical correction is performed using the Rastelli procedure, which includes a ventricular septal patch to direct blood from the left ventricle to the aorta and a valved conduit to connect the right ventricle to the pulmonary artery. This report is of a 34-year-old Thai man who presented with pulmonary stenosis and heart failure 24 years after surgical correction with the Rastelli procedure for congenital D-TGA, VSD, and pulmonary atresia. CASE REPORT A 34-year-old Thai man presented with dyspnea on moderate exertion. His cardiovascular examination revealed a median sternal surgical scar, parasternal heaving, a grade III systolic ejection murmur at the left upper parasternal border, and a single second heart sound. Echocardiography demonstrated degenerative calcification of a severely stenosed pulmonary valve and impaired right ventricular function. A color Doppler M-mode echocardiogram showed VSD patch leakage. A computed tomography scan with 3-dimensional heart reconstruction demonstrated a significantly stenosed branch pulmonary artery. Right and left heart catheterization confirmed the multi-site stenoses were hemodynamically significant. The patient underwent surgery for VSD closure, placement of a right-ventricle-to-pulmonary-artery conduit with a polytetrafluoroethylene graft, and pulmonary artery plasty to correct the stenosis at the branch of the pulmonary artery. CONCLUSIONS The long-term complications of the Rastelli-type operation seen for D-TGA with a VSD and pulmonary atresia included a right-ventricle-to-pulmonary-artery conduit obstruction, VSD patch leakage, and re-stenosis of the peripheral pulmonary stenosis. Multimodal imaging was informative in planning for reoperation.

Comparison of the HAS-BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct-acting oral anticoagulants.

AIMS: This study aimed to evaluate the performance of HAS-BLED and ORBIT scores in predicting bleeding risk among Asian patients with nonvalvular atrial fibrillation (NVAF) using direct-acting oral anticoagulants (DOACs). METHODS: A retrospective chart review was conducted among adult patients receiving DOACs for ≥6 months during January 2013 to December 2017 in 10 tertiary care hospitals in Thailand. The area under the receiver operating curve (AUROC) method or C-statistic was used to test the diagnostic accuracy for bleeding risk classification of HAS-BLED and ORBIT scores. The predictive performances of the two scores were compared using DeLong's method. RESULTS: A total of 961 NVAF patients, 52.5% warfarin-naïve and 47.5% warfarin-experienced, with mean age of 74.25 ± 10.08 years, were included in the analysis. Mean HAS-BLED and ORBIT scores of the cohort were 1.98 ± 1.10 and 2.37 ± 1.71, respectively. During the mean follow-up time of 1.55 ± 1.13 years, 34 patients experienced major bleeding (2.28 events/100 patient-year). For the overall cohort, both the HAS-BLED and ORBIT scores showed similarly moderate predictive performance on bleeding with C-statistic (95% confidence interval) of 0.65 (0.57-0.74) and 0.64 (0.56-0.71), respectively. There was no statistical significance between the two scores (P = .62). Analysis based on the status of previous warfarin use was consistent with the overall cohort. Based on the calibration analysis, both HAS-BLED and ORBIT scores possessed moderate ability to identify those who experienced major bleeding from those who did not. CONCLUSION: Both HAS-BLED and ORBIT bleeding risk scores had moderate predictive performance in Asian NVAF patients receiving DOACs.

Effects of short-term bisoprolol on perioperative myocardial injury in patients undergoing non-cardiac surgery: a randomized control study.

The protective role of preoperative beta-blocker in patients undergoing non-cardiac surgery is unknown. We aimed to evaluate the effects of beta-blocker on perioperative myocardial injury in patients undergoing non-cardiac surgery. We consecutively enrolled 112 patients undergoing non-cardiac surgery. They were randomly allocated to receive bisoprolol or placebo given at least 2 days preoperatively and continued until 30 days after surgery. The primary outcome was incidence of perioperative myocardial injury defined by a rise of high-sensitive troponin-T (hs-TnT) more than 99th percentile of upper reference limit or a rise of hs-TnT more than 20% if baseline level is abnormal. Baseline characteristics were comparable between bisoprolol and placebo in randomized cohort Mean age was 62.5 ± 11.8 years and 76 (67.8%) of 112 patients were male. Among 112 patients, 49 (43.8%) underwent vascular surgery and 63 (56.2%) underwent thoracic surgery. The median duration of assigned treatment prior to surgery was 4 days (2-6 days). We did not demonstrate the significant difference in the incidence of perioperative myocardial injury [52.6% (30 of 57 patients) vs. 49.1% (27 of 55 patients), P = 0.706]. In addition, the incidence of intraoperative hypotension was higher in bisoprolol group than placebo group in patients undergoing non-cardiac surgery [70.2% (40 of 57 patients) vs. 47.3% (26 of 55 patients), P = 0.017]. We demonstrated that there was no statistically significant difference in perioperative myocardial injury observed between patients receiving bisoprolol and placebo who had undergone non-cardiac surgery.