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.

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.

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 metformin on atrial and ventricular arrhythmias: evidence from cell to patient.

Metformin has been shown to have various cardiovascular benefits beyond its antihyperglycemic effects, including a reduction in stroke, heart failure, myocardial infarction, cardiovascular death, and all-cause mortality. However, the roles of metformin in cardiac arrhythmias are still unclear. It has been shown that metformin was associated with decreased incidence of atrial fibrillation in diabetic patients with and without myocardial infarction. This could be due to the effects of metformin on preventing the structural and electrical remodeling of left atrium via attenuating intracellular reactive oxygen species, activating 5' adenosine monophosphate-activated protein kinase, improving calcium homeostasis, attenuating inflammation, increasing connexin-43 gap junction expression, and restoring small conductance calcium-activated potassium channels current. For ventricular arrhythmias, in vivo reports demonstrated that activation of 5' adenosine monophosphate-activated protein kinase and phosphorylated connexin-43 by metformin played a key role in ischemic ventricular arrhythmias reduction. However, metformin failed to show anti-ventricular arrhythmia benefits in clinical trials. In this review, in vitro and in vivo reports regarding the effects of metformin on both atrial arrhythmias and ventricular arrhythmias are comprehensively summarized and presented. Consistent and controversial findings from clinical trials are also summarized and discussed. Due to limited numbers of reports, further studies are needed to elucidate the mechanisms and effects of metformin on cardiac arrhythmias. Furthermore, randomized controlled trials are needed to clarify effects of metformin on cardiac arrhythmias in human.

Anti-Factor Xa Activity of Standard and Japan-Specific Doses of Rivaroxaban in Thai Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Recommended rivaroxaban doses for stroke prevention in atrial fibrillation (SPAF) are 20 and 15 mg/day in patients with normal and reduced renal function, respectively, but lower doses (15 and 10 mg) have been tested and approved in Japan. It is not known whether 15 and 10 mg rivaroxaban are appropriate in other Asian populations. This study compared the anti-Factor Xa (FXa) activity of 20 and 15 mg rivaroxaban in Thai patients with normal renal function and 15 and 10 mg rivaroxaban in patients with reduced renal function.Methods and Results:Sixty non-valvular atrial fibrillation patients receiving rivaroxaban (mean [±SD] age 69.3±9.1 years, mean creatinine clearance 59.2±22.7 mL/min) were enrolled. The anti-FXa activity of standard rivaroxaban and Japan-specific doses was measured at peak and trough concentrations. Median anti-FXa activity at peak concentrations was significantly higher for the standard than Japan-specific dose. Median anti-FXa activity measured at the trough was significantly higher for the standard dose only in those with impaired renal function. A higher proportion of patients receiving the Japan-specific rather than standard dose had anti-FXa activity at peak concentrations within the expected range (87.7% vs. 64.4%; P=0.001). One-third of those receiving the standard dose had anti-FXa activity higher than the expected range. CONCLUSIONS: A significantly higher proportion of Thai patients receiving the Japan-specific dose of rivaroxaban had anti-FXa activity at peak concentrations within the expected range.

Anti-Factor Xa Activity of Fixed-Dose Fondaparinux in Low-Body-Weight Patients With Acute Coronary Syndrome.

BACKGROUND: Fixed-dose 2.5 mg of fondaparinux subcutaneous injection once daily has been recommended in treatment of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) irrespective of body weight (BW). However, data on anti-factor Xa (anti-FXa) activity of fondaparinux are scarce in low-BW patients. OBJECTIVE: We aimed to assess anti-FXa activity of fondaparinux in low-BW patients (BW < 50 kg) compared with normal-BW patients (BW ≥ 50 kg) who presented with NSTE-ACS. METHODS: This is a prospective cohort study of patients with NSTE-ACS receiving fondaparinux. Anti-FXa activity was measured 4 hours after 2.5 mg subcutaneous injection of fondaparinux after the first 2 doses. RESULTS: Among 87 enrolled patients, 18 (21%) had BW <50 kg. Patients in the low-BW group were older and had lower creatinine clearance. Median duration of fondaparinux therapy was 3 (IQR 2-4) days. Anti-FXa activity after the first dose of fondaparinux was similar between the low-BW and normal-BW groups (0.40 ± 0.15 vs 0.40 ± 0.17 mg/L, P = 0.914). However, anti-FXa activity after the second dose of fondaparinux was significantly higher in the low-BW group as compared with the normal-BW group (0.53 ± 0.10 vs 0.44 ± 0.16 mg/L, P = 0.011). Multivariate analysis showed that BW was the only independent factor that inversely correlated with anti-FXa activity. There was only 1 bleeding event during hospitalization in the normal-BW group and none in the low-BW group. CONCLUSION AND RELEVANCE: Anti-FXa activity of the second dose of fondaparinux was higher in low-BW patients but still within the expected range.

Effects of dapagliflozin vs vildagliptin on cardiometabolic parameters in diabetic patients with coronary artery disease: a randomised study.

AIMS: Sodium glucose co-transporter-2 inhibitors have been shown to reduce cardiovascular events and heart failure in type 2 diabetic (T2D) patients with high cardiovascular risk. Dipeptidyl peptidase-4 inhibitors showed neutral effects and may increase risk of heart failure. We aimed to compare cardiometabolic effects of dapagliflozin and vildagliptin in T2D patients with coronary artery disease (CAD). METHODS: Forty-nine T2D patients with CAD were randomly assigned to dapagliflozin (n = 25) or vildagliptin (n = 24) for 6 months in a double-blind fashion. Cardiometabolic parameters were collected at baseline and at the end of treatments. RESULTS: Mean age was 63.2 ± 7.9 years (female 46.9%). Baseline characteristics did not differ between two groups. At 6 months, HbA1C significantly decreased in both dapaglifozin and vildagliptin groups (0.6 ± 1.0% vs 0.8 ± 1.4%, P = 0.22, respectively). There was no difference between the changes in lipid profiles. Body mass index decreased in patients receiving dapagliflozin, whereas it increased in those receiving vildagliptin (-1.27 [95% confidence interval -2.01, -0.53] vs 1.72 [0.72, 2.72] kg, P < 0.001). The reduction in systolic blood pressure and high-sensitivity troponin T was observed in the dapagliflozin group (-9.87 [-18.00, -1.15] mmHg and 2.49 [-4.50, -0.47] pg/mL) but not in vildagliptin group (-1.97 [-9.42, 5.48] mmHg and 1.98 [-0.02, 3.97] pg/mL). The mean haemoglobin increased in the dapagliflozin group, whereas the mean platelet volume increased in the vildagliptin group. There was no significant change in the inflammatory markers in both the groups. CONCLUSIONS: The extraglycaemic effects of dapagliflozin and vildagliptin on cardiometabolic parameters in T2D with CAD were different. The more favourable effects of dapagliflozin compared to vildagliptin may have explained the cardiovascular benefits observed only in sodium glucose co-transporter-2 inhibitors.

Radiofrequency ablation of accessory pathways in patients with the Wolff-Parkinson-White syndrome: long-term risk of mortality and coronary events.

Aims: The long-term outcomes of radiofrequency catheter ablation (RFCA) in patients with Wolff-Parkinson-White syndrome (WPW) remain unclear. We investigated the impact of RFCA on the long-term risk of coronary events and mortality in WPW patients. Methods and results: We conducted a prospective cohort study utilizing the Taiwan National Health Insurance Research Database. Between 2000 and 2003, WPW patients with no prior coronary artery disease (CAD) history, aged over 18 years, who underwent RFCA were identified. WPW patients without RFCA were matched with propensity-score 1:4 matching for confounding coronary risk factors. The study outcomes were total mortality and coronary events. A total of 1524 matched non-ablated WPW patients (Group 1) and 381 ablated WPW patients (Group 2) were included. After a mean follow-up of 9.6 ± 2.9 and 10.3 ± 1.9 years, respectively, ablation group demonstrated a lower incidence of mortality compared with non-ablation group (17 vs. 26/1000 person-years, P < 0.001; adjusted HR: 0.57, 95% CI: 0.44-0.7). However, ablation group had a higher incidence of coronary events compared with non-ablation group (47 vs. 82/1000 person-years, P < 0.001; adjusted HR: 1.69, 95% CI: 1.4-2.04). Conclusion: The ablation-treated WPW patients had lower risk of total mortality but higher risk of coronary events than non-ablated WPW patients during the long-term follow-up. Coronary artery injury produced by RFCA may account for the increased risk of coronary events. Therefore, the ablation strategies to avoid coronary artery injury should be implemented.

Vascular access site complication in transfemoral coronary angiography between uninterrupted warfarin and heparin bridging.

BACKGROUND: Warfarin discontinuation with heparin bridging is a common practice in patients receiving warfarin prior to elective coronary angiography (CAG). The uninterrupted warfarin strategy has been suggested to be alternative option for patients with high thromboembolic risk. Therefore, we aimed to assess the safety of elective transfemoral CAG during uninterrupted warfarin therapy compared to heparin bridging. METHODS: This study was a randomized open-label design with blinded event evaluation. The 110 consecutive patients (age ≥ 18 years) receiving warfarin before the planned transfemoral CAG were randomly assigned to either heparin bridging or uninterrupted warfarin with targeted INR (2.0-3.0). The primary outcome was the incidence of major vascular access site complications. RESULTS: The baseline characteristics were comparable between two groups (mean age was 60.1 ± 7.8 years, 49 males). The mean INR on the day of CAG of heparin bridging and uninterrupted warfarin groups was 1.2 ± 0.3 and 2.2 ± 0.5 (P < 0.001). The major vascular access site complications occurred in 3 of 55 (5.5%) heparin-bridging patients and in none of 55 uninterrupted warfarin patients (P = 0.243). The total vascular access site complications occurred in 6 (10.9%) heparin-bridging and one (1.8%) uninterrupted warfarin patients (P = 0.113). No patient developed either other bleeding or thromboembolic events during 7 days after CAG. CONCLUSIONS: We demonstrated that an uninterrupted warfarin strategy did not increase vascular access site complications in patients undergoing transfemoral CAG compared to heparin bridging therapy. Due to the safety and the ease of uninterrupted warfarin strategy, this approach should be encouraged in patients receiving long-term warfarin who undergo elective transfemoral CAG.

Is non-HDL-cholesterol a better predictor of long-term outcome in patients after acute myocardial infarction compared to LDL-cholesterol? : a retrospective study.

BACKGROUND: It has recently been shown that non-high density lipoprotein cholesterol (non-HDL-C) may be a better predictor of cardiovascular risk than low density lipoprotein cholesterol (LDL-C). Based on known ethic differences in lipid parameters and cardiovascular risk prediction, we sought to study the predictability of attaining non-HDL-C target and long-term major adverse cardiovascular event (MACE) in Thai patients after acute myocardial infarction (AMI) compared to attaining LDL-C target. METHODS: We retrospectively obtained the data of all patients who were admitted at Maharaj Nakorn Chiang Mai hospital due to AMI during 2006-2013. The mean non-HDL-C and LDL-C during long-term follow-up were used to predict MACE at each time point. The patients were classified as target attainment if non-HDL-C <100 mg/dl and/or LDL-C <70 mg/dl. The MACE was defined as combination of all-cause death, nonfatal coronary event and nonfatal stroke. RESULTS: During mean follow-up of 2.6 ± 1.6 years among 868 patients after AMI, 34.4% achieved non-HDL-C target, 23.7% achieved LDL-C target and 21.2% experienced MACEs. LDL-C and non-HDL-C were directly compared in Cox regression model. Compared with non-HDL-C <100 mg/dl, patients with non-HDL-C of >130 mg/dl had higher incidence of MACEs (HR 3.15, 95% CI 1.46-6.80, P = 0.003). Surprisingly, LDL-C >100 mg/dl was associated with reduced risk of MACE as compared to LDL <70 mg/dl (HR 0.42, 95% CI 0.18-0.98, p = 0.046) after direct pairwise comparison with non-HDL-C level. CONCLUSIONS: Non-attaining non-HDL-C goal predicted MACE at long-term follow-up after AMI whereas non-attaining LDL-C goal was not associated with the higher risk. Therefore, non-HDL-C may be a more suitable target of dyslipidemia treatment than LDL-C in patients after AMI.

QT dispersion in HIV-infected patients receiving combined antiretroviral therapy.

BACKGROUND: A higher prevalence of QT prolongation has been reported among human immunodeficiency virus (HIV)-infected patients. Previous studies have demonstrated that QT dispersion is a better predictor of serious ventricular tachyarrhythmia and cardiac mortality than corrected QT (QTc) interval. However, data of QT dispersion in HIV-infected patients receiving a combined antiretroviral therapy (cART) is limited. We sought to assess QTc interval and QT dispersion in HIV-infected patients receiving cART. The association between QT parameters and heart rate variability (HRV) was also examined. METHODS: Ninety-one HIV-infected patients receiving cART (male = 33, mean age = 44 ± 10 years) and 70 HIV-seronegative subjects (male = 25, mean age = 44 ± 8 years) were enrolled in the study. In a resting 12-lead electrocardiogram, QT interval was measured by the tangent method in all leads with well-defined T waves. The QT dispersion was defined as the difference between maximum and minimum QTc intervals in any of 12 leads. RESULTS: The baseline characteristics were not different between the two groups. We demonstrated the significantly longer mean QTc interval (420 ± 21 vs. 409 ± 21 ms, P < 0.001), and greater QT dispersion in HIV-infected group compared to the control group (85 ± 29 vs. 55 ± 23 ms, P < 0.001). Among the HIV-infected patients, those who had lower CD4 lymphocyte count (<350 cells/mm(3)) tended to have greater QT dispersion (92 ± 28 vs. 81 ± 29 ms, P = 0.098). There were no associations between QT parameters and either HRV or cART regimens. CONCLUSIONS: HIV-infected patients receiving cART were associated with prolonged QTc interval and increased QT dispersion, independent of autonomic dysfunction and antiretroviral drugs, which may have led to the potentially higher risk of ventricular arrhythmia and cardiac mortality.

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.

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 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.

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.

Heart rate variability and heart rate turbulence in HIV-infected patients receiving combination antiretroviral therapy.

BACKGROUND: Previous studies have demonstrated the presence of autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients. However, the data in those receiving combination antiretroviral therapy (cART) are conflicting. The aim of this study was to assess the autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) analysis in HIV-infected patients receiving cART. METHODS: Eighty-one HIV-infected patients receiving cART and 42 control subjects were enrolled in the study. The HRV and HRT parameters were assessed on 24-hour digital Holter electrocardiogram recordings. RESULTS: Baseline characteristics were comparable between HIV-infected and control subjects, except the higher fasting glucose and triglyceride and lower high-density lipoprotein cholesterol observed in HIV-infected patients. All components of HRV were significantly reduced in HIV-infected patients. After adjustment with biochemical parameters, most of the HRV parameters were still significantly reduced in HIV-infected patients. However, HRV parameters reflecting vagal activity were no longer different between 2 groups. In addition, HRT parameters did not differ between HIV-infected and control subjects. The standard deviation of normal-to-normal intervals significantly correlated with CD4 lymphocyte counts in HIV-infected patients but did not with protease inhibitors therapy. CONCLUSIONS: We demonstrated the overall decrease in HRV in HIV-infected patients receiving cART. The metabolic disturbance observed in HIV-infected patients possibly accounted for decreased vagal activity.

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.

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.

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.

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.