Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients.

BACKGROUND: We aimed to compare the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients. Additionally, the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced cardiotoxicity were determined. METHODS: HER2-positive (n = 37) and HER2-negative (n = 37) breast cancer patients were enrolled. Cardiac function assessment and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at three months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all three-time points was processed for measuring cardiac injury biomarkers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment were also processed for measuring systemic oxidative stress and 85 metabolome levels. RESULTS: Cardiac injury and systolic dysfunction 2 weeks after completion of doxorubicin treatment were comparable between these two groups of patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively. The changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment. CONCLUSIONS: The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, and these changes might serve as severity and prognostic markers of doxorubicin-induced cardiotoxicity. TRIAL REGISTRATION: The study was conducted under ethical approval from the Institutional Review Board of the Faculty of Medicine, Chiang Mai University (Registration number: MED-2563-07001; Date: April 28, 2020). The study also complied with the Declaration of Helsinki.

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.

Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial.

Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies.

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.

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.

Prospective randomised trial examining the impact of an educational intervention versus usual care on anticoagulation therapy control based on an SAMe-TT2R2 score-guided strategy in anticoagulant-naïve Thai patients with atrial fibrillation (TREATS-AF): a study protocol.

INTRODUCTION: The burden of atrial fibrillation (AF) in Thailand is high and associated with increased morbidity, mortality and healthcare costs. Vitamin K antagonists (eg, warfarin), commonly used for stroke prevention in patients with AF in Thailand, are effective but are often suboptimally controlled. We aim to evaluate the impact of an SAMe-TT2R2 score-guided strategy and educational intervention compared to usual care on anticoagulation control expressed by the time in therapeutic range (TTR) at 12 months, in anticoagulant-naïve Thai patients with AF. METHODS AND ANALYSIS: Multicentre, open-label, parallel-group, randomised controlled trial conducted in Thailand among adult patients (age: 18 years) with AF who are anticoagulant naïve. Patients will be randomised to one of two groups; an SAMe-TT2R2 score-guided strategy with educational intervention and usual care versus usual care alone. The planned follow-up period is 12 months. The primary outcome is TTR at 12 months. Secondary outcomes include: (1) TTR at 6 months; (2) thromboembolic and bleeding events at 12 months; (3) composite major adverse cardiovascular events at 12 months; (4) change in patients' knowledge of AF between baseline and 6 months and 12 months; (5) cost effectiveness; (6) quality of life at baseline, 6 months and 12 months using EQ-5D-5L (Thai version) and (7) patient satisfaction/perceptions of the TREAT intervention. An embedded qualitative study will assess patient perceptions of the TREAT intervention. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Review Committee, Ministry of Public Health of Thailand, and registered in the Thai Clinical Trials Registry. The results of this trial will be submitted for publication in a peer-reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided to all participants prior to publication. TRIAL REGISTRATION NUMBER: TCTR20180711003.

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.

Effect of early pendulum exercise on shoulder function after cardiac rhythm management device implantation.

PURPOSE: Patients who are post-implantation of cardiac rhythm management devices (CRMDs) are commonly instructed to restrict ipsilateral arm movement to reduce risk of lead dislodgement. This immobilization practice increases risk of shoulder-related pain leading to limited shoulder function. We aimed to assess effect of pendulum exercise on shoulder function in patients after CRMD implantation. METHODS: This study was a prospective, randomized, open-blinded end point study conducted with 200 patients undergoing CRMD implantation. They were randomized into two groups, standard care (control) and pendulum exercise (experimental) groups. The shoulder function was assessed using QuickDASH-TH scores and measurement of the range of motion (ROM) of shoulder abduction and flexion before and 1 month after implantation. RESULTS: Baseline characteristics did not differ between the two groups. The lower incidence of shoulder ROM reduction after CRMD implantation was demonstrated in the pendulum exercise group compared to the control group in both flexion (16.8% vs. 40.4%, P < 0.001) and abduction (9.9% vs. 32.3%, P < 0.001). A lower disability of shoulder function after implantation assessed by QuickDASH-TH scores was also noted in the exercise group compared to control (15.2 ± 16.4 vs. 23.4 ± 18.1, P = 0.001). Two patients in the control group and one in the exercise group had atrial lead dislodgement on the day following the procedure. CONCLUSIONS: Early pendulum exercise with ipsilateral arm after CRMD implantation was safe and resulted in lower incidence of limited shoulder ROM and less disability of shoulder function compared to control group. TRIAL REGISTRATION: The study was registered in clinicaltrials.in.th , and the identification number is TCTR20180612003.

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.

Peripheral Artery Occlusive Disease Among Patients With Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitors: A Cross-Sectional Case-Control Study.

BACKGROUND: There were some reports of peripheral artery occlusive disease (PAOD) associated with nilotinib usage in chronic myeloid leukemia (CML). These complications in other tyrosine kinase inhibitors are revealed as unknown. MATERIALS AND METHODS: We determined the prevalence of PAOD in patients with CML as compared with matched-control population by cross-sectional case-control study. Peripheral artery occlusive disease was screened by ankle-brachial index (ABI). RESULTS: In total, 78 CML and 156 matched-control patients were included. The median age was 55 years. In all, 61 (78.2%) were on imatinib and 13 (16.7%) were on nilotinib, whereas 4 patients (5.2%) were on dasatinib. Prevalence of low ABI (<0.9) was 9.0%, and nilotinib users had the highest prevalence of low ABI of 30.7%. All cases with low ABI were not shown to be clinically overt of PAOD. There were well-balanced characteristics between cases of CML and matched control except in higher levels of hypercholesterolemia in the control. Interestingly, CML had more amounts of pathologic ABI than the control (odds ratio: 2.09, 95% confidence interval: 0.71-6.21), and diagnosis of diabetes found it to be independent of the risk of PAOD. CONCLUSIONS: Peripheral artery occlusive disease was higher among patients with CML than the control, especially in patients who had diabetes.

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.

Ivabradine reduced ventricular rate in patients with non-paroxysmal atrial fibrillation.

BACKGROUND: It has been shown that If channels can be found in AV node, apart from the sinus node. Previous animal studies showed that If inhibitor resulted in the rate-dependent reduction in AV node conduction during atrial fibrillation (AF). Therefore, we aimed to examine the effect of ivabradine on ventricular rate in patients with non-paroxysmal AF. METHOD: This study was a prospective randomized, double blind, placebo-controlled study. Ivabradine, 5mg twice a day (n=21), or placebo (n=11) was administered for 1month to adult patients with non-paroxysmal AF, in addition to standard therapy. The primary end point was the change in mean ventricular rate between baseline and 1month, as assessed by 24-hour Holter. RESULTS: The baseline characteristics did not differ between ivabradine and placebo groups (mean age was 59.7±13.3years, male 62.5%). Mean 24-hour ventricular rate at baseline was comparable between 2 groups. We found that ivabradine significantly decreased mean ventricular rate from 86.0±10.9beats/min to 79.2±9.6beats/min (p<0.001). In contrast, no significant change in ventricular rate was observed in placebo group (84.3±11.2 vs. 82.9±9.9beats/min, p=0.469). The effect of ivabradine on rate reduction was significantly greater than placebo (6.9±6.3 vs. 1.4±6.0beats/min, p=0.024). No drug-related adverse effects were observed in both groups. CONCLUSION: We demonstrated that ivabradine significantly decreased ventricular rate during AF compared to placebo. Therefore, ivabradine can be a potential treatment to improve ventricular control in patients with non-paroxysmal AF. Due to the small sample size, larger studies are needed to confirm this effect of ivabradine.