Clinical Outcomes of Patients with Atrial Fibrillation who Survived from Bleeding Event: The Results from COOL-AF Thailand Registry.

BACKGROUND: Bleeding events are often reported among patients with atrial fibrillation (AF), irrespective of antithrombotic use. This study is to determine clinical outcomes of patients with AF who survived from bleeding event. METHODS: We analyzed data from COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) Thailand registry. Outcomes of patients who experienced any bleeding were compared with patients who had never bleed. Time updated multivariate Cox-proportional hazard models were used to estimate the risk for clinical outcomes of patients with and without bleeding. RESULTS: Of total 3,405 patients (mean age: 67.8 ± 11.3 years; 41.9% female) in COOL-AF registry, 609 patients (17.9%) reported bleeding event occurs and 568 patients (93.3%) survived though hospital discharge. Patients who survived major bleeding (n = 126) were at increased risk for both death (adjusted hazard ratio [HR]: 4.44, 95% confidence interval [CI]: 2.91-6.75, p < 0.001) and stroke/systemic embolism (adjusted HR: 4.49, 95% CI: 2.19-9.24, p < 0.001). Minor bleeding also increased subsequent death (adjusted HR: 2.13, 95% CI: 1.56-2.90, p < 0.001). Up to 30% of patients who survived major bleeding and 6.3% of minor bleedings discontinued oral anticoagulation. Discontinuation was associated with very high death rate (42.1%), whereas patients who resumed oral anticoagulation after bleeding had lower mortality (10%). The most common causes of death in patients who survived a bleeding event were not related to cardiovascular causes nor bleeding. CONCLUSION: Patients with AF who have bleeding events have an increased risk for subsequent death and stroke and systemic embolism. These patients should be identified as vulnerable clinically complex patients and require a holistic approach to their AF management.

Molnupiravir versus favipiravir in at-risk outpatients with COVID-19: A randomized controlled trial in Thailand.

OBJECTIVES: Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. METHODS: In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. RESULTS: Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (-1.0%; Newcombe 95.2% CI: -2.4% to -0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). CONCLUSIONS: Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. THAI CLINICAL TRIALS REGISTRY ID: TCTR20230111009.

Systolic blood pressure visit-to-visit variability and outcomes in Asian patients with atrial fibrillation.

We aimed to assess the association between SBP-VVV and outcomes in Asian patients with atrial fibrillation (AF). AF patients in the COOL-AF registry with SBP measured at baseline, and at least two other visits were studied. We defined SBP-VVV using the standard deviation (SD) of average SBP. Patients were categorized according to the quartiles of SBP SD. The associations between SBP-VVV and outcomes were assessed in the adjusted Cox model. We studied 3172 patients (mean age 67.7 years; 41.8% female), with the prevalence of hypertension being 69%. Warfarin was used in 69% of patients, whereas 7% received non-vitamin K antagonist oral anticoagulants. The minimum and maximum SD of average SBP in the study population was 0.58 and 56.38 mmHg respectively. The cutoff of SD of average SBP for each quartile in our study were 9.09, 12.15, and 16.21 mmHg. The rates of all-cause mortality, ischemic stroke or systemic embolization (SSE), major bleeding, and intracranial hemorrhage (ICH) were 3.10, 1.42, 2.09, and 0.64 per 100 person-years, respectively. Compared with the first quartile, patients in the fourth quartile had a significantly higher risk of mortality (adjusted HR 1.60, 95%CI 1.13-2.25), bleeding (aHR 1.92, 95%CI 1.25-2.96) and ICH (aHR 3.51, 95%CI 1.40-8.76). The risk of SSE was not significantly different among the quartiles. SBP-VVV had a significant impact on the long-term outcomes of Asian patients with AF, particularly mortality and bleeding. Adequate SBP control and maintaining SBP stability over time may improve outcomes for AF patients.

Myocardial scar and left ventricular ejection fraction classification for electrocardiography image using multi-task deep learning.

Myocardial scar (MS) and left ventricular ejection fraction (LVEF) are vital cardiovascular parameters, conventionally determined using cardiac magnetic resonance (CMR). However, given the high cost and limited availability of CMR in resource-constrained settings, electrocardiograms (ECGs) are a cost-effective alternative. We developed computer vision-based multi-task deep learning models to analyze 12-lead ECG 2D images, predicting MS and LVEF < 50%. Our dataset comprises 14,052 ECGs with clinical features, utilizing ground truth labels from CMR. Our top-performing model achieved AUC values of 0.838 (95% CI 0.812-0.862) for MS and 0.939 (95% CI 0.921-0.954) for LVEF < 50% classification, outperforming cardiologists. Moreover, MS predictions in a prevalence-specific test dataset recorded an AUC of 0.812 (95% CI 0.810-0.814). Extracted 1D signals from ECG images yielded inferior performance, compared to the 2D approach. In conclusion, our results demonstrate the potential of computer-based MS and LVEF < 50% classification from ECG scan images in clinical screening offering a cost-effective alternative to CMR.

2024 Consensus Statement on Coronary Stenosis and Plaque Evaluation in CT Angiography From the Asian Society of Cardiovascular Imaging-Practical Tutorial (ASCI-PT).

The Asian Society of Cardiovascular Imaging-Practical Tutorial (ASCI-PT) is an instructional initiative of the ASCI School designed to enhance educational standards. In 2021, the ASCI-PT was convened with the goal of formulating a consensus statement on the assessment of coronary stenosis and coronary plaque using coronary CT angiography (CCTA). Nineteen experts from four countries conducted thorough reviews of current guidelines and deliberated on eight key issues to refine the process and improve the clarity of reporting CCTA findings. The experts engaged in both online and on-site sessions to establish a unified agreement. This document presents a summary of the ASCI-PT 2021 deliberations and offers a comprehensive consensus statement on the evaluation of coronary stenosis and coronary plaque in CCTA.

Expert recommendations for the management of iron deficiency in patients with heart failure in Asia.

BACKGROUND: Iron deficiency is a common comorbidity in heart failure (HF) and is independently associated with a worse quality-of-life and exercise capacity, as well as increased risk of hospitalization, regardless of anemia status. Although international guidelines have provided recommendations for the management of iron deficiency in patients with HF, guidelines in Asia are less established, and practical use of guidelines for management of iron deficiency is limited in the region. METHODS: A panel comprising cardiologists from China, Hong Kong, India, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, and Thailand convened to share insights and provide guidance for the optimal management of iron deficiency in patients with HF, tailored for the Asian community. RESULTS: Expert opinions were provided for the screening, diagnosis, treatment and monitoring of iron deficiency in patients with HF. It was recommended that all patients with HF with reduced ejection fraction should be screened for iron deficiency, and iron-deficient patients should be treated with intravenous iron. Monitoring of iron levels in patients with HF should be carried out once or twice yearly. Barriers to the management of iron deficiency in patients with HF in the region include low awareness of iron deficiency amongst general physicians, lack of reimbursement for screening and treatment, and lack of proper facilities for administration of intravenous iron. CONCLUSIONS: These recommendations provide a structured approach to the management of iron deficiency in patients with HF in Asia.

External Validation of COOL-AF Scores in the Asian Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Background: The COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) risk scores for death, bleeding, and thromboembolic events (TEs) were derived from the COOL-AF cohort from Thailand and require external validation. Objectives: The authors sought to externally validate the COOL-AF scores in the APHRS (Asia-Pacific Heart Rhythm Society) registry and to compare their performance in the ESC-EHRA (European Society of Cardiology-European Heart Rhythm Association) EORP-AF (EURObservational Research Programme in Atrial Fibrillation) General Long-Term Registry. Methods: We studied 3,628 APHRS and 8,825 EORP-AF patients. Receiver operating characteristic (ROC) curves and Cox regression analyses were used to test the predictive value of COOL-AF scores and to compared them with the CHA2DS2-VASc and HAS-BLED scores. Results: Patients in the EORP-AF were older, had a higher prevalence of male sex, and were at higher thromboembolic and hemorrhagic risk than APHRS patients. After 1 year of follow-up in APHRS and EORP-AF, the following events were recorded: 87 (2.4%) and 435 (4.9%) death for any causes, 37 (1.0%) and 111 (1.3%) major bleeding, and 25 (0.7%) and 109 (1.2%) TEs, respectively. In APHRS, the COOL-AF scores showed moderate-to-good predictive value for all-cause mortality (area under the curve [AUC]: 0.77; 95% CI: 0.71-0.83), major bleeding (AUC: 0.68; 95% CI: 0.60-0.76), and TEs (AUC: 0.61; 95% CI: 0.51-0.71), and were similar to the CHA2DS2-VASc and HAS-BLED scores. In EORP-AF, the predictive value of COOL-AF for all-cause mortality (AUC: 0.68; 95% CI: 0.65-0.70) and major bleeding (AUC: 0.61; 95% CI: 0.60-0.62) was modest and lower than in APHRS. In EORP-AF, the COOL-AF score for TE was inferior to the CHA2DS2-VASc score. Conclusions: The COOL-AF risk scores may be an easy tool to identify Asian patients with AF at risk for death and major bleeding and performs better in Asian than in European patients with AF. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia [AF-Registry]; NCT04807049).

Time in target range of systolic blood pressure and clinical outcomes in atrial fibrillation patients: results of the COOL-AF registry.

We aimed to investigate the relationship between time in target range of systolic blood pressure (SBP-TTr) and clinical outcomes in patients with atrial fibrillation (AF). We analyzed the results from multicenter AF registry in Thailand. Blood pressure was recorded at baseline and at every 6 monthly follow-up visit. SBP-TTr were calculated using the Rosendaal method, based on a target SBP 120-140 mmHg. The outcomes were death, ischemic stroke/systemic embolism (SSE), major bleeding, and heart failure. A total of 3355 patients were studied (mean age 67.8 years; 41.9% female). Average follow-up time was 32.1 ± 8.3 months. SBP-TTr was classified into 3 groups according to the tertiles. The incidence rates of all-cause death, SSE, major bleeding, and heart failure were 3.90 (3.51-4.34), 1.52 (1.27-1.80), 2.2 (1.90-2.53), and 2.83 (2.49-3.21) per 100 person-years, respectively. Patients in the 3rd tertile of SBP-TTr had lower rates of death, major bleeding and heart failure with adjusted hazard ratios 0.62 (0.48-0.80), p < 0.001, 0.64 (0.44-0.92), p = 0.016, and 0.61 (0.44-0.84), p = 0.003, respectively, compared to 1st SBP-TTr tertile. In conclusion, high SBP-TTr was associated with better clinical outcomes compared to other groups with lower SBP-TTr. This underscores the importance of good blood pressure control in AF patients.

Non-vitamin K Antagonist Oral Anticoagulant, Warfarin, and ABC Pathway Adherence on Hierarchical Outcomes: Win Ratio Analysis of the COOL-AF Registry.

BACKGROUND: Atrial fibrillation (AF) Better Care (ABC) pathway adherence is associated with improved outcomes. Clinical trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are as least as effective as warfarin for stroke prevention in AF patients. The Win Ratio method, analyzing hierarchical composite outcomes considering event timing and severity, has limited data on its use in Asians. OBJECTIVES: We aim to apply Win Ratio in a registry to access the comparative effectiveness of NOACs versus warfarin and ABC adherence versus nonadherence in Asian patients with AF. METHODS: Our study included nonvalvular AF patients from the nationwide prospective COOL-AF registry in Thailand. The NOAC-treated group was compared with the warfarin-treated group using the Win Ratio, with the following order: all-cause death, intracranial hemorrhage (ICH), ischemic stroke/transient ischemic attack/systemic embolism, non-ICH major bleeding, and myocardial infarction or heart failure. ABC pathway adherence versus nonadherence was also compared. A Win Ratio greater than 1.00 indicating a better outcome. RESULTS: The analysis included 2,568 patients, with 228 in the NOAC group and 2,340 in the warfarin group. The NOAC group had more wins than the warfarin group, with an unmatched Win Ratio of 1.64 (95% confidence interval [CI]: 1.22-2.20; p < 0.001). When compared with nonadherence, ABC pathway adherence was associated with a Win Ratio of 1.57 (95% CI: 1.33-1.85; p < 0.001). CONCLUSION: This Win Ratio analysis demonstrates the significant benefits of NOACs over warfarin and ABC pathway adherence over nonadherence in reducing the composite outcome in patients with AF.

Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation: An Asian Perspective.

Optimal dosing of direct oral anticoagulants (DOACs) for stroke prevention in "gray area" patients with atrial fibrillation (AF) remains a challenge for clinicians. In Asia, this is concerning in patients who are very elderly, have low body weight, and are at a high risk of bleeding. This review aims to summarize the dose reduction criteria for DOACs, discuss the evidence on dosing of DOACs across Asian regions, and collate opinions from authors across Asia. Nonrecommended dosing of DOACs is common in Asia, primarily due to the fear of bleeding, with the total clinical benefit of higher dosing being overlooked. The ELDERCARE-AF (Edoxaban Low-Dose for Elder Care-Atrial Fibrillation Patients) trial and real-world case studies provide some evidence on the use of low-dose DOACs in gray area patients. Opinions on dose adjustment guidance, concomitant medication adjustments, and therapeutic drug monitoring were collated. Research is needed to fill the evidence gaps on optimal DOAC doses for gray area patients.

Clinical outcomes of obese and nonobese patients with atrial fibrillation according to associated metabolic abnormalities: A report from the COOL-AF registry.

BACKGROUND: The primary objective was to determine the influence of obesity and associated metabolic status on clinical outcomes of Asian patients with atrial fibrillation (AF). METHODS: This study was based on a prospective multicenter of patients with nonvalvular AF. Patients were classified as obese and nonobese and being metabolic unhealthy was defined as having at least one of the three cardiovascular risk factors including dyslipidemia, hypertension, or diabetes mellitus. Outcomes were a primary composite outcome of all-cause death, ischemic stroke/systemic embolism (SSE), acute myocardial infarction (MI), and heart failure (HF), as well as the individual end points. RESULTS: There were a total of 3141 enrolled patients (mean age 67.4 ± 11.1 years; 41.0% female), of whom 1566 (49.9%) were obese and 2564 (81.6%) were metabolic unhealthy. During a mean follow-up of 32.2 ± 8.3 months, the incidence rate of the composite outcome, all-cause death, SSE, MI, and HF were 7.21 (6.63-7.82), 3.86 (3.45-4.30), 1.48 (1.23-1.77), 0.47 (0.33-0.64), and 2.84 (2.48-3.23) per 100 person-years, respectively. Metabolic unhealthy nonobese subjects were at higher risk of the composite outcomes than metabolic unhealthy obese subjects with hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.17-1.66, p < .001. Metabolic unhealthy obese subjects tend to have an increased risk of the composite outcomes compared to those metabolic healthy obese (HR 1.36, 95% CI 0.91-2.02, p = .133). Metabolic healthy obese subjects were not associated with increased risk. CONCLUSIONS: Metabolic unhealthy obese subjects were associated with an increased risk of adverse outcomes in AF patients, whereas metabolically healthy obesity was not associated with an increased risk.

Net clinical benefit of oral anticoagulants in Asian patients with atrial fibrillation based on a CHA2DS2-VASc score.

BACKGROUND: This study was conducted to assess the net clinical benefit (NCB) for oral anticoagulant (OAC) in atrial fibrillation (AF) patients according to the CHA2DS2-VASc score. METHODS: Patients with AF were prospectively recruited in the COOL AF Thailand registry from 2014 to 2017. The incidence rate of thromboembolic (TE) events and major bleeding (MB) was calculated. Cox proportional hazards model was used to compare the TE and MB rate in patients with and without OACs in CHA2DS2-VASc score of 0-1 and ≥ 2, respectively. The survival analysis was performed based on CHA2DS2-VASc score. The NCB of OACs was defined as the TE rate prevented minus the MB rate increased multiplied by a weighting factor. RESULTS: A total of 3,402 AF patients were recruited. An average age of patients was 67.38 ± 11.27 years. Compared to non-anticoagulated patients, the Kaplan Meier curve showed anticoagulated patients with CHA2DS2-VASc score of 2 or more had the lower thromboembolic events with statistical significance (p = 0.043) and the higher MB events with statistical significance (p = 0.018). In overall AF patients, there were positive NCB in warfarin patients with CHA2DS2-VASc score of 3 or more while there were positive NCB in DOACs patients regardless of CHA2DS2-VASc score. Females with CHA2DS2-VASc score of 3 or more had a positive NCB regardless of OACs type. Good anticoagulation control (TTR ≥65%) improved an NCB in males with CHA2DS2-VASc score of 3 or more. CONCLUSIONS: AF patients with CHA2DS2-VASc score of 3 or more regardless warfarin or DOACs had a positive NCB. The NCB of OACs was more positive for DOACs compared to warfarin and for females compared to males.

Safety and clinical impact of adenosine stress perfusion cardiac magnetic resonance in Asian patients with known or suspected coronary artery disease.

BACKGROUND: Adenosine stress cardiac magnetic resonance (CMR) imaging is increasingly utilized for evaluating patients with known or suspected coronary artery disease (CAD). This study aims to assess the safety and clinical impact of adenosine stress CMR in a tertiary care setting in Thailand. METHODS: A total of 3,768 consecutive patients aged 18 years and above who underwent adenosine stress CMR between 2017 and 2020 were included in the study. Patient records were reviewed to collect data on clinical characteristics, hemodynamic measurements, complications during or immediately after CMR, and the rates of clinical changes resulting from CMR. RESULTS: Among the included patients, the primary indications for adenosine stress CMR were risk stratification in suspected CAD (70.8%) and the assessment of myocardial ischemia/viability in patients with known CAD (26.5%). There were no reported deaths or acute myocardial infarctions during the procedure. Major complications, specifically acute pulmonary edema requiring hospital observation or admission for further management, occurred in four patients (0.11%), all of whom were elderly (ranging from 75 to 91 years) with a history of heart failure. Non-major complications were observed in 13.7% of patients, with dyspnea (9.8%) and mild chest pain (5.6%) being the most common. CMR provided a completely new diagnosis in 26.2% of patients. Overall, stress CMR resulted in a change in diagnosis or management for 48% of patients. CONCLUSION: Adenosine stress CMR was found to be safe and to have a significant impact on clinical management in Asian patients with known or suspected CAD. These findings support the use of adenosine stress CMR as a valuable tool for evaluating and guiding treatment decisions in this patient population.

Increased small extracellular vesicle levels and decreased miR-126 levels associated with atrial fibrillation and coexisting diabetes mellitus.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Diabetes mellitus (DM) is one of the risk factors for the development of stroke and thromboembolism in patients with AF. Early identification may reduce the incidence of complications and mortality in AF patients. HYPOTHESIS: AF patients with DM have different pattern of small extracellular vesicle (sEV) levels and sEV-derived microRNA (miRNA) expression compared with those without DM. METHODS: We compared sEV levels and sEV-miRNA expression in plasma from AF patients with and without DM using nanoparticle tracking analysis and droplet digital polymerase chain reaction, respectively. RESULTS: We observed a significant increase in total sEV levels (p = .004) and a significant decrease in sEV-miR-126 level (p = .004) in AF patients with DM. Multivariate logistic regression analysis revealed a positive association between total sEV levels and AF with DM (p = .019), and a negative association between sEV-miR-126 level and AF with DM (p = .031). The combination of clinical data, total sEVs, and sEV-miR-126 level had an area under the curve of 0.968 (p < .0001) for discriminating AF with DM, which was shown to be significantly better than clinical data analysis alone (p = .0368). CONCLUSIONS: These results suggest that an increased level of total sEV and a decreased sEV-miR-126 level may play a potential role in the pathophysiology and complications of AF with DM, especially endothelial dysfunction, and can be considered as an applied biomarker for distinguishing between AF with and without DM.

Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

AIMS: Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects. METHODS: A multicenter, nationwide prospective FH registry was established in Thailand. Our data were compared with those of the European Atherosclerosis Society-FH Studies Collaboration. Multiple logistic regression analyses were performed for variables associated with lipid-lowering medication (LLM) use and the attainment of low-density lipoprotein-cholesterol (LDL-C) goal. RESULTS: The study includes 472 subjects with FH (mean age at FH diagnosis: 46±12 years, 61.4% women). A history of premature coronary artery disease was found in 12%. The percentage of LLM use in subjects with a Dutch Lipid Clinic Network score of ≥ 6 (probable or definite FH) in our registry (64%) was slightly lower than the regional data but higher than the global data. Among those who received statins, 25.2% and 6.4% achieved LDL-C levels of ＜100 mg/dL and ＜70 mg/dL, respectively. Women with FH were less likely to achieve LDL-C ＜70 mg/dL (adjusted odds ratio: 0.22, 95% confidence interval: 0.06-0.71, p=0.012). CONCLUSIONS: FH in Thailand was diagnosed late, and treatment was inadequate for the majority of subjects. Women with FH were less likely to achieve LDL-C goals. Our insights could potentially help raise awareness and narrow the gap in patient care.

Visit-to-Visit Heart Rate Variability in the Prediction of Clinical Outcomes of Patients with Atrial Fibrillation.

BACKGROUND: Visit-to-visit heart rate variability (VVV-HR) has been associated with adverse cardiovascular outcomes. We aimed to determine the predictive value of VVV-HR for adverse clinical outcomes in patients with nonvalvular atrial fibrillation (AF). METHODS: We used data from a prospective multicenter AF registry of 27 hospitals in Thailand during 2014 to 2017. After the baseline visit, patients were followed up every 6 months until 3 years. VVV-HR was calculated from the standard deviation of heart rate data from baseline visit and every follow-up visit. VVV-HR was categorized into four groups according to the quartiles. Clinical outcomes were all-cause death, ischemic stroke/systemic embolism (SE), and heart failure. Cox proportional hazard models were used for multivariable analysis. RESULTS: There were a total of 3,174 patients (mean age: 67.7 years; 41.8% female). The incidence rates of all-cause death, ischemic stroke/SE, and heart failure were 3.10 (2.74-3.49), 1.42 (1.18-1.69), and 2.09 (1.80-2.42) per 100 person-years respectively. The average heart rate was 77.8 ± 11.0 bpm and the average of standard deviation of heart rate was 11.0 ± 5.9 bpm. VVV-HR Q4 was an independent predictor of all-cause death, ischemic stroke/SE, and heart failure with adjusted hazard ratios of 1.45 (95% confidence interval: 1.07-1.98), 2.02 (1.24-3.29), and 2.63 (1.75-3.96), respectively. VVV-HR still remained a significant predictor of clinical outcomes when analyzed based on coefficient of variation and variability independent of mean. CONCLUSION: VVV-HR is an independent predictor for adverse clinical outcomes in patients with AF. A J-curve appearance was demonstrated for the effect of VVV-HR on all-cause death.

Three-year outcomes of patients with non-valvular atrial fibrillation: the COOL-AF registry.

BACKGROUND: Clinical outcomes of patients with non-valvular atrial fibrillation (AF) in Asian populations may be different from non-Asians. In this study, we aimed to determine the incidence of ischemic stroke/systemic embolism (SSE), major bleeding, and death, and the predictors for clinical outcomes in a contemporary Asian cohort of newly diagnosed AF patients. METHODS: This is a prospective multicenter nationwide registry of patients with AF from 27 hospitals in Thailand. Baseline data and follow-up data were collected every 6 months until 3 years. Data collections included demographic, medical history, laboratory, and medication details. Clinical outcomes were SSE, major bleeding, and all-cause mortality. Incidence rates for each clinical outcome were calculated and presented as rate per 100 person-years. Univariate and multivariate analysis was performed to determine the independent predictors for clinical outcomes. RESULTS: There was a total of 3405 patients: mean age was 67.8 ± 11.3 years, 1981 (58.2%) were male. During 30.8 ± 9.7 months follow-up, there was a total of 132 SSE (3.9%), 191 major bleeding (5.6%), and 357 all-cause deaths (10.5%). The incidence rates of SSE, major bleeding, and death were 1.56 (1.30-1.84), 2.26 (1.96-2.61), and 4.17 (3.33-4.25), per 100 person-years respectively. Independent predictors for clinical outcomes were age, type of AF, and the presence of comorbid conditions. CONCLUSION: The incidence rate of SSE, major bleeding, and death remains high reflecting the unmet needs in AF management.

Predicting the Absolute Risk of Ischemic Stroke in Asian Patients with Atrial Fibrillation: Comparing the COOL-AF Risk Score with CARS/mCARS Models for Absolute Risk and the CHA2DS2-VASc Score.

BACKGROUND: The aims of this study were (1) to validate the CARS and mCARS methods in an Asian population with atrial fibrillation (AF) and (2) to compare the CARS and mCARS models for absolute risk using the COOL-AF method and CHA2DS2VASc scores for the prediction of ischemic stroke or systemic embolism (SSE). METHODS: We analyzed the results from a prospective nationwide multicenter AF registry. Follow-up data were collected for 3 years. The main outcomes were SSE. Predictive models of the 3-year SSE of the COOL-AF model, the CHA2DS2VASc score, the CARS for the no-OAC group, and the mCARS for the OAC group were developed and evaluated by C-statistics, and calibration plots were created for the whole group, as well as for oral anticoagulant (OAC) users and no-OAC patients. RESULTS: We studied 3405 patients (mean age: 67.8 years; 58.2% male, 75.4% OAC). The incidence rates of SSE were 1.51 (1.26-1.78), 1.93 (1.39-2.60), and 1.37 (1.10-1.68) for all patients, no-OAC patients, and OAC patients, respectively. For the whole population, the COOL-AF score had a C-statistic of 0.697 (0.682-0.713), which was superior to the CHA2DS2-VASc [0.655 (0.639-0.671)]. For the no-OAC group, the CARS predicted SSE with a C-statistic of 0.685 (0.652-0.716), which was similar to the CHA2DS2-VASc [0.684 (0.651-0.7150] and COOL-AF models [0.692 (0.659-0.723)]. For the OAC group, the mCARS had a C-statistic of 0.687 (0.669-0.705) that was similar to the COOL-AF [0.704 (0.686-0.721)] and better than the CHA2DS2-VASc score [0.655 (0.637-0.674)]. CONCLUSIONS: The calculation of the individual absolute risks using the CARS and mCARS models can predict SSE in an Asian population. Small differences were evident between the COOL-AF and CHA2DS2-VASc scores.

Comparative validation of HAS-BLED, GARFIELD-AF and ORBIT bleeding risk scores in Asian people with atrial fibrillation treated with oral anticoagulant: A report from the COOL-AF registry.

AIMS: Comparative data between the HAS-BLED, GARFIELD-AF and ORBIT score are limited in anticoagulated Asian patients with atrial fibrillation (AF). We compared the performance of the 3 scores in a nationwide registry. METHODS: AF patients treated with oral anticoagulants in the COOL-AF registry were studied. We fitted the variables of the HAS-BLED, GARFIELD-AF and ORBIT score to major bleeding in Cox model. We explored a modified HAS-BLED by addition of sex and body weight. Discrimination, calibration, net reclassification index (NRI) and decision curve analysis were used to compare the performance of the 3 models. RESULTS: Of 3402 patients in the registry, 2568 patients who received oral anticoagulant at baseline were studied. Majority of patients (91.1%) received warfarin. The rate of major bleeding was 2.11 per 100 person-years. The C-statistics of the GARFIELD-AF, HAS-BLED, modified HAS-BLED and ORBIT score were 0.65 (95% confidence interval [CI] 0.63-0.67), 0.66 (95%CI 0.64-0.68), 0.69 (95%CI 0.67-0.71) and 0.64 (95%CI 0.62-0.66) respectively. There was good agreement between predicted and observed bleeding in the deciles of HAS-BLED and GARFIELD-AF scores, while the modified HAS-BLED score and ORBIT score overestimated the risk in the last decile. The modified HAS-BLED score had superior NRI than the HAS-BLED score (26.9%, 95%CI 9.7%-42.2%) and the ORBIT score (31.9%, 95%CI 9.0-53.6%). The NRI between the modified HAS-BLED and GARFIELD-AF score was similar. The net benefit curve of the 4 models were overlapping among different thresholds. CONCLUSIONS: The clinical utility for bleeding prediction of GARFIELD-AF, HAS-BLED, modified HAS-BLED and ORBIT scores were similar in anticoagulated Asian patients with AF participating in the COOL-AF registry. We found no advantage of the ORBIT over HAS-BLED score for bleeding risk prediction, even in direct oral anticoagulant users.