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.

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.

Predicting Heart Failure in Patients with Atrial Fibrillation: A Report from the Prospective COOL-AF Registry.

BACKGROUND: This study aimed to determine risk factors and incidence rate and develop a predictive risk model for heart failure for Asian patients with atrial fibrillation (AF). METHODS: This is a prospective multicenter registry of patients with non-valvular AF in Thailand conducted between 2014 and 2017. The primary outcome was the occurrence of an HF event. A predictive model was developed using a multivariable Cox-proportional model. The predictive model was assessed using C-index, D-statistics, Calibration plot, Brier test, and survival analysis. RESULTS: There were a total of 3402 patients (average age 67.4 years, 58.2% male) with mean follow-up duration of 25.7 ± 10.6 months. Heart failure occurred in 218 patients during follow-up, representing an incidence rate of 3.03 (2.64-3.46) per 100 person-years. There were ten HF clinical factors in the model. The predictive model developed from these factors had a C-index and D-statistic of 0.756 (95% CI: 0.737-0.775) and 1.503 (95% CI: 1.372-1.634), respectively. The calibration plots showed a good agreement between the predicted and observed model with the calibration slope of 0.838. The internal validation was confirmed using the bootstrap method. The Brier score indicated that the model had a good prediction for HF. CONCLUSIONS: We provide a validated clinical HF predictive model for patients with AF, with good prediction and discrimination values.

Left Atrial Diameter in the Prediction of Thromboembolic Event and Death in Atrial Fibrillation.

Background: This study aimed to determine the predictive value of left atrial diameter (LAD), and the incremental prognostic value of LAD in combination with CHA2DS2-VASc score for predicting thromboembolic event and all-cause death in patients with non-valvular atrial fibrillation (AF). Methods: This is a prospective study from 27 hospitals during 2014−2017. LADi is LAD data indexed by body surface area, and LADi in the 4th quartile (LADi Q4) was considered high. Results: A total of 2251 patients (mean age 67.4 years, 58.6% male) were enrolled. Mean follow-up duration was 32.3 months. Rates of thromboembolic events and all-cause death were significantly higher in LADi Q4 patients than in LADi Q1−3 patients (2.89 vs. 1.11 per 100 person-years, p < 0.001, and 7.52 vs. 3.13 per 100 person-years, p < 0.001, respectively). LADi Q4 is an independent predictor of thromboembolic events and all-cause death with an adjusted hazard ratio and 95% confidence interval of 1.94 (1.24−3.05) and 1.81 (1.38−2.37), respectively. LADi has incremental prognostic value on top of the CHA2DS2-VASc score with the increase in global chi-square for thromboembolism (p = 0.005) and all-cause death (p < 0.001). Conclusions: LADi is an independent predictor of thromboembolic event and has incremental prognostic value in combination with CHA2DS2-VASc score in AF patients.

The Rate of Clinical Outcomes in Atrial Fibrillation according to Antithrombotic Strategy: The COOL-AF Registry.

Background: Ischemic stroke/transient ischemic attack (TIA), major bleeding, and death are common outcomes in atrial fibrillation (AF) patients, so appropriate antithrombotic therapy is crucial. The objective of this study was to investigate the rate of ischemic stroke/TIA, major bleeding, and death compared among AF patients who received oral anticoagulant (OAC) alone, antiplatelet alone, or OAC plus antiplatelet. Methods: Prospective data from the COOL-AF Registry (Thailand's largest multicenter nationwide AF registry) were analyzed. Clinical, laboratory, and medication data were collected at baseline and during follow-up. Clinical outcomes, including ischemic stroke/TIA, major bleeding, and death, were collected. Results: There were 3,148 patients included. Mean age was 68.1 ± 10.8 years and 1,826 (57.7%) were male. AF was paroxysmal in 998 (31.7%), persistent in 603 (19.2%), and permanent in 1,547 (49.1%). The mean follow-up duration was 25.7 ± 10.6 months. The median rates of ischemic stroke/TIA, major bleeding, and death were 1.49 (1.21-1.81), 2.29 (1.94-2.68), and 3.89 (3.43-4.40) per 100 person-years. Antiplatelet alone, OAC plus antiplatelet, and OAC alone were used in 582 (18.5%), 308 (9.8%), and 2,258 (71.7%) patients, respectively. Antiplatelet alone significantly increased the risk of ischemic stroke/TIA and death compared to OAC alone. OAC plus antiplatelet significantly increased the risk of death compared to OAC alone. Conclusions: Antiplatelet was used in 890 (28.3%) AF, of whom 582 (18.5%) received antiplatelet alone, and 308 (9.8%) received antiplatelet and OAC. OAC plus antiplatelet significantly increased the risk of death without additional stroke prevention benefit. Antiplatelet alone should not be used in patients with AF.

Soluble ST2 in the prediction of heart failure and death in patients with atrial fibrillation.

BACKGROUND: Biomarkers may be a useful marker for predicting heart failure (HF) or death in patients with atrial fibrillation (AF). HYPOTHESIS: Soluble ST2 (sST2) may be a good biomarker for the prediction of HF or death in patients with AF. METHODS: This is a prospective study of patients with nonvalvular AF. Clinical outcomes were HF or death. Clinical and laboratory data were compared between those with and without clinical outcomes. Univariate and multivariate analysis was performed to determine whether sST2 is an independent predictor for heart failure or death in patients with nonvalvular AF. RESULTS: A total of 185 patients (mean age: 68.9 ± 11.0 years) were included, 116 (62.7%) were male. The average sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were 31.3 ± 19.7 ng/ml and 2399.5 ± 6853.0 pg/ml, respectively. Best receiver operating characteristic (ROC) cut off of sST2 for predicting HF or death was 30.14 ng/ml. Seventy-three (39.5%) patients had an sST2 level ≥30.14 ng/ml, and 112 (60.5%) had an sST2 level <30.14 ng/dl. The average follow-up was 33.1 ± 6.6 months. Twenty-nine (15.7%) patients died, and 33 (17.8%) developed HF during follow-up. Multivariate analysis revealed that high sST2 to be an independent risk factor for death or HF with a HR and 95% CI of 2.60 (1.41-4.78). The predictive value of sST2 is better than NT-proBNP, and it remained significant in AF patients irrespective of history of HF, and NT-proBNP levels. CONCLUSIONS: sST2 is an independent predictor of death or HF in patients with AF irrespective of history of HF or NT-proBNP levels.

Efficacy of R2CHA2DS2-VA score for predicting thromboembolism in Thai patients with non-valvular atrial fibrillation.

BACKGROUND: There is no data specific to the addition of renal dysfunction and age 50-64 years as risk parameters to the CHA2DS2-VA score, which is known as the R2CHA2DS2-VA score, among NVAF patients. Accordingly, the aim of this study was to validate the R2CHA2DS2-VA score for predicting thromboembolism in Thai NVAF patients. METHODS: Thai NVAF patients were prospectively enrolled in a nationwide multicenter registry from 27 hospitals during 2014-2020. Each component of the CHA2DS2-VA and R2CHA2DS2-VA scores was scored and recorded. The main outcomes were thromboembolism, including ischemic stroke, transient ischemic attack (TIA), and/or systemic embolism. The annual incidence rate of thromboembolism among patients in each R2CHA2DS2-VA and CHA2DS2-VA risk score category is shown as hazard ratio (HR) and 95% confidence interval (95% CI). The performance of the R2CHA2DS2-VA and CHA2DS2-VA scores was demonstrated using c-statistics. Net reclassification index was calculated. Calibration plat was used to assess agreement between observed probabilities and predicted probabilities of both scoring system. RESULTS: A total of 3402 patients were enrolled during 2014-2020. The average age of patients was 67.38 ± 11.27 years. Of those, 46.9% had renal disease, 30.7% had a history of heart failure, and 17.1% had previous stroke or TIA. The average R2CHA2DS2-VA and CHA2DS2-VA scores were 3.92 ± 1.92 and 2.98 ± 1.43, respectively. Annual thromboembolic risk increased with incremental increase in R2CHA2DS2-VA and CHA2DS2-VA scores. Oral anticoagulants had benefit in stroke prevention in NVAF patients with an R2CHA2DS2-VA score of 2 or more (adjusted HR: 0.630, 95% CI 0.413-0.962, p = 0.032). The c-statistics were 0.630 (95% CI 0.61-0.65) and 0.627 (95% CI 0.61-0.64), for R2CHA2DS2-VA and CHA2DS2-VA scores respectively. NRI was 2.2%. The slope and R2 of the calibration plot were 0.73 and 0.905 for R2CHA2DS2-VA and 0.70 and 0.846 for CHA2DS2-VA score respectively. CONCLUSIONS: R2CHA2DS2-VA score was found to be at least as good as CHA2DS2-VA score for predicting thromboembolism in Thai patients with NVAF. Similar to CHA2DS2-VA score, thromboembolism increased with incremental increase in R2CHA2DS2-VA score.

Average Systolic Blood Pressure and Clinical Outcomes in Patients with Atrial Fibrillation: Prospective Data from COOL-AF Registry.

PURPOSE: Hypertension is associated with incident atrial fibrillation (AF) and AF-related complications. We investigated the associations between average systolic blood pressure (SBP) and outcomes in a nationwide cohort of Asian patients with non-valvular atrial fibrillation (NVAF). PATIENTS AND METHODS: A multicenter nationwide registry of patients with NVAF in Thailand was conducted during 2014-2017. Clinical data, including blood pressure, were recorded at baseline and then every 6 months. Average SBP was calculated from the average of SBP from every visit. Cox regression models were used to calculate the rate of clinical outcomes of interest, ie ischemic stroke or transient ischemic attack (TIA), intracerebral hemorrhage (ICH), and all-cause death. Average SBP was categorized into three groups: <120, 120-140, and ≥140 mmHg. RESULTS: A total of 3402 patients were included, and the mean age was 67.4±11.3 years. The mean (±SD) baseline and average SBPs were 128.5±18.5 and 128.0±13.4 mmHg, respectively. The mean follow-up duration was 25.7±10.6 months. The median rate of ischemic stroke/TIA, ICH, and all-cause death was 1.43 (1.17-1.74), 0.70 (0.52-0.92), and 3.77 (3.33-4.24) per 100 person-years, respectively. The rate of ischemic stroke/TIA and ICH was lowest in patients with average SBP <120 mmHg, and highest among those with average SBP ≥140 mmHg. The death rates were consistent with a J-curve effect, being lowest in patients with an average SBP 120-140 mmHg. Sustained SBP control is more important than the SBP from a single visit. CONCLUSION: Sustained control of SBP was significantly associated with a reduction in adverse clinical outcomes in patients with NVAF.

Age-Related Clinical Outcomes of Patients with Non-Valvular Atrial Fibrillation: Insights from the COOL-AF Registry.

PURPOSE: We aimed to compare the rate of clinical outcomes among three age groups (<65, 65-74, and ≥75 years) of adult patients with non-valvular atrial fibrillation (NVAF). PATIENTS AND METHODS: We prospectively enrolled NVAF patients from 27 Thailand medical centers. The following were collected at baseline: demographic data, risk factors, comorbid conditions, laboratory data, and medications. The clinical outcomes were ischemic stroke (IS) or transient ischemic attack (TIA), major bleeding (MB), intracerebral hemorrhage (ICH), heart failure (HF), and death. All events were adjudicated. Patients were categorized according to age group into three groups; age <65, 65-74, and ≥75 years. RESULTS: Among the 3402 patients that were enrolled during 2014-2017, the mean age was 67.4±11.3 years, and 2073 (60.9%) were older. The average follow-up was 25.7±10.6 months. Oral anticoagulants were given in 75.4% of patients (91.1% of OAC was warfarin). The incidence rate of IS/TIA, MB, ICH, HF, and death was 1.43 (1.17-1.74), 2.11 (1.79-2.48), 0.70 (0.52-0.92), 3.03 (2.64-3.46), and 3.77 (3.33-4.24) per 100 person-years, respectively. The risk of IS/TIA, MB, ICH, HF, and death increased with age both before and after adjustment for potential confounders. Even though OAC reduced the risk of IS/TIA, it increased the risk of MB. Net clinical benefit (NCB) analysis favored oral anticoagulant (OAC) in the high-risk subset of older adults. CONCLUSION: Older adult NVAF patients had a significantly increased risk of IS/TIA, MB, ICH, HF, and death compared to younger NVAF before and after adjustment for potential confounders. Strategies to reduce overall risk, including OAC use and choice and integrated care, should be implemented.

Poor Time in Therapeutic Range Control is Associated with Adverse Clinical Outcomes in Patients with Non-Valvular Atrial Fibrillation: A Report from the Nationwide COOL-AF Registry.

BACKGROUND: Warfarin remains the most commonly used oral anticoagulant (OAC) in Thailand for stroke prevention among patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the relationship between time in therapeutic range (TTR) after warfarin initiation and clinical outcomes of NVAF. METHODS: TTR was calculated by the Rosendaal method from international normalized ratio (INR) data acquired from a nationwide NVAF registry in Thailand. Patients were followed-up every six months. The association between TTR and clinical outcomes was analyzed. RESULTS: There was a total of 2233 patients from 27 hospitals. The average age was 68.4 ± 10.6 years. The average TTR was 53.56 ± 26.37%. Rates of ischemic stroke/TIA, major bleeding, ICH, and death were 1.33, 2.48, 0.76, and 3.3 per 100 person-years, respectively. When patients with a TTR < 65% were compared with those with TTR ≥ 65%, the adjusted hazard ratios (aHR) for the increased risks of ischemic stroke/TIA, major bleeding, ICH, and death were 3.07, 1.90, 2.34, and 2.11, respectively. CONCLUSION: Poor TTR control is associated with adverse clinical outcomes in patients with NVAF who were on warfarin. Efforts to ensure good TTR (≥65%) after initiation of warfarin are mandatory to minimize the risk of adverse clinical outcomes.