Background: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. Methods: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. Results: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. Conclusion A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Purpose: Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. Materials and Methods: Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m2 ) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. Results: During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). Conclusion Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC.ClinicalTrials.gov (NCT02786095)

Background: The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF). Methods: In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia. Results: Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type). Conclusion Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.

Purpose: The incidence of stroke and/or systemic thromboembolism (SSE) has not been properly evaluated in well-anticoagulated atrial fibrillation (AF) patients. This study investigated the incidence of SSE according to CHA2DS2-VASc score in contemporary well-anticoagulated Korean AF patients. Materials and Methods: From the prospective multicenter COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry, we identified 9503 patients with non-valvular AF (mean age, 68±8 years; female 35.5%) enrolled between June 2016 and May 2020 with eligible follow-up visits. Stroke incidence in the CODE-AF registry was compared with that in an oral anticoagulant (OAC)-naïve AF cohort from the Korean National Health Insurance database. Results: The usage rates of OACs and antiplatelet agents were 73.5% (non-vitamin K OACs, 56.4%; warfarin, 17.1%) and 23.8%, respectively. During a mean follow-up period of 26.3±9.6 months, 163 (0.78 per 100 person-years) patients had SSE. The incidence rate (per 100 person-years) of SSE was 0.77 in the total population, 0.26 in low-risk patients [CHA2DS2-VASc score 0 (male) or 1 (female)], and 0.88 in high-risk patients (CHA2DS2-VASc score ≥2). Contemporary AF patients had a stroke rate that was about one-fifth the stroke rate reported in a Korean OAC-naïve AF cohort. In this cohort, most risk factors for CHA2DS2-VASc score showed significant associations with SSE. Female sex was not associated with an increased risk of stroke/SSE in well-anticoagulated AF patients. Conclusion Contemporary AF patients have a stroke rate about one-fifth that in OAC-naïve AF patients and exhibit different stroke risk factors.

Background and Objectives: In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. Methods: This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA 2 DS 2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. Results: Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25 the and 75 the percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. Conclusions In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.

Background/Aims: Comparative occurrence of ischemic stroke for rhythm versus rate control strategy in patients with non-valvular atrial fibrillation (NVAF) is still inconclusive. The purpose of this study was to investigate whether the rhythm control strategy is associated with a lower risk of ischemic stroke compared to the rate control strategy in NVAF patients. Methods: The CODE-AF registry prospectively enrolled 6,280 consecutive patients who were treated for NVAF at 10 tertiary referral centers in South Korea. Of these, 2,513 NVAF patients (age, 67 ± 10 years; male, 61.8%) were clinically followed up for over 1-year and divided into rate and rhythm control groups. Results: Those treated with the rhythm control strategy were younger and had less proportions of underlying disease compared to those treated with the rate control strategy. After the propensity matching analysis, those treated with the rhythm control strategy had similar baseline characteristics including the CHA 2 DS 2 -VASC score compared to those treated with the rate control strategy.The rate of oral anticoagulation, all bleeding, and hospitalization were also similarly between the two groups. The incidence rate of ischemic stroke in the rhythm control group was significantly lower than in the rate control group (0.7 vs. 6.9 per 1,000 person-years, p = 0.011). Conclusions The rhythm control strategy demonstrated a beneficial effect to lower the risk of ischemic stroke during a 1-year follow-up compared to the rate control strategy.

Idiopathic renal hypouricemia (iRHUC) is a rare hereditary disease caused by a defect in urate handling of renal tubules. Type 1 renal hypouricemia (RHUC1) is diagnosed with confirmation of a mutation in SLC22A12 gene which encodes a renal urate-anion exchanger (URAT1). The majority of iRHUC patients are asymptomatic, especially during childhood, and thus many cases go undiagnosed or they are diagnosed late in older age with complications of hematuria, renal stones, or acute kidney injury (AKI). We report a case of a 7-year-old boy with subtle symptoms such as general weakness and dizziness and revealed hypouricemia and incidental nephrolithiasis. Homozygous mutations were detected in the SLC22A12(c.774G>A) by molecular analysis. The present case suggests that fractional excretion of uric acid (FEUA) screening could be better followed by the coincidental discovery of hypouricemia, to prevent conflicting complications of iRHUC, even with normal urine uric acid to creatinine ratio (UUA/UCr), and sequential genetic analysis if needed.

Idiopathic renal hypouricemia (iRHUC) is a rare hereditary disease caused by a defect in urate handling of renal tubules. Type 1 renal hypouricemia (RHUC1) is diagnosed with confirmation of a mutation in SLC22A12 gene which encodes a renal urate-anion exchanger (URAT1). The majority of iRHUC patients are asymptomatic, especially during childhood, and thus many cases go undiagnosed or they are diagnosed late in older age with complications of hematuria, renal stones, or acute kidney injury (AKI). We report a case of a 7-year-old boy with subtle symptoms such as general weakness and dizziness and revealed hypouricemia and incidental nephrolithiasis. Homozygous mutations were detected in the SLC22A12(c.774G>A) by molecular analysis. The present case suggests that fractional excretion of uric acid (FEUA) screening could be better followed by the coincidental discovery of hypouricemia, to prevent conflicting complications of iRHUC, even with normal urine uric acid to creatinine ratio (UUA/UCr), and sequential genetic analysis if needed.

Background: Symptom burden is an important factor in determining the treatment of atrial fibrillation (AF). AF is frequently accompanied by heart failure (HF). This study investigated the characteristics of AF symptoms with concomitant HF. Methods: A total of 4885 patients with AF were consecutively enrolled through a prospective observational registry (the Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation [CODE-AF] registry). Clinically diagnosed HF was divided into three categories (preserved, mid-range, and reduced ejection fraction [EF]). Symptom severity was assessed using the European Heart Rhythm Association (EHRA) classification. Results: The presence of AF-related symptoms was comparable irrespective of concomitant HF. Patients with HF with reduced EF demonstrated severe (EHRA classes 3 and 4) and atypical symptoms. HF with preserved EF was also associated with atypical symptoms. Female sex and AF type were associated with the presence of symptoms in AF without HF, and non-maintenance of sinus rhythm and increased left atrial pressure (E/e′ ≥ 15) were factors related to the presence of symptoms in AF with HF. Conclusion AF with concomitant HF presented with more severe and atypical symptoms than AF without HF. Maintaining the sinus rhythm and reducing the E/e’ ratio are important factors for reducing symptoms in AF with concomitant HF.

Purpose: Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. This study investigated anticoagulation patterns and outcomes in patients with chronic kidney disease (CKD). Materials and methods: In a prospective observational registry (CODE-AF), 3445 patients with non-valvular AF including 1129 with CKD (estimated glomerular filtration rate ≤ 60 mL min−1 1.73 m−2) were identified between June 1, 2016, and July 3, 2017. Results: Compared with patients with no-CKD, patients with CKD more frequently had a high stroke risk (94.9% vs. 67.0%, p < 0.001) and higher NOAC usage rate (61.1% vs. 47.8%, p < 0.001). Among 718 patients with renal indication for dose reduction (RIDR), 7.5% were potentially overdosed. Among 2587 patients with no-RIDR, 79% were potentially underdosed. Compared with patients with no-RIDR, the underdose rates of dabigatran (0% vs. 88.6%, p = 0.001) and rivaroxaban (0% vs. 79.5%, p = 0.001) were lower in patients with RIDR. However, the underdose rate of apixaban was not different (62.5% vs. 53.9%, p = 0.089). The overdose rate of dabigatran (7.5% vs. 0%) and rivaroxaban (13.7% vs. 0%) was higher in RIDR than in no-RIDR patients. Stroke/transient ischemic attack was significantly higher in CKD patients (1.4 vs. 0.6 per 100 person-years, p = 0.045). Aspirin significantly increased minor bleeding in CKD patients compared with controls (p = 0.037). Conclusion CKD patients might have a high stroke risk and NOAC usage rate. The underdose rate of NOACs decreased in CKD patients, except for apixaban. Aspirin significantly increased minor bleeding in CKD patients.