Pil Sung Yang

CHA2DS2-VASc Score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) for Stroke in Asian Patients with Atrial Fibrillation: A Korean Nationwide Sample Cohort Study

Background and Purpose— The CHA2DS2-VASc stroke score (congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65–74, female) is used in most guidelines for risk stratification in atrial fibrillation (AF), but most data for this score have been derived in Western populations. Ethnic differences in stroke risk may be present. Our objective was to investigate risk factors for stroke in AF and application of the CHA2DS2-VASc score in an Asian AF population from Korea. Methods— A total of 5855 oral anticoagulant–naive nonvalvular AF patients aged ≥20 years were enrolled from Korea National Health Insurance Service Sample cohort from 2002 to 2008 and were followed up until December 2013. Results— The incidence rates (per 100 person-years) of ischemic stroke were 3.32 in the total population, being 0.23 in low-risk (CHA2DS2-VASc score 0 [male] or 1 [female]) and 4.59 in high-risk patients (CHA2DS2-VASc ≥2). Incidence rates of ischemic stroke or the composite thromboembolism end point showed a clear increase with increasing CHA2DS2-VASc score. On multivariable analysis, significant associations between CHA2DS2-VASc risk factors and ischemic stroke were observed; however, the significance of vascular disease or diabetes mellitus was attenuated after multivariate adjustment, and female sex (hazard ratio, 0.73; 95% confidence interval, 0.64–0.84) had a lower risk of ischemic stroke than males. Patients who were categorized as low risk consistently had an event rate <1% per year. Conclusions— The performance of CHA2DS2-VASc score in Asians is comparable with that in Western populations. The score shows good performance in defining the truly-low-risk AF patients for stroke/thromboembolism.

Clinical implication of an impaired fasting glucose and prehypertension related to new onset atrial fibrillation in a healthy Asian population without underlying disease: a nationwide cohort study in Korea

Aims For healthy populations without comorbidities, whether prehypertension and impaired fasting glucose (IFG) are associated with new onset atrial fibrillation (AF) is not well known. Methods and results We included 366 507 subjects (age ≥20 years) not diagnosed with non-valvular AF from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2003 to 2008. In total, 139 306 subjects diagnosed with AF-related comorbidities were excluded, and a 227 102 healthy population was followed up until 2013. The body mass index (BMI), blood pressure (BP), and fasting blood glucose (BG) level were acquired during National health check-ups. Subjects with IFG [hazard ratio (HR) 1.16, P = 0.017] had a higher AF risk and the diastolic BP (HR 1.11, P = 0.045) was a stronger indicator for an AF incidence than the systolic BP. After dividing the subjects into two mutually exclusive groups, AF incidence was increased dramatically by the combination effect of both prehypertension and an IFG in BMI <25 kg/m2 group, but, in BMI ≧25 kg/m2 group, did not show this tendency. An IFG related to AF risk was more prominent in the BMI <25 kg/m2 population (HR 1.18, P = 0.025) than those with a BMI ≥25 kg/m2, and subjects with both an IFG and prehypertension had a greater AF risk (HR 1.27, P = 0.016) than those without. Conclusion Even in a healthy Asian populations without comorbidities, prehypertension and IFG were important risk factors of AF. Specifically, when prehypertension, including systolic and diastolic BPs, was finally combined with the IFG, the risk of new onset AF was increased especially in the BMI <25 kg/m2 group.

CHA2DS2-VASc Score for Identifying Truly Low-Risk Atrial Fibrillation for Stroke: A Korean Nationwide Cohort Study

Background and Purpose— As the threshold of stroke risk for initiating oral anticoagulants is lowered after the introduction of the nonvitamin K antagonist oral anticoagulants, the focus of stroke prevention in patients with nonvalvular atrial fibrillation has shifted away from predicting high-risk patients toward initially identifying patients with a truly low risk of ischemic stroke, who do not need antithrombotic therapy. We tested the predictive ability of the congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack (doubled; CHADS2), congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74, female (CHA2DS2-VASc), and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk stratification schemes in oral anticoagulants naive patients with atrial fibrillation in a Korean nationwide sample cohort. Methods— From January 2002 to December 2008, a total of 5855 oral anticoagulant naive patients with nonvalvular atrial fibrillation aged ≥20 years were enrolled from Korea National Health Insurance Service-Sample Cohort database and were followed-up until December 2013. Results— At baseline, the proportions categorized as low risk using CHADS2, CHA2DS2-VASc, and ATRIA risk stratification schemes were 1049 (17.9%), 860 (14.7%), and 3280 (56.0%), respectively. During follow-up, the low-risk category using CHADS2, CHA2DS2-VASc, and ATRIA scores was retained in 811 (13.9%), 667 (11.4%), and 2729 (46.6%) patients, respectively. Rates of ischemic stroke (100 person-years) in the low risk categories of CHADS2, CHA2DS2-VASc, and ATRIA scores were 0.42, 0.26, and 1.43, respectively. CHA2DS2-VASc had the best sensitivity (98.8% versus 85.7% in CHADS2 and 74.8% in ATRIA) and negative predictive value (98.8% versus 95.3% for CHADS2 and 93.7% for ATRIA) for the prediction of stroke incidence and was best for the prediction of the absence of ischemic stroke during 5 years of follow-up (odds ratio, 16.4 [95% confidence interval, 8.8–30.8]). Conclusions— The CHA2DS2-VASc score shows good performance in defining truly low-risk Asian patients with atrial fibrillation for stroke compared with CHADS2 and ATRIA scores.

Associations of Abdominal Obesity and New‐Onset Atrial Fibrillation in the General Population

Background Higher height and weight are known to be associated with higher risk of atrial fibrillation (AF); however, whether the risk of AF is related to abdominal obesity is unclear. Methods and Results We studied 501 690 adults (mean age: 47.6±14.3 years; 250 664 women [50.0%]) without baseline AF in the National Sample Cohort released by the National Health Insurance Service in Korea. Body mass index (underweight defined as <18.5; normal, 18.5 to <25.0; overweight, 25.0 to <30.0; and obese, ≥30.0) and waist circumference (abdominal obesity defined as ≥90 cm for men and ≥80 cm for women) were evaluated. During a mean follow‐up of 3.9±1.3 years, 3443 participants (1432 women [41.6%]) developed AF. In multivariable models adjusted for clinical variables, the AF risk of underweight, overweight, and obese individuals increased by 21% (95% confidence interval, 1.01–1.45, P=0.043), 14% (95% confidence interval, 1.06–1.23, P<0.001), and 52% (95% confidence interval, 1.30–1.78, P<0.001), respectively, compared with those with normal body mass index. AF risk with confounder‐adjusted hazards for abdominal obesity was 18% (95% confidence interval, 1.10–1.27, P<0.001). The increased AF risk was present in abdominally obese individuals regardless of body mass index except for the obese group. In subgroup analysis, abdominal obesity by waist circumference conferred increased risk of new‐onset AF, particularly in participants without comorbidities. Conclusions Abdominal obesity is an important, potentially modifiable risk factor for AF in nonobese Asian persons. These data suggest that interventions to decrease abdominal obesity may reduce the population burden of AF.

Korean atrial fibrillation network genome-wide association study for early-onset atrial fibrillation identifies novel susceptibility loci

Aims Some genetic susceptibility loci for atrial fibrillation (AF) identified by genome-wide association studies (GWAS) in a European database showed ethnic differences in the Asian population. We explored novel AF susceptibility variants for patients with early-onset AF (≤60 years old) among Korean patients who underwent AF catheter ablation. Methods and results A genome-wide association study (GWAS) was conducted with 672 cases (≤60 years old, Yonsei AF Ablation cohort) and 3700 controls (Korea Genome Epidemiology Study). Association analysis was performed under an additive model of logistic regression, and replication study was conducted with 200 independent cases of Korean AF Network and 1812 controls. Five previously proven genetic loci (1q24/PRRX1, 4q25/PITX2, 10q24/NEURL, 12q24/TBX5, and 16q22/ZFHX3) were validated. Two novel genetic loci associated with early-onset AF were found on chromosomes 1q32.1/PPFIA4 (rs11579055, P = 6.84 × 10-10) and 4q34.1/HAND2 (rs8180252, P = 1.49 × 10-11) and replicated in an additional independent sample of the Korean AF Network. The identified loci implicate candidate genes that encode proteins related to cell-to-cell connection, hypoxic status, or long non-coding RNA. Conclusion Two novel genetic loci for early-onset AF were identified in Korean patients who underwent catheter ablation. One of the novel susceptibility loci on chromosome 4 has strong associations with previously proven gene in a European ancestry database.

Clinical Significance of Additional Ablation of Atrial Premature Beats after Catheter Ablation for Atrial Fibrillation

Purpose The clinical significance of post-procedural atrial premature beats immediately after catheter ablation for atrial fibrillation (AF) has not been clearly determined. We hypothesized that the provocation of immediate recurrence of atrial premature beats (IRAPB) and additional ablation improves the clinical outcome of AF ablation. Materials and Methods We enrolled 200 patients with AF (76.5% males; 57.4±11.1 years old; 64.3% paroxysmal AF) who underwent catheter ablation. Post-procedure IRAPB was defined as frequent atrial premature beats (≥6/min) under isoproterenol infusion (5 µg/min), monitored for 10 min after internal cardioversion, and we ablated mappable IRAPBs. Post-procedural IRAPB provocations were conducted in 100 patients. We compared the patients who showed IRAPB with those who did not. We also compared the IRAPB provocation group with 100 age-, sex-, and AF-type-matched patients who completed ablation without provocation (No-Test group). Results 1) Among the post-procedural IRAPB provocation group, 33% showed IRAPB and required additional ablation with a longer procedure time (p=0.001) than those without IRAPB, without increasing the complication rate. 2) During 18.0±6.6 months of follow-up, the patients who showed IRAPB had a worse clinical recurrence rate than those who did not (27.3% vs. 9.0%; p=0.016), in spite of additional IRAPB ablation. 3) However, the clinical recurrence rate was significantly lower in the IRAPB provocation group (15.0%) than in the No-Test group (28.0%; p=0.025) without lengthening of the procedure time or raising complication rate. Conclusion The presence of post-procedural IRAPB was associated with a higher recurrence rate after AF ablation. However, IRAPB provocation and additional ablation might facilitate a better clinical outcome. A further prospective randomized study is warranted.

Relation of Chronic Obstructive Pulmonary Disease to Cardiovascular Disease in the General Population

Chronic obstructive pulmonary disease (COPD) is a major health problem that contributes to substantial morbidity and mortality globally. This study investigated the relation between COPD and the risk of cardiovascular disease in the general population. We evaluated the cardiovascular effect of COPD using Korean National Health Insurance Service data from 2002 to 2013. We compared selected cardiovascular disease risk factors depending on pulmonary function using the Korean Health and Nutritional Examination Survey (KNHANES, n = 24,429) data. COPD was diagnosed in 11,771 patients (2.4%) in the National Health Insurance Service cohort. During the follow-up period (45.5 ± 14.9 months), subjects with COPD had lower cumulative survival rate for all-cause mortality, cardiovascular mortality, and sudden cardiac death (SCD, all p values <0.001). COPD was associated with an increased risk of all-cause mortality even after adjustment for potential confounding variables (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.33 to 1.55, p <0.001). However, COPD did not significantly increase the risk of cardiovascular mortality (HR 1.02, 95% CI 0.84 to 1.22, p = 0.876) and SCD (HR 1.07, 95% CI 0.79 to 1.44, p = 0.664) when adjusted for potential confounding variables. Analysis of the KNHANES cohort showed that systolic blood pressure, current smoking status, and Framingham risk score increased progressively with a decrease in pulmonary function (all p <0.001). In conclusion, COPD was associated with all-cause mortality, but not with cardiovascular mortality and SCD, whereas poor pulmonary function was associated with a heightened cardiovascular risk.

A stepwise approach to conduit puncture for electrophysiological procedures in patients with Fontan circulation

Aims In patients with Fontan circulation, the conduit may be punctured for electrophysiological procedures. We evaluated the feasibility and safety of a stepwise approach to conduit puncture in adults who have undergone Fontan operation. Methods and results We included 13 consecutive patients with lateral tunnel or extracardiac conduit Fontan circulation [median age (interquartile range), 24.0 (16.0-25.0) years; seven men] who had undergone electrophysiological procedures. We performed a stepwise approach to conduit puncture: 1st, Brockenbrough needle; 2nd, Brockenbrough needle with snare; 3rd, extra-steep Brockenbrough needle with/without snare; 4th radiofrequency transseptal needle with/without snare; 5th, wiring through the puncture; 6th, conduit dilation with angioplasty balloon; 7th, non-compliant or cutting balloon; and 8th, Inoue dilator. In 12 patients, conduit puncture was successful. In two, one, and two patients with a lateral tunnel made of the pericardium or right atrial wall, conduit puncture was performed by steps 1st, 2nd, and 4th, respectively. In one, three, two, and one patient with the Goretex lateral tunnel or extracardiac conduit, conduit puncture was performed by steps 1st, 6th, 7th, and 8th, respectively. Puncture time was significantly longer in patients with Goretex conduits than with pericardial conduits [62.0 (50.0-120.0) and 11.5 (10.0-14.8) min, respectively; P < 0.001]. A snare was necessary in patients with angles ≤ 35° between the conduit wall and vertical line. Conclusion A stepwise conduit puncture approach is feasible and safe in patients with lateral tunnel and extracardiac conduit Fontan circulation. Goretex conduit puncture was more difficult than pericardial conduit puncture.

Long-Term Prognosis of Patients with an Implantable Cardioverter-Defibrillator in Korea

Purpose The objective of this study was to elucidate the long-term prognosis of patients with implantable cardioverter-defibrillators (ICDs) in Korea. Materials and Methods We enrolled 405 patients (age, 57.7±16.7 years; 311 men) who had undergone ICD implantation. The patients were divided into three groups: heart failure (HF) and ICD for primary (group 1, n=118) and secondary prevention (group 2, n=93) and non-HF (group 3, n=194). We compared appropriate and inappropriate ICD therapy delivery among the groups and between high- (heart rate ≥200 /min) and low-rate (<200 /min) ICD therapy zones. Results During the follow-up period (58.9±49.8 months), the annual appropriate ICD therapy rate was higher in group 2 (10.4%) than in groups 1 and 3 (6.1% and 5.9%, respectively, p<0.001). There were no significant differences in annual inappropriate ICD therapy rate among the three groups. In group 1, the annual appropriate ICD therapy rate was significantly lower in patients with a high-rate versus a low-rate therapy zone (4.5% and 9.6%, respectively, p=0.026). In group 3, the annual inappropriate ICD therapy rate was significantly lower in patients with a high-rate versus a low-rate therapy zone (3.1% and 4.0%, respectively, p=0.048). Conclusion Appropriate ICD therapy rates are not low in Korean patients with ICD, relative to prior large-scale studies in Western countries. Appropriate and inappropriate ICD therapy could be reduced by a high-rate therapy zone in patients with HF and ICD for primary prevention, as well as non-HF patients, respectively.

Clinical characteristics of complex aortic plaque in patients with non-valvular atrial fibrillation

BACKGROUND Although complex aortic plaque (CxAoP) is a component of the CHA2DS2-VASc score in patients with atrial fibrillation (AF), it is underestimated without detection by trans-esophageal echocardiogram (TEE). We have evaluated the incidence and significance of CxAoP among patients with non-valvular AF (NVAF). METHODS We included 981 patients with NVAF who underwent catheter ablation (59.1±11.1years old, 73.7% male, 70.2% paroxysmal AF). All of the patients underwent pre-procedural TEE evaluation. Left atrial (LA)-cardioembolic (CE) milieu was defined as a dense spontaneous echo-contrast or LA appendage flow velocity≤20cm/s. RESULTS CxAoP was present in 8.3% of patients, and independently associated with age (OR 1.07, 95% CI 1.03-1.10, p<0.001), male sex (OR 2.34, 95% CI 1.29-4.24, p=0.005), and CHA2DS2-VASc score≥2 (OR 3.33, 95%CI 1.42-7.77, p=0.005). The presence of LA-CE milieu overlapped with CxAoP in only 11% of patients. Patients with CxAoP had a higher prevalence of hypertension (p=0.004), smoking history (p=0.008), paroxysmal AF (PAF, p<0.001), and a smaller LA volume index (p<0.001) than those with LA-CE milieu. The prevalence of persistent AF among patients with a history of stroke was significantly lower in the presence of CxAoP than in those with LA-CE milieu (p=0.014). CHA2DS2-VASc score was underestimated in 11% of high-risk patients (CHA2DS2-VASc score≥2) due to undetected CxAoP. CONCLUSIONS CxAoP may contribute to the risk of stroke by a different mechanism than LA-CE milieu in patients with NVAF. Imaging assessment for CxAoP affects thromboembolic risk stratification and decision making for stroke prevention in patients with NVAF.