Publications by authors named "Boyoung Joung"

418 Publications

Ablation and antiarrhythmic drug effects on deficient atrial fibrillation: A computational modeling study.

Front Cardiovasc Med 2022 19;9:942998. Epub 2022 Jul 19.

Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Introduction: Atrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 () gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and deficient) using computational modeling.

Methods: We included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks.

Results: At the baseline AF, mean DF ( = 0.003), and Smax ( < 0.001) were significantly lower in deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, < 0.001) without changing the DF or Smax. Although a deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate ( = 0.014), lower DF ( < 0.001), and lower Smax ( = 0.001) in deficient AF than in wild-type patients. In the clinical setting, the genetic risk score did not affect the AF ablation rhythm outcome (Log-rank = 0.273).

Conclusion: Consistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the deficient patients.
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http://dx.doi.org/10.3389/fcvm.2022.942998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343754PMC
July 2022

Clinical Usefulness of Virtual Ablation Guided Catheter Ablation of Atrial Fibrillation Targeting Restitution Parameter-Guided Catheter Ablation: CUVIA-REGAB Prospective Randomized Study.

Korean Circ J 2022 Jul 11. Epub 2022 Jul 11.

Department of Cardiology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.

Background And Objectives: We investigated whether extra-pulmonary vein (PV) ablation targeting a high maximal slope of the action potential duration restitution curve (Smax) improves the rhythm outcome of persistent atrial fibrillation (PeAF) ablation.

Methods: In this open-label, multi-center, randomized, and controlled trial, 178 PeAF patients were randomized with 1:1 ratio to computational modeling-guided virtual Smax ablation (V-Smax) or empirical ablation (E-ABL) groups. Smax maps were generated by computational modeling based on atrial substrate maps acquired during clinical procedures in sinus rhythm. Smax maps were generated during the clinical PV isolation (PVI). The V-Smax group underwent an additional extra-PV ablation after PVI targeting the virtual high Smax sites.

Results: After a mean follow-up period of 12.3±5.2 months, the clinical recurrence rates (25.6% vs. 23.9% in the V-Smax and the E-ABL group, p=0.880) or recurrence appearing as atrial tachycardia (11.1% vs. 5.7%, p=0.169) did not differ between the 2 groups. The post-ablation cardioversion rate was higher in the V-Smax group than E-ABL group (14.4% vs. 5.7%, p=0.027). Among antiarrhythmic drug-free patients (n=129), the AF freedom rate was 78.7% in the V-Smax group and 80.9% in the E-ABL group (p=0.776). The total procedure time was longer in the V-Smax group (p=0.008), but no significant difference was found in the major complication rates (p=0.497) between the groups.

Conclusions: Unlike a dominant frequency ablation, the computational modeling-guided V-Smax ablation did not improve the rhythm outcome of the PeAF ablation and had a longer procedure time.

Trial Registration: ClinicalTrials.gov Identifier: NCT02558699.
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http://dx.doi.org/10.4070/kcj.2022.0113DOI Listing
July 2022

Generation of a heterozygous TPM1-E192K knock-in human induced pluripotent stem cell line using CRISPR/Cas9 system.

Stem Cell Res 2022 Aug 28;63:102878. Epub 2022 Jul 28.

Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea. Electronic address:

E192K missense mutation of TPM1 has been found in different types of cardiomyopathies (e.g., hypertrophic cardiomyopathy, dilated cardiomyopathy, and left ventricular non-compaction), leading to systolic dysfunction, diastolic dysfunction, and/or tachyarrhythmias. Here, we generated a heterozygous TPM1-E192K knock-in human induced pluripotent stem cell (iPSC) line using CRISPR/Cas9-based genome editing system. The cells exhibit normal karyotype, typical stem cell morphology, expression of pluripotency markers and differentiation ability into three germ layers. Accordingly, this cell line could provide a useful cell resource for exploring the pathogenic role of TPM1-E192K mutation in different types of cardiomyopathies.
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http://dx.doi.org/10.1016/j.scr.2022.102878DOI Listing
August 2022

Lower pulmonary vein-to-left atrium volume ratio predicts poor rhythm outcome after atrial fibrillation catheter ablation.

Front Cardiovasc Med 2022 15;9:934168. Epub 2022 Jul 15.

Department of Internal Medicine, Division of Cardiology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Although left atrial (LA) dimension (LAD) is one of the predictors of atrial fibrillation (AF) recurrence after catheter ablation, repetitive recurrences occur in patients without enlarged LAD. We explored the predictive value of pulmonary vein (PV) to LA volume percent ratio (PV/LA%vol) for rhythm outcomes after AF catheter ablation (AFCA). We included 2913 patients (73.5% male, 60.0 [52.0-67.0] years old, 60.6% paroxysmal AF) who underwent AFCA. We evaluated the association between PV/LA%vol and AF recurrence after AFCA and compared the predictive value for AF recurrences according to the LA size with LAD. We additionally investigated the association between PV/LA%vol and gene using a genome-wide association study. LAD affected 1-year recurrence only in the highest tertile group (T3, = 0.046), but PV/LA%vol determined 1-year recurrence in all LAD groups (T1, = 0.044; T2, = 0.021; and T3, = 0.045). During 20.0 (8.0-45.0) months of follow-up, AF recurrence rate was significantly higher in patients with lower PV/LA%vol (Log-rank = 0.004, HR 0.91 [0.84-1.00], = 0.044). In the T1 and T2 LAD groups, predicting AF recurrences was better with PV/LA%vol than with LAD (AUC 0.63 vs. 0.51, < 0.001 at T1; AUC 0.61 vs. 0.50, = 0.007 at T2). We replicated -related rs12646447, which was independently associated with PV/LA%vol (β = 0.15 [0-0.30], = 0.047). In conclusion, smaller PV volumes after LA volume adjustments have genetic background of gene and predictive value for poorer rhythm outcomes after AFCA, especially in patients without LA enlargement.
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http://dx.doi.org/10.3389/fcvm.2022.934168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334901PMC
July 2022

Association of changes in cardiovascular health levels with incident cardiovascular events and mortality in patients with atrial fibrillation.

Clin Res Cardiol 2022 Jul 13. Epub 2022 Jul 13.

Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

Background: Risk factor management is crucial in the management of atrial fibrillation (AF). We investigated the association of changes in cardiovascular health (CVH) levels after AF diagnosis with incident cardiovascular events and mortality.

Methods: From the Korea National Health Insurance Service database, 76,628 patients newly diagnosed with AF (2005-2015) with information on health examinations before and after AF diagnosis were assessed. According to the change in the 12-point CVH score before and after AF diagnosis, patients were stratified into four groups: consistently low (score 0-7 to 0-7), high-to-low (8-12 to 0-7), low-to-high (0-7 to 8-12), and consistently high (8-12 to 8-12) CVH levels. Risks of cardiovascular events and death were analyzed using weighted Cox regression models with inverse probability of treatment weighting (IPTW) for balance across study groups.

Results: The mean age of study participants was 58.3 years, 50,285 were men (63.1%), and the mean follow-up was 5.5 years. After IPTW, low-to-high (hazard ratio [95% confidence interval], 0.83 [0.76-0.92]) and consistently high (0.80 [0.74-0.87]) CVH levels were associated with a lower risk of ischemic stroke than consistently low CVH. Low-to-high (0.66 [0.52-0.84]) and consistently high (0.52 [0.42-0.64]) CVH levels were associated with a lower risk of acute myocardial infarction. Maintaining high CVH was associated with reduced risks of heart failure hospitalization (0.85 [0.75-0.95]) and all-cause death (0.82 [0.77-0.88]), respectively, compared with consistently low CVH.

Conclusions: Improving CVH levels and maintaining high CVH levels after AF diagnosis is associated with lower risks of subsequent cardiovascular events and mortality.
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http://dx.doi.org/10.1007/s00392-022-02058-3DOI Listing
July 2022

Optimal Rhythm Control Strategy in Patients With Atrial Fibrillation.

Korean Circ J 2022 Jul;52(7):496-512

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.

For almost 20 years, data regarding the effect of rhythm control therapy for atrial fibrillation (AF) on cardiovascular prognosis in comparison with rate control therapy has not been conclusive. The safety of rhythm control and anticoagulation therapy has generally improved. Recently, it was revealed that a rhythm-control strategy reduced the risk of adverse cardiovascular events than usual rate control in patients with recent AF (diagnosed within 1 year). Within 1 year after the AF diagnosis, early initiation of rhythm control led to more favorable cardiovascular outcomes than rate control. Early rhythm control reduced the risks of stroke and heart failure-related admission than rate control. Moreover, rhythm control was associated with lower dementia risk than rate control. Finally, early rhythm control treatment was also effective in patients with asymptomatic AF but less effective in older adults. Therefore, in patients with AF, rhythm control should be considered at earlier stages, regardless of symptom.
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http://dx.doi.org/10.4070/kcj.2022.0078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257152PMC
July 2022

Case Report: Delayed Ventricular Pseudoaneurysm After Radiofrequency Ablation of Left Posteromedial Papillary Muscle Ventricular Tachycardia.

Front Cardiovasc Med 2022 15;9:887190. Epub 2022 Jun 15.

Division of Cardiology, Yonsei University Health System, Seoul, South Korea.

A 74-year-old woman presented with incessant wide complex tachycardia that was refractory to cardioversions. Successful radiofrequency catheter ablation was performed on the left ventricular posteromedial papillary muscle. An inaudible steam pop has occurred during the procedure, but we confirmed that there were no complications during the procedure and short-term follow-up of echocardiography. Two months after the procedure, an asymptomatic pseudoaneurysm was identified at the ablation site that had not been observed in the short-term follow-up.
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http://dx.doi.org/10.3389/fcvm.2022.887190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240706PMC
June 2022

Serum exosomal long noncoding RNAs as a diagnostic biomarker for atrial fibrillation.

Heart Rhythm 2022 May 31. Epub 2022 May 31.

Division of Cardiology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Exosomal long noncoding RNAs (lncRNAs) are known as ideal diagnostic biomarkers of various diseases. However, there are no reports on the use of serum exosomal lncRNAs as diagnostic biomarkers for atrial fibrillation (AF).

Objective: The purpose of this study was to explore serum exosomal lncRNAs as a useful tool for diagnosing AF.

Methods: Serum exosomes from patients with persistent AF and controls were isolated using a polymer-based exosome precipitation kit. We conducted a multiphase process including screening and 2 independent validation phases. In the screening phase, serum exosomal lncRNA expression profiles were examined using RNA sequencing analysis. In 2 validation phases, we evaluated the expression levels of candidate exosomal lncRNAs using quantitative reverse transcription polymerase chain reaction. Finally, we performed different statistical and functional analyses.

Results: After the screening phase, we identified 26 differentially expressed lncRNAs (ie, 15 upregulated and 11 downregulated lncRNAs with a |fold change| ≥2 and P <.05) in serum exosomes from patients with persistent AF compared with controls. We then screened out 6 exosomal lncRNAs as biomarker candidates following parameters: read length ≥200 nucleotides; exon number ≥2; and coding potential score <0.1. In 2 validation phases, exosomal lncRNAs LOC105377989 and LOC107986997 were consistently upregulated in the serum of patients with persistent AF compared with controls (P <.0001). Moreover, both exosomal lncRNAs exhibited significant diagnostic validity for AF. Notably, exosomal lncRNA LOC107986997 was involved in AF-related pathophysiological mechanisms.

Conclusion: Serum-derived exosomal lncRNA LOC107986997 could serve as a potential biomarker for AF diagnosis.
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http://dx.doi.org/10.1016/j.hrthm.2022.05.033DOI Listing
May 2022

Association of Gender With Clinical Outcomes in a Contemporary Cohort of Patients With Atrial Fibrillation Receiving Oral Anticoagulants.

Korean Circ J 2022 Aug 26;52(8):593-603. Epub 2022 Apr 26.

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.

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 (CHADS-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%, p0.001) than men. During a median (25 and 75 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.

Trial Registration: ClinicalTrials.gov Identifier: NCT02786095.
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http://dx.doi.org/10.4070/kcj.2021.0399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353255PMC
August 2022

Association between exercise habit changes and mortality following a cardiovascular event.

Heart 2022 May 19. Epub 2022 May 19.

Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Korea

Objective: To investigate the associations between exercise habit changes following an incident cardiovascular event and mortality in older adults.

Methods: We analysed the relationship between exercise habit change and all-cause, cardiovascular and non-cardiovascular deaths in adults aged ≥60 years between 2003 and 2012 who underwent two consecutive health examinations within 2 years before and after diagnosis of cardiovascular disease (CVD). They were categorised into four groups according to exercise habit changes: persistent non-exercisers, exercise dropouts, new exercisers and exercise maintainers. Differences in baseline characteristics were adjusted using inverse probability of treatment weighting.

Results: Of 6076 participants, the median age was 72 (IQR 69-76) years and men accounted for 50.6%. Compared with persistent non-exercisers (incidence rate (IR) 4.8 per 100 person-years), new exercisers (IR 3.5, HR 0.73, 95% CI 0.58 to 0.91) and exercise maintainers (IR 2.9, HR 0.53, 95% CI 0.38 to 0.73) were associated with reduced risk of all-cause death. The rate of non-cardiovascular death was significantly lower in new exercisers (IR 2.3, HR 0.73, 95% CI 0.56 to 0.95) and exercise maintainers (IR 2.3, HR 0.61, 95% CI 0.42 to 0.90) than in persistent non-exercisers (IR 3.2). Also, trends towards reduced cardiovascular death in new exercisers and exercise maintainers were observed (p value for trend <0.001).

Conclusions: More virtuous exercise trajectories in older adults with CVD are associated with lower mortality rates. Our results support public health recommendations for older adults with CVD to perform physical activity.
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http://dx.doi.org/10.1136/heartjnl-2022-320882DOI Listing
May 2022

Age and Outcomes of Early Rhythm Control in Patients With Atrial Fibrillation: Nationwide Cohort Study.

JACC Clin Electrophysiol 2022 05;8(5):619-632

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: This study sought to investigate whether the effects of early rhythm control differ according to age.

Background: Rhythm control, compared with usual care among patients recently diagnosed with atrial fibrillation (AF), was found to be associated with a lower risk of adverse cardiovascular outcomes. It is unclear whether the results can be generalized for older adults.

Methods: This retrospective population-based cohort study included 31,220 patients with AF, from the Korean National Health Insurance Service database, undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis. A composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared in subgroups stratified by age.

Results: Compared with rate control, early rhythm control was associated with a lower risk of the primary composite outcome in patients <75 years of age (HR: 0.80; 95% CI: 0.72-0.88). The protective association between early rhythm control and cardiovascular outcomes exhibited a linear decrease with advancing age, with declined benefits in patients ≥75 years of age (HR: 0.94; 95% CI: 0.87-1.03; P = 0.045). Trends toward lower risks of ischemic stroke (HR: 0.78; 95% CI: 0.67-0.90) and acute myocardial infarction (HR: 0.63; 95% CI: 0.41-0.97) were observed in the older adults. No significant differences in safety outcomes were found across different ages.

Conclusions: The beneficial association of early rhythm control with cardiovascular outcomes was attenuated with increasing age, with the larger benefits in younger patients <75 years of age. No differences were found by age in treatment-related safety outcomes.
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http://dx.doi.org/10.1016/j.jacep.2022.02.014DOI Listing
May 2022

Electrical Posterior Box Isolation in Repeat Ablation for Atrial Fibrillation: A Prospective Randomized Clinical Study.

JACC Clin Electrophysiol 2022 05 23;8(5):582-592. Epub 2022 Feb 23.

Yonsei University Health System, Seoul, Republic of Korea. Electronic address:

Objectives: This study investigated whether additional electrical posterior box isolation (POBI) may improve the rhythm outcome of repeat ablation in atrial fibrillation (AF).

Background: Although electrically reconnected pulmonary veins (PVs) are the main mechanism of AF recurrence, it is unclear whether linear ablation in addition to circumferential PV isolation (CPVI) improves rhythm outcomes after repeat ablation.

Methods: The authors prospectively randomized 150 patients with PV reconnection undergoing redo procedures to either a CPVI-alone group (n = 75) or an additional POBI group (n = 75). The primary endpoint was AF recurrence after a single procedure, and the secondary endpoints were recurrence pattern, cardioversion rate, and response to antiarrhythmic drugs.

Results: After a median follow-up of 17 months, the clinical recurrence rate did not significantly differ between the CPVI-alone and additional-POBI groups (30.7% vs 30.7%; log-rank P =0.828). Of the 46 patients with clinical recurrence, the recurrences as atrial tachycardia (8.7% vs 30.4%; P =0.137) and cardioversion rates (21.7% vs 47.8%; P =0.122) were not significantly different between the CPVI-alone and additional-POBI groups. Major complication rates did not differ between the 2 groups (1.3% vs 5.3%; P = 0.363), but the total ablation time was significantly longer in the additional-POBI group than in the CPVI-alone group (median: 1,084 [IQR: 704-1,664] vs 1,595 [IQR: 1,244-2,302] seconds; P < 0.001).

Conclusions: Among patients undergoing redo AF ablation with reconnected PVs, the addition of POBI to CPVI did not improve rhythm outcomes or influence overall safety, whereas leading to a longer ablation time than that with CPVI alone. (Comparison of Circumferential Pulmonary Vein Isolation and Complex Pulmonary Vein Isolation Additional Linear Ablation for Recurred Atrial Fibrillation After Previous Catheter Ablation: Prospective Randomized Trial [RILI Trial]; NCT02747498).
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http://dx.doi.org/10.1016/j.jacep.2022.01.003DOI Listing
May 2022

Association of Light-Intensity Physical Activity With Mortality in the Older Population: A Nationwide Cohort Study.

Front Cardiovasc Med 2022 22;9:859277. Epub 2022 Apr 22.

Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Background: There is a paucity of information about mortality related to light-intensity physical activity (LPA) in the older population. We examine the associations between physical activity and mortality, focusing on the effect of light-intensity physical activity and the dose-response relationship between physical activity and mortality.

Methods: We analyzed a total of 58,537 participants aged ≥ 65 years (mean age, 73.9 ± 5.8 years; male, 36.0%) in the Korean National Health Insurance Service database between 2009 and 2012. The Date of the end of follow-up was December 31, 2013. Individuals were divided into four categories according to physical activity intensity: totally sedentary (43.3%), LPA only (35.8%), LPA and moderate- to vigorous-intensity physical activity (MVPA) (16.3%), MVPA only (4.5%). Physical activity was quantified using standardized self-reported questionnaires which composed of the duration and frequency of physical activity.

Results: During a mean follow-up of 39.6 ± 14.0 months, 5,651 (9.7%) deaths occurred. Compared with totally sedentary individuals, those in the LPA only, LPA and MVPA, and MVPA only groups showed 26% [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.68-0.82], 27% (HR 0.73, 95% CI 0.63-0.84), and 34% (HR 0.66, 95% CI 0.54-0.79) lower all-cause mortality risk, showing an inverse relationship between physical activity intensity and mortality risk. In contrast, the LPA only, LPA and MVPA, and MVPA only groups represented a stronger inverse association with CV mortality (LPA: HR 0.76, 95% CI 0.62-0.92; LPA with MVPA: HR 0.74, 95% CI 0.55-0.999; MVPA, HR 0.57, 95% CI 0.37-0.87). Among participants performing LPA alone, participants performing less than the recommended dose of physical activity had lower all-cause mortality than those with sedentary activity (1-249 MET-min/week: HR 0.74, 95% CI 0.67-0.82, 250-499 MET-min/week: HR 0.65, 95% CI 0.59-0.72).

Conclusion: Physical activity, even low doses of LPA, was associated with reduced mortality risk in the elderly population. This study may motivate sedentary individuals to engage in any physical activity for mortality benefits.
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http://dx.doi.org/10.3389/fcvm.2022.859277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072650PMC
April 2022

Diabetes Mellitus Is an Independent Risk Factor for a Stiff Left Atrial Physiology After Catheter Ablation for Atrial Fibrillation.

Front Cardiovasc Med 2022 28;9:828478. Epub 2022 Mar 28.

Division of Cardiology, Department of Internal Medicine, Yonsei University Health System, Seoul, South Korea.

Background: Scar tissue formation after catheter ablation for atrial fibrillation (AF) may adversely affect the diastolic properties of the left atrium (LA), which can result in a stiff LA physiology in a small proportion of patients. In this study, we aimed to explore the relationship between diabetes mellitus and a stiff LA physiology after AF catheter ablation (AFCA).

Methods: A total of 1,326 patients who underwent de novo AFCA, and baseline and 1-year follow-up echocardiographies were enrolled. After 1:3 propensity score (PS) matching for age, sex, and AF type, we compared 211 patients with DM with 633 patients without DM. A stiff LA physiology was defined as estimated pulmonary arterial pressure increase of >10 mmHg and a right ventricular systolic pressure of >35 mmHg at 1-year follow-up echocardiography. Pulmonary vascular resistance (PVR) was estimated using echocardiographic parameters.

Results: Among the 844 PS-matched patients, a stiff LA physiology was observed in 32 patients (4.1%). The patients with DM showed a higher peak LA pressure ( < 0.001) and greater LA wall stress ( = 0.001) than did those without. A stiff LA physiology was independently associated with DM [Odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.02-5.59, = 0.045], empirical extra-pulmonary vein LA ablation (OR = 3.14, 95% CI 1.07-9.3, = 0.038) and the ΔPVR (OR = 1.78, 95% CI 1.37-2.31, < 0.001). The ΔPVR was independently associated with DM (β = 0.37, 95% CI 0.06-0.67, = 0.020) and a stiff LA physiology (β = 1.40, 95% CI 0.70-2.10, < 0.001). During the 38.8 ± 29.3months follow-up, the incidence of the clinical recurrence of AF was significantly higher in the patients with a stiff LA physiology than in those without (log rank = 0.032).

Conclusion: A stiff LA physiology was independently associated with DM because of the relatively small decrease in the PVR after AFCA in this population. The patients with a stiff LA physiology had worse rhythm outcomes after AFCA than those without.
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http://dx.doi.org/10.3389/fcvm.2022.828478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995895PMC
March 2022

Small extracellular vesicles derived from patients with persistent atrial fibrillation exacerbate arrhythmogenesis via miR-30a-5p.

Clin Sci (Lond) 2022 04;136(8):621-637

Department of Cardiology, Yonsei University College of Medicine, Seoul, Korea.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles that contribute to the pathogenesis of atrial fibrillation (AF). Here, we investigated the role of sEVs derived from patients with persistent AF in the pathophysiology of AF. First, we evaluated the pathological effects of sEVs derived from the peripheral blood of patients with persistent AF (AF-sEVs). AF-sEVs treatment reduced cell viability, caused abnormal Ca2+ handling, induced reactive oxygen species (ROS) production and led to increased CaMKII activation of non-paced and paced atrial cardiomyocytes. Next, we analyzed the miRNA profile of AF-sEVs to investigate which components of AF-sEVs promote arrhythmias, and we selected six miRNAs that correlated with CaMKII activation. qRT-PCR experiment identified that miR-30a-5p was significantly down-regulated in AF-sEVs, paced cardiomyocytes, and atrial tissues of patients with persistent AF. CaMKII was predicted by bioinformatics analysis as a miR-30a-5p target gene and validated by a dual luciferase reporter; hence, we evaluated the effects of miR-30a-5p on paced cardiomyocytes and validated miR-30a-5p as a pro-arrhythmic signature of AF-sEVs. Consequently, AF-sEVs-loaded with miR-30a-5p attenuated pacing-induced Ca2+-handling abnormalities, whereas AF-sEVs-loaded with anti-miR-30a-5p reversed the change in paced cardiomyocytes. Taken together, the regulation of CaMKII by miR-30a-5p revealed that miR-30a-5p is a major mediator for AF-sEVs-mediated AF pathogenesis. Accordingly, these findings suggest that sEVs derived from patients with persistent AF exacerbate arrhythmogenesis via miR-30a-5p.
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http://dx.doi.org/10.1042/CS20211141DOI Listing
April 2022

Impact of the COVID-19 Pandemic and Public Restrictions on Outcomes After Catheter Ablation of Atrial Fibrillation.

Front Cardiovasc Med 2022 24;9:836288. Epub 2022 Mar 24.

Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Background: Here we aimed to analyze changes in the outcomes of atrial fibrillation (AF) catheter ablation (AFCA) during the coronavirus disease 2019 (COVID-19) pandemic and examine the relationship between rhythm outcomes and the stringency of government social distancing measures.

Methods: We included 453 patients who underwent AFCA between May 2018 and October 2019 (pre-COVID-19 era) and 601 between November 2019 and April 2021 (COVID-19 era). The primary outcome was late recurrence, defined as any episode of AF or atrial tachycardia documented after a 3-month blanking period. A multivariable Cox regression analysis was performed to estimate the relative hazards of AF recurrence in the two eras.

Results: In the study population (24.3% women; median age, 60 years), 660 (62.6%) patients had paroxysmal AF. Among those with paroxysmal AF, the late recurrence rate was significantly lower in the COVID-19 era than in the pre-COVID-19 era [9.4% vs. 17.0%, respectively, log-rank = 0.004; adjusted hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.35-0.90] during a median follow-up of 11 months. In patients with persistent AF, the late recurrence rate did not significantly differ between the pre-COVID-19 and COVID-19 era groups (18.9% vs. 21.5%, respectively; log-rank = 0.523; adjusted HR 0.84, 95% CI 0.47-1.53) during the median follow-up of 11 months.

Conclusion: A decrease in AF recurrence after catheter ablation was observed in patients with paroxysmal AF during the COVID-19 outbreak, whereas no change was observed in those with persistent AF.
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http://dx.doi.org/10.3389/fcvm.2022.836288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987708PMC
March 2022

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry).

Front Cardiovasc Med 2022 22;9:787869. Epub 2022 Mar 22.

Department of Cardiology, College of Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.

Background: Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively).

Methods: Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61-80 bpm, 81-110 bpm, and >110 bpm.

Results: A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61-80 bpm group: hazard ratio, 0.66; 95% CI, 0.46-0.94; p = 0.021; 81-110 bpm group: hazard ratio, 0.60; 95% CI, 0.40-0.90; p = 0.013). Especially, HFpEF patients with HR 81-110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011).

Conclusion: In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.
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http://dx.doi.org/10.3389/fcvm.2022.787869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980522PMC
March 2022

Anti-atrial Fibrillation Effects of Pulmonary Vein Isolation With or Without Ablation Gaps: A Computational Modeling Study.

Front Physiol 2022 17;13:846620. Epub 2022 Mar 17.

Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Background: Although pulmonary vein isolation (PVI) gaps contribute to recurrence after atrial fibrillation (AF) catheter ablation, the mechanism is unclear. We used realistic computational human AF modeling to explore the AF wave-dynamic changes of PVI with gaps (PVI-gaps).

Methods: We included 40 patients (80% male, 61.0 ± 9.8 years old, 92.5% persistent AF) who underwent AF catheter ablation to develop our realistic computational AF model. We compared the effects of a complete PVI (CPVI) and PVI-gap (2-mm × 4) on the AF wave-dynamics by evaluating the dominant frequency (DF), spatial change of DF, maximal slope of the action potential duration restitution curve (Smax), and AF defragmentation rate (termination or change to atrial tachycardia), and tested the effects of additional virtual interventions and flecainide on ongoing AF with PVI-gaps.

Results: Compared with the baseline AF, CPVIs significantly reduced extra-PV DFs ( < 0.001), but PVI-gaps did not. COV-DFs were greater after CPVIs than PVI-gaps ( < 0.001). Neither CPVIs nor PVI-gaps changed the mean Smax. CPVIs resulted in higher AF defragmentation rates (80%) than PVI-gaps (12.5%,  < 0.001). In ongoing AF after PVI-gaps, the AF defragmentation rates after a wave-breaking gap ablation, extra-PV DF ablation, or flecainide were 60.0, 34.3, and 25.7%, respectively ( = 0.010).

Conclusion: CPVIs effectively reduced the DF, increased its spatial heterogeneity in extra-PV areas, and offered better anti-AF effects than extra-PV DF ablation or additional flecainide in PVI-gap conditions.
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http://dx.doi.org/10.3389/fphys.2022.846620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968313PMC
March 2022

Stroke and Systemic Thromboembolism according to CHADS-VASc Score in Contemporary Korean Patients with Atrial Fibrillation.

Yonsei Med J 2022 Apr;63(4):317-324

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.

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 CHADS-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 [CHADS-VASc score 0 (male) or 1 (female)], and 0.88 in high-risk patients (CHADS-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 CHADS-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.

Study Registration: ClinicalTrials.gov (NCT02786095).
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http://dx.doi.org/10.3349/ymj.2022.63.4.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965433PMC
April 2022

Sex difference in atrial fibrillation recurrence after catheter ablation and antiarrhythmic drugs.

Heart 2022 Mar 24. Epub 2022 Mar 24.

Division of Cardiology, Yonsei University Health System, Seoul, Korea (the Republic of)

Objective: The risk of recurrence after atrial fibrillation (AF) catheter ablation (AFCA) is higher in women than in men. However, it is unknown whether a sex difference exists in antiarrhythmic drug (AAD) responsiveness among patients with recurrence.

Methods: Among 2999 consecutive patients (26.5% women, 58.3±10.9 years old, 68.1% paroxysmal AF) who underwent de novo AFCA, we compared and evaluated the sex differences in rhythm outcome in 1094 patients with recurrence and in 788 patients who subsequently underwent rhythm control with AAD.

Results: During a follow-up of 48.2±34.9 months, 1094 patients (36.5%) had AF recurrence after AFCA, and 508 of 788 patients (64.5%) had AF recurrence under AAD. Although the rhythm outcome of a de novo AFCA was worse (log-rank p=0.041, HR 1.28, 95% CI 1.02 to 1.59), p=0.031) in women, AAD response after postprocedural recurrences was better in women than in men (log-rank p=0.003, HR 0.75, 95% CI 0.59 to 0.95, p=0.022), especially in women older than 60 years old (log-rank p=0.003). In 249 patients who underwent repeat procedure after AAD use, the pulmonary vein (PV) reconnection rate (62.7% vs 76.8%, p=0.048) was lower in women than in men but not the existence of extra-PV trigger (37.8% vs 25.4%, p=0.169).

Conclusions: Although women showed worse rhythm outcomes than men after AFCA, the post-AFCA AAD response was better in elderly women than in men.

Trial Registration Number: NCT02138695.
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http://dx.doi.org/10.1136/heartjnl-2021-320601DOI Listing
March 2022

Restitution Slope Affects the Outcome of Dominant Frequency Ablation in Persistent Atrial Fibrillation: CUVIA-AF2 Analysis Based on Computational Modeling Study.

Front Cardiovasc Med 2022 3;9:838646. Epub 2022 Mar 3.

Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea.

Introduction: Although the dominant frequency (DF) localizes the reentrant drivers and the maximal slope of the action potential duration (APD) restitution curve (Smax) reflects the tendency of the wave-break, their interaction has never been studied. We hypothesized that DF ablation has different effects on atrial fibrillation (AF) depending on Smax.

Methods: We studied the DF and Smax in 25 realistic human persistent AF model samples (68% male, 60 ± 10 years old). Virtual AF was induced by ramp pacing measuring Smax, followed by spatiotemporal DF evaluation for 34 s. We assessed the DF ablation effect depending on Smax in both computational modeling and a previous clinical trial, CUVIA-AF (170 patients with persistent AF, 70.6% male, 60 ± 11 years old).

Results: Mean DF had an inverse relationship with Smax regardless of AF acquisition timing ( < 0.001). Virtual DF ablations increased the defragmentation rate compared to pulmonary vein isolation (PVI) alone ( = 0.015), especially at Smax <1 (61.5 vs. 7.7%, = 0.011). In post-DF ablation defragmentation episodes, DF was significantly higher ( = 0.002), and Smax was lower ( = 0.003) than in episodes without defragmentation. In the analysis of CUVIA-AF2, we replicated the inverse relationship between Smax and DF ( = -0.47, < 0.001), and we observed better rhythm outcomes of clinical DF ablations in addition to a PVI than of empirical PVI at Smax <1 [hazard ratio 0.45, 95% CI (0.22-0.89), = 0.022; log-rank = 0.021] but not at ≥ 1 (log-rank = 0.177).

Conclusion: We found an inverse relationship between DF and Smax and the outcome of DF ablation after PVI was superior at the condition with Smax <1 in both and clinical trials.
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http://dx.doi.org/10.3389/fcvm.2022.838646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927985PMC
March 2022

Association of Physical Activity With Primary Cardiac Arrest Risk in the General Population: A Nationwide Cohort Study of the Dose-Response Relationship.

Mayo Clin Proc 2022 04 11;97(4):716-729. Epub 2022 Mar 11.

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul. Electronic address:

Objective: To quantify the dose-response relationship between moderate to vigorous physical activity and primary cardiac arrest (PCA).

Patients And Methods: There were 504,840 participants older than 18 years who underwent the Korean National Health Screening Program, including a self-administered questionnaire for physical activity from January 1, 2009, through December 31, 2014. Physical activity levels were converted into metabolic equivalent tasks (METs) per week and categorized to correspond with multiples of public health recommendations. We evaluated the quantitative and categorical dose-response relationship between physical activity and PCA.

Results: A curvilinear dose-response relationship between physical activity and PCA was observed; the benefits started at two-thirds (5 MET-hour/week) of the United States and World Health Organization guidelines-recommended minimum (7.5 MET-hour/week) and continued to 5 times (40 MET-hour/week) the recommended minimum (P nonlinearity <.001). The largest benefit was noted at a level of 2 to 3 times the recommended minimum (hazard ratio, 0.6; 95% CI, 0.4 to 0.8). In addition, there was no evidence of an increased PCA risk at a level more than 5 times the recommended minimum (hazard ratio, 0.7; 95% CI, 0.5 to 1.1). These associations were consistent regardless of age, sex, body mass index, comorbid conditions, and estimated 10-year risk for cardiovascular disease.

Conclusion: The beneficial effect of physical activity on PCA started at two-thirds of the recommended minimum and continued to 5 times the recommended minimum. No excess risk for PCA was present among individuals with activity levels more than 5 times the recommended minimum regardless of cardiovascular disease or lifestyle risk factor presence.
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http://dx.doi.org/10.1016/j.mayocp.2021.10.003DOI Listing
April 2022

Prognostic Cardiac Magnetic Resonance Markers of Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy for Predicting Heart Failure Outcomes.

J Am Heart Assoc 2022 03 9;11(6):e023167. Epub 2022 Mar 9.

Division of Cardiology Department of Internal medicine Severance Cardiovascular HospitalYonsei University College of Medicine Seoul South Korea.

Background Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic resonance (CMR) with clinical outcomes including heart failure (HF)-related events in ACM. Methods and Results We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF-related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow-up of 34 months, there were 13 (22%) HF-related events, and 20 (30%) ventricular tachycardia events. Kaplan-Meier survival analysis revealed that HF-related events occurred only in patients with LV LGE (+) (versus LV LGE (-), log-rank =0.006), and the events were not significantly different regarding right ventricular LGE (log-rank >0.999). When categorized by median value for each mapping parameter, HF-related events occurred more in patients with higher native T1 (versus lower native T1, log-rank =0.002), and higher T2 (versus lower T2, log-rank =0.002), higher extracellular volume (versus lower extracellular volume, log-rank =0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers. Conclusions LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF-related event risk in patients with ACM.
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http://dx.doi.org/10.1161/JAHA.121.023167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075293PMC
March 2022

Machine Learning-Predicted Progression to Permanent Atrial Fibrillation After Catheter Ablation.

Front Cardiovasc Med 2022 16;9:813914. Epub 2022 Feb 16.

Division of Cardiology, Yonsei University Health System, Seoul, South Korea.

Introduction: We developed a prediction model for atrial fibrillation (AF) progression and tested whether machine learning (ML) could reproduce the prediction power in an independent cohort using pre-procedural non-invasive variables alone.

Methods: Cohort 1 included 1,214 patients and cohort 2, 658, and all underwent AF catheter ablation (AFCA). AF progression to permanent AF was defined as sustained AF despite repeat AFCA or cardioversion under antiarrhythmic drugs. We developed a risk stratification model for AF progression (STAAR score) and stratified cohort 1 into three groups. We also developed an ML-prediction model to classify three STAAR risk groups without invasive parameters and validated the risk score in cohort 2.

Results: The STAAR score consisted of a stroke (2 points, = 0.003), persistent AF (1 point, = 0.049), left atrial (LA) dimension ≥43 mm (1 point, = 0.010), LA voltage <1.109 mV (2 points, = 0.004), and PR interval ≥196 ms (1 point, = 0.001), based on multivariate Cox analyses, and it had a good discriminative power for progression to permanent AF [area under curve (AUC) 0.796, 95% confidence interval (CI): 0.753-0.838]. The ML prediction model calculated the risk for AF progression without invasive variables and achieved excellent risk stratification: AUC 0.935 for low-risk groups (score = 0), AUC 0.855 for intermediate-risk groups (score 1-3), and AUC 0.965 for high-risk groups (score ≥ 4) in cohort 1. The ML model successfully predicted the high-risk group for AF progression in cohort 2 (log-rank < 0.001).

Conclusions: The ML-prediction model successfully classified the high-risk patients who will progress to permanent AF after AFCA without invasive variables but has a limited discrimination power for the intermediate-risk group.
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http://dx.doi.org/10.3389/fcvm.2022.813914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890475PMC
February 2022

2021 Asia Pacific Heart Rhythm Society (APHRS) practice guidance on atrial fibrillation screening.

J Arrhythm 2022 Feb 28;38(1):31-49. Epub 2021 Dec 28.

Charles Perkins Centre The University of Sydney Sydney Australia.

In this paper, the Asia Pacific Heart Rhythm Society (APHRS) sought to provide practice guidance on AF screening based on recent evidence, with specific considerations relevant to the Asia-Pacific region. A key recommendation is opportunistic screening for people aged ≥65 years (all countries), with systematic screening to be considered for people aged ≥75 years or who have additional risk factors (all countries).
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http://dx.doi.org/10.1002/joa3.12669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851593PMC
February 2022

Ischemic Stroke in Non-Gender-Related CHADS-VA Score 0~1 Is Associated With HFPEF Score Among the Patients With Atrial Fibrillation.

Front Cardiovasc Med 2021 8;8:791112. Epub 2022 Feb 8.

Division of Cardiology, Yonsei University Health System, Seoul, South Korea.

Background: Ischemic strokes (ISs) can appear even in non-gender-related CHADS-VA scores 0~1 patients with atrial fibrillation (AF). We explored the determinants associated with IS development among the patients with non-gender-related CHADS-VA score 0~1 AF.

Methods And Results: In this single-center retrospective registry data for AF catheter ablation (AFCA), we included 1,353 patients with AF (24.7% female, median age 56 years, and paroxysmal AF 72.6%) who had non-gender-related CHADS-VA score 0~1, normal left ventricular (LV) systolic function, and available HFPEF score. Among those patients, 113 experienced IS despite a non-gender-related CHADS-VA score of 0~1. All included patients underwent AFCA, and we evaluated the associated factors with IS in non-gender-related CHADS-VA score 0~1 AF. Patients with ISs in this study had a lower estimated glomerular filtration rate (eGFR) ( < 0.001) and LV ejection fraction (LVEF; = 0.017), larger LA diameter ( < 0.001), reduced LA appendage peak velocity ( < 0.001), and a higher baseline HFPEF score ( = 0.018) relative to those without ISs. Age [odds ratio (OR) 1.11 (1.07-1.17), < 0.001, Model 1] and HFPEF score as continuous [ 1.31 (1.03-1.67), = 0.028, Model 2] variable were independently associated with ISs by multivariate analysis. Moreover, the eGFR was independently associated with IS at low CHADS-VA scores in both Models 1 and 2. AF recurrence was significantly higher in patients with IS (log-rank < 0.001) but not in those with high HFPEF scores (log-rank = 0.079), respectively.

Conclusions: Among the patients with normal LVEF and non-gender-related CHADS-VA score 0~1 AF, the high HFPEF score, and increasing age were independently associated with IS development (ClinicalTrials.gov Identifier: NCT02138695).
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http://dx.doi.org/10.3389/fcvm.2021.791112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862762PMC
February 2022

Impact of Physical Activity on All-Cause Mortality According to Specific Cardiovascular Disease.

Front Cardiovasc Med 2022 4;9:811058. Epub 2022 Feb 4.

Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Background: Patients with cardiovascular disease (CVD) tend to have higher mortality rates and reduced physical activity (PA). We aimed to evaluate the effect of PA on mortality in older adults with specific CVD.

Methods: We enrolled 68,223 participants ( = 23,871 with CVD, = 44,352 without CVD) aged ≥65 years with available physical activity data between 2005 and 2012 from the Korean National Health Insurance Service of Korea-Senior database. CVD was defined as a history of ischemic stroke, transient ischemic attack, heart failure, myocardial infarction, and peripheral artery disease.

Results: Patients with CVD were older than those without CVD. Compared with the sedentary group, the physically active groups with and without CVD had a lower incidence and risk of all-cause death during a median follow up period of 42 (interquartile range 30-51) months. A 500 metabolic equivalent task-min/week increase in PA resulted in an 11% and 16% reduction in the risk of mortality in the non-CVD and CVD groups, respectively. With regard to specific CVDs, the risk of mortality progressively reduced with increasing PA in patients with heart failure or myocardial infarction. However, the reduction reached a plateau in patients with stroke or peripheral artery disease, but was significantly greater in patients with stroke (20% vs. without stoke, 11%, P = 0.006) or heart failure (13% vs. without heart failure, 11%; P = 0.045).

Conclusions: PA was associated with a reduced risk of all-cause mortality in older adults with and without CVD. The benefits of PA in patients with CVD, especially patients with stroke or heart failure, were greater than those without.
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http://dx.doi.org/10.3389/fcvm.2022.811058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855984PMC
February 2022

Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation.

Stroke 2022 06 3;53(6):1873-1882. Epub 2022 Feb 3.

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (D.K., E.J., H.T.Y., T.-H.K., J.-S.U., J.-Y.K., H.-N.P., M.-H.L.' B.J.).

Background: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF.

Methods: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately.

Results: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHADS-VASc score of at least 3.

Conclusions: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.
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http://dx.doi.org/10.1161/STROKEAHA.121.036757DOI Listing
June 2022

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Circulation 2022 02 31;145(5):392-409. Epub 2022 Jan 31.

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø (M.L.L.).

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055018DOI Listing
February 2022

Genome-wide association study-based prediction of atrial fibrillation using artificial intelligence.

Open Heart 2022 01;9(1)

Cardiology, Yonsei University Health System, Seodaemun-gu, Seoul, Korea (the Republic of)

Objective: We previously reported early-onset atrial fibrillation (AF) associated genetic loci among a Korean population. We explored whether the AF-associated single-nucleotide polymorphisms (SNPs) selected from the Genome-Wide Association Study (GWAS) of an external large cohort has a prediction power for AF in Korean population through a convolutional neural network (CNN).

Methods: This study included 6358 subjects (872 cases, 5486 controls) from the Korean population GWAS data. We extracted the lists of SNPs at each p value threshold of the association statistics from three different previously reported ethnical-specific GWASs. The Korean GWAS data were divided into training (64%), validation (16%) and test (20%) sets, and a stratified K-fold cross-validation was performed and repeated five times after data shuffling.

Results: The CNN-GWAS predictive power for AF had an area under the curve (AUC) of 0.78±0.01 based on the Japanese GWAS, AUC of 0.79±0.01 based on the European GWAS, and AUC of 0.82±0.01 based on the multiethnic GWAS, respectively. Gradient-weighted class activation mapping assigned high saliency scores for AF associated SNPs, and the obtained the highest saliency score. The CNN-GWAS did not show AF prediction power by SNPs with non-significant p value subset (AUC 0.56±0.01) despite larger numbers of SNPs. The CNN-GWAS had no prediction power for odd-even registration numbers (AUC 0.51±0.01).

Conclusions: AF can be predicted by genetic information alone with moderate accuracy. The CNN-GWAS can be a robust and useful tool for detecting polygenic diseases by capturing the cumulative effects and genetic interactions of moderately associated but statistically significant SNPs.

Trial Registration Number: NCT02138695.
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http://dx.doi.org/10.1136/openhrt-2021-001898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796259PMC
January 2022
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