Evaluation of ventricular pacing suppression algorithms in dual chamber pacemaker: Results of "LEADER" study.

Background: There is limited research on the intra-individual efficacy of ventricular pacing minimization algorithms developed by Biotronik-the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual-chamber pacemaker. Methods: The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3-month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow-up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results: Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion: The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Atrial fibrillation and risk of sudden cardiac arrest in young adults.

AIMS: Evidence of an association between atrial fibrillation (AF) and sudden cardiac arrest (SCA) in young adults is limited. In this study, we aim to evaluate this association in a general population aged between 20 and 39 years. METHODS AND RESULTS: Young adults who underwent health check-ups between 2009 and 2012 were screened from a nationwide healthcare database in South Korea. A history of AF diagnosis before the health check-ups was identified based on the relevant International Classification of Diseases, 10th edition codes reported in the database. Associations between an established diagnosis of AF and the risk of SCA during follow-up were examined. A total of 6 345 162 young people were analysed with a mean follow-up duration of 9.4 years. The mean age was 30.9 ± 5.0 years, and 5875 (0.09%) individuals were diagnosed with AF. During follow-up, SCA occurred in 5352 (0.08%) individuals, and the crude incidence was 0.56 and 0.09 events per 1000 person-years for participants with and without AF, respectively. Individuals with AF had a 3.0-fold higher risk in a multivariate model adjusted for age, sex, lifestyle, anthropometric data, and medical comorbidities (adjusted hazard ratio 2.96, 95% confidence interval 1.99-4.41, P < 0.001). Both incident and prevalent AFs were associated with an increased risk of SCA, with no significant differences between the two groups. CONCLUSION: Atrial fibrillation was associated with a significantly higher risk of SCA developing in healthy young adults. Whether the rate or rhythm control influences the risk of SCA in young patients with AF remains to be examined.

Modulating the Thermoresponsive Characteristics of PLGA-PEG-PLGA Hydrogels via Manipulation of PLGA Monomer Sequences.

Hydrogels are promising materials for biomedical applications, particularly in drug delivery and tissue engineering. This study highlights thermoresponsive hydrogels, specifically poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA triblock copolymers, and introduces a feed rate-controlled polymerization (FRCP) method. By utilizing an organic catalyst and regulating the monomer feed rate, the sequence distribution of PLGA within the triblock copolymer is controlled. Various analyses, including 13C NMR and rheological measurements, were conducted to investigate the impact of sequence distribution. Results show that altering sequence distribution significantly influences the sol-gel transition, hydrophobicity-hydrophilicity balance, and drug release profile. Increased sequence uniformity lowers the glass transition temperature, raises the sol-gel transition temperature due to enhanced hydrophilicity, and promotes a more uniform drug (curcumin) distribution within the PLGA domain, resulting in a slower release rate. This study emphasizes the importance of PLGA sequence distribution in biomedical applications and the potential of FRCP to tailor thermoresponsive hydrogels for biomedical advancements.

Association of fatty liver index with sudden cardiac arrest in young adults.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) contributes to cardiovascular events. Therefore, we aimed to identify the association of MASLD, as indicated by the fatty liver index (FLI), on sudden cardiac arrest (SCA) in young adults. METHODS: We analyzed data from adults aged 20-39 years, who underwent health examinations between 2009 and 2012, sourced from the Korean National Health Insurance Service database. The presence of MASLD was determined using the FLI, which was calculated based on an individual's body mass index, waist circumference, gamma-glutamyl transferase and triglyceride levels. The primary outcome was the occurrence of SCA during the follow-up period, until December 2020. RESULTS: Of the total 5,398,082 individuals analyzed, 4,021,056 (74.5 %) had a normal FLI (FLI <30), 837,943 (15.5 %) were within the intermediate range (30-60), and 539,083 (10.0 %) demonstrated a high FLI (≥60). Individuals with a high FLI were older, and comprised a higher proportion of men with hypertension, diabetes mellitus, dyslipidemia, heart failure, and myocardial infarction. During follow-up, SCA occurred in 4255 individuals (0.08 %). The group with a high FLI exhibited an increased incidence (incidence rate, 0.19) and elevated risk of SCA (hazard ratio, 3.04). Adjustment of covariates revealed a 55 % increased risk of SCA in the high FLI group (adjusted hazard ratio 1.55, 95 % confidence interval 1.41-1.70, p < 0.001). Moreover, the influence of a high FLI on SCA risk was more pronounced in women compared to men. Additionally, an increase in relevant cardiometabolic conditions was associated with an elevated risk of SCA. CONCLUSIONS: Among young adults, a high risk of MASLD, as indicated by the FLI, revealed an increased risk of SCA. Furthermore, the association of FLI with the risk of SCA varied by sex and cardiometabolic conditions.

Long-term clinical impact of early recurrence of atrial tachyarrhythmia after cryoballoon ablation in patients with atrial fibrillation.

INTRODUCTION: The impact of early recurrence of atrial tachyarrhythmia (ERAT) within the 90-day blanking period on long-term outcomes in atrial fibrillation (AF) patients undergoing cryoballoon ablation (CBA) is controversial. This study aimed to assess the relationship between ERAT and late recurrence of atrial tachyarrhythmia (LRAT) post-CBA. METHODS: Utilizing data from a multicenter registry in Korea (May 2018 to June 2022), we analyzed the presence and timing of ERAT (<30, 30-60, and 60-90 days) and its association with LRAT risk after CBA. LRAT was defined as any recurrence of AF, atrial flutter, or atrial tachycardia lasting more than 30 s beyond the 90 days. RESULTS: Out of 2636 patients, 745 (28.2%) experienced ERAT post-CBA. Over an average follow-up period of 21.2 ± 10.3 months, LRAT was observed in 874 (33.1%) patients. Patients with ERAT had significantly lower 1-year LRAT freedom compared to those without ERAT (42.6% vs. 85.5%, p < .001). Multivariate analysis identified ERAT as a potential predictor of LRAT, with a hazard ratio (HR) of 3.98 (95% confidence interval [CI], 3.47-4.57). Significant associations were noted across all examined time frames (HR, 3.84; 95% CI, 3.32-4.45 in <30 days, HR, 5.53; 95% CI, 4.13-7.42 in 30-60 days, and HR, 4.29; 95% CI, 3.12-5.89 in 60-90 days). This finding was consistently observed across all types of AF. CONCLUSION: ERAT during the 90-day blanking period strongly predicts LRAT in AF patients undergoing CBA, indicating a need to reconsider the clinical significance of this period.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

Association of Antiarrhythmic Drug Therapy With Syncope and Pacemaker Implantation in Patients With Atrial Fibrillation.

BACKGROUND: Early rhythm control therapy mainly with antiarrhythmic drugs (AADs) for new-onset atrial fibrillation (AF) reduces major adverse cardiovascular events. However, negative dromotropic effects of AADs via ion channel blocking may cause bradyarrhythmias. OBJECTIVES: This study aimed to evaluate the association between AAD use and the risk of pacemaker implantation or syncope in patients with new-onset AF receiving early rhythm control therapy with AADs. METHODS: This study was based on data from the Korean National Health Insurance Service system. We screened all new-onset AF diagnoses that occurred from 2013 to 2019 and identified patients who were prescribed AADs within 1 year of AF diagnosis. The risk of pacemaker implantation or syncope was compared between AAD users and nonusers. RESULTS: A total of 770,977 new-onset AF cases were identified and 142,141 patients were prescribed AADs. After multivariate adjustment, use of AADs was associated with 3.5-, 2.0-, and 5.0-fold increased risk of pacemaker implantation or syncope, syncope, and pacemaker implantation, respectively. Propensity score-matched analysis revealed similar results, demonstrating a significant association between AAD use and the risk of pacemaker implantation or syncope. This association was consistent across various subgroups. Women were more susceptible to adverse effects of AADs than men. CONCLUSIONS: This study showed an association between AADs and risk of pacemaker implantation or syncope, a consistent finding across various subgroups. Precise evaluation of such risk should be undertaken before prescription of AADs.

Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

BACKGROUND: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION: This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.

Alcohol and the risk of all-cause death, atrial fibrillation, ventricular arrhythmia, and sudden cardiac arrest.

The risk of having atrial fibrillation (AF) is associated with alcohol intake. However, it is not clear whether sudden cardiac arrest (SCA) and ventricular arrhythmia (VA) including ventricular tachycardia, flutter, or fibrillation have similar associations with alcohol. We aimed to evaluate the association of alcohol intake with all-cause death, new-onset AF, VA, and SCA using single cohort with a sufficient sample size. A total of 3,990,373 people without a prior history of AF, VAs, or SCA was enrolled in this study based on nationwide health check-up in 2009. We classified the participants into four groups according to weekly alcohol consumption, and evaluated the association of alcohol consumption with each outcome. We observed a significant association between mild (hazard ratio [HR] = 0.826; 95% confidence interval [CI] = 0.815-0.838) to moderate (HR = 0.930; 95% CI = 0.912-0.947) drinking with decreased risk of all-cause mortality. However heavy drinking (HR = 1.108; 95% CI = 1.087-1.129) was associated with increased all-cause death. The risk of new-onset AF was significantly associated with moderate (HR = 1.129; 95% CI = 1.097-1.161) and heavy (HR = 1.298; 95% CI = 1.261-1.337) drinking. However, the risk of SCA showed negative association with all degrees of alcohol intake: 20% (HR = 0.803; 95% CI = 0.769-0.839), 15% (HR = 0.853; 95% CI = 0.806-0.902), and 8% (HR = 0.918; 95% CI = 0.866-0.974) lower risk for mild, moderate, and heavy drinkers, respectively. Mild drinking was associated with reduced risk of VA with moderate and heavy drinking having no associations. In conclusion, the association between alcohol and various outcomes in this study were heterogeneous. Alcohol might have different influences on various cardiac disorders.

Temporal elevation of blood pressure is associated with increased risk of sudden cardiac arrest.

Hypertension is a known risk factor for sudden cardiac arrest (SCA). However, the role of temporal changes in blood pressure on the risk of SCA is not fully understood. This study was conducted to determine whether a temporal increase or decrease in blood pressure is associated with the risk of SCA. This study was based on nationwide healthcare insurance data. Individuals who underwent nationwide health check-ups in 2009 and 2011 were analyzed. A total of 2,801,153 individuals were evaluated for 8100 SCA events during the 17, 740, 420 person-years of follow-up. In a multivariate analysis, there were linear association between the degree of temporal elevation of systolic blood pressure (SBP) and the risk of SCA: (i) adjusted-hazard ratio (HR) 1.11 (p = 0.001) in 10 ≤ ΔSBP < 20 (mmHg) group; (ii) adjusted-HR 1.40 (p < 0.001) in 20 ≤ ΔSBP < 40 group; and (iii) adjusted-HR 1.88 (p < 0.001) in 40 ≤ ΔSBP group as compared with the reference group (- 10 ≤ ΔSBP < 10). Temporal increase in diastolic blood pressure (DBP) also a showed significant association with SCA risk with the highest risk observed in ∆DBP ≥ 25 group (adjusted-HR 1.61; p < 0.001) as compared with the reference group (- 5 ≤ ΔDBP < 5). The association between SBP and SCA was not affected by age, sex, presence of diabetes mellitus, or baseline SBP. In conclusion, a temporal increase in blood pressure was significantly associated with the occurrence of SCA, and this association was consistent across all subgroups. However, a temporary decrease in blood pressure does not reduce the risk of SCA. Prevention of elevated blood pressure may play an important role in preventing SCA.

Performance and Physician Experience of INGEVITY+ Active Fixation Leads: Prospective INGEVITY+ Lead Clinical Study in Korea.

Background: Boston Scientific INGEVITY+ pacing lead (Boston Scientific, Marlborough, MA, USA) has been upgraded to INGEVITY. The performance of the INGEVITY+ pacing lead has not yet been reported. This study aimed to evaluate the short- and long-term safety, effectiveness, and handling experience of INGEVITY+ leads. Methods: Consecutive patients were included from 9 institutions in Korea, where 400 leads (200 right ventricular active fixation leads and 200 right atrial active fixation leads) were implanted or attempted in 200 subjects. Results: During the implantation, only one patient required a lead change because of lead screw failure. The handling questionnaires of the lead received very positive feedback with 88% of operators agreeing that it is easy for leads to pass through small vessels or vessels with multiple leads. At the 3-month follow-up, 95.7% of RA leads and 99.5% of RV leads had pacing thresholds less than 1.5 V. A total of 92.4% of atrial leads had amplitudes greater than 1.5 mV, and 96.5% of ventricular leads had sensing amplitudes greater than 5 mV at 3 months. A total of 99.8% had impedances between 300 and 1,300 ohms. The lead-related complication-free rate for all leads during follow-up was 100%, and the overall rates of lead dislodgment, perforation, and pericardial effusion were all 0.0%. Conclusions: The INGEVITY+ pacing lead exhibited exceptional clinical performance, with a high complication-free rate throughout the 3-month follow-up period. In addition, the lead displayed excellent electrical characteristics, and the lead-handling experience was reported to be very good.

Association of temporal change in body mass index with sudden cardiac arrest in diabetes mellitus.

BACKGROUND: Underweight imposes significant burden on cardiovascular outcomes in patients with diabetes mellitus. However, less is known about the impact of serial change in body weight status measured as body mass index (BMI) on the risk of sudden cardiac arrest (SCA). This study investigated the association between SCA and temporal change in BMI among patients with diabetes mellitus. METHODS: Based on Korean National Health Insurance Service database, participants with diabetes mellitus who underwent health examination between 2009 and 2012 and had prior health examination data (four years ago, 2005-2008) were retrospectively analyzed. BMI was measured at baseline (2005-2008) and 4-year follow-up health examination (2009-2012). Patients were classified in four groups according to the body weight status and its temporal change: sustained non-underweight, sustained underweight, previous underweight, and newly developed underweight. Primary outcome was defined as occurrence of SCA. RESULTS: A total of 1,355,746 patients with diabetes mellitus were included for analysis, and SCA occurred in 12,554 cases. SCA was most common in newly developed underweight (incidence rate = 4.45 per 1,000 person-years), followed by sustained underweight (incidence rate = 3.90), previous underweight (incidence rate = 3.03), and sustained non-underweight (incidence rate = 1.34). Adjustment of covariates resulted highest risk of SCA in sustained underweight (adjusted hazard ratio = 2.60, 95% confidence interval [2.25-3.00], sustained non-underweight as a reference), followed by newly developed underweight (2.42, [2.15-2.74]), and previous underweight (2.12, [1.77-2.53]). CONCLUSIONS: In diabetes mellitus, sustained underweight as well as decrease in body weight during 4-year follow-up imposes substantial risk on SCA. Recovery from underweight over time had relatively lower, but yet increased risk of SCA. Both underweight and dynamic decrease in BMI can be associated with increased risk of SCA.

The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Impact of pulmonary artery pressure on recurrence after catheter ablation in patients with atrial fibrillation.

Background: The pulmonary veins play a major role in the pathogenesis of atrial fibrillation (AF) and may be affected by cardiac remodeling due to pulmonary vascular dysfunction. It remains to be determined whether pulmonary artery pressure (PAP) is associated with the recurrence of AF after radiofrequency catheter ablation (RFCA). Methods: Consecutive patients with paroxysmal and persistent AF who underwent RFCA, including wide circumferential pulmonary vein isolation, were analyzed. Systolic PAP was measured using transthoracic echocardiography, and clinical outcomes were compared between patients with PAP <35 mmHg and those with PAP ≥35 mmHg. Results: Among 2,379 patients (mean age 56.7 ± 10.6 years, 77% men), 1,893 (79.6%) had PAP <35 mmHg and 486 (20.4%) had PAP ≥35 mmHg. During the median follow-up of 25.4 months, in patients with paroxysmal AF (n = 1,294), the recurrence rate was significantly greater in the PAP ≥35 mmHg group than in the PAP <35 mmHg group (35.1% vs. 23.8%, log-rank p = 0.008). However, in patients with persistent AF (n = 1,085), the recurrence rate was not significantly different between the two groups (52.2% vs. 49.7%, log-rank p = 0.409). Multivariate analysis using Cox regression showed that PAP ≥35 mmHg was significantly associated with clinical recurrence (hazard ratio 1.19, 95% confidence interval 1.02-1.40, p = 0.027). Conclusion: This study showed that a higher PAP was associated with an increased risk of recurrence after RFCA in patients with paroxysmal AF, suggesting a mechanism by which a pulmonary vascular pathology may cause impairment of the pulmonary veins and remodeling of the left atrium.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands.

BACKGROUND AND OBJECTIVES: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. METHODS: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. RESULTS: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). CONCLUSIONS: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Rhythm Control and Cardiovascular or Cerebrovascular Outcomes in Patients with Atrial Fibrillation: A Study of the CODE-AF Registry.

BACKGROUND: It is not clear whether the data regarding rhythm control during atrial fibrillation (AF) contained in AF registries is prognostically significant. Thus, this study investigated the relationship between rhythm control and cardiovascular outcomes in patients in contemporary AF registries. METHODS: This study was conducted using data from 6670 patients with AF receiving oral anticoagulation in the CODE-AF registry. We used propensity overlap weighting to account for differences in baseline characteristics between the rhythm control and rate control groups. The primary outcome was a composite of the rate of death due to cardiovascular causes, stroke, acute coronary syndrome, and heart failure. The secondary outcomes were individual components of the primary outcome. RESULTS: In the CODE-AF registry, 5407 (81.1%) patients were enrolled three months after AF diagnosis. During a median follow-up period of 973 days (interquartile range: 755-1089 days), a primary outcome event occurred in 72 patients in the rhythm control group (1.4 events per 100 person-years) and in 211 patients in the rate control group (1.8 events per 100 person-years). However, after overlap weighting, the incidence rates were 1.4 and 1.5 events per 100 person-years, respectively. No significant difference was found in either the primary outcome (weighted HR: 0.87; 95% CI: 0.66-1.17; p = 0.363) or secondary outcomes between the rhythm control and rate control groups. CONCLUSION: In a prospective AF registry in which most of the population was enrolled at least three months after AF diagnosis, no difference in the risk of cardiovascular or cerebrovascular outcomes was found between the rhythm control and rate control groups, suggesting the early rhythm control should be considered to improve the outcome of patients.