European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

BACKGROUND: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. METHODS AND RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

The Effects of Radiofrequency Catheter Ablation for Atrial Fibrillation on Right Ventricular Function.

BACKGROUND AND OBJECTIVE: The effects of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) on right ventricular (RV) function are not well known. METHODS: Patients who underwent RFCA for AF and underwent pre- and post-procedural echocardiography were enrolled consecutively. Fractional area change (FAC), RV free-wall longitudinal strain (RVFWSL), and RV 4-chamber strain including the ventricular septum (RV4CSL) were measured. Changes in FAC, RVFWSL, and RV4CSL before and after RFCA were compared among paroxysmal AF (PAF), persistent AF (PeAF), and long-standing persistent AF (LSPeAF) groups. RESULTS: A total of 164 participants (74 PAF, 47 PeAF, and 43 LSPeAF; age, 60.8 ± 9.8 years; men, 74.4%) was enrolled. The patients with PeAF and LSPeAF had worse RV4CSL (p<0.001) and RVFWSL (p<0.001) than those with PAF and reference values. Improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared with the PAF and LSPeAF groups (ΔRV4CSL, 8.4% [5.1, 11.6] in PeAF vs. 1.0% [-1.0, 4.1] in PAF, 1.9% [-0.2, 4.4] in LSPeAF, p<0.001; ΔRVFWSL, 9.0% [6.9, 11.5] in PeAF vs. 0.9% [-1.4, 4.9] in PAF, 1.0% [-1.0, 3.6] in LSPeAF, p<0.001). In patients without recurrence, improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared to the LSPeAF group. CONCLUSIONS: RV systolic function is more impaired in patients with PeAF and LSPeAF than in those with PAF. RV systolic function is more improved after RFCA in patients with PeAF than in those with PAF or LSPeAF.

Using computed tomogram atrial myocardial thickness maps in high-power short-duration radiofrequency pulmonary vein isolation: UTMOST AF.

Background: High-power short-duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods: We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT-guided CPVI (WT, n = 108) and conventional CPVI (control, n = 104). Both groups used an open irrigated-tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4-2.1 mm, and 11 s at <1.4 mm) according to the computed tomogram-myocardial thickness color map. Results: After a mean follow-up of 13.4 ± 7.0 months, the WT and control groups showed no significant difference regarding clinical recurrence rate (13.9% vs. 5.8%, respectively; p = .061) and major complication rate (4.6% vs. 3.8%, respectively; p > .999). The total procedure time, cardioversion rate, and post-procedural AAD prescription rates did not significantly differ between the groups. Conclusions: The LAWT-guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50-60 W-HPSD CPVI in patients with PAF.

Association of extra-pulmonary vein triggers with low-voltage area and clinical recurrence in patients with atrial fibrillation undergoing catheter ablation.

Background and Objectives: Although extra-pulmonary vein (PV) triggers (ExPVTs) play a role in atrial fibrillation (AF) recurrence after catheter ablation (AFCA), the mechanism is unknown. We explored whether the locations of ExPVTs were associated with low-voltage scar areas (LVAs). Methods: Among 2255 consecutive patients who underwent a de novo AFCA, 1696 (male 72.1%, median 60 years old, paroxysmal 64.7%) were included who underwent isoproterenol provocation and voltage mapping of the left atrium (LA) during their procedures. We investigated the associations between ExPVTs and their mean LA voltage and colocalization of ExPVTs within LVAs (<0.2 mV). Results: We observed ExPVTs in 181 (10.7%) patients (60 in the LA, 99 in the right atrium [RA], 16 biatrial, and 6 unmappable). A lower mean LA voltage was independently associated with the existence of ExPVTs (OR 0.77 per 1 SD mV increase, 95% CI 0.60-0.99, p = .039). Among 76 patients who had ExPVTs[LA], 43 (56.6%) had ExPVTs within LVAs. During a median of a 42-month follow-up, patients with ExPVTs had a higher AF recurrence than those without (HR 1.87, 95% CI 1.48-2.37, Log-rank p < .001), but colocalization of ExPVTs and LVAs (Log-rank p = .544) and the anatomical location of ExPVTs (Log-rank p = .084) did not affect the rhythm outcome. Conclusions: The presence of ExPVTs was associated with low LA voltage and poor rhythm outcome post-AFCA, but the colocalization of ExPVTs and LVA in LA did not affect rhythm outcome.

Anti- and pro-fibrillatory effects of pulmonary vein isolation gaps in human atrial fibrillation digital twins.

Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm (p < 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p < 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.

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.

Racial Differences in Ischemic and Hemorrhagic Stroke: An Ecological Epidemiological Study.

BACKGROUND: This study aimed to evaluate racial differences in the incidence of stroke by conducting an ecological epidemiological study using UK Biobank and Korean nationwide data. METHODS: This study used individual data from the Korean National Health Insurance Service-Health Screening and UK Biobank, which included participants who underwent health examinations between 2006 and 2010. We included 112,750 East Asians (50.7% men, mean age: 52.6 years) and 210,995 Caucasians (44.7% men, mean age: 55.0 years) who were not diagnosed with atrial fibrillation, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease, or cancer. The primary outcome was defined as a composite of ischemic and hemorrhagic stroke. RESULTS: East Asians tended to have a lower body mass index (23.7 vs. 26.4 kg/m2, p < 0.001) and a higher proportion of participants who did not engage in moderate-to-vigorous physical activity (49.6% vs. 10.7%, p < 0.001) than Caucasians. During the follow-up, East Asians had higher 5-year incidence rates (presented as per 1,000 person-years) for primary outcome (1.73 vs. 0.50; IR ratio [IRR]: 3.48, 95% confidence interval [CI]: 3.13-3.88), ischemic stroke (1.23 vs. 0.33; IRR: 3.70, 95% CI: 3.25-4.21), hemorrhagic stroke (0.56 vs. 0.18; IRR: 3.20, 95% CI: 2.67-3.84), and atrial fibrillation-related stroke (0.19 vs. 0.09; IRR: 2.04, 95% CI: 1.55-2.68). CONCLUSION: Based on this ecological epidemiological study, racial differences in stroke incidence were robust to a variety of statistical analyses, regardless of the subtype. This suggests the need for region-specific approaches to stroke prevention.

Racial Differences in Bleeding Risk: An Ecological Epidemiological Study Comparing Korea and United Kingdom Subjects.

BACKGROUND: This study aimed to evaluate racial differences in bleeding incidence by conducting an ecological epidemiological study using data from Korea and the United Kingdom. METHODS: We included healthy participants from the Korean National Health Insurance Service-Health Screening and the UK Biobank who underwent health examinations between 2006 and 2010 and had no comorbidities or history of medication use. Finally, 112,750 East Asians (50.7% men, mean age 52.6 years) and 210,995 Caucasians (44.7% men, mean age 55.0 years) were analyzed. The primary outcome was composed of intracranial hemorrhage (ICH) and bleeding from the gastrointestinal, respiratory, and genitourinary systems. RESULTS: During the follow-up, primary outcome events occurred in 2,110 East Asians and in 6,515 Caucasians. East Asians had a 38% lower 5-year incidence rate compared with Caucasians (3.88 vs. 6.29 per 1,000 person-years; incidence rate ratio [IRR]: 0.62, 95% confidence interval [CI]: 0.59-0.65). East Asians showed a lower incidence of major bleeding (IRR: 0.86, 95% CI: 0.81-0.91), bleeding from the gastrointestinal (IRR: 0.53, 95% CI: 0.49-0.56), and genitourinary systems (IRR: 0.49, 95% CI: 0.44-0.53) compared with Caucasians. The incidence rates of ICH (IRR: 3.20, 95% CI: 2.67-3.84) and bleeding from the respiratory system (IRR: 1.28, 95% CI: 1.11-1.47) were higher in East Asians. Notably, East Asians consuming alcohol ≥3 times/week showed a higher incidence of the primary outcome than Caucasians (IRR: 1.12, 95% CI: 1.01-1.25). CONCLUSION: This ecological study revealed significant racial differences in bleeding incidence, influenced by anatomical sites and lifestyle habits, underscoring the need for tailored approaches in bleeding management based on race.

Atrial fibrillation: comorbidities, lifestyle, and patient factors.

Modern anticoagulation therapy has dramatically reduced the risk of stroke and systemic thromboembolism in people with atrial fibrillation (AF). However, AF still impairs quality of life, increases the risk of stroke and heart failure, and is linked to cognitive impairment. There is also a recognition of the residual risk of thromboembolic complications despite anticoagulation. Hence, AF management is evolving towards a more comprehensive understanding of risk factors predisposing to the development of this arrhythmia, its' complications and interventions to mitigate the risk. This review summarises the recent advances in understanding of risk factors for incident AF and managing these risk factors. It includes a discussion of lifestyle, somatic, psychological, and socioeconomic risk factors. The available data call for a practice shift towards a more individualised approach considering an increasingly broader range of health and patient factors contributing to AF-related health burden. The review highlights the needs of people living with co-morbidities (especially with multimorbidity), polypharmacy and the role of the changing population demographics affecting the European region and globally.

Associations of combined polygenic risk score and glycemic status with atrial fibrillation, coronary artery disease and ischemic stroke.

BACKGROUND: It is unknown whether high hemoglobin A1c (HbA1c) is associated with increases in the risk of cardiovascular disease among individuals with elevated genetic susceptibility. We aimed to investigate the association between HbA1c and atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke according to the polygenic risk score (PRS). METHODS: The UK Biobank cohort included 502,442 participants aged 40-70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. This study included 305,605 unrelated individuals with available PRS and assessed new-onset AF, CAD, and ischemic stroke. The participants were divided into tertiles based on the validated PRS for each outcome. Within each PRS tertiles, the risks of incident events associated with HbA1c levels were investigated and compared with HbA1c < 5.7% and low PRS. Data were analyzed from November 2022 to May 2023. RESULTS: Of 305,605 individuals, 161,605 (52.9%) were female, and the mean (SD) age was 56.6 (8.1) years. During a median follow-up of 11.9 (interquartile range 11.1-12.6) years, the incidences of AF, CAD, and ischemic stroke were 4.6, 2.9 and 1.1 per 100 person-years, respectively. Compared to individuals with HbA1c < 5.7% and low PRS, individuals with HbA1c ≥ 6.5% and high PRS had a 2.67-times higher risk for AF (hazard ratio [HR], 2.67; 95% confidence interval (CI), 2.43-2.94), 5.71-times higher risk for CAD (HR, 5.71; 95% CI, 5.14-6.33) and 2.94-times higher risk for ischemic stroke (HR, 2.94; 95% CI, 2.47-3.50). In the restricted cubic spline models, while a U-shaped trend was observed between HbA1c and the risk of AF, dose-dependent increases were observed between HbA1c and the risk of CAD and ischemic stroke regardless PRS tertile. CONCLUSIONS: Our results suggest that the nature of the dose-dependent relationship between HbA1c levels and cardiovascular disease in individuals with different PRS is outcome-specific. This adds to the evidence that PRS may play a role together with glycemic status in the development of cardiovascular disease.

Clinical Characteristics and Rhythm Outcomes in Patients With Atrial Myopathy After Successful Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Although successful atrial fibrillation (AF) ablation can maintain sinus rhythm and reduce the left atrial (LA) dimension, blunted LA reverse remodeling can be observed in patients with atrial myopathy. We explored the potential mechanisms and long-term outcomes in patients with blunted LA reverse remodeling after successful AF catheter ablation. METHODS AND RESULTS: We included 1685 patients who underwent baseline and 1-year follow-up echocardiograms, had a baseline LA dimension ≥40 mm, and did not have a recurrence of AF within a year. The patients were divided into tertile groups according to the delta value of the change in LA dimension on the preprocedure and 1-year postprocedure echocardiography. After propensity score matching for age, sex, AF type, and LA dimension, 1272 patients were finally included in the analyses (424 in each group; the least/blunted, moderate, and the most reverse remodeling group). The patients in the T1 group (blunted LA reverse remodeling) were independently associated with higher left ventricular mass index (odds ratio [OR], 1.014 [95% CI, 1.005-1.022], P=0.001), change in ΔH2FPEF score (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder, filling pressure) score (OR, 1.445 [95% CI, 1.121-1.861], P=0.004), ventricular epicardial adipose tissue volume (OR, 1.010 [95% CI, 1.003-1.017], P=0.003), thinner LA wall thickness (OR, 0.461 [95% CI, 0.271-0.785], P=0.004), lower LA voltage (OR, 0.670 [95% CI, 0.499-0.899], P=0.008), and showed higher long-term AF recurrence (log-rank P<0.001) than other groups. CONCLUSIONS: Blunted LA reverse remodeling after AF catheter ablation, which is suggestive of atrial myopathy, was independently associated with a larger ventricular epicardial adipose tissue volume and worsening of H2FPEF score. Blunted LA reverse remodeling after AF catheter ablation was also an independent predictor for higher recurrences of AF post-1-year AF catheter ablation.

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.

Multimorbidity in atrial fibrillation for clinical implications using the Charlson Comorbidity Index.

BACKGROUND: Predicting survival in atrial fibrillation (AF) patients with comorbidities is challenging. This study aimed to assess multimorbidity in AF patients using the Charlson Comorbidity Index (CCI) and its clinical implications. METHODS: We analyzed 451,368 participants from the Korea National Health Insurance Service-Health Screening cohort (2002-2013) without prior AF diagnoses. Patients were categorized into new-onset AF and non-AF groups, with a high CCI defined as ≥4 points. Antithrombotic treatment and outcomes (all-cause death, stroke, major bleeding, and heart failure [HF] hospitalization) were evaluated over 9 years. RESULTS: In total, 9.5% of the enrolled patients had high CCI. During follow-up, 12,241 patients developed new-onset AF. Among AF patients, antiplatelet drug use increased significantly in those with high CCI (adjusted odds ratio [OR] 1.05, 95%confidence interval [CI] 1.02-1.08, P < .001). However, anticoagulants were significantly less prescribed in patients with high CCI (OR 0.97, 95%CI 0.95-0.99, P = .012). Incidence of adverse events (all-cause death, stroke, major bleeding, HF hospitalization) progressively increased in this order: low CCI without AF, high CCI without AF, low CCI with AF, and high CCI with AF (all P < .001). Furthermore, high CCI with AF had a significantly higher risk compared to low CCI without AF (all-cause death, adjusted hazard ratio [aHR] 2.52, 95% CI 2.37-2.68, P < .001; stroke, aHR 1.43, 95% CI 1.29-1.58, P < .001; major bleeding, aHR 1.14, 95% CI 1.04-1.26, P = .007; HF hospitalization, aHR 4.75, 95% CI 4.03-5.59, P < .001). CONCLUSIONS: High CCI predicted increased antiplatelet use and reduced oral anticoagulant prescription. AF was associated with higher risks of all-cause death, stroke, major bleeding, and HF hospitalization compared to high CCI.

Association between Obesity and Heart Failure and Related Atrial Fibrillation: Patient-Level Data Comparisons of Two Cohort Studies.

PURPOSE: Heart failure (HF) and atrial fibrillation (AF) frequently coexist, with over 50% patients with HF having AF, while one-third of those with AF develop HF. Differences in obesity-mediated association between HF and HF-related AF among Asians and Europeans were evaluated. MATERIALS AND METHODS: Using the Korean National Health Insurance Service-Health Screening (K-NHIS-HealS) cohort and the UK Biobank, we included 394801 Korean and 476883 UK adults, respectively aged 40-70 years. The incidence and risk of HF were evaluated based on body mass index (BMI). RESULTS: The proportion of obese individuals was significantly higher in the UK Biobank cohort than in the K-NHIS-HealS cohort (24.2% vs. 2.7%, p<0.001). The incidence of HF and HF-related AF was higher among the obese in the UK than in Korea. The risk of HF was higher among the British than in Koreans, with adjusted hazard ratios of 1.82 [95% confidence interval (CI), 1.30-2.55] in K-NHIS-HealS and 2.00 (95% CI, 1.69-2.37) in UK Biobank in obese participants (p for interaction <0.001). A 5-unit increase in BMI was associated with a 44% greater risk of HF-related AF in the UK Biobank cohort (p<0.001) but not in the K-NHIS-HealS cohort (p=0.277). CONCLUSION: Obesity was associated with an increased risk of HF and HF-related AF in both Korean and UK populations. The higher incidence in the UK population was likely due to the higher proportion of obese individuals.

Artificial intelligence-enhanced 12-lead electrocardiography for identifying atrial fibrillation during sinus rhythm (AIAFib) trial: protocol for a multicenter retrospective study.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes. Methods and analysis: We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan-Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI. Discussion: This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases. Ethics and dissemination: The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions. Clinical Trial Registration: [cris.nih.go.kr], identifier (KCT0007881).

Comparison of pulmonary vein isolation using cryoballoon, high-power short-duration, and conventional radiofrequency ablation for atrial fibrillation: a propensity score-weighted study.

Background: The comparative efficacy, saftey, and heart rate variability (HRV) parameters after pulmonary vein isolation using cryoballoon (Cryo-PVI), high-power short-duration (HPSD-PVI), and conventional radiofrequency ablation (conventional-PVI) for atrial fibrillation (AF) is unclear. Materials and methods: In this propensity score-weighted, retrospective analysis of a single-center cohort, we analyzed 3,395 patients (26.2% female, 74.5% paroxysmal AF) who underwent AF catheter ablation without an empirical left atrial ablation. Procedural factors, recurrence rates, complication rates, and the post-procedural HRV parameters were compared across the Cryo-PVI (n = 625), HPSD-PVI (n = 748), and conventional-PVI (n = 2,022) groups. Results: Despite the shortest procedural time in the Cryo-PVI group (74 min for Cryo-PVI vs. 104 min for HPSD-PVI vs. 153 min for conventional-PVI, p < 0.001), the major complication (p = 0.906) and clinical recurrence rates were similar across the three ablation groups (weighted log-rank, p = 0.824). However, the Cryo-PVI group was associated with a significantly lower risk of recurrent AF in patients with paroxysmal AF [weighted hazard ratio (WHR) 0.57, 95% confidence interval (CI) 0.37-0.86], whereas it was associated with a higher risk of recurrent AF in patients with persistent AF (WHR 1.41, 95% CI 1.06-1.89, p for interaction of <0.001) compared with the conventional-PVI group. In the subgroup analysis for the HRV, the Cryo-PVI group had the highest low-frequency-to-high-frequency ratio at 1-year post-procedure, whereas the HPSD-PVI group had the lowest low-frequency-to-high-frequency ratio at 1-year post-procedure (p < 0.001). Conclusions: The Cryo-PVI group had better rhythm outcomes in patients with paroxysmal AF but worse rhythm outcomes in patients with persistent AF and a higher long-term post-procedural sympathetic nervous activity and sympatho-vagal balance compared with the conventional-PVI group.

Engineered small extracellular vesicle-mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy.

Small-interfering RNA (siRNA) therapy is considered a powerful therapeutic strategy for treating cardiac hypertrophy, an important risk factor for subsequent cardiac morbidity and mortality. However, the lack of safe and efficient in vivo delivery of siRNAs is a major challenge for broadening its clinical applications. Small extracellular vesicles (sEVs) are a promising delivery system for siRNAs but have limited cell/tissue-specific targeting ability. In this study, a new generation of heart-targeting sEVs (CEVs) has been developed by conjugating cardiac-targeting peptide (CTP) to human peripheral blood-derived sEVs (PB-EVs), using a simple, rapid and scalable method based on bio-orthogonal copper-free click chemistry. The experimental results show that CEVs have typical sEVs properties and excellent heart-targeting ability. Furthermore, to treat cardiac hypertrophy, CEVs are loaded with NADPH Oxidase 4 (NOX4) siRNA (siNOX4). Consequently, CEVs@siNOX4 treatment enhances the in vitro anti-hypertrophic effects by CEVs with siRNA protection and heart-targeting ability. In addition, the intravenous injection of CEVs@siNOX4 into angiotensin II (Ang II)-treated mice significantly improves cardiac function and reduces fibrosis and cardiomyocyte cross-sectional area, with limited side effects. In conclusion, the utilization of CEVs represents an efficient strategy for heart-targeted delivery of therapeutic siRNAs and holds great promise for the treatment of cardiac hypertrophy.

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.

Metabolic syndrome as an independent risk factor for glaucoma: a nationally representative study.

BACKGROUND: Central insulin resistance contributes to glaucoma development. Given the close association between metabolic syndrome MetS and insulin resistance, this study aimed to determine whether MetS is associated with glaucoma risk. METHODS: We analyzed data from 11,499 adults aged ≥ 19 years in the 2019-2021 Korean National Health and Nutrition Examination Survey and applied sampling weights to represent the general Korean population. Participants were classified into groups with or without MetS. Ocular hypertension (HTN) was defined as intraocular pressure > 21 mmHg. Primary open-angle glaucoma (POAG) was diagnosed based on the results of a visual field test and optical coherence tomography using the criteria published by the International Society for Geographic and Epidemiological Ophthalmology. We further divided POAG into normal tension (NTG) and POAG with ocular HTN. A spline curve was drawn to determine the dose-response relationship between the number of MetS components and risk of POAG. Odds ratios (ORs) with 95% confidence interval (CI) for POAG according to MetS status were estimated using weighted logistic regression analyses. RESULTS: The prevalence of POAG was 5.7% and 3.5%, respectively, in groups with and without MetS. We identified a dose-response relationship between the number of MetS components and risk of POAG. Unadjusted ORs (95% CI) for POAG in the group with MetS was 1.85 (1.52-2.25), compared with those without MetS. The trends persisted in adjusted models. The fully-adjusted OR (95% CI) for POAG was 1.47 (1.04-2.09) in the group with MetS. Subgroup analysis revealed that a significant relationship remained only in the NTG group (fully adjusted OR, 1.50; 95% CI 1.05-2.15). CONCLUSIONS: A comprehensive ophthalmological assessment should be considered for persons with MetS who are at increased risk of POAG, particularly NTG.