Effects of antiarrhythmic drug responsiveness and diagnosis-to-ablation time on outcomes after catheter ablation for persistent atrial fibrillation.

Background: The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods: We included data from 1038 AAD-resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD-partial responders; those maintaining PeAF on AAD were AAD-non-responders. We determined the DAT cutoff for best discriminating long-term rhythm outcomes using a maximum log-likelihood estimation method based on the Cox proportional hazard regression model. Results: Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD-non-responders. AAD-non-responders had a higher body mass index and a larger left atrial diameter than AAD-partial-responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33-2.30; log-rank p < .001) compared to AAD-partial-responders. The maximum log-likelihood estimation showed bimodal cutoffs at 22 and 40 months. The optimal DAT cutoff rhythm outcome was 22 months, which discriminated better in the AAD-partial-responders than in the AAD-non-responders. Conclusions: Both DAT and AAD responsiveness influenced AFCA rhythm outcomes. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF was changed to paroxysmal AF during AAD therapy.

Differentiating Left Atrial Pressure Responses in Paroxysmal and Persistent Atrial Fibrillation: Implications for Diagnosing Heart Failure With Preserved Ejection Fraction and Managing Atrial Fibrillation.

BACKGROUND: Increased left atrial pressure (LAP) contributes to dyspnea and heart failure with preserved ejection fraction in patients with atrial fibrillation (AF). The purpose of this study was to investigate the differences in baseline LAP and LAP response to rapid pacing between paroxysmal and persistent AF. METHODS AND RESULTS: This observational study prospectively enrolled 1369 participants who underwent AF catheter ablation, excluding those with reduced left ventricular ejection fraction. H2FPEF score was calculated by echocardiography and baseline characteristics. Patients underwent LAP measurements during AF, sinus rhythm, and heart rates of 90, 100, 110, and 120 beats per minute (bpm), induced by right atrial pacing and isoproterenol. The baseline LAP-peak in the persistent AF group consistently exceeded that in the paroxysmal AF (PAF) group across each H2FPEF score subgroup (all P<0.05). LAP-peak increased with pacing (19.5 to 22.5 mm Hg) but decreased with isoproterenol (20.4 to 18.4 mm Hg). Under pacing, patients with PAF exhibited a significantly lower LAP-peak (90 bpm) than those with persistent AF (17.7±8.2 versus 21.1±9.3 mm Hg, P<0.001). However, there was no difference in LAP-peak (120 bpm) between the 2 groups (22.1±8.1 versus 22.9±8.4 mm Hg, P=0.056) because the LAP-peak significantly increased with heart rate in the group with PAF. CONCLUSIONS: Patients with PAF exhibited lower baseline LAP with greater increases during rapid pacing compared with individuals with persistent AF, indicating a need to revise the H2FPEF score for distinguishing PAF from persistent AF and emphasizing the importance of rate and rhythm control in PAF for symptom control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02138695.

All-Cause Death and Major Adverse Events in Atrial Fibrillation with Frailty: Observations from the Korea National Health Insurance Service Data.

Background: Atrial fibrillation (AF) is an indicator of frailty in old patients. This study aimed to investigate the effect of frailty on the use of oral anticoagulants (OAC) and clinical outcomes in a nationwide cohort of patients with new-onset AF. Methods: This study included 451,368 participants without AF from the Korea National Health Insurance Service-Health Screening cohort between 2002 and 2009. The Hospital Frailty Risk Score was retrospectively calculated for each patient using all available International Classification of Disease 10th revision diagnostic codes. According to the aggregate score, patients were divided into two groups: the participants without frailty ( < 5 points) and the participants with frailty ( ≥ 5 points). The primary outcome was death from any cause, and the secondary outcomes were cardiovascular death, ischemic stroke, major bleeding, and heart failure admission. Results: With up to 7.2 ± 1.5 years of follow-up, 11,953 participants (median age, 67 [interquartile range, 59.5-74.5] years; 7200 [60.2%] males) developed new-onset AF. Among the patients with AF, 3224 (26.9%) had frailty. Frailty was significantly associated with old age, female sex, polypharmacy, and other comorbidities. In patients with AF, frailty was negatively associated with OAC prescription after new-onset AF (p < 0.001). Compared to patients without frailty, patients with frailty had a significantly higher incidence and risk of all-cause death (hazard ratio [HR] 2.88, 95% confidence interval [CI] 2.65-3.14), cardiovascular death (HR 2.42, 95% CI 2.10-2.80), ischemic stroke (HR 2.25, 95% CI 2.02-2.51), major bleeding (HR 2.44, 95% CI 2.17-2.73), and heart failure admission (HR 1.29, 95% CI 1.09-1.52). In subgroup analysis, when compared to the non-OAC group, the risks associated with frailty were significantly lower in the OAC group for all-cause death, cardiovascular death, ischemic stroke, and heart failure admission. Conclusions: Frailty was negatively associated with the use of OAC and was a predictor of poor prognosis owing to the association of frailty with death, thromboembolic events, bleeding, and heart failure admission. However, OAC use was associated with lower risks related to frailty for all-cause death and major adverse cardiovascular events in patients with AF.

Clinical Implications of Polypharmacy for Patients with New-Onset Atrial Fibrillation Based on Real-World Data: Observations from the Korea National Health Insurance Service Data.

Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations.

The associations of leukocyte telomere length and intermediary cardiovascular phenotype with adverse cardiovascular outcomes in the white population.

The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2-12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72-0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84-0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74-0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.

Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

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.

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.

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.

Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are vital contributors to the growth, metastasis, and therapeutic resistance of various cancers, including hepatocellular carcinoma (HCC). However, the exact phenotype of TAMs and the mechanisms underlying their modulation for therapeutic purposes have not been determined. Here, we present compelling evidence that glutamine-derived aspartate in TAMs stimulates spermidine production through the polyamine synthesis pathway, thereby increasing the translation efficiency of HIF-1α via eIF5A hypusination. Consequently, augmented translation of HIF-1α drives TAMs to undergo an increase glycolysis and acquire a metabolic phenotype distinct from that of M2 macrophages. Finally, eIF5A levels in tumor stromal lesions were greater than those in nontumor stromal lesions. Additionally, a higher degree of tumor stromal eIF5A hypusination was significantly associated with a more advanced tumor stage. Taken together, these data highlight the potential of inhibiting hypusinated eIF5A by targeting glutamine metabolism in TAMs, thereby opening a promising avenue for the development of novel therapeutic approaches for HCC.

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.

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.

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.

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.

Potential role of the cell-penetrating peptide-conjugated soluble N-ethylmaleimide-sensitive factor attachment protein receptor motif of vesicle-associated membrane protein 2-patterned peptide in novel cosmeceutical skin product development.

AIM: This study aimed to investigate and verify the effect of cell-penetrating peptide (CPP)-conjugated soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) motif of vesicle-associated membrane protein 2 (VAMP2)-patterned peptide (INCI name: Acetyl sh-Oligopeptide-26 sh-Oligopeptide-27 SP, trade name: M.Biome-BT) on improving skin function in vitro. METHODS: The cytotoxicity of CPP-conjugated SNARE motif of VAMP2-patterned peptide (CVP) was investigated using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay against B16-F10 cells and human dermal fibroblasts (HDFs) and a reconstructed skin irritation test. The anti-wrinkle activity of M.Biome-BT was determined by assessing the release of norepinephrine and dopamine in PC-12 cells via ELISA. The skin-whitening effects of CVP were assessed in B16-F10 cells by measuring the intra- and extracellular melanin contents and expression levels of melanin production-related genes, such as microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and TRP-2. RESULTS: CVP is not cytotoxic to B16-F10 cells and HDFs, and no skin irritation was observed. CVP treatment considerably diminished K+ -induced norepinephrine and dopamine secretion compared with the non-treated control group (62% and 40%, respectively). Additionally, the inhibition ability of CVP on norepinephrine and dopamine release was comparable to that of botulinum neurotoxin type A (BoNT/A). CVP also increased intracellular melanin content in a dose-dependent manner, whereas extracellular melanin content decreased (76%-85%). However, CVP treatment did not affect the mRNA expression of MITF, TYR, TRP-1, and TRP-2. These results suggest that CVP does not inhibit melanin production; however, it may induce a whitening effect by inhibiting melanin transport. CONCLUSIONS: Taken together, our findings indicate that CVP could be used as an active and safe cosmeceutical ingredient for antiaging applications.

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.

Association between hearing loss and high-sensitivity C-reactive protein: the Kangbuk Samsung Cohort Study.

Background: Hearing loss (HL) is linked to an elevated risk of cardiovascular diseases (CVDs). The pathogeneses of HL and CVD commonly involve inflammatory responses. Previous studies investigated elevated levels of inflammatory biomarkers in subjects with HL, however, their findings did not demonstrate statistical significance. In our cross-sectional and longitudinal study, we investigated the correlation between HL and increased high-sensitivity C-reactive protein (hsCRP) levels to determine how HL is associated with CVDs. Methods: We conducted a cross-sectional study with workers aged over 18 years who underwent health check-ups at our institution between 2012 and 2018 (n = 566,507), followed by conducting a longitudinal study of workers aged > 18 who underwent health checkups at least twice at our institution between 2012 and 2018 (n = 173,794). The definition of HL was as an average threshold of ≥ 20 dB in pure-tone air conduction at 0.5, 1.0, and 2.0 kHz in both ears. The incidence of increased hsCRP levels throughout the follow-up period was defined as a level exceeding 3 mg/L. Logistic regression and generalized estimating equations were performed to estimate the risk of increased hsCRP levels according to the occurrence of HL in groups stratified by age. Results: In the cross-sectional study, the multivariate-adjusted odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.02-1.34); the OR was 0.99 (95% CI: 0.80-1.22) in those under 40 and 1.28 (1.08-1.53) in those over 40. In the longitudinal study, the multivariable-adjusted OR was 1.05 (95% CI: 0.92-1.19); the OR was 1.10 (95% CI: 0.90-1.35) in those under 40 and 1.20 (1.01-1.43) in those over 40. Conclusions: This cross-sectional and longitudinal study identified an association between HL and increased hsCRP levels in workers aged over 40 years.