Association of Adding Salt to Foods and Potassium Intake with Incident Atrial Fibrillation in the UK Biobank Study.

Background: High sodium and low potassium consumption are related to hypertension and cardiovascular disease. We aimed to determine the relationship between the frequency of salt addition and potassium consumption with the risk of new-onset atrial fibrillation (AF). Methods: Our study used the UK Biobank cohort, which included over 500,000 individuals enrolled from the United Kingdom between 2006 and 2010. This study involved 416,868 participants who filled out the dietary recall regarding the frequency of salt addition. Results: During follow-up, 19,164 (4.6%) developed AF. The incidence of new-onset AF was increased based on the frequency of salt addition (never/rarely 3.83; always 4.72 per 1000 person-years). Compared with the group that never/rarely added salt, those adding salt always were at significantly higher risk of incident AF after adjusting for multiple variables (hazard ratio (HR) 1.15; 95% confidence interval (CI) 1.06-1.24), and additional adjustment of dietary and total energy consumption (HR 1.37; 95% CI 1.08-1.73). In the subgroup analysis, the risk of AF incident according to the frequency of salt addition significantly increased in low urine potassium levels compared to high (p for interaction = 0.046). In the subgroup analysis for AF patients, higher salt addition frequency was related to increased all-cause mortality. Conclusions: Our study demonstrated that adding salt to foods more frequently increases the risk of incident AF, even after adjusting for dietary and total energy consumption. In the high urine potassium group, the impact of high sodium consumption on incident AF was attenuated.

Assessment of Antitachycardia Pacing in Primary Prevention Patients: The APPRAISE ATP Randomized Clinical Trial.

Importance: The emergence of novel programming guidelines that reduce premature and inappropriate therapies along with the availability of new implantable cardioverter-defibrillator (ICD) technologies lacking traditional endocardial antitachycardia pacing (ATP) capabilities requires the reevaluation of ATP as a first strategy in terminating fast ventricular tachycardias (VTs) in primary prevention ICD recipients. Objective: To assess the role of ATP in terminating fast VTs in primary prevention ICD recipients with contemporary programming. Design, Setting, and Participants: This global, prospective, double-blind, randomized clinical trial had an equivalence design with a relative margin of 35%. Superiority tests were performed at interim analyses and the final analysis if equivalence was not proven. Patients were enrolled between September 2016 and April 2021 at 134 sites in 8 countries, with the last date of follow-up on July 6, 2023. Patients were required to have an indication for a primary prevention ICD, including left ventricular ejection fraction less than or equal to 35%. Interventions: Patients were randomized in a 1:1 ratio to receive ATP plus shock vs shock only. Main Outcomes and Measures: The primary end point was time to first all-cause shock. Secondary end points included time to first appropriate shock, time to first inappropriate shock, all-cause mortality, and the composite of time to first all-cause shock plus all-cause mortality. Results: A total of 2595 patients were randomized (mean age, 63.9 years; 22.4% were females). At a mean follow-up of 38 months, first all-cause shock occurred in 129 participants in the ATP plus shock group and 178 participants in the shock only group. The hazard ratio (HR) for the primary end point was 0.72 (95.9% CI, 0.57-0.92), with P = .005 for superiority of the ATP plus shock group over the shock only group. During follow-up in an intention-to-treat analysis, the total shock burden per 100 patient-years was not statistically different, at 12.3 and 14.9, respectively (P = .70). Conclusions and Relevance: The use of a single burst of ATP prior to shock in primary prevention ICD recipients with modern ICD detection programming prolonged the time to first all-cause ICD shock. Trial Registration: ClinicalTrials.gov Identifier: NCT02923726.

Establishment of two human induced pluripotent stem cell lines from familial long QT syndrome type 1 patients carrying KCNQ1 mutation.

Long QT syndrome type 1 (LQT1) is a rare heart disorder caused by a loss-of-function mutation in the KCNQ1 gene that causes loss of Kv7.1 channel function, which can lead to Palpitations, Syncope, and Sudden cardiac arrest. We derived induced pluripotent stem cells from PBMC of LQT1 patients carrying a pathogenic variant (c.734G>A; p.Gly245Glu). The non-integrative Sendai virus-mediated iPSC reprogramming method was used for iPSC line generation. These iPSC cell lines exhibit stem cell pluripotency, differentiation capability, and cell morphology, resulting in a reliable cell source to study the effects of KCNQ1 mutation in disease-specific cell types.

Predictors of success in left bundle branch area pacing with stylet-driven pacing leads: a multicenter investigation.

Purpose: Although left bundle branch area pacing (LBBAP) is an emerging conduction system pacing modality, it is unclear which parameters predict procedural success and how many implant attempts are acceptable. This study aimed to assess predictors of successful LBBAP, left bundle branch (LBB) capture, and factors associated with the number of LBBAP implant attempts. Methods: This retrospective observational multicenter study was conducted in Korea. LBBAP was attempted in 119 patients; 89.3% of patients had bradyarrhythmia (atrioventricular block 82.4%), and 10.7% of patients had heart failure (cardiac resynchronization therapy) indication. Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results: The acute success rate of lead implantation in LBBAP was 95.8% (114 of 119 patients) and that of LBB capture was 82.4% (98 of 119 patients). Fewer implant attempts were associated with LBBAP success (three or fewer vs. over three times, p = 0.014) and LBB capture (three or fewer vs. over three times, p = 0.010). In the multivariate linear regression, the patients with intraventricular conduction delay (IVCD) required a greater number of attempts than those without IVCD [estimates = 2.33 (0.35-4.31), p = 0.02], and the larger the right atrial (RA) size, the more the attempts required for LBBAP lead implantation [estimates = 2.08 (1.20-2.97), p < 0.001]. Conclusion: An increase in the number of implant attempts was associated with LBBAP procedural failure and LBB capture failure. The electrocardiographic parameter IVCD and the echocardiographic parameter RA size may predict the procedural complexity and the number of lead implant attempts for LBBAP.

Impact of Atrial Fibrillation with Rapid Ventricular Response on Atrial Fibrillation Recurrence: From the CODE-AF Registry.

Background/Objectives: Relatively little has been established about the association of rapid ventricular response (RVR) with further recurrence of atrial fibrillation (AF). This study investigated the impact of RVR on the recurrence of AF. Methods: Data were obtained from a multicenter, prospective registry of non-valvular AF patients. RVR was defined as AF with a ventricular rate > 110 bpm. The primary endpoint was the recurrence of AF, defined as the first AF detected on 12-lead electrocardiography during follow-up. Secondary endpoints included manifestation of AF during follow-up and major adverse cardiovascular events (MACEs), a composite of thromboembolic events, major bleeding, myocardial infarction, and death. Results: Among 5533 patients, 493 (8.9%) presented RVR. Patients with RVR were younger, had smaller left atrial diameters, and more frequently had paroxysmal AF. During the mean follow-up duration of 28.6 months, the RVR group exhibited significantly lower recurrence of AF (hazard ratio: 0.58, 95% confidence interval: 0.53-0.65, p < 0.001). There was no significant difference in the occurrence of MACEs between patients with RVR and those without RVR (0.96, 0.70-1.31, p = 0.800). AF with RVR was identified as an independent negative predictor of AF recurrence (0.61, 0.53-0.71, p < 0.001). Conclusions: In patients with AF, those with RVR had a significantly lower recurrence of AF without an increase in MACEs. RVR is a favorable marker that may benefit from early rhythm control.

Artificial intelligence estimated electrocardiographic age as a recurrence predictor after atrial fibrillation catheter ablation.

The application of artificial intelligence (AI) algorithms to 12-lead electrocardiogram (ECG) provides promising age prediction models. We explored whether the gap between the pre-procedural AI-ECG age and chronological age can predict atrial fibrillation (AF) recurrence after catheter ablation. We validated a pre-trained residual network-based model for age prediction on four multinational datasets. Then we estimated AI-ECG age using a pre-procedural sinus rhythm ECG among individuals on anti-arrhythmic drugs who underwent de-novo AF catheter ablation from two independent AF ablation cohorts. We categorized the AI-ECG age gap based on the mean absolute error of the AI-ECG age gap obtained from four model validation datasets; aged-ECG (≥10 years) and normal ECG age (<10 years) groups. In the two AF ablation cohorts, aged-ECG was associated with a significantly increased risk of AF recurrence compared to the normal ECG age group. These associations were independent of chronological age or left atrial diameter. In summary, a pre-procedural AI-ECG age has a prognostic value for AF recurrence after catheter ablation.

Renal Outcomes of Rhythm Control in Patients Recently Diagnosed With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with impaired renal function and chronic kidney disease (CKD). OBJECTIVES: This study assessed the effects of rhythm control on renal function compared with rate control among patients recently diagnosed with AF. METHODS: A total of 20,886 patients with AF and available baseline estimated glomerular filtration rate (eGFR) data undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis in 2005 to 2015, were identified from the Korean National Health Insurance Service database. The composite outcome of ≥30% decline in eGFR, acute kidney injury, kidney failure, or death from renal or cardiovascular causes was compared with the use of propensity overlap weighting between rhythm or rate control strategies in patients with or without significant CKD (eGFR <60 mL/min/1.73 m2). RESULTS: Of the included patients (median age 62 years, 32.7% female), 2,213 (10.6%) had eGFR <60 mL/min/1.73 m2. Among patients with significant CKD, early rhythm control, compared with rate control, was associated with a lower risk of the primary composite outcome (weighted incidence rate: 2.77 vs 3.92 per 100 person-years; weighted HR: 0.70; 95% CI: 0.52-0.95). In patients without significant CKD, there was no difference in the risk of the primary composite outcome between rhythm and rate control groups (weighted incidence rate: 3.41 vs 3.21 per 100 person-years; weighted HR: 1.06; 95% CI: 0.96-1.18). No differences in safety outcomes were found between rhythm and rate control strategies in patients without or with significant CKD. CONCLUSIONS: Among patients with AF and CKD, early rhythm control was associated with lower risks of adverse renal outcomes than rate control was.

The anticoagulation one year after ablation of atrial fibrillation in patients with atrial fibrillation (ALONE-AF) trial: Study protocol.

Background: The ideal long-term antithrombotic strategy for patients after successful catheter-based atrial fibrillation (AF) ablation is still uncertain. Presently, practices vary, and the advantages of oral anticoagulation (OAC) for the post-ablation population are not clearly established. To date, no randomized trials have addressed this therapeutic question. This study aimed to evaluate whether no OAC therapy is superior to apixaban in reducing the risk of stroke, systemic embolism, or major bleeding among patients without apparent recurrent atrial arrhythmias for at least 1 year after their AF ablation procedure. Methods: The ALONE-AF trial is a prospective, multicenter, open-label, randomized study with blinded outcome assessment. Patients with AF who have at least one non-gender stroke risk factor (as determined by the CHA2DS2-VASc score) and no documented recurrences of atrial arrhythmia for at least 12 months post-ablation will be randomly assigned to apixaban 5 mg b.i.d. or no OAC therapy. The primary endpoint is a composite outcome of stroke, systemic embolism, and major bleeding. Key secondary outcomes include clinically relevant non-major bleeding, all-cause mortality, myocardial infarction, transient ischemic attack, quality of life, and frailty analysis. Participants will be followed for a period of 2 years. The estimated total sample size is 840 subjects, with 420 subjects in each arm. Conclusion: The ALONE-AF trial aims to provide robust evidence for the optimal anticoagulation strategy for patients with stroke risk factors following successful AF ablation.

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.

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.

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.

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.

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.

Clinical and pathophysiologic determinants of catheter ablation outcome in hypertrophic cardiomyopathy with atrial fibrillation.

Background: Hypertrophic cardiomyopathy (HCM) is frequently associated with atrial fibrillation (AF). We compared clinical, echocardiographic, and electrophysiological parameters between HCM subtypes and those without HCM at AF catheter ablation (AFCA) and analyzed post-AFCA reverse remodeling and AF recurrence based on HCM presence and subtype. Methods: Among 5161 consecutive patients who underwent de novo AFCA, we included HCM patients and control patients who were age-, gender-, and AF type-matched. Between AF-HCM patients and controls, we compared baseline values for left atrium (LA) wall thickness (LAWT), reverse remodeling at 1-year follow-up, and procedural outcomes over the course of follow-up between two groups. Results: A total of 122 AF-HCM patients and 318 control patients were included. AF-HCM patients had more frequent heart failure and higher LA diameter, E/Em, and LA pressure (all, p < .001). However, LAWT did not differ from control group. A year after AFCA, degree of LA reverse remodeling was significantly lower in AF-HCM than in control group (ΔLA dimension, p = .025). Nonapical HCM (HR 1.71; 95% CI 1.05-2.80), persistent AF (HR 1.46; 95% CI 1.05-2.04), and LA dimension (HR 1.04; 95% CI 1.01-1.06) were independent risk factors for AF recurrence. During 78.0 months of follow-up, nonapical HCM patients showed higher AF recurrence rate than both apical HCM (log-rank p = .005) and control patients (log-rank p = .002). Conclusions: The presence of HCM, particularly nonapical HCM, displayed increased LA hemodynamic loading with diastolic dysfunction and had poorer rhythm outcomes after AFCA compared to both apical HCM and control group.

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.

Small extracellular vesicle-mediated CRISPR-Cas9 RNP delivery for cardiac-specific genome editing.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Although clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing holds immense potential for genetic manipulation, its clinical application is hindered by the absence of an efficient heart-targeted drug delivery system. Herein, we developed CRISPR-Cas9 ribonucleoprotein (RNP)-loaded extracellular vesicles (EVs) conjugated with cardiac-targeting peptide (T) for precise cardiac-specific genome editing. RNP complexes containing Cas9 and single guide RNA targeting miR-34a, an MI-associated molecular target, were loaded into EVs (EV@RNP). Gene editing by EV@RNP attenuated hydrogen peroxide-induced apoptosis in cardiomyocytes via miR-34a inhibition, evidenced by increased B-cell lymphoma 2 levels, decreased Bcl-2-associated X protein levels, and the cleavage of caspase-3. Additionally, to improve cardiac targeting in vivo, we used click chemistry to form functional T-EV@RNP by conjugating T peptides to EV@RNP. Consequently, T-EV@RNP-mediated miR-34a genome editing might exert a protective effect against MI, reducing apoptosis, ameliorating MI injury, and facilitating the recovery of cardiac function. In conclusion, the genome editing delivery system established by loading CRISPR/Cas9 RNP with cardiac-targeting EVs is a powerful approach for precise and tissue-specific gene therapy for cardiovascular disease.

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.

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.