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Atrial fibrillation (AF) affects more than 33 million individuals worldwide 1 and has a complex heritability 2 . We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF. This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.

Significant racial/ethnic differences exist in the incidence of atrial fibrillation (AF). However, less is known about racial/ethnic differences in quality of life (QoL), treatment, and outcomes associated with AF. Using data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we compared clinical characteristics, QoL, management strategies, and long-term outcomes associated with AF among various racial/ethnic groups. We analyzed 9,542 participants with AF (mean age 74 ± 11 years, 43% women, 91% white, 5% black, 4% Hispanic) from 174 centers. Compared with AF patients identified as white race, patients identified as Hispanic ethnicity and those identified as black race were younger, were more often women, and had more cardiac and noncardiac comorbidities. Black patients were more symptomatic with worse QoL and were less likely to be treated with a rhythm control strategy than other racial/ethnic groups. There were no significant racial/ethnic differences in CHA2DS2-VASc stroke or ATRIA bleeding risk scores and rates of oral anticoagulation use were similar. However, racial and ethnic minority populations treated with warfarin spent a lower median time in therapeutic range of international normalized ratio (59% blacks vs 68% whites vs 62% Hispanics, P < .0001). There was no difference in long-term outcomes associated with AF between the 3 groups at a median follow-up of 2.1 years. Relative to white and Hispanic patients, black patients with AF had more symptoms, were less likely to receive rhythm control interventions, and had lower quality of warfarin management. Despite these differences, clinical events at 2 years were similar by race and ethnicity.

The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non–East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non–East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non–East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia.

ObjectivesHigher body mass index (BMI) is an important risk factor for atrial fibrillation (AF). The adipokines leptin, adiponectin and resistin are correlates of BMI, but their association with incident AF is not well known. We explored this relationship in a large cohort of postmenopausal women.MethodsWe studied an ethnically diverse cohort of community-dwelling postmenopausal women aged 50–79 who were nationally recruited at 40 clinical centres as part of the Women's Health Initiative investigation. Participants underwent measurements of baseline serum leptin, adiponectin and resistin levels and were followed for incident AF. Adipokine levels were log transformed and normalised using inverse probability weighting. Cox proportional hazard regression models were used to estimate associations with adjustment for known AF risk factors.ResultsOf the 4937 participants included, 892 developed AF over a follow-up of 11.1 years. Those with AF had higher mean leptin (14.9 pg/mL vs 13.9 pg/mL), adiponectin (26.3 ug/mL vs 24.5 ug/mL) and resistin (12.9 ng/mL vs 12.1 ng/mL) levels. After multivariable adjustment, neither log leptin nor log adiponectin levels were significantly associated with incident AF. However, log resistin levels remained significantly associated with incident AF (HR=1.57 per 1 log (ng/mL) increase, p=0.006). Additional adjustment for inflammatory cytokines only partially attenuated the association between resistin and incident AF (HR=1.43, p=0.06 adjusting for C-reactive protein (CRP); HR=1.39, p=0.08 adjusting for IL-6). Adjusting for resistin partially attenuated the association between BMI and incident AF (HR=1.14 per 5 kg/m2, p=0.006 without resistin; HR=1.12, p=0.02 with resistin).ConclusionsIn women, elevated levels of serum resistin are significantly associated with higher rates of incident AF and partially mediate the association between BMI and AF. In the same population, leptin and adiponectin levels are not significantly associated with AF.

The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women. We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims. Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups. In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians.

Atrial fibrillation (AF) occurs frequently in patients with chronic obstructive pulmonary disease. Epidemiologic studies have found inconsistent associations between lung function and AF, and none have studied pulmonary emphysema, which overlaps only partially with chronic obstructive pulmonary disease in the general population. The aim of this study was to assess the relation among lung function measured by spirometry, the percentage of emphysema-like lung on computed tomography, and incident AF. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study following 6,814 subjects free of clinical cardiovascular disease, including AF, at baseline. Spirometry was performed in a subset of 3,965 participants. Percentage emphysema was defined on baseline computed tomographic scans as lung regions <950 Hounsfield units. Incident AF was identified from hospital discharge diagnosis and Medicare claims data. Cox proportional hazards models were used to assess independent associations of lung volumes and percentage emphysema with AF. A total of 3,811 participants with valid spirometric results were included in this study. The mean age was 64.5 ± 9.8 years, and 49.4% were men. AF developed in 149 subjects (3.8%) over a mean follow-up period of 4.1 years after spirometry. Lower levels of forced expiratory volume at 1 second and forced vital capacity were associated with a higher risk for AF (hazard ratios 1.21 and 1.19 per 500 ml, respectively, p <0.001) after adjustment for demographic and cardiovascular risk factors. Percentage emphysema was not significantly related to AF. In conclusion, in a multiethnic community-based sample of subjects free of cardiovascular disease at baseline, functional airflow limitation was related to a higher risk for AF.

Atrial fibrillation (AF) is common in patients with heart failure (HF) and portends a worsened prognosis. Because of the low enrollment of African American subjects (AAs) in randomized HF trials, there are little data on AF in AAs with HF. This post hoc analysis reviews characteristics and outcomes of AA patients with AF in A-HeFT. A total of 1,050 AA patients with New York Heart Association class III/IV systolic HF, well treated with neurohormonal blockade (87% β-blockers, 93% angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker), were randomized to an added fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo. Atrial fibrillation was confirmed in 174 (16.6%) patients at baseline and in an additional 9 patients who developed AF during the study, for a final cohort of 183 (17.4%). Comparison of patients with AF versus no AF revealed the following: mean age 61 ± 12 versus 56 ± 13 years ( P < .001), systolic blood pressure (BP) 124 ± 18 versus 127 ± 18 mm Hg ( P = .044), diastolic BP 74 ± 11 versus 77 ± 10 mm Hg ( P = .002), creatinine level 1.4 ± 0.5 versus 1.2 ± 0.5 mg/dL ( P < .001), and brain natriuretic peptide 431 ± 443 versus 283 ± 396 pg/mL ( P < .001). No significant difference was observed in ejection fraction, left ventricular end-diastolic diameter, or quality-of-life scores. However, AF increased the risk of mortality significantly among AA patients ( P = .018), and the use of FDC I/H reduced the risk of mortality in patients with AF (HR 0.21, P = .002). African Americans with HF and AF (vs no AF) were older, had lower BP, and had higher creatinine and brain natriuretic peptide levels. Mortality and morbidity were worse when AF was present, and these data suggest that there may be an enhanced survival benefit with the use of FDC I/H in AA patients with HF and AF.

Black patients have higher rates of stroke than White patients. Paradoxically, atrial fibrillation (AF) affects twice as many White patients compared with Black patients. Transthyretin cardiac amyloidosis (ATTR-CA) is associated with both AF and strokes. We hypothesized that although Black patients with ATTR-CA have a lower incidence of AF, when diagnosed with AF, they have increased thromboembolic events. Patients with ATTR-CA (n = 558) at 3 international centers were retrospectively identified. We compared baseline characteristics, presence of AF, outcomes of thromboembolism (stroke, transient ischemic attack, and peripheral embolism), major bleed, and mortality by race. Of all patients, 367 of 488 White patients (75%) were diagnosed with AF compared with 39 of 70 Black patients (56%) (p = 0.001). Black patients with AF had a hazard ratio of 5.78 (95% confidence interval 2.30 to 14.50) for time to first thromboembolic event compared with White patients. There were no racial differences in major bleeding. Black patients with AF more often lacked anticoagulation (p = 0.038) and had higher incidence of labile international normalized ratio (p <0.001). In conclusion, these data suggest that although Black patients with ATTR-CA have lower incidence of AF, they have increased thromboembolic events compared with White patients. These findings may be related to treatment discrepancies, time in therapeutic range for warfarin, and disparities in healthcare.

•Racial and ethnic minoritized populations were less likely to be treated with catheter ablation.•Disparities exist in the utilization of direct current cardioversion and antiarrhythmic drugs.•Black patients had increased all-cause mortality, heart failure hospitalization, and stroke rates compared to White patients.•Future studies exploring the cause of these disparities are needed. Rhythm control strategies are a key component of atrial fibrillation (AF) therapy, with recent reports suggesting racial and ethnic disparities in their utilization. We aimed to determine differences in the utilization of catheter ablation (CA), direct current cardioversion (DCCV), and anti-arrhythmic drugs (AAD) among different racial and ethnic groups. We searched PubMed/MEDLINE, EMBASE, and Cochrane Library (from inception to January 31st, 2024) for studies including adults with AF and reporting CA, DCCV, or AAD utilization rates in at least 2 racial and ethnic groups. Our primary outcome was the likelihood of Black, Hispanic, and Asian individuals undergoing each rhythm control strategy compared to White patients. Pooled estimates were calculated with a random-effects model and were reported as odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Nineteen studies were included comprising 12,598,109 patients. The pooled ORs (95% CI) of undergoing CA for Black individuals was 0.68 (95% CI 0.56 to 0.83), for Hispanic individuals was 0.72 (95% CI 0.63 to 0.82), and for Asian individuals was 0.64 (95% CI 0.48 to 0.86), compared to White individuals. The likelihood of undergoing DCCV (OR [95% CI]) was lower in Black (0.69 [95% CI 0.57 to 0.82]), Hispanic (0.67 [95% CI 0.57 to 0.80]), Asian (0.68 [95% CI 0.64 to 0.72]) patients compared to White patients. Our results identified that racial and ethnic minoritized groups with AF are significantly less likely to undergo treatment with a rhythm control strategy. In conclusion, these findings highlight a significant gap in healthcare delivery that stakeholders, healthcare systems, and clinicians should address. [Display omitted]

Evidence suggests an association between autonomical nervous system (ANS) function and atrial fibrillation (AF) development. We sought to examine the association of baseline resting heart rate (RHR) and short-term heart rate variability (HRV) as surrogates of (ANS) with incident AF in individuals without previous cardiovascular disease. A total of 6,261 participants of the Multi-Ethnic Study of Atherosclerosis who were free of AF and diagnosed cardiovascular disease were enrolled. Three standard 10-second, 12-lead electrocardiograms (ECG) were used to measure RHR, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Cox proportional hazards models adjusted for demographics, atrioventricular nodal agents, and known cardiovascular risk factors were used to examine the association of baseline RHR, and log transformed SDNN and RMSDD with incident AF. Over a mean follow-up of 11.3 ± 3.7 years, 754 (12%) participants developed AF. Spline curve analysis revealed a nonlinear association between RHR, HRV, and incident AF. In fully adjusted models higher (but not lower) baseline RHR (RHR >76 beats/min) was associated with incident AF (hazard ratio 1.48 95% confidence interval 1.18 to 1.86). Additionally, lower values of RMSDD and SDNN and higher values of RMSDD were independently associated with incident AF. In conclusion, cardiac ANS dysregulation indicated as higher RHR and lower HRV is associated with incident AF independent of known cardiovascular risk factors.