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The objective of the study was to examine the joint associations of albuminuria and electrocardiographic left atrial abnormality (ECG-LAA) with incident atrial fibrillation (AF) and whether this relationship varies by race. This analysis included 6670 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. ECG-LAA was defined as P-wave terminal force in V1 [PTFV1] >5000 μV × ms. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. Incident AF events through 2015 were ascertained from hospital discharge records and study-scheduled electrocardiograms. Cox proportional hazard models were used to examine the association of "no albuminuria + no ECG-LAA (reference)", "isolated albuminuria", "isolated ECG-LAA" and "albuminuria + ECG-LAA" with incident AF. Over a median follow-up of 13.8 years, 979 incident cases of AF occurred. In adjusted models, the concomitant presence of ECG-LAA and albuminuria was associated with a higher risk of AF than either ECG-LAA or albuminuria in isolation (HR (95% CI): 2.43 (1.65–3.58), 1.33 (1.05–1.69), and 1.55 (1.27–1.88), respectively (interaction p-value = 0.50). Effect modification by race was observed with a 4-fold greater AF risk in Black participants with albuminuria + ECG-LAA (HR (95%CI): 4.37 (2.38–8.01) but no significant association in White participants (HR (95% CI) 0.60 (0.19–1.92) respectively; (interaction p-value for race x albuminuria-ECG-LAA combination = 0.05). Concomitant presence of ECG-LAA and albuminuria confers a higher risk of AF compared to either one in isolation with a stronger association in Blacks than Whites. • Impact of combination of albuminuria and ECG left atrial abnormality (ECG-LAA) on atrial fibrillation (AF) risk is unknown. • Concomitant presence of albuminuria and ECG-LAA is associated with a greater risk of AF than each predictor in isolation. • Only Black individuals with concomitant albuminuria and ECG-LAA have a higher risk of incident AF. • These findings raise the possibility of a differential mechanistic pathway to AF according to race-ethnicity. [ABSTRACT FROM AUTHOR]

Background: Cryoballoon ablation (CBA) is one of the most commonly used technologies designed for pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF), although the dosing of CBA remains controversial. We evaluated the long‐term efficacy and safety of a novel individualized strategy of CBA compared to radiofrequency ablation (RFA) for patients with PAF. Methods: In this observational study, symptomatic patients with drug‐refractory paroxysmal AF were prospectively consented and enrolled in four centers, being assigned either to the CBA or RFA arm for ablation. In the CBA group, we used a time to isolation (TTI) – based dosing protocol. The primary endpoint was the recurrence of atrial arrhythmia >30 s following a 90‐day blanking period. The secondary endpoint was procedure‐related complications and procedure parameters. Results: A total of 500 patients were recruited in either the CBA group (n = 247) or the RFA group (n = 253) between January 2017 and July 2018. After a median follow‐up of 778 days, the atrial tachyarrhythmia‐free survival was 71.7% in the CBA group and 67.0% in the RFA group. CBA and RFA displayed similar major or minor complication occurrence, while the former had a significantly shorter procedure duration (82.5 min vs. 141.1 min, p <.001) and left atrial dwell time (60.1 min vs. 109.9 min, p <.001) but longer fluoroscopy exposure (13.8 min vs. 8.1 min, p <.001). Conclusion: Compared to RFA, our TTI‐based CBA dosing protocol showed comparable efficacy and safety, with a significantly reduced procedure duration in patients with PAF. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia affecting over 6 million people in the U.S. Fatigue is a frequent symptom of AF, yet no underlying biological mechanisms have been identified in AF-related fatigue as in other chronic conditions such as cancer or HIV fatigue (inflammation, tissue injury). We aimed to identify biomarkers and correlates of AF-fatigue in ARIC participants. Methods: Participants with AF from ARIC visit 5 (2011–2013) were included in the study. Multiple linear regression was used to estimate the association of high sensitivity troponin (hs-TnT), N-terminal fragment B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) levels with self-reported fatigue (SF-12 and PROMIS Fatigue Scale), depressive symptoms (Center for Epidemiological Studies Depression survey), and physical functioning (Short Physical Performance Battery) scores. All biomarkers underwent natural-log transformation. Results: There were 446 participants (mean age: 78 y ± 5; 44% women). In adjusted analyses, NT-proBNP was associated with AF-fatigue (β: 0.11, 95% CI: 0.03, 0.19), increased depressive symptoms (β: 0.44, 95% CI: 0.19, 0.70), and decreased physical function (β: −0.48, 95% CI: −0.72, −0.23). Hs-TnT was also associated with elevated AF-fatigue (β: 0.24, 95% CI: 0.09, 0.39) along with decreased physical function (β: −1.19, 95% CI: -1.64, −0.75). No significant associations were found with hsCRP and fatigue. Conclusion: Increased levels of cardiac injury biomarkers, depressive symptoms, and decreased physical function were associated with AF-fatigue. Inflammation was not associated with AF-fatigue; other physiological pathways, such as cardiac overload or myocardial injury may be more relevant in AF-fatigue. [ABSTRACT FROM AUTHOR]

The effect of intensive versus standard blood pressure (BP) lowering on the risk of atrial fibrillation (AF) is uncertain. Intensive BP lowering is associated with a lower risk of AF among patients with hypertension. We searched PubMed, EMBASE, and CENTRAL (inception to June 5, 2020) for randomized controlled trials evaluating the effect of intensive versus standard (target systolic BP < 140 mmHg) BP lowering on incident AF. We assessed heterogeneity using the I2 statistic then usedfixed-effects meta-analysis models to report pooled treatment effects and 95% confidence intervals. We also tested for publication bias by three funnel plot-based methods. The quality of each study was assessed with the Cochrane Risk of Bias tool. We assessed 16 candidate studies for eligibility from 2,312 published articles, but only three randomized clinical trials were eligible for inclusion and included a combined 12,219 participants with hypertension: Cardio-Sis (Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica), ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial), and SPRINT (Systolic Blood Pressure Intervention Trial). The target systolic BP in the intensive BP arm was <120 mmHg for participants in SPRINT and ACCORD-BP, but <130 mmHg for participants in Cardio-Sis. Participants randomized to intensive BP lowering had significantly lower risk of incident AF compared with those randomized to standard BP lowering (AF incidence 2.2% vs. 3.0%, respectively; pooled hazard ratio (95% confidence interval): 0.74 (0.59 -- 0.93)).Intensive BP lowering is associated with a significantly lower risk of incident AF in patients with hypertension. These findings add to the current evidence supporting the benefits of intensive BP control. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) frequently coexists in the setting of myocardial infarction (MI), being associated with increased mortality. Nonetheless, temporal trends in the occurrence of AF complicating MI and in the prognosis of these patients are not well described. We examined temporal trends in prevalence of AF in the setting of MI and the effect of AF on prognosis in the community. We studied a population-based sample of 20,049 validated first-incident nonfatal hospitalized MIs among 35- to 74-year old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 2009. Prevalence of AF in the setting of MI increased from 11% to 15% during the 23-year study period. The multivariable adjusted odds ratio for prevalent AF, per 5-year increment, was 1.11 (95% confidence interval 1.04 to 1.19). Overall, in patients with MI, AF was associated with increased 1-year case fatality (odds ratio 1.47, 95% confidence interval 1.07 to 2.01) compared with those without AF. However, there was no evidence that the impact of AF on MI survival changed over time or differed over time by sex, race, or MI classification (all p values >0.10). In conclusion, co-occurrence of AF in MI slightly increased between 1987 and 2009. The adverse impact of AF on survival in the setting of MI was consistent throughout. In the setting of MI, co-occurrence of AF should be viewed as a critical clinical event, and treatment needs unique to this population should be explored further. [ABSTRACT FROM AUTHOR]

Previous research suggests that elevated pulse pressure (PP) is a risk factor for atrial fibrillation (AF) independently of mean arterial pressure (MAP). PP may serve as an indirect measure of aortic stiffness (reduced distensibility), but whether directly measured aortic distensibility is related to risk for AF has not yet been studied. This analysis included 6,630 participants aged 45 to 84 years from the Multi-Ethnic Study of Atherosclerosis. At baseline, blood pressure and other relevant covariates were measured using standardized protocols. Magnetic resonance imagingebased aortic distensibility was measured in 3,441 participants. Incident AF was identified from hospitalization discharge codes and Medicare claims. Multivariate Cox models were used to estimate the association of blood pressure components and aortic distensibility with AF risk. During a mean follow-up of 7.8 years, 307 AF events (137 among those with aortic distensibility measurements) were identified. In multivariateadjusted models simultaneously including MAP and PP, each 1-SD increase in PP was associated with a 29% increased risk of AF (95% confidence interval 5% to 59%, p = 0.02), with MAP not being associated with increased AF risk. Overall, aortic distensibility was not consistently associated with AF risk: after removing outliers, each 1-SD increase in aortic distensibility was associated with a 9% increased risk ofAF(95% confidence intervalL22% to 51%, p = 0.63). In conclusion, in this large community-based cohort, we found that PP, but not MAP or aortic distensibility, was a significant risk factor for AF, emphasizing the importance of PP when assessing the risk for developing AF. Our results cast doubt on the clinical utility of aortic distensibility as a predictor for the development of AF. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a common heart rhythm disorder that is associated with an increased risk of stroke and heart failure (HF). Initially, an association between AF and ion channel dysfunction was identified, classifying the pathology as a predominantly electrical disease. More recently it has been recognized that fibrosis and structural atrial remodeling play a driving role in the development of this arrhythmia also in these cases. Purpose: Understanding the role of fibrosis in genetic determined AF could be important to better comprise the pathophysiology of this arrhythmia and to refine its management also in nongenetic forms. In this review we analyze genetic and epigenetic mechanisms responsible for AF and their link with atrial fibrosis, then we will consider analogies with the pathophysiological mechanism in nongenetic AF, and discuss consequent therapeutic options. [ABSTRACT FROM AUTHOR]

The article presents a study that examined the association between atrial fibrillation (AF) and increased risk of sudden cardiac death (SCD).The study reveals the link between incident AF and increased risk of SCD and non-SCD in the general population. It proposes additional research to identify predictors of SCD in patients with AF.

Introduction: Epidemiological studies report a male predominance in lone atrial fibrillation (LAF). Phenotypic differences between sporadic and familial LAF could aid in deciding which cases should undergo family screening. We sought to determine gender distribution in sporadic and familial LAF, gender-based differences, and phenotypic differences between sporadic and familial LAF. Methods: Since November 2000, 192 unrelated LAF probands were recruited. Sporadic LAF was defined as the absence of a family history of LAF. Familial LAF was classified as possible if one first- or second-degree relative had LAF, or confirmed if ≥ 2 relatives had LAF. Affected relatives (n = 87) of 34 confirmed familial probands were also evaluated. For unrelated LAF probands, differences in proportions and means were tested using χ2 and ANOVA, respectively. Difference in gender ratio among the family history groups was tested using mixed models. Results: Male proportion was greater among sporadic (82%) and possible familial probands (84%) than confirmed familial probands (62%), and affected relatives (54%), P < 0.001. Sporadic LAF was more common in men (62%) than women (51%), P = 0.03. More women were affected by palpitation and nocturnal symptoms than men. More patients had permanent AF in the confirmed familial group (27%), compared with the possible familial (7%) and the sporadic LAF group (8%), P = 0.05, but no other phenotypic discriminators were identified. Conclusions: Male predilection for LAF is attenuated as the likelihood of dominant Mendelian inheritance increases. Increased frequency of “sporadic” LAF among men could be partially due to X-linked recessive inheritance. Finally, sporadic and familial LAF are clinically indistinguishable. [ABSTRACT FROM AUTHOR]

Introduction: Right ventricular apical (RVA) pacing creates ventricular dyssynchrony and may compromise left ventricular ejection fraction (LVEF). The impact of RVA pacing in patients who have undergone atrioventricular junction (AVJ) ablation for atrial fibrillation (AF) is unclear. We sought to determine whether RVA pacing after AVJ ablation for patients with AF compromises LVEF in the short- or long-term. Methods/Results: We studied 286 patients with AF who underwent AVJ ablation and RVA pacing at our institution between 1990 and 2002. Patients were stratified into a short-term follow-up group (LVEF reassessed by echocardiography within a year after AVJ ablation, n = 134) and a long-term group (LVEF reassessed after a year, n = 152). Among all 286 patients (mean follow-up 20 months), we observed no change in mean LVEF after AVJ ablation and RVA pacing (48% before vs. 48% after, P = 0.42). Short-term follow-up patients had a statistically significant improvement in mean LVEF (46% before vs. 49% after, P = 0.03), whereas there was no statistically significant change in mean LVEF in long-term follow-up patients (49% before vs. 48% after, P = 0.37). Only 9% of short-term patients, 15% of long-term patients, and 1% of patients with baseline LVEF ≤ 40% experienced ≥10% absolute decrease in LVEF. Baseline LVEF > 40% was a multivariate predictor of LVEF decline. Conclusions: RVA pacing after AVJ ablation does not compromise LVEF in the short- or long-term for the vast majority of patients. Better predictors are needed to help us select patients for biventricular pacing after AVJ ablation. [ABSTRACT FROM AUTHOR]

To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort. We studied 6496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8 ± 5.3, 59% women, 23% black) who attended the 2011–2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%–49% for HF with midrange ejection fraction (HFmEF), and ≥ 50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF. Among eligible participants, 393 had HF (HFpEF = 232, HFmEF = 41, HFrEF = 35 and unclassified HF = 85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6–9.9) for HFpEF, 8.1 (4.3–15.3) for HFmEF, 10.0 (5.0–20.2) for HFrEF, 8.8 (5.6–14.0) for unclassified HF]. Among participants without AF at baseline (n = 5761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6–3.2) for HFpEF, 5.0 (2.7–9.3) for HFmEF, 3.5 (1.7–7.6) for HFrEF, 1.9 (0.9–3.7) for unclassified HF]. AF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies. • The association of heart failure (HF) subtypes with atrial fibrillation (AF) risk in the community is unclear. • Prevalence of AF was 7-10 times higher and AF rates were 2-5 times higher across HF subtypes compared to no HF. • Prevalence and incidence of AF was highest among individuals with HF with reduced ejection (HFrEF) fraction. Risk of AF in HF with midrange EF was more comparable to HFrEF than HF with preserved EF. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a heritable, genetically heterogeneous disorder. To identify gene defects that cause or confer susceptibility to AF, a cohort of 268 unrelated patients with idiopathic forms of familial and sporadic AF was recruited. LMNA, encoding the nuclear membrane proteins, lamin A/C, was selected as a candidate gene for lone AF based on its established association with a syndrome of dilated cardiomyopathy, conduction system disease, and AF. Comprehensive mutation scanning identified only 1 potentially pathogenic mutation. In conclusion, LMNA mutations rarely cause lone AF and routine genetic testing of LMNA in these patients does not appear warranted. [Copyright &y& Elsevier]

Supplemental Digital Content is available in the text. Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with substantial morbidity, mortality, and healthcare use. Great strides have been made in stroke prevention and rhythm control strategies, yet reducing the incidence of AF has been slowed by the increasing incidence and prevalence of AF risk factors, including obesity, physical inactivity, sleep apnea, diabetes mellitus, hypertension, and other modifiable lifestyle-related factors. Fortunately, many of these AF drivers are potentially reversible, and emerging evidence supports that addressing these modifiable risks may be effective for primary and secondary AF prevention. A structured, protocol-driven multidisciplinary approach to integrate lifestyle and risk factor management as an integral part of AF management may help in the prevention and treatment of AF. However, this aspect of AF management is currently underrecognized, underused, and understudied. The purpose of this American Heart Association scientific statement is to review the association of modifiable risk factors with AF and the effects of risk factor intervention. Implementation strategies, care pathways, and educational links for achieving impactful weight reduction, increased physical activity, and risk factor modification are included. Implications for clinical practice, gaps in knowledge, and future directions for the research community are highlighted. [ABSTRACT FROM AUTHOR]

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) guidelines recommend amiodarone as the preferred antiarrhythmic medication (AAM) in patients with left ventricular hypertrophy (LVH), due to potential pro‐arrhythmic risk with other AAM. However, there are limited data to support this assertion. Methods: We retrospectively analyzed the records of 8204 patients who were prescribed AAM for AF and had transthoracic echocardiogram (TTE) at the multicenter, VA Midwest Health Care Network from 2000 to 2021. We excluded patients without LVH (septal or posterior wall dimension ≤1.4 cm). The primary outcome variable was all‐cause mortality during antiarrhythmic therapy or within 6 months after stopping it. Propensity‐stratified analyses were performed between amiodarone versus non‐amiodarone (Vaughan‐Williams Class I and III) AAM. Results: A total of 1277 patients with LVH (mean age 70.2 ± 9.5 years) were included in the analysis. Of these, 774 (60.6%) were prescribed amiodarone. Baseline characteristics of the two comparison groups were similar after propensity adjustment. After a median 1.40 years of follow‐up, 203 (15.9%) patients died. Incidence rates per 100 patient‐year follow‐up was 9.02 (7.58–10.66) for amiodarone and 4.98 (3.91–62.56) for non‐amiodarone. In propensity‐stratified analysis, amiodarone use was associated with 1.58 times higher risk of mortality (95% CI 1.03–2.44; p =.038). Sub‐group analysis in 336 (26.3%) patients with severe LVH showed no difference in mortality (HR 1.41, 95% CI 0.82–2.43, p =.21). Conclusion: Among patients with AF and LVH, amiodarone was associated with a significantly higher mortality risk than other AAM. [ABSTRACT FROM AUTHOR]

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time. [ABSTRACT FROM AUTHOR]

Atrial myopathy is characterized by changes in left atrial function and size and may promote atrial fibrillation and cardiac thromboembolism. This study assessed the association between echocardiographic measures of left atrial function and ischemic stroke and examined whether they can improve stroke prediction beyond that achieved by the CHA2DS2-VASc score variables. Visual Abstract. Left Atrial Function and Stroke.: Atrial myopathy is characterized by changes in left atrial function and size and may promote atrial fibrillation and cardiac thromboembolism. This study assessed the association between echocardiographic measures of left atrial function and ischemic stroke and examined whether they can improve stroke prediction beyond that achieved by the CHA2DS2-VASc score variables. Background: Atrial myopathy—characterized by changes in left atrial function and size—may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or stroke, whether analysis of left atrial function and size can improve ischemic stroke prediction is unknown. Objective: To evaluate the association of echocardiographic left atrial function (reservoir, conduit, and contractile strain) and left atrial size (left atrial volume index) with ischemic stroke and determine whether these measures can improve the stroke prediction achieved by CHA 2 DS 2 -VASc score variables. Design: Prospective cohort study. Setting: ARIC (Atherosclerosis Risk in Communities) study. Participants: 4917 ARIC participants without prevalent stroke or AF. Measurements: Ischemic stroke events (2011 to 2019) were adjudicated by physicians. Left atrial strain was measured using speckle-tracking echocardiography. Results: Over 5 years, the cumulative incidences of ischemic stroke in the lowest quintiles of left atrial reservoir, conduit, and contractile strain were 2.99% (95% CI, 1.89% to 4.09%), 3.18% (CI, 2.14% to 4.22%), and 2.15% (CI, 1.09% to 3.21%), respectively, and that of severe left atrial enlargement was 1.99% (CI, 0.23% to 3.75%). On the basis of the Akaike information criterion, left atrial reservoir strain plus CHA 2 DS 2 -VASc variables was the best predictive model. With the addition of left atrial reservoir strain to CHA 2 DS 2 -VASc variables, 11.6% of the 112 participants with stroke after 5 years were reclassified to higher risk categories and 1.8% to lower risk categories. Among the 4805 participants who did not develop stroke, 12.2% were reclassified to lower and 12.7% to higher risk categories. Decision curve analysis showed a predicted net benefit of 1.34 per 1000 people at a 5-year risk threshold of 5%. Limitation: Underascertainment of subclinical AF. Conclusion: In people without prior AF or stroke, when added to CHA 2 DS 2 -VASc variables, left atrial reservoir strain improves stroke prediction and yields a predicted net benefit, as shown by decision curve analysis. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background Ceruloplasmin (CP) may promote structural changes in the atrium making it more arrhythmogenic. We assessed the associations between CP, CP-associated genetic variants, and incident atrial fibrillation (AF) in the Atherosclerosis Risk in Communities (ARIC) study. Methods and results We studied 10,059 men and women without prevalent AF aged 53 to 75 years in 1996–1998 and followed through 2012. Circulating CP was measured in stored blood samples obtained in 1996–1998. Polymorphisms rs11708215 and rs13072552, previously associated with CP concentrations, were measured in 10,059 and 8829 participants respectively. AF was ascertained from study electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox models were run to study the association between circulating CP, CP-associated polymorphisms, and the incidence of AF. Over 10.5 years of mean follow-up, 1357 cases of AF were identified. After adjusting for traditional risk factors and biomarkers, higher levels of circulating CP were associated with incident AF (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11, 1.61 comparing top to bottom quartiles). Both rs11708215 and rs13072552 were significantly associated with CP levels. Presence of the CP-increasing alleles in rs11708215 and rs13072552, however, were significantly associated with lower risk of AF in whites (HR 0.84, 95%CI 0.76, 0.94, p = 0.002 and HR 0.83; 95%CI 0.69, 0.99, p = 0.043 respectively per CP-increasing allele in the final adjusted model) but not in African Americans. Conclusions Even though higher CP concentrations were associated with increased AF risk, genetic variants associated with higher CP decreased the risk of AF in whites. Our results suggest that circulating CP levels may not be causally related to risk of incident AF. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is widely perceived to originate from the left atrium (LA). Whether increases in right ventricular (RV) afterload in older adults play an etiological role in AF genesis independent of LA and left ventricular (LV) remodeling is unknown.Research Question: Is higher RV afterload associated with greater AF risk independent of LA and LV remodeling?Study Design and Methods: In this observational prospective study, we included 2,246 community-dwelling older adults (mean age, 75 years) without known cardiovascular disease, with LV ejection fraction > 50%, LA volume index < 34 mL/m2, and E/e' ratio < 14 and a measurable functional tricuspid regurgitation jet velocity. From 2D-echocardiograms, we estimated pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR). We ascertained incident AF (through 2018) from hospital discharge codes and death certificates. We estimated hazard ratios (HR) by Cox regression.Results: During follow-up (median, 6.3 years; interquartile interval, 5.5-6.9 years), 215 participants developed AF. AF risk was significantly higher in the third (vs first) tertile of PASP (HR, 1.65; 95% CI, 1.08-2.54) and PVR (HR, 1.38; 95% CI, 1.00-2.08) independent of LA and LV structure and function, heart rate, BMI, prevalent sleep apnea, systemic BP, antihypertensive medications, and lung, kidney, and thyroid function. These associations persisted after further exclusion of participants with tricuspid regurgitation jet velocity > 2.8 m/s and lateral and septal mitral annular velocity above age- and sex-specific reference limits.Interpretation: In older adults, higher RV afterload is associated with greater AF risk independent of LA and LV remodeling. Future research should focus on confirming this novel association and elucidate underlying mechanisms. [ABSTRACT FROM AUTHOR]

The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. The present study aimed to understand the variation and disparity in awareness of AF in China. The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7–62.9%) and 10,202 (8.2%, 95%CI 5.4–10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0–42.9%) and 6.3% (95%CI 3.6–9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2–8.2%) and 5.2% (95%CI 2.7–7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations. • Only 55.3% patients with AF and 8.2% adults without AF were aware of AF in China. • The prevalence of AF awareness was consistently lower in rural areas than those in urban areas. • Lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Timing and trajectories of cardiovascular risk factor (CVRF) development in relation to atrial fibrillation (AF) have not been described previously. We assessed trajectories of CVRF and incidence of AF over 25 years in the ARIC study (Atherosclerosis Risk in Communities).Methods: We assessed trajectories of CVRF in 2456 individuals with incident AF and 6414 matched control subjects. Subsequently, we determined the association of CVRF trajectories with the incidence of AF among 10 559 AF-free individuals (mean age, 67 years; 52% men; 20% blacks). Risk factors were measured during 5 examinations between 1987 and 2013. Cardiovascular events, including incident AF, were ascertained continuously. We modeled the prevalence of risk factors and cardiovascular outcomes in the period before and after AF diagnosis and the corresponding index date for control subjects using generalized estimating equations. Trajectories in risk factors were identified with latent mixture modeling. The risk of incident AF by trajectory group was examined with Cox models.Results: The prevalence of stroke, myocardial infarction, and heart failure increased steeply during the time close to AF diagnosis. All CVRFs were elevated in AF cases compared with controls >15 years before diagnosis. We identified distinct trajectories for all the assessed CVRFs. In general, individuals with trajectories denoting long-term exposure to CVRFs had increased AF risk even after adjustment for single measurements of the CVRFs.Conclusions: AF patients have increased prevalence of CVRF many years before disease diagnosis. This analysis identified diverse trajectories in the prevalence of these risk factors, highlighting their different roles in AF pathogenesis. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine if there is an association between atrial arrhythmias and brain amyloid-β (Aβ), measured on florbetapir (FBP) PET. 346 nondemented participants from the Atherosclerosis Risk in Communities study underwent FBP-PET, 185 also wore Zio® XT Patch. The associations between global cortical Aβ (> 1.2 standardized uptake value ratio) and history of atrial fibrillation, zio-defined atrial tachycardia and premature atrial contractions, each, were evaluated. Among nondemented community-dwelling older adults, we did not find an association between atrial arrhythmias and Aβ. Other brain pathology may underlie the association described between atrial arrhythmias and cognition. [ABSTRACT FROM AUTHOR]

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Objective: Highest dominant-frequency (DF) drivers maintaining atrial fibrillation (AF) activities are effective ablation targets for restoring sinus rhythms in patients. This study aims to investigate whether AF drivers with highest activation rate can be noninvasively localized by means of a frequency-based cardiac electrical imaging (CEI) technique, which may aid in the planning of ablation strategy and the investigation of the underlying mechanisms of AF. Method: A total of seven out of 13 patients were recorded with spontaneous paroxysmal or persistent AF and analyzed. The biatrial DF maps were reconstructed by coupling 5-s BSPM with CT-determined patient geometry. The CEI results were compared with ablation sites and DFs found from BSPMs. Results: CEI imaged left-to-right maximal frequency gradient (7.42 ± 0.66 Hz versus 5.85 ± 1.2 Hz, LA versus RA, p < 0.05) in paroxysmal AF patients. Patients with persistent AF were imaged with a loss of the intrachamber frequency gradient and a dispersion of the fast sources in both chambers. CEI was able to capture the AF behaviors, which were characterized by short-term stability, dynamic transition, and spatial repetition of the highest DF sites. The imaged highest DF sites were consistent with ablation sites in patients studied. Conclusions: The frequency-based CEI allows localization of AF drivers with highest DF and characterization of the spatiotemporal frequency behaviors, suggesting the possibility for individualizing treatment strategy and advancing understanding of the underlying AF mechanisms. Significance : The establishment of noninvasive imaging techniques localizing AF drivers would facilitate management of this significant cardiac arrhythmia. [ABSTRACT FROM PUBLISHER]

Background: Although inflammation is involved in the development of atrial fibrillation (AF), the association of white blood cell (WBC) count and differential with AF has not been thoroughly examined in large cohorts with extended follow-up. Methods: We studied 14,500 men and women (25% blacks, 55% women, mean age 54) free of AF at baseline (1987–89) from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort in the United States. Incident AF cases through 2010 were identified from study electrocardiograms, hospital discharge records and death certificates. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with WBC count and differential. Results: Over a median follow-up time of 21.5 years for the entire cohort, 1928 participants had incident AF. Higher total WBC count was associated with higher AF risk independent of AF risk factors and potential confounders (HR 1.09, 95% CI 1.04–1.15 per 1-standard deviation [SD] increase). Higher neutrophil and monocyte counts were positively associated with AF risk, while an inverse association was identified between lymphocyte count and AF (multivariable adjusted HRs 1.16, 95% CI 1.09–1.23; 1.05, 95% CI 1.00–1.11; 0.91, 95% CI 0.86–0.97 per 1-SD, respectively). No significant association was identified between eosinophils or basophils and AF. Conclusions: High total WBC, neutrophil, and monocyte counts were each associated with higher AF risk while lymphocyte count was inversely associated with AF risk. Systemic inflammation may underlie this association and requires further investigation for strategies to prevent AF. [ABSTRACT FROM AUTHOR]

Rigatelli and Zuin also suggest that we consider amyloid deposition in the left atrium as an explanation for our findings. In addition, although the prevalence of cardiac amyloidosis appears to be increasing, it is still a relatively rare condition.[5] Drs Chen and Lin comment that we did not adjust for alcohol consumption and former smoking status in our analysis. Comment & Response B In Reply b In response to our study[1] on echocardiographic measures of left atrial function and size with incident dementia, Drs Rigatelli and Zuin inquire whether a subanalysis restricted to or excluding participants with an atrial septal defect could be conducted. [Extracted from the article]

Background Little is known about the incidence of and risk factors for sick sinus syndrome (SSS), a common indication for pacemaker implantation. Objectives This study sought to describe the epidemiology of SSS. Methods This analysis included 20,572 participants (mean baseline age 59 years, 43% male) in the ARIC (Atherosclerosis Risk In Communities) study and the CHS (Cardiovascular Health Study), who at baseline were free of prevalent atrial fibrillation and pacemaker therapy, had a heart rate of ≥50 beats/min unless using beta blockers, and were identified as of white or black race. Incident SSS cases were identified by hospital discharge International Classification of Disease-revision 9-Clinical Modification code 427.81 and validated by medical record review. Results During an average 17 years of follow-up, 291 incident SSS cases were identified (unadjusted rate 0.8 per 1,000 person-years). Incidence increased with age (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.47 to 2.05 per 5-year increment), and blacks had a 41% lower risk of SSS than whites (HR: 0.59; 95% CI: 0.37 to 0.98). Incident SSS was associated with greater baseline body mass index, height, N-terminal pro-B-type natriuretic peptide, and cystatin C, with longer QRS interval, with lower heart rate, and with prevalent hypertension, right bundle branch block, and cardiovascular disease. We project that the annual number of new SSS cases in the United States will increase from 78,000 in 2012 to 172,000 in 2060. Conclusions Blacks have a lower risk of SSS than whites, and several cardiovascular risk factors were associated with incident SSS. With the aging of the population, the number of Americans with SSS will increase dramatically over the next 50 years. [ABSTRACT FROM AUTHOR]

Premature atrial contractions (PACs) are associated with increased risk of atrial fibrillation (AF) and ischemic stroke. Although lifestyle and risk factor modification reduces AF incidence, their relationship to PACs frequency is unclear. We assessed the association of Life's Simple 7 (LS7) and individual LS7 factors in midlife with PACs frequency in late life in the Atherosclerosis Risk in Communities (ARIC) Study. We followed 1924 participants from ARIC clinic Visit 3 (1993‐–95) to Visit 6 (2016–17) when a 2-week continuous heart rhythm monitor (Zio®XT Patch) was applied. LS7 factors were assessed at Visit 3 and a composite score was calculated. PACs frequency was categorized as minimal (<0.1%), occasional (≥ 0.1%–5%) and frequent (>5%). Logistic regression was used to evaluate the association of LS7 score and individual factors with PACs frequency. Each 1-point LS7 score increase was associated with lower odds of frequent PACs vs. no PACs (OR [95% CI]: 0.87 [0.78, 0.98]) and frequent PACs vs. occasional PACs (OR [95% CI]: 0.88 [0.79, 0.98]). Of the individual LS7 factors, compared with ideal physical activity, poor physical activity was associated with 81% higher odds of frequent PACs vs. no PACs. Compared with ideal BMI, poor BMI was associated with 41% higher odds of occasional PACs vs. no PACs. Lifestyle risk factors, particularly physical activity and BMI, are associated with higher odds of PACs frequency. More research is needed to determine whether modifying these risk factors in midlife would prevent frequent PACs, and thereby prevent AF and stroke in older age. • Lifestyle risk factors play an important role in the pathogenesis of premature atrial contractions (PACs) • Obesity and poor physical activity in midlife were associated with an increased frequency of PACs in late life • A lower Life's Simple 7 score was associated with a higher odds of frequent PACs as compared to occasional and minimal PACs [ABSTRACT FROM AUTHOR]

Background: The burden imposed by multimorbidity on outcomes and on the effectiveness of atrial fibrillation therapies in elderly adults with atrial fibrillation is unknown.Methods: Patients with nonvalvular atrial fibrillation ages ≥75 years in the MarketScan Medicare Supplemental database from 2007-2015. Prevalence of 14 chronic conditions at the time of atrial fibrillation diagnosis were obtained and classified as cardiometabolic or noncardiometabolic. Cox regression estimated the associations of the number and type of conditions with stroke, severe bleeding, and heart failure hospitalizations. Tests for interaction were assessed between atrial fibrillation treatments and multimorbidity.Results: Among 275,617 patients with atrial fibrillation (mean age 83 years, 51% women), the mean (SD) number of conditions per participant was 3.0 (2.1). Over a mean follow-up of 23 months, 7814 strokes, 13,622 severe bleeds, and 19,252 heart failure events occurred. After adjustment, an increase in the number of cardiometabolic conditions was associated with greater risk of stroke (hazard ratio [HR] 1.07; 95% confidence interval [CI], 1.05-1.10), severe bleeding (HR 1.09; 95% CI, 1.07-1.11), and heart failure (HR 1.19, 95% CI, 1.18-1.20). In contrast, number of noncardiometabolic conditions had weak or null associations with risk of cardiovascular endpoints. Overall, the effectiveness of atrial fibrillation treatment on stroke and heart failure were similar across multimorbidity status, but bleeding risk associated with atrial fibrillation treatments was higher in patients with overall and subgroup multimorbidity.Conclusion: Cardiometabolic multimorbidity was associated with worse outcomes and modified bleeding risk in atrial fibrillation patients. These findings underscore the impact of cardiometabolic conditions on atrial fibrillation outcomes and highlights the need to incorporate multimorbidity management in atrial fibrillation treatment guidelines. [ABSTRACT FROM AUTHOR]

Background: Outcomes among atrial fibrillation (AF) patients may differ according to race/ethnicity and sex due to differences in biology, the prevalence of cardiovascular risk factors, and the use and effectiveness of AF treatments. We aimed to characterize patterns of cardiovascular risk across subgroups of AF patients by sex and race/ethnicity, since doing so may provide opportunities to identify interventions. We also evaluated whether these patterns changed over time. Methods: We utilized administrative claims data from the Optum Clinformatics® Datamart database from 2009 to 2015. Patients with AF with ≥6 months of enrollment prior to the first non-valvular AF diagnosis were included in the analysis. Final analysis utilized Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular outcomes stratified by sex and race/ethnicity. An additional analysis stratified outcomes by calendar year of AF diagnosis to evaluate changes in outcomes over time. Results: In a cohort of 380,636 AF patients, women had a higher risk of ischemic stroke [HR (95% CI): 1.25 (1.19, 1.31)] and lower risk of heart failure and myocardial infarction [HR (95% CI): 0.91 (0.88, 0.94) and 0.81 (0.77, 0.86), respectively)] compared to men. Black patients had elevated risk across all endpoints compared to whites, while Hispanics and Asian Americans showed no significant differences in any outcome compared to white patients. These sex and race/ethnic differences did not change over time. Conclusions: We found sex and race/ethnic differences in risk of cardiovascular outcomes among AF patients, without evidence of improvement over time. [ABSTRACT FROM AUTHOR]

In this article the authors reflect on complications, including thromboembolism and embolic stroke, that are associated with atrial fibrillation. They are supportive of developing precise stroke risk stratification in atrial fibrillation patients and of conducting research on the efficacy of using atrial fibrillation in low risk patients.

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Objective: Whether endogenous testosterone concentrations are associated with atrial fibrillation (AF) development is not well established. We assessed the association between plasma total testosterone concentrations and incident AF in a population-based longitudinal study.Study Design: Using data from the prospective Atherosclerosis Risk in Communities (ARIC) study, we identified incident AF among 9282 participants who had plasma total testosterone measured by liquid chromatography tandem mass spectrometry at Visit 4 (1996-1998).Main Outcome Measures: AF cases were identified by electrocardiograms performed during study visits, hospital records/discharge codes, and death certificates through 2013. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident AF across quartiles of plasma total testosterone, stratified by sex, with multivariable Cox models.Results: The mean age of the participant sample at ARIC Visit 4 was 63 years (range 52-75); 54.5% were women. Mean (SD) plasma total testosterone levels were 537 ng/dL (213) for men and 27.6 ng/dL (34.7) for women. Over a mean of 13.7 years of follow-up, 1664 incident cases of AF were identified. Comparing those in the highest quartile of plasma total testosterone concentration to those in the lowest quartile and after adjustment for potential confounding variables, there was a positive association between plasma total testosterone and incident AF in men (HR 1.33, 95% CI 1.07, 1.66), but no such association in women (HR 0.99, 95% CI 0.80, 1.22). Conclusion A higher plasma total testosterone concentration was associated with a modestly greater incidence rate of AF in men. [ABSTRACT FROM AUTHOR]

Objective: Oral anticoagulation (OAC) prescribed to AF patients for the prevention of cardioembolic complications likely has the added benefit of preventing venous thromboembolism (VTE). This study evaluated, among AF patients who are anticoagulated, whether type of OAC was associated with subsequent VTE risk.Methods: Non-valvular AF patients prescribed OACs between 2010 and September 2015 were identified via the MarketScan administrative claims databases. OACs included warfarin and direct OACs (DOACs: dabigatran, rivaroxaban, and apixaban). Incident VTE was defined by ICD-9-CM codes. Patients were matched on age, sex, CHA2DS2-VASc, and high-dimensional propensity scores. The final analysis included 117,912 AF patients.Results: In total, 1357 VTE events accrued over a mean follow-up of 484 days. In multivariable-adjusted, propensity score-matched Cox models, relative to new users of warfarin, risk of incident VTE was lower among new users of dabigatran [hazard ratio (95% confidence interval) = 0.55 (0.47-0.66)] and apixaban [0.51 (0.39-0.68)], but similar among new users of rivaroxaban [1.01 (0.87-1.19)]. In head-to-head DOAC comparisons, VTE risk was lower among users of dabigatran [0.48 (0.36-0.64)] and apixaban [0.61 (0.47-0.78)] vs rivaroxaban. Findings were mostly similar across patient sub-groups.Conclusions: In this large practice-based population of AF patients prescribed OACs for primary prevention of stroke and systemic embolization, subsequent risk of VTE was lowest among those prescribed apixaban and dabigatran, while risk was similar with prescriptions for warfarin and rivaroxaban. Among AF patients prescribed OACs, lowering the risk of VTE may be an additional benefit of apixaban and dabigatran, beyond the reduced bleeding risk observed in randomized clinical trials. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)—prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA2DS2-VASc score would improve its ability to predict AF-related ischemic stroke. Methods: We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. Results: Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33–2.55) independent of CHA2DS2-VASc variables, and that resulted in meaningful improvement in stroke prediction. The β estimate was approximately twice that of the CHA2DS2-VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P2-CHA2DS2-VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51–0.69) to 0.67 (0.60–0.75) in ARIC and 0.68 (0.52–0.84) to 0.75 (0.60–0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13–0.39) and 0.51 (0.18–0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96–1.44) and 0.82 (0.36–1.39), respectively. Conclusions: Abnormal P-wave axis—an ECG correlate of left atrial abnormality— improves ischemic stroke prediction in AF. Compared with CHA2DS2-VASc, the P2-CHA2DS2-VASc is a better prediction tool for AF-related ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether early cardiology involvement shortly after atrial fibrillation (AF) diagnosis is associated with favorable outcomes in AF patients who have cancer.Objectives: The purpose of this study was to examine the relationship between early cardiology involvement after AF diagnosis in patients with history of cancer.Methods: This study examined associations of early cardiology involvement with oral anticoagulation use, stroke, and bleeding among nonvalvular AF patients (n = 388,045; mean age 68 ± 15 years; 59% male) with a history of cancer (past or active) from the MarketScan database (2009 to 2014). International Classification of Disease-9th Revision-Clinical Modification codes in any position were used to identify cancer diagnosis prior to AF diagnosis. Provider specialty and filled anticoagulant prescriptions 3 months prior to and 6 months after AF diagnosis were obtained. Poisson regression models were used to compute the probability of an oral anticoagulant prescription fill, and Cox regression was used to estimate the risks of stroke and major bleeding.Results: A total of 64,016 (17%) AF patients had a history of cancer. Cardiology involvement was less likely to occur among patients with a history of cancer than those without (relative risk [RR]: 0.92 [95% confidence interval (CI): 0.91 to 0.93]). Patients with history of cancer were less likely to fill prescriptions for anticoagulants (RR: 0.89 [95% CI: 0.88 to 0.90]) than those without cancer, and similar results were observed across cancer types. Patients with cancer were more likely to fill prescriptions for anticoagulants (RR: 1.48 [95% CI: 1.45 to 1.52]) if seen by a cardiologist. A reduced risk of stroke (hazard ratio: 0.89 [95% CI: 0.81 to 0.99]) was observed among all cancer patients who were seen by a cardiology provider, without an increased risk of bleeding (hazard ratio: 1.04 [95% CI: 0.95 to 1.13]). Similar results were observed when the analysis was stratified by active versus remote history of cancer.Conclusions: Although AF patients with cancer were less likely to see a cardiologist, or fill anticoagulant prescriptions, cardiology involvement was associated with increased anticoagulant prescription fills and favorable AF-related outcomes in AF patients with cancer. [ABSTRACT FROM AUTHOR]

Background: No scores presently exist to predict bleeding in atrial fibrillation (AF) populations using direct oral anticoagulants (DOACs). We used data from two independent healthcare claims databases to develop and validate a predictive model of major bleeding in a contemporary AF population. Methods: Patients with non-valvular AF initiating oral anticoagulation were identified in the MarketScan databases from 2007–2014. Using Cox regression models in 1000 bootstrapped samples, we developed a model that selected variables predicting major bleeding in the first year after anticoagulant initiation. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009–2015. The discriminative ability of existing bleeding scores were individually evaluated and compared with the new bleeding model termed Anticoagulation-specific Bleeding Score (ABS) in both MarketScan and Optum. Results: Among 119,083 patients with AF initiating oral anticoagulation in the derivation cohort, 4,030 experienced a bleeding event. The variable selection model identified 15 variables (including individual type of oral anticoagulant) associated with major bleeding. Discrimination of the model was modest [c-statistic 0.68, 95% confidence interval (CI) 0.67–0.69]. The model was subsequently applied to 81,285 AF patients in the validation data set (3,238 bleeding events), showing similar discrimination (c-statistic 0.68, 95% CI 0.67–0.69). In both cohorts, the predictive performance of the ABS was better than the existing models for bleeding prediction in AF. Conclusions: We developed a model that uses administrative healthcare data for the identification of AF patients at higher risk of bleeding after initiation of oral anticoagulation, taking into account the lower bleeding risk in DOAC compared to warfarin users. [ABSTRACT FROM AUTHOR]

We previously reported that incident atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. We now aimed to identify predictors of SCD in persons with AF from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort study. We included all participants who attended visit 1 (1987–89) and had no prior AF (n = 14,836). Incident AF was identified from study electrocardiograms and hospitalization discharge codes through 2012. SCD was physician-adjudicated. We used cause-specific Cox proportional hazards models, followed by stepwise selection (backwards elimination, removing all variables with p>0.10) to identify predictors of SCD in participants with AF. AF occurred in 2321 (15.6%) participants (age 45–64 years, 58% male, 18% black). Over a median of 3.3 years, SCD occurred in 110 of those with AF (4.7%). Predictors of SCD in AF included higher age, body mass index (BMI), coronary heart disease, hypertension, diabetes, current smoker, left ventricular hypertrophy, increased heart rate, and decreased albumin. Predictors associated only with SCD and not other cardiovascular (CV) death included increased BMI (HR per 5-unit increase, 1.15, 95% CI, 0.97–1.36, p = 0.10), increased heart rate (HR per SD increase, 1.18, 95% CI 0.99–1.41, p = 0.07), and low albumin (HR per SD decrease 1.23, 95% CI 1.02–1.48, p = 0.03). In the ARIC study, predictors of SCD in AF that are not associated with non-sudden CV death included increased BMI, increased heart rate, and low albumin. Further research to confirm these findings in larger community-based cohorts and to elucidate the underlying mechanisms to facilitate prevention is warranted. [ABSTRACT FROM AUTHOR]

Background: Although current alcohol consumption is a risk factor for incident atrial fibrillation (AF), the more clinically relevant question may be whether alcohol cessation is associated with a reduced risk. Methods and results: We studied participants enrolled in the Atherosclerosis Risk in Communities Study (ARIC) between 1987 and 1989 without prevalent AF. Past and current alcohol consumption were ascertained at baseline and at 3 subsequent visits. Incident AF was ascertained via study ECGs, hospital discharge ICD-9 codes, and death certificates. Of 15,222 participants, 2,886 (19.0%) were former drinkers. During a median follow-up of 19.7 years, there were 1,631 cases of incident AF, 370 occurring in former consumers. Former drinkers had a higher rate of AF compared to lifetime abstainers and current drinkers. After adjustment for potential confounders, every decade abstinent from alcohol was associated with an approximate 20% (95% CI 11–28%) lower rate of incident AF; every additional decade of past alcohol consumption was associated with a 13% (95% CI 3–25%) higher rate of AF; and every additional drink per day during former drinking was associated with a 4% (95% CI 0–8%) higher rate of AF. Conclusions: Among former drinkers, the number of years of drinking and the amount of alcohol consumed may each confer an increased risk of AF. Given that a longer duration of abstinence was associated with a decreased risk of AF, earlier modification of alcohol use may have a greater influence on AF prevention. [ABSTRACT FROM AUTHOR]

Aims: Undetected atrial fibrillation (AF) may be common in the heart failure with preserved ejection fraction (HFpEF) population, and failure to detect this may lead to the missing of opportunities to prevent associated subclinical cerebral infarctions (SCIs) and cognitive decline.Methods and Results: We studied 1527 participants in the Atherosclerosis Risk in Communities (ARIC) Study, who underwent echocardiography, brain magnetic resonance imaging (MRI) and detailed cognitive assessment during 2011-13. Prevalences of SCI as detected by brain MRI were compared among the following groups: participants with no HFpEF/no AF; those with no HFpEF/AF; those with HFpEF/no AF, and those with HFpEF/AF. Cognitive scores were also compared. Prevalences of HFpEF and AF in this sample were 13.2% and 5.7%, respectively. Participants with HFpEF but no prior diagnosis of AF had a high prevalence of SCI by brain MRI (29.3%), which was similar to those in the no HFpEF/AF (24.5%) and HFpEF/AF (23.5%) groups, but higher than that in the no HFpEF/no AF subjects (17.3%). The odds of having SCI were higher in participants with HFpEF/no AF than in the no HFpEF/no AF group even after adjustment for potential confounders (odds ratio 1.56, 95% confidence interval 1.06-2.30). Individuals with HFpEF and SCI had lower cognitive scores than the reference (no HFpEF/no SCI) and HFpEF/no SCI groups.Conclusions: Subclinical cerebral infarctions were prevalent in subjects in the ARIC cohort with HFpEF and no prior AF diagnosis and are associated with measurable cognitive deficits. Although other sources of emboli may be possible, these data suggest that paroxysmal AF may be underdiagnosed in this population. There may be a role for earlier anticoagulation in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Aims: Undetected atrial fibrillation (AF) may be common in the heart failure with preserved ejection fraction (HFpEF) population, and failure to detect this may lead to the missing of opportunities to prevent associated subclinical cerebral infarctions (SCIs) and cognitive decline. Methods and results: We studied 1527 participants in the Atherosclerosis Risk in Communities (ARIC) Study, who underwent echocardiography, brain magnetic resonance imaging (MRI) and detailed cognitive assessment during 2011-13. Prevalences of SCI as detected by brain MRI were compared among the following groups: participants with no HFpEF/no AF; those with no HFpEF/AF; those with HFpEF/no AF, and those with HFpEF/AF. Cognitive scores were also compared. Prevalences of HFpEF and AF in this sample were 13.2% and 5.7%, respectively. Participants with HFpEF but no prior diagnosis of AF had a high prevalence of SCI by brain MRI (29.3%), which was similar to those in the no HFpEF/AF (24.5%) and HFpEF/AF (23.5%) groups, but higher than that in the no HFpEF/no AF subjects (17.3%). The odds of having SCI were higher in participants with HFpEF/no AF than in the no HFpEF/no AF group even after adjustment for potential confounders (odds ratio 1.56, 95% confidence interval 1.06-2.30). Individuals with HFpEF and SCI had lower cognitive scores than the reference (no HFpEF/no SCI) and HFpEF/no SCI groups. Conclusions Subclinical cerebral infarctions were prevalent in subjects in the ARIC cohort with HFpEF and no prior AF diagnosis and are associated with measurable cognitive deficits. Although other sources of emboli may be possible, these data suggest that paroxysmal AF may be underdiagnosed in this population. There may be a role for earlier anticoagulation in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) is the most common clinically-significant cardiac arrhythmia and is strongly associated with increased risk of stroke and other cardiovascular diseases. Validated prediction models for AF using traditional risk factors have been developed, but the added predictive value of novel risk factors is uncertain. Hypothesis: Novel biomarkers and measurements identified via machine learning will improve prediction of 5-year AF risk, beyond variables included in the base Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AF model. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study comprised of men and women aged 45-84 years from six US communities; 3530 participants (mean age 61.3 years, 51.4% female) with complete data on all candidate variables were included in the analysis. Physician-adjudicated AF was defined based on ICD-9 codes, supplemented by Centers for Medicare and Medicaid Services inpatient and outpatient hospital claims. Novel candidate variables previously identified with the random survival forests machine learning method were evaluated for their ability to improve prediction performance in Cox regression models. A parsimonious model was selected using LASSO. Results: During an average 11.4-year follow-up, 436 participants had an AF event. Most novel candidate variables did not significantly improve prediction performance when added to the CHARGE-AF Enriched model (Table). The parsimonious LASSO model included age, weight, current smoking, NT-proBNP, and ln(CAC+1) score. The novel model achieved good discrimination (c-statistic: 0.781, 95% CI: 0.762-0.800) and calibration (χ2: 6.0, p=0.54). Conclusions: Compared with the CHARGE-AF Score, only CAC score added significantly to AF risk prediction. A parsimonious MESA score containing only five variables performed as well as CHARGE-AF and a 24-item score ("All Predictors") derived by machine learning. [ABSTRACT FROM AUTHOR]

Background: Cardiac autonomic perturbations frequently antecede onset of paroxysmal atrial fibrillation (AF). Interventions that influence autonomic inputs to myocardium may prevent AF. However, whether low heart rate or heart rate variability (HRV), which are noninvasive measures of cardiac autonomic dysfunction, are associated with AF incidence is unclear.Objectives: This study sought to study the association between HRV and risk of AF.Methods: This study included 11,715 middle-aged adults in the ARIC (Atherosclerosis Risk In Communities) cohort with heart rate and HRV measures obtained from 2-min electrocardiogram recordings performed at baseline (1987 to 1989). These measures included SD of normal-to-normal RR intervals, high-frequency (HF) (0.15 to 0.40 Hz), low-frequency (0.04 to 0.15 Hz), and the low-frequency/HF ratio (denoting a greater sympathetic to parasympathetic dominance). Incident AF cases were ascertained by electrocardiogram at ARIC follow-up visits, hospital discharge diagnosis, or death certificates through 2011.Results: During an average follow-up of 19.4 years, 1,580 or 13.5% of participants developed AF. A baseline heart rate <60 beats/min was associated modestly with an increased risk of AF. Lower overall HRV as well as increased sympathetic/parasympathetic tone were associated independently with a higher risk of AF; the hazard ratio for each 1 SD lower SD of normal-to-normal RR intervals was 1.14 (95% confidence interval: 1.08 to 1.21), for HF was 1.12 (95% confidence interval: 1.06 to 1.17), and for low frequency/HF was 1.08 (95% confidence interval: 1.03 to 1.14).Conclusions: Cardiac autonomic dysfunction denoted by low resting short-term HRV was associated with higher AF incidence. A low heart rate may be associated with higher AF risk. Further studies are needed to determine whether interventions in the general population to restore autonomic balance may prevent AF. [ABSTRACT FROM AUTHOR]