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BackgroundThe association of electrocardiographic (ECG) markers of atrial cardiomyopathy with heart failure (HF) and its subtypes is unclear.MethodsThis analysis included 6,754 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. Five ECG markers of atrial cardiomyopathy (P-wave terminal force in V1 [PTFV1], deep-terminal negativity in V1 [DTNV1], P-wave duration [PWD], P-wave axis [PWA], advanced intra-atrial block [aIAB]) were derived from digitally recorded electrocardiograms. Incident HF events through 2018 were centrally adjudicated. An ejection fraction (EF) of 50% at the time of HF was used to classify HF as HF with reduced EF (HFrEF), HF with preserved EF (HFpEF), or unclassified HF. Cox proportional hazard models were used to examine the associations of markers of atrial cardiomyopathy with HF. The Lunn-McNeil method was used to compare the associations in HFrEF vs. HFpEF.Results413 HF events occurred over a median follow-up of 16 years. In adjusted models, abnormal PTFV1 (HR (95%CI): 1.56(1.15–2.13), abnormal PWA (HR (95%CI):1.60(1.16–2.22), aIAB (HR (95%CI):2.62(1.47–4.69), DTNPV1 (HR (95%CI): 2.99(1.63–7.33), and abnormal PWD (HR (95%CI): 1.33(1.02–1.73), were associated with increased HF risk. These associations persisted after further adjustments for intercurrent AF events. No significant differences in the strength of association of each ECG predictor with HFrEF and HFpEF were noted.ConclusionsAtrial cardiomyopathy defined by ECG markers is associated with HF, with no differences in the strength of association between HFrEF and HFpEF. Markers of atrial Cardiomyopathy may help identify individuals at risk of developing HF.

Abstract Aims To evaluate the association of physical activity (PA) with atrial fibrillation (AF) incidence in an elderly population. Methods We studied 5166 participants of the Atherosclerosis Risk in Communities cohort examined in 2011–2013 free of AF. Self-reported PA was evaluated with a validated questionnaire. Weekly minutes of leisure-time moderate to vigorous physical activity (MVPA) were calculated and categorized using the 2018 Physical Activity Guidelines for Americans (no activity [0 min/week], low [> 0–

Abstract Background The high prevalence of falling among older adults constitutes a major public and clinical health concern. Many elderly persons may develop activities-specific restriction due to the risk of falling. This highlights the need for relevant evaluative tools. Methods This cross-sectional study used activities-specific performance frequency indicators to quantify activity restrictions in elderly participants, with all measures based on items from the Activities-Specific Balance Confidence (ABC) scale. Specifically, we tested for correlations between activities-specific performance frequency and balance confidence, functional balance/mobility, and fall history. There were 88 elderly participants, including 28 with stroke, 30 with Parkinson’s disease, and 30 with no neurological diseases. In addition to their activities-specific performance frequency measures, we collected a series of demographic and health-related characteristics from each participant. We analyzed between-group differences in activities-specific performance frequency and other demographic and health-related characteristics via the one-way analysis of variance and Kruskal-Wallis test. Next, we used the Spearman’s rank correlation test and binary logistic regression to investigate the correlations between activities-specific performance frequency and demographic/other health-related characteristics. Results There were significant group differences in performance frequency for all ABC activity items except for walking around the house, average ABC scores, and functional balance/mobility among normal older adults, participants with strokes and those with Parkinson's disease. Activities-specific performance frequency showed stronger correlations with activities-relevant functional mobility (r=0.250-0.713 for 15 items with significant correlations, 13 activity items with r≧0.4) than with balance confidence (r=0.279-0.668 for 13 items with significant correlations, 10 activity items with r≧0.4). The performance frequency of walking in crowds/bumped was the most sensitive measure for predicting fallers (odd ratio=3.310, p

Abstract Background Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed. Methods We studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. Results At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34–1.49; HR men = 1.21, 95% CI 1.15–1.28, p

Abstract Background Stiff arteries increase left ventricular (LV) end-systolic workload, leading over time to left atrial and ventricular remodeling, and providing the substrate for atrial fibrillation (AF) development. We investigated if carotid femoral pulse wave velocity (cfPWV), a measure of central arterial stiffness, is associated with incident AF. Methods In 2011–2013, cfPWV was measured in 3882 participants of the Atherosclerosis Risk in Communities Cohort Study (ARIC) without prevalent AF. Participants were followed through 2017 for the incidence of AF. Individuals were categorized in cfPWV quartiles based on visit measurements. Multivariable Cox regression models were used to evaluate the association of cfPWV with incident AF. Results Mean age was 75 years (SD 5), 60% were female and 20% were African American. Over a median follow-up of 5.5 years we identified 331 incident cases of AF. cfPWV demonstrated U-shaped associations with AF risk. In models adjusted for age, race, center, sex, education levels, and hemodynamic and clinical factors, hazard ratios (HR) of AF for participants in the first, third and fourth quartiles were 1.49 (95% CI 1.06, 2.10), 1.59 (1.14, 2.10), and 1.56(1.10, 2.19), respectively, compared to those in the second quartile. Conclusion Among community-dwelling older adults, low and high central arterial stiffness is associated with AF risk.

Abstract Background Fear of falling (FoF) and physical activity (PA) are important psychological and behavioral factors associated with falls. No instrument quantifies the link between these two factors to evaluate the risk of falls. We aimed to design a scale linking FoF with PA (Composite Activities-specific Risk of Falls Scale, CARFS) for people with various disability levels. Methods First, we designed a questionnaire comprising 40 balance-related activities from the International Classification of Functioning, Disability, and Health (ICF) for a pilot survey. Second, participants were interviewed about their activities-specific FoF degree and PA frequency. The participants comprised 30 community-dwelling older adults, hospitalized patients with strokes, and those with spinal cord injuries, each with different disability levels. Third, the content validity of the items was evaluated twice by 12 experienced rehabilitation professionals: one based on experience and the other on the survey responses. Items with a higher than moderate relevance in both evaluations were included in the CARFS. The panel of professionals discussed and voted on the contribution of FoF and PA on the CARF score. Finally, the scale sensitivity in distinguishing disability levels was analyzed to evaluate the population suitability to the CARFS. Results The CARFS included 14 activities. A five-point Likert scale was used to quantify degree of FoF (A) and frequency of PA (B). The CARF score (C), which was determined using the eq. C = A+(4-B) + A × B/2, reflected sensitivity to disability levels in most items. Conclusions The CARFS has strong content validity for measuring risk of falls in relation to the FoF and PA of people with various disability levels. It has a potential to provide a guide for designing individualized exercise- and behavior-focused fall prevention programs and enable the precise trtrun 0acking of program effectiveness as a multidimensional outcome measure.

Background Electronic medical records are increasingly used to identify disease cohorts; however, computable phenotypes using electronic medical record data are often unable to distinguish between prevalent and incident cases. Methods and Results We identified all Olmsted County, Minnesota residents aged ≥18 with a first‐ever International Classification of Diseases, Ninth Revision (ICD‐9) diagnostic code for atrial fibrillation or atrial flutter from 2000 to 2014 (N=6177), and a random sample with an International Classification of Diseases, Tenth Revision (ICD‐10) code from 2016 to 2018 (N=200). Trained nurse abstractors reviewed all medical records to validate the events and ascertain the date of onset (incidence date). Various algorithms based on number and types of codes (inpatient/outpatient), medications, and procedures were evaluated. Positive predictive value (PPV) and sensitivity of the algorithms were calculated. The lowest PPV was observed for 1 code (64.4%), and the highest PPV was observed for 2 codes (any type) >7 days apart but within 1 year (71.6%). Requiring either 1 inpatient or 2 outpatient codes separated by >7 days but within 1 year had the best balance between PPV (69.9%) and sensitivity (95.5%). PPVs were slightly higher using ICD‐10 codes. Requiring an anticoagulant or antiarrhythmic prescription or electrical cardioversion in addition to diagnostic code(s) modestly improved the PPVs at the expense of large reductions in sensitivity. Conclusions We developed simple, exportable, computable phenotypes for atrial fibrillation using structured electronic medical record data. However, use of diagnostic codes to identify incident atrial fibrillation is prone to some misclassification. Further study is warranted to determine whether more complex phenotypes, including unstructured data sources or using machine learning techniques, may improve the accuracy of identifying incident atrial fibrillation.

Background Cardiovascular risk factors are associated with cognitive decline and dementia. Magnetic resonance imaging provides sensitive measurement of brain morphology and vascular brain injury. However, associations of risk factors with brain magnetic resonance imaging findings have largely been studied in White participants. We investigated associations of race, ethnicity, and cardiovascular risk factors with brain morphology and white matter (WM) injury in a diverse population. Methods and Results In the Multi‐Ethnic Study of Atherosclerosis, measures were made in 2018 to 2019 of total brain volume, gray matter and WM volume, and WM injury, including WM hyperintensity volume and WM fractional anisotropy. We assessed cross‐sectional associations of race and ethnicity and of cardiovascular risk factors with magnetic resonance imaging measures. Magnetic resonance imaging data were complete in 1036 participants; 25% Black, 15% Chinese‐American, 19% Hispanic, and 41% White. Mean (SD) age was 72 (8) years and 53% were women. Although WM injury was greater in Black than in White participants in a minimally adjusted model, additional adjustment for cardiovascular risk factors and socioeconomic status each attenuated this association, rendering it nonsignificant. Overall, greater average WM hyperintensity volume was associated with older age and current smoking (69% greater vs never smoking); lower fractional anisotropy was additionally associated with higher diastolic blood pressure, use of antihypertensive medication, and diabetes. Conclusions We found no statistically significant difference in measures of WM injury by race and ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. In all racial and ethnic groups, older age, current smoking, hypertension, and diabetes were strongly associated with WM injury.

IntroductionThe newly developed Composite Activity-related Risk of Falls Scale (CARFS) is designed to measure composite activity-related risk of falls (CARF) in relation to the activity-specific fear of falling and physical behavior. This study tested the reliability and validity of the CARFS in older people with various health statuses and persons with stroke or spinal cord injury.MethodsParticipants included 70 older adults, 38 persons with stroke, and 18 with spinal cord injury. They were first surveyed using a combined questionnaire including the CARFS and activity-specific balance confidence (ABC) scale in addition to items asking for personal and disease-related information, fall history, walking independence levels for examining internal consistency, ceiling and floor effects, and convergent validity in each participant group. One week after the initial survey, 33 older participants were reexamined using the CARFS to analyze test-retest reliability, where a minimal detectable change was found. Significance was set at α = 0.05 for all analyses.ResultsThe CARFS showed excellent test-retest reliability in the dimensions of fear of falling, physical behavior, and CARF [ICC (3,1) = 0.972, 0.994, and 0.994, respectively for their overall score], with a minimal detectable change of 3.944 in the older population. The internal consistency of CARFS items was excellent in the older participants, good in participants with stroke or spinal cord injury (Cronbach's alpha = 0.945, 0.843, 0.831 in each participant group, respectively). No ceiling and floor effects were demonstrated in the wide range of people. For the convergent validity, overall CARF score was significantly correlated with the average ABC score in each participant group (rho = −0.824, −0.761, and −0.601, respectively; p < 0.01), and was significantly correlated with walking independence levels in each participant group (rho = −0.636, −0.423, and −0.522, respectively; p < 0.01). It showed weak correlation with the number of previous falls only in participants with stroke (rho = 0.291, p = 0.076).ConclusionThe CARFS is a reliable and valid tool for measuring fall risk in older people and persons with stroke or spinal cord injury.

Background Black Americans have more atrial fibrillation risk factors but lower atrial fibrillation risk than White Americans. Left atrial (LA) enlargement and/or dysfunction, frequent atrial tachycardia (AT), and premature atrial contractions (PAC) are associated with increased atrial fibrillation risk. Racial differences in these factors may exist that could explain the difference in atrial fibrillation risk. Methods and Results We included 2133 ARIC (Atherosclerosis Risk in Communities) study participants (aged 74±4.5 years[mean±SD], 59% women, 27% Black participants) who had echocardiograms in 2011 to 2013 and wore the Zio XT Patch (a 2‐week continuous heart monitor) in 2016 to 2017. Linear regression was used to analyze (1) differences in AT/day or PAC/hour between Black and White participants, (2) differences in LA measures between Black and White participants, and (3) racial differences in the association of LA measures with AT or PAC frequency. Compared with White participants, Black participants had a higher prevalence of cardiovascular risk factors and disease, lower AT frequency, greater LA size, and lower LA function. After multivariable adjustments, Black participants had 37% (95% CI, 24%–47%) fewer AT runs/day than White participants. No difference in PAC between races was noted. Greater LA size and reduced LA function are associated with more AT and PAC runs; however, no race interaction was present. Conclusions Differences in LA measures are unlikely to explain the difference in atrial fibrillation risk between Black and White individuals. Despite more cardiovascular risk factors and greater atrial remodeling, Black participants have lower AT frequency than White participants. Future research is needed to elucidate the protective mechanisms that confer resilience to atrial arrhythmias in Black individuals.

Abstract Background Hypertension is an established risk factor for the development of atrial fibrillation (AF). We evaluated the association and population impact of hypertension, defined using the new 2017 guidelines, on risk of AF. Methods In this analysis, we included 14,915 participants in the Atherosclerosis Risk in Communities study without history of AF. Participants underwent blood pressure measurements at baseline and their antihypertensive medication use was assessed. Incident AF was ascertained from study electrocardiograms, hospital records and death certificates. Cox proportional models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of AF among individuals with hypertension based on the JNC7 and 2017 ACC/AHA guidelines. Poisson models were used to obtain risk ratios and calculate population-attributable fractions (PAFs). Results We identified 2891 cases of incident AF during 21.4 years of mean follow-up. Prevalence of hypertension was 34 and 48% under the JNC7 and 2017 ACC/AHA definitions, respectively. HRs (95%CI) of AF in hypertensives versus non-hypertensives were 1.44 (1.32, 1.56) and 1.37 (1.26, 1.48) after multivariable adjustment under the old and new guidelines, respectively. The corresponding PAF (95%CI) using the old and new guidelines were 11% (8, 13%) and 13% (9, 16%), respectively. Conclusions Overall, our analysis shows that even though the prevalence of hypertension using the new criteria is 40% higher than with the old criteria, this does not translate into meaningful increases in AF attributable to hypertension. These results suggest that prevention or treatment of hypertension based on the new (versus old) guidelines may have limited impact on AF incidence.

Background Atrial fibrillation (AF) increases the risk of stroke and extracranial systemic embolic events (SEEs), but little is known about the magnitude of the association of AF with SEE. Methods and Results This analysis included 14 941 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 54.2±5.8, 55% women, 74% White) without AF at baseline (1987–1989) followed through 2017. AF was identified from study ECGs, hospital discharges, and death certificates, while SEEs were ascertained from hospital discharges. CHA2DS2‐VASc was calculated at the time of AF diagnosis. Cox regression was used to estimate associations of incident AF with SEE risk in the entire cohort, and between CHA2DS2‐VASc score and SEE risk in those with AF. Among eligible participants, 3114 participants developed AF and 270 had an SEE (59 events in AF). Incident AF was associated with increased risk of SEE (hazard ratio [HR], 3.58; 95% CI, 2.57–5.00), after adjusting for covariates. The association of incident AF with SEE was stronger in women (HR, 5.26; 95% CI, 3.28–8.44) than in men (HR, 2.68; 95% CI, 1.66–4.32). In those with AF, higher CHA2DS2‐VASc score was associated with increased SEE risk (HR per 1‐point increase, 1.24; 95% CI, 1.05–1.47). Conclusions AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA2DS2‐VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict adverse outcomes and guide treatment decisions in people with AF.

Background Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. Methods and Results We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007–2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD‐9‐CM] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [HR], 1.16; 95% CI, 1.12–1.20) and heart failure (HR, 1.33; 95% CI, 1.29–1.36) but not ischemic stroke (HR, 0.96; 95% CI, 0.92–1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy (HR, 0.87; 95% CI, 0.76–0.99) than among those with polypharmacy (HR, 0.98; 95% CI, 0.91–1.07; P=0.02 for interaction). Conclusion Polypharmacy is common among patients ≥75 with AF, is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ≥75 may lead to improved outcomes.

Background Atrial fibrillation (AF) is associated with cognitive decline. Whether left atrial enlargement (LAE), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Methods and Results Participants (n=3391; mean age, 75±5 years; 59% women) underwent cognitive tests and 2‐dimensional echocardiograms at visit 5 (2011–2013) and follow‐up cognitive tests at visit 6 (2016–2017). LAE was defined as left atrium volume index ≥34 mL/m2. AF was ascertained using study ECGs and hospitalization discharge codes. We assessed the association of AF and LAE with (a) cognitive domain scores at visit 5 and (b) cognitive domain score changes between visit 5 and visit 6. At visit 5, compared with the reference group (without AF, normal left atrium), participants with LAE and AF had significantly lower global cognition (Z score, −0.24; 95% CI, −0.38 to −0.10), whereas participants with AF and without LAE and participants with LAE and without AF did not have lower global cognition. In longitudinal analysis, compared with the reference group, participants with AF but without LAE had significantly greater decline in global cognition (Z score, −0.13; 95% CI, −0.21 to −0.06). However, LAE, with or without AF, was not associated with greater cognitive decline. Conclusion Although LAE with AF was significantly associated with lower cognitive function in cross‐sectional analysis, LAE, with or without AF, was not associated with greater cognitive decline over 5 years, highlighting the importance of evaluating longitudinal cognitive function. Future studies should have longer follow‐up and evaluate left atrium function.

Background Abnormal P‐wave indices (PWIs)—reflecting underlying left atrial abnormality—are associated with increased risk of stroke independent of atrial fibrillation. We assessed whether abnormal PWIs are associated with incident dementia and greater cognitive decline, independent of atrial fibrillation and ischemic stroke. Methods and Results We included 13 714 participants (mean age, 57±6 years; 56% women; 23% black) who were followed for dementia through the end of 2015. (Abnormal P‐wave terminal force in lead V1, ≥4000 μV×ms), abnormal P‐wave axis (>75° or 120 ms), and advanced interatrial block were determined from ECGs at visits 2 to 4. Dementia was adjudicated by an expert panel using data from cognitive tests and hospitalization International Classification of Diseases codes. Cognitive function was measured longitudinally using 3 neuropsychological tests. Cox proportional hazards models were used to assess the association between time‐dependent abnormal PWIs with incident dementia. Linear regression models were used to evaluate PWIs with cognitive function over time. At the conclusion of the study, 19%, 16%, 28%, and 1.9% of participants had abnormal P‐wave terminal force in lead V1, abnormal P‐wave axis, prolonged P‐wave duration, and advanced interatrial block, respectively. During mean follow‐up of 18 years, there were 1390 (10%) dementia cases. All abnormal PWIs except advanced interatrial block were associated with an increased risk of dementia even after adjustment for incident atrial fibrillation and stroke: multivariable hazard ratio of abnormal P wave terminal force in lead V1=1.60, 95% CI, 1.41 to 2.83; abnormal P‐wave axis, hazard ratio =1.36, 95% CI, 1.17 to 2.57; prolonged P‐wave duration, hazard ratio=1.60, 95% CI, 1.42 to 1.80. Only abnormal P‐wave terminal force in lead V1 was associated with greater decline in global cognition. Conclusions Abnormal PWIs are independently associated with an increased risk of dementia. This novel finding should be replicated in other cohorts and the underlying mechanisms should be evaluated.

Abstract: Randomized clinical trials comparing direct oral anticoagulants (DOACs) to warfarin in cancer patients have not been performed. We evaluated the effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of DOACs, in a large population of cancer patients with nonvalvular atrial fibrillation (AF). Using the MarketScan databases, we identified 16 096 AF patients (mean age, 74 years) initiating oral anticoagulant and being actively treated for cancer between 2010 and 2014. Anticoagulant users were matched by age, sex, enrollment date, and drug initiation date. Study end points were identified with diagnostic codes and included ischemic stroke, severe bleeding, other bleeding, and venous thromboembolism (VTE). Cox regression was used to estimate associations of anticoagulants with study end points. Compared with warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users, whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of ischemic stroke did not differ among anticoagulant users. Compared with warfarin, rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07, 0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and severe bleeding than rivaroxaban users. In this population of patients with AF and cancer, DOAC users experienced lower or similar rates of bleeding and stroke compared with warfarin users, and a lower rate of incident VTE.

Abstract Background Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population. Methods We selected NVAF patients initiating oral anticoagulant use in 2010–2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes. Results The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups. Conclusion In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Background Circulating NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, a well‐known indicator of atrial wall stress and remodeling, inversely correlate with body mass index. Both are strongly predictive of atrial fibrillation (AF). Their potential interaction in relation to incident AF, however, has not been explored. Methods and Results In total, 9556 participants of the ARIC (Atherosclerosis Risk in Communities) study who had 2 measurements of NT‐proBNP and no baseline AF or heart failure were followed from 1996 to 1998 through 2016 for the occurrence of incident AF. Participants were categorized as obese (body mass index ≥30) and nonobese (body mass index

Background The association of antidepressant medication type with the risk of cardiovascular disease (CVD) is unclear. We hypothesized that selective serotonin reuptake inhibitors (SSRIs) are associated with lower risks of CVD events relative to tricyclics and other non‐SSRI antidepressants. Methods and Results We studied 2027 participants from the ARIC (Atherosclerosis Risk in Communities) study (mean age 63±10 years; 29% men; 78% white) treated with antidepressants at some time between 1987 and 2013. Antidepressant usage was confirmed by participants bringing pill bottles to study visits. CVD events in the study sample were identified, including atrial fibrillation, heart failure, myocardial infarction, and ischemic stroke. Hazard ratios were used to compare CVD events adjusted for sociodemographic and clinical risk factors in SSRIs users (47%) versus non‐SSRI users. Participants were followed from antidepressant initiation up to 2016 for a median of 13.5 years. We identified 332 atrial fibrillation, 365 heart failure, 174 myocardial infarction and 119 ischemic stroke events. CVD risk was similar for SSRIs and non‐SSRI antidepressant users (hazard ratio, 1.10; 95% CI, 0.86–1.41 for atrial fibrillation; hazard ratio, 0.98; 95% CI, 0.77–1.25 for heart failure; hazard ratio, 0.91; 95% CI, 0.64–1.29 for myocardial infarction; and hazard ratio, 1.07; 95% CI, 0.70–1.63 for ischemic stroke). Conclusions SSRI use was not associated with reduced risk of incident CVD compared with non‐SSRI antidepressant use. These results do not provide evidence supporting the use of SSRIs compared with tricyclics and other non‐SSRI antidepressants in relation to CVD risk.

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke, heart failure, cognitive decline, dementia, myocardial infarction, sudden cardiac death (SCD), and all-cause death. Although these associations are firmly established, our understanding of the underlying mechanisms remains incomplete. Accumulating evidence suggests that left atrial (LA) abnormality or atrial cardiomyopathy may explain the relationship of AF to the aforementioned outcomes. P-wave indices (PWIs) reflect underlying atrial remodeling. In this mini review, we define representative PWIs, discuss state-of-the-art knowledge on the relationship between abnormal PWIs and AF-related cardiovascular outcomes (focusing on ischemic stroke and sudden cardiac death), and propose directions for future research. Our ultimate goal is to present a practical way forward to advance the emerging field of LA abnormality or atrial cardiomyopathy.

Background Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation (AF). Conversely, whites may have a lower risk of heart failure (CHF). N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels are higher in whites, predict incident AF, and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT‐proBNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT‐proBNP. The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT‐proBNP (CHS: 40% higher than blacks; 95% CI, 29–53; ARIC: 39% higher; 95% CI, 33–46) and had a greater risk of incident AF compared with blacks (CHS: adjusted hazard ratio, 1.60; 95% CI, 1.31–1.93; ARIC: hazard ratio, 1.93; 95% CI, 1.57–2.27). NT‐proBNP levels explained a significant proportion of the racial difference in AF risk (CHS: 36.2%; 95% CI, 23.2–69.2%; ARIC: 24.6%; 95% CI, 14.8–39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI, 1.05–1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI, 0.94–1.23), CHF‐related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT‐proBNP levels. No consistent relationship between race and CHF was observed.

(1) Background: Magnesium supplementation may be effective for the prevention of cardiometabolic diseases, but the mechanisms are unclear. Proteomic approaches can assist in identifying the underlying mechanisms. (2) Methods: We collected repeated blood samples from 52 individuals enrolled in a double-blind trial which randomized participants 1:1 to oral magnesium supplementation (400 mg magnesium/day in the form of magnesium oxide) or a matching placebo for 10 weeks. Plasma levels of 91 proteins were measured at baseline with follow-up samples using the Olink Cardiovascular Disease III proximity extension assay panel and were modeled as arbitrary units in a log2 scale. We evaluated the effect of oral magnesium supplementation for changes in protein levels and the baseline association between serum magnesium and protein levels. The Holm procedure was used to adjust for multiple comparisons. (3) Results: Participants were 73% women, 94% white, and had a mean age of 62. Changes in proteins did not significantly differ between the two intervention groups after correction for multiple comparisons. The most statistically significant effects were on myoglobin [difference −0.319 log2 units, 95% confidence interval (CI) (−0.550, −0.088), p = 0.008], tartrate-resistant acid phosphatase type 5 (−0.187, (−0.328, −0.045), p = 0.011), tumor necrosis factor ligand superfamily member 13B (−0.181, (−0.332, −0.031), p = 0.019), ST2 protein (−0.198, (−0.363, −0.032), p = 0.020), and interleukin-1 receptor type 1 (−0.144, (−0.273, −0.015), p = 0.029). Similarly, none of the associations of baseline serum magnesium with protein levels were significant after correction for multiple comparisons. (4) Conclusions: Although we did not identify statistically significant effects of oral magnesium supplementation in this relatively small study, this study demonstrates the value of proteomic approaches for the investigation of mechanisms underlying the beneficial effects of magnesium supplementation. Clinical Trials Registration: ClinicalTrials.gov NCT02837328.

Background Oral anticoagulants (OACs) in patients with atrial fibrillation (AF), in addition to reducing stroke risk, could also prevent adverse cognitive outcomes. The purpose of this study was to compare the risk of dementia incidence across patients with AF initiating different OACs. Methods and Results We identified patients with nonvalvular AF initiating OACs in 2 US healthcare claim databases, MarketScan (2007–2015) and Optum Clinformatics (2009–2015). Dementia, comorbidities, and use of medications were defined on the basis of inpatient and outpatient claims. We performed head‐to‐head comparisons of warfarin, dabigatran, rivaroxaban, and apixaban in propensity score–matched cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of incident dementia for each propensity score–matched cohort and meta‐analyzed database‐specific results. We analyzed 307 099 patients with AF from the MarketScan database and 161 346 from the Optum database, of which 6572 and 4391, respectively, had a diagnosis of incident dementia. The mean follow‐up of each cohort ranged between 0.7 and 2.2 years. Patients initiating direct OACs experienced lower rates of dementia than those initiating warfarin (dabigatran: HR, 0.85; 95% CI, 0.71–1.01; rivaroxaban: HR, 0.85; 95% CI, 0.76–0.94; apixaban: HR, 0.80; 95% CI, 0.65–0.97). There were no differences in rates of dementia comparing direct OAC user groups (dabigatran versus rivaroxaban: HR, 1.02; 95% CI, 0.79–1.32; dabigatran versus apixaban: HR, 0.92; 95% CI, 0.63–1.36; apixaban versus rivaroxaban: HR, 1.01; 95% CI, 0.86–1.19). Conclusions Patients with AF initiating direct OACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular direct OAC in relation to dementia rates.

BackgroundAlthough peripheral artery disease as defined by ankle‐brachial index (ABI) is associated with incident atrial fibrillation (AF), questions remain about the risk of AF in borderline ABI (>0.90 to 1.4). We evaluated the association of borderline ABI and ABI >1.4 in the ARIC (Atherosclerosis Risk in Communities) study, a population‐based prospective cohort study. Methods and ResultsWe included 14 794 participants (age, 54.2±5.8 years, 55% women, 26% blacks) with ABI measured at the baseline (1987–1989) and without AF. AF was identified from hospital records, death certificates, and ECGs. Using Cox proportional hazards, we evaluated the association between ABI and AF. During a median follow‐up of 23.3 years, there were 2288 AF cases. After adjustment for cardiovascular risk factors, hazard ratio (HR) (95% confidence interval) for AF among individuals with ABI 1.4 was not associated with increased AF risk. ABI ≤0.9 and borderline ABI were associated with a higher risk of AF compared with ABI 1.0 to 1.4. Demographics‐adjusted HRs (95% confidence interval) were 1.43 (1.17–1.75) and 1.32 (1.16–1.50), respectively. However, the associations of ABI ≤0.9 and borderline ABI with AF were attenuated after adjusting for cardiovascular risk factors (HR [95% confidence interval], 1.10 [0.90–1.34] and 1.14 [1.00–1.30]), respectively. ConclusionsPeripheral artery disease indicated by low ABI, including borderline ABI, is a weak risk factor for AF. ABI >1.4 is not associated with an increased AF risk. The relationship between peripheral artery disease and AF appears to be mostly explained by traditional atherosclerotic risk factors.

BackgroundThe American Heart Association has defined metrics of ideal cardiovascular health known as Life's Simple 7 (LS7) to prevent cardiovascular disease. We examined the association between LS7 and incident atrial fibrillation (AF) in a biracial cohort of middle‐ and older‐aged adults without known cardiovascular disease. Methods and ResultsThis analysis included 13 182 ARIC (Atherosclerosis Risk in Communities) study participants (mean baseline age=54±5.7 years; 56% women; 25% black) free of AF and cardiovascular disease. An overall LS7 score was calculated as the sum of the LS7 component scores and classified as inadequate (0‐4), average (5‐9), or optimal (10‐14) cardiovascular health. The primary outcome was incident AF, identified primarily by ECG and hospital discharge coding of AF through December 31, 2014. A total of 2266 (17%) incident AF cases were detected over a median follow‐up of 25.1 years. Compared with the inadequate category (n=1057), participants in the average (n=8629) and optimal (n=3496) categories each had a lower risk of developing AF in a multivariable Cox proportional hazards model (hazard ratio 0.59, 95% confidence interval 0.51, 0.67 for average; and hazard ratio 0.38, 95% confidence interval 0.32, 0.44 for optimal). In a similar model, a 1‐point‐higher LS7 score was associated with a 12% lower risk of incident AF (hazard ratio 0.88, 95% confidence interval 0.86, 0.89). ConclusionsA higher LS7 score is strongly associated with a lower risk of AF in individuals without baseline cardiovascular disease. Determining whether interventions that improve the population's cardiovascular health also reduce AF incidence is needed.

BackgroundPrevious studies have reported that atrial fibrillation (AF) is associated with cognitive decline and dementia. These studies, however, had limited follow‐up, were based mostly on white and highly selected populations, and did not account for attrition. We evaluated the association of incident AF with 20‐year change in cognitive performance (accounting for attrition) and incident dementia in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and ResultsWe analyzed data from 12 515 participants (mean age, 56.9 [SD, 5.7] years in 1990–1992; 56% women and 24% black) from 1990 to 1992 through 2011 to 2013. Incident AF was ascertained from study ECGs and hospital discharge codes. Cognitive tests were performed in 1990 to 1992, 1996 to 1998, and 2011 to 2013. Incident dementia was clinician adjudicated. We used generalized estimating equations and Cox proportional hazards models to assess the association of time‐dependent AF with change in Z scores of cognitive tests and incident dementia, respectively. During 20 years, 2106 participants developed AF and 1157 participants developed dementia. After accounting for cardiovascular risk factors, including ischemic stroke, the average decline over 20 years in global cognitive Z score was 0.115 (95% confidence interval, 0.014–0.215) greater in participants with AF than in those without AF. Further adjustment for attrition by multiple imputation by chained equations strengthened the association. In addition, incident AF was associated with an increased risk of dementia (hazard ratio, 1.23; 95% confidence interval, 1.04–1.45), after adjusting for cardiovascular risk factors, including ischemic stroke. ConclusionsAF is associated with greater cognitive decline and increased risk of dementia, independent of ischemic stroke. Because cognitive decline is a precursor to dementia, our findings prompt further investigation to identify specific treatments for AF that will delay the trajectory of cognitive decline and, thus, prevent dementia in patients with AF.

BackgroundDifferences in anticoagulation rates and direct oral anticoagulant use by provider specialty may identify an area of practice improvement to reduce future stroke events in patients with atrial fibrillation (AF). Methods and ResultsWe examined anticoagulant prescription fills in 388 045 (mean age, 68±15 years; 59% male) patients with incident AF from the MarketScan databases between 2009 and 2014. Provider specialty and filled anticoagulant prescriptions around the time of AF diagnosis (3 months before through 6 months after) were obtained from outpatient services and pharmacy claims. We estimated the association of provider specialty (cardiology versus primary care) with filling oral anticoagulant prescriptions, adjusting for patient characteristics. The risk of stroke and bleeding events also was explored. A total of 235 739 patients (61%) had a cardiology provider claim, whereas 152 306 (39%) were exclusively managed by primary care. Patients seen by cardiology providers were more likely to fill anticoagulant prescriptions than those seen by primary care (39% versus 27%; relative risk, 1.39; 95% confidence interval [CI], 1.37–1.40). Differences were observed for direct oral anticoagulants (relative risk, 1.74; 95% CI, 1.71–1.78) and warfarin (relative risk, 1.24; 95% CI, 1.22–1.26). A reduced risk of stroke events was observed among those seen by cardiology providers (hazard ratio, 0.90; 95% CI, 0.86–0.94) compared with primary care, without an increased bleeding risk (hazard ratio, 1.03; 95% CI, 0.98–1.07). ConclusionsPatients seen by an outpatient cardiology provider shortly after AF diagnosis were more likely to initiate oral anticoagulation and were at lower risk of future stroke events without a higher rate of bleeding. Early referral to cardiology specialists may increase initiation of anticoagulant therapies and improve outcomes in AF.

BackgroundAtrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12‐lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12‐lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality. Methods and ResultsWe utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12‐lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3–2.0; P

BackgroundAtrial fibrillation (AF) has been associated with faster cognitive decline and increased dementia risk. Factors associated with dementia in patients with AF have been seldom studied. Methods and ResultsWe studied 6432 individuals from the ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study). In 2011 to 2013, participants underwent a physical exam, echocardiography, detailed cognitive assessments, and a subset, brain magnetic resonance imaging. Dementia and mild cognitive impairment (MCI), as well as etiology of MCI/dementia, Alzheimer's disease–related or vascular, were adjudicated by an expert panel. AF was defined by study ECGs and past hospitalizations. We used logistic regression to estimate odds ratios and 95% CI of MCI/dementia by AF status and to assess cross‐sectional correlates of MCI/dementia in patients with AF. Among 6432 participants, 611 (9.5%) had prevalent AF. AF was associated with increased odds of dementia and MCI (odds ratio, 95% CI, 2.25, 1.64–3.10, and 1.28, 1.04–1.56, respectively). Prevalence of Alzheimer's disease–related MCI/dementia and vascular MCI/dementia were higher in participants with AF than without AF (odds ratio, 95% CI, 1.29, 1.04–1.61, and 1.50, 0.99–2.25, respectively). In multivariable analyses, older age, lower body mass index, diabetes mellitus, stroke, and APOE genotype were associated with dementia prevalence in participants with AF. In models evaluating MCI/dementia subtypes, diabetes mellitus was associated with Alzheimer's disease–related MCI/dementia, whereas male sex and stroke were risk factors for vascular MCI/dementia. ConclusionsIn a large, community‐based study, AF was associated with higher prevalence of MCI and dementia. Controlling cardiometabolic risk factors is a potential target for prevention of adverse cognitive outcomes in AF patients.

Left ventricular non-compaction (LVNC) cardiomyopathy is a rare congenital disorder, classified by the American Heart Association as a primary genetic cardiomyopathy and characterized by multiple trabeculations within the left ventricle. LVNC cardiomyopathy has been associated with 3 major clinical manifestations: heart failure, atrial and ventricular arrhythmias and thromboembolic events, including stroke. In this case report, we describe a female patient with apparently isolated LVNC in whom pause-dependent polymorphic ventricular tachycardia suggesting torsades de pointes occurred in the presence of a normal QT interval.

BackgroundWe evaluated the association of carotid intima‐media thickness (cIMT), carotid plaque, carotid distensibility coefficient (DC), and aortic pulse wave velocity (PWV) with incident atrial fibrillation (AF) and their role in improving AF risk prediction beyond the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)‐AF risk score. Methods and ResultsWe analyzed data from 3 population‐based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study (n=13 907); Multi‐Ethnic Study of Atherosclerosis (MESA; n=6640), and the Rotterdam Study (RS; n=5220). We evaluated the association of arterial indices with incident AF and computed the C‐statistic, category‐based net reclassification improvement (NRI), and relative integrated discrimination improvement (IDI) of incorporating arterial indices into the CHARGE‐AF risk score (age, race, height weight, systolic and diastolic blood pressure, antihypertensive medication use, smoking, diabetes, previous myocardial infarction, and previous heart failure). Higher cIMT (meta‐analyzed hazard ratio [95% CI] per 1‐SD increment, 1.12 [1.08–1.16]) and presence of carotid plaque (1.30 [1.19–1.42]) were associated with higher AF incidence after adjustment for CHARGE‐AF risk‐score variables. Lower DC and higher PWV were associated with higher AF incidence only after adjustment for the CHARGE‐AF risk‐score variables excepting height, weight, and systolic and diastolic blood pressure. Addition of cIMT or carotid plaque marginally improved CHARGE‐AF score prediction as assessed by the relative IDI (estimates, 0.025–0.051), but not when assessed with the C‐statistic and NRI. ConclusionsHigher cIMT, presence of carotid plaque, and greater arterial stiffness are associated with higher AF incidence, indicating that atherosclerosis and arterial stiffness play a role in AF etiopathogenesis. However, arterial indices only modestly improve AF risk prediction.

BackgroundExisting equations for prediction of atrial fibrillation (AF) have been developed and validated in white and African‐American populations. Whether these models adequately predict AF in more racially and ethnically diverse populations is unknown. Methods and ResultsWe studied 6663 men and women 45 to 84 years of age without AF at baseline (2000–2002) enrolled in the Multi‐Ethnic Study of Atherosclerosis (MESA). Of these, 38% were non‐Hispanic whites, 28% non‐Hispanic African Americans, 22% Hispanics, and 12% Chinese Americans. AF during follow‐up was ascertained from hospitalization discharge codes through 2012. Information collected at baseline was used to calculate predicted 5‐year risk of AF using the previously published simple CHARGE‐AF model, which only includes clinical variables, and a biomarker‐enriched CHARGE‐AF model, which also considers levels of circulating N‐terminal of the prohormone B‐type natriuretic peptide and C‐reactive protein. For comparison purposes, we also assessed performance of the 10‐year Framingham AF model. During a mean follow‐up of 10.2 years, 351 cases of AF were identified. The C‐statistic of the CHARGE‐AF models were 0.779 (95% CI, 0.744–0.814) for the simple model and 0.825 (95% CI, 0.791–0.860) for the biomarker‐enriched model. Calibration was adequate in the biomarker‐enriched model (χ2=7.9; P=0.55), but suboptimal in the simple model (χ2=25.6; P=0.002). In contrast, the 10‐year Framingham score had a C‐statistic (95% CI) of 0.746 (0.720–0.771) and showed poor calibration (χ2=57.4; P

Clinical Research. Presentation type: Oral Presentation. Introduction: Recent evidence from hospital-based cohorts suggests that the CHA2DS2-VASc score may be used to predict ischemic stroke in individuals without atrial fibrillation (AF). We aimed to evaluate the association of the CHA2DS2-VASc score for incident ischemic stroke, with and without AF, among community-dwelling individuals. Methodology: We included all participants from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 4 (1996–98) and had no prior AF, stroke, and were not on warfarin. Incident AF was ascertained from study ECGs and hospital discharge diagnosis codes, and stroke was physician-adjudicated. AF cases were matched with non-AF controls based on CHA2DS2-VASc variables, and participants were censored if they began anticoagulants during the follow-up period. Time-to-event and competing risk analyses were used to calculate the incidence rates of ischemic stroke by CHA2DS2-VASc score, stratified by AF status. RESULTS: This analysis included 4,039 participants (mean age, 74.6 ± 6.8 years; 50% women; 14% blacks) of whom 1,180 had incident AF. After a mean follow-up of 5.1 ± 4.2 years, 182 (4.5%) developed ischemic stroke. Higher CHA2DS2-VASc score was associated with higher incidence of ischemic stroke in participants with and without AF. In participants without AF, the absolute 1-year risk remained low (0.6%) even in those with CHA2DS2-VASc score of ⩾6. In participants with AF, the absolute 1-year risk of ischemic stroke was 3.2% even in those with CHA2DS2-VASc score of 0–1) Conclusion: The risk of ischemic stroke is low across CHA2DS2-VASc score categories in community-dwelling individuals without AF. Individuals with AF are at high risk for ischemic stroke even with low CHA2DS2-VASc score, suggesting the need for stroke prevention in individuals with AF and one CHA2DS2-VASc stroke risk factor.

Low magnesium may increase the risk of atrial fibrillation. We conducted a double-blind pilot randomized trial to assess adherence to oral magnesium supplementation (400 mg of magnesium oxide daily) and a matching placebo, estimate the effect on circulating magnesium concentrations, and evaluate the feasibility of using an ambulatory heart rhythm monitoring device (ZioPatch) for assessing premature atrial contractions. A total of 59 participants were randomized; 73% were women, and the mean age was 62 years. A total of 98% of the participants completed the follow-up. In the magnesium supplement group, 75% of pills were taken, and in the placebo group, 83% were taken. The change in magnesium concentrations was significantly greater for those given the magnesium supplements than for those given the placebo (0.07; 95% confidence interval: 0.03, 0.12 mEq/L; p = 0.002). The ZioPatch wear time was approximately 13 of the requested 14 days at baseline and follow-up. There was no difference by intervention assignment in the change in log premature atrial contractions burden, glucose, or blood pressure. Gastrointestinal changes were more common among the participants assigned magnesium (50%) than among those assigned the placebo (7%), but only one person discontinued participation. In sum, compliance with the oral magnesium supplementation was very good, and acceptance of the ZioPatch monitoring was excellent. These findings support the feasibility of a larger trial for atrial fibrillation (AF) prevention with oral magnesium supplementation.