Population Attributable Fraction of Total Stroke Associated with Modifiable Risk Factors in the United States.

Stroke is a leading cause of death in the United States across all race/ethnicity and sex groups, though disparities exist. We investigated the potential for primary prevention of total first stroke for Americans aged 20 and older, stratified by sex and race/ethnicity. Specifically, we calculated population attributable fractions (PAF) of first stroke for 7 potentially modifiable risk factors: smoking, physical inactivity, poor diet, obesity, hypertension, diabetes, and atrial fibrillation. PAFs are a function of (1) the relative risk of first stroke for people with the exposure and (2) the prevalence of the risk factor in the population. Relative risks came from recent meta-analyses and sex-race/ethnicity-specific prevalence estimates came from the 2015-2018 NHANES or Multi-Ethnic Study of Atherosclerosis (for atrial fibrillation only). Approximately 1/3 (35.7% [CI: 21.6%-49.0%]) for women, 32.7% [CI: 19.2%-45.1%] for men) of strokes were attributable to the 7 risk factors we considered. A 20% proportional reduction in stroke risk factors would result in approximately 37,000 fewer strokes annually in the United States. The estimated PAF was highest for non-Hispanic Black women (39.3% [CI: 24.8%-52.3%]) and lowest for non-Hispanic Asian men (25.5% [CI: 14.6%-36.2%]). For most groups, obesity and hypertension were the largest contributors to stroke rates.

Ion channel dysfunction and fibrosis in atrial fibrillation: Two sides of the same coin.

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.

Percutaneous left atrial appendage occlusion and risk of stroke, hospitalized bleeding and death in Medicare beneficiaries.

PURPOSE: Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee-for-service coverage 20% sample databases (2015-18) who had AF and an elevated CHA2DS2-VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death. METHODS: Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA2DS2-VASc score, and HAS-BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used. RESULTS: Median follow-up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86-1.52], 0.98 [0.86-1.10]). There was a 2.94-fold (95% CI: 2.50-3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years. CONCLUSION: In this analysis of real-world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post-procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications.

Association of diabetes and glycemic control with left atrial function: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Although glycemic status is associated with impaired cardiac structure and function, less is known on left atrial (LA) function across the glycemic spectrum. We evaluated the association of diabetes and glycemic control with LA function in a community-based cohort of older adults. METHODS AND RESULTS: This cross-sectional analysis included 5075 participants from the Atherosclerosis Risk in Communities Study (mean age 75.5 years, 58 % women, and 20 % Black adults) with echocardiographic strain data for LA reservoir, conduit, and contractile function. Multivariable linear regression was used to assess associations of diabetes status and glycemic control with LA function. In participants without diabetes, we used ordinal linear regression to evaluate associations of fasting glucose and HbA1c with LA function. Compared to individuals with a normal fasting glucose, prevalent diabetes was associated with 0.68 % lower LA conduit function (95 % confidence interval (CI): 1.11 to -0.25) and prediabetes a 0.47 % reduction (95 % CI: 0.85 to -0.09) in fully adjusted analyses. Persons with diabetes and high HbA1c (HgbA1c ≥ 7 % vs <7 %) had 1.05 % lower LA conduit function (95 % CI: 1.63, -0.48). Among individuals without diagnosed diabetes, higher fasting glucose, but not HbA1c, was significantly associated with worse LA conduit function. No significant associations were observed for LA reservoir and contractile function. CONCLUSIONS: A history of diabetes, prediabetes, and higher fasting glucose levels in persons without diabetes were associated with worse LA conduit function. Corroborative research is needed in prospective cohorts as well as studies that explore underlying mechanisms.

Left Atrial Mechanical Dysfunction and the Risk for Ischemic Stroke in People Without Prevalent Atrial Fibrillation or Stroke : A Prospective Cohort Study.

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 CHA2DS2-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 CHA2DS2-VASc variables was the best predictive model. With the addition of left atrial reservoir strain to CHA2DS2-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 CHA2DS2-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.

Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

Validation of a Zio XT Patch Accelerometer for the Objective Assessment of Physical Activity in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Combination devices to monitor heart rate/rhythms and physical activity are becoming increasingly popular in research and clinical settings. The Zio XT Patch (iRhythm Technologies, San Francisco, CA, USA) is US Food and Drug Administration (FDA)-approved for monitoring heart rhythms, but the validity of its accelerometer for assessing physical activity is unknown. OBJECTIVE: To validate the accelerometer in the Zio XT Patch for measuring physical activity against the widely-used ActiGraph GT3X. METHODS: The Zio XT and ActiGraph wGT3X-BT (Actigraph, Pensacola, FL, USA) were worn simultaneously in two separately-funded ancillary studies to Visit 6 of the Atherosclerosis Risk in Communities (ARIC) Study (2016-2017). Zio XT was worn on the chest and ActiGraph was worn on the hip. Raw accelerometer data were summarized using mean absolute deviation (MAD) for six different epoch lengths (1-min, 5-min, 10-min, 30-min, 1-h, and 2-h). Participants who had ≥3 days of at least 10 h of valid data between 7 a.m-11 p.m were included. Agreement of epoch-level MAD between the two devices was evaluated using correlation and mean squared error (MSE). RESULTS: Among 257 participants (average age: 78.5 ± 4.7 years; 59.1% female), there were strong correlations between MAD values from Zio XT and ActiGraph (average r: 1-min: 0.66, 5-min: 0.90, 10-min: 0.93, 30-min: 0.93, 1-h: 0.89, 2-h: 0.82), with relatively low error values (Average MSE × 106: 1-min: 349.37 g, 5-min: 86.25 g, 10-min: 56.80 g, 30-min: 45.46 g, 1-h: 52.56 g, 2-h: 54.58 g). CONCLUSIONS: These findings suggest that Zio XT accelerometry is valid for measuring duration, frequency, and intensity of physical activity within time epochs of 5-min to 2-h.

Mortality associated with antiarrhythmic medication for atrial fibrillation among patients with left ventricular hypertrophy.

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.

Association of abnormal p-wave parameters with brain MRI morphology: The atherosclerosis risk in communities neurocognitive study (ARIC-NCS).

BACKGROUND: Recent evidence indicates that abnormal P-wave parameters (PWPs)-ECG markers of atrial myopathy-are associated with incident dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. However, the mechanisms remain unclear and may include subclinical vascular brain injury. Hence, we evaluated the association of abnormal PWPs with brain MRI correlates of vascular brain injury in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: ARIC-NCS participants who underwent 3T brain MRI scans in 2011-2013 were included. PWPs were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, lacunar infarcts, cerebral microhemorrhages, brain volumes, and white matter disease (WMD) volume. We used weighted multivariable logistic and linear regression to evaluate the associations of abnormal PWPs with brain MRI outcomes. RESULTS: Among 1715 participants (mean age, 76.1 years; 61% women; 29% Black), 797 (46%) had ≥1 abnormal PWP. After multivariable adjustment, including adjusting for prevalent AF, abnormal P-wave terminal force in lead V1 (aPTFV1) and prolonged P-wave duration (PPWD) were associated with increased odds of both cortical (OR 1.41; 95% CI, 1.14 to 1.74 and OR 1.30; 95% CI, 1.04 to 1.63, respectively) and lacunar infarcts (OR 1.36; 95% CI, 1.15 to 1.63 and OR 1.37; 95% CI, 1.15 to 1.65, respectively). Advanced interatrial block (aIAB) was associated with higher odds of subcortical microhemorrhage (OR 2.04; 95% CI, 1.36 to 3.06). Other than a significant association between aPTFV1 with lower parietal lobe volume, there were no other significant associations with brain or WMD volume. CONCLUSION: In this exploratory analysis of a US community-based cohort, ECG surrogates of atrial myopathy are associated with a higher prevalence of brain infarcts and microhemorrhage, suggesting subclinical vascular brain injury as a possible mechanism underlying the association of atrial myopathy with dementia.

Growth Differentiation Factor 15 and the Subsequent Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a stress-responsive biomarker associated with several types of cardiovascular diseases. However, conflicting results have been reported regarding its association with incident atrial fibrillation (AF) in the general population. METHODS: In 10 234 White and Black Atherosclerosis Risk in Communities (ARIC) Study participants (mean age 60 years, 20.5% Blacks) free of AF at baseline (1993 to 1995), we quantified the association of GDF-15 with incident AF using Cox regression models. GDF-15 concentration was measured by an aptamer-based proteomic method. AF was defined as AF diagnosis by electrocardiogram at subsequent ARIC visits or AF diagnosis in hospitalization records or death certificates. Harrell's c-statistic and categorical net reclassification improvement were computed for risk discrimination and reclassification. RESULTS: There were 2217 cases of incident AF over a median follow-up of 20.6 years (incidence rate 12.3 cases/1000 person-years). After adjusting for potential confounders, GDF-15 was independently associated with incident AF, with a hazard ratio (HR) of 1.42 (95% CI, 1.24-1.62) for the top vs bottom quartile. The result remained consistent (HR 1.23 [95% CI, 1.07-1.41]) even after further adjusting for 2 cardiac biomarkers, cardiac troponin T and natriuretic peptide. The results were largely consistent across demographic subgroups. The addition of GDF-15 modestly improved the c-statistic by 0.003 (95% CI, 0.001-0.006) beyond known risk factors of AF. CONCLUSIONS: In this community-based biracial cohort, higher concentrations of GDF-15 were independently associated with incident AF, supporting its potential value as a clinical marker of AF risk.

Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC Study.

BACKGROUND: CKD is associated with sudden cardiac death and atrial fibrillation (AF). However, other types of arrhythmia and different measures of the burden of arrhythmias, such as presence and frequency, have not been well characterized in CKD. METHODS: To quantify the burden of arrhythmias across CKD severity in 2257 community-dwelling adults aged 71-94 years, we examined associations of major arrhythmias with CKD measures (eGFR and albuminuria) among individuals in the Atherosclerosis Risk in Communities study. Participants underwent 2 weeks of noninvasive, single-lead electrocardiogram monitoring. We examined types of arrhythmia burden: presence and frequency of arrhythmias and percent time in arrhythmias. RESULTS: Of major arrhythmias, there was a higher prevalence of AF and nonsustained ventricular tachycardia among those with more severe CKD, followed by long pause (>30 seconds) and atrioventricular block. Nonsustained ventricular tachycardia was the most frequent major arrhythmia (with 4.2 episodes per person-month). Most participants had ventricular ectopy, supraventricular tachycardia, and supraventricular ectopy. Albuminuria consistently associated with higher AF prevalence and percent time in AF, and higher prevalence of nonsustained ventricular tachycardia. When other types of arrhythmic burden were examined, lower eGFR was associated with a lower frequency of atrioventricular block. Although CKD measures were not strongly associated with minor arrhythmias, higher albuminuria was associated with a higher frequency of ventricular ectopy. CONCLUSIONS: CKD, especially as measured by albuminuria, is associated with a higher burden of AF and nonsustained ventricular tachycardia. Additionally, eGFR is associated with less frequent atrioventricular block, whereas albuminuria is associated with more frequent ventricular ectopy. Use of a novel, 2-week monitoring approach demonstrated a broader range of arrhythmias associated with CKD than previously reported.

Association of Echocardiographic Measures of Left Atrial Function and Size With Incident Dementia.

Importance: Atrial myopathy-characterized by alterations in left atrial (LA) function and size-is associated with ischemic stroke, independent of atrial fibrillation (AF). Electrocardiographic markers of atrial myopathy are associated with dementia, but it is unclear whether 2-dimensional echocardiographic (2DE)-defined LA function and size are associated with dementia. Objective: To examine the association of LA function and size with incident dementia. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a community-based prospective cohort. An exploratory, retrospective analysis was conducted. ARIC centers are located in Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and suburban Minneapolis, Minnesota. For this analysis, visit 5 (2011-2013) served as the baseline. Participants without prevalent AF and stroke and who had 2DEs in 2011-2013 were included and surveilled through December 31, 2019. Exposures: LA function (reservoir strain, conduit strain, contractile strain, emptying fraction, passive emptying fraction, and active emptying fraction), and LA size (maximal and minimal volume index) as evaluated by 2DE. Main Outcomes and Measures: Dementia cases were identified using in-person and phone cognitive assessments, hospitalization codes, and death certificates. Cox proportional hazards models were used. Results: Among 4096 participants (mean [SD] age, 75 [5] years; 60% women; 22% Black individuals), 531 dementia cases were ascertained over a median follow-up of 6 years. Dementia incidence for the lowest LA quintile was 4.80 for reservoir strain, 3.94 for conduit strain, 3.29 for contractile strain, 4.20 for emptying fraction, 3.67 for passive emptying fraction, and 3.27 for active emptying fraction per 100 person-years. After full-model adjustments, there were statistically significant associations between measures of LA function and dementia; the hazard ratios (HRs) from the lowest vs highest quintile for reservoir strain were 1.98 (95% CI, 1.42-2.75); for conduit strain, 1.50 (95% CI, 1.09-2.06); for contractile strain, 1.57 (95% CI, 1.16-2.14); for emptying fraction, 1.87 (95% CI, 1.31-2.65); and for active emptying fraction, 1.43 (95% CI, 1.04-1.96). LA passive emptying fraction was not significantly associated with dementia (HR, 1.26 [95% CI, 0.93-1.71]). Dementia incidence for the highest LA maximal volume index quintile was 3.18 per 100 person-years (HR for highest vs lowest quintile, 0.77 [95% CI, 0.58-1.02]) and for the highest minimal volume index quintile was 3.50 per 100 person-years (HR for the highest vs lowest quintile, 0.95 [95% CI, 0.71-1.28]). Both measures were not significantly associated with dementia. These findings were robust to sensitivity analyses that excluded participants with incident AF or stroke. Conclusions and Relevance: In this exploratory analysis of a US community-based cohort, several echocardiographic measures of lower LA function were significantly associated with an increased risk of subsequent dementia. Measures of LA size were not significantly associated with dementia risk. These findings suggest that impaired LA function may be a risk factor associated with dementia.

2021 ISHNE/ HRS/ EHRA/ APHRS collaborative statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society.

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/ Heart Rhythm Society/ European Heart Rhythm Association/ Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.

Serum magnesium and burden of atrial and ventricular arrhythmias: The Atherosclerosis Risk in Communities (ARIC) Study.

INTRODUCTION: Low serum magnesium (Mg) is associated with an increased incidence of atrial and ventricular arrhythmias. A richer phenotyping of arrhythmia indices, such as burden or frequency, may provide etiologic insights. OBJECTIVES: To evaluate cross-sectional associations of serum Mg with burden of atrial arrhythmias [atrial fibrillation (AF), premature atrial contractions (PAC), supraventricular tachycardia (SVT)], and ventricular arrhythmias [premature ventricular contractions (PVC), non-sustained ventricular tachycardia (NSVT)] over 2-weeks of ECG monitoring. METHODS: We included 2513 ARIC Study visit 6 (2016-2017) participants who wore the Zio XT Patch-a leadless, ambulatory ECG-monitor-for up to 2-weeks. Serum Mg was modeled categorically and continuously. AF burden was categorized as intermittent or continuous based on the percent of analyzable time spent in AF. Other arrhythmia burdens were defined by the average number of abnormal beats per day. Linear regression was used for continuous outcomes; logistic and multinomial regression were used for categorical outcomes. RESULTS: Participants were mean ± SD age 79 ± 5 years, 58% were women and 25% black. Mean serum Mg was 0.82 ± 0.08 mmol/L and 19% had hypomagnesemia (<0.75 mmol/L). Serum Mg was inversely associated with PVC burden and continuous AF. The AF association was no longer statistically significant with further adjustment for traditional lifestyle risk factors, only the association with PVC burden remained significant. There were no associations between serum Mg and other arrhythmias examined. CONCLUSIONS: In this community-based cohort of older adults, we found little evidence of independent cross-sectional associations between serum Mg and arrhythmia burden.

The prevalence of atrial fibrillation on 48-hour ambulatory electrocardiography in African Americans compared to Whites: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: A lower prevalence of atrial fibrillation (AF), but paradoxically higher burden of cardiovascular disease risk factors, has been observed among African Americans compared to Whites in studies of AF identified by mostly 12-lead electrocardiograms (ECGs) and clinically. METHODS: We performed 48-hour ambulatory electrocardiography (aECG) in a biracial sample of 1,193 participants in the Atherosclerosis Risk in Communities (ARIC) (mean age = 78 years, 62% African Americans, 64% female). Atrial fibrillation was identified from aECG, study visit ECGs, and discharge codes from cohort hospitalizations. We used covariate-adjusted logistic regression to estimate prevalence odds ratios (ORs) for AF in African Americans versus Whites, with adjustment for sampling and nonresponse. RESULTS: African Americans were more likely than Whites to have hypertension and diabetes but less likely to have coronary heart disease. The prevalence of AF detected by aECG or ARIC study ECG (adjusted for age and coronary heart disease) was lower in African Americans than Whites (2.7% vs 5.0%). White men had a higher (although not significant) AF prevalence of 7.8% compared to the other race and gender groups at 2.3%-2.8%. The adjusted OR for AF was 0.49 (0.24-0.99) comparing African Americans to Whites. Findings were similar when AF was defined to include prior AF hospitalizations (OR = 0.42, 0.25-0.72). There were no significant differences by race for asymptomatic or paroxysmal AF. CONCLUSIONS: Atrial fibrillation was less prevalent in African American than white older adults, regardless of detection method. Although overall detection of new AF cases with aECG was low, future studies should consider longer-term monitoring to characterize AF by race.

Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters.

BACKGROUND: Head-up tilt (HUT) is widely used for diagnostic evaluation of patients with suspected vasovagal syncope (VVS), but also offers an opportunity to study VVS pathophysiology. In this regard, it is known that plasma epinephrine (Epi) levels and Epi/norepinephrine (NE) ratio are markedly increased from baseline at the time of HUT-induced VVS. However, whether these changes contribute to VVS susceptibility remains uncertain. OBJECTIVE: We hypothesized that if catecholamines contributed to VVS directly, then a greater increase of plasma Epi and Epi/NE ratio early during HUT would be associated with shorter time to syncope. METHODS: The patient population comprised 33 individuals (14 men, 43 ± 2 years) with suspected VVS in whom 70° HUT reproduced symptoms. Arterial Epi and NE concentrations were collected at baseline (supine) and 2 minutes of HUT. Linear, exponential, and multiple regression were used to access the association between changing catecholamine levels and time to syncope. RESULTS: Mean ± SD time to positive HUT was 11 (7.6) minutes. Higher plasma Epi levels (pg/mL) both at baseline and at 2 minutes upright correlated with shorter time to syncope (baseline, R = -0.35, P = 0.048; and 2 minutes, R = -0.58, P = 0.001). Similarly, a greater Epi/NE ratio at 2 minutes head-up correlated with earlier time to syncope (R = -0.49, P = 0.007). These relationships remained significant after adjusting for age and sex (P = 0.006 and 0.02, respectively). CONCLUSION: Greater Epi levels and Epi/NE ratio early during HUT were associated with shorter time to VVS, suggesting a possible contribution to VVS susceptibility.

Factors Associated With Fatigue in Persons With Atrial Fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study.

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 (ß: 0.11, 95% CI: 0.03, 0.19), increased depressive symptoms (ß: 0.44, 95% CI: 0.19, 0.70), and decreased physical function (ß: -0.48, 95% CI: -0.72, -0.23). Hs-TnT was also associated with elevated AF-fatigue (ß: 0.24, 95% CI: 0.09, 0.39) along with decreased physical function (ß: -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.

Use of Sodium-Glucose Cotransporter-2 Inhibitors and Angiotensin Receptor-Neprilysin Inhibitors in Patients With Atrial Fibrillation and Heart Failure From 2021 to 2022: An Analysis of Real-World Data.

BACKGROUND: Contemporary use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi) in patients with atrial fibrillation (AF) and heart failure (HF) has not been described. METHODS AND RESULTS: We analyzed the MarketScan databases for the period January 1, 2021 to July 30, 2022. Validated algorithms were used to identify patients with AF and HF, and to classify patients into HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF). We assessed the prevalence of SGLT2i and ARNi use overall and by HF type. Additionally, we explored correlates of lower use, including demographics and comorbidities. The study population included 60 927 patients (mean age, 75 years; 43% women) diagnosed with AF and HF (85% with HFpEF, 15% with HFrEF). Prevalence of ARNi use was 11% overall (30% in HFrEF, 8% in HFpEF), whereas the corresponding figure was 6% for SGLT2i (13% in HFrEF, 5% in HFpEF). Use of both medications increased over the study period: ARNi from 9% to 12% (22%-29% in HFrEF, 6%-8% in HFpEF), and SGLT2i from 3% to 9% (6%-16% in HFrEF, 2%-7% in HFpEF). Female sex, older age, and specific comorbidities were associated with lower use of these 2 medication types overall and by HF type. CONCLUSIONS: Use of ARNi and SGLT2i in patients with AF and HF is suboptimal, particularly among women and older individuals, though use is increasing. These results underscore the need for understanding reasons for these disparities and developing interventions to improve adoption of evidence-based therapies among patients with comorbid AF and HF.