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Abstract Background This systematic review aims to determine the impact of isolated diastolic hypertension (IDH) on cardiovascular outcomes. Methods We searched only English language articles on PubMed and SCOPUS until July 31, 2023 to investigate the association between IDH and cardiovascular outcomes. Results This meta-analysis of 19 studies evaluated the impact of different hypertension diagnostic guidelines (ACC/AHA: American Heart Association/American College of Cardiology; JNC7: Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; NICE/ESC: National Institute for Health and Care Excellence/European Society of Cardiology) on hypertension-related outcomes. Studies had varying sample sizes (173 to 2,969,679 participants) and study designs. In cohort studies using JNC7 guidelines, IDH was linked to increased cardiovascular disease (CVD) risk (HR: 1.45, 95% CI 1.17, 1.74), CVD mortality (HR: 1.54, 95% CI 1.23, 1.84), and coronary heart disease (CHD) risk (HR: 1.65). In studies using ACC/AHA guidelines, associations with CVD risk and CVD mortality were weaker [HR: 1.16 (95% CI 1.06, 1.25) and 1.10 (95% CI 0.95, 1.25), respectively]. Subgroup analysis revealed differences in outcomes on the basis of age and sex. Cross-sectional studies did not show significant associations with JNC7 and ACC guidelines; NICE guidelines were not used in cross-sectional studies. Conclusion IDH is associated with an increased risk of CVD. Higher diastolic blood pressure cutoffs were associated with higher cardiovascular risk. This association varied by study design and effect modification by sex and race influenced the association.

Background Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome‐wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. Methods and Results We performed genome‐wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2‐stage analysis (genome‐wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single‐stage genome‐wide meta‐analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2‐degrees of freedom joint main and interaction and 1‐degree of freedom interaction P values. In 2‐stage and single‐stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2‐degrees of freedom joint main and interaction P value

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio® XT Patch [aged 72–94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (β = 0.30, 95% CI: 0.16–0.44) and executive function scores (β = 0.38, 95% CI: 0.22–0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22–0.67) or dementia (OR = 0.25, 95% CI: 0.08–0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

Abstract Beneficial and adverse associations with arrhythmias have been reported for omega-3 fatty acids (omega-3 FA) and Vitamin D. The 12 lead electrocardiogram (ECG) contains quantitative measures reflecting diverse aspects of electrophysiology that might provide insights into mechanisms underlying these associations. In a pre-specified ancillary study of the VITaminD and omegA-3 (VITAL) trial, we examined the effect of 1 g of marine omega-3 FA per day, comprised of 460 mg eicosapentanoic acid and 380 mg of docosahexaenoic acid, and 2000 IU VitaminD3 per day on ECG characteristics associated with atrial and ventricular arrhythmias among individuals age 50 years or greater. A total of 911 study participants underwent ECGs at baseline and again at 2 years after the randomization. Individuals randomized to active omega-3 FA demonstrated significant net increase in PR-interval duration (p = 0.005) and P-wave duration (p = 0.03) as well significant net decrease in P-wave amplitude (p = 0.037) as compared to placebo. RMSSD increased to a greater extent in the omega-3 FA arm compared to placebo (p = 0.040). For Vitamin D3, the Cornell voltage increased to a lesser extent in the participants assigned to active treatment as compared to placebo (p = 0.044). There were no other significant differences in QRS, QTc, Cornell voltage or heart rate. Thus, randomized treatment with omega-3 FA supplements resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction. Vitamin D3 supplementation resulted in modest reductions in progressive LV voltage suggestive of a potential antihypertrophic effect. Trial registration ClinicalTrials.gov Identifiers: NCT01169259, NCT02178410 (06/26/2010 and 06/30/2014).

Abstract The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non‐spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non‐spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non‐spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.

The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

Abstract Background Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. Objective Characterize the relationship between SMI on ECG and CAC. Methods Eligible participants from the Multi‐Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000–2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross‐sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. Results Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0–261.7] vs. 0 [0–81.5]; p

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

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.

Accurate classification of genetic variants is critical for research and patient care. Here, the authors report that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide support for variant pathogenicity.

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–

Summary: Premature atrial contractions (PACs) are frequently observed on electrocardiograms and are associated with increased risks of atrial fibrillation (AF), stroke, and mortality. In this study, we aimed to identify genetic susceptibility loci for PAC frequency. We performed a genome-wide association study meta-analysis with PAC frequency obtained from ambulatory cardiac monitoring in 4,831 individuals of European ancestry. We identified a genome-wide significant locus at the SCN5A gene. The lead variant, rs7373862, located in an intron of SCN5A, was associated with an increase of 0.12 [95% CI 0.08–0.16] standard deviations of the normalized PAC frequency per risk allele. Among genetic variants previously associated with AF, there was a significant enrichment in concordance of effect for PAC frequency (n = 73/106, p = 5.1 × 10−5). However, several AF risk loci, including PITX2, were not associated with PAC frequency. These findings suggest the existence of both shared and distinct genetic mechanisms for PAC frequency and AF.

Introduction Chronic hypertension is associated with left ventricular hypertrophy. Recent evidence suggests that secondhand smoke (SHS) exposure is associated with chronic hypertension, so we sought to examine the relationship between secondhand smoke exposure and electrocardiographic left ventricular (LV) mass among non-smokers. Methods This analysis included 4982 non-smoker participants from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤10 ng/mL, a biomarker for tobacco exposure. SHS exposure was defined as serum cotinine level ≥1 ng/mL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs no exposure) with estimated LV mass index. In similar models, we also examined the associations of LV mass index across quartiles of serum cotinine (reference group, 1st quartile) and in subgroups stratified by age, race, sex, hypertension, and obesity. Results About 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 g/m 2 increase in LV mass index, with a dose-response relationship between higher serum cotinine and LV mass index. These results were consistent in men and women, Whites and non-Whites, elderly and non-elderly, and those with and without hypertension. Significant effect modification was present among obese individuals with an estimated 4.8 g/m 2 increase in LV mass index (interaction p=0.01). Conclusions In a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. Effect modification was present among obese individuals. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas, especially in countries or regions with less-stringent public health policies.

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.

Background Age‐related left atrial (LA) structural and functional abnormalities may be related to subclinical cerebral infarcts (SCIs) and stroke. We evaluated the association of 3‐dimensional echocardiographic LA contractility parameters with SCIs and stroke across the spectrum of tertiles of age increment in elderly patients with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation. Methods and Results We enrolled 407 participants (mean age, 76±8 years; 40% men) from ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study) undergoing a brain magnetic resonance imaging and 3‐dimensional echocardiographic examinations in 2011 to 2013. The sample was analyzed among age tertiles and subgroups: no cerebral magnetic resonance imaging–detectable infarcts (n=315), magnetic resonance imaging–diagnosed SCIs (n=58), and clinically diagnosed stroke (n=34). The frequency of SCIs significantly increased over age tertiles (P trend 0.023). LA global longitudinal strain—a 3‐dimensional echocardiographic index of LA reservoir function—and E/e’ divided by LA global longitudinal strain—an index of LA stiffness—worsened across age tertiles (P trend 0.014 and 0.001, respectively), and only in the categories of SCIs (P trend

Background Long‐term data to study recent trends in the incidence of atrial fibrillation (AF), overall and among sex and race groups, are scarce. We evaluated the 30‐year trends in the incidence of AF in the ARIC (Atherosclerosis Risk in Communities) study cohort and explored race and sex differences in these trends. Methods and Results We included 15 343 men and women aged 45 to 64 years in 1987 to 1989 without AF from 4 US communities in the ARIC cohort. Incident AF was identified based on study ECGs, hospital discharge codes, and death certificates through 2017. We calculated age and period‐specific incidence rates (IRs) of AF. We used Poisson regression to calculate IR ratios of AF over time adjusting for age, sex, and race. A total of 3241 AF cases were identified during a mean (SD) follow‐up of 22 years (8.4 years) (599 in Black participants, 2642 in White participants, 1582 in women, and 1659 in men). Overall, the IR of AF in the ARIC cohort was 9.6 per 1000 person‐years (6.9 in Black participants, 10.5 in White participants, 8.1 in women, and 11.6 in men). Age‐specific IR by time period did not show significant changes over time. In a model adjusted for sex, race, and age group, the rate of AF did not change significantly from 1987 to 1991 compared with 2012 to 2017 (IR ratio, 1.10 [95% CI, 0.88–1.36] comparing 2012–2017 with 1987–1991). Similarly, no evidence of changes over time in AF rates were identified in men and women or White and Black participants separately. Conclusions Even though IRs of AF increase as age increases, our analysis provided evidence suggesting that the overall IRs of AF have not changed over time in a multicenter cohort of Black and White individuals in the United States from 1987 to 2017.

Introduction: Subclinical changes to cardiac structure and function detected with echocardiography precede the development of clinical heart failure (HF) in persons with chronic kidney disease (CKD). Circulating cardiac biomarkers may reflect these pathophysiological changes. This study investigated associations between established biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP] and high-sensitivity troponin T [hsTnT]) and novel biomarkers (growth differentiation factor 15 [GDF-15], galectin-3 [Gal-3], and soluble ST-2 [sST-2]), using echocardiographic measurements in persons with CKD. Methods: In cross-sectional analyses among 2101 participants with mild to moderate CKD in the Chronic Renal Insufficiency Cohort (CRIC), biomarker levels measured at baseline were evaluated with echocardiographic measurements 1 year later. These included left ventricular mass index (LVMI), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and left atrial diameter (LAD). Multivariable linear regression analyses tested associations of each biomarker with echocardiographic measurements, adjusting for covariates. Results: GDF-15 was significantly associated with higher LVMI (1.0 g/m2.7; 95% CI, 0.4–1.7), LVESV (0.4 ml/m2.7; 95% CI, 0.0–0.7), and LVEDV (0.6 ml/m2.7; 95% CI, 0.1–1.1), but not with LVEF or LAD. These findings were not significant when adjusting for NT-proBNP and hsTnT. Gal-3 and sST-2 had no significant associations. Higher levels of NT-proBNP and hsTnT were associated with all echocardiographic measurements. Conclusion: In patients with CKD, the novel biomarker GDF-15, a marker of inflammation and tissue injury, and clinical biomarkers NT-proBNP and hsTnT, were associated with echocardiographic measurements of subclinical cardiovascular disease. Collectively, these biomarkers may highlight biological pathways that contribute to the development of clinical HF.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Abstract Background Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities. Methods We examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by

Abstract Background While studies of the left atrium (LA) have demonstrated associations between volumes and emptying fraction with atrial fibrillation (AF), the contribution of right atrial (RA) abnormalities to incident AF remains poorly understood. Objectives Assess the association between RA structure and function with incident AF using feature-tracking cardiovascular magnetic resonance (CMR). Methods This is a prospective cohort study of all participants in the Multi-Ethnic Study of Atherosclerosis with baseline CMR, sinus rhythm, and free of clinical cardiovascular disease at study initiation. RA volume, strain, and emptying fraction in participants with incident AF (n = 368) were compared against AF-free (n = 2779). Cox proportional-hazards models assessed association between variables. Results Participants were aged 60 ± 10 yrs., 55% female, and followed an average 11.2 years. Individuals developing AF had higher baseline RA maximum volume index (mean ± standard deviation [SD]: 24 ± 9 vs 22 ± 8 mL/m2, p = 0.002) and minimum volume index (13 ± 7 vs 12 ± 6 mL/m2, p

Background It is unknown if stroke symptoms in the absence of a stroke diagnosis are a sign of subtle cardioembolic phenomena. The objective of this study was to examine associations between atrial fibrillation (AF) and stroke symptoms among adults with no clinical history of stroke or transient ischemic attack (TIA). Methods and Results We evaluated associations between AF and self‐reported stroke symptoms in the national, prospective REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort. We conducted cross‐sectional (n=27 135) and longitudinal (n=21 932) analyses over 8 years of follow‐up of REGARDS participants without stroke/transient ischemic attack and stratified by anticoagulant or antiplatelet agent use. The mean age was 64.4 (SD±9.4) years, 55.3% were women, and 40.8% were Black participants; 28.6% of participants with AF reported stroke symptoms. In the cross‐sectional analysis, comparing participants with and without AF, the risk of stroke symptoms was elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (odds ratio [OR], 2.22; 95% CI, 1.89–2.59) or antiplatelet agents only (OR, 1.92; 95% CI, 1.61–2.29) but not for adults with AF taking anticoagulants (OR, 1.08; 95% CI, 0.71–1.65). In the longitudinal analysis, the risk of stroke symptoms was also elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (hazard ratio [HR], 1.41; 95% CI, 1.21–1.66) or antiplatelet agents only (HR, 1.23; 95% CI, 1.04–1.46) but not for adults with AF taking anticoagulants (HR, 0.86; 95% CI, 0.62–1.18). Conclusions Stroke symptoms in the absence of a stroke diagnosis may represent subclinical cardioembolic phenomena or “whispering strokes.” Future studies examining the benefit of stroke symptom screening may be warranted.

Background: Serum magnesium (Mg) has been reported to be inversely associated with the risk of atrial fibrillation (AF), coronary artery disease (CAD), and major adverse cardiovascular events (MACE). The association between serum Mg and the risk of MACE, heart failure (HF), stroke, and all-cause mortality among patients with AF has not been evaluated. Objective: We aim to examine whether higher serum Mg is associated with a lower risk of MACE, heart failure (HF), stroke, and all-cause mortality among patients with AF. Methods: We evaluated prospectively 413 participants of the Atherosclerosis Risk in Communities (ARIC) Study with a diagnosis of AF at the time of Mg measurement participating in visit 5 (2011–2013). Serum Mg was modeled in tertiles and as a continuous variable in standard deviation units. Endpoints (HF, MI, stroke, cardiovascular (CV) death, all-cause mortality, and MACE) were identified and modeled separately using Cox proportional hazard regression adjusting for potential confounders. Results: During a mean follow-up of 5.8 years, there were 79 HFs, 34 MIs, 24 strokes, 80 CV deaths, 110 MACEs, and 198 total deaths. After adjustment for demographic and clinical variables, participants in the second and third tertiles of serum Mg had lower rates of most endpoints, with the strongest inverse association for the incidence of MI (HR 0.20, 95% CI 0.07, 0.61) comparing top to bottom tertile. Serum Mg modeled linearly as a continuous variable did not show clear associations with endpoints except MI (HR 0.50, 95% CI 0.31, 0.80). Due to the limited number of events, the precision of most estimates of association was relatively low. Conclusions: Among patients with AF, higher serum Mg was associated with a lower risk of developing incident MI and, to a lesser extent, other CV endpoints. Further studies in larger patients with AF cohorts are needed to evaluate the role of serum Mg in preventing adverse CV outcomes in these patients.

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.

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zebrafish ECG reading GUI (zERG), a program to acquire measurements from traces that commercial software cannot examine owing to erroneous peak calling. We evaluate normal ECG trait variation, revealing highly reproducible intervals and wave amplitude variation largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS and QT intervals. With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiological phenotypes.

Background Atrial fibrillation is associated with increased stroke risk; available risk prediction tools have modest accuracy. We hypothesized that circulating stroke risk biomarkers may improve stroke risk prediction in atrial fibrillation. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort study of 30 239 Black and White adults age ≥45 years. A nested study of stroke cases and a random sample of the cohort included 175 participants (63% women, 37% Black adults) with baseline atrial fibrillation and available blood biomarker data. There were 81 ischemic strokes over 5.2 years in these participants. Adjusted for demographics, stroke risk factors, and warfarin use, the following biomarkers were associated with stroke risk (hazard ratio [HR]; 95% CI for upper versus lower tertile): cystatin C (3.16; 1.04–9.58), factor VIII antigen (2.77; 1.03–7.48), interleukin‐6 (9.35; 1.95–44.78), and NT‐proBNP (N‐terminal B‐type natriuretic peptide) (4.21; 1.24–14.29). A multimarker risk score based on the number of blood biomarkers in the highest tertile was developed; adjusted HRs of stroke for 1, 2, and 3+ elevated blood biomarkers, compared with none, were 1.75 (0.57–5.40), 4.97 (1.20–20.5), and 9.51 (2.22–40.8), respectively. Incorporating the multimarker risk score to the CHA2DS2VASc score resulted in a net reclassification improvement of 0.34 (95% CI, 0.04–0.65). Conclusions Findings in this biracial cohort suggested the possibility of substantial improvement in stroke risk prediction in atrial fibrillation using blood biomarkers or a multimarker risk score.

Abstract Background Subclinical myocardial injury (SCMI) determined from the Electrocardiographic Cardiac Infarction/Injury Score (CIIS) is associated with increased risk of cardiovascular disease and mortality. We hypothesized that SCMI prevalence and association with mortality would differ by race, categorized as non‐Hispanic White (White), non‐Hispanic Black (Black), and Mexican American. Methods Our analysis included 5,852 participants (age 58.5 ± 13.2 years; 54% women, 52% Whites, 23% Blacks, and 25% Mexican American participants) from the National Health and Nutrition Examination Survey (NHANES III, 1988–94) who were free of cardiovascular disease at the time of enrollment. SCMI was defined as the presence of CIIS ≥ 10 score points on the 12‐lead ECG. Prevalence of SCMI and its association with cardiovascular mortality were examined in each race/ethnic group in models adjusted for sociodemographics and common cardiovascular risk factors. Results SCMI prevalence was 23.4% in Whites, 21.8% in Blacks, and 18.0% in Mexican Americans. Compared to Whites, Blacks were as likely to have SCMI (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.80–1.13), while Mexican Americans were less likely (OR 0.74, 95% CI 0.62–0.88). SCMI was not associated with increased risk of cardiovascular mortality in either Whites (hazard ratio [HR] 1.18, 95% CI 0.95–1.48) or Blacks (HR 1.19, 95% CI 0.79–1.80). In contrast, SCMI in Mexican Americans was associated with increased risk of cardiovascular mortality (HR 1.74, 95% CI 1.13–2.67, p

Background High blood pressure (BP) is a well‐known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi‐Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000–2018 in MESA and 1987–2017 in ARIC study), we calculated individual long‐term mean, trend, and detrended visit‐to‐visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance‐weighted meta‐analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit‐to‐visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02–1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01–1.15). For pulse pressure as well, higher visit‐to‐visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00–1.37). In addition, higher long‐term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08–1.70). Conclusions Antecedent visit‐to‐visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.

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.

Abstract Background Retrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk. Objectives We sought to confirm this in a prospective cohort with adjudicated outcomes. Methods We evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003‐2007). Medicare claims were used to identify new cancer diagnoses during follow‐up. Using incidence‐density sampling, participants who developed cancer were matched by age, sex, race, and education 1:4 to control participants who had not developed cancer. Participants were prospectively followed through 2015 for an expert‐adjudicated ATE, defined as acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent ATE. Results In this analysis, 836 REGARDS participants with incident cancer were matched to 3339 control participants without cancer. In the 30 days after cancer diagnosis, 0.60% (n = 5) of the participants had an ATE; most of these events occurred near the time of cancer diagnosis. After adjustment for demographics, geographic region, and cardiovascular risk factors, compared to the noncancer controls, participants with incident cancer had an increased risk of ATE in the first 30 days after diagnosis (hazard ratio, 5.8; 95% confidence interval, 2.1‐15.9). There was no association between cancer diagnosis and ATE beyond 30 days. Cancers with known metastases and types considered high risk for venous thromboembolism had the strongest associations with ATE. Conclusions Incident cancer is associated with an increased short‐term risk of ATE independent of vascular risk factors.

Abstract Background Electrocardiographic left ventricular hypertrophy (ECG‐LVH) represents preclinical cardiovascular disease and predicts cardiovascular disease morbidity and mortality. While the newly developed Peguero‐Lo Presti ECG‐LVH criteria have greater sensitivity for LVH than the Cornell voltage and Sokolow–Lyon criteria, its short‐term repeatability is unknown. Therefore, we characterized the short‐term repeatability of Peguero‐Lo Presti ECG‐LVH criteria and evaluate its agreement with Cornell voltage and Sokolow–Lyon ECG‐LVH criteria. Methods Participants underwent two resting, standard, 12‐lead ECGs at each of two visits one week apart (n = 63). We defined a Peguero‐Lo Presti index as a sum of the deepest S wave amplitude in any single lead and lead V4 (i.e., SD + SV4) and defined Peguero‐Lo Presti LVH index as ≥ 2,300 µV among women and ≥ 2,800 µV among men. We estimated repeatability as an intraclass correlation coefficient (ICC), agreement as a prevalence‐adjusted bias‐adjusted kappa coefficient (κ), and precision using 95% confidence intervals (CIs). Results The Peguero‐Lo Presti index was repeatable: ICC (95% CI) = 0.94 (0.91–0.97). Within‐visit agreement of Peguero‐Lo Presti LVH was high at the first and second visits: κ (95% CI) = 0.97 (0.91–1.00) and 1.00 (1.00–1.00). Between‐visit agreement of the first and second measurements at each visit was comparable: κ (95% CI) = 0.90 (0.80–1.00) and 0.93 (0.85–1.00). Agreement of Peguero‐Lo Presti and Cornell or Sokolow–Lyon LVH on any one of the four ECGs was slightly lower: κ (95% CI) = 0.71 (0.54–0.89). Conclusion The Peguero‐Lo Presti index and LVH have excellent repeatability and agreement, which support their use in clinical and epidemiological studies.

Background Psychosocial factors predict heart disease risk, but our understanding of underlying mechanisms is limited. We sought to evaluate the physiologic correlates of psychosocial factors by measuring their relationships with heart rate variability (HRV), a measure of autonomic health, in the ARIC (Atherosclerosis Risk in Communities) study. We hypothesize that increased psychosocial stress associates with lower HRV. Methods and Results We studied 9331 participants in ARIC with short‐term HRV data at visits 2 and 4. The mean (SD) age was 54.4 (5.7) years, 55% were women, and 25% were Black. Psychosocial factors included: (1) vital exhaustion (VE), (2) anger proneness, a personality trait, and (3) perceived social support. Linear models adjusted for sociodemographic and cardiovascular risk factors. Low frequency HRV (ln ms2) was significantly lower in the highest versus lowest quartiles of VE (B=−0.14, 95% CI, −0.24 to −0.05). When comparing this effect to age (B=−0.04, 95% CI, −0.05 to −0.04), the difference was equivalent to 3.8 years of accelerated aging. Perceived social support associated with lower time‐domain HRV. High VE (versus low VE) also associated with greater decreases in low frequency over time, and both anger and VE associated with greater increases in resting heart rate over time. Survival analyses were performed with Cox models, and no evidence was found that HRV explains the excess risk found with high VE and low perceived social support. Conclusions Vital exhaustion, and to a lesser extent anger and social support, were associated with worse autonomic function and greater adverse changes over time.

Background High levels of supraventricular ectopy are associated with greater risk of atrial fibrillation, stroke, and death. Little information is available about differences by race/ethnicity in the extent of supraventricular ectopy, or about whether high levels of supraventricular ectopy are associated with impaired left atrial (LA) function and LA enlargement. Methods and Results In the MESA (Multi‐Ethnic Study of Atherosclerosis), 1148 participants (47% men; mean age, 67 years) had cardiovascular magnetic resonance imaging in 2010 to 2012, followed by 14‐day ambulatory electrocardiographic monitoring in 2016 to 2018. We analyzed participant characteristics and cardiovascular magnetic resonance measures of LA function and structure in relation to average count of premature atrial contractions (PACs) per hour and average number of runs per day of supraventricular tachycardia. In adjusted regression analyses, older age, male sex, White race, elevated NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), and a history of clinically detected atrial fibrillation were associated with more PACs/hour. Chinese and Hispanic participants had on average fewer PACs/hour than White participants (Chinese participants, 31% less [95% CI, 8%–49%]; Hispanic participants, 38% less [95% CI, 19%–52%]). Greater LA total emptying fraction was associated with fewer PACs/hour (per SD, 16% fewer PACs/hour [95% CI, 7%–25% fewer PACs/hour]). Larger LA minimum volume was associated with more PACs/hour (per SD, 7% more PACs/hour [95% CI, 2%–13% more PACs/hour]). Associations of LA volumes with runs of supraventricular tachycardia/day were similar in direction but were weaker. Conclusions Impaired LA function and LA enlargement were associated with more PACs/hour on extended ambulatory electrocardiographic monitoring. Measurement of supraventricular ectopy may provide information about the extent of atrial myopathy.

Background Higher body mass index (BMI) is associated with increased risk of incident atrial fibrillation (AF), but it is not known whether this relationship varies by race/ethnicity. Methods and Results Eligible participants (6739) from MESA (Multi‐Ethnic Study of Atherosclerosis) were surveilled for incident AF using MESA hospital surveillance, scheduled MESA study ECG, and Medicare claims data. After a median 13.8 years of follow‐up, 970 participants (14.4%) had incident AF. With BMI modeled categorically in a Cox proportional hazards model, only those with grade II and grade III obesity had increased risks of AF (hazard ratio [HR], 1.50; 95% CI, 1.14–1.98, P=0.004 for grade II obesity and HR, 2.13; 95% CI, 1.48–3.05, P

Objective: ─ To assess the role of traditional risk factors in explaining the association between cumulative social risk exposure and disparities in CVD death among US adults. Methods: ─ The study included 15,906 participants from the Third National Health and Nutrition Examination Survey III who were CVD-free at enrollment. Baseline social risk factors (minority race, poverty-income ratio

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 The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF‐15 (growth differentiation factor‐15), galectin‐3, sST2 (soluble suppression of tumorigenesis‐2), hsTnT (high‐sensitivity troponin T), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score

Background Atrial fibrillation (AF) is associated with a 5‐fold increased stroke risk. While most patients with AF warrant anticoagulation, optimal treatment remains uncertain for patients with AF without cardiovascular comorbidities because the risk of stroke in this population has not been well‐characterized. Methods and Results Participants (N=28 253; 55% women, mean age 64.6±9.4 years), from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study (2003–present) were classified into 1 of 4 groups based on the presence or absence of AF and the presence or absence of cardiovascular comorbidities. Cox proportional hazards analysis was used to compare the risk of stroke between groups. During 244 560 person‐years of follow‐up (median 8.7 years), 1206 strokes occurred. Compared with patients with neither AF nor cardiovascular comorbidities, we did not find an increased stroke risk (hazard ratio [HR], 1.23; 95% CI, 0.62–2.18 [P=0.511]) among participants with AF alone. Participants without AF but with cardiovascular comorbidities had both an elevated stroke risk (HR, 1.77; 95% CI, 1.48–2.18 [P

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.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

Abstract Background Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Results Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Conclusions Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Abstract Background and purpose With the emergence of long-term electrocardiogram (ECG) recordings that extend several days beyond the typical 24–48 h, the development of new tools to measure heart rate variability (HRV) and QT variability is needed to utilize the full potential of such extra-long-term ECG recordings. Methods In this report, we propose a new nonlinear time–frequency analysis approach, the concentration of frequency and time (ConceFT), to study the HRV QT variability from extra-long-term ECG recordings. This approach is a generalization of Short Time Fourier Transform and Continuous Wavelet Transform approaches. Results As proof of concept, we used 14-day ECG recordings to show that the ConceFT provides a sharpened and stabilized spectrogram by taking the phase information of the time series and the multitaper technique into account. Conclusion The ConceFT has the potential to provide a sharpened and stabilized spectrogram for the heart rate variability and QT variability in 14-day ECG recordings.

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

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 We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin T, galectin‐3, growth differentiation factor‐15, and soluble ST‐2. Incident AF (“AF event”) was defined as a hospitalization for AF. During a median follow‐up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log‐transformed NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log‐high‐sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose–response relationship in categorical analyses. Although log‐soluble ST‐2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log‐galectin‐3 (HR 1.05; 95% CI, 0.91, 1.22) and log‐growth differentiation factor‐15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and high‐sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease.

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.