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ObjectivesTestosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men.MethodsWe utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration.ResultsTestosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use.ConclusionsThis study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not.

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P

Background: Cardiac troponin T is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Serum levels of high sensitivity cardiac troponin T (hs-TnT) reflect subclinical myocardial injury in ambulat

BackgroundGenome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.ObjectiveTo identify novel genetic variants associated with resting heart rate in African Americans.MethodsTen cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)).ResultsFourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans.ConclusionsAn intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Wesley T O’Neal,1 Sanjay Venkatesh,2 Stephen T Broughton,2 William F Griffin,3 Elsayed Z Soliman4,5 1Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA; 2Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Internal Medicine, Medical University of South Carolina, Charleston, SC, USA; 4Department of Internal Medicine, Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 5Epidemiological Cardiology Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, and it places a substantial burden on the health care system. Despite improvements in our understanding of AF pathophysiology, we have yet to develop targeted preventive therapies. Recently, numerous biological markers have been identified to aid in the prediction of future AF events. Subclinical markers of atrial stress, inflammation, endothelial dysfunction, kidney dysfunction, and atherosclerosis have been linked to AF. The connection between these markers and AF is the identification of subclinical states in which AF propagation is likely to occur, as these conditions are associated with abnormal atrial remodeling and fibrosis. Additionally, several risk scores have been developed to aid in the identification of at-risk patients. The practicing clinician should be aware of these subclinical markers, as several of these markers improve the predictive abilities of current AF risk scores. Knowledge of these subclinical markers also provides clinicians with a better understanding of AF risk factors, and the opportunity to reduce the occurrence of AF by incorporating well-known cardiovascular disease risk factor modification strategies. In this review, we highlight several novel biological markers that have improved our understanding of AF pathophysiology and appraise the utility of these markers to improve our ability to predict future AF events. Keywords: biological markers, prediction, atrial fibrillation

Emily B Levitan,1 Christopher Gamboa,1 Monika M Safford,2 Dana V Rizk,3 Todd M Brown,4 Elsayed Z Soliman,5 Paul Muntner11Department of Epidemiology, 2Division of Preventive Medicine, 3Division of Nephrology, 4Division of Cardiology, University of Alabama at Birmingham, Birmingham, AL, USA; 5Epidemiological Cardiology Research Center, Wake Forest University School of Medicine, Winston Salem, NC, USABackground: Individuals with unrecognized myocardial infarction (UMI) have similar risks for cardiovascular events and mortality as those with recognized myocardial infarction (RMI). The prevalence of cardioprotective medication use and blood pressure and low-density lipoprotein cholesterol control among individuals with UMI is unknown.Methods: Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were recruited between May 2004 and October 2007 received baseline twelve-lead electrocardiograms (n = 21,036). Myocardial infarction (MI) status was characterized as no MI, UMI (electrocardiogram abnormalities consistent with MI without self-reported history; n = 949; 4.5%), and RMI (self-reported history of MI; n = 1574; 7.5%).Results: For participants with no MI, UMI, and RMI, prevalence of use was 38.4%, 44.4%, and 75.7% for aspirin; 18.0%, 25.8%, and 57.2% for beta blockers; 31.7%, 38.7%, and 55.0% for angiotensin converting enzyme inhibitors or angiotensin receptor blockers; and 28.1%, 33.9%, and 64.1% for statins, respectively. Participants with RMI were 35% more likely to have low-density lipoprotein cholesterol < 100 mg/dL than participants with UMI (prevalence ratio = 1.35, 95% confidence interval 1.19–1.52). Blood pressure control (

Background: Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid-lowering medication use with AF risk.Methods and Results: We analyzed 13 969 participants (25% African American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities study. Fasting high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987-1989) and each of 3 follow-up visits. The incidence of AF was ascertained through 2007. The association of the use of statins and other lipid-lowering medications with AF was estimated in 13 044 Atherosclerosis Risk in Communities participants attending visit 2 (1990-1992), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years, there were 1433 incident AF cases. Multivariable hazard ratios (HRs) and 95% CIs of AF associated with a 1-SD increase in lipid levels were as follows: HDLc, 0.97 (0.91-1.04); LDLc, 0.90 (0.85-0.96); total cholesterol, 0.89 (0.84-0.95); and triglycerides, 1.00 (0.96-1.04). Participants taking lipid-lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82-1.13) compared with those not taking medications, whereas those taking statins had an adjusted HR of 0.91 (0.66-1.25) compared with those taking other lipid-lowering medications.Conclusions: Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. However, HDLc and triglycerides were not independently associated with AF incidence. No association was found between the use of lipid-lowering medications and incident AF. [ABSTRACT FROM AUTHOR]

Background: It remains debated whether to include resting electrocardiogram (ECG) in the routine care of human immunodeficiency virus (HIV)-infected patients.Methods: This analysis included 4518 HIV-infected patients (28% women and 29% blacks) from the Strategies for Management of Antiretroviral Therapy study, a clinical trial aimed to compare 2 HIV treatment strategies. ECG abnormalities were classified using the Minnesota Code. Cox proportional hazards analysis was used to examine the association between baseline ECG abnormalities and incident cardiovascular disease (CVD).Results: More than half of the participants (n = 2325, or 51.5%) had either minor or major ECG abnormalities. Minor ECG abnormalities (48.6%) were more common than major ECG abnormalities (7.7%). During a median follow-up of 28.7 months, 155 participants (3.4%) developed incident CVD. After adjusting for the study-treatment arms, the presence of major, minor, and either minor or major ECG abnormalities was significantly predictive of incident CVD (hazard ratio [95% confidence interval]: 2.76 [1.74-4.39], P < .001; 1.58 [1.14-2.20], P = .006; 1.57 [1.14-2.18], P = .006, respectively). However, after adjusting for demographics, CVD risk factors, and HIV characteristics (full model), presence of major ECG abnormalities were still significantly predictive of CVD (1.83 [1.12-2.97], P = .015) but not minor or major abnormalities taken together (1.26 [0.89-1.79], P = .18; 1.25 [0.89-1.76], P = .20, respectively). Individual ECG abnormalities that significantly predicted CVD in the fully adjusted model included major isolated ST-T abnormalities, major prolongation of QT interval, minor isolated ST-T, and minor isolated Q-QS abnormalities.Conclusion: Nearly 1 in 2 of the HIV-infected patients in our study had ECG abnormalities; 1 in 13 had major ECG abnormalities. Presence of ECG abnormalities, especially major ECG abnormalities, was independently predictive of incident CVD. These results suggest that the ECG could provide a convenient risk-screening tool in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is common among patients with end-stage renal disease, but few data are available on its prevalence among adults with chronic kidney disease (CKD) of lesser severity. methods and results: We evaluated the association of CKD with ECG-detected AF among 26 917 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of African-American and white US adults ≥45 years of age. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation and albuminuria was defined as a urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by renal function: no CKD (eGFR ≥60 mL/min/1.73 m(2) without albuminuria, n=21 081), stage 1 to 2 CKD (eGFR ≥60 mL/min/1.73 m(2) with albuminuria n=2938), stage 3 CKD (eGFR 30 to 59 mL/min/1.73 m(2), n=2683) and stage 4 to 5 CKD (eGFR <30 mL/min/1.73 m(2), n=215). The prevalence of AF among participants without CKD, and with stage 1 to 2, stage 3, and stage 4 to 5 CKD was 1.0%, 2.8%, 2.7% and 4.2%, respectively. Compared with participants without CKD, the age-, race-, and sex-adjusted odds ratios for prevalent AF were 2.67 (95% confidence interval, 2.04 to 3.48), 1.68 (95% confidence interval, 1.26 to 2.24) and 3.52 (95% confidence interval, 1.73 to 7.15) among those with stage 1 to 2, stage 3, and stage 4 to 5 CKD. The association between CKD and prevalent AF remained statistically significant after further multivariable adjustment and was consistent across numerous subgroups.Conclusions: Regardless of severity, CKD is associated with an increased prevalence of AF among US adults. [ABSTRACT FROM AUTHOR]

BACKGROUND: Because of economic constraints, identification of patients at high risk for ischemic stroke who may benefit from further evaluation and aggressive control of their risk factors carries a special importance in low-resources settings. We sought to examine the use of the negative component of the P wave in V(1) in the standard electrocardiogram, referred to as P-wave terminal force (PTF), as a risk stratification tool of ischemic stroke in Africans living in Malawi, a sub-Saharan African country where stroke is a strongly emerging health problem. METHODS: This was a case-comparison study where 92 patients with ischemic stroke were compared with an equal number of subjects in an age- and sex-matched comparison group. The sensitivity and specificity of abnormal PTF, defined as PTF greater than or equal to 4mm-s, to diagnose ischemic stroke were calculated. Univariate and multivariable logistic regression analysis was used to estimate the odds of ischemic stroke associated with abnormal PTF. RESULTS: Abnormal PTF was present in 54% of patients with stroke compared with only 17% of the comparison group (P < .001). The specificity and sensitivity of PTF was 82% and 54%, with positive and negative predictive values of 76% and 64%, respectively. PTF was associated with ischemic stroke in a univariate analysis (odds ratio [OR] 5.7; 95% confidence interval [CI] 2.9-11.1), a multivariate analysis adjusting for common ischemic stroke risk factors (OR 2.8; 95% CI 2.4-3.4), and even with further adjustment for echocardiographically measured left atrial size (OR 2.1; 95% CI 1.9-2.4). CONCLUSIONS: PTF greater than or equal to 4mm-s is associated with the risk of ischemic stroke in Africans independently from ischemic stroke risk factors. Given its reasonable sensitivity and specificity to predict ischemic stroke, PTF greater than or equal to 4mm-s could be used as a risk stratification tool to discriminate between patients at high and low risk of ischemic stroke, and subsequently identify patients who may benefit from further evaluation and aggressive control of their risk factors. [ABSTRACT FROM AUTHOR]

A United States national sample of 20,962 participants (57% women, 44% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study provided general population estimates for electrocardiographic (ECG) abnormalities among black and white men and women. The participants were recruited from 2003 to 2007 by random selection from a commercially available nationwide list, with oversampling of blacks and those from the stroke belt, with a cooperation rate of 49%. The measurement of risk factors and 12-lead electrocardiograms (centrally coded using Minnesota code criteria) showed 28% had ≥1 major ECG abnormality. The prevalence of abnormalities was greater (≥35%) for those ≥65 years old, with no differences between blacks and whites. However, among men <65 years, blacks had more major abnormalities than whites, most notably for atrial fibrillation, major Q waves, and left ventricular hypertrophy. Men generally had more ECG abnormalities than women. The most common ECG abnormalities were T-wave abnormalities. The average heart rate-corrected QT interval was longer in women than in men, similar in whites and blacks, and increased with age. However, the average heart rate was greater in women than in men and in blacks than in whites and decreased with age. The prevalence of ECG abnormalities was related to the presence of hypertension, diabetes, blood pressure, and age. In conclusion, black men and women in the United States have a significantly greater prevalence of ECG abnormalities than white men and women at age 45 to 64 years; however, these proportions, although larger, tended to equalize or reverse after age 65. [ABSTRACT FROM AUTHOR]

Background: The relationship between self-rated health (SRH) and cardiovascular events in individuals with hypertension, but without diabetes mellitus, is understudied., Methods: We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). SRH was categorized into excellent, very good, good and fair/poor. Using multivariable Cox regression, we estimated hazard ratios and 95% confidence intervals (CIs) for the association of SRH with both all-cause mortality and a composite of cardiovascular events (the primary outcome), which was defined to include myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure, and cardiovascular death., Results: We included 9319 SPRINT participants (aged 67.9 ± 9 years, 35.6% women) with a median follow-up of 3.8 years. Compared with SRH of excellent, the risk [hazard ratio (95% CI)] of the primary outcome associated with very good, good, and fair/poor SRH was 1.11(0.78-1.56), 1.45 (1.03-2.05), and 1.87(1.28-2.75), respectively. Similarly, compared with SRH of excellent, the risk of all-cause mortality [hazard ratio (95% CI)] associated with very good, good, and fair/poor SRH was 1.13 (0.73-1.76), 1.72 (1.12-2.64), and 2.11 (1.32-3.38), respectively. Less favorable SRH (LF-SRH) was also associated with a higher risk of each component of the primary outcome and serious adverse events (SAE)., Conclusion: Among individuals with hypertension, SRH is independently associated with the risk of incident cardiovascular events, all-cause mortality, and SAE. Our study suggest that guidelines should consider the potential significance of including SRH in the clinical history of patients with hypertension., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets., Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories., Results: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; P interaction =0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively., Conclusions: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar., Competing Interests: J.A. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Ortho Clinical Diagnostics, Quidel Cardiovascular Inc, and Siemen’s Health Care Diagnostics. He has been named a co-owner on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” C.M. Ballantyne reports consulting and research support from Abbott and Roche Diagnostics. J.D. Berry reports grant support from the National Institutes of Health, Roche Diagnostics, and Abbott Diagnostics, consulting fees from Roche Diagnostics, and the Cooper Institute. The other authors report no conflicts.

Background: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring., Objective: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring., Methods: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models., Results: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring., Conclusion: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making., Competing Interests: Disclosures Dr Perez is a consultant for Apple Inc, Boston Scientific, Janssen, Bristol Myers Squibb, and Thryv Inc and has ownership interest in QALY, Inc. Dr Wheeler had prior consulting income from BioTelemetry. Dr Froelicher has stock interest in Cardiac Insight (electrocardiographic patch company employed in this study) and is contracted by Cardiac Insight to develop patch interpretation software. The remaining authors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The association of malignant left ventricular hypertrophy (LVH), a specific subphenotype of LVH characterized by elevated levels of high-sensitivity cardiac troponin (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), with cognitive decline remains understudied., Methods: This post-hoc analysis included a total of 8,027 (67.9 ± 9.3 years) SPRINT MIND trial participants who had with at least 1 follow-up cognitive assessment. Participants were classified into 6 groups on the basis of LVH status on electrocardiogram (ECG), and elevations in levels of hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL at baseline visit. Multivariate Cox proportional hazard models were used to examine the association of LVH/biomarker groups with incident probable dementia, mild cognitive impairment (MCI) and a composite of MCI/probable dementia., Results: Over a median follow-up period of 5 years, there were 306, 597, and 818 incidents of MCI, probable dementia and a composite of MCI/probable dementia, respectively. Compared with participants without LVH and normal biomarker levels, those with concomitant LVH and elevated levels of both biomarkers were associated with a higher risk of probable dementia (HR, 2.50; 95% CI (1.26-4.95), MCI (HR, 1.78; 95% CI (0.99-3.23) and the composite of MCI/ probable dementia (HR, 1.89; 95% CI, 1.16-3.10)., Conclusions: Among SPRINT participants, malignant LVH is associated with incident probable dementia and mild cognitive impairment. These findings underscore the potential utility of measuring hs-cTnT and NT-proBNP levels when LVH is detected on ECG, aiding in the differentiation of individuals with a favorable risk for cognitive impairment from those with a higher risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Assessment of cardiac structure and function improves risk prediction of new-onset atrial fibrillation (AF) in different populations. We aimed to comprehensively compare standard and newer measures of cardiac structure and function in improving prediction of AF in a cohort of older adults without history of AF and stroke., Methods: We included 5050 participants without prevalent AF and stroke (mean age 75 ± 5 years, 59% women and 22% Black) from the Atherosclerosis Risk in Communities (ARIC) study who underwent complete 2-dimensional echocardiography, including speckle-tracking analysis of the left ventricle (LV) and left atrium (LA). We assessed the association of cardiac measures with incident AF (including atrial flutter) and quantified the extent to which these measures improved model discrimination and risk classification of AF compared with the CHARGE-AF score., Results: Over a median follow-up time of 7 years, 676 participants developed AF (incidence rate, 2.13 per 100 person-years). LV mass index and wall thickness, E/e' and measures of LA structure and function, but not LV systolic function, were associated with incident AF, after accounting for confounders. Above all, LA reservoir strain, contraction strain, and LA minimal volume index (C-statistics [95%Confidence interval]: 0.73 [0.70,0.75], 0.72 [0.70,0.75] and 0.72 [0.69,0.75], respectively) significantly improved the risk discrimination of the CHARGE-AF score (baseline C-statistic: 0.68 [0.65,0.70]) and achieved the highest category-based net reclassification improvement (29%, 24% and 20%, respectively)., Conclusions: In a large cohort of older adults without prevalent AF and stroke, measures of LA function improved the prediction of AF more than other conventional cardiac measures., (Published by Oxford University Press on behalf of the European Society of Cardiology 2024.)

Competing Interests: Disclosures None.

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

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.

Background: We explored whether the reported racial differences in subclinical myocardial injury (SCMI) are due to variations in the prevalence or differential impact of the SCMI risk factors., Methods: This analysis included 3074 Whites, 1337 Blacks, and 1441 Mexican Americans from the Third National Health and Nutrition Examination Survey who were free of cardiovascular disease. SCMI was defined from standard electrocardiograms as a cardiac infarction/injury score ≥ 10 points. Multivariable logistic regression analysis was used to assess the association of SCMI with its risk factors stratified by race. Multiplicative interaction between each risk factor and race was also examined., Results: Overall prevalence of SCMI was 20.3%, with Mexican Americans exhibiting a lower prevalence than Whites and Blacks (16.5%, 20.4%, and 20.7%, respectively). Whites had more prevalence of dyslipidemia and smoking. Mexican Americans had more diabetes, while Blacks had more hypertension, obesity, and left ventricular hypertrophy. Significant risk factors for SCMI were older age, lower income (<20 K), smoking, diabetes, and no regular exercise. The association of SCMI with age was more pronounced in Mexican Americans (p-value for interaction 0.03), whereas the associations of SCMI with smoking, no-regular exercise, and diabetes were stronger in Whites (p-value for interaction 0.04, 0.001, 0.007, respectively)., Conclusions: Heterogeneity in the racial differences in the prevalence of SCMI risk factors exists, but they do not explain racial differences in SCMI. The stronger associations of smoking, diabetes, and no regular exercise with SCMI partially explain the higher prevalence of SCMI in Whites., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: High blood pressure (BP) induces left atrial structural and functional remodeling that increases susceptibility to atrial arrhythmia. We hypothesized that lower systolic BP (SBP) levels are associated with a lower prevalence of premature atrial contractions (PACs) in patients with hypertension., Methods: This analysis included 4,697 participants (mean age 62±13.1 years, 50% women, 25.6% blacks) with hypertension from the Third National Health and Nutrition Examination Survey who did not have a prior history of cardiovascular disease (CVD). Multivariable logistic regression was used to examine the cross-sectional association between SBP and prevalence of PACs ascertained from 12-lead resting electrocardiograms. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality., Results: Approximately 1.6% (n=74) of participants had baseline PACs. Patients with SBP ≤140 mmHg had a lower prevalence of PACs than those with SBP ≥140 mmHg (1.1% vs. 1.9%, p-value=0.01). In a multivariable logistic regression model, each 10 mmHg decrease in SBP was associated with a 12% lower odds of PACs (OR (95%CI): 0.88 (0.77-0.99)). During 14 years of follow-up, 645 CVD deaths occurred. In a multivariable-adjusted Cox model, presence of PACs was associated with a 78% increased risk of CVD mortality (HR (95%CI): 1.78 (1.23-2.60))., Conclusions: In patients with hypertension, lower SBP levels are associated with a lower prevalence of PACs, and presence of PACs is associated with a higher risk of CVD mortality risk. These findings highlight the potential role of BP lowering in the management of cardiac arrhythmias., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Lower left atrial (LA) function is associated with increased risk for cardiovascular disease events; data on risk factors for impaired LA function are limited. We evaluated the effect of cumulative systolic blood pressure (cSBP) from midlife to older age on LA strain in adults with normal LA size., Methods: We included participants in the Atherosclerosis Risk in Communities study with LA strain measured on the visit 5 echocardiogram (2011-13), excluding those with atrial fibrillation and LA volume index >34 mL/m 2 . The cSBP was calculated from visit 1 (1987-89) through visit 5. Linear regression models were used to evaluate associations between cSBP and LA strain measures., Results: A total of 3,859 participants with a mean (SD) age of 75.2 (5.0) years were included in the analysis; 725 (18.8%) were Black and 2,342 (60.7%) were women. After adjusting for demographics, cardiovascular disease risk factors, heart failure, and coronary heart disease, each 10 mm Hg increase in cSBP was associated with 0.32% (95% CI, -0.52%, -0.13%) and 0.37% (95% CI, -0.51%, -0.22%) absolute reduction in LA reservoir and conduit strain, respectively. Associations were attenuated after adjustment for left ventricular (LV) systolic and diastolic function and mass (-0.12%: 95% CI, -0.31, 0.06 for reservoir strain; and -0.24%: 95% CI -0.38%, -0.10% for conduit strain). In subgroup analyses, the association of cSBP with conduit strain was statistically significant among those with normal LV systolic and diastolic function., Conclusions: Cumulative exposure to elevated blood pressure from midlife to late life was modestly associated with lower LA reservoir and conduit strain in older adults with normal LA size, mostly related to the effect of blood pressure on LV function and mass. However, the association of cSBP and LA conduit strain in subgroups with normal LV function suggests that LA remodeling in response to hypertension occurs before LV dysfunction is detected on echocardiography., Competing Interests: Disclosures A.A., A.M.S., P.L.L., and L.Y.C. have all received National Institutes of Health funding related to the subject matter of this manuscript. A.S. has received research support from Novartis through Brigham and Women’s Hospital and consulting fees from Philips Ultrasound and Janssen outside of the submitted work. S.S. has received grants or contracts from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI outside the submitted work. K.M. received research support from Resolve to Save Lives outside of the submitted work. S.S. has received consulting feeds from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. The remaining authors have nothing to disclose., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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 CHA 2 DS 2 -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 CHA 2 DS 2 -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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The impact of oral anticoagulants (OACs) on cognitive impairment and dementia in patients with atrial fibrillation (AF) is not well characterized. This systematic review aims to address this knowledge gap. Methods: SCOPUS and PubMed searches were conducted to identify articles in the English language investigating the association between the use of OACs and cognitive impairment and dementia. We excluded non-original research studies and studies that did not report data on cognitive impairment or included patients who underwent open heart surgery or had psychiatric illnesses or cancer. Results : Out of 22 studies ( n = 606,404 patients), 13 studies ( n = 597,744 patients) reported a reduction in cognitive impairment/dementia in those undergoing thromboprophylaxis. Using direct oral anticoagulants (DOACs) was associated with a lower incidence of cognitive impairment in 10 studies ( n = 284,636 patients). One study found that patients undergoing dual therapy ( n = 6794 patients) had a greater incidence of cognitive impairment compared to those undergoing monotherapy ( n = 9994 patients). Three studies ( n = 61,991 patients) showed that AF patients on DOACs had a lower likelihood of dementia diagnosis than those on vitamin K antagonists (VKAs). Dementia incidence was lower when VKAs were under good control. Conclusions : The use of oral anticoagulants has the potential to prevent cognitive impairment and dementia in patients with AF. Since most of the published research on this subject is observational in nature, more randomized controlled trials are needed to fully understand the effect of anticoagulants on cognitive function.

Background : Although the link between lead exposure and patterns of cardiovascular disease (CVD) has been reported, its association with silent myocardial infarction (SMI) remains unexplored. We aimed to assess the association between blood lead levels (BLLs) and SMI risk. Methods : We included 7283 (mean age 56.1 ± 2.52 years, 52.5% women) participants free of CVD from the Third National Health and Nutrition Examination Survey. BLL was measured using graphite-furnace atomic absorption spectrophotometry. SMI was defined as ECG evidence of myocardial infarction (MI) without history of MI. The association between SMI and BLLs was examined using multivariable logistic regression. Results : SMI was detected in 120 participants with an unweighted prevalence of 1.65%. Higher BLL correlated with higher SMI prevalence across BLL tertiles. In multivariable-adjusted models, participants in the third BLL tertile had more than double the odds of SMI (OR: 3.42, 95%CI: 1.76-6.63) compared to the first tertile. Each 1 µg/dL increase in BLL was linked to a 9% increase in SMI risk. This association was consistent across age, sex, and race subgroups. Conclusions : Higher BLLs are associated with higher odds of SMI in the general population. These results underscore the significance of the ongoing efforts to mitigate lead exposure and implement screening strategies for SMI in high-risk populations.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation., Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy., Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium., Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508)., Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage., Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52])., Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

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 × 10 6 : 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.

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., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Introduction: The association and the racial differences of the electrocardiographic markers of left atrial abnormality (ECG-LAA) with heart failure (HF) are unclear., Methods: We examined the cross-sectional association of ECG-LAA, defined as deep terminal negativity of P wave in V1 (DTNPV1) with HF in 8460 participants (51.5% women, 60.3 ± 13.5 age and 49.8% Whites) from the US Third National Health and Nutrition Examination Survey. We excluded participants without P-wave in their ECG or with ECG findings that interfere with measurements of P-wave. DTNPV1 was automatically measured from ECGs processed at a central lab. Values of DTNPV1 ≥ 100 μV were considered abnormal. Past medical history of HF was identified through health interviews. Multivariable logistic regression analysis was used to examine the associations of DTNPV1 with HF., Results: Abnormal DTNPV1 was detected in 3.2% (n = 271) of the participants. HF was significantly more common in individuals with abnormal, compared to those with normal, DTNPV1 (14.7% vs. 4.8%, respectively; p-value <0.001). In a model adjusted for socio-demographics and cardiovascular risk factors, ECG-LAA was associated with 98% increased odds of HF (OR (95% CI): 1.98 (1.30-3.01), p < 0.001). This association was stronger in non-White (vs. White) participants (OR (95% CI): 3.14 (1.82-5.43) vs. 1.01 (0.51-1.97), respectively; interaction p-value =0.01), but consistent in subgroups stratified by age and sex., Conclusions: ECG-LAA, defined as abnormal DTNPV1, is associated with an increased risk of HF, underscoring the role of atrial disease in developing HF. Racial differences in this association exist, possibly suggesting considering ECG-LAA in personalized assessments of HF risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF); however, to the best of our knowledge, their combined effect on the risk of HF has not yet been explored. Therefore, we examined the joint associations of albuminuria and electrocardiographic-LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. A total of 8,511 participants from the Systolic Blood Pressure Intervention Trial (SPRINT) were included. Electrocardiographic-LVH was present if any of the following criteria were present: Cornell voltage, Cornell voltage product, or Sokolow-Lyon. Albuminuria was defined as urine albumin/creatinine ratio ≥30 mg/g. ADHF was defined as hospitalization or emergency department visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF. Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with greater risk of ADHF than either albuminuria or LVH in isolation (hazard ratio [95% confidence interval]: 4.95 [3.22 to 7.62], 2.04 [1.39 to 3.00], and 1.47 [0.93 to 2.32], respectively, additive interaction p = 0.01). The effect of intensive blood pressure in reducing ADHF was attenuated in participants with coexisting albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p = 0.26). In conclusion, albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in reducing ADHF risk did not vary significantly across albuminuria/LVH combinations., Competing Interests: Declaration of Competing Interest Dr. Chen receives funding from the National Heart, Lung, and Blood Institute (R01 HL141288, R01 HL126637, K24 HL155813). The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is a progressive condition with high global incidence. HF has two main subtypes: HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). There is an inherent need for simple yet effective electrocardiogram (ECG)-based artificial intelligence (AI; ECG-AI) models that can predict HF risk early to allow for risk modification., Objective: The main objectives were to validate HF risk prediction models using Multi-Ethnic Study of Atherosclerosis (MESA) data and assess performance on HFpEF and HFrEF classification., Methods: There were six models in comparision derived using ARIC data. 1) The ECG-AI model predicting HF risk was developed using raw 12-lead ECGs with a convolutional neural network. The clinical models from 2) ARIC (ARIC-HF) and 3) Framingham Heart Study (FHS-HF) used 9 and 8 variables, respectively. 4) Cox proportional hazards (CPH) model developed using the clinical risk factors in ARIC-HF or FHS-HF. 5) CPH model using the outcome of ECG-AI and the clinical risk factors used in CPH model (ECG-AI-Cox) and 6) A Light Gradient Boosting Machine model using 288 ECG Characteristics (ECG-Chars). All the models were validated on MESA. The performances of these models were evaluated using the area under the receiver operating characteristic curve (AUC) and compared using the DeLong test., Results: ECG-AI, ECG-Chars, and ECG-AI-Cox resulted in validation AUCs of 0.77, 0.73, and 0.84, respectively. ARIC-HF and FHS-HF yielded AUCs of 0.76 and 0.74, respectively, and CPH resulted in AUC = 0.78. ECG-AI-Cox outperformed all other models. ECG-AI-Cox provided an AUC of 0.85 for HFrEF and 0.83 for HFpEF., Conclusion: ECG-AI using ECGs provides better-validated predictions when compared to HF risk calculators, and the ECG feature model and also works well with HFpEF and HFrEF classification., (© 2023 Heart Rhythm Society.)

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria, i.e. the increased QRS complex amplitude in defined leads. The classical ECG diagnostic paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces. These increased forces are reflected in the augmented QRS amplitude in the corresponding leads. However, the clinical observations document increased QRS amplitude only in the minority of patients with LVH. The low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The association of hypertension (HTN) severity and control with the risk of incident atrial fibrillation (AF) is unclear., Hypothesis: Increased HTN severity and poorer blood pressure control would be associated with an increased risk of incident AF., Methods: This analysis included 9485 participants (mean age 63 ± 8 years; 56% women; 35% Black). Participants were stratified into six mutually exclusive groups at baseline-normotension (n = 1629), prehypertension (n = 704), controlled HTN (n = 2224), uncontrolled HTN (n = 4123), controlled apparent treatment-resistant hypertension (aTRH) (n = 88), and uncontrolled aTRH (n = 717). Incident AF was ascertained at the follow-up visit, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. Multivariable logistic regression analyses adjusted for demographic and clinical variables., Results: Over an average of 9.3 years later, 868 incident AF cases were detected. Compared to those with normotension, incident AF risk was highest for those with aTRH (controlled aTRH: odds ratio (OR) 2.95; 95% confidence interval (CI) 1.60, 5.43, & uncontrolled aTRH: OR 2.47; 95% CI 1.76, 3.48). The increase in AF risk was smaller for those on no more than three antihypertensive agents regardless of their blood pressure control (controlled OR 1.72; 95% CI 1.30, 2.29 and uncontrolled OR 1.56; 95% CI 1.14, 2.13)., Conclusions: The risk of developing AF is increased in all individuals with HTN. Risk is highest in those aTRH regardless of blood pressure control. A more aggressive approach that focuses on lifestyle and pharmacologic measures to either prevent HTN or better control HTN during earlier stages may be particularly beneficial in reducing related AF risk., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Abnormalities in myocardial substrate, including diffuse and replacement fibrosis, increase the risk of cardiovascular disease (CVD). Data are sparse on whether electrocardiogram (ECG) measures, coupled with circulating biomarkers, may aid in identifying cardiac fibrosis. This study aimed to determine whether 12-lead ECG and biomarkers together augment the prediction of cardiac fibrosis in participants who are free of known CVD. This is a cross-sectional analysis in the MESA (Multiethnic Study of Atherosclerosis) study at visit 5 (2010 to 2012), with measurements of biomarkers (cardiac troponin T and growth differentiation factor-15), gadolinium-enhanced cardiac magnetic resonance imaging, and ECG. Logistic regression associations of ECG measures with cardiac magnetic resonance surrogates of fibrosis (highest quartile extracellular volume [interstitial fibrosis] and late gadolinium enhancement [replacement fibrosis]) were adjusted for demographics and risk factors. Using the C-statistic, we evaluated whether adding ECG measures and biomarkers to clinical characteristics improved the prediction of either type of fibrosis. There were 1,170 eligible participants (aged 67.1 ± 8.6 years). Among the ECG measures, QRS duration (odds ratio [OR] 1.41 per 10 ms, 95% confidence interval [CI] 1.10 to 1.81), major ST-T abnormalities (OR 3.03, 95%CI 1.20, 7.65), and abnormal QRS-T angle (OR 6.32, 95%CI 3.00, 13.33) were associated with replacement fibrosis, whereas only abnormal QRS-T angle (OR 3.05, 95%CI,1.69, 5.48) was associated with interstitial fibrosis. ECG markers, in addition to clinical characteristics, improved the prediction of replacement fibrosis (p = 0.002) but not interstitial fibrosis. The addition of cardiac troponin T and growth differentiation factor-15 to the ECG findings did not significantly improve the model discrimination for either type of cardiac fibrosis. In CVD free participants, simple ECG measures are associated with replacement fibrosis and interstitial fibrosis. The addition of these measures improves identification of replacement but not interstitial fibrosis. These findings may help refine the identification of myocardial scar in the general population., Competing Interests: Declaration of Competing Interest Dr. deFilippi has received funding for Inova to measure biomarkers from Roche Diagnostics. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02)., Conclusion: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)