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Background: Global electrical heterogeneity (GEH) is associated with sudden cardiac death (SCD) in adults of 45 years and above. However, GEH has not been previously measured in young athletes. The goal of this study was to establish a reference for vectorcardiograpic (VCG) metrics in male and female athletes., Methods: Skiers (n = 140; mean age 19.2 ± 3.5 years; 66% male, 94% white; 53% professional athletes) were enrolled in a prospective cohort. Resting 12-lead ECGs were interpreted per the International ECG criteria. Associations of age, sex, and athletic performance with GEH were studied., Results: In age and training level-adjusted analyses, male sex was associated with a larger T vector [T peak magnitude +186 (95% CI 106-266) µV] and a wider spatial QRS-T angle [+28.2 (17.3-39.2)°] as compared to women. Spatial QRS-T angle in the ECG left ventricular hypertrophy (LVH) voltage group (n = 21; 15%) and normal ECG group did not differ (67.7 ± 25.0 vs. 66.8 ± 28.2; p = 0.914), suggesting that ECG LVH voltage in athletes reflects physiological remodeling. In contrast, skiers with right ventricular hypertrophy (RVH) voltage (n = 26, 18.6%) had wider QRS-T angle (92.7 ± 29.6 vs. 66.8 ± 28.2°; p = 0.001), larger SAI QRST (194.9 ± 30.2 vs. 157.8 ± 42.6 mV × ms; p < 0.0001), but similar peak SVG vector magnitude (1976 ± 548 vs. 1939 ± 395 µV; p = 0.775) as compared to the normal ECG group. Better athletic performance was associated with the narrower QRS-T angle. Each 10% worsening in an athlete's Federation Internationale de' Ski downhill ranking percentile was associated with an increase in spatial QRS-T angle by 2.1 (95% CI 0.3-3.9) degrees (p = 0.013)., Conclusion: Vectorcardiograpic adds nuances to ECG phenomena in athletes., (© 2018 Wiley Periodicals, Inc.)

Aim: Our goal was to investigate the effect of a global XYZ median beat construction and the heart vector origin point definition on predictive accuracy of ECG biomarkers of sudden cardiac death (SCD)., Methods: Atherosclerosis Risk In Community study participants with analyzable digital ECGs were included (n = 15,768; 55% female, 73% white, mean age 54.2 ± 5.8 y). We developed an algorithm to automatically detect the heart vector origin point on a median beat. Three different approaches to construct a global XYZ beat and two methods to locate origin point were compared. Global electrical heterogeneity was measured by sum absolute QRST integral (SAI QRST), spatial QRS-T angle, and spatial ventricular gradient (SVG) magnitude, azimuth, and elevation. Adjudicated SCD served as the primary outcome., Results: There was high intra-observer (kappa 0.972) and inter-observer (kappa 0.984) agreement in a heart vector origin definition between an automated algorithm and a human. QRS was wider in a median beat that was constructed using R-peak alignment than in time-coherent beat (88.1 ± 16.7 vs. 83.7 ± 15.9 ms; P < 0.0001), and on a median beat constructed using QRS-onset as a zeroed baseline, vs. isoelectric origin point (86.7 ± 15.9 vs. 83.7 ± 15.9 ms; P < 0.0001). ROC AUC was significantly larger for QRS, QT, peak QRS-T angle, SVG elevation, and SAI QRST if measured on a time-coherent median beat, and for SAI QRST and SVG magnitude if measured on a median beat using isoelectric origin point., Conclusion: Time-coherent global XYZ median beat with physiologically meaningful definition of the heart vector's origin point improved predictive accuracy of SCD biomarkers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Implantable cardioverter-defibrillators (ICDs) improve survival of systolic heart failure (HF) patients who are at risk of sudden cardiac death (SCD). We recently showed that electrocardiographic (ECG) global electrical heterogeneity (GEH) is independently associated with SCD in the community-dwelling cohort and developed GEH SCD risk score. The Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study is a retrospective multicenter cohort designed with two goals: (1) validate an independent association of ECG GEH with sustained ventricular tachyarrhythmias and appropriate ICD therapies and (2) validate GEH ECG risk score for prediction of sustained ventricular tachyarrhythmias and appropriate ICD therapies in systolic HF patients with primary prevention ICD., Methods: All records of primary prevention ICD recipients with available data for analysis are eligible for inclusion. Records of ICD implantation in patients with inherited channelopathies and cardiomyopathies are excluded. Raw digital 12-lead pre-implant ECGs will be used to measure GEH (spatial QRST angle, spatial ventricular gradient magnitude, azimuth, and elevation, and sum absolute QRST integral). The primary endpoint is defined as a sustained ventricular tachyarrhythmia event with appropriate ICD therapy. All-cause death without preceding sustained ventricular tachyarrhythmia with appropriate ICD therapy will serve as a primary competing outcome. The study will draw data from the academic medical centers., Results: We describe the study protocol of the first multicenter retrospective cohort of primary prevention ICD patients with recorded at baseline digital 12-lead ECG., Conclusion: Findings from this study will inform future trials to identify patients who are most likely to benefit from primary prevention ICD., Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT03210883.

The purpose of this study was to develop optimal configuration of adhesive ECG patches placement on the torso, which would provide the best agreement with the Frank orthogonal ECGs. Ten seconds of orthogonal ECG followed by 3-5min of ECGs using patches at 5 different locations simultaneously on the torso were recorded in 50 participants at rest in sitting position. Median beat was generated for each ECG and 3 patch ECGs that best correlate with orthogonal ECGs were selected for each participant. For agreement analysis, spatial QRS-T angle, spatial QRS and T vector characteristics, spatial ventricular gradient, roundness, thickness and planarity of vectorcardiographic (VCG) loops were measured. Key VCG parameters showed high agreement in Bland-Altman analysis (spatial QRS-T angle on 3-patch ECG vs. Frank ECG bias 0.3 (95% limits of agreement [-6.23;5.71 degrees]), Lin's concordance coefficient=0.996). In conclusion, newly developed orthogonal 3-patch ECG can be used for long-term VCG monitoring., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The goal of this study was to compare the time series predictors of beat-to-beat variability in repolarization in healthy individuals., Methods: Spatial QRS- and T-vector amplitudes, spatial QRS-T, RR' and TT' angles, RR' and QT intervals, and QRS- and T-loop roundness were measured on 453 consecutive sinus beats in 168 healthy subjects (mean age 39.8±15.6years; 50% men; 93% white). Panel time-series regression models were adjusted by age, sex, and race. Appropriate time series of ECG metrics served as predictors and outcomes., Results: Increase in T-loop roundness index by 0.1 was associated with 1.1° (95%CI 0.9-2.2; P=0.048) increase in corresponding TT' angle. One unit increase in a respiration index was associated with 4ms (95%CI 0.6-7.0; P=0.021) increase in QT interval., Conclusions: Spatial TT' angle and beat-to-beat variability in T-loop roundness represent intrinsic measures of repolarization variability. QT interval variability characterizes the effect of respiration and heart rate variability., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Vectorcardiography (VCG), developed 100years ago, characterizes clinically important electrophysiological properties of the heart. In this study, VCG QRS loop roundness, planarity, thickness, rotational angle, and dihedral angle were measured in 81 healthy control subjects (39.0±14.2y; 51.8% male; 94% white), and 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (68.0±7.8y, 37.5% male). The angle between two consecutive QRS vectors was defined as the rotational angle, while dihedral angle quantified planar alteration over the QRS loop. In VT subjects, planarity index decreased (0.63±0.22 vs. 0.88±0.10; P=0.014), and dihedral angle was significantly more variable (variance of dihedral angle, median (IQR): 897(575-1450) vs. 542(343-773); P=0.029; rMSSD: 47.7±12.7 vs. 35.1±13.1; P=0.027). Abnormal electrophysiological substrate in VT patients is characterized by the appearance of QRS loop folding, likely due to local conduction block. The presence of fragmented QRS complexes on the 12-lead ECG had low sensitivity (31%) for detecting QRS loop folding on the VCG., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We constructed an intracardiac vectorcardiogram from 3 configurations of intracardiac cardiovertor defibrilator (ICD) electrograms (EGMs). Six distinctive 3 lead combinations were selected out of five leads: can to right ventricular coil (RVC); RVC to superior vena cava coil (SVC); atrial lead tip (A-tip) to right ventricular (RV)-ring; can to RV-ring; RV-tip to RVC, in a patient with dual chamber ICD. Surface spatial QRS-T angle (119.8°) was similar to intracardiac spatial QRS-T angle derived from ICD EGMs combination A (101.3°), B (96.1°), C (92.8°), D (95.2), E (99.0), F (96.2) and median (101.5). Future validation of the novel method is needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Recently we showed the predictive value of sum absolute QRST integral (SAI QRST) and repolarization lability for risk stratification of sudden cardiac death (SCD) in heart failure patients. The goal of this study was to compare SAI QRST and metrics of depolarization and repolarization variability in healthy men and women., Methods: Orthogonal ECGs were recorded at rest for 10 minutes in 160 healthy men and women (mean age 39.6±14.6, 80 men). Mean spatial TT' angle, and normalized variances of T loop area, of spatial T vector amplitude, of QT interval and Tpeak-Tend area were measured for assessment of repolarization lability. Normalized variances of spatial QRS vector and QRS loop area characterized variability of depolarization. In addition, variability indices (VI) were calculated to adjust for normalized heart rate variance. SAI QRST was measured as the averaged arithmetic sum of areas under the QRST curve., Results: Men were characterized by shorter QTc (430.3±21.7 vs. 444.7±22.2 ms; P<0.0001) and larger SAI QRST (282.1±66.7 vs. 204.9±58.5 mV*ms; P<0.0001). Repolarization lability negatively correlated with spatial T vector amplitude. Adjusted by normalized heart rate variance, QT variability index was significantly higher in women than in men (-1.54±0.38 vs. -1.70±0.33; P = 0.017). However, in multivariate logistic regression after adjustment for body surface area, QTc, and spatial T vector amplitude, healthy men had 1.5-3 fold higher probability of having larger repolarization lability, as compared to healthy women (T vector amplitude variability index odds ratio 3.88 (95%CI 1.4-11.1; P = 0.012)., Conclusions: Healthy men more likely than women have larger repolarization lability.

Background: Methodological difficulties associated with QT measurements prompt the search for new electrocardiographic markers of repolarization heterogeneity., Objective: We hypothesized that beat-to-beat 3-dimensional vectorcardiogram variability predicts ventricular arrhythmia (VA) in patients with structural heart disease, left ventricular systolic dysfunction, and implanted implantable cardioverter-defibrillators (ICDs)., Methods: Baseline orthogonal electrocardiograms were recorded in 414 patients with structural heart disease (mean age 59.4 ± 12.0; 280 white [68%] and 134 black [32%]) at rest before implantation of ICD for primary prevention of sudden cardiac death. R and T peaks of 30 consecutive sinus beats were plotted in 3 dimensions to form an R peaks cloud and a T peaks cloud. The volume of the peaks cloud was calculated as the volume within the convex hull. Patients were followed up for at least 6 months; sustained VA with appropriate ICD therapies served as an end point., Results: During a mean follow-up time of 18.4 ± 12.5 months, 61 of the 414 patients (14.73% or 9.6% per person-year of follow-up) experienced sustained VA with appropriate ICD therapies: 41 of them were white and 20 were black. In the multivariate Cox model that included inducibility of VA and use of beta-blockers, the highest tertile of T/R peaks cloud volume ratio significantly predicted VA (hazard ratio 1.68, 95% confidence interval 1.01 to 2.80; P = .046) in all patients. T peaks cloud volume and T/R peaks cloud volume ratio were significantly smaller in black subjects (median 0.09 [interquartile range 0.04 to 0.15] vs. median 0.11 [interquartile range 0.06 to 0.22], P = .002)., Conclusion: A relatively large T peaks cloud volume is associated with increased risk of VA in patients with structural heart disease and systolic dysfunction., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 infection is associated with an increased risk of late cardiovascular (CV) outcomes. However, more data is needed to describe the electrophysiologic (EP) manifestation of post-acute CV sequelae of COVID-19. We compared two cohorts of adult patients with SARS-CoV-2 polymerase chain reaction (PCR) test and an electrocardiogram (ECG) performed between March 1, 2020, and September 13, 2020, in a retrospective double-cohort study, "Cardiovascular Risk Stratification in Covid-19" (CaVaR-Co19; NCT04555187). Patients with positive PCR comprised a COVID-19(+) cohort (n = 41; 61% women; 80% symptomatic), whereas patients with negative tests formed the COVID-19(−) cohort (n = 155; 56% women). In longitudinal analysis, comparing 3 ECGs recorded before, during, and on average 40 days after index COVID-19 episode, after adjustment for demographic and socioeconomic characteristics, baseline CV risk factors and comorbidities, use of prescription medications (including QT-prolonging drugs) before and during index COVID-19 episode, and the longitudinal changes in RR' intervals, heart rhythm, and ventricular conduction type, only in the COVID-19(+) cohort QTc increased by +30.2(95% confidence interval [CI] 0.1–60.3) ms and the spatial ventricular gradient (SVG) elevation increased by +13.5(95%CI 1.2–25.9)°. In contrast, much smaller, statistically nonsignificant changes were observed in the COVID-19(−) cohort. In conclusion, post-acute CV sequelae of SARS-CoV-2 infection manifested on ECG by QTc prolongation and rotation of the SVG vector upward. [ABSTRACT FROM AUTHOR]

Background: Electrocardiographic (ECG) markers of antiarrhythmic drug (AAD) activity could be used to optimize efficacy and minimize toxicity. Vectorcardiographic global electrical heterogeneity (GEH) is associated with ventricular arrhythmias and sudden death, but it is unclear how GEH measurements change in response to AADs.Objective: The purpose of this study was to characterize acute effects of AADs on GEH measurements.Methods: We analyzed double-blind placebo-controlled trial data from healthy volunteers given 1 dose of placebo, dofetilide, quinidine, ranolazine, or verapamil on subsequent visits. Serial ECGs and plasma drug concentrations were collected. Vectorcardiographic GEH parameters (spatial ventricular gradient [SVG], spatial QRST angle, sum absolute QRST integral, and SVG-QRS peak angle) were measured. Placebo-corrected change from baseline was regressed on drug concentration stratified by sex using linear mixed effects models.Results: Among 22 persons (11 (50%) male median age 27 ± 5 years), 5232 ECGs were analyzed. Dofetilide and quinidine were associated with significant changes in more GEH parameters (5) compared with verapamil (2) and ranolazine (1). The most notable change occurred in SVG azimuth, with largest changes (degrees per unit normalized drug concentration) in dofetilide (6.1; 95% confidence interval [CI] 4.2-8.0) and quinidine (9.4; 95% CI 6.7-12.0), and smaller effects in verapamil (4.4; 95% CI 2.9-5.9) and ranolazine (5.4; 95% CI 3.5-7.3). AAD-induced GEH changes significantly differed in men and women.Conclusion: AADs change GEH measurements. These changes, which differ by sex, are likely driven by alterations in ion channel function and dispersion of depolarization or repolarization. GEH measurement may allow early assessment of favorable or adverse AAD effects. [ABSTRACT FROM AUTHOR]

Background: Electric excitation initiates myocardial mechanical contraction and coordinates myocardial pumping. We hypothesized that ECG global electric heterogeneity (GEH) and its longitudinal changes are associated with cardiac structure and function.Methods and Results: Participants from the ARIC study (Atherosclerosis Risk in Communities) (N=5114; 58% female; 22% blacks) with resting 12-lead ECGs (visits 1-5) and echocardiographic assessment of left ventricular (LV) ejection fraction, LV global longitudinal strain, LV mass index, LV end-diastolic volume index, and LV end-systolic volume index at visit 5 were included. Longitudinal analysis included ARIC participants (N=14 609) with measured GEH at visits 1 to 4. GEH was quantified by spatial ventricular gradient, QRS-T angle, and sum absolute QRS-T integral. Cross-sectional and longitudinal regressions were adjusted for manifest and subclinical cardiovascular disease. Having 4 abnormal GEH parameters was associated with a 6.4% (95% confidence interval, 5.5-7.3) LV ejection fraction decline, a 24.2 g/m2 (95% confidence interval, 21.5-26.9) increase in LV mass index, a 10.3 mL/m2 (95% confidence interval, 8.9-11.7) increase in LV end-diastolic volume index, and a 7.8 mL/m2 (95% confidence interval, 6.9-8.6) increase in LV end-systolic volume index. Altogether, clinical and ECG parameters accounted for approximately one third of LV volume and 20% of systolic function variability. The associations were significantly stronger in cardiovascular disease. Sum absolute QRS-T integral increased by 20 mV*ms for each 3-year period in participants who demonstrated LV dilatation at visit 5. Sudden cardiac death victims demonstrated rapid GEH worsening, whereas those with LV dysfunction demonstrated slow GEH worsening. Healthy aging was associated with a distinct pattern of spatial ventricular gradient azimuth decrement.Conclusions: GEH is a marker of subclinical abnormalities in cardiac structure and function. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: From experiments, we know that the heterogeneity of action potential duration and morphology is an important mechanism of ventricular tachyarrhythmia. Electrocardiogram (ECG) markers of repolarization lability are known; however, lability of depolarization has not been systematically studied. We propose a novel method for the assessment of variability of both depolarization and repolarization phases of the cardiac cycle. Methods: Baseline orthogonal ECGs of 81 patients (mean ± SD age, 56 ± 13 years; 61 male [75%]) with structural heart disease and implanted single-chamber implantable cardioverter defibrillator (ICD) were analyzed. Clean 30-beat intervals with absence of premature beats were then selected. Baseline wandering was corrected before analysis. Peaks of R wave and peaks of T wave were detected for each beat, and the axis magnitude was calculated. The peaks were plotted to show clouds of peaks and then used to construct a convex hull, and the volumes of the R peaks cloud and T peaks cloud and ratio of volumes were calculated. Results: During a mean (SD) follow-up period of 13 (10) months, 9 of the 81 patients had sustained ventricular tachycardia or ventricular fibrillation (VT/VF) and received appropriate ICD therapies. All ICD events were adjudicated by three independent electrophysiologists. There was no statistically significant difference in the volume of T-wave peaks or R-wave peaks between patients with and without VT or VF during follow-up; however, R/T peaks cloud volume ratio was significantly lower in patients with subsequent VT/VF (22.4 ± 25.4 versus 13.1 ± 7.9, P = .024). Conclusions: Larger volume of T peaks cloud, measured during 30 beats of three-dimensional ECG, is associated with higher risk of sustained ventricular tachyarrhythmias and appropriate ICD therapies. New method to assess temporal variability of repolarization in three-dimensional ECGs by measuring volume of peak clouds shows potential for further exploration for VT/VF risk stratification. [Copyright &y& Elsevier]