Introduction: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT. We aimed to compare the effects of aCRT and conventional CRT on electrical dyssynchrony. Methods: We conducted a double-blind, randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrodes body surface mapping. We measured electrical dyssynchrony on the epicardial surface using noninvasive electrocardiographic imaging (ECGI) before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. Results: We randomized 27 participants (mean age 64±12 y; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 155±21 ms; strict left bundle branch block (LBBB) in 13%) to conventional CRT (n=15) versus aCRT (n=12). In atypical LBBB (n=11;41%) with S-waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in those who met the strict LBBB criteria. As compared to baseline, VEU reduced post-CRT in aCRT (median reduction 18.9 (interquartile range 4.3-29.2 ms; P=0.034), but not in conventional CRT (21.4 (-30.0 to 49.9 ms; P=0.525) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. Conclusion: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar.

Background. Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months. Methods. This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson's chi-square test for binary outcomes. Effect size was measured using Cohen's d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test. Results. Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P=0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P=0.013), and 24-hour urine CrCL (P=0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P=0.049) and a trend toward better renal function (P=0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P=0.01) at 24 months. Conclusions. EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.

Multiple studies reported clinical benefits of adaptive cardiac resynchronization therapy (aCRT) over conventional CRT; however, their effect on electrical dyssynchrony was not studied. The objective of this study was to compare the effects of aCRT and conventional CRT on electrical dyssynchrony. In this trial we randomized 27 patients (mean age 64±12 y; 34% female; 53% ischemic cardiomyopathy; left ventricular ejection fraction 28±8%; QRS duration 155±21 ms; 56% left bundle branch block (LBBB) of which 15% met strict LBBB criteria) to conventional CRT (n=15) versus aCRT (n=12). Electro-anatomical data were collected through cardiac computed tomography and 128-electrodes body surface mapping (figure). Electrical dyssynchrony on the epicardial surface was calculated using noninvasive electrocardiographic imaging (ECGI) before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean LV and RV activation times. Electrical dyssynchrony index (EDI) was calculated as the standard deviation of local epicardial activation times. In atypical LBBB (n=11;41%), conduction block occurred in the anterior RV, whereas in strict LBBB (n=4;15%), it was observed near the interventricular groove (figure). As compared to baseline, VEU decreased post-CRT in aCRT (median reduction 18.9 (interquartile range 4.3-29.2 ms; P=0.034), but not in conventional CRT (21.4 (-30.0 to 49.9 ms; P=0.525) group. No differences in the degree of change in VEU and EDI indices were found between the treatment groups. The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar.

Background Mechanisms of arrhythmogenicity in hypertrophic cardiomyopathy (HCM) are not well understood. Objective To characterize an electrophysiological substrate of HCM in comparison to ischemic cardiomyopathy (ICM), or healthy individuals. Methods We conducted a prospective case-control study. The study enrolled HCM patients at high risk for ventricular tachyarrhythmia (VT) [n = 10; age 61 ± 9 years; left ventricular ejection fraction (LVEF) 60 ± 9%], and three comparison groups: healthy individuals (n = 10; age 28 ± 6 years; LVEF > 70%), ICM patients with LV hypertrophy (LVH) and known VT (n = 10; age 64 ± 9 years; LVEF 31 ± 15%), and ICM patients with LVH and no known VT (n = 10; age 70 ± 7 years; LVEF 46 ± 16%). All participants underwent 12-lead ECG, cardiac CT or MRI, and 128-electrode body surface mapping (BioSemi ActiveTwo, Netherlands). Non-invasive voltage and activation maps were reconstructed using the open-source SCIRun (University of Utah) inverse problem-solving environment. Results In the epicardial basal anterior segment, HCM patients had the greatest ventricular activation dispersion [16.4 ± 5.5 vs. 13.1 ± 2.7 (ICM with VT) vs. 13.8 ± 4.3 (ICM no VT) vs. 8.1 ± 2.4 ms (Healthy); P = 0.0007], the largest unipolar voltage [1094 ± 211 vs. 934 ± 189 (ICM with VT) vs. 898 ± 358 (ICM no VT) vs. 842 ± 90 μV (Healthy); P = 0.023], and the greatest voltage dispersion [median (interquartile range) 215 (161–281) vs. 189 (143–208) (ICM with VT) vs. 158 (109–236) (ICM no VT) vs. 110 (106–168) μV (Healthy); P = 0.041]. Differences were also observed in other endo-and epicardial basal and apical segments. Conclusion HCM is characterized by a greater activation dispersion in basal segments, a larger voltage, and a larger voltage dispersion through LV. Clinical Trial Registration www.clinicaltrials.gov Unique identifier: NCT02806479.

Background—The risk of sudden cardiac death (SCD) is known to be dynamic. However, the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing non-sudden cardiac death (non-SCD). Methods—Atherosclerosis Risk In Community study participants with analyzable ECGs in sinus rhythm were included (n=15,716; 55% female, 73% white, age 54.2±5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity and traditional ECG metrics (heart rate, QRS, QTc) were measured. Adjudicated SCD was the primary outcome; non-SCD was competing outcome. Time-dependent area under the receiver operating characteristic curve (ROC(t) AUC) analysis was performed to assess the prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years using survival analysis framework. Reclassification improvement as compared to clinical risk factors (age, sex, race, diabetes, hypertension, coronary heart disease, stroke) was measured. Results—Over a median 24.4 y follow-up, there were 577 SCDs (incidence 1.76 (95%CI 1.63-1.91)/1,000 person-years), and 829 non-SCDs [2.55 (95%CI 2.37-2.71)]. No ECG biomarkers predicted SCD within 3 months after ECG recording. Within 6 months, spatial ventricular gradient (SVG) elevation predicted SCD (AUC 0.706; 95%CI 0.526-0.886), but not a non-SCD (AUC 0.527; 95%CI 0.303-0.75). SVG elevation more accurately predicted SCD if ECG was recorded 6 months before SCD (AUC 0.706; 95%CI 0.526-0.886) than 2 years before SCD (AUC 0.608; 95%CI 0.515-0.701). Within the first 3 months after ECG recording, only SVG azimuth improved reclassification of the risk beyond clinical risk factors: 18% SCD events were reclassified from low or intermediate risk to a high-risk category. Long-term, QRS-T angle was the strongest predictor of SCD (AUC 0.710; 95%CI 0.668-0.753 for ECG recorded within 10 years before SCD). Conclusion—Short-term and long-term predictive accuracy of ECG biomarkers of SCD differed, reflecting differences in transient vs. persistent SCD substrates. The dynamic predictive accuracy of ECG biomarkers should be considered for competing SCD risk scores. The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD (triggers or transient substrates) versus markers identifying persistent substrate.

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.

Background In patients with end‐stage kidney disease, sudden cardiac death is more frequent after a long interdialytic interval, within 6 hours after the end of a hemodialysis session. We hypothesized that the occurrence of paroxysmal arrhythmias is associated with changes in heart rate and heart rate variability in different phases of hemodialysis. Methods and Results We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort. Continuous ECG monitoring was performed using an ECG patch, and short‐term heart rate variability was measured for 3 minutes every hour (by root mean square of the successive normal‐to‐normal intervals, spectral analysis, Poincaré plot, and entropy), up to 300 hours. Out of enrolled participants (n=28; age 54±13 years; 57% men; 96% black; 33% with a history of cardiovascular disease; left ventricular ejection fraction 70±9%), arrhythmias were detected in 13 (46%). Nonsustained ventricular tachycardia occurred more frequently during/posthemodialysis than pre‐/between hemodialysis (63% versus 37%, P=0.015). In adjusted for cardiovascular disease time‐series analysis, nonsustained ventricular tachycardia was preceded by a sudden heart rate increase (by 11.2 [95% CI 10.1–12.3] beats per minute; P<0.0001). During every‐other‐day dialysis, root mean square of the successive normal‐to‐normal intervals had a significant circadian pattern (Mesor 10.6 [ 95% CI 0.9–11.2] ms; amplitude 1.5 [95% CI 1.0–3.1] ms; peak at 02:01 [95% CI 20:22–03:16] am; P<0.0001), which was replaced by a steady worsening on the second day without dialysis (root mean square of the successive normal‐to‐normal intervals −1.41 [95% CI −1.67 to −1.15] ms/24 h; P<0.0001). Conclusions Sudden increase in heart rate during/posthemodialysis is associated with nonsustained ventricular tachycardia. Every‐other‐day hemodialysis preserves circadian rhythm, but a second day without dialysis is characterized by parasympathetic withdrawal.

Background: Global electrical heterogeneity (GEH) is a useful predictor of adverse clinical outcomes. However, reproducibility of GEH measurements on 10-second routine clinical ECG is unknown. Methods: Data of the prospective cohort study of incident hemodialysis patients (n=253; mean age 54.6±13.5y; 56% male; 79% African American) were analysed. Two random 10-second segments of 5-minute ECG recording in sinus rhythm were compared. GEH was measured as spatial QRS-T angle, spatial ventricular gradient (SVG) magnitude and direction (azimuth and elevation), and a scalar value of SVG measured by (1) sum absolute QRST integral (SAI QRST), and (2) QT integral on vector magnitude signal (iVM QT ). Bland-Altman analysis was used to calculate agreement. Results: For all studied vectorcardiographic metrics, agreement was substantial (Lin`s concordance coefficient >0.98), and precision was perfect (>99.99%). 95% limits of agreement were ±14 ° for spatial QRS-T angle, ±13 ° for SVG azimuth ±4 ° for SVG elevation, ±14 mV*ms for SVG magnitude, and ±17 mV*ms for SAI QRST. SAI QRST and iVM QT were in substantial agreement with each other. Conclusion: Reproducibility of a 10-second automated GEH ECG measurements was substantial, and precision was perfect.

Background In end-stage kidney disease the dialytic cycle relates to the rate of sudden cardiac death. We hypothesized that circadian, dialytic cycles, paroxysmal arrhythmias, and cardiovascular risk factors are associated with periodic changes in heart rate and heart rate variability (HRV) in incident dialysis patients. Methods We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort (n=28; age 54±13 y; 57% men; 96% black; 33% with a history of structural heart disease; left ventricular ejection fraction 70±9%). Continuous ECG monitoring was performed using an ECG patch (Zio Patch, iRhythm) and short-term HRV was measured for three minutes every hour. HRV was measured by root mean square of the successive normal-to-normal intervals (rMSSD), high and low frequency power, Poincaré plot, and sample and Renyi entropy. Results Arrhythmias were detected in 46% (n=13). Non-sustained ventricular tachycardia (VT) was more frequent during dialysis or within 6 hours post-dialysis, as compared to pre-or between-dialysis (63% vs. 37%, P=0.015), whereas supraventricular tachycardia was more frequent pre-/ between-dialysis, as compared to during-/ post-dialysis (84% vs. 16%, P=0.015). In adjusted for cardiovascular disease and its risk factors autoregressive conditional heteroscedasticity panel (ARCH) model, VT events were associated with increased heart rate by 11.2 (95%CI 10.1-12.3) bpm (P<0.0001). During regular dialytic cycle, rMSSD demonstrated significant circadian pattern (Mesor 10.6(0.9-11.2) ms; Amplitude 1.5(1.0-3.1) ms; Peak at 02:01(20:22-03:16) am; P<0.0001), which was abolished on a second day interdialytic extension (adjusted ARCH trend for rMSSD −1.41(−1.67 to −1.15) ms per 24h; P<0.0001). Conclusion Cardiac arrhythmias associate with dialytic phase. Regular dialytic schedule preserves physiological circadian rhythm, but the second day without dialysis is characterized by parasympathetic withdrawal and a steady increase in sympathetic predominance. Subject Terms Arrhythmias, Autonomic Nervous System, Electrocardiology (ECG), Treatment.

Introduction: Poincare plot asymmetry has been associated with sustained ventricular tachyarrhythmias, implicating involvement of the autonomic nervous system. An association between sudden cardiac death (SCD) and Poincare plot asymmetry has not previously been studied in a general population cohort. Porta index measures time asymmetry in heart rate variability (HRV), corresponding to disproportionate relative tachycardic predominance. Hypothesis: We hypothesized that increasing tachycardic asymmetry as measured by Porta Index is associated with SCD. Methods: We analyzed 10-second ECG in 14,247 participants across 5 visits in the Atherosclerosis Risk in Communities (ARIC) cohort (mean age 54.1±5.87y; 6,380 [45%] men; 10,569 [74%] white, 1,582 [11%] with prevalent cardiovascular disease (CVD)). Participants with atrial fibrillation, premature contractions, sinoatrial (SA) or atrioventricular (AV) blocks II-III were excluded. Only normal sinus beats were included in the semi-automated analysis. Accuracy of automated R-peak detection was manually validated. SCD, non-SCD, and non-cardiac death served as competing outcomes in a Fine and Gray competing risk model. Results: Overall, there was larger variability in Porta index within the same participant from visit to visit (50.0±12.1) than between different participants (50.0±8.4). Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95% CI 1.52-1.82], 742 non-SCD (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95% CI 12.1-13.0]) per 1,000 person-years. In time-updated analysis, Porta index was independently associated with increased risk of SCD (HR 1.13 [1.04-1.23]). Neither non-sudden cardiac death nor non-cardiac death are associated with Porta ndex. Conclusion: Time-updated Poincare Plot asymmetry as measured by Porta index, reflecting tachycardic runs longer than bradycardic runs, is independently associated with SCD in the community. Poincare plot asymmetry requires further study.

The Selvester score (SS) was created to estimate myocardial infarct size from the QRS complex on the ECG. We hypothesized that SS is associated with sudden cardiac death (SCD). ECGs from baseline and subsequent visits of the Atherosclerosis Risk in Communities (ARIC) study (N = 15,722; mean age 54.

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.

Introduction: The association between premature ventricular contractions (PVCs) and Sudden Cardiac Death (SCD) remains controversial. Hypothesis: We hypothesized that PVCs are associated with SCD. Methods: Presence of PVCs was detected on 12-lead ECG recorded at baseline or any of 4 follow-up visits in 15,667 participants (pts) (mean age: 54.2 + 5.8 Yrs; 55% female; 73% Whites) of the Atherosclerosis Risk in Communities (ARIC) study. For validation cohort, we included baseline and 9 follow-up visits ECG data in 5,846 pts (mean age: 72.8+ 5.6 yrs; 57.7% female, 84.2% whites) from Cardiovascular Health Study (CHS). Competing risk analyses models were constructed to test the association between time-updated PVCs and SCD risk. Model 1 was adjusted for age, sex, race and study center. Model 2 in addition was adjusted for time-updated coronary heart disease, heart failure, atrial fibrillation, stroke, and hypertension. Results: In ARIC pts, across all study visits, PVCs were observed in 2.6% of the ECGs; 99.7% of pts were PVC-free at least once; 8.8% of pts had PVC at least once. 97.7% of pts without PVCs remained PVC-free at the next visit; 19.1% of pts with detected PVC had PVC at the next visit; 2.4% of pts who were PVC-free on previous ECG, transitioned to having PVC on subsequent visit ECG. In CHS, across all 10 yearly study visits, on average, PVC was observed on 4.85% of ECG recordings; 99.4% of participants were PVC-free at least once; 21.9% of pts had PVC at least once. 96.4% of PVC-free pts remained free from PVC at the next visit. 30.6% of pts with detected PVC on a given ECG had PVC at the next visit. 3.6% of pts who did not have PVC on previous ECG, transitioned to having PVC at the next visit. 69.4% of pts with PVC on a given ECG transitioned to being PVC-free next year. In adjusted competing risk analysis PVC was associated with SCD, but not with non-sudden cardiac death or non-cardiac death (Table). Conclusions: Time-updated presence of PVC on a short 10-sec resting 12-lead ECG is associated with SCD.

INTRODUCTION:The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a life-saving device. Recording of a specialized 3-lead electrocardiogram (ECG) is required for S-ICD eligibility assessment. The goals of this study were: (1) evaluate the effect of ECG filtering on S-ICD eligibility, and (2) simplify S-ICD eligibility assessment by development of an S-ICD ineligibility prediction tool, which utilizes the widely available routine 12-lead ECG. METHODS AND RESULTS:Prospective cross-sectional study participants [n = 68; 54% male; 94% white, with wide ranges of age (18-81 y), body mass index (19-53), QRS duration (66-150 ms), and left ventricular ejection fraction (37-77%)] underwent 12-lead supine, 3-lead supine and standing ECG recording. All 3-lead ECG recordings were assessed using the standard S-ICD pre-implantation ECG morphology screening. Backward, stepwise, logistic regression was used to build a model for 12-lead prediction of S-ICD eligibility. Select electrocardiogram waves and complexes: QRS, R-, S, and T-amplitudes on all 12 leads, averaged QT interval, QRS duration, and R/T ratio in the lead with the largest T wave (R/Tmax) were included as predictors. The effect of ECG filtering on ECG morphology was evaluated. A total of 9 participants (13%) failed S-ICD screening prior to filtering. Filtering at 3-40 Hz, similar to the S-ICD default, reduced S-ICD ineligibility to 4%. A regression model that included RII, SII-aVL, TI, II, aVL, aVF, V3-V6, and R/Tmax perfectly predicted S-ICD eligibility, with an Area Under the Receiver Operating Characteristic Curve of 1.0. CONCLUSION:Routine clinical 12-lead ECG can be used to predict S-ICD eligibility. ECG filtering may improve S-ICD eligibility.

Extracardiac factors such as respiration, fluid overload and body habitus have important effects on the ECG voltage. Vectorcardiographic (VCG) Global Electrical Heterogeneity (GEH) is associated with sudden cardiac death (SCD). Risk of SCD is especially high in end-stage renal disease patients (ESRD) on dialysis. However, extracardiac factors challenge ECG interpretation in ESRD patients. The effects of extracardiac factors on GEH have not been fully studied. To assess effects of extracardiac factors on ECG, we conducted a multi-scale study. An experimental data of ESRD patients and a previously developed biophysically detailed heart-torso model were used to investigate the effects of respiration, fluid overload and body habitus on the VCG and GEH.

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.