Electrocardiographic Early Repolarization Research Articles

Increased Prevalence of the Electrocardiographic Early Repolarization Pattern in Young Patients With Vagally Mediated Syncope: A Case-Control Study

BackgroundElectrocardiographic early repolarization (EER) is linked with idiopathic ventricular fibrillation in adults. It is frequently seen in children, with poorly understood significance. Some evidence suggests that it could be a vagally mediated phenomenon. A retrospective case-control study was undertaken to test the hypothesis that EER is more common among children with typical vasovagal syncope (VVS) than among their peers with nonvagal syncope (NVS) or with no syncope. MethodsPatients aged 4-18 years with syncope were identified by a single-centre database search followed by a review of history for features of VVS (n = 150) or NVS (n = 84). The first available electrocardiogram (ECG) for VVS or for NVS was retrieved. Age- and sex-matched children with no known syncope or heart disease were then identified (n = 216). ECGs were assessed separately for EER based on published criteria by 2 observers blinded to patients’ clinical status. ResultsMean age was 12.3 ± 3.2 years, and heart rate was 74.2 ± 16.5 beats/min. EER was more prevalent in VVS (33.3%) than among patients with NVS (19.1%; odds ratio: 2.29; confidence interval: 1.32-5.50) or among those with no syncope (12.5%; odds ratio: 3.14; confidence interval: 1.81-5.46). Heart rates were significantly lower in VVS and NVS (heart rate: 70.1 ± 13.8 and 70.7 ± 12.4 beats/min, respectively) compared with children with no syncope (heart rate: 78.2 ± 18.0 beats/min), both P < 0.001. ConclusionsEER is more common in paediatric patients with VVS than those with NVS or without syncope, consistent with a possible vagal contribution to the ECG finding.

Evaluation of Atrial Electromechanical Delay and Left Atrial Phasic Function in Individuals with Electrocardiographic Early Repolarization Pattern.

Atrial electromechanical delay (EMD) and left atrial (LA) phasic function have been demonstrated to be predictors for the development of atrial fibrillation (AF). In the present study, we aimed to evaluate atrial EMD and LA phasic function in individuals with electrocardiographic early repolarization pattern (ERP). Eighty consecutive individuals with ERP and 40 age- and gender-matched control subjects without ERP were compared in this cross-sectional study. Atrial electromechanical coupling (Pa') was measured from lateral mitral annulus (Pa'lateral), septal mitral annulus (Pa'septal), and lateral tricuspid annulus (Pa'tricuspid) using tissue Doppler echocardiography to calculate intra- and inter-atrial EMD. LA maximal volume, LA minimal volume, and LA volume before atrial contraction were calculated using the biplane area-length method to assess LA phasic function. LA diameter, LA volume index, Pa'lateral, Pa'septal, Pa'tricuspid electrical activity and intra-left atrial EMD were significantly increased in the ERP patients. Mitral lateral, septal, tricuspid lateral annular tissue Doppler s' and e' waves were significantly decreased in the ERP patients. There were no significant difference between the groups in terms of interatrial EMD, intra-right atrial EMD, LA total emptying volume and LA total emptying fraction indicating LA reservoir function, LA passive emptying volume and LA passive emptying fraction indicating LA conduit function, LA active emptying volume and LA active emptying fraction indicating LA pump function. Left atrial EMD parameters are affected in individuals with ERP, but LA phasic functions are not affected. Further prospective studies are needed to clarify whether individuals with ERP have an increased susceptibility to AF.

Role of electrocardiographic early repolarization pattern in long-term outcomes of a community-based middle-aged and geriatric ambulatory population: a prospective cohort study

In some studies, electrocardiographic early repolarization pattern (ERP) has been associated with an increased risk of death from cardiac causes. However, little is known about the prognostic significance of ERP in the middle-aged and geriatric general populations. We investigated the prevalence and long-term prognostic significance of early repolarization pattern (ERP) on electrocardiograms (ECGs) in the Healthy Aging Longitudinal Study (HALST) cohort of 4615 middle-aged and geriatric community-dwelling Han Chinese adults from Taiwan. The study subjects were followed-up for 95±22 months. A positive ERP of ≥0.1 mV was observed in 889 (19.3%) of the subjects. Kaplan-Meier survival curve analysis showed that ERP was not associated with all-cause and cardiovascular mortality (log-rank test, P=0.13 and 0.84, respectively). Cox regression analysis after adjusting for covariables revealed that age, blood pressure, smoking, diabetes, stroke, chronic kidney disease, and corrected QT interval (QTc) were associated with increased risk of all-cause mortality (P<0.05). Age, and stroke were risk factors associated with increased risk of cardiovascular mortality (P<0.05). However, ERP alone was not associated with all-cause or cardiovascular mortality. These findings show that ERP is common in the middle-aged and geriatric Han-Chinese individuals from the HALST cohort and is not associated with all-cause or cardiovascular mortality.

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10–8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10–12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 – STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

Early repolarization pattern on ECG recorded before the acute coronary event does not predict ventricular fibrillation during ST-elevation myocardial infarction

Generally considered benign, electrocardiographic (ECG) early repolarization (ER) pattern was claimed to be an indicator of increased susceptibility to ventricular arrhythmias during acute ischemia. The purpose of this study was to assess in a nonselected population whether ER pattern documented before ST-elevation myocardial infarction (STEMI) is associated with risk of hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) during acute STEMI. For STEMI patients admitted for primary percutaneous coronary intervention from 2007-2010, the latest ECGs recorded before STEMI were exported in digital format. After excluding ECGs with paced rhythm and QRS duration ≥120 ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER pattern and VT/VF during the first 48 hours of STEMI was tested using logistic regression. ECGs recorded before STEMI were available for 1584 patients. Of these patients, 124 did not meet inclusion criteria, leaving 1460 patients available for analysis (age 68 ± 12 years; 67% male). ER pattern was present in 272 patients (18.6%; ER+ group). ER+ and ER- groups did not differ with regard to clinical characteristics. VT/VF during the first 48 hours of STEMI occurred in 19 ER+ (7.0%) and 105 ER- patients (8.8%; P = .398). ER was not associated with any VT/VF (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.47-1.29; P = .324); VT/VF before reperfusion (OR 0.48; 95% CI 0.23-1.001; P = .051); or reperfusion-related VT/VF (OR 1.28; 95% CI 0.55-3.01; P = .569). In a nonselected population of STEMI patients, the ER pattern on ECG recorded before the acute coronary event was not associated with VT/VF during the first 48 hours of STEMI.

The many faces of early repolarization syndrome: A single-center case series

Early repolarization syndrome (ERS) is a rare but increasingly recognized cause of malignant ventricular arrhythmias. The purpose of this study was to characterize the presentations and treatments of ERS at our institution. We performed a retrospective chart review of all patients presenting to our institution between 2008 and 2019 with ERS. Exclusion criteria included Brugada syndrome, positive provocative testing with class I antiarrhythmic drugs, metabolic disturbances, or structural heart disease. Of 10 patients identified with ERS, 8 were men with a mean age of 30 ± 17 years at diagnosis. Documented arrhythmias included ventricular fibrillation in 7 of 10, polymorphic ventricular tachycardia in 3 of 10, and monomorphic ventricular tachycardia in 3 of 10 patients. Atrial fibrillation was diagnosed in 3 of 10, and atrioventricular block was seen in 2 of 10. J waves and/or electrocardiographic early repolarization patterns were dynamic in 7 of 10. Arrhythmias occurred at rest in 8 of 10 and with exertion in 2 of 10. Only 1 patient had a family history of sudden death, and 4 of 10 patients had variants of uncertain significance on genetic testing. Quinidine effectively suppressed arrhythmias in 5 of 5 patients but required dose escalation to >1 g/d in 3 of 5 patients. Abnormal epicardial electrograms were recorded over the inferolateral left ventricle in 2 patients who underwent mapping and were successfully ablated. Premature ventricular contraction triggers were also targeted for ablation in 3 patients. ERS is a heterogeneous condition and may be associated with both atrial and ventricular arrhythmias, atrioventricular block, dynamic electrocardiographic changes, and variable triggers. In addition to targeting premature ventricular contraction triggers, mapping and ablation of abnormal epicardial electrograms may be a potential future treatment strategy.

Electrocardiographic early repolarization is associated with future ventricular arrhythmia after acute myocardial infarction-Systematic Review and Meta-Analysis.

BackgroundEarly repolarization (ER) has been linked to ventricular arrhythmia (VA) and sudden cardiac death in patients without structural heart disease. We aimed to assess the latest evidence on whether ER is associated with future VA after acute myocardial infarction (AMI).MethodsWe performed a comprehensive search on the topic that assesses ER and VA/adverse cardiovascular events in AMI. We included studies with sufficient details on ER and VA, we also performed a meta‐analysis on their morphology.ResultsA total of 3350 subjects from 9 studies were included. Five hundred and twenty‐one (15.55%) had ER and 2829 (84.45%) did not. On meta‐analysis, ER (+) in AMI was associated with VA with a pooled odds ratio (OR) of 3.58 (2.70‐4.73), P < 0.001; heterogeneity I 2 34%. Subgroup analysis of patients with ST‐segment elevation myocardial infarction (STEMI) showed an OR of 2.79 [1.98‐3.93], P < 0.001; heterogeneity I 2 0%. Inferior location of ER (+) was associated with VA OR 3.98 [1.86‐8.53], P = 0.008; I 2 67%. Notching had a 5.41 [3.52‐8.32], P < 0.001; low heterogeneity I 2 0% of having VA. Pooled OR for J‐point elevation was 4.72 [2.63‐8.46], P < 0.001; I 2 25%. Horizontal ST‐segment was associated with VA with an OR of 4.30 [1.89‐975], P < 0.001; I 2 59%. Lateral location and slurred morphology were not associated with VA. Upon sensitivity analysis for inferior location and horizontal ST‐segment, removal of a study reduces heterogeneity significantly.ConclusionEarly repolarization especially those with the inferior location, notching morphology, an elevated J‐point and horizontal ST‐segment had a higher likelihood of VA in AMI including STEMI patients.

Cardiac Early Repolarization Pattern Anomalies Among Children and Adolescents With and Without Attention-Deficit Hyperactivity Disorder: A Community Observational Study.

Our research had 2 aims, first, to determine if electrocardiographic early repolarization pattern anomalies (ERPAs) were more likely present among children and adolescents diagnosed with attention-deficit hyperactivity disorder (ADHD; n = 416) when compared with non-ADHD children (n = 187), and second, to asses if ADHD patients whose parents report severe ADHD psychometric scores were more likely to have ERPA in their surface ECG (electrocardiography) when compared with other ADHD patients with mild to moderate dysfunction or no dysfunction. In our unmatched case-control study, ERPA was recognized when there was an end QRS notch (J wave) or slur on the downslope of a prominent R wave with and without ST-segment elevation and the peak of the notch or J wave (Jp) ≥0.1 mV in ≥2 contiguous leads, excluding V1-V3 anterior lead, and QRS duration (measured in leads in which a notch or slur is absent) <120 ms or ST-segment elevation >0.1 mV in ≥2 contiguous leads, excluding V1-V3, and QRS duration <120 ms. The DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria were used to diagnose ADHD. Our data analysis suggested a significant association between ERPA presence and ADHD (n = 603, P = .020). Our logistic regression model suggests that patients with ERPA (n = 167) were 2.778 times more likely to have a diagnosis of ADHD after controlling for age, gender, and ethnicity (95% confidence interval for odds ratio 1.087-7.100, P = .033). Multiple regression models suggested that age, P < .001; gender, P < .001; ERPA, P = .004; and ERPA leads number, P = .022, were significant predictors of global parental ADHD worry scale. Hispanic and black ethnicity were not significant predictors. Consequently, the presence of ERPA should be reported in all ECGs done in children and adolescents for prospective behavioral phenotype and/or arrhythmia risk stratification analysis.

The early repolarization pattern: Echocardiographic characteristics in elite athletes.

The electrocardiographic early repolarization (ER) pattern is associated with idiopathic ventricular fibrillation and increased long-term cardiovascular mortality. Whether structural cardiac aberrations influence the phenotype is unclear. Since ER is particularly common in athletes, we evaluated its prevalence and investigated predisposing echocardiographic characteristics and cardiopulmonary exercise capacity in a cohort of elite athletes. A total of 623 elite athletes (age 21±5years) were examined during annual preparticipation screening from 2006 until 2012 including electrocardiography, echocardiography, and exercise testing. ECGs were analyzed with focus on ER. All athletes participated in a clinical follow-up. The prevalence of ER was 17% (108/623). ER-positive athletes were predominantly male (71%, 77/108), showed a lower heart rate (57.1±9.3bpm versus 60.0±11.2bpm; p=0.015) and a higher lean body mass compared to ER-negative participants (88.1%±5.6% versus 86.5%±6.3%; p=0.015). Echocardiographic measurements and cardiopulmonary exercise capacity in male and female athletes with and without ER largely showed similar results. Only the notching ER subtype (n=15) was associated with an increased left atrial diameter (OR 7.01, 95%CI 1.65-29.83; p=0.008), a higher left ventricular mass (OR 1.02, 95%CI 1.00-1.03; p=0.038) and larger relative heart volume (OR 1.01, 95%CI 1.00-1.01; p=0.01). During a follow-up of 7.4±1.5years, no severe cardiovascular event occurred in the study sample. In elite athletes presence of ER is not associated with distinct alterations in echocardiography and cardiopulmonary exercise. Athletes presenting with ER are rather male, lean with a low heart rate.

Electrocardiographic early repolarization characteristics and clinical presentations in the young: a benign finding or worrisome marker for arrhythmias.

The early ECG repolarization QRS pattern (ERp), with J-point elevation of 0.1mV in two contiguous inferior and/or lateral leads, can be associated with ventricular arrhythmias among adults. The significance of an ERp in the young is unknown. The purpose of this study was to assess the prevalence of ERp among young patients (pts), describe and correlate the characteristics with clinical presentations and any arrhythmias. This was a 1y retrospective review of ECGs obtained from patients referred specifically for documented arrhythmias, possible arrhythmia-related symptoms or sports clearance. ECGs were analyzed for ERp (J-point, ascending/horizontal patterns, location) and correlated with presenting complaints. Of 301 patient ECGs, an ERp was found in 177 (59%), (pts age 11.7±4.3y); 54% male; 23% Caucasian. Of these, 6 pts had a family history of sudden cardiac death. Arrhythmias (72% atrial) occurred in 22 pts. Only 3 pts had ventricular arrhythmias (1 successfully ablated). The ascending ST segment and elevated J-point occurred in 77% and 51% of pts with and without arrhythmias respectively. In 73% of all pts, the ERp location was in inferior/lateral leads. Neither gender, ethnicity, large J-point, lead location, nor the combination of a horizontal ST segment with large J-point correlated with any arrhythmias. ERp, especially the diffuse ascending pattern, is common among the young, in those of European ethnicity, found equally in both genders, and with no apparent correlation with atrial nor ventricular arrhythmias.

Electrocardiographic Early Repolarization: A Scientific Statement From the American Heart Association.

The early repolarization (ER) pattern (ERP), initially described as elevation of the ST segment of ≥1 leads on the 12-lead ECG, has long been considered a benign phenomenon. However, more recent studies have demonstrated positive, negative, and neutral associations between an ERP and various end points, including all-cause, cardiac, and arrhythmic mortality. These recent studies have used more complex or heterogeneous definitions of ER, including J-wave or J-point elevation and QRS complex notching or slurring, with or without concomitant ST-segment elevation. Other studies have identified an increased prevalence of ERP in survivors of spontaneous ventricular fibrillation (VF) or cardiac arrest. As a result, considerable confusion remains concerning the definition of ERP, its prognostic significance, and whether additional evaluation or treatment is warranted. These issues are especially important because the prevalence of ERP may be as high as 10% in the general population and even higher in some healthy subgroups. The writing group performed a comprehensive literature search and developed recommendations based on the results of the current literature. We searched MEDLINE (via PubMed), EMBASE, and the Cochrane Library to identify relevant primary scientific articles, guideline statements, and review articles in the literature. Search terms included, but were not limited to, early repolarization, J-point elevation, J wave, Haissaguerre syndrome, sudden cardiac death, idiopathic ventricular fibrillation, ventricular fibrillation, cardiac repolarization reserve, sudden unexplained death syndrome, and Osborn waves. We also reviewed the references of highly cited documents and citing documents. The recommendations were voted on, and 80% agreement was required for inclusion. The purposes of this document are as follows:

Prevalence and impact on outcome of electrocardiographic early repolarization patterns among stroke patients: a prospective observational study.

Early repolarization pattern (ER) gained attention as a risk factor for ventricular arrhythmia and sudden cardiac death in the general population. While electrocardiographic abnormalities are frequent findings in stroke patients, data on ER pattern in this population are lacking. We assessed the prevalence of ER pattern in consecutive acute stroke patients at a tertiary stroke center. Functional outcome after 90 days was analyzed to determine the effect of an ER pattern on mortality. Multivariate logistic regression analysis was used to identify factors associated with an ER pattern. Out of 1141 consecutive stroke patients 771 patients remained for analysis after application of exclusion criteria. ER was observed in 62 (8.04%) patients. ER was more prevalent among subjects with intracerebral and subarachnoidal hemorrhage (13.0%) than among patients with ischemic stroke (7.0%; p = 0.024). Multiple regression analysis revealed QRS-duration (OR 0.972 95% CI 0.950-0.994, p = 0.012), QT-duration (OR 1.009, 95% CI 1.004-1.014, p = 0.001) and mechanical ventilation on admission (OR 0.320, 95% CI 0.136-0.752, p = 0.009) as independent predictors for ER. Overall ER on admission was not associated with increased mortality at 3-month follow-up (ER 11.3% vs. non-ER 9.2%; p = 0.582). ER is frequently found among patients with acute cerebrovascular events and is more prevalent in patients with hemorrhagic compared to ischemic events. Our study yields no evidence that ER is associated with worse outcome or mortality after stroke.

Incidence of atrial tachyarrhythmias in patients with early repolarization syndrome and Brugada syndrome: analysis of patients with implantable cardioverter defibrillators

Purpose: The electrocardiographic early repolarization syndrome (ERS) is associated with a risk of sudden cardiac death (SCD). It has not been known whether the arrhythmogenic substrate in patients with ERS is restricted to the ventricular level. The aim of this retrospective study was to evaluate the incidence of inappropriate shocks (IS) due to atrial tachyarrhythmias (ATAs) in patients with ERS as compared with Brugada syndrome (BrS). Methods: We analyzed data from 47 consecutive patients diagnosed with ERS and BrS who underwent implantable cardioverter defibrillator (ICD) implantation from May 1998 to December 2011. Three in patients with BrS had paroxysmal atrial fibrillation (AF). The clinical data were collected and analyzed for all events with shocks. Results: Seventeen patients with ERS (age 38.6±11.1, male=14) and 30 patients with BrS (43.6±11.3, male = 29) were enrolled. Twelve patients experienced AF after defibrillation for ventricular arrhythmia (6 in ERS vs. 6 in BrS, P = NS). During a mean follow-up of 5.3±4.5 years in the ERS and 4.4±4.0 years in the BrS, five patients received appropriate shock (3 in ERS vs. 2 in BrS, P = 0.25). There was no significant difference in the prevalence of ATAs in patients who diagnosed ERS compared with patients in BrS from pre- to post- ICD implantation (9 in ERS vs. 12 in BrS, P = 0.54). Three of 17 (17.6%) ERS and 6 of 30 (20.0%) BrS patients received IS due to ATAs during this periods (Figure, P = 0.72). ![Figure][1] Figure 1 Conclusions: ATA occurred not infrequently in patients with ERS and ICD implantation. There were no differences in the occurrence of ATA and IS in patients with ERS as compared to patients with BrS. [1]: pending:yes

The prevalence of electrocardiographic early repolarization in an adult cohort with chronic kidney disease and its impact upon all-cause mortality and progression to dialysis

Background: Electrocardiographic early repolarization (ER) occurring in <5% of general/atherosclerotic populations, is a marker of sudden cardiac death (SCD). The prevalence of ER in chronic kidney disease (CKD) patients, in whom SCD is common, is unknown. We aimed to determine the prevalence, contributing factors, and relationship of ER to all-cause mortality and progression to dialysis in CKD patients.Methods: A retrospective study of 197 patients with stage 3–5 CKD. Full demographic data were collected including cardiovascular risk factors and history. All patients underwent a 12-lead ECG, analysed for the presence of ER and other ECG findings. ER was defined as elevation of the QRS-ST junction (J point) by at least 0.1 mV from baseline with slurring/notching of the QRS complex. The primary and secondary endpoints were all cause mortality and progression to dialysis respectively at 1 year. To control for the effects of CKD, we evaluated the ECGs of 39 healthy renal transplant donors (RTD).Results: CKD patients had a mean age of 61.5 (±16.1). Prevalence of ER in pre-dialysis patients with CKD stage 4 and 5 was higher than in RTD (26.4 vs. 7.7%, p = 0.02). ER frequency increased with CKD stage (stage 3: 7.7%, stage 4: 29.7%, and pre-dialysis stage 5: 24.6%), but decreased in dialysis patients (13%). On multivariate analysis only the QRS duration was a significant independent predictor of ER (OR 0.97, 95% CI, 0.94–0.99, p = 0.01). At 1-year follow-up, there were 24 (12%) deaths in the patients with CKD of whom 5 (21%) had ER. ER was not a predictor of all cause mortality (p = 1.00) and had no effects on the rate of progression to dialysis (p = 0.67).Conclusions: ER is more common in pre-dialysis CKD patients, compared to healthy RTD but is not associated with increased 1-year mortality or entry onto dialysis programs. Further longitudinal studies are indicated to determine whether this increased prevalence of ER is associated with the rate of SCD seen in this population.

Insights into the genome-wide association studies of the electrocardiographic early repolarization pattern

s The presence of J waves and ST-segment elevations on the electrocardiogram (ECG), today commonly termed the early repolarization pattern (ERP), was first described by Grant et al back in 1951. In the following decades, it was onsidered a normal ECG variant but this assumption was ramatically changed in 2008 when 2 groups reported a igh prevalence of ERP in patients with idiopathic ventriclar fibrillation and sudden cardiac death. The ERP is a common ECG finding, more common in African Americans and athletes, and is found in 1%–13% of the general population. Although no consensus definition exists, ERP has previously been defined by a J wave or J point (QRS-ST junction) of at least 1 mm (0.1 mV) in at least 2 contiguous leads in the inferior leads (II, III, aVF), lateral leads (I, aVL, and V4-V6), or both. Today, the association between ERP and life-threatening arrhythmias has generally led to the entity termed early repolarization syndrome (ERS)—also termed the “J-wave syndromes”—by some authors. Most recently, ERP has been divided into subtypes in order to identify the pathologic variants. The horizontal or descending ST segment confers to the highest risk of arrhythmic death. The inheritable component of the ERP has slowly come into focus in recent years. In the Framingham Heart Study, siblings of ERP subjects had twice the likelihood of a ERP than non-ERP subjects. Furthermore, in a German tudy, ERP was around twice as likely if one parent was iagnosed with the disease. Recently, variants in 6 genes have been associated with ERP/ERS: KCNJ8, CACNA1C, CACNB2b, CACNA2D1, BCC9, and SCN5A. These genes encode the sodium, otassium, and calcium currents, and it is hypothesized hat changes in the cellular repolarization pattern give ise to the characteristic surface ECG. These genes have

Association of Early Repolarization and Sudden Cardiac Death During an Acute Coronary Event

Electrocardiographic early repolarization (ER) pattern has been previously associated with arrhythmic mortality and with an increased risk of ventricular fibrillation. We hypothesized that there is an association between ER and sudden cardiac death (SCD) during an acute coronary event. The present study included 432 consecutive victims of SCD because of acute coronary event and 532 survivors of such an event, in whom 12-lead ECGs recorded before and unrelated to the event could be evaluated. SCDs were verified by medicolegal autopsy to be because of acute coronary event. ER was defined as an elevation of the QRS-ST junction in at least 2 inferior or lateral leads, manifested as QRS notching or slurring. The prevalence of ER pattern ≥0.1 mV was more common in cases (62/432; 14.4%) than controls (42/532; 7.9%) (P=0.001). The victims of SCD were younger, were more commonly men and smokers, had lower body mass index, had elevated heart rate, had prolonged QRS complex, and had lower prevalence of history of prior cardiovascular disease than controls. After adjustments for baseline differences, the odds ratio for J waves without ST-segment elevation in the SCD group was 2.15 (95% CI, 1.20-3.85; P=0.01). Higher prevalence of ER in a standard 12-lead ECG in victims of SCD than in survivors of an acute coronary event suggests that the presence of ER increases the vulnerability to fatal arrhythmia during acute myocardial ischemia and provides a plausible mechanistic link between this ECG pattern and higher arrhythmic mortality of middle-aged/elderly subjects.

A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern.

The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases. To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP. We ascertained ERP on the basis of electrocardiograms in 3 large community-based cohorts from Europe and the United States: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed genome-wide association studies in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached P ≤ 1 × 10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages. Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9 ± 8.9 years, 30.3% women; ERP negative: 47.5 ± 9.4 years, 54.2% women). After meta-analysis, 8 single nucleotide polymorphisms reached P ≤ 1 × 10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95% confidence interval 0.36-0.61; P = 6.9 × 10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95% confidence interval 1.25-1.69; P = 8.5 × 10(-7)). In the replication step (7151 individuals), none of the 8 variants replicated, and combined meta-analysis results failed to reach genome-wide significance. In a genome-wide association study, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations.

Enhanced Transmural Dispersion of Repolarization in Patients with J Wave Syndromes

Recently, great attention has been paid to the risk stratification of asymptomatic patients with an electrocardiographic early repolarization (ER) pattern. We investigated several repolarization parameters including the Tpeak-Tend interval and Tpeak-Tend/QT ratio in healthy individuals and patients with J wave syndrome who were aborted from sudden cardiac death. Ninety-two subjects were enrolled: 12 patients with ventricular fibrillation associated with J waves, 40 healthy subjects with an uneventful ER pattern and 40 healthy control subjects (C) without any evident J waves. Using ambulatory electrocardiogram recordings, the average QT interval, corrected QT interval (QTc), Tpeak-Tend (Tp-e) interval, which is the interval from the peak to the end of the T wave, and Tp-e/QT ratio were calculated. Using ANOVA and post hoc analysis, there was no significant difference in the average QT and QTc in all 3 groups (QT; 396 ± 27 vs 405 ± 27 vs 403 ± 27 m, QTc; 420 ± 26 vs 421 ± 21 vs 403 ± 19 milliseconds in the C, ER pattern and J groups, respectively). The Tp-e interval and Tp-e/QT ratio were significantly more increased in the J wave group than the ER Pattern group (Tp-e: 86.7 ± 14 milliseconds vs 68 ± 13.2 milliseconds, P < 0.001, Tp-e/QT; 0.209 ± 0.04 vs 0.171 ± 0.03, P < 0.001), but they did not significantly differ between the C and ER pattern groups (Tp-e: 68.6 ± 7.5 vs 68 ± 13.2, P = 0.97, Tp-e/QT 0.174 ± 0.02 vs 0.171 ± 0.03, P = 0.4). As novel markers of heterogeneity of ventricular repolarization, Tpeak-Tend interval and Tp-Te/QT ratio are significantly increased in patients with J wave syndromes compared to age and sex-matched uneventful ER.

The Electrocardiographic Early Repolarization Pattern in Athletes

The clinical evaluation of athletes during symptom evaluation or pre-participation screening often involves interpretation of the 12-lead electrocardiogram (ECG). Differentiating abnormal ECG findings suggestive of underlying cardiovascular disease from benign findings caused by exercise-induced cardiac adaptations can be challenging, and recent clinical guidelines have been created for this purpose. One of the most common ECG findings in athletes is the early repolarization pattern (ERP), characterized by diffuse J-point elevation and concave ST-segment elevation, and long regarded as a normal variant. However, recently published data suggest that the ERP may be a marker of increased risk for sudden cardiac death (SCD) in the general population. The observation that the ERP can indicate increased SCD risk has important implications for the clinician charged with the care of athletes. This review will describe the evolving understanding of the ERP and will explore the relevance of the ERP for the care of athletes.

Abstract 9945: Concomitant Early Repolarization Increases Occurrences of Ventricular Fibrillation in Patients with Acute Myocardial Infarctions

Background: Previous studies demonstrated that there is an increased prevalence of electrocardiographic early repolarization among patients with a history of idiopathic ventricular fibrillation (VF). Early repolarization is also associated with life threatening ventricular tachyarrhythmias in patients with chronic coronary artery disease. However, no studies have clarified whether or not there is an association between electrocardiographic early repolarization and the VF occurrences after the onset of acute myocardial infarction (AMI). Methods: This study included 220 consecutive patients with AMIs (69±11 years; 57 females) in whom 12-lead ECGs before the AMI onset could be evaluated. The patients were classified based on the VF occurrence within 48 hours after the AMI onset. Sustained VF was defined as that lasting longer than 30 seconds or that required electrical cardioversion. Early repolarization was electrocardiographically defined as an elevation of the QRS-ST junction of &gt;0.1 mV from baseline in at least 2 inferior or lateral leads, manifested as QRS slurring or notching. Results: Twenty-one (10%) patients experienced an episode of VF within 48 hours of AMI onset. Compared to the patients without VF, the VF patients had a higher prevalence of early repolarization (p&lt;0.001) and male gender (p&lt;0.05), a shorter duration from onset to admission (p&lt;0.05), and a greater number of diseased coronary arteries (p&lt;0.05) and Killip class (p&lt;0.001). A multivariate analysis revealed that early repolarization (odds ratio [OR]=6.45; 95% confidence interval [CI]= 2.07-20.40; p&lt;0.01), a time from onset to admission less than 180 minutes (OR=3.54; 95% CI=1.08-11.53; p&lt;0.05), and a Killip class greater than I (OR=11.43; 95% CI=3.22-40.59; p&lt;0.001) were independent predictors of VF occurrences. Conclusion: The presence of early repolarization increases the risk of VF occurrences within 48 hours after the AMI onset.