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Mechanisms underlying the development of the electrocardiographic and arrhythmic manifestations of early repolarization syndrome.

ABSTRACT: Early repolarization pattern in the ECG has been associated with increased risk for ventricular tachycardia/fibrillation (VT/VF), particularly when manifest in inferior leads. This study examines the mechanisms underlying VT/VF in early repolarization syndrome (ERS). Transmembrane action potentials (APs) were simultaneously recorded from 2 epicardial sites and 1 endocardial site of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a pseudo-ECG. Transient outward current (Ito) was recorded from epicardial myocytes isolated from the inferior and lateral LV of the same heart. J wave area (pseudo-ECG), epicardial AP notch magnitude and index were larger in inferior vs. lateral wall preparations at baseline and after exposure to provocative agents (NS5806+verapamil+acetylcholine (ACh)). Ito density was greater in myocytes from inferior vs. lateral wall (18.4 ± 2.3pA/pF vs. 11.6 ± 2.0pA/pF; p<0.05). A combination of NS5806 (7 ?M) and verapamil (3 ?M) or pinacidil (4 ?M), used to pharmacologically model the genetic defects responsible for ERS, resulted in prominent J-point and ST-segment elevation. ACh (3 ?M), simulating increased vagal tone, precipitated phase-2-reentry-induced polymorphic VT/VF. Using identical protocols, inducibility of arrhythmias was 3-fold higher in inferior vs. lateral wedges. Quinidine (10 ?M) or isoproterenol (1 ?M) restored homogeneity and suppressed VT/VF. Our data support the hypothesis that 1) ERS is caused by a preferential accentuation of the AP notch in the LV epicardium; 2) this repolarization defect is accentuated by elevated vagal tone; 3) higher intrinsic levels of Ito account for the greater sensitivity of the inferior LV wall to development of VT/VF; and 4) quinidine and isoproterenol exert ameliorative effects by reversing the repolarization abnormality.

SUBMITTER: Koncz I

PROVIDER: S-EPMC3943882 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Project description:Background Dispersion and gradients in repolarization have been associated with life-threatening arrhythmias, but are difficult to quantify precisely from surface electrocardiography. The objective of this study was to evaluate electrocardiographic imaging (ECGI) to noninvasively detect repolarization-based abnormalities. Methods and Results Ex vivo data were obtained from Langendorff-perfused pig hearts (n=8) and a human donor heart. Unipolar electrograms were recorded simultaneously during sinus rhythm from an epicardial sock and the torso-shaped tank within which the heart was suspended. Regional repolarization heterogeneities were introduced through perfusion of dofetilide and pinacidil into separate perfusion beds. In vivo data included torso and epicardial potentials recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, and ventricular pacing. For both data sets, ECGI accurately reconstructed T-wave electrogram morphologies when compared with those recorded by the sock (ex vivo: correlation coefficient, 0.85 [0.52-0.96], in vivo: correlation coefficient, 0.86 [0.52-0.96]) and repolarization time maps (ex-vivo: correlation coefficient, 0.73 [0.63-0.83], in vivo: correlation coefficient, 0.76 [0.67-0.82]). ECGI-reconstructed repolarization time distributions were strongly correlated to those measured by the sock (both data sets, R2 ≥0.92). Although the position of the gradient was slightly shifted by 8.3 (0-13.9) mm, the mean, max, and SD between ECGI and recorded gradient values were highly correlated (R2=0.87, 0.75, and 0.86 respectively). There was no significant difference in ECGI accuracy between ex vivo and in vivo data. Conclusions ECGI reliably and accurately maps potentially critical repolarization abnormalities. This noninvasive approach allows imaging and quantifying individual parameters of abnormal repolarization-based substrates in patients with arrhythmogenesis, to improve diagnosis and risk stratification.

Project description:Background Early repolarization pattern (ERP) is considered a common training-related and benign ECG finding in young adult athletes. Few data exist on ERP in the pediatric athletes population. Therefore, we aimed to evaluate the ERP prevalence, characteristics, and prognosis in pediatric athletes aged ≤16 years. Methods and Results Eight-hundred eighty-six consecutive pediatric athletes engaged in 17 different sports (mean age, 11.7±2.5 years; 7-16 years) were enrolled and prospectively evaluated with medical history, physical examination, resting and exercise ECGs, and transthoracic echocardiography during their preparticipation screening. Known cardiovascular diseases associated with sudden cardiac death was considered exclusion criteria. Athletes were followed up yearly for 4 years. The prevalence of ERP was 117 (13.2%), equally distributed in both sexes (P=0.072), irrespectively of body mass index and classification of sports. The most common ERP localizations were inferolateral and inferior leads (53.8% and 27.3%, respectively). Notching J-point morphology was the most prevalent (70%), and rapidly ascending ST elevation (96%) was the most common ST-segment morphology. Athletes with ERP were older (P<0.001) had lower rest and recovery heart rates (P<0.001), increased precordial and limb R-wave voltages (P<0.001), increased R/S Sokolow index (P<0.001), and longer PR interval (P=0.006) in comparison with the athletes without ERP. Neither major cardiovascular nor arrhythmic events, nor sudden cardiac death were recorded over a median follow-up of 4.2 years. One hundred seventeen (80.3%) athletes with ERP exhibited a persistent ERP. ERP localization and J-point morphology changed during follow-up in 11 (11.7%) and 17 (18%) of athletes, respectively. Conclusions ERP is common in pediatric athletes. It was mostly located in the inferolateral leads and associated with concave ascending ST segment with other training-related ECG changes. The lack of either sudden cardiac death or cardiomyopathies linked to sudden cardiac death over follow-up suggests that in pediatric athletes, ERP may be considered a benign training-related ECG phenomenon with a potential dynamic pattern.

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Mechanisms underlying the development of the electrocardiographic and arrhythmic manifestations of early repolarization syndrome.

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