Significance and mechanisms of the electrocardiographic pattern of early repolarization

This editorial refers to ‘Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years’ by J. Siebermair et al., on pages 718–725. Early repolarization (ER) is a common electrocardiographic (ECG) finding characterized by J-point and ST-segment elevation in two or more contiguous leads. The presence of ER pattern in the precordial leads (V1–V3) is still considered a benign phenomenon and is it has been generally viewed as a marker of good health. After some case reports pointing to the arrhythmogenic potential of ER, a series of case-control studies have described an apparent over-presentation of J waves, i.e. terminal QRS notching and/or slurring in infero-lateral leads with and without ST-segment elevation, in patients with idiopathic ventricular fibrillation (IVF).1–4 Thereafter, infero-lateral QRS notching and slurring, referred to as ER ECG pattern, have also been demonstrated to carry an increased risk of sudden cardiac death and mortality in general population.5,6 The terminology and the criteria of J-point elevations, J-waves, and ER have been under debate in recent years. Depending on the diagnostic criteria, ER ECG pattern in the inferior/lateral leads has been reported to be present in 1–24% of the middle-aged general population,7 and in 15–70% of IVF cases.1–3,8 The lack of consistency in the diagnostic criteria of ECG pattern of ER may partly explain the large heterogeneity in the prevalence and prognostic significance of this ECG phenomenon between the different studies. A consensus group has now created criteria for diagnostics, which will hopefully result in more homogeneous interpretations of the ER patterns.9 The identification of individuals with ER patterns at high risk of ventricular arrhythmias and sudden death continues to be a challenge as the various ECG phenotypes are fairly common in the general population, but only a small subset experience an arrhythmic event. With the present knowledge, any screening for ER in completely asymptomatic individuals is not legitimate. However, in patients with IVF or resuscitated cardiac arrest in whom there is no obvious aetiology, the correct diagnosis of ER pattern has clinical importance, since these individuals have a high risk of recurrent VF episodes and electrical storm after implantation of cardioverter-defibrillator and quinidine treatment has been proposed to prevent these episodes.1 The study by Siebermair et al.10 in this issue of EP-Europace confirmed these prior findings showing that the patients with an initial diagnosis of IVF who had an ER ECG pattern had a higher risk of appropriate ICD shocks than those without ER. One limitation of this study, as also commented by the authors, is that at the time of diagnosis of IVF modern imaging and genetic diagnostic methods were not available. Therefore, the initial sample size may be somewhat heterogeneous. For example, repeated genetic testing has revealed specific gene mutations in up to 20% of the patients initially diagnosed as IVF.10 Current technology also permits magnetic resonance imaging in patients with implanted cardioverter-defibrillator, which can reveal cardiac structural abnormalities in some of the IVF patients. This emphasizes the need for repeated diagnostic testing of IVF patients, which will eventually limit the number of patients belonging to this clinical entity. The mechanisms and pathophysiologic background of ER are still unknown. It is not yet known, whether the ER syndrome is in fact an inherited channelopathy or a sporadic arrhythmia disorder, since only a few familial cases have been reported so far. Understanding the genetic basis of ER is still in its infancy with only a few reports implicating monogenic background. The reported genes involve KCNJ8 gene, CACNA1C, CACNB2, CACNA2D1, and the SCN5A gene.7 All these gene mutations enhance the underlying inward–outward current imbalance responsible for accelerated epicardial repolarization, but the causal relationship of these gene mutations to ER syndrome and their functional significance are not fully established. It has also been proposed that ER syndrome may belong to a spectrum or J-wave syndromes, since it shares many features similar to Brugada syndrome. Obvious differences exist between these two syndromes, however. For example, the presence of atrial fibrillation is common in Brugada syndrome, but the study in this journal showed that IVF patients with ER ECG pattern do not often experience episodes of atrial fibrillation.10 This observation has also been reported in general population samples with ER ECG pattern. Finally, it is not completely resolved, whether the ER ECG pattern reflects depolarization or repolarization abnormality.11 Most investigators feel that ER is a repolarization disorder, similar to Brugada syndrome or long-QT syndrome. Recent observations of the fragmented epicardial electrograms of the right ventricle and a success of epicardial catheter ablation of these foci in patients with Brugada syndrome suggest that structural conduction delay may be one of the pathophysiologic mechanisms of this syndrome.12 This observation has partly challenged the concept that Brugada syndrome is an inherited ion channel disorder. Similar conduction abnormalities in the inferior and/or lateral epicardial wall of the left ventricle may well be responsible also for the ER syndrome, but understanding the exact mechanisms of ER still awaits a lot of future studies. This work was supported in part by the Sigrid Juselius Foundation, and the Finnish Academy of Science, Helsinki, Filand. Conflict of interest: none declared.