Several recently published studies provided additional evidence of the link between the presence of early repolarisation (ER) especially in the inferior and lateral leads and increased risk of major arrhythmic events in ischaemic heart disease (IHD). Part et al. (Int J Cardiol 2014; 176:327) reported that among 266 patients with acute ST elevation myocardial infarction (STEMI) who underwent primary PCI, those with ER (n=76) had higher incidence of ventricular (21% vs 8%, p=0.004) and atrial arrhythmias (28% vs 12%, p=0.001) during hospital stay compared to those without ER. The recurrence of atrial and ventricular arrhythmias during 12 month follow-up, however, was similar (and rare) in patients with and without ER. Özcan et al. (Japanese J Cardiol 2014; 64:164) also reported that among 521 consecutive patients with acute STEMI who underwent primary PCI, those with ER on admission (n=61) had higher incidence of ventricular tachycardia or fibrillation (20% vs 11%, p=0.04) and higher mortality (7% vs 3%, p=0.001) during the hospitalization period compared to those without ER (n=460). During the follow-up period of 21±10 months, mortality was also higher in the ER group (13% vs 4%, p=0.01). Finally, a meta-analysis on four case-control studies (1244 subjects in total) and two cohort studies (291 subjects) addressing the association between ER and cardiac events in patients with IHD found odds ratio (OR) for cardiac events of 2.40 (95% CI: 1.76-3.27, p=0.01) in those with ER (presented at the American College of Cardiology Scientific Sessions 2014; JACC 2014; 63:A335). Importantly, inferior (OR 1.1, p=0.40) and lateral distribution of ER (OR 1.1, p=0.20) was not associated with increased risk of cardiac events, whereas notched QRS configuration demonstrated quite modest albeit significant association with cardiac events (OR 1.6, 1.0-2.6, p=0.02).
These reports are in concert with other studies demonstrating the link between ER and increased risk of arrhythmic events of mortality in patients with idiopathic VF (Haissaguerre et al., NEJM 2008; 358:2016), the Brugada syndrome (Circ Arrhythm Electrophysiol 2009; 2:154; Heart Rhythm 2008; 5:1685; JACC 2014; 63:2131), congenital long QT syndrome (Heart Rhythm 2014; 11:1632), or general population (Heart Rhythm 2014; 11:1701). However, prospective studies in professional athletes (in whom ER seems to be considerably more common that in most, if not all, other patient or population groups) failed to document significant difference in the arrhythmic risk between patients with and without ER (Serra Grima et al. Am J Med, in press; Quattrini et al. Heart Rhythm 2014; 11:1974). In the largest published so-far study on ethnically and racially diverse group of 211,920 in- and out patients (excluding those with acute coronary syndromes and ventricular pacing), ER also was not associated with increased mortality during a median follow-up of 8.0±2.6 years.
Early Repolarisation and Risk of Life-Threatening Arrhythmias: Making practical sense of the available information
The so-called “syndrome of early repolarisation” (ER) was considered until recently an ECG oddity whose only clinical significance was its potential to mimic (and even be misdiagnosed as) acute coronary syndrome with ST segment elevation. Case reports challenging this perception began to appear in the 1980’s, but the real shift in opinion came in 2008 when Haissaguerre et all. reported in a case-controlled study increased incidence of ER in 206 survivors of idiopathic ventricular fibrillation (VF) compared to 412 matched controls with no heart disease (31% vs 5%, p<0.001) (NEJM 2008; 358:2016). Several other studies with similar patient populations and results followed shortly.
ER associated with high risk of VF is already a recognised malignant primary arrhythmia syndrome with relatively well established ECG phenotype and likely genetic origin (ER syndrome, HRS / EHRA / APHRS Expert Consensus Statement; Heart Rhythm 2013; 10:1932). Similarly to the Brugada syndrome in the early 1990s, the ER syndrome carved out yet another chunk from the so-called “idiopathic ventricular fibrillation”.
The clinical significance of ER in patients with other diseases such as IHD (including acute STEMI) seems much less clear. Currently, the presence of ER alone in this context does not seem to justify any additional preventive intervention (e.g. ICD implantation). Obviously, this is even more valid for populations with smaller arrhythmic risk (e.g. general population). In this context, ER seems to join for the time being the long list of arrhythmia risk-stratifiers which identify subpopulations with increased arrhythmic risk (and/or cardiac or total mortality) but have little if any practical value for the treatment of individual patients in everyday practice. Other examples of such arrhythmia risk-stratifiers include prolonged QTc or Tpeak-Tend interval, decreased heart rate variability/turbulence/baroreflex sensitivity, increased microvolt T wave alternans, increased beat-to-beat variability of the QT interval and other dynamic features of ventricular repolarisation, abnormal morphology of ventricular repolarisation quantified by some mathematical methods (e.g. principal component analysis, etc.) and many others.
From practical point of view, the true impact of ER on the cause of acute MI seems difficult to establish because a) most patients do not have an ECG recorded before the event and even if they do have, this particular ECG may not show (or show less expressed/more benign form of) ER due to its dynamic variability (e.g. rate-dependence), and b) in acute STEMI, ER obviously cannot be assessed in leads with ST elevation due to the MI, especially Sclarovsky-Birnbaum grade III ischaemia pattern (with terminal QRS distortion) or “tombstone” ST-elevation pattern. I also wonder whether/to what extent the ER changes in acute STEMI can be modified even in leads without ST elevation by ischaemia-related remote ECG changes (e.g. reciprocal ST changes).