Early Repolarization: Not as Innocent as Once Thought!

January 5, 2011

By Rachel Bond, MD PGY-2

Faculty Peer Reviewed

For many years, the electrocardiogram, a seemingly simple transthoracic interpretation of the electrical activity of the heart captured and externally recorded, has fascinated healthcare professionals.  An aspect of the electrocardiogram which has piqued curiosity consist of an interesting pattern referred to as “early repolarization.”  Early repolarization is a slurring or notching producing a hump-like feature called a J wave, typically found at the junction at the end of the QRS complex and the beginning of the ST segment.  In a normal ECG, the transition of ventricular depolarization into ventricular repolarization corresponds on the surface ECG to this J-point, where an abrupt transition from the QRS complex to the ST-segment occurs.  Deviation of the J-point from the isoelectric line leads to the presence of a J-deflection.  This typically produces a concave upward curve towards the T wave, helping to differentiate it from the convex, ‘tomb-stone’ waves seen with infarct.  The leads associated with the J wave, commonly shown as ST-segment elevations (a.k.a. J point elevations) typically involve the anterior precordial leads (V1-V3).  Recently, data has looked into early repolarization localized to the inferolateral leads.

As reported by Wellens[i], approximately 2-5% of the population demonstrates the early repolarization changes on electrocardiogram; this population mostly consists of men, young adults, athletes, and people of African American heritage.  Early repolarization previously was felt to be a rather benign feature; however, experimental studies, isolated case reports and independent case studies have shown its potential arrhythmogenic effects.

One such study by Haïssaguerre et al.[ii] evaluated the clinical association between early repolarization in the inferolateral leads and idiopathic ventricular arrhythmias leading to syncope and/or sudden cardiac death.  The study conducted was a case–control study involving 206 case subjects with a prior history of idiopathic ventricular fibrillation (IVF).  The primary endpoint was to assess the prevalence of early repolarization and evaluate its potential relationship with any observed arrhythmias, as monitored by implantable defibrillators.  In the study, early repolarization prevalence was compared between case subjects who had previously experienced an episode of IVF prior to the study and control subjects with no known heart disease.  Early repolarization occurred statistically more frequently in the case subjects with IVF than the control subjects (31% vs. 5%, P<0.001).  Furthermore, in select subjects, the origin of ectopy that initiated ventricular arrhythmia was mapped to sites concordant with the localization of the early repolarization abnormality and showed accentuation of early repolarization prior to the actual arrhythmia.  In the study, electrocardiography was performed during an arrhythmic period (including frequent premature ventricular contractions and episodes of IVF) in 18 case subjects, and all subjects showed a consistent increase in the amplitude of early repolarization so that the J-point amplitude increased from 2.6±1 mm to 4.1±2 mm (P<0.001).  In six subjects with early repolarization recorded only in inferior leads, all ectopy originated from the inferior ventricular wall.

As mentioned by Haïssaguerre et al, the link between this electrocardiographic pattern and malignant arrhythmias is supported by both the accentuated repolarization before the onset of arrhythmia seen in a few of the case subjects and the origin of triggering beats from the region of early repolarization (as described above).  To further elaborate on this statement, defibrillator monitoring performed in the study showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without (41% vs. 23%).  The hazard ratio for recurrence was 2.1 (95% CI, 1.2 to 3.5; P = 0.008).  Among patients with a prior history of IVF, an increased prevalence of early repolarization was found; as such, this case-study was the first to hypothesize this clinical association.

In the NEJM in December 2009, Tikkanen et al[iii] investigated the long-term outcomes associated with early repolarization on the electrocardiogram.  This evaluation was an extension of the data described by Haïssaguerre et al. above, as well as additional case-studies.[iv] The Tikkanen study sought to emphasize the prognostic significance of the J point pattern in the inferolateral leads which were hypothesized to be more arrhythmogenic than the more commonly studied anterior precordial leads (leads v1 through v3).

The study by Tikkanen et al. (iii) was a community-based study to assess the prevalence of the early repolarization pattern and its long-term prognosis in a large, middle-aged Finnish population (mean age, 44 ± 8 years) with a long follow-up time (mean (±SD) period 30±11 years).  The study was conducted by evaluating the inferior and lateral J-point elevations independently to clarify the significance of localization on a resting 12-lead electrocardiogram of 5676 men and 5188 women from the general Finish population.  Two predefined cutoff points (≥0.1 mV and >0.2 mV) were made to assess the significance of the amplitude of J-point elevation from baseline.  Survival data was used to assess the prognosis for subjects who had an early repolarization pattern.

Findings showed that the early repolarization pattern of 0.1 mV was present in 630 subjects (5.8%), 384 (3.5%) of which occurred in the inferior leads and 262 (2.4%) in lateral leads, with elevations in both leads in 16 subjects (0.1%).  Upon further review, it was found that J-point elevation of at least 0.1 mV in the inferior leads was associated with a similar increased risk of death from cardiac causes (adjusted relative risk, 1.28; 95% confidence interval [CI], 1.04 to 1.59; P = 0.03) when compared to these elevations in the lateral leads (adjusted relative risk of 1.34; 95% CI, 1.04 to 1.74; P= 0.03).  In addition, 36 subjects (0.3%) with J-point elevation of more than 0.2 mV in inferior leads had a markedly elevated risk of death from cardiac causes (adjusted relative risk, 2.98; 95% CI, 1.85 to 4.92; P<0.001) when compared to that in the lateral leads, where the data was not statistically significant (adjusted relative risk, 1.61; 95% CI, 0.83 to 3.10; P = 0.19).  In addition, J-point elevations of more than 0.2 mV in the inferior leads had a statistically significant risk of death from arrhythmia (adjusted relative risk, 2.92; 95% CI, 1.45 to 5.89; P = 0.01) when compared to that in the lateral leads where it was not statistically significant.

Based on the findings above, early repolarization in the inferior leads appeared to be a strong predictor of death from cardiac causes or from arrhythmia than J-point elevation in the lateral leads.  In addition to the location of the early-repolarization pattern, the amplitude of the J-point elevation had great prognostic value.  There was a significantly higher risk of death from cardiac causes among subjects with a markedly elevated J point (>0.2 mV) than among those with a more moderate elevation (≥0.1 mV).

In keeping with the study populations demographics and characteristics, case studies found to have the early repolarization pattern were more likely to be of the male sex and have lower baseline heart rates (ii).  Of note, in the patient populations studied, very few belonged to the subgroups that have been shown to have a high prevalence of early repolarization in the anterior precordial leads (e.g., athletes, young males, blacks).  In addition, although early repolarization has more commonly been studied in the anterior precordial leads, the studies discussed above have shown the increased association between arrhythmias and J point elevations originating from the inferolateral portion of the heart.  All of this data is clearly laid out by Haïssaguerre et al and Tikkanen et al; however, what is not clear is how the early repolarization pattern localized to the inferior leads increase the risk of death from cardiac and arrhythmic causes.

One hypothesis is the concept that the J-point elevation is a marker of increased transmural heterogeneity of ventricular repolarization.  In addition, the left ventricular base defined by the inferolateral leads is an area known to have increased current density.  As such, having an episode of early repolarization in an area with known increased current density is what can make the myocardium more vulnerable to ventricular tachyarrhythmias[v] [vi].  This vulnerability may be amplified under certain conditions such as a cardiac ischemic event, the use of specific drugs, various levels of autonomic tone, electrolyte disturbances, channelopathies and/or structural cardiac abnormalities.  This hypothesis can be further defended by the fact the anti-arrhythmic, quinidine, which is known to restore electrical homogeneity, aborted arrhythmias in a certain number of the patient population studied (ii).

So where does this information lead us?

When confronted with a patient with an episode of sudden cardiac death, ventricular tachyarrhythmia or syncope with ECG findings of early repolarization localized to the inferolateral leads, the practitioner should rule out all more commonly studied ischemic and non-ischemic causes, including, but not limited to, the long-QT syndrome, the short-QT syndrome, the Brugada syndrome, and arrhythmogenic right ventricular dysplasia (i).  Once these conditions have been excluded, it can be implied that the inferolateral J point elevation which represents early repolarization in an area with increased current density is what predisposed to the event.  As such, these studies presented above suggest that these inferolateral J point elevations should be used as important diagnostic signs to detect high-risk persons with a history of “unexplained” syncope and/or a familial incidence of sudden death at a young age.

Possible interventions for such situations include the known standard of care with the implantation of defibrillators for secondary prevention in addition to the use of anti-arrhythmic agents and/or cardiac ablation in patients who have been ruled out for all other ischemic and non-ischemic causes.  Haissaguerre et al. (ii) evaluated ICD implantation which was inserted primarily for secondary prevention and used in the study to assess the likelihood of recurrence of the arrhythmic event.  The study also evaluated how the anti-arrhythmic agent quinidine, which has been shown to restore transmural electrical homogeneity and abort arrhythmic activity in patients with J-point elevations, diminished the electrocardiographic pattern and eliminated recurrent arrhythmias in four out of four subjects given the medication.  In addition, catheter ablation was shown to eliminate ectopy in approximately 60% of the population studied (five out of a total of eight subjects evaluated); however, this was only a short term elimination.  Although these interventions were focused on a small number of patients evaluated, there appears to be some promising preventive and/or curative measures which need to be further studied before costly procedures and medications should be prescribed for this particular patient population.

In conclusion, one can postulate that J point elevations in the anterior precordial leads are less arrhythmogenic (i.e. more benign) than J point elevations in the inferior leads, especially in patients presenting to the hospital with an episode of syncope and/or sudden cardiac death.  There should be close monitoring on telemetry and consideration of further causes and treatment options once other, more commonly studied, ischemic and non-ischemic cardiac causes are ruled out.  Unfortunately, there are no studies as of yet looking at appropriate interventions in asymptomatic patients with incidental findings of inferior J point elevations (i.e. ICD implantation for primary prevention); however, based on the data above I would favor letting the patient know of this finding, providing them with a copy of their ECG to keep in their pocket in case of an emergency, suggesting referral to a cardiologist and taking a concise cardiac and family history to prepare for possible future events.

Until there is better data, physicians are left with the observation that in some persons with findings of early repolarization in the inferolateral area on an electrocardiogram, life-threatening ventricular tachyarrhythmias may occur and may progress to sudden cardiac death.  Since there are many persons who fit such a picture but do not appear to have excess risk, further data is needed to reveal how to identify patients who are at high risk for such an arrhythmias and what preventive measures can be done to stop it.  Until then, I would recommend a close caution on these asymptomatic patients, to keep them, just that, asymptomatic.

Dr. Bond is a second year resident at NYU Langone Medical Center

Faculty peer reviewed by Steven Fowler,MD,  Department of Medicine (Cardiology), NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

[i] Wellens HJ. Early Repolarization Revisited. N Engl J Med May 8, 2008. 358:2063-2065.  http://www.clinicalcorrelations.org/wp-includes/js/tinymce/plugins/paste/pasteword.htm?ver=327-1235#_ednref1

[ii] Haïssaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008; 358:2016-23.  http://www.clinicalcorrelations.org/wp-includes/js/tinymce/plugins/paste/pasteword.htm?ver=327-1235#_edn2

[iii] Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA, Reunanen A, Huikuri HV. Long-Term Outcome Associated with Early Repolarization on Electrocardiography. N Engl J Med 2009; 361:2529-2537. http://www.clinicalcorrelations.org/wp-includes/js/tinymce/plugins/paste/pasteword.htm?ver=327-1235#_edn3

[iv] Rosso R, Kogan E, Belhassen B, et al. J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol 2008;52:1231-8.  http://www.clinicalcorrelations.org/wp-includes/js/tinymce/plugins/paste/pasteword.htm?ver=327-1235#_edn4

[v] Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J-wave. Circulation; 1996;93:372-9.  http://www.clinicalcorrelations.org/wp-includes/js/tinymce/plugins/paste/pasteword.htm?ver=327-1235#_ednref5

[vi] Gussak I, Antzelevitch C. Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms. J Electrocardiol 2000;33:299-309.  http://www.clinicalcorrelations.org/wp-includes/js/tinymce/plugins/paste/pasteword.htm?ver=327-1235#_edn6

3 Responses to Early Repolarization: Not as Innocent as Once Thought!

  1. ishmeal bradley on January 5, 2011 at 2:55 pm

    great article discussing a common finding that we see in the ER and on the wards.

  2. ARIFUL MOWLA on January 7, 2011 at 10:26 am

    Great Insight on the topic repolarization and how these asymptomatic patients can have better treatment within the Cardiology environment.

  3. Ken Grauer on September 20, 2011 at 3:34 pm

    Overall an excellent review of a timely subject by Dr. Bond! I have 2 Questions: i) Do we truly KNOW that anterior ST elevation in an “early repol” pattern is benign (Why should this pattern when seen in anterior leads be so different than when seen in inferior leads?) – and – ii) Am I reading your conclusion in your 2nd-to-last paragraph correctly – namely that you are saying wrt looking at appropriate interventions in asymptomatic patients with incidental findings of inferior J point ST elevations – that referral to a cardiologist is routinely indicated? IF so – I maintain that this would result in an awful large number of referrals to cardiology for a condition that most of the time will end up being benign, and for which no universally agreed upon approach has been decided. What I believe we ALL should take from these interesting recent studies (as you emphasize) – is that Early Repolarization is NOT as “benign” as we used to think – and especially in a subgroup of patients with syncope/presyncope/positive family history or potentially malignant arrhythmias – IF there is early repol (esp. in the inferior leads) – that person should probably be sent to a cardiologist for further assessment. THANKS again for an excellent job in reviewing these articles! – Ken Grauer, MD (ekgpress@mac.com)

Leave a Reply

Your email address will not be published. Required fields are marked *

*