Early repolarisation syndrome

1. EARLY REPOLARISATION SYNDROME

2. The perception that ER was a benign finding devoid of clinical
significance changed as case reports, case–control studies, and
population studies established a link between the presence of ER and
an increased risk for arrhythmic death and in particular idiopathic
ventricular fibrillation (VF)

3. Causes of SCD with a normal heart
Wolff-Parkinson-White syndrome
Long QT syndrome
Catecholaminergic polymorphic VT with normal QT interval
Brugada syndrome
Short QT syndrome
Commotio cordis

4. The term early repolarization (ER), also known as "J-waves" or "J-point
elevation", has long been used to characterize a QRS-T variant on the
ECG.
Most literature defines ER as being present on the ECG when there is J-
point elevation of ≥0.1 mV in two adjacent leads with either a slurred
or notched morphology.
Historically, ER has been considered a marker of good health because it
is more prevalent in athletes, younger persons, and at slower heart
rates.
However, numerous more recent reports have suggested an
association between ER and an increased risk for arrhythmic death and
idiopathic VF.

5. While some level of increased risk of sudden cardiac death has been
reported in persons with ER, the relatively high prevalence of the ER
pattern in the general population (5 to 13 percent)
in comparison to the incidence of idiopathic VF (approximately 10
cases per 100,000 population) means that the
ER pattern will nearly always be an incidental ECG finding with no
clinical implications.
However, a primary arrhythmic disorder such as idiopathic VF due to
ER is far more likely when associated with syncope or resuscitated
sudden cardiac death in the absence of other etiologies.

6. DEFINITION
The definition of early repolarization (ER) is based on well-defined ECG
findings.
ECG findings
A sharp well-defined positive deflection or notch immediately following a
positive QRS complex at the onset of the ST segment.
The presence of slurring at the terminal part of the QRS complex (since the J-
wave or J-point elevation may be hidden in the terminal part of the QRS
complex, resulting in the slurring of the terminal QRS complex).
Most literature defines ER as being present on the ECG when there is J-point
elevation of ≥0.1 mV in two adjacent leads with either a slurred or notched
morphology

11. ER pattern versus ER syndrome
ER is an ECG finding.
Two terms, distinguished by the presence or absence of symptomatic
arrhythmias, have been used to describe patients with this ECG finding
ER pattern
Patient with appropriate ECG findings in the absence of symptomatic
arrhythmias.
ER syndrome
Patient with both appropriate ECG findings and symptomatic arrhythmias.

12. Persons with either the ER pattern or ER syndrome can have identical
findings on surface ECG.
However, the mere presence of ER pattern on ECG should not lead to a
classification of ER syndrome in the absence of symptoms or
documented VF.
Rarely, ER may be associated with the primary arrhythmic disorder
idiopathic ventricular fibrillation (VF) in the absence of structural heart
disease.
Given the prevalence of ER pattern in the general population and the
exceedingly low incidence of idiopathic VF, the diagnosis of idiopathic
VF due to malignant ER is a diagnosis of exclusion.

13. Myocardial Physiology
Contractile Cells
• Special aspects
The action potential of a contractile cell
• Ca2+ plays a major role again
• Action potential is longer in duration than a “normal” action potential
due to Ca2+ entry
• Phases
4 – resting membrane potential @ -90mV
0 – depolarization
» Due to gap junctions or conduction fiber action
» Voltage gated Na+ channels open… close at 20mV
1 – temporary repolarization
» Open K+ channels allow some K+ to leave the cell
2 – plateau phase
» Voltage gated Ca2+ channels are fully open (started during initial
depolarization)
3 – repolarization
» Ca2+ channels close and K+ permeability increases as slower activated
K+ channels open, causing a quick repolarization

17. PATHOPHYSIOLOGY
ER mechanistically demonstrates some similarities to Brugada Syndrome and
short QT syndrome (SQTS).
Higher epicardial Ito current relative to endocardium
↓
More pronounced phase 1 notch of epicardial AP relative to that of
endocardium
↓
J point elevation
Resultant is an augmented ventricular transmural gradient
Dispersion of repolarisation a/w ER increases phase 2 re entry resulting
premature ventricular ectopics

20. GENETIC BASIS AND INHERITANCE OF ER
The genetic basis of ER syndrome continues to be elucidated, with the
evidence restricted to either case reports or preliminary studies that
fall short of clearly identifying the genetic basis of ER.
The reported implicated gene mutations involve the KCNJ8 gene
(responsible for the ATP sensitive potassium channel Kir6.1 -
I KATP current), CACNA1C, CACNB2, CACNA2D1 genes (responsible for
the cardiac L-type calcium channel - I Ca.L current), and the SCN5A gene
(responsible for the sodium channel - I Na current)

21. Prevalence
Several population studies have estimated that the prevalence of ER
ranges from 5 to 13 percent of persons.
In a study of 10,864 middle-aged Finnish subjects (52 percent males,
mean age 44 ± 8 years), the prevalence of ER was 5.8 percent (3.5
percent in inferior leads and 2.4 percent in the lateral leads, and in both
in 0.1 percent).
In a population based case-cohort study of individuals of central-
European descent (n = 6213, age range 35 to 74 years), the prevalence
of ER was 13.1 percent (4.4 percent in the antero-lateral leads and 7.6
percent in the inferior leads, 1 percent in both).

22. In the CARDIA (Coronary Artery Risk Development in Young Adults)
study, 5069 participants (mean age 25 years, 45 percent male, 52
percent black), 941 persons (18.6 percent) had ER on baseline ECG .
After 20 years, there was marked (50 percent) loss to follow-up;
however, only 119 of 2505 persons (4.8 percent) of the remaining
participants still had evidence of ER.

23. Inheritance of ER pattern
The ER pattern may be sporadic or inherited, although first-degree
relatives of a person with the ER pattern appear to have a two to
threefold higher likelihood of also having the ER pattern on ECG.
While the vast majority of ER is likely sporadic, familial ER appears to
be transmitted in an autosomal dominant fashion.
In one study that evaluated participants in the Framingham Heart
Study (n = 3995) and the Health 2000 Survey (n = 5489), siblings of
individuals with ER pattern had increased unadjusted odds of having
ER pattern on their ECG (odds ratio [OR] 2.22, 95% CI 1.01-4.85),
suggesting heritability of the ER pattern in the general population.

24. In a study of 505 families, individuals for whom at least one parent
had the ER pattern had a 2.5-fold risk for ER pattern.
Familial transmission appeared more frequent when the mother was
affected (3.8-fold versus 1.8-fold). Heritability was also higher when
ER was in the inferior leads or had a notched morphology.
In a study of four families affected by ER syndrome with a combined
22 sudden cardiac deaths, the ER pattern was present in 36 percent of
screened family members (61 out of 171), with transmission in a
fashion consistent with autosomal dominant inheritance

25. Arrhythmic risk
In one case-control study which compared 206 subjects with idiopathic
VF with 412 healthy control subjects, ER was more prevalent in
subjects with idiopathic VF (31 versus 5 percent), and ER was greater in
magnitude in case subjects than in control subjects (J-point elevation,
2.0 versus 1.2 mm).
Patients with idiopathic VF who had ER were also more likely to
experience syncope or cardiac arrest during sleep than were those
without ER. During a mean follow-up of 61 ± 50 months, ICD
monitoring showed a higher incidence of recurrent VF in case subjects
with ER than in those without (hazard ratio, 2.1; 95% confidence
interval, 1.2 to 3.5).

26. Even though ER is fairly common in the general population, idiopathic
VF is rare.
In one report, which estimated the incidence of idiopathic VF, the
estimated risk of developing idiopathic VF in an individual younger
than 45 years is 3 in 100,000.
The risk increased to 11 in 100,000 when J waves were present.
Although ER increased the relative risk of sudden cardiac death (SCD),
the absolute risk was very low.
Therefore the incidental identification of ER should not be interpreted
as a high-risk marker for arrhythmic death due to the relatively low
odds of SCD based on ER alone.

27. Athletes with early repolarization
Whether athletes with ER have an increased prevalence of ER and an
increased risk for arrhythmic death is controversial.
The prevalence of J-point elevation among 121 young athletes was reported
at 22 percent, a prevalence rate higher than seen in the general population.
However, an ER prevalence rate of up to 44 percent has also been reported in
athletes.
The reported higher prevalence of ER in athletes likely is related to the
physiological balance in autonomic tone favoring the parasympathetic tone
and its regulation of the action potential.
Another case control study reported that ER was four times more prevalent
among athletes with a history of cardiac arrest (n = 21) than among healthy
athletes (n = 365).

28. However, in this study, the prevalence of ER in the control group of
athletes was substantially lower (7.9 percent) in comparison with
other studies. The presence of ER increased the probability of
arrhythmic death from approximately 2 per million to 3.5 per million
in this population of competitive athletes.
In young healthy athletes from Finland (n = 62) and the United States
(n = 503), an ascending ST segment was the common form of ER,
which has not been associated with an increased arrhythmic risk.
Amongst athletes with ER, all but one of the Finnish (96 percent) and
85 percent of US athletes had an ascending ST variant after ER.
Notably, the association of ER with arrhythmic risk is typically at rest
or during sleep and not during physical activity when J-point elevation
is typically markedly reduced or eliminated.

29. CLINICAL MANIFESTATIONS AND DIAGNOSIS
ER pattern
The ER pattern is nearly always a benign incidental ECG finding.
There are no specific signs or symptoms attributed to the ER pattern, which is
identified through the use of a standard ECG.
In the absence of syncope or sudden cardiac arrest, no additional testing is
required in persons with the ER pattern.

30. ER syndrome
May rarely present with syncope
Most persons with the ER pattern identified on ECG who experience
an isolated episode of syncope, especially syncope which appears
non-cardiac in origin, will not be diagnosed with the ER syndrome in
the absence of additional data showing ventricular fibrillation.
The diagnosis of ER syndrome is most commonly considered in a
survivor of sudden cardiac death (SCD) with ECG evidence of
ventricular fibrillation (VF) and an apparently structurally normal
heart following extensive testing.

31. A systematic assessment of the survivors of sudden cardiac death without
evidence of infarction or left ventricular dysfunction is reported to
establish a causative diagnosis in the majority of cases.
Systematic evaluation includes:
Cardiac monitoring
Signal-averaged ECG
Exercise testing
Echocardiogram
Cardiac magnetic resonance imaging
Evaluation of coronary arteries, typically with invasive angiography
Intravenous adrenaline and sodium channel blocker challenge
Targeted genetic testing should also be considered when a phenotype is
suggested by the above evaluation (eg, long QT syndrome, Brugada
syndrome, catecholaminergic polymorphic ventricular tachycardia)

32. In patients whose evaluation revealed no identifiable cardiac pathology,
idiopathic VF and the ER syndrome should be considered.
A careful review of all available ECGs for evidence of ER is warranted,
particularly around the time of the cardiac arrest.
ER syndrome causing VF may be diagnosed when:
Other etiologies have been systematically excluded
When J-point elevation is augmented immediately preceding VF
ER syndrome causing VF is probable when:
Other etiologies have been systematically excluded
ER pattern exists or increased parasympathetic tone provokes ER
Cardiac arrest occurs at rest or during sleep

33. Prognostic variables
Distribution and amplitude of ER
Morphology of the ST segment
Gender
Family history
Slurring versus notching
Ethnicity
Association with other cardiac pathology

35. DIFFERENTIAL DIAGNOSIS
ER versus Brugada syndrome
Some individuals with Brugada syndrome also have ER (approximately 12
percent) as variants in genes encoding the L-type calcium channel, ATP-
sensitive potassium channel, and sodium channels have been associated
with both of these conditions .
Additionally, some ECG characteristics of ER resemble features of the
Brugada ECG, including J waves, pause and bradycardia dependent
accentuation, the dynamic nature of the ECG manifestations, short-coupled
extra-systole-induced polymorphic ventricular tachycardia/VF, and
suppression of the ECG features and arrhythmia
with isoproterenol and quinidine .

36. However, the Brugada ECG feature of provocation by sodium channel
blocker is not observed in ER.
In fact, sodium channel blockers in most patients with ER attenuate the
J-point, whereas the J-point is augmented by sodium-channel blockers
in the right precordial leads in patients with a Brugada ECG.
Furthermore, a positive signal-averaged ECG and structural
abnormalities in the right ventricular outflow tract are not consistently
observed and have not been reported in patients with ER, respectively.

38. ER versus acute pericarditis
As is seen in ER, there is J-point elevation with resultant ST segment
elevation in patients with acute pericarditis.
Symptom presentation is markedly different in the two conditions.
Unlike ER, most patients with acute pericarditis have ST elevations
diffusely in most or all limb and precordial leads.
Additionally, patients with acute pericarditis often have deviation of
the PR segment, which is not present in ER.

39. ER versus acute myocardial injury
While patients with acute myocardial injury due to ST elevation
myocardial infarction (STEMI) can initially have elevation of the J-
point with concave ST segment elevation, the ST segment elevation
typically becomes more pronounced and convex (rounded upward)
as the infarction persists.
However, the primary distinguishing factor between ER and acute
myocardial injury is the presence of clinical symptoms such as chest
pain or dyspnea.

41. For patients with the incidental finding of the ER pattern on their ECG, we
recommend observation without therapy ( Grade 1A ).
For patients with ER and ongoing acute VF (VF storm) requiring frequent
defibrillation, we suggest intravenous isoproterenol ( Grade 2C ).
For patients with ER syndrome with prior resuscitated SCD due to VF, we
recommend implantation of an implantable cardioverter-defibrillator (ICD)
for secondary prevention of SCD ( Grade 1A ).
For patients with ER syndrome and recurrent VF, we suggest the use
of quinidine , a class IA antiarrhythmic drug, for chronic suppressive therapy
(Grade 2C ).
Patients with ER syndrome who have had an ICD placed but who have had
no documented recurrent arrhythmias do not require chronic anti
arrhythmic drug due to potential side effects from antiarrhythmic drugs