early repolarisation syndrome (2)

{Early repolarisation syndrome

Dr Vinit Kumar

Definition Prevalence and Arrhythmic

Risk Mechanism of ERP Genetic basis Clinical manifestations Diagnosis Prognostic variables Therapy Conclusion.

Definition

In 1976 by Kambara and Phillips suggested that early repolarization was defined by: 1) end-QRS notching or slurring;2) elevation of the ST-segment; and 3) an upwardsloping ST-segment followed by a tall, symmetrical T-wave.

Haissaguerre et al. defined early repolarization as “an elevation of the QRS-ST-segment junction (J-point) in at least 2 leads” (within the same territory; e.g., inferior or lateral leads) as being a sign of early repolarization.The amplitude of the J-point elevation had to be at least 0.1 mV above the baseline level, as either QRS slurring or notching. The amplitude and slope of the ST-segment were not part of the definition

Definition

Tikkanen et al. definition also measured the degree of J-point elevation, which was stratified at levels of 0.1 and 0.2 mV. These investigators also introduced the concept of the ST-segment slope,showing that a horizontal or downwardsloping ST-segment is associated with greater arrhythmic risk

{Prevalence and Arrhythmic Risk

The prevalence of early repolarization in the general population varies from 1% to 9%, depending on

age (predominant in young adults), race (highest among black populations), gender (predominant in men), and the criterion for J point elevation (0.05 mV versus 0.1 mV) In a study of a community-based general population of

10,864 middle-aged subjects, the prevalence of early repolarization (J point elevation >0.1 mV) was

Overall- 5.8%, inferior leads- 3.5%, lateral leads-2.4%, both- 0.1% J point elevation > 0.2 mV, Overall- 0.33%.

The ST segment after the J point was horizontal or descending – 71.5% rapidly ascending - 28.5%. incidence - idiopathic VF

age <45 years - 3:100 000.

J-waves- 11:100 000

The presence of ER is associated with 3 times the risk of developing VF, but the overall risk is still negligible

ER syndrome - syncope or cardiac arrest is

attributed to ER after systematic exclusion of other etiologies.

N Engl J Med 2008;358:2016-23.

Another concurrent case–control study also demonstrated a higher prevalence of ER (42%) among survivors of idiopathic VF compared with controls (13%, P<0.01)

ER increases the RR of arrhythmic events, the AR remains very low.

Incidental identification of ER should not be interpreted as a high risk marker.

Clinical decisions are driven by the presence and severity of symptoms and comorbidities

{Mechanism of Early Repolarization andIdiopathic Ventricular Fibrillation

the association of ER with arrhythmic risk is typically at rest or during sleep,and not during physical activity.

Early repolarization

Prominent phase 1 notch larger transient-outward K+ current (Ito) -

epicardium Greater net repolarizing (outward) current

flow during phase 1. In ER -enhancement in epi net outward

current, enhancement of the endo-to-epi AP differences manifests as J-waves which reflects current flow from depolarized

endo to substantially-repolarized epi - phase 1

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Genetic Basis

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Case Report: This young female (14 years) was resuscitated in 2001 following an episode of sudden death due to VF. All examinations including coronary angiogram with ergonovine injection, MRI, and flecainide or isoproterenol infusion were normal. The patient had multiple (>100) recurrences of VF unresponsive to beta-blockers, lidocaine/mexiletine, verapamil, and amiodarone. Recurrences of VF were associated with massive accentuation of the early repolarization pattern at times mimicking acute myocardial ischemia. Coronary angiography during an episode with 1.2 mV J/ST elevation was normal. Isoproterenol infusion acutely suppressed electrical storms, while quinidine eliminated all recurrences of VF and restored a normal ECG over a follow-up of 65 months. Genomic DNA sequencing of KATPchannel genes showed missense variant in exon 3 (NC_000012) of the KCNJ8 gene, a subunit of the KATP channel, conferring predisposition to dramatic repolarization changes and ventricular vulnerability.

Haissaguerre et al Ventricular fibrillation with prominentearly repolarization associated with a rare variant of KCNJ8/KATP channel.J Cardiovasc Electrophysiol. 2009;20:93–98.

ER vs Brugada

J-waves, pause/bradycardia dependent

accentuation dynamic nature - ECG pattern, suppression of the ECG features and

arrhythmia with isoproterenol and quinidine.

not seen

provocation by sodium channel blocker Some individuals with Brugada syndrome may also

have ER (approximately 12%)

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Clinical Manifestations

Life-threatening arrhythmias are often the first and unexpected manifestation of ERsyndrome

Incidental ECG finding – present intermittently. Repeated measurements from 542 subjects with ER demonstrated the

subsequent absence of ER in≈20%. Even in the cardiac arrest population, 58% of patients whose

arrest was attributed to ER syndrome had ≥1 ECG that did not demonstrate the ER pattern during their hospitalization

There is no proven provocative test to identify concealed ER. Conflicting evidence - association between syncope and ER

Classification – arrythmic risk associated spatial distribution

Type 1 (ER in the lateral precordial leads) - healthy male athletes and - largely benign.

Type 2 (ER in the inferior or inferolateral leads) a moderate risk.

Type 3 (ER globally in the inferior,lateral, and right precordial leads) - highest risk.

Brugada syndrome is classified as type 4 (j-wave/point elevation in the right precordial leads).

ST characteristics are incremental to the location with a clear higher risk associated with the horizontal or down-sloping pattern.

ER pattern on ECG should not lead to classification of a ER syndrome

other etiologies have been excluded J-point elevation is augmented immediately

preceding VF. Systematic assessment of survivors of SCD

without evidence of infarction or left ventricular dysfunction.

Diagnosis of Ventricular Fibrillation resultingfrom Early Repolarization Syndrome

other etiologies excluded

High risk baseline ER pattern orIncreased parasympathetic tone provokes

high risk ER characteristics or Cardiac arrest occurs during sleep/at rest

PROBABLE ERS

current guidelines do not recommend genetic testing

cardiac monitoring Echocardiogram evaluation of coronary

arteries Signal averaged ECG exercise testing cardiac MRI intravenous epinephrine

and sodium channel blocker challenge

A careful review of all available ECGs for evidence of ER is warranted, particularly around the time of the cardiac arrest

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Prognostic Variables of the EarlyRepolarization Pattern

• Electrocardiographic Markers

• Sex, Family History, and Ethnicity

• Autonomic Tone

Electrocardiographic Markers

inferior location greater amplitude of ER horizontal or down-sloping ST-segment QRS notching vs slurring highest risk - ER of high amplitude (≥0.2

mV) in the inferior limb leads + horizontal or descending ST-segment

Horizontal ST-segment after early repolarization

Sex, Family History, and Ethnicity

Males African descent

Autonomic Tone

Bradycardia-dependent augmentation of ER is observed in both VF cases and healthy controls

Tachycardia tends to normalize ER. night when parasympathetic tone is

augmented

54bpm 68bpm 73bpm

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Early Repolarization modifying riskof underlying Cardiac Pathology

Much more common modifier in the context of structural heart disease and primary electric disorders ↑ risk of ischemic VF in the event of a myocardial

infarction/ischemia ER - inferior leads -increased risk of life-threatening

ventricular arrhythmias in patients with chronic CAD , after adjustment for LVEF

Predict higher risk of sudden death in nonischemic cardiomyopathy patient

ER + Brugada pattern with a ECG is an incremental predictor of arrhythmic events ARVC short QT syndrome .

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Therapies for Early Repolarization Syndrome

isoproterenol infusion - acute cases , immediately suppressed electric storms

Isoproterenol - initiatedat1.0 μg/min, targeting a20% increase in heart rate or an absolute heart rate 90. bpm, quinidine - chronic cases, decreased recurrent VF

suppresses outward currents - Ito, restored a normal ECG

Adrenergic activation – enhancing inward currents ( L type Ca2+ current) –offset the net outward K+ current excess

Drug Therapy

Implantable Cardioverter-Defibrillator

is indicated after cardiac arrest. highly effective in terminating ventricular

arrhythmias in nearly all cases.

no current risk stratification strategy for asymptomatic patients

Syncope attributed to ER appears clinically uncommon and warrants an aggressive attempt to verify that syncope is related to arrhythmia.

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Inheritance of Early Repolarizationand Family Screening

heritability in the general population and within families.

Siblings - ↑ unadjusted odds of ER ( odds ratio,2.22 ,P= 0.047)

A study involving 505 Caucasian nuclear families reported that individuals with ≥1 parent with ER had a 2.5-fold increased incidence of demonstrating the ER pattern.

Heritability - higher - inferior leads - notched morphology AD inheritance pattern with incomplete penetrance

Currently no recommendation to screen the families in individuals with asymptomatic ER.

To conclude

The ER syndrome as a primary arrhythmogenic disorder causing VF is very rare.

lack of clinically useful risk stratifying tools or an established provocative test for identifying malignant ER, despite some ECG features that are associated with a higher risk.

As such, patients with asymptomatic ER and no family history of malignant ER should be reassured that their ECG is a normal variant, until such time as better tools enable risk stratification.

All patients with ER should continue to have modifiable cardiac risk factors addressed

As in a war when you don’t know

well your enemy ,it is better to

maintain a constant precaution and

look for as many information as

possible in order to avoid defeat

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Thank you