Early Repolarisation Syndrome

The early repolarisation pattern is J-point elevation of at least 0.1 mV (1 mm) in at least two contiguous inferior or lateral leads, shown as notching or slurring of the terminal QRS, with a QRS duration under 120 ms.

It is found in about 1 to 13% of the general population, more often in young men, athletes and people of African descent, and is almost always benign.

Early repolarisation syndrome is diagnosed when the pattern is present in a person resuscitated from unexplained ventricular fibrillation or polymorphic ventricular tachycardia, or in a sudden death victim with a negative autopsy and the pattern on an earlier ECG.

The absolute risk of idiopathic ventricular fibrillation in a person with the pattern is small, in the order of 1 in 10,000 each year, but it rises when high risk ECG features, syncope or a family history of sudden death are present.

By lead distribution, type 1 involves the lateral leads (common in athletes, low risk), type 2 the inferior or inferolateral leads (higher risk), and type 3 the inferior, lateral and right precordial leads (highest risk, linked to electrical storm).

Familial clustering occurs, and variants in KCNJ8, CACNA1C, CACNB2, CACNA2D1, SCN5A and ABCC9 are found in a minority.

Pathophysiology. A larger transient outward potassium current in the epicardium than in the endocardium creates a transmural voltage gradient that inscribes the J wave. Reduced inward sodium or calcium current, or increased outward current (for example the ATP-sensitive potassium current), widens the gradient.

Phase 2 re-entry and short coupled ventricular premature beats from the Purkinje network or papillary muscles then trigger ventricular fibrillation. Bradycardia, pauses, vagal tone and hypothermia increase J-wave amplitude, and sympathetic stimulation reduces it, which explains why events cluster at rest and during sleep.

Most people with the pattern are asymptomatic and the finding is incidental on an ECG taken for another reason. Early repolarisation syndrome presents with syncope, resuscitated cardiac arrest or recurrent ventricular fibrillation (electrical storm), usually at rest or during sleep and often at night. Examination is normal. A family history of sudden unexplained death is present in a minority.

Features that mark higher risk:

• J-point elevation of 0.2 mV (2 mm) or more
• Inferior or inferolateral distribution
• Horizontal or descending ST segment after the J point (an upsloping ST segment is low risk)
• J-wave amplitude that increases after pauses or at slow heart rates
• Short coupled ventricular premature beats
• Unexplained syncope
• Male sex

Red flags.

• Syncope or resuscitated arrest with the pattern and no other cause
• Polymorphic ventricular tachycardia, ventricular fibrillation, or recurrent shocks from an implanted defibrillator
• J-point elevation of 0.2 mV or more with a horizontal or descending ST segment in inferior or inferolateral leads
• J-wave amplitude that grows after a pause or during bradycardia
• Sudden unexplained death under 40 years in a relative

• 12-lead ECG. Measure J-point elevation against the PR or TP baseline in leads II, III, aVF, I, aVL and V4 to V6. Record the ST segment shape after the J point, the maximum J-point amplitude and the lead distribution. Repeat after exercise: in benign forms J-wave amplitude usually falls as heart rate rises.
• Ambulatory ECG for 24 to 48 hours for dynamic J-wave behaviour, ventricular ectopy and pauses. Prolonged external or implantable monitoring for unexplained syncope.
• Secondary causes. Potassium, calcium and magnesium, core temperature, troponin, thyroid function and toxicology.
• Echocardiography and cardiac MRI to exclude structural disease and myocarditis. Coronary angiography in survivors of arrest to exclude ischaemia or spasm.
• Genetic testing. Low yield, so reserved for arrest survivors and families with several affected members. Cascade ECG screening of first degree relatives when the proband has the syndrome.
• Programmed ventricular stimulation does not predict events and is not used for risk stratification.

Differential diagnosis.

• Brugada syndrome (coved ST elevation in V1 to V3)
• Acute pericarditis (diffuse concave ST elevation with PR depression and evolving changes)
• Acute ST elevation myocardial infarction (convex ST elevation, reciprocal depression, evolution)
• Hyperkalaemia and hypercalcaemia
• Hypothermia (Osborn waves, bradycardia, tremor artefact)
• Left ventricular hypertrophy and bundle branch block with secondary repolarisation change
• Arrhythmogenic right ventricular cardiomyopathy (epsilon waves, T wave inversion in V1 to V3)
• Short QT syndrome
• Takotsubo syndrome and myocarditis
• Idiopathic ventricular fibrillation without J-point elevation
• Neurally mediated syncope and epilepsy

• Asymptomatic pattern: no treatment, no antiarrhythmic drugs and no restriction of sport. Family screening is not needed unless there is a family history of sudden unexplained death or of the syndrome.
• Unexplained syncope with the pattern: exclude neurally mediated, orthostatic and structural causes, and use prolonged or implantable monitoring. An implantable cardioverter defibrillator is considered when syncope looks arrhythmic and high risk ECG features or a family history of sudden death are present.
• Survivors of ventricular fibrillation or sustained polymorphic ventricular tachycardia with no other cause: implantable cardioverter defibrillator for secondary prevention. Programme long detection durations and high rate zones to limit inappropriate shocks.
• Recurrent ventricular fibrillation, repeated shocks or electrical storm:
  • Defibrillate pulseless or unstable rhythms.
  • Isoprenaline 1 microgram/min intravenously by infusion, increased every 5 to 10 minutes to a sinus rate of 90 to 120/min, usual maximum 10 microgram/min, continued for hours to days until quinidine takes effect, then weaned. Continuous ECG and blood pressure monitoring. Avoid with active myocardial ischaemia and severe hypertension.
  • Quinidine sulphate 200 to 300 mg orally every 8 hours (usual total 600 to 900 mg daily), maximum 1,200 mg daily in this setting, long term. Check ECG for QTc (reduce or stop if QTc over 500 ms), full blood count (thrombocytopenia), liver enzymes and diarrhoea. Reduce in severe liver or kidney impairment under level monitoring. Contraindicated in complete atrioventricular block without a pacemaker, myasthenia gravis and previous quinidine induced thrombocytopenia. It doubles digoxin levels (halve the digoxin dose), potentiates warfarin and interacts with CYP2D6 and CYP3A4 drugs.
  • Beta blockers and amiodarone have no proven protective effect.
  • Catheter ablation of triggering ventricular premature beats (Purkinje or papillary muscle origin) in a specialist centre for recurrences despite quinidine, or when quinidine is unobtainable or not tolerated. Quinidine is unavailable in many regions.

Special groups.

• Athletes: an asymptomatic athlete with an ascending ST segment and no family history needs no restriction. A symptomatic athlete is withdrawn from sport until evaluated.
• Hypothermia: Osborn waves resolve with rewarming and need no antiarrhythmic therapy.
• Pregnancy: continue quinidine under specialist supervision, with device follow up.

Monitoring. Device interrogation every 3 to 6 months with remote monitoring. ECG yearly and after each quinidine dose change. Full blood count and liver enzymes at baseline, after 2 weeks, then every 3 to 6 months on quinidine. Ambulatory ECG yearly or with symptoms.

Referral and escalation. Refer every symptomatic patient and arrest survivor to an inherited cardiac conditions centre. Urgent for syncope, device shocks or storm.