Andrew Grace

Royal Papworth Hospital - University of Cambridge

Consultant: Acutus Medical Inc., Bardy Diagnostics

Boston Scientific Inc. (member PSAB) and Founder, Electus Medical Inc.

Clinical Spectrum of Early Repolarization Syndrome

Heart Rhythm Congress, Birmingham, Monday 8th October 2018

Normal Variant: Vagotonia (courtesy of Dr D Wilton)

The Electrocardiology of Coronary Artery Disease. Leo Schamroth. Blackwell. 1975

Normal Variant: Vagotonia (courtesy of Dr D Wilton)

The Electrocardiology of Coronary Artery Disease. Leo Schamroth. Blackwell. 1975

ST-Segment Elevation in Conditions other than Myocardial Infarction. Wang K et al. N Engl J Med 2003;349:2128-2135

Electrocardiograms Showing ST-Segment Elevation and Normal Variants

ST-Segment Elevation in Conditions other than Myocardial Infarction. Wang K et al. N Engl J Med 2003;349:2128-2135

Electrocardiograms Showing ST-Segment Elevation and Normal Variants

90% young malesConcave ST

ST-Segment Elevation in Conditions other than Myocardial Infarction. Wang K et al. N Engl J Med 2003;349:2128-2135

Electrocardiograms Showing ST-Segment Elevation and Normal Variants

ER patternNotch J point V4

ST-Segment Elevation in Conditions other than Myocardial Infarction. Wang K et al. N Engl J Med 2003;349:2128-2135

Electrocardiograms Showing ST-Segment Elevation and Normal Variants

Normal VariantTerminal T-wave

InversionsST coved

Journal of Electrocardiology 2000; 33:299-309

Journal of Electrocardiology 2000; 33:299-309

Sudden Cardiac Arrest Associated with Early Repolarization

N Engl J Med 2008;358:2016-2023

• ER more prevalent in idiopathic VF survivors

(206) vs. controls (412)

• 31% vs. 5% (p<0.001)

• ER positive individuals more likely to have

further ICD therapy during follow-up (HR 2.1)

Sudden Cardiac Arrest Associated with Early Repolarization

N Engl J Med 2008;358:2016-2023

Sudden Cardiac Arrest Associated with Early Repolarization

N Engl J Med 2008;358:2016-2023

Sudden Cardiac Arrest Associated with Early Repolarization

N Engl J Med 2008;358:2016-2023

Sudden Cardiac Arrest Associated with Early Repolarization

N Engl J Med 2008;358:2016-2023

Sudden Cardiac Arrest Associated with Early Repolarization

N Engl J Med 2008;358:2016-2023

TERMINOLOGY (2012)

Perez, Friday & Froelicher Am J Med 2012; 125:843-844

Perez, Friday & Froelicher Am J Med 2012; 125:843-844

TERMINOLOGY (2012)

Long-Outcome Associated with Early Repolarization

Tikkanen et al. N Engl J Med 2009;361:2529-37

• 10864 middle aged men f/u 30±11 years• ER pattern 630 (5.8%) inferior leads

Survival-free cardiac Survival-free arrhythmia

Significance of associated ST segment

HR 0.89 (0.52-1.55)

ER – inf. ascending/upsloping

No ER

Tikkanen Circulation 2011; 123:2666-2673

Significance of associated ST segment

HR 0.89 (0.52-1.55) HR 1.43 (1.05-1.94)

ER – inf. ascending/upsloping

ER – inf. Horizontal/descending

No ER

Tikkanen Circulation 2011; 123:2666-2673

38 years, Asian, male, VF survivor

Early Repolarization in Population

• Prevalence 6-13 % - decreases with age

• Benign Prognosis

– Inferior J-point elevation ≥ 0.2mV – HR 3.15 – only 0.3% pop

• Usual ER pattern and VF – absolute risk v. low

– Idiopathic VF <45 years – 3/100,000 p.a.

– ER pattern with J waves – 11/100,000 p.a.

Obeyesekere et al. Circulation 2013; 127: 1620-1629

Prevalence of Early Repolarization (age/sex)

Noseworthy et al. J Am Coll Cardiol 2011; 57:2284-9

HRS/EHRA/APHRS CONSENSUS STATEMENT

Europace 2013; 15:1389-1406

HRS/EHRA/APHRS CONSENSUS STATEMENT

Europace 2013; 15:1389-1406

HRS/EHRA/APHRS CONSENSUS STATEMENT

Europace 2013; 15:1389-1406

HRS/EHRA/APHRS CONSENSUS STATEMENT

Europace 2013; 15:1389-1406

Early Repolarization in Athletes

• Prevalence 20-50%

– Frequently associated with ST elevation and rapidly ascending ST segment

– More common in lateral leads

• Benign Prognosis (probably)

– Small cohorts have not shown increased risk

– Single case-control sudy showed association with athletic SCD

• Prevalence increases with period of training

– 37.2% to 52.7% after period of training1

• Association with structural athletic changes (probably)

– No association with LV remodeling1

– J waves associated with increased LVIDd, max. wall thickness and LV mass2

1Noseworthy et al. Circ. AE 2011; 2Quattrini et al. Heart Rhythm 2014

ECG example – athletic appearance

29 years, Caucasian, male, soccer player, 44 bpm, ERP infero-lateral, LV+

Obeyesekere Circulation 2013; 127: 1620-1629

Mechanisms: Hypothetical

Obeyesekere Circulation 2013; 127: 1620-1629

Mechanisms: Hypothetical

Mapping EP substrate in ERS (29 total, 17 malignant)

Zhang et al. JACC Clinical EP 2017; 127: 3:894-904

PR interval – 50 loci identified by GWAS (N=92,000)

Van Setten et al. Nature Communications 2018; 127:9:2904

DEEP PHENOTYPING INDIVIDUALS

Conclusions

• ERS – here to stay – undoubted clinical signals

• Discernible patterns and stratified risk (clinical)

• ECG diagnosis – but ECG patterns e.g. PR interval familial anyway

• Need better phenotyping tools to provide platform for genetic studies