Fragmentation of the QRS Complex as a Prognostic Sign in Brugada

Syndrome

DOUGLAS P. ZIPES, MDDISTINGUISHED PROFESSORKRANNERT INSTITUTE OF CARDIOLOGYINDIANA UNIVERSITY SCHOOL OF MEDICINEEDITOR-IN-CHIEF HEARTRHYTHMSEPTEMBER 5, 2013

Figure 1. Different morphologies of an fQRS on a 12-lead ECG.

Das M K et al. Circulation 2006;113:2495-2501

Copyright © American Heart Association

Figure 2. Twelve-lead ECG, showing an fQRS (various RSR′ patterns; QRS duration <120 ms) in inferior leads that is correlated with an inferior wall MI on a myocardial perfusion study

(QRS complexes are enlarged in the lower row).

Das M K et al. Circulation 2006;113:2495-2501Copyright © American Heart Association

Figure 3

Source: Heart Rhythm 2009; 6:S8-S14 (DOI:10.1016/j.hrthm.2008.10.019 )

Copyright © 2009 Terms and Conditions

Kaplan-Meier analysis: all-cause mortality in patients with fragmented (fQRS group) and without fragmented QRS (non-fQRS group)

I

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

V1

V2

Male (55 y.o.), aborted sudden death

VF initiation (ICD monitoring)

Fragmented QRS (fQRS) in Brugada syndrome

Source: Heart Rhythm 2009; 6:S34-S43 (DOI:10.1016/j.hrthm.2009.07.018 )

Copyright © 2009 Heart Rhythm Society Terms and Conditions

ELECTROPHYSIOLOGIC BASIS OF EP AND ECG CHANGES

Source: Heart Rhythm 2009; 6:S34-S43 (DOI:10.1016/j.hrthm.2009.07.018 )

Copyright © 2009 Heart Rhythm Society Terms and Conditions

REPOLARIZATION HYPOTHESIS OF ECG CHANGES

1

2

3

4

Epi

ECG

Endo

100 ms

1 2

1 2

1 2

Epi

Mid

Endo

ECG

100 ms

1 2

1 2

1 2Endo

Epi

EpiAPD map

270(ms)

200

PVC activation map

Epi

Endo

Epi

130

150

80

12

3

4 (ms)

70130

14010

Morita, Zipes, et al

Morita, Zipes, et al. Heart Rhythm 2009; 6:S34-S43 (DOI:10.1016/j.hrthm.2009.07.018 )Copyright © 2009 Heart Rhythm Society Terms and Conditions

HETEROGENEITY IS CRITICAL

c 462

RVAI

445

(ms)

LVa b

Pilsicainide

497 401

RVOT

B. QT Map

ST elevation and QT dispersion in body surface mapping

Modified from Morita, Zipes et al. Heart Rhythm 2008;5:725

61 M VFPost pilsicainide

500

450

400

(ms)

a

b

c

d

0.8

0.4

0

(mV)

- 0.2a

b

c

d

dc

A. ST Map

C. ECG

Source: Heart Rhythm 2009; 6:S34-S43 (DOI:10.1016/j.hrthm.2009.07.018 )

Copyright © 2009 Heart Rhythm Society Terms and Conditions

DEPOLARIZATION BASIS OF ECG CHANGES

HRA

His

CS

RVA

Conus branch (Epi)

RVOT(Endo)

ECG (V2)

Epicardial mapping in Brugada syndrome

RVOT-Epi

RVOT-Endo

Filter : 30-300 Hzdelayed potential

RVOT-Epi

RVOT-Endo

Filter : 0.05-300 Hz Local QT

433 ms

350 ms

200 ms

Nagase et al. JACC 2008; 51:1154Nagase et al. JACC 2002; 39:1992

Depolarization hypothesis: Wilde, PostemaJMCC 2010

Examples of f-QRS in Brugada syndrome.

Morita Zipes et al. Circulation 2008;118:1697-1704

f-QRS and LP. Upper panel shows ECGs in lead V2

Morita Zipes et al. Circulation 2008;118:1697-1704

Copyright © American Heart Association

Spontaneous variations of f-QRS and ST elevation

Morita Zipes et al. Circulation 2008;118:1697-1704

Copyright © American Heart Association

SUDDEN DEATH 6 MONTHS AFTER LAST ECG

Incidence of fQRS

• Incidence of fQRS in Brugada syndorme: 50/115 pts (43%)

• fQRS can be recorded within 1.5 months of their initial visit to hospital

p<0.01

(%)Incidence of f-QRS

Morita, Zipes et al. Circulation 2009; 118:1697

f-QRS (-)

f-QRS (+)

5 10

100

50

0(yrs.)

(%)

0

Recurrent syncope due to VF

f-QRS (-)

f-QRS (+)

Fragmented QRS

Morita, Zipes et al. Circulation 2009; 118:1697

KH 　 50y.o. Male 1890840

IIHRA

RVA

RVOT

MAP

TVARV

RVOT

I

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

Fatty infiltration at RV in Brugada syndrome

Depolarization abnormality in Brugada syndrome

• Decrease in Na+ current

• Myocardial injury ( fatty infiltration, fibrosis, myocarditis ）

• PQ 、 QRS 、 HV prolongation 、 fragmented QRS 、 delayed potential 、 late potential

• Index of poor prognosis?

• Depolarization abnormality can be associated with onset of VF.

Figure 1 ECG Presentation in Brugada Syndrome Examples of electrocardiographic (ECG) traces (A to C) . (A) A 35-year-old male patient with presenting spontaneous type I ECG; (B) 30-year-old male patient presenting with type III ECG (left panel) con...Silvia G. Priori , Maurizio Gasparini , Carlo Napolitano , Paolo Della Bella , Andrea Ghidini Ottonelli , Biagio S...Risk Stratification in Brugada Syndrome : Results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) Registry

Journal of the American College of Cardiology Volume 59, Issue 1 2012 37 - 45

ECG Presentation in Brugada Syndrome in the PRELUDE trial: Examples of electrocardiographic (ECG) traces

Silvia G. Priori , Maurizio Gasparini , Carlo Napolitano , Paolo Della Bella , Andrea Ghidini Ottonelli , Biagio S...Risk Stratification in Brugada Syndrome : Results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) Registry

Journal of the American College of Cardiology Volume 59, Issue 1 2012 37 - 45

Survival According to Refractory Period and QRS-f Kaplan-Meier survivorship analysis of arrhythmic event-free survival

Morita, Zipes Heart Rhythm 2009; 6:665-671 (DOI:10.1016/j.hrthm.2009.01.007 )Copyright © 2009 Heart Rhythm Society Terms and Conditions

EPICARDIAL ABLATION IN CANINES

Source: Heart Rhythm 2009; 6:665-671 (DOI:10.1016/j.hrthm.2009.01.007 )

Copyright © 2009 Heart Rhythm Society Terms and Conditions

Source: Heart Rhythm 2009; 6:665-671 (DOI:10.1016/j.hrthm.2009.01.007 )

Copyright © 2009 Heart Rhythm Society Terms and Conditions

Figure 7

Source: Heart Rhythm 2009; 6:665-671 (DOI:10.1016/j.hrthm.2009.01.007 )

Copyright © 2009 Heart Rhythm Society Terms and Conditions

Left lateral view of the right ventricular outflow tract (RVOT) displays the difference in ventricular electrograms between the endocardial (ENDO) and epicardial (EPI) site of the

anterior RVOT of the same patient (patient 4) as Figure 2.

Nademanee K et al. Circulation 2011;123:1270-1279

Copyright © American Heart Association

A scattered plot of all electrograms (n=827 points) recorded from the 9 patients from the 4 major areas: right ventricular (RV) epicardium, anterior right ventricular outflow tract (RVOT)

epicardium, left ventricular (LV) epicardium, and RV endocardium.

Nademanee K et al. Circulation 2011;123:1270-1279

Copyright © American Heart Association

Figure 1

SACHER ET AL. Heart Rhythm (DOI:10.1016/j.hrthm.2013.05.023 )Copyright © Heart Rhythm Society Terms and Conditions

Source: Heart Rhythm (DOI:10.1016/j.hrthm.2013.05.023 )

Copyright © Heart Rhythm Society Terms and Conditions

Reduced sodium channel function unmasks residual embryonic slow conduction in the adult right

ventricular outflow tract Circ Res 113:137

• Adult mice heterozygous for a mutation associated with Brugada syndrome (Scn5a1798insD/+).

• In embryonic heart, conduction velocity was lower in the RVOT than in the right ventricular free wall.

• In hearts of Scn5a1798insD/+ mice and in normal hearts treated with ajmaline, conduction was slower in the RVOT than in the right ventricular wall.

• The slowly conducting embryonic phenotype is maintained in the fetal and adult RVOT and is unmasked when cardiac sodium channel function is reduced.

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