Fragmentation of the QRS Complex
as a Prognostic Sign in Brugada
Syndrome
DOUGLAS P. ZIPES, MD
DISTINGUISHED PROFESSOR
KRANNERT INSTITUTE OF CARDIOLOGY
INDIANA UNIVERSITY SCHOOL OF MEDICINE
EDITOR-IN-CHIEF HEARTRHYTHM
SEPTEMBER 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;113:2495-2501
Copyright © American Heart Association
Figure 3
Kaplan-Meier analysis: all-cause mortality in patients with
fragmented (fQRS group) and without fragmented QRS (non-fQRS group)
Source: Heart Rhythm 2009; 6:S8-S14 (DOI:10.1016/j.hrthm.2008.10.019 )
Copyright © 2009 Terms and Conditions
Fragmented QRS (fQRS) in Brugada syndrome
Male (55 y.o.), aborted sudden death
V1
I
aVR
V1
V4
II
aVL
V2
V5
III
aVF
V3
V6
VF initiation (ICD monitoring)
V2
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
Source: Heart Rhythm 2009; 6:S34-S43 (DOI:10.1016/j.hrthm.2009.07.018 )
Copyright © 2009 Heart Rhythm Society Terms and Conditions
APD map
Epi
ECG
1
Epi
2
Epi
(ms)
270
Endo
1
2
1
2
2
Mid 1
2
Endo 1
2
Epi
1
ECG
10
140
2
100 ms
Epi 1
70
2
3
Epi
80
130
150
Endo
Morita, Zipes, et al
3
4
100 ms
200
PVC activation map
130
1
(ms)
Endo 4
HETEROGENEITY IS CRITICAL
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
ST elevation and QT dispersion in body surface mapping
A. ST Map
61 M VF
Post pilsicainide
B. QT Map
Pilsicainide
(mV)
0.8
(ms)
500
0.4
450
b
b
0
- 0.2
a
a
400
d
d
c
C. ECG
a
c
RVOT
497
b
LV
RVAI
401
c
c
462
d
445
Modified from Morita, Zipes et al. Heart Rhythm 2008;5:725
(ms)
DEPOLARIZATION BASIS OF 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
Epicardial mapping in Brugada syndrome
Conus branch (Epi)
HRA
RVOT
(Endo)
ECG (V2)
Filter : 30-300 Hz
RVOT-Epi
delayed potential
RVOT-Endo
His
Filter : 0.05-300 Hz
RVOT-Epi
Local QT
433 ms
CS
RVA
Nagase et al. JACC 2008; 51:1154
Nagase et al. JACC 2002; 39:1992
RVOT-Endo
350 ms
200 ms
Depolarization hypothesis: Wilde, Postema
JMCC 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
SUDDEN DEATH 6 MONTHS AFTER LAST ECG
Morita Zipes et al. Circulation 2008;118:1697-1704
Copyright © American Heart Association
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
(%)
Incidence of f-QRS
p<0.01
Morita, Zipes et al. Circulation 2009; 118:1697
Fragmented QRS
f-QRS (+)
Recurrent syncope due to VF
(%)
f-QRS (-)
100
f-QRS (-)
50
f-QRS (+)
0
0
5
10 (yrs.)
Morita, Zipes et al. Circulation 2009; 118:1697
Fatty infiltration at RV in Brugada syndrome
KH 50y.o. Male 1890840
V1
I
II
V2
V3
III
aVR
V4
aVL
V5
aVF
II
HRA
RVA
RVOT
MAP
RVOT
V6
RV
TVA
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.
ECG Presentation in Brugada Syndrome in the PRELUDE trial:
Examples of electrocardiographic (ECG) traces
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
Survival According to Refractory Period and QRS-f Kaplan-Meier
survivorship analysis of arrhythmic event-free survival
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
EPICARDIAL ABLATION IN CANINES
Morita, Zipes
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
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.
Presidents Need to Know about
Sudden Death
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Reads “Ripples in Opperman’s Pond” “The Black Widows.”