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Fragmentation of the QRS Complex as a Prognostic Sign in Brugada Syndrome DOUGLAS P. ZIPES, MD DISTINGUISHED PROFESSOR KRANNERT INSTITUTE OF CARDIOLOGY.

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Presentation on theme: "Fragmentation of the QRS Complex as a Prognostic Sign in Brugada Syndrome DOUGLAS P. ZIPES, MD DISTINGUISHED PROFESSOR KRANNERT INSTITUTE OF CARDIOLOGY."— Presentation transcript:

1 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

2 Figure 1. Different morphologies of an fQRS on a 12-lead ECG. Das M K et al. Circulation 2006;113: Copyright © American Heart Association

3 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: Copyright © American Heart Association

4 Figure 3 Source: Heart Rhythm 2009; 6:S8-S14 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S8-S14 Copyright © 2009 Terms and ConditionsTerms and Conditions Kaplan-Meier analysis: all-cause mortality in patients with fragmented (fQRS group) and without fragmented QRS (non-fQRS group)

5 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

6 Source: Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S34-S43 Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions ELECTROPHYSIOLOGIC BASIS OF EP AND ECG CHANGES

7 Source: Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S34-S43 Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions REPOLARIZATION HYPOTHESIS OF ECG CHANGES

8 Epi ECG Endo 100 ms Epi Mid Endo ECG 100 ms Endo Epi APD map 270 (ms) 200 PVC activation map Epi Endo Epi (ms) Morita, Zipes, et al

9 Morita, Zipes, et al. Heart Rhythm 2009; 6:S34-S43Morita, Zipes, et al. Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm ) Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions HETEROGENEITY IS CRITICAL

10 c 462 RVAI 445 (ms) LV a b Pilsicainide RVOT B. QT Map ST elevation and QT dispersion in body surface mapping Modified from Morita, Zipes et al. Heart Rhythm 2008;5: M VF Post pilsicainide (ms) a b c d (mV) a b c d d c A. ST Map C. ECG

11 Source: Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S34-S43 Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions DEPOLARIZATION BASIS OF ECG CHANGES

12 HRA His CS RVA Conus branch (Epi) RVOT (Endo) ECG (V2) Epicardial mapping in Brugada syndrome RVOT-Epi RVOT-Endo Filter : Hz delayed potential RVOT-Epi RVOT-Endo Filter : Hz Local QT 433 ms 350 ms 200 ms Nagase et al. JACC 2008; 51:1154 Nagase et al. JACC 2002; 39:1992

13 Depolarization hypothesis: Wilde, Postema JMCC 2010

14 Examples of f-QRS in Brugada syndrome. Morita Zipes et al. Circulation 2008;118:

15 f -QRS and LP. Upper panel shows ECGs in lead V2 Morita Zipes et al. Circulation 2008;118: Copyright © American Heart Association

16 Spontaneous variations of f-QRS and ST elevation Morita Zipes et al. Circulation 2008;118: Copyright © American Heart Association SUDDEN DEATH 6 MONTHS AFTER LAST ECG

17 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

18 f-QRS (-) f-QRS (+) (yrs.) (%) 0 Recurrent syncope due to VF f-QRS (-) f-QRS (+) Fragmented QRS Morita, Zipes et al. Circulation 2009; 118:1697

19 KH 50y.o. Male II HRA RVA RVOT MAP TVA RV RVOT I II III aVR aVL aVF V1 V2 V3 V4 V5 V6 Fatty infiltration at RV in Brugada syndrome

20 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.

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

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

23 Morita, Zipes Heart Rhythm 2009; 6: (DOI: /j.hrthm ) Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions EPICARDIAL ABLATION IN CANINES

24 Source: Heart Rhythm 2009; 6: (DOI: /j.hrthm )Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

25 Source: Heart Rhythm 2009; 6: (DOI: /j.hrthm )Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

26 Figure 7 Source: Heart Rhythm 2009; 6: (DOI: /j.hrthm )Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

27 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: Copyright © American Heart Association

28 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: Copyright © American Heart Association

29 Figure 1 SACHER ET AL. Heart Rhythm SACHER ET AL. Heart Rhythm (DOI: /j.hrthm ) Copyright © Heart Rhythm Society Terms and ConditionsTerms and Conditions

30 Source: Heart Rhythm (DOI: /j.hrthm )Heart Rhythm Copyright © Heart Rhythm Society Terms and ConditionsTerms and Conditions

31 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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33 Presidents Need to Know about Sudden Death Israeli President Shimon Peres Reads Ripples in Oppermans Pond US Past President Bill Clinton The Black Widows. THANK YOU FOR YOUR ATTENTION

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35 Morita et al

36 SUMMARY OF CHANGES Morita et al

37 Figure 7 Source: Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S34-S43 Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

38 Figure 4. Effects of recording site and filtering on f-QRS. Morita H et al. Circulation 2008;118: Copyright © American Heart Association

39 Figure 5. Differences in ECG parameters between patients with and without f-QRS. Morita H et al. Circulation 2008;118: Copyright © American Heart Association

40 Figure 8. Experimental model of Brugada syndrome. Morita H et al. Circulation 2008;118: Copyright © American Heart Association

41 Figure 2 Source: Heart Rhythm 2009; 6: (DOI: /j.hrthm )Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

42 Figure 6 Source: Heart Rhythm 2009; 6: (DOI: /j.hrthm )Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

43 Source: Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S34-S43 Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions T wave changes

44 FRAGMENTATION OF THE QRS COMPLEX AS A PROGNOSTIC SIGN IN BRUGADA SYNDROME BRUDAGA SYNDROME: 20 YEARS OF SCIENTIFIC PROGRESS DOUGLAS P. ZIPES, MD DISTINGUISHED PROFESSOR KRANNERT INSTITUTE OF CARDIOLOGY INDIANA UNIVERSITY SCHOOL OF MEDICINE EDITOR-IN-CHIEF HEARTRHYTHM SEPTEMBER 5, 2013

45 Brugada syndrome 71 y.o. Male SCN5A (-); Syncope at 8:30 a.m. V1 V2 I II III aVR aVL aVF V1 V2 V3 V4 V5 V6

46 Brugada Syndrome in Discussion: The mechanism of the conduction disturbances, the abnormal repolarization and the ventricular arrhythmia can only be speculative at present. Brugada P, Brugada J. J Am Coll Cardiol 1992;20:

47 Source: Heart Rhythm 2009; 6:S34-S43 (DOI: /j.hrthm )Heart Rhythm 2009; 6:S34-S43 Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

48 Recurrence of syncope due to ventricular arrhythmia Morita H et al. Circulation 2008;118: Copyright © American Heart Association

49 SynchronizedEpi Delay (46ms) Epi End Trans Delay Brugada syndrome model Patients ECG ECG Epi 1 Epi 2 End Epi 1 Epi 2 End AT = 28 ms AT = 30 ms AT = 76 ms AT = 30 ms Morita et al. Circulation 2009; 118:1697

50 Figure 5 Source: Heart Rhythm 2009; 6: (DOI: /j.hrthm )Heart Rhythm 2009; 6: Copyright © 2009 Heart Rhythm Society Terms and ConditionsTerms and Conditions

51 A. BrS ECG repolarization abnormality) C. BrS ECG repolarization + depolarization abnormalities Conduction delay B. BrS ECG depolarization abnormality) Conduction delay D. BrS ECG saddle-back) E. BrS ECG(Type 0 ECG) Epicardial action potentials Endocardial action potentials Voltage gradient: epiendo Voltage gradient: endoepi ECG Action potential

52 F. BrS ECG repolarization heterogeneity). BrS ECG (phase 2 reentry)


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