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California Heart Rhythm SymposiumSan Francisco, CASeptember 8, 2012
“ J Wave Syndromes. Mechanisms”
Charles AntzelevitchMasonic Medical Research Laboratory
Utica, NY 13501
Gilead Sciences - Research Support and ConsultantshipAstraZeneca - Research Support and ConsultantshipCardiome - Research SupportMerck - Research SupportPopulation Council - Research Support Buchang Group - Research Support
NIH - Research SupportNYSTEM - Research SupportAHA - Research SupportNew York State &Florida Masons - Research Support
Disclosures & Acknowledgments
Action Potential StudiesSilvio LitovskyAnton LukasS. Krishnan
Action Potential StudiesSilvio LitovskyAnton LukasS. Krishnan
Voltage Clamp StudiesAndrew ZygmuntJonathan CordeiroHelen Diana (Dan Hu)Hector Barajas-MartinezJanire UrrutiaYoshiyasu Aizawa
Voltage Clamp StudiesAndrew ZygmuntJonathan CordeiroHelen Diana (Dan Hu)Hector Barajas-MartinezJanire UrrutiaYoshiyasu Aizawa
Perfused Wedge StudiesGan-Xin YanSerge SicouriWataru ShimizuJose Di DiegoA. BurashnikovJeffrey FishGi-Byoung NamTetsuro EmoriMasahiko KondoMasato TsuboiFabrice ExtramianaChinmay PatelEyal NofYoshino MinouraIstván Koncz
Perfused Wedge StudiesGan-Xin YanSerge SicouriWataru ShimizuJose Di DiegoA. BurashnikovJeffrey FishGi-Byoung NamTetsuro EmoriMasahiko KondoMasato TsuboiFabrice ExtramianaChinmay PatelEyal NofYoshino MinouraIstván Koncz
In Vivo and Modeling StudiesVladislav V. Nesterenko
In Vivo and Modeling StudiesVladislav V. Nesterenko
Stem Cell & Molecular BiologyXavier Michael JesudossBobby Cherian KallukalamYuesheng WuMayurika DesaiJackie Treat
Stem Cell & Molecular BiologyXavier Michael JesudossBobby Cherian KallukalamYuesheng WuMayurika DesaiJackie Treat
CollaboratorsSami Viskin, Michel Haissaguerre, Mel Scheinman, Minoru Horie , Yoshifusa Aizawa, Arthur Wilde, Andras Varro, Michael Glickson, Michael Eldar, Liron Miler, Michael Ackerman, Jon
Steinberg, Pedro, Josep & Ramon Brugada, Wee Nademanee, Fiorenzo Gaita, Carla Giustetto, Martin Borggrefe,, Peter Schwartz, Lia Crotti, Michael Sanguinetti, Mike Ackerman, Christian Wolpert, Rainer Schimpf, Christian Veltmann, Lior Gepstein
CollaboratorsSami Viskin, Michel Haissaguerre, Mel Scheinman, Minoru Horie , Yoshifusa Aizawa, Arthur Wilde, Andras Varro, Michael Glickson, Michael Eldar, Liron Miler, Michael Ackerman, Jon
Steinberg, Pedro, Josep & Ramon Brugada, Wee Nademanee, Fiorenzo Gaita, Carla Giustetto, Martin Borggrefe,, Peter Schwartz, Lia Crotti, Michael Sanguinetti, Mike Ackerman, Christian Wolpert, Rainer Schimpf, Christian Veltmann, Lior Gepstein
Molecular GeneticsGuido PollevickAlejandra GuerchicoffRyan PfeifferElena BurashnikovGabriel CaceresColleen Puleo
Molecular GeneticsGuido PollevickAlejandra GuerchicoffRyan PfeifferElena BurashnikovGabriel CaceresColleen Puleo
Characteristics of the J Wave
•Also referred to as an Osborn wave•A distinct J wave is commonly
observed in the baseline ECG of some animal species, including baboons and dogs.
•A distinct J wave is rarely observed in humans under normal conditions, although an elevated J point is commonly encountered
•In humans and animals, the appearance of a prominent J wave in the ECG is considered pathognomonic of hypothermia, hypercalcemia, the Brugada syndrome, early repolarization pattern or other arrhythmogenic syndromes
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Restitution of J wave parallels that of action potential notch
Yan and Antzelevitch. Circulation 93:372-379, 1996
Cellular Basis for the J Wave
Transmural distribution of the Ito-mediated action potential notch is responsible for the inscription of the electrocardiographic J wave
Yan and Antzelevitch. Circulation 93:372-379, 1996
Early Repolarization Patterns
Modified from Antzelevitch et al, JACC, 2011
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Antzelevitch C.. J Cardiovasc Electrophys 12:268, 2001
Type 1
Brugada Syndrome
V1
V2
V3 V6
V5
V4
Ventricular Arrhythmias in Brugada Syndrome
BrS1 3p21 INa SCN5A, Nav1.5 11-28%
BrS2 3p24 INa GPD1L Rare
BrS3 12p13.3 ICa CACNA1C, Cav1.2 6.6%
BrS4 10p12.33 ICa CACNB2b, Cavβ2b 4.8%
BrS5 19q13.1 INa SCN1B, Navβ1 1.1%
BrS6 11q13-14 Ito KCNE3, MiRP2 Rare
BrS7 11q23.3 INa SCN3B, Navβ3 Rare
BrS8 12p11.23 IK-ATP KCNJ8, Kir6.1 2%
BrS9 7q21.11 ICa CACNA2D1, Cavα2δ 1.8%
BrS10 1p13.2 Ito KCND3, Kv4.3 Rare
BrS11 17p13.1 INa MOG1 Rare
Genetic Basis for Brugada SyndromeCausative Genes
Locus Ion Channel Gene/Protein % of Probands
5
15q24-q25 If HCN4
7q35 IKr KCNH2, HERG
Xq22.3 Ito KCNE5 (KCNE1-like)
Genetic Basis for Brugada SyndromeModulatory Genes
Locus Ion Channel Gene/Protein
I. Antiarrhythmic drugs Na+ channel blockers
Class IC drugs (Flecainide, Pilsicainide, Propafenone)Class IA drugs (Ajmaline, Procainamide, Disopyramide, Cibenzoline)
Ca2+ channel blockers (Verapamil) Beta Blockers (Propranolol intoxication)
II. Antianginal drugs Ca2+ channel blockers (Nifedipine, Diltiazem) Nitrates (Isosorbide dinitrate, Nitroglycerine) K+ channel openers (Nicorandil)
III. Psychotropic drugs Tricyclic antidepressants (Amitriptyline, Nortriptyline, Desipramine, Clomipramine) Tetracyclic antidepressants (Maprotiline)Phenothiazine (Perphenazine, Cyamemazine) Selective serotonin reuptake inhibitors (Fluoxetine) LithiumAnticonvulsants (clonazepam)Antipsychotics (Trifluoperazine, Loxapine)
IV. Other drugs Histaminic H1 receptor antagonists DimenhydrinateDiphenhydramineCocaine intoxicationAlcohol Intoxication
Drug-induced Brugada Syndrome
Modified from Antzelevitch. PACE 29:1130-1159, 2006 and Shimizu, J Electrocardiol, 2005
Amitriptyline-induced Brugada Syndrome
Minoura et al.J Cardiovasc Electrophysiol 23:423-32, 2012
Intrinsic HeterogeneityIntrinsic HeterogeneityAccentuate Notch &Cause Loss of APDDome in Epicardium
Accentuate Notch &Cause Loss of APDDome in Epicardium
Dispersion of RepolarizationTransmural Epicardial
QT interval Phase 2 reentry
Dispersion of RepolarizationTransmural Epicardial
QT interval Phase 2 reentry
ST Segment(Vulnerable Window)
ST Segment(Vulnerable Window)
ExtrasystoleExtrasystole
VT/VF (Reentry)VT/VF (Reentry)
Brugada Syndrome
INa, ICaINa, ICaI to, IKr , IKs, IK-ATP , ICl(Ca)
I to, IKr , IKs, IK-ATP , ICl(Ca)
Transmural Dispersion of Repolarization
Transmural Dispersion of Repolarization
Phase 2 Reentry in RV Epicardium
Phase 2 Reentry in RV Epicardium
Phase 2 Reentry-induced VT/VF
Phase 2 Reentry-induced VT/VF
Epi 1
Epi 2
ECG
500 msec
50mV
50mV
0.5mV
50mV
200 msec
0
0
0
0
4 3
21
200 msec
50mV
0 0 0Epi M Endo
4
3
2
1
Antzelevitch. Am J Physiol 293:H2024-38, 2007
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Journal of Molecular and Cellular Cardiology 49 (2010) 543–553
Therapy - Brugada Syndrome
Devices or Ablative� ICD ? Pacemaker? Ablation or Cryosurgery
PharmacologicΧ Amiodarone - does not protect (Brugada et al. Circulation, 1998)
Χ β Blockers - do not protect (Brugada et al, 1998, Nademanee et al)
� β Adrenergic agonists – Isoproterenol (Miyazaki et al, 1996; Shimizu et al, )
� Phosphodiesterase Inhibitors-cilostazol(Tsuchiya et al., JCE 13: 698, 2002)
Χ Class IC antiarrhythmics – Flecainide, Propafenone - contraindicatedΧ Class IA antiarrhythmics
Χ Procainamide, Disopyramide - contraindicated� Quinidine (Yan and Antzelevitch, 1999; Alings et al, 2001; Belhassan et al, 1999)
? Tedisamil? AVE0118
� Anti-androgen therapy � I to Blocker - cardioselective and ion channel specific? Late INa agonist – dmLSB (Danshen derivative)
Devices or Ablative� ICD ? Pacemaker? Ablation or Cryosurgery
PharmacologicΧ Amiodarone - does not protect (Brugada et al. Circulation, 1998)
Χ β Blockers - do not protect (Brugada et al, 1998, Nademanee et al)
� β Adrenergic agonists – Isoproterenol (Miyazaki et al, 1996; Shimizu et al, )
� Phosphodiesterase Inhibitors-cilostazol(Tsuchiya et al., JCE 13: 698, 2002)
Χ Class IC antiarrhythmics – Flecainide, Propafenone - contraindicatedΧ Class IA antiarrhythmics
Χ Procainamide, Disopyramide - contraindicated� Quinidine (Yan and Antzelevitch, 1999; Alings et al, 2001; Belhassan et al, 1999)
? Tedisamil? AVE0118
� Anti-androgen therapy � I to Blocker - cardioselective and ion channel specific? Late INa agonist – dmLSB (Danshen derivative)
↑ ICa
↓ I to
Early Repolarization Pattern Predisposes to
Development of Polymorphic VT/VF via a Brugada Syndrome-like
Mechanism
Yan an Antzelevitch, Circulation, 1999Gussak and Antzelevitch, J Electrocardiol, 2000
Antzelevitch and Yan, Heart Rhythm7:549-58, 2010 Haïssaguerre et al., N Engl J Med 358:2016-23, 2008
Early Repolarization
Patternand SCD
31% of IVFvs.
5% of Controls
ER was defined as QRS-ST junction elevation of > 0.1 mV manifested as QRS slurring or
notching
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Nam, Kim, Antzelevitch, N Engl J Med 358:2078-79, 2008Nam…Antzelevitch. Eur Heart J. 31:330-9, 2010
Early Repolarization
Patternand SCD
60% of IVFvs.
3.3% of Controls
4 developed electrical storms
Tikannen et al, N Engl J Med 361, 2009.
Kaplan–Meier Curves for Death from Cardiac Causes and from Arrhythmia in Subjects with J-Point Elevation
Early Repolarization Is an Independent Predictor of Occurrences of Ventricular Fibrillation in the Very Early Phase of Acute Myocardial Infarction
Yoshihisa Naruse, MD; Hiroshi Tada, MD; Yoshie Harimura, MD; Mayu Hayashi, MD; Yuichi Noguchi, MD; Akira Sato, MD; Kentaro Yoshida, MD; Yukio Sekiguchi, MD; Kazutaka Aonuma, MD
Background—Recent evidence has linked early repolarization (ER) to idiopathic ventricular fibrillation (VF) in patients without structural heart disease. However, no studies have clarified whether or not there is an association between ER and the VF occurrences after the onset of an acute myocardial infarction (AMI).
Methods and Results—This study retrospectively included 220 consecutive patients with an AMI (57 female; mean age, 69±11 years) in whom the 12-lead ECGs before the AMI onset could be evaluated. The patients were classified on the basis of a VF occurrence within 48 hours after the AMI onset. Early repolarization was defined as an elevation of the QRS-ST junction of >0.1 mV from baseline in at least 2 inferior or lateral leads, manifested as QRS slurring or notching. Twenty-one (10%) patients had a VF occurrence within 48 hours of the AMI onset. A multivariate analysis revealed that ER (odds ratio [OR], 7.31; 95% confidence interval [CI], 2.21–24.14; P<0.01), a time from the onset to admission of <180 minutes (OR, 3.77; 95% CI, 1.13–12.59; P<0.05), and a Killip class greater than I (OR, 13.60; 95% CI, 3.43–53.99; P<0.001) were independent predictors of VF occurrences. As features of the ER pattern, a J-point elevation in the inferior leads, greater magnitude of the J-point elevation, notched morphology of the ER, and ER with a horizontal/descending ST segment, all were significantly associated with a VF occurrence.
Conclusions—The presence of ER increased the risk of VF occurrences within 48 hours after the AMI onset.
Clinical Trial Registration Information—http://www.umin.ac.jp; Identifier: UMIN000005533.
(Circ Arrhythm Electrophysiol. 2012;5:506-513.)
Genetic Basis for Early Repolarization Syndrome
Locus Ion Channel Gene/Protein % of Probands
ERS1 12p11.23 IK-ATP KCNJ8, Kir6.1
ERS2 12p13.3 ICa CACNA1C,CaV1.2 4.1%
ERS3 10p12.33 ICa CACNB2b, Cavβ2b 8.3
ERS4 7q21.11 ICa CACNA2D1, Cavα2d 4.1%
ERS5 12p12.1 IK-ATP ABCC9, SUR2A
ERS6 3p21 INa SCN5A, NaV1.5
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KCNJ8 mutation (S422L)
Barajas-Martinez et al. Heart Rhythm, Nov. 3, 2011 Epub ahead of print
Gain of Function in IK-ATP due to
reduced sensitivity of the KCNJ8-S422L
mutant KATP
channels to ATP
Barajas-Martinez et al.Heart Rhythm 9:548-55, 2012
ERS Type 3SCN5A (NaV1.5) -G1297G FSX22
+ABCC9 (SUR2A)-V734I
Gain of Function in IK-ATP due to reduced
sensitivity of the ABCC9 (SUR2A)-
V734I mutant KATPchannels to ATP
Hu et al.Unpublished data, 2012
Early Repolarization Pattern Predisposes to
Development of Polymorphic VT/VF via a Brugada Syndrome-like
Mechanism
Yan an Antzelevitch, Circulation, 1999Gussak and Antzelevitch, J Electrocardiol, 2000
Antzelevitch and Yan, Heart Rhythm7:549-58, 2010
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J Wave Syndromes
Brugada Syndrome Early Repolarization
Syndrome
Outward shift of repolarizing current during early phase of the action potential
Phase 2 Reentry
I Na, I CaI Na, I Ca
I toI to
I K-ATPI K-ATPI K-AChI K-ACh
I K-ATPI K-ATP
?
I Na, I CaI Na, I Ca
BrS ERS Possible Mechanism(s)Region Associated with highest arrhythmic risk
RVOT Inferior myocardium
Increased levels of Ito
Male Predominance Yes (75%) Yes (80%) Testosterone modulation of ion currents underlying the epicardial AP notch
Average age of first event ~35-40 42Dynamicity of ECG High High Autonomic modulation of ion channel currents underlying
early phases of the epicardial AP
VT/VF trigger Short-coupled PVC
Short-coupled PVC
Phase 2 reentry
Ameliorative response to quinidine
Yes Yes Inhibition of Ito and possible vagolytic effect
Ameliorative response to Isoproterenol and cilostazol
Yes Yes Increased ICa and faster heart rate
Ameliorative response to pacing
Yes Yes Reduced availability of Ito due to slow recovery from inactivation
Vagally-mediated accentuation of ECG pattern
Yes Yes Direct effect to inhibit ICaand indirect effect to increase Ito (due to slowing of heart rate)
Features Common to Brugada and Early Repolarization Syndromesand Possible Underlying Mechanisms
RVOT=right ventricular outflow tract, AP=action potential; PVC=premature ventricular contraction
Continuous Spectrum Between BrS and ERS
• Brugada (BrS) and Early Repolarization (ERS) Syndromes share similar ECG characteristics, clinical outcomes, risk factors and arrhythmic characteristics.
• BrS and ERS share a common arrhythmic platform related to amplification of Ito-mediated J waves.
• Although BrS and ERS differ with respect to the magnitude and lead location of abnormal J wave manifestation, they can be considered to represent a continuous spectrum of phenotypic expression, termed J wave syndromes.
Hypothesis
TherapyEarly Repolarization Syndrome
Devices � ICD
Pharmacologic? Amiodarone - (3 out of 10) (Haïssaguerre et al . JACC 53: 612, 2009)Χ β Blockers - do not protect (Haïssaguerre et al . JACC 53: 612, 2009)Χ Verapamil - does not protect (Haïssaguerre et al . JACC 53: 612, 2009)
� Β Adrenergic agonists –Isoproterenol (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
� Class IA antiarrhythmics� Quinidine (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
Χ Class IB antiarrhythmics – Lidocaine, Mexiletine – do not protect (Haïssaguerre et al . 2009)Χ Class IC antiarrhythmics – Flecainide, Propafenone – contraindicated ?
� I to Blocker - cardioselective and ion channel specific� Anti-androgen therapy ?
Devices � ICD
Pharmacologic? Amiodarone - (3 out of 10) (Haïssaguerre et al . JACC 53: 612, 2009)Χ β Blockers - do not protect (Haïssaguerre et al . JACC 53: 612, 2009)Χ Verapamil - does not protect (Haïssaguerre et al . JACC 53: 612, 2009)
� Β Adrenergic agonists –Isoproterenol (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
� Class IA antiarrhythmics� Quinidine (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
Χ Class IB antiarrhythmics – Lidocaine, Mexiletine – do not protect (Haïssaguerre et al . 2009)Χ Class IC antiarrhythmics – Flecainide, Propafenone – contraindicated ?
� I to Blocker - cardioselective and ion channel specific� Anti-androgen therapy ?
↑ ICa
↓ I to
10
Modified from Antzelevitch and Yan.
Heart Rhythm 7:549-58. 2010
J Wave SyndromesInherited Acquired
ER in Lateral Leads
ERS Type 1
ER in inferior or infero-lateral leads
ERS Type 2
Global ER
ERS Type 3
BrugadaSyndrome
Ischemia-mediatedVT/VF
Hypothermia-mediatedVT/VF
Anatomic LocationAntero-lateral left
ventricleInferior left ventricle
Left and right ventricles
Right ventricle
Left and right ventriclesLeft and right
ventricles
Leads Displaying J-wave / J-point elevation
I, V4-V6 II, III, aVF Global V1-V3 Any of 12 leads Any of 12 leads
Response of J wave or ST Elevation to:
Bradycardia or pause N/A N/A
Na+ channel blockers N/A N/A
Sex Dominance Male Male Male Male Male70,71 Either gender
VT/VFRare
ER pattern is common inhealthy athletes11,31,51
Yes21,23Yes
ElectricalStorms7,27
Yes Yes Yes
Response toQuinidine :
Limited data
J wave/ST Elevation
VT/VF 59
Response toIsoproterenol :
Limited data N/A N/A
J wave/ST Elevation
VT/VF
EP= electrophysiology; N/A=not available; ERS=early repolarization syndrome; VT=ventricular tachycardia; VF=ventricular fibrillation
Effect of age and gender on ST segment elevation
Ezaki et al, Circ J, 2010
Effect of Androgen-deprivation on ST segment Elevation
Ezaki et al, Circ J, 2010
Disappearance of ST Segment Elevation in Brugada Patient after Orchiectomy
Matsuo K, et al., PACE, 2003
Case 2
V1
V2
V1
V2
Age 57 59 61 63 65 67 68
71 74 75 77 79 80 81Age
1960 1962 1964 1966 1968 1970 1971
1974 1977 1978 1980 1982 1983 1984
Castration
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Chronic exposure to testosterone (4 weeks) increases expression of
Transient Outward Current (I to)
in induced pluripotent stem cell-derived cardiomyocytes
10 µm 20 µm
Barajas-Martinez, Hu et al., Unpublished data
Testosterone 1 uM
Testosterone 1 uM (n=20)
TherapyEarly Repolarization Syndrome
Devices � ICD
Pharmacologic? Amiodarone - (3 out of 10) (Haïssaguerre et al . JACC 53: 612, 2009)Χ β Blockers - do not protect (Haïssaguerre et al . JACC 53: 612, 2009)Χ Verapamil - does not protect (Haïssaguerre et al . JACC 53: 612, 2009)
� Β Adrenergic agonists –Isoproterenol (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
� Class IA antiarrhythmics� Quinidine (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
Χ Class IB antiarrhythmics – Lidocaine, Mexiletine – do not protect (Haïssaguerre et al . 2009)Χ Class IC antiarrhythmics – Flecainide, Propafenone – contraindicated ?
� I to Blocker - cardioselective and ion channel specific� Anti-androgen therapy ?
Devices � ICD
Pharmacologic? Amiodarone - (3 out of 10) (Haïssaguerre et al . JACC 53: 612, 2009)Χ β Blockers - do not protect (Haïssaguerre et al . JACC 53: 612, 2009)Χ Verapamil - does not protect (Haïssaguerre et al . JACC 53: 612, 2009)
� Β Adrenergic agonists –Isoproterenol (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
� Class IA antiarrhythmics� Quinidine (Yan and Antzelevitch, 1999; Haïssaguerre et al . 2009)
Χ Class IB antiarrhythmics – Lidocaine, Mexiletine – do not protect (Haïssaguerre et al . 2009)Χ Class IC antiarrhythmics – Flecainide, Propafenone – contraindicated ?
� I to Blocker - cardioselective and ion channel specific� Anti-androgen therapy ?
↑ ICa
↓ I to
Thank You Risk Stratification of Patients with Early Repolarization Pattern
• Available data clearly indicate that incidental discovery of a J wave on routine screening should not be interpreted as a marker of “high risk” for SCD since the odds for this leading to a fatal outcome is relatively low.
• However, mounting evidence suggests that careful attention should be paid to subjects with “high risk” ER.
• Available data clearly indicate that incidental discovery of a J wave on routine screening should not be interpreted as a marker of “high risk” for SCD since the odds for this leading to a fatal outcome is relatively low.
• However, mounting evidence suggests that careful attention should be paid to subjects with “high risk” ER.
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Risk Stratification of Patients with Early Repolarization Pattern
Who is at risk?1) J point or ST segment elevation of 0.2 mV or greater in
inferior and infero-lateral or global leads. 2) Appearance of distinct and prominent J waves.3) Association of ER pattern with abbreviated QT intervals.4) Short-coupled extrasystoles5) Transient J wave augmentation or fluctuation of J wave
portends a high risk for VF in patients with ER.6) Association with Horizontal or Descending ST segment7) Association of ER pattern with SCD, Unexplained
syncope, or unexplained family history of SCD.
Who is at risk?1) J point or ST segment elevation of 0.2 mV or greater in
inferior and infero-lateral or global leads. 2) Appearance of distinct and prominent J waves.3) Association of ER pattern with abbreviated QT intervals.4) Short-coupled extrasystoles5) Transient J wave augmentation or fluctuation of J wave
portends a high risk for VF in patients with ER.6) Association with Horizontal or Descending ST segment7) Association of ER pattern with SCD, Unexplained
syncope, or unexplained family history of SCD.
Genetic Screening Utica, NY
• Brugada Syndrome• Familial Atrial Fibrillation • Catecholamine-sensitive VT• Non-ischemia VT/VF in young • Post-MI QT prolongation and TdP• Progressive Conduction Disease• Sudden death in infants & children(including SIDS)
• Acquired Long QT Syndrome (or unusual forms of congenital LQTS)
• Short QT syndrome
Inherited Cardiac Arrhythmias and Sudden Cardiac Death
• Molecular Genetics• Molecular Biology• Electrophysiology
Molecular Genetics Wing
Risk Stratification of Patients with Early Repolarization Pattern
Who is at risk?1) J point or ST segment elevation of 0.2 mV or greater in
inferior and infero-lateral or global leads. 2) Appearance of distinct and prominent J waves.3) Association of ER pattern with abbreviated QT intervals.4) Short-coupled extrasystoles5) Transient J wave augmentation or fluctuation of J wave
portends a high risk for VF in patients with ER.6) Association with Horizontal or Descending ST segment7) Association of ER pattern with SCD, Unexplained
syncope, or unexplained family history of SCD.
Who is at risk?1) J point or ST segment elevation of 0.2 mV or greater in
inferior and infero-lateral or global leads. 2) Appearance of distinct and prominent J waves.3) Association of ER pattern with abbreviated QT intervals.4) Short-coupled extrasystoles5) Transient J wave augmentation or fluctuation of J wave
portends a high risk for VF in patients with ER.6) Association with Horizontal or Descending ST segment7) Association of ER pattern with SCD, Unexplained
syncope, or unexplained family history of SCD.
Action Potential StudiesSilvio LitovskyAnton LukasS. Krishnan
Action Potential StudiesSilvio LitovskyAnton LukasS. Krishnan
Voltage Clamp StudiesAndrew ZygmuntJonathan CordeiroHelen Diana (Dan Hu)Hector Barajas-MartinezJanire UrrutiaYoshiyasu Aizawa
Voltage Clamp StudiesAndrew ZygmuntJonathan CordeiroHelen Diana (Dan Hu)Hector Barajas-MartinezJanire UrrutiaYoshiyasu Aizawa
Perfused Wedge StudiesGan-Xin YanSerge SicouriWataru ShimizuJose Di DiegoA. BurashnikovJeffrey FishGi-Byoung NamTetsuro EmoriMasahiko KondoMasato TsuboiFabrice ExtramianaChinmay PatelEyal NofYoshino MinouraIstván Koncz
Perfused Wedge StudiesGan-Xin YanSerge SicouriWataru ShimizuJose Di DiegoA. BurashnikovJeffrey FishGi-Byoung NamTetsuro EmoriMasahiko KondoMasato TsuboiFabrice ExtramianaChinmay PatelEyal NofYoshino MinouraIstván Koncz
In Vivo and Modeling StudiesVladislav V. Nesterenko
In Vivo and Modeling StudiesVladislav V. Nesterenko
Stem Cell & Molecular BiologyXavier Michael JesudossBobby Cherian KallukalamYuesheng WuMayurika DesaiJackie Treat
Stem Cell & Molecular BiologyXavier Michael JesudossBobby Cherian KallukalamYuesheng WuMayurika DesaiJackie Treat
CollaboratorsSami Viskin, Michel Haissaguerre, Mel Scheinman, Arthur Wilde, Andras Varro, Michael
Glickson, Michael Eldar, Liron Miler, Michael Ackerman, Minoru Horie, Jon Steinberg, Pedro, Josep & Ramon Brugada, Wee Nademanee, Fiorenzo Gaita, Carla Giustetto, Martin
Borggrefe,, Peter Schwartz, Lia Crotti, Michael Sanguinetti, Mike Ackerman, Christian Wolpert, Rainer Schimpf, Christian Veltmann, Michael Sanguinetti, Lior Gepstein
CollaboratorsSami Viskin, Michel Haissaguerre, Mel Scheinman, Arthur Wilde, Andras Varro, Michael
Glickson, Michael Eldar, Liron Miler, Michael Ackerman, Minoru Horie, Jon Steinberg, Pedro, Josep & Ramon Brugada, Wee Nademanee, Fiorenzo Gaita, Carla Giustetto, Martin
Borggrefe,, Peter Schwartz, Lia Crotti, Michael Sanguinetti, Mike Ackerman, Christian Wolpert, Rainer Schimpf, Christian Veltmann, Michael Sanguinetti, Lior Gepstein
Molecular GeneticsGuido PollevickAlejandra GuerchicoffRyan PfeifferElena BurashnikovGabriel CaceresColleen Puleo
Molecular GeneticsGuido PollevickAlejandra GuerchicoffRyan PfeifferElena BurashnikovGabriel CaceresColleen Puleo