Disclosures St. Jude medical Honorarium Recipient Boston - PDF document

10/10/2015 Geonomic Arrhythmia Syndromes: ECG Recognition and Therapy Melvin Scheinman, MD Disclosures St. Jude medical Honorarium Recipient Boston scientific Honorarium Recipient Medtronick Honorarium Recipient Amgen Panel Member Biotronik Honorarium Recipient Tremura Honorarium Recipient Bio-Sence Webster Honorarium Recipient 1

10/10/2015 Genetics of Sudden Cardiac Death 1. Ion Channelopathy A. Long and Short QT syndromes, K + , Na + Ca ++ . B Brugada Na +, Ca ++ C Early Repolarization Syndromes D CPV T Ca ++ 2. Sarcomeric Protein Abnormalities (IHSS) ARVD intercellular connection abnormalities 3. IHSS 2

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10/10/2015 • CLINICAL EXPRESSION OF SODIUM CHANNEL ABNORMALITIES • • GAIN OF FUNCTION • • LONG QT SYNDROME (LQT3) • • LOSS OF FUNCTION • • BRUGADA SYNDROME • • IDIOPATHIC CARDIAC CONDUCTION DISEASE • CONGENITAL SINUS NODE DYSFUNCTION 4

10/10/2015 Brugada: Pathophysiology SCN5A Sodium Channel Predicted structure of SCN5A. Green: mutations causing Brugada syndrome Red: mutations causing long QT syndrome Major Genetic Abnormalities for LQTS Type Current Gene B Subunit Clinical features LQT1 Ik s KCNQ 1 MinK a) Sx with stress, especially swimming b) Responsive to beta-blockers,AICD seldom required LQT2 Ik r KCNH 2 MiRP1 a) Stress, auditory b) Partially responsive to beta-blockers LQT3 In a SCN5A a) Sx at rest b) Unresponsive to beta-blockers c) Higher mortality 5

10/10/2015 ECG Analyses for LQTS Use leads II, V 5 /V 6 avoid V 2 /V 3 1. 2. Average 3-5 beats 3. Stable rhythm 4. Bazett correction is not accurate for HR < 50 (under corrects) or > 90-100 (over corrects) 6

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10/10/2015 Diagnosis of Congenital LQS 1. QT prolongation and pattern of T wave 2. Response to epinephrine / exercise 3. Family screening Genetic testing – very valuable if positive 4. Wilde JACC 54:143 ‘ 09 8

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10/10/2015 Long-QT Syndrome in adults (Registry) LQT1 = 428 LQT2 = 302 LQT3 = 82 H.R. 1. Cardiac event prior to age 18 2.43 2. LQT1 > LQT2 2.27 3. Female gender 2.77 4. QTc > 500 10.07 5. Beta Blocker Rx 0.41 Source: JACC 49:329 ‘ 07 Treatment of LQTS 1.Beta blockers for all forms (LQT1,2,3) 2.Pacemaker/Defibrillator 3.Left Cervical sympathectomy 4.Mexilitine,Flecainide and Ranolazine for LQT3 5.Beta blockers for pregnancy especially LQT2 10

10/10/2015 BRUGADA SYNDROME • First described in 1992 in 8 patients with aborted sudden cardiac death • Characterized by: – ECG findings of RBBB and persistent ST segment elevation in V 1 -V 3 – Structurally normal hearts – Propensity for life threatening ventricular arrhythmias Brugada: Diagnosis ECG Findings 11

10/10/2015 ASYMPTOMATIC PROVOCABLE BY DRUGS AVOID SODIUM CHANNEL BLOCKERS/TREAT FEVER SYNCOPE/ABORTED SCD AICD DRUG THERAPY QUINIDINE AMINOPHYLLINE IV ISUPREL FOR VF STORM 12

10/10/2015 Definition of early repolarization: 1. Elevation of QRS-ST junction (J wave) in at least 1mm in 2 leads 2. Slurring of terminal QRS into the ST segment or notching 3. These findings were limited to inferior and/or lateral leads Haissaguerre NEJM May ’ 08 13

10/10/2015 ARVD(DEFINITION) • A DISEASE CHARACTERIZED BY FIBROFATTY REPLACEMENT OF THE FREE WALL OF THE RV • STRUCTURAL ABNORMALITIES PREDISPOSE TO VENTRICULAR ARRHYTHMIAS AND RISK FOR SUDDEN DEATH • APPEARS TO BE GENETICALLY TRANSMITTED IN @ 30%-50% 14

10/10/2015 Figure 1 Figure 1 Fibro-fatty tissue infiltration of the right ventricle free wall in a patient with ARVC/D. http://reference.findtarget.com/search/Arrhythmogenic%20right%20ventricular%20dysplasia/ Lombardi et al Ped Card 01/2011 15

10/10/2015 19 – 45 < 1% males < 3% females 19 – 45 Marcus, F. Am J Cardiol;95:1070 16

10/10/2015 ARVD Therapy 1. Beta blockers (Sotalol) 2. Amiodarone 3. Catheter ablation 4. AICD M S 17

10/10/2015 CPVT Treatment 1. Beta blockers (ineffective in 30%) 2. Beta blockers + Ca ++ channel blockers 3. Flecainide 4. AICD, Cervical Sympathectomy 5. Cardiac transplantation 18