Disclosure Statement Honorarium & Consultation Medtronic Inc. - PDF document

9/14/2019 Disclosure Statement • Honorarium & Consultation Medtronic Inc. Biosense Webster Inc. • Research Fundings. Medtronic Inc. Biosense Webster Inc. Koonlawee Nademanee, M.D, FHRS, FACC, FAHA, CCDS. Distinguished Professor of Medicine • Royalty Chulalongkorn University, Thailand & Bumrungrad Hospital, Thailand Biosense Webster Inc Pacific Rim Research Institute in Los Angeles & Bangkok, Thailand Funding Sources • Thai National Research Council . SGUL-London Thailand Bordeux • CAPRE (Cardiac Arrest Prevention Research and Education) • Gumpanart Veerakul Foundation of Thailand. • Apichai Khongphatthanayothin • Michel Haïssaguerre • Elijah Behr • Grant-in Aid from Adventist Health Care at White Memorial • Montawatt Amnueypol • Meleze Hocini • Magdi Saba • Tachapong Ngarmukos • Frederic Sacher Medical Center, Los Angeles. • Biosense-Cordis Webster, Inc. Netherlands Japan Others • Grant-in-Aid Bumrungrad Hospital • USA • Akihigo Nogami • Grant-in-Aid Bangkok Medical center & Vejdusit Foundation • Arthur Wilde • Vietnam (Tuan • Hiroshi Nakagawa • Pieter Nguyen Xuan) Bangkok Thailand. • Japp Jan Smit • Burma • Grant-in-Aid Medtronic, Inc • Cambodia 1

9/14/2019 Brugada Syndrome: Underlying Discussion Outlines Electrophysiologic Mechanisms • Underlying Electrophysiologic mechanisms -Evidence of depolarization abnormality • Repolarization disorder. • Brugada Syndrome substrates - Characteristics and Pathology of the Substrates. - Ablation of the substrates. • Depolarization Disorder, • Combined BrS and ER syndrome • A World-Wide Br ugada A blation of V F Substrate O ngoing Multicenter (BRAVO) Registry 2

9/14/2019 Brugada Syndrome Intrinsic Epi M Endo 0 0 0 Heterogeneity 50 mV I Na, I Ca Accentuate Notch & Cause Loss of APD I to , I Kr , I Ks, I K-ATP , Dome in 200 msec I Cl(Ca) Epicardium Dispersion of Repolarization 0 4 3 1 2 Transmural 4 Transmural Epicardial Dispersion of 0 Repolarization 3 Phase 2 Reentry 0 in RV QT interval Phase 2 reentry 2 Epicardium 0 50 Phase 2 Reentry- mV ST Segment induced VT/VF 1 200 msec (Vulnerable Window) Epi 1 50 mV Extrasystole 50 Epi 2 mV 0.5 ECG mV VT/VF 500 msec (Reentry) Area of RVOT myocardium, showing Section of RVOT myocardium, interstitial fibrosis (red) in showing prominent fatty addition to slight fatty Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over infiltration the anterior right ventricular outflow tract epicardium. Circulation 2011; 123: 1270-1279. infiltration Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, Likittanasombat K, Bhuripanyo K, Ngarmukos T . Ruben et al. Circulation 2005;112;2769-2777 3

9/14/2019 Nademanee et al. Circulation; 2011; 123; 1270-1279 Nademanee et al. Circulation; 2011; 123; 1270-1279 Summary • Abnormal delayed depolarization – Identified exclusively over anterior RVOT epicardium. – Characterized by abnormal prolonged fractionated late potentials. • Catheter ablation over this area of abnormal potentials. – Normalization of the Brugada ECG pattern – Preventing VT/VF episodes, both spontaneously occurring or induced via PES. 4

9/14/2019 Summary • Abnormal delayed depolarization – Identified exclusively over anterior RVOT epicardium. – Characterized by abnormal prolonged fractionated late potentials. • Catheter ablation over this area of abnormal potentials. – Normalization of the Brugada ECG pattern – Preventing VT/VF episodes, both spontaneously occurring or induced via PES. J Am Coll Cardiol 2015;66:1976 – 86 Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome Koonlawee Nademanee, MD,* Hariharan Raju, PHD, Sofia V. De Noronha, PHD, Michael Papadakis, MD, Lanurence Robinson, MBBS, Stephen Rothery, BSc, Naomasa Makita, MD, Shinya Kowase, MD, Nakorn Boonmee, MD, Vorapot Vitayakritsirikul, MD, Samrerng Ratanarapee, MD, Sanjay Sharma, MD, Allard C. Van der Wal, MD, ** Michael Christiansen, MD, Hanno L. Tan, MD, ** Arthur A. Wilde, MD, ** Fractionated Akihiko Nogami, MD, Marry N. Sheppard,MD, Gumpanart Veeakul, MD, Elijah R. Behr, MD electrogram de Bakker J M , and Wittkampf F H Circ Arrhythm Electrophysiol. 2010;3:204-213 5

9/14/2019 Reduced Cx43 Expression Open Heart Epicardial Ablation vs Control BrS Epicardial Fibrosis * * ** Biopsy site 6

9/14/2019 ECG Changes Interstitial, Epicardial and Focal Replacement Fibrosis Post-Ablation- Pre-Ablation Post-Ablation Ajmaline ** Epicardial Biopsy 7

9/14/2019 Overlapping Cardiomyopathy & Arrhythmia Conduction hypothesis Phenotype • Is BrS a subclinical cardiomyopathic disease Mechanism of conduction abnormalities ? or ionchannelopathy or both? • Zigzag conduction (increased distance) • A generalized disease of: • Reduced electrical coupling - Myocardial architecture -Myocyte electrical coupling • Reduced excitability -Predilection for severity in RVOT • Current-to-load mismatch 8

9/14/2019 320 ms 390 ms 230 ms CB 120 ms 150 ms CB CB CB A 52 year old Thai male who had out of hospital cardiac arrests. ICD was Arrhythmias in conduction hypothesis implanted with sporadic ICD discharged for occasional VF episodes. 10 Years after index events, he experienced an ICD storm due to recurrent VF episodes Normal excitability Subepicardium Re-entry after INa reduction 9

9/14/2019 CardioInsight Workflow WORKFLOW STEPS AND PRACTICAL CONSIDERATIONS Record VF data in EP lab • Induce VF & record Place the sensor vest on CT Scan to define heart- Manual heart and vest Create and display 3D electro- using CIT system patient torso geometry segmentation anatomical maps 2 min per single beat 15 min 15 min 30 min 5-30 min map ▪ CIT personnel will place vest and operate system ▪ Entire workflow (including CT) must be done on same day ▪ CT scan (attached) ▪ Field of view (FOV) includes the entire patient torso ▪ Requires saving DICOM images to CD or USB stick ▪ Navigation patches underneath vest could decrease mapping resolution 37 Introduction: CardioInsight | Confidential z 2 10

9/14/2019 Propagation movie 2 Septal focal Figure-of-eight at RVOT 11

9/14/2019 Conclusions Baseline Ajmaline • In vivo evidence in BrS • Normal imaging BUT: Strongest data yet to support depolarization hypothesis Epicardial conduction delay Correlation with, interstitial and focal fibrosis Ablation abolishes type 1 pattern and VF BrS Substrates are Expansive • Abnormal low-voltage late potential How & When fractionated signals: To – Not exclusively over anterior RVOT Ablate Brugada Substrate epicardium but also commonly present in the RV body and inferolateral aspect of the RV epicardium 12

9/14/2019 When to Ablate BrS Substrates: How to Ablate BrS Substrates HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndrome 1. Detail Epicardial and Endocardial mapping. Class IIb 2. Use of Sodium Channel blockade to enhance the • Quinidine may be considered in asymptomatic patients with a BrS substrates. diagnosis of BrS with a spontaneous type 1 ECG. - Ajmaline, Procainamide, Flecainide, pilsicainide. • Catheter ablation may be considered in patients with a - Warm saline diagnosis ofBrS and history of arrhythmic storms or repeated appropriate ICD shocks. New Ablation End Points How to Ablate BrS Substrates Primary End Point: 1. Detail Epicardial and Endocardial mapping. ❖ Elimination of all abnormal late-fractionated electrograms. 2. Use of Sodium Channel blockade to enhance the BrS substrates. Secondary End Point: - Ajmaline, Procainamide, Flecainide, pilsicainide. - Warm saline ❖ Non – inducible VT/VF. 3 Use of saline-irrigated tip catheter, preferably with ❖ Normalization of the BrS ECG pattern. contact sensor 13

9/14/2019 BrS Treatment Options • ICD. VDO • Quinidine. ไฟล์ไม่ขึ้น • Ablation Increase in Ablation Treatment For BrS Brugada J, Papone C Cir Arrhyth Electrophysiology 2015 Study N Age/ Male (%) Spont- History of VT/VF SCN5A ICD BrS ECG episodes (%) (%) (%) Nademanee 60 34 (100%) (75%) 100% 10% 100% Papone et al 135 39 (78%) (23%) 47% 24% 100% Zhang et al 11 48 (100%) 82% 100% 40% 73% Chung et al 15 41 (100%) 53% 100% 20% Combined 12 30-40 100% 100% NA 100% Several Case reports 14

9/14/2019 A 33 years old male with a history of aborted sudden cardiac death with multiple ICD discharges: (BH 7) BrS ERS YS Co-Localizing of VF Drivers and abnormal Fractionated EGM 15

9/14/2019 Co-Localizing of VF Drivers and abnormal Fractionated EGM A World-Wide Br ugada A blation of V F Substrate Distribution of VF Substrates O ngoing Multicenter (BRAVO) Registry • 106 BrS with ICD (median age =38; 1 Female) 100% 2 - 90 cardiac arrest survivors 21% % 21% - 16 Syncope • 98 Percutaneous epicardial ablations. • 8 Open thoracotomy ablation 16