Disclosure Statement Honorarium & Consultation Medtronic Inc. - - PDF document

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Koonlawee Nademanee, M.D, FHRS, FACC, FAHA, CCDS. Distinguished Professor of Medicine Chulalongkorn University, Thailand & Bumrungrad Hospital, Thailand Pacific Rim Research Institute in Los Angeles & Bangkok, Thailand

Disclosure Statement

• Honorarium & Consultation

Medtronic Inc. Biosense Webster Inc.

• Research Fundings.

Medtronic Inc. Biosense Webster Inc.

• Royalty

Biosense Webster Inc

Funding Sources

• Thai National Research Council .
• CAPRE (Cardiac Arrest Prevention Research and Education)

Foundation of Thailand.

• Grant-in Aid from Adventist Health Care at White Memorial

Medical Center, Los Angeles.

• Biosense-Cordis Webster, Inc.
• Grant-in-Aid Bumrungrad Hospital
• Grant-in-Aid Bangkok Medical center & Vejdusit Foundation

Bangkok Thailand.

• Grant-in-Aid Medtronic, Inc

SGUL-London

• Elijah Behr
• Magdi Saba

Netherlands

• Arthur Wilde
• Pieter
• Japp Jan Smit

Thailand

• Gumpanart Veerakul
• Apichai Khongphatthanayothin
• Montawatt Amnueypol
• Tachapong Ngarmukos

Japan

• Akihigo Nogami
• Hiroshi Nakagawa

Others

• USA
• Vietnam (Tuan

Nguyen Xuan)

• Burma
• Cambodia

Bordeux

• Michel Haïssaguerre
• Meleze Hocini
• Frederic Sacher

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Discussion Outlines

• Underlying Electrophysiologic mechanisms
• Evidence of depolarization abnormality
• Brugada Syndrome substrates
• Characteristics and Pathology of the

Substrates.

• Ablation of the substrates.
• Combined BrS and ER syndrome
• A World-Wide Brugada Ablation of VF Substrate Ongoing

Multicenter (BRAVO) Registry

Brugada Syndrome: Underlying Electrophysiologic Mechanisms

• Repolarization disorder.
• Depolarization Disorder,

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Intrinsic Heterogeneity

Accentuate Notch & Cause Loss of APD Dome in Epicardium

Dispersion of Repolarization Transmural Epicardial QT interval Phase 2 reentry ST Segment

(Vulnerable Window)

Extrasystole VT/VF

(Reentry)

Brugada Syndrome

INa, ICa Ito, IKr, IKs, IK-ATP, ICl(Ca) Transmural Dispersion of Repolarization Phase 2 Reentry in RV Epicardium

Phase 2 Reentry- induced VT/VF Epi 1 Epi 2 ECG

500 msec 50 mV 50 mV 0.5 mV

50 mV 200 msec 4 3 2 1

200 msec 50 mV

Epi M Endo

4 3 2 1

Section of RVOT myocardium, showing prominent fatty infiltration

Area of RVOT myocardium, showing interstitial fibrosis (red) in addition to slight fatty infiltration Ruben et al. Circulation 2005;112;2769-2777

Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation 2011; 123: 1270-1279. Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, Likittanasombat K, Bhuripanyo K, Ngarmukos T .

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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.

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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.

Fractionated electrogram de Bakker J M , and Wittkampf F H Circ Arrhythm Electrophysiol. 2010;3:204-213

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, ** Akihiko Nogami, MD, Marry N. Sheppard,MD, Gumpanart Veeakul, MD, Elijah R. Behr, MD

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Reduced Cx43 Expression

Control BrS

vs

Open Heart Epicardial Ablation

** Biopsy site

* *

Epicardial Fibrosis

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Interstitial, Epicardial and Focal Replacement Fibrosis

ECG Changes

Pre-Ablation Post-Ablation Post-Ablation- Ajmaline ** Epicardial Biopsy

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Overlapping Cardiomyopathy & Arrhythmia Phenotype

• Is BrS a subclinical cardiomyopathic disease
• r ionchannelopathy or both?
• A generalized disease of:
• Myocardial architecture
• Myocyte electrical coupling
• Predilection for severity in RVOT

Mechanism of conduction abnormalities ? Conduction hypothesis

• Zigzag conduction (increased distance)
• Reduced electrical coupling
• Reduced excitability
• Current-to-load mismatch

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CB CB CB 320 ms 390 ms 230 ms 120 ms 150 ms CB

Normal excitability Re-entry after INa reduction

Arrhythmias in conduction hypothesis

Subepicardium

A 52 year old Thai male who had out of hospital cardiac arrests. ICD was implanted with sporadic ICD discharged for occasional VF episodes. 10 Years after index events, he experienced an ICD storm due to recurrent VF episodes

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CardioInsightWorkflow WORKFLOW STEPS AND PRACTICAL CONSIDERATIONS

Place the sensor vest on patient CT Scan to define heart- torso geometry Record VF data in EP lab

• Induce VF & record

using CIT system 37 z Introduction: CardioInsight | Confidential

15 min

Create and display 3D electro- anatomical maps Manual heart and vest segmentation

▪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

15 min 30 min 5-30 min

2 min per single beat map

2

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2

Propagation movie

Figure-of-eight at RVOT Septal focal

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Conclusions

• In vivo evidence in BrS
• Normal imaging BUT:

Epicardial conduction delay Correlation with, interstitial and focal fibrosis Ablation abolishes type 1 pattern and VF

Strongest data yet to support depolarization hypothesis

Baseline Ajmaline

BrS Substrates are Expansive

• Abnormal low-voltage late potential

fractionated signals:

– Not exclusively over anterior RVOT epicardium but also commonly present in the RV body and inferolateral aspect

• f the RV epicardium

How & When To Ablate Brugada Substrate

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When to Ablate BrS Substrates:

HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndrome

Class IIb

• Quinidine may be considered in asymptomatic patients with a

diagnosis of BrS with a spontaneous type 1 ECG.

• Catheter ablation may be considered in patients with a

diagnosis ofBrS and history of arrhythmic storms or repeated appropriate ICD shocks.

How to Ablate BrS Substrates

• 1. Detail Epicardial and Endocardial mapping.
• 2. Use of Sodium Channel blockade to enhance the

BrS substrates.

• Ajmaline, Procainamide, Flecainide,

pilsicainide.

• Warm saline

New Ablation End Points

Primary End Point:

❖Elimination of all abnormal late-fractionated electrograms.

Secondary End Point:

❖ Non – inducible VT/VF. ❖ Normalization of the BrS ECG pattern.

How to Ablate BrS Substrates

• 1. Detail Epicardial and Endocardial mapping.
• 2. Use of Sodium Channel blockade to enhance the

BrS substrates.

• Ajmaline, Procainamide, Flecainide,

pilsicainide.

• Warm saline

3 Use of saline-irrigated tip catheter, preferably with contact sensor

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VDO ไฟล์ไม่ขึ้น

BrS Treatment Options

• ICD.
• Quinidine.
• Ablation

Brugada J, Papone C Cir Arrhyth Electrophysiology 2015

Increase in Ablation Treatment For BrS

Study N Age/ Male (%) Spont- BrS ECG History of VT/VF episodes (%) SCN5A (%) ICD (%) 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 Several Case reports 12 30-40 100% 100% NA 100%

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ERS

YS

A 33 years old male with a history of aborted sudden cardiac death with multiple ICD discharges: (BH 7)

Co-Localizing of VF Drivers and abnormal Fractionated EGM

9/14/2019 16 Co-Localizing of VF Drivers and abnormal Fractionated EGM

Distribution of VF Substrates

100% 21% 21% 2 %

A World-Wide Brugada Ablation of VF Substrate Ongoing Multicenter (BRAVO) Registry

• 106 BrS with ICD (median age =38; 1 Female)
• 90 cardiac arrest survivors
• 16 Syncope
• 98 Percutaneous epicardial ablations.
• 8 Open thoracotomy ablation

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106 Symptomatic BrS 79 Brugada ECG pattern only 73 Normalized EKG All had no VF recurrence (100%) 6 Brugada ECG presence 3 VF recurrence (50%) 27 Brugada + ER Pattern 19 BrS EKG normalized 3 VF recurrence (16%) 8 BrS or ER presence 5 VF recurrence (63%)

* * *

* Repeat ablations

1st Ablation

Outcomes of Ablations: BRAVO (N = 106; follow-up period = 39 ±30 months)

> 10 VF- shocks 5-9 VF- shocks 1-4 VF- shocks 0 VF- shocks Pre-ablation 39 22 33 12 (11%) After 1ST ablation 1 18 87 (82%) After last ablation (mean 1.2± 0.6) 4 102 (96%)

Conclusion

Patients with a pure Brugada syndrome without concomitant Early repolarization syndrome who has normal EKG after catheter ablation of the BrS substrates, especially after sodium channel blockade could possibly be treated without ICD.

Curing Brugada Syndrome? Key Questions

• Do we understand the substrates and underlying

electrophysiologic mechanisms?

• Substrate change over a period of time?
• Effects of Ablation?
• How does one know that durable and permanent lesions

have been achieved?

• No residual substrates left behind?
• Can ablation cause another arrhythmogenic site?

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Ultimate Questions

If the Brugada ECG pattern in BrS patients is completely eliminated by ablations, do they then have no more risk of VF occurrence or sudden cardiac death and do not need ICD?

BRAVE STUDY DESIGN