Disclosure LARIAT Update SentreHeart, Inc Consultant Equity holder - - PDF document

8/11/2016 1

LARIAT Update Disclosure

SentreHeart, Inc

• Consultant
• Equity holder

Catheter - Based Surgery

• Open Chest
• Cardiopulmonary Bypass
• Technique Variability Closure
• Performed with another open

procedure

• Percutaneous & Image Guided
• Immediate, Complete, Permanent
• Training Required on New Techniques

Performed in OR Performed in cath lab

Restore Maintain Protect

Electrical Isolation LAA Exclusion

Merits of an Epicardial LAA Closure Approach

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LARIAT System

EndoCATH

Occlusion Balloon

FindrWIRZ LARIAT

Suture Delivery Device

TM TM TM

Left Atrium Left Atrial Appendage

Percutaneous, epicardial placement of pre‐tied suture loop

LAA ligation with the LARIAT Suture Delivery Device

Pre CT 45D Post CT

LAA No LAA

LAA ligation results in a permanent LAA closure

LA LAA

Bartus et al., Circ AE 7:764-767, 2014

Time to TEE follow‐up 1y 96d+77d 45d+15d 1yr 1yr Closure 64/65 17/17 22/22 230/259 449/480 98% 100% 100% 89% 94% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Bartus Massumi Stone Pillarsetti Lakkireddy

% Closure

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Percentage of Leaks in Watchman and LARIAT LAA Closures

Pillarisetti et al., Heart Rhythm 2015

Leak After LARIAT

Soni et al., JACC Cardiovascular Interventions 2015

Treatment of Leak

Soni et al., JACC Cardiovascular Interventions 2015 0% 2% 4% 6% 8% 10% 12% 14% 16% 18% 20% 1 2 3 4 5 6

CHADS2 score

Event Rate (% patient‐years)

CHADS2 score of the LARIAT Population

National Registry of AF Stroke rate National Registry of AF Stroke rate with ASA

6.2% Expected ER Observed ER: 1% Reduction of 80%

N=139 patients Mean F/U 2.9 +/- 1.1 years 405 patient-years

LAA ligation in patients with contraindications to OAC therapy

Sievert et al., JACC EP 2015

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A B

Kaplan-Meier Curves

Survival Stroke

Adverse Events

• Pulmonary embolus

1 (0.7%)

– Periprocedural death

• Cardiac Perforation

2 (1.4%)

– Surgery

• Late Hemopericardium

1 (0.7%)

• Late Pericardial effusion

1 (0.7%)

• Pericarditis (>2 days)

8 (5.8%)

• LA thrombus

2 (1.4%)

Adverse Events Requiring Intervention (3.6%) Additional Adverse Events (8.6%)

Watchman

Reddy et al JACC 2013

ACP

Tzikas et al EuroIntervention 2015

LARIAT

Sievert et al JACC EP 2015

Number of patients 150 1,047 139 Age 72.5 7.4 75±8 67±11 Mean CHADs2 score 2.8 1.2 4.43 2.4 +1.2 Mean follow-up 14.4 + 8.6 months, 13 months 35 + 12 months Patient-years 176.9 1,349 401 Absolute # strokes/systemic embolism 4 (stroke) 9 (strokes), 9 (TIA) 31 (systemic embolism) 4 (strokes) Event rate (patient- years) 2.3% 0.7% stroke 0.7% TIA 2.3% systemic embolism 1%

LAA closure in patients with contraindication to OAC therapy

Next Generation LARIAT +

Snare width increased from 40mm to 45mm

• Allows treatment of patients with

LAAs > 40mm

Stainless Steel Wire Braid on Catheter Shaft Improved “torque‐ability” of catheter

“L” Marker Platinum‐Iridium “L” Marker

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Procedural Improvements

• Use of micro-puncture needle for pericardial

access

• Post-procedural use of colchicine

Acute & Longterm Outcomes of Percutaneous Left Atrial Appendage Suture Ligation: Results From A United States Multicenter Evaluation

• D. Lakkireddy MD, M. Afzal MD, R. Lee, MD PhD, H. Nagaraj MD, D Tschopp MD, B Gidney MD, C. Ellis

MD,E. Altman MD, B Lee MD, S Kar MD, N. Bhadwar MD, M Sanchez MD, V Gadiyarum MD, R. Evonich MD, A. Rasekh MD, J. Cheng MD, F. Cuoco, S. Chandok MD, S.Gunda MD, M. Reddy MD, P. Cuculich MD,

• A. D. Gibson MD, J Nath MD, R. Ferrelll MD, E. Matthew MD, D. Wilber MD

Lakkireddy et al. Heart Rhythm13:1030–1036, 2016

0.2% 0.2% 0.7% 0.5% 0.0% 0.5% 2.0%

0.0% 1.0% 2.0% 3.0% 4.0% 5.0% 6.0% Procedural Related Mortality Pts requiring surgery Cardiac Perfs (no surgery) Pts needing transfusion Peri‐procedural stroke Structural Injury All Complications

Acute & Longterm Outcomes with LARIAT

Lakkireddy et al., Heart Rhythm 2016

2.7% 1.2% 4.5% 8.4%

0.5% 0.0% 1.0% 1.5% 0.0% 1.0% 2.0% 3.0% 4.0% 5.0% 6.0% 7.0% 8.0% 9.0%

Pericarditis w >2wks w NSAIDs Late peri effusion Late pleural effusion Total

Acute & Longterm Outcomes of LARIAT

No Colchicine n=332 W/ Colchicine n=380

Colchicine versus No-Colchicine

Lakkireddy et al., Heart Rhythm 2016

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• 85 of 85 patients underwent successful completion of the LARIAT+

procedure.

• 83 of 85 (98%) patients with acute complete LAA closure.
• One serious adverse event due to a RV perforation due to a sheath.
• 89% LAA closure at 3 months

Tilz Europace 2015 Tilz RR1, Foran J2, Bartus K3, Gafoor S4, Wong T2, Rillig A1, Fink T1, Lin T1, Myc J2, Lee R5, Sievert H4, Karl‐Heinz Kuck

1AK St. Georg, Hamburg 2Royal Brompton, London, England 3Department of Cardiovascular Surgery and Transplantology, Jagiellonian University, John Paul II Hospital in Krakow, Krakow,

Poland

4CardioVascular Center Frankfurt

Initial European Experience with a novel percutaneous epicardial suture delivery device for LAA exclusion

LARIATRS

(Retractable Snare)

Enables complete retraction of snare post suture deployment and tightening

• Ease of use during removal of LARIAT
• Minimal manipulation of suture that

may lead to reduced leaks (Current complete closure success rate >93%)

• Broader LAA anatomic compatibility, ie

reverse “C”s

FDA and CE mark clearances in place

LAA Isolation Improves Ablation Outcomes

Left Atrial Appendage : An Underrecognized Trigger Site of Atrial Fibrillation

Di Biase et al., Circulation. 2010;122:109-118

Texas Cardiac Center, San Francisco, California, USA; University of KaArrhythmia Institute at St. David’s Medical Center, Austin, Texas, USA; California Pacific Medical nsas, Kansas City, USA; Cardiac Arrhythmia Research Centre, Centro Cardiologico Monzino IRCCS, Milan, Italy;

Effect of Empirical Left Atrial Appendage Isolation on Long- term Procedure Outcome in Patients with Long-standing Persistent AF undergoing Ablation: Results from the BELIEF Randomized Trial ClinicalTrials.gov Identifier: NCT01362738

Luigi Di Biase, J. David Burkhardt, MD, Prasant Mohanty, Sanghamitra Mohanty, , Javier E. Sanchez, Chintan Trivedi, Mahmut Güneş, Yalçın Gökoğlan, Carola Gianni, Rodney P. Horton,

• G. Joseph Gallinghouse, Shane Bailey, Jason D. Zagrodzky,

Steven C. Hao, Richard H. Hongo, Salwa Beheiry, Pasquale Santangeli, Michela Casella, Antonio Dello Russo, Amin Al-Ahmad, Patrick Hranitzky, Dhanujaya R. Lakkireddy, Claudio Tondo, Andrea Natale.

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AIM

Assess whether in patients with Long Standing Persistent AF the EMPIRICAL ELECTRICAL ISOLATION of the left atrial appendage (LAA) in addition to extensive PV antrum and triggers ablation could improve freedom from AF/AT at follow up in a in a multicenter randomized trial.

Di Biase, Natale et al, LBT ESC 2015

Kaplan–Meier curves: single procedure success rate

At the 12 month follow-up, 48(56%) in group 1 and 25 (28%) in group 2 were recurrence-free off-AAD after a single procedure. (Log-rank p=0.001, unadjusted HR 1.92 [1.3 to 2.9]).

Di Biase, Natale et al, LBT ESC 2015

Cumulative Overall Success After 1.3 Procedures

The cumulative success after multiple procedures was 65 (76%) in group 1 and 49 (56%) in group 2 ALL THE PATIENTS UNDERWENT LAA ISOLATION (Log-rank p= 0.003, unadjusted HR 2.24 [95% CI 1.3-3.8])

Di Biase, Natale et al, LBT ESC 2015

Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation after Electrical Isolation of the Left Atrial Appendage for Treatment of Atrial Tachyarrhythmias: An undescribed and under recognized complication of left atrial catheter ablation

Andreas Rillig , MD, Roland R. Tilz, MD, Tina Lin, MD, Christian Heeger, MD, Anita Arya, PHD, Andreas Metzner, MD, Shibu Mathew, MD, Erik Wissner, MD, Hisaki Makimoto, MD, PHD, Peter Wohlmuth, Karl- Heinz Kuck, MD, Feifan Ouyang, MD

LAA thrombus

Mechanical standstill Thrombus formation

LAA thrombus in 21%, and three patients had a stroke while on OAC

Rillig et al., Circ EP 2016 (in press)

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Sick et al., JACC 2007

When should you exclude the LAA: Before or After PVI?

Feasibility and Safety of Combined PVI and LAA closure

Ablation for Atrial Fibrillation in Combination With Left Atrial Appendage Closure: First Results of a Feasibility Study

Martin J. Swaans, MD; Martijn C. Post, MD, PhD; Benno J.W.M. Rensing, MD, PhD; Lucas V.A. Boersma, MD, PhD J Am Heart Assoc. 2012

Combined catheter ablation and left atrial appendage closure as a hybrid procedure for the treatment of atrial fibrillation

Calvo N, Salterain N, Arguedas H, Macias A, Esteban A, García de Yébenes M1, Gavira JJ, Barba J, García-Bolao I. Europace 2015

Does left atrial appendage closure improve the success of pulmonary vein isolation? Results

• f a randomized clinical trial

Alexander Romanov, Evgeny Pokushalov, Sergey Artemenko, Akmal Yakubov, Ilya Stenin, Evgeny Kretov, Oleg Krestianinov, Igor Grazhdankin, Dejan Risteski, Alexander Karaskov, Jonathan S. Steinberg J Interv Card Electrophysiol 44:9-16, 2015 Sick et al., JACC 2007

PVI and LAA electrical isolation should be done before LAA closure with an LAA implant

*

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AF ablation post LAA closure

Patient (#) LAA-closure device (size) Time from LAA- closure to LA- ablation (days) PAF/PersAF Previous LA- ablation Index procedure Follow-up: Device related complications assessed by TEE (days) Follow-up: AT/AF-recurrence (longest follow-up, days) Follow-up: Clinical complications 1 ACP (22mm) 234 PAF

• CPVI

0 (759) 0 (622) 2 WATCHMAN (33mm) 182 PAF CPVI CPVI 0 (778) 1 (778) 3 WATCHMAN (21mm) 133 PAF

• CPVI

0 (464) 0 (466) 4 WATCHMAN (24mm) 105 PersAF CPVI Ablation of anterior line, ostial potentials and mitral isthmus line 0 (504) 0 (400) 5 WATCHMAN (24mm) 41 PAF

• CPVI

0 (187) 0 (188) 6 WATCHMAN (27mm) 92 PAF

• CPVI

Ablation of an anterior line 0 (218) 1 (218) 7 WATCHMAN (27mm) 756 PersAF CPVI and LAA- isolation via ablation

• f anterior and mitral

isthmus line Re-isolation of LAA via mitral isthmus line 0 (1006) 0 (1006) 8 WATCHMAN (27mm) 63 PersAF

• CPVI

Ablation of CFAEs in CS and LA, anterior line and mitral isthmus line Thrombus (113) 1 (673)

Heeger, ...Tilz, Heart Rhythm, accepted for publication

C D

LA WATCHMAN AV LA WATCHMAN AV Thrombu s

CTA of Watchman device

Courtesy of VJ Swarup

LAA Ligation of the LAA

The Effects of LAA Ligation on LAA Electrical Activity

Frederick T. Han M.D.*1, Krzysztof Bartus M.D., Ph.D.* 2, Dhanunjaya Lakkireddy, MD3, Francia Rojas, MD4, Jacek Bednarek, M.D., Ph.D.5, Boguslaw Kapelak, M.D., Ph.D.2, Magdalena Bartus Ph.D. 6, Nitish Badhwar M.B.B.S., FHRS7, Mathew Earnest, MD3, Miguel Valderrabano, M.D4, Randall J. Lee M.D., Ph.D7,8,9,

N = 30 N = 38

Han et al., Heart Rhythm 11:864–870, 2014

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Effect of Endoepicardial Percutaneous Left Atrial Appendage Ligation on Arrhythmia Burden in Patients with Atrial Fibrillation

Afzal et al., Heart Rhythm 2015

Sequential Percutaneous LAA ligation and pulmonary vein isolation in patients with persistent AF: Initial results of a feasibility study

Nitish Badhwar, Dhanunjaya Lakkireddy, Mitsuharu Kawamura, Frederick T. Han, Sivaraman K. Iyer, Brian S. Moyers, Thomas A. Dewland, Chris Woods, Ryan Ferrell, Jayanth Nath, Mathew Earnes, Randall J. Lee

Conversion of Persistent Atrial Fibrillation to Sinus Rhythm After LAA Ligation

Badhwar et al., HRS abstract 2015 Courtesy of David Wilbur

LAA-LA Registry

0% 10% 20% 30% 40% 50% 60% 70% LARIAT + Ablation Ablation Only Total

Recurrence Rate

Lakkireddy, et al.

24/69 42/69 66/13 8

*JACC EP: 2015

• 69 consecutive patients undergoing LAA

ligation with LARIAT system followed by AF ablation vs ablation only.

• Primary Outcome: Recurrence of AF @ 12M
• ff AAD

– Defined as recurring AF episodes >30 sec via 24hr holter monitor

• AF recurrence was lower in the LARIAT group

(35% vs 61% p=0.028) after the first ablation

• Fewer patients in the LARIAT group needed

repeat ablation (16% vs 33% p=0.018)

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Restore Maintain Protect

Role of LAA Ligation in Patients with AF

Electrical Isolation Atrial debulking LAA Exclusion