Disclosure Left Atrial Appendage Closure SentreHeart, Inc - PDF document

10/1/16 Disclosure Left Atrial Appendage Closure – SentreHeart, Inc Identifying the Patients Who Will • Consultant Benefit the Most • Equity holder WARFARIN It’s Not the Answer Too little = Stroke Too much = Hemorrhage A cardiac disease that kills Risks increase with age by producing emboli Low compliance The most severe TARGET consequence of AF is Contraindications potentially life threatening INR 1 2 3 4 5 embolic events 1

10/1/16 Endocardial vs Pericardial LAA Closure Devices Available in Ease of Use No LA foreign body the US Atriclip LARIAT Watchman Watchman is FDA approved for stroke prevention Atriclip and LARIAT are FDA approved, but not for stroke prevention Closure Efficacy Complications WATCHMAN Clinical History PROTECT AF 4 Year: CV and All-Cause Mortality Watchman device was non-inferior to warfarin in PROTECT-AF preventing strokes; FDA concerned with acute safety 800 pts, 59 sites events CAP Registry Significantly improved safety results 566 pts, 26 sites PREVAIL Improved success and procedural safety confirmed with 400 pts, < 50 new and experienced operators sites Superior to warfarin for primary efficacy, CV death, and PROTECT-AF all-cause mortality at 4 years Long-term F/U Reddy, VY et al. JAMA. 2014; 312(19):1988-1998. In the US, WATCHMAN is an investigational device, limited by applicable law to investigational use only and not available forsale. CE Mark 2005 2

10/1/16 Watchman FDA Approval Watchman FDA Approval CONTRAINDICATIONS INDICATIONS FOR USE • Intracardiac thrombus is visualized by echocardiographic This device is indicated to reduce the risk of imaging. thromboembolism from the left atrial appendage (LAA) • An ASD repair or closure device or a PFO repair or closure in patients with non-valvular atrial fibrillation who: device is present. • The LAA anatomy will not accommodate a device Any of the • Are at increased risk for stroke and systemic embolism customary contraindications for other percutaneous based on CHADS2 or CHA2DS2-VASc scores and are catheterization procedures (e.g., patient size too small to recommended for anticoagulation therapy accommodate TEE probe or required catheters) or conditions • Are deemed by their physicians to be suitable for warfarin (e.g., active infection, bleeding disorder) are present. • Have an appropriate rationale to seek a non- • There are contraindications to the use of warfarin, aspirin, or pharmacologic alternative to warfarin, taking into account clopidogrel. the safety and effectiveness of the device compared to • The patient has a known hypersensitivity to any portion of the warfarin. device material or the individual components Dabigatran Rivaroxaban Apixaban Oral Anticoagulants Mechanism Direct Thrombin Factor Xa Inhibitor Factor Xa Inhibitor DISCONTINUATION RATES Inhibitor Dose 110 mg or 150 mg 2x/ 20 mg/day 5 mg 2x/ day day *2.5 mg 2x/day 25 NOAC Efficacy in Superior (150 mg) noninferior superior 20 preventing Noninferior (110 mg) Warfarin embolic events 15 Significantly less less less Hemorrhagic (110 mfg) stroke More (150 mg) 10 at GI bleeding Not specified Major GI bleeding less 5 (110mg) Epitaxis and hematuria 0 All bleeding Less (at 110 mg) less RE-LY ARISTOTLE ROCKET-AF events Similar (at 150mg) Dabigatran Apixaban Rivaroxaban *2.5 mg twice daily if two or more: age >80, weight <60 kg or Cr > 1.5 (25% renal excretion). NEJM 2009;361:1139-51 NEJM 2011;365:981-92 NEJM 2011;365:883-91 Excluded if Cr > 2.5 3

10/1/16 Patients with Limited to NO options Potential Incidence of Major Bleeding Anticoagulatant Annual Rate for *Potential number of Major Bleed patients >65 yo with major Patients with contraindications to OAC therapy bleeding/year (x1000) Dabigatran 3.32% 60.4 150 mg 2x/day • 82 year old woman with Rivaroxaban 3.6% 65.6 15 – 20 mg/day paroxsysmol AF Apixaban 2.13% 38.8 5 mg 2x/day • History of both ICH and Warfarin 3.09% - 3.57% 56.2 - 65.0 cardioembolic stroke, hypertension • TEE reveals LAA thrombus *Assumes 50% of AF patients treated with AF on OAC Wallentin, L., et al.,. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet, 2010, 376 (9745), 975-983. Patel, M. R., et al.. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 2011, 365 (10), 883-891. Granger, C.B., et al., Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med, 2011. 365 (11): p. 981-92. Ischemic Stroke : AF and previous Intracranial bleeding as contraindication for OAC (n=5,441) by CHADS 2 -VASC Stroke and Bleeding Risk in Patients Study population 20 Adjusted stroke rate in the general AF population (adapted from Lip et al. ‡) 18 with AF and OAC Contraindications 16 14 12 Bjorn Redfors, MD, PhD, William A. Gray, MD, Randall J. Lee MD, Kenneth A. Ellenbogen MD, 10 Machaon Bonafete PhD, PhD, Ori Ben-Yehuda, MD 8 % 6 4 2 0 5 6 7 8 9 0 1 2 3 4 Presented by Ben-Ydhuda at TCT 2015 n=1 n=141 n=1,330 n=883 n=593 n=272 n=47 n=330 n=642 n=1,202 ‡Stroke 2010;41(12):2731-8 4

10/1/16 Bleeding Rates- by CHADS 2 Incidence and Outcomes of Patients with Atrial Fibrillation and Major Bleeding Complications: Findings from the Gastrointestinal, genitourinary, or respiratory tract bleeding that required transfusion or TREAT-AF Study surgical intervention. Daniel W. Kaiser MD1, Randall J. Lee MD PhD2, Jun Fan MS3, Susan S. Schmitt PhD3, Mintu P. Turakhia MD MAS FACC1,3 Bleeding 1Department of Medicine, Stanford University School of Medicine (Stanford, CA); 2University of California San Francisco 3Veterans Affairs Palo Alto Health Care System (Palo Alto, CA) 16.0% • In the mean follow-up of 4.2 years, 11.5% of patients had 14.0% 12.0% a major bleed 10.0% • Patients with prior bleeding complications had greater 8.0% risk of subsequent events including TIA, ischemic stroke, 6.0% repeat bleeding events, and death. 4.0% • OAC started in 25% within 90 days of major bleeding 2.0% event and was associated with a reduced stroke risk (HR 0.0% 0.85), reduced risk of death (HR 0.88), and increased 0 1 2 3 4 5 6 risk of major bleed (HR 1.49). n=5,693 n=12,017 n=15,071 n=6,191 n=1,162 n=81 n=3,033 CHADS 2 Score Presented by Kaiser at ACC 2015 LAA Exclusion in OAC Contraindicated Patients Watchman Safety Profile Watchman ACP LARIAT Reddy et al JACC 2013 Tzikas et al Sievert et al JACC EP EuroIntervention 2015 2015 Number of patients 150 1,047 139 Age 72.5 7.4 75±8 67 ± 11 Mean CHADs2 2.8 1.2 4.43 2.4 +1.2 score Mean follow-up 14.4 + 8.6 13 months 35 + 12 months months, Patient-years 176.9 1,349 401 Absolute # 4 (stroke) 9 (strokes), 9 (TIA) 4 (strokes) strokes/systemic 31 (systemic embolism embolism) Event rate (patient- 2.3% 0.7% stroke 1% years) 0.7% TIA 2.3% systemic Boersma et al. Eur Heart J. 2016 embolism 5

10/1/16 Acute & Longterm Outcomes of Percutaneous Merits of an Epicardial LAA Closure Left Atrial Appendage Suture Ligation: Results Approach From A United States Multicenter Evaluation 6.0% 5.0% 4.0% • Multicenter registry. 18 US centers. • Safety results of 424 consecutive LARIAT procedures. Restore Maintain Protect 3.0% • Micropuncture access technique utilized 2.0% Electrical Isolation LAA Exclusion 2.0% 1.0% 0.7% 0.5% 0.5% 0.2% 0.2% 0.0% 0.0% Procedural Related Pts requiring Cardiac Perfs (no Pts needing Peri-procedural Structural Injury All Complications Mortality surgery surgery) transfusion stroke Lakkireddy et al. Heart Rhythm 2016 Thoracoscopic Appendage Exclusion With an Atriclip Clinical success of various ablation techniques for persistent/long-standing persistent atrial fibrillation Device As a Solo Treatment for Focal Atrial Tachycardia Stefano Benussi, Patrizio Mazzone, Giuseppe Maccabelli, Pasquale Vergara, Antonio Grimaldi, Alberto Pozzoli, Pietro Spagnolo, Ottavio Alfieri, and Paolo Della Bella Brooks AG, et al. Outcomes of long standing persistent AF: A systematic review. Heart Rhythm . 2010; 7:835-46 Circulation 123(14):1575-1578, 2011 6

10/1/16 Fibrillating Areas Isolated within he the Left Atrium after Catheter Ablation of Radiofrequency Linear Catheter Ablation Long-Standing Persistent Atrial Fibrillation 5-Year Outcomes of the Hamburg Sequential Ablation Strategy Roland Richard Tilz, MD, Andreas Rillig, MD, Anna-Maria Thum, Anita Arya, MD, Peter Wohlmuth,Andreas Metzner, MD, Shibu Mathew, MD, Yasuhiro Yoshiga, MD, Erik Wissner, MD, Karl-Heinz Kuck, MD, Feifan Ouyang, MD After the first ablation procedure, sinus rhythm was documented in 41 of 202 (20.3%) patients. After multiple procedures, sinus rhythm was maintained in 91 of 202 (45.0%) patients JACC 2012;60:1921–9. Rostock…..Haissaguerre JCE 17:807-812, 2006 Conversion of Persistent Atrial Fibrillation to Sinus Rhythm After LAA Ligation • Multi-center, prospective randomized superiority trial Badhwar et al., HRS abstract 2015 • Comparing LAA ligation and PVI versus PVI in patients with persistent and longstanding persistent AF Courtesy of David Wilbur 7