Update on atrial fibrillation management Disclosure Catheter - PDF document

12/1/17 Update on atrial fibrillation management Disclosure Catheter Ablation of Atrial Fibrillation: SentreHeart, Inc What Does 2018 Hold? Apama Medical/Boston Scientific • Consultant • Equity holder 1

12/1/17 AF PAROXYSMAL PERSISTENT AF LONG STANDING AF . PERMANENT AF . Diagnosis Standard “Historical” Treatment for AF 33.5 Million WW 3 High BP CHD Rheumatic HD 4 Hyperthyroidism 2 Obesity/Diabetes Restore Maintain Protect Behaviors Increase Sleep Apnea Risk HX of AF Alcohol and Caffeine High Stress 1 INTRODUCTION GROWTH MATURITY DECLINE AFIRM Trial RACE-2 Trial The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. N Engl J Med Van Gelder IC et al. N Engl J Med 2010;362:1363-1373. 2002;347:1825-1833. 2

12/1/17 2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus WARFARIN Statement on Catheter and Surgical Ablation of Atrial Fibrillation Too little = Stroke It’s Not the Answer Too much = Hemorrhage Risks increase with age Low compliance TARGET Contraindications INR 1 2 3 4 5 Dabigatran Rivaroxaban Apixaban Oral Anticoagulants Mechanism Direct Thrombin Inhibitor Factor Xa Inhibitor Factor Xa Inhibitor DISCONTINUATION RATES Dose 110 mg or 150 mg 2x/ day 20 mg/day 5 mg 2x/ day *2.5 mg 2x/day 25 NOAC Efficacy in Superior (150 mg) noninferior superior 20 Warfarin preventing embolic Noninferior (110 mg) events 15 Significantly less (110 mfg) lesless less Hemorrhagic More (150 mg) 10 stroke at GI bleeding Not specified (110mg) Major GI bleeding less 5 Epitaxis and hematuria 0 All bleeding events Less (at 110 mg) less RE-LY ARISTOTLE ROCKET-AF 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

12/1/17 Patients with Limited to NO options LAA Closure Devices Available in the US Patients with contraindications to OAC therapy Watchman Atriclip LARIAT • 82 year old woman with paroxsysmol AF • History of both ICH and cardioembolic stroke, hypertension Watchman is FDA approved for stroke prevention • TEE reveals LAA thrombus Atriclip and LARIAT are FDA approved, but not for stroke prevention RACE 3 AF Risk Factor Modification Risk Factor Driven Upstream Therapy in • HTN Early Atrial Fibrillation • DM The Routine versus Aggressive upstream rhythm • Obesity Control for prevention of Early persistent atrial • Sleep Apnea fibrillation in heart failure study • Alcohol Michiel Rienstra, Anne H. Hobbelt, Marco Alings, Jan G.P. Tijssen, Marcelle D. Smit, • Excercise Johan Brügemann, Bastiaan Geelhoed, Robert G. Tieleman, Hans L. Hillege, Raymond Tukkie, Dirk J. Van Veldhuisen, Harry J.G.M. Crijns, Isabelle C. Van Gelder, for the RACE 3 Investigators Presented at the ESC in Barcelona 2017 4

12/1/17 Hypothesis and trial design Flowchart Patients with early persistent AF and HF § Hypothesis: Risk factor driven upstream therapy is superior to conventional therapy for Causal treatment of AF and HF maintenance of sinus rhythm in patients with early persistent AF and HF Risk factor driven upstream Conventional § RACE 3 trial design: § Prospective, randomized, open label, superiority trial Upstream therapy consists of: § Investigator-initiated 1) Mineralocorticoid receptor antagonist ECV after 3 weeks 2) Statin § Multicenter: 14 sites in The Netherlands and 3 in United Kingdom 3) ACE-inhibitors and/or Guideline-recommended § Enrolment between 2009 and 2015 angiotensin-receptor blockers rhythm and rate control 4) Cardiac rehabilitation: § 1 year follow-up -physical activity 7-day Holter at 1-year -dietary restrictions Primary endpoint Conclusions Sinus rhythm at 1-year Conclusion and implication 100 % of patients 75% 63% 80 § The RACE 3 study shows that risk factor driven upstream therapy, 60 including treatment of risk factors and change of lifestyle, is effective and feasible to improve maintenance of sinus rhythm in patients with early 40 persistent AF and HF 20 0 Upstream Conventional § The effect of upstream therapy on reduction of risk factors and cardiovascular diseases, instead of atrial remodeling, was favourable Odds ratio 1.765 Lower 95% confidence limit 1.115 Superiority hypothesis was proven (p=0.021) 5

12/1/17 Case History Treatment Options • 78 year old male h/o CM, COPD and persistent AF • PVI • Admitted to hospital with SOB • AVJ with PM • EP consulted to consider PVI vs AVJ and PM • Rate control with OAC therapy • Physical exam reveals pt on O2, mildly elevated JVP , • Restore and maintain sinus rhythm with AADs diffuse bilateral rhonchi, minimal pedal edema • Cardioversion • ECG reveals AF with rate of 126 bpm • LVEF of 33% by echo The CASTLE-AF Trial Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation Primary Endpoint Inclusion Criteria • All-cause mortality • Symptomatic PAF or Persistent AF • Worsening heart failure admissions • Failure or intolerance to AAD or unwillingness to take AAD • LVEF < 35% • NYHA class > II 6

12/1/17 CASTLE-AF Treatment Protocol Conventional therapy Ablation therapy • Pulmonary Vein Isolation • ACC/AHA/ESC 2006 guidelines for treatment of AF in heart failure patients Additional lesions • • Efforts to maintain sinus rhythm were • At the discretion of the operator recommended Repeat ablation after blanking period • In the case of rate control strategy: • – 60 and 80 bpm at rest 90 and 115 bpm – • OAC therapy was initiated if not already strated, and maintained throughout the study. INR between 2.0-3.0 7

12/1/17 Clinical success of various ablation techniques for Pivotal Trials persistent/long-standing persistent atrial fibrillation • Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA) • EAST Trial Brooks AG, et al. Outcomes of long standing persistent AF: A systematic review. Heart Rhythm . 2010; 7:835-46 8

12/1/17 New Technologies A C D B Summary: • After the first ablation procedure, sinus rhythm was documented in 41/202 (20.3%) patients. • After multiple procedures, sinus rhythm was maintained in 91/202 (45.0%) patients. JACC 2012;60:1921-9 Do Rotors Drive Persistent AF? STAR AF II Trial PVI: Triggers PVI + CFE: Triggers + substrate PVI + lines: Triggers + substrate CONFIRM Trial Ø 107 procedures (76% persistent AF) Ø PVI (n=71) vs. PVI + rotor (n=36) Ø Rotors identified in 98/101 persistent AF cases Narayan, S. M., Krummen, D. E., Shivkumar, K., Clopton, P., Rappel, W. J., & Miller, J. M. (2012). Journal of Verma A et al. NEJM 2015; 372: 1812-1822 the American College of Cardiology , 60 (7), 628–636. 9

12/1/17 Non-PV Focal Triggers Initiating AF “Gold Standard” for Non- Pharmacological Treatment of AF Ø Non PV Triggers (N=83) Initiating AF 68/401 patients (17%) Cox Maze III Cut and sew Maze * * * * * 4 * * * * * * * 4 * * * *** * * * * * * * * * * * 15 * * ** * * * * * 4 * 11 RA 19 AVNRT LA * * * ** * * * * 1AVRT * * ** * *** * * ** * * * Alonso et al. Pace 2003 Benefit of LAA Closure UCSF Sub-X MAZE (Epicardial) “Cut and sew” AF, Hx TE, No OAC Cox-Maze AF, No TE, No OAC B AF, Hx TE, OAC AF, No TE, OAC AF, No Risk, No TE, No OAC Post maze, No OAC, No LAA Cox J., et al. J Thorac Cardiovasc Surg 1999;118:833-840 Prasad SM. J Thorac Cardiovasc Surg. 2003;126:1822-28. 10

12/1/17 Fibrillating Areas Isolated within he the Left Atrium after E A C Radiofrequency Linear Catheter Ablation F B D LAA Rostock…..Haissaguerre JCE 17:807-812, 2006 LAA Isolation Improves Ablation Outcomes Left Atrial Appendage : An Underrecognized Trigger Site of Atrial Fibrillation 15% 68% 74% Circulation . 2011;123:1575-1578 Di Biase et al., Circulation . 2010;122:109-118 11

12/1/17 Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation after Electrical Isolation of Combined PVI and LAA Exclusion 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 Mechanical standstill Thrombus formation LAA thrombus LAA thrombus in 21%, and three patients had a stroke while on OAC Sick et al., JACC 2007 PVI should be done before LAA closure with an Combined PVI and LAA occlusion LAA implant Catheter ablation can compromise LAA implant integrity Leaks Dislodgement D L Throm A bus WATCH Potential benefits: MAN A V • Restoration of sinus rhythm with PVI • Stroke prevention without need for OAC therapy after LAA occlusion device 12