Contemporary Surgical Therapy for Atrial Fibrillation John F. Grehan, M.D., Ph.D. AllinaHealth United Heart and Vascular Clinic Minneapolis Heart Institute Grand Rounds April 1, 2013 Objectives Provide a understanding of AF pathophysiology and clinical impact on the surgical population Understand the rationale for the Maze IV lesion set Review preoperative considerations and proper classification of AF patients Understand how to safely and efficiently complete each step of the concomitant Maze IV procedure Discuss postoperative and post discharge considerations Overview • • • • • • • • • Pathophysiology of Atrial Fibrillaiton Rationale for Concomitant Treatment Challenges to the Adoption of Treatment Rationale for the Cox Maze IV lesion set ABLATE Study Patient Selection Criteria Post ABLATE Trial Summary Conclusions AF Pathophysiology & Patient Impacts Rev A Pathogenesis of AF • Multiple-wavelet hypothesis1 • Focal mechanism with fibrillatory conduction2 • “Autonomic” hypothesis3 Taken from 2007 HRS Guidelines 1. Moe GK, Abildskov JA. Am Heart J. 1959;58(1):59-70. 2. Konings KT, et al. Circulation. 1994;89(4):1665-1680. 3. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):1043-1065. Focal Origin of AF RA • LA 94% of atrial triggers in PVs (45 pts) • The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of AF • These foci respond to treatment with RF ablation Hassaiguerre M, NEJM, 1998. 17 SVC FO Pulmonary Veins 6 IVC CS 31 11 Pulmonary Veins • Myocardium extends 1–4cm into vein • Complex fiber orientation • Site of embryological pacemaker tissue • Exhibits automaticity and triggered activity • Lower refractory periods Myocardium extends from the atrium along the pulmonary vein Macro-Reentrant Circuits Substrate modification occurs due to near continuous firing in the cells and some cells with the atria begin to fire without being (externally) activated creating additional triggers The Rationale for the Maze IV Lesion Set Risks of Untreated AF – Target Population • Structural heart disease requiring: – Mitral valve surgery – Aortic valve surgery – Coronary artery bypass • Mayo Clinic/Cleveland Clinic Investigations: – Compared subjects with Preoperative AF vs. no AF – No AF Ablation surgery performed – Statistical matching Indication Citation Number of Patients CABG Quader et al Annals of Thor Surgery 2004 46984 Aortic Valve Ngaage et al Annals of Thor Surgery 2006 1487 Mitral Valve Ngaage et al Annals of Thor Surgery, 2007 2821 Risks of Untreated AF in Cardiac Surgery Patients CABG • > 20% increase in mortality by 10 yrs • Increased post op morbidity (2 X stroke) Aortic Valve • Worse late survival (RR = 1.5) • More post op stroke (16% vs. 5%) and CHF (25% vs. 10%) Mitral Valve • 18% difference in survival by 10 yrs • Increase in late cardiac events/stroke (32% difference) Midterm survival in patients treated for atrial fibrillation: A propensity-matched comparison to patients without a history of atrial fibrillation 3262 consecutive patients 813 with AF and 2449 w/out AF undergoing cardiac surgery April 2004 to April 2009. The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2012.02.006 Improved Patient Survival With Concomitant MAZE Procedure Compared With Heart Surgery Alone Conclusions. The restoration of sinus rhythm by a Maze procedure combined with heart surgery markedly improved long-term survival in this series. Ann Thorac Surg 2009;87:440-7 Conclusions. AF associated with mitral valve disease should be treated, because restoration of the sinus rhythm might lead to a lower incidence of thrombo-embolism and valve-related complications in the later period. Challenges to Adoption Concomitant AF Treatment 25 Years of Surgical AF Treatment 2012 2002 1987 1st Cut and Sew Maze Dr. Cox reports high success rates with “Cut and Sew” Maze procedure. Cox Maze IV Using RF Clamp Period of significant trial and error in energy sources and lesion sets to increase adoption and reproducibility. FDA Approval of AtriCure Synergy clamp for AF Treatment (NPAF) Opportunity to standardize procedure through rigorous training. Do Societies Recognize Surgical AF Treatment Or Is This Still Considered “Investigational?” “It is advisable that all patients with documented AF referred for other cardiac surgeries undergo a left or biatrial procedure for AF at an experienced center, unless it… will add significant risk… Heart Rhythm Society, European Heart Rhythm Association, and European Cardiac Arrhythmia Society, in collaboration with the American College of Cardiology, American Heart Association, and Society of Thoracic Surgeons. Consensus Statement on CA and Surgical AF 2012 The ISMICS Consensus Recommendations Concomitant surgical ablation is recommended to increase the incidence of sinus rhythm both at shortand long-term follow-up (class 1, level A) to improve ejection fraction and exercise tolerance (class 2a, level A) and to reduce the risk of stroke and thromboembolic events, to improve long-term survival (class 2a, level A). Under-Treatment by Procedure MV/Aortic Valve Procedures with AF Diagnosis Coronary Artery Bypass with AF Diagnosis 27,000 61% 55,000 93% 4,000 7% 17,000 39% Concomitant AF Concomitant AF No Concomitant AF No Concomitant AF (ICD-9 427.31) Source: Agency for Health Care Quality and Research (AHRQ) Cost and Utilization Project Nationwide Inpatient Sample 2009 Structural Heart Disease Procedures with PreExisting AF Diagnosis 50,000US Concomitant AF Treatment Rates – STS Database Untreated Treated Number of Patients 40,000 33% 30,000 20,000 24% 67% 10,000 0 28% 52% 48% Mitral Valve 76% 62% (1) Aortic Valve (1) Isolated CABG Total (Mitral + Aortic + Isolated CABG) Source: Gammie, Annals 2008;85:909-15 Surgeon Survey, “Why Don’t You Routinely Perform Maze Procedure on Surgical Patients with Pre-Op AF? 35% 30% Highest Scoring Reasons 25% 20% 15% 10% 5% 0% Adds complexity to primary procedure Added “on pump” time Results may not be reproducible Added patient risks Lack of consensus on to primary what works procedure Adds costs Refering physician Do we increase the operative risk by adding the Cox Maze III procedure to aortic valve replacement and coronary artery bypass surgery? Ad et al. J Thorac Cardiovasc Surg Jan 2012 Keys to Maze IV Adoption • Standardization on concomitant procedure • Focus on safety and efficacy • Provide reference materials and support throughout the learning curve • Build a substantial body of evidence on durability of outcomes Rationale for the Maze IV Lesion Set Surgical Treatment of Atrial Fibrillation: The Cox Maze Procedure • Are all the left atrial lesions necessary? • There have been virtually no randomized trials, but there are observational data. Surgical Treatment of Atrial Fibrillation : How about pulmonary vein isolation alone ? PULMONARY VEIN ISOLATION ALONE IS NOT EFFECTIVE IN PATIENTS WITH PERMANENT AF AND VALVULAR HEART DISEASE • 105 patients with AF undergoing valve surgery were randomly assigned to three groups: “U” or “7” linear cryoablation of left atrium or PV isolation • Mean ablation time: 18 ± 3, 15 ± 4, 14 ± 4 minutes for U, 7, and PVI respectively. Gaita et al. Circulation 2005;111:136-142 • Mean follow-up: 41 ± 17 months • Successful lesion creation by EAM: 0% 65% 71% (0/17) (11/17) (12/17) U lesions 7 lesions PVI • NSR at last follow-up: 76% 76% 29% (13/17) (13/17) (5/17) Gaita et al. Circulation 2005;111:136-142 U lesions 7 lesions PVI PULMONARY VEIN CRYOABLATION FOR CHRONIC AF • 101 pts having concomitant cardiac surgery underwent PVI with spherical cryoprobe • Mean age: 63 ± 12 years • Mean AF duration 3.4 ± 3.3 years • NSR at discharge: 75% • NSR at last follow up: 53% • NSR without AA drugs at last followup: 25% Isobe et al.Circ J 2005;69:446-455 Left Atrial Lesions of the Cox-Maze IV Right atrial lesion set of the Cox Maze IV CM-IV: Predictors of Late Recurrence Multivariate Analysis (n=282) Months to f/u 1. 2. 3 6 12 % Freedom from Afib 89% 93% 89% % Freedom Afib/Off AADs 63% 79% 78% Recurrence Variables OR, CI p- value Box lesion set 0.38 [0.167-0.871] 0.022 LA diameter Early ATAs 1.42 [1.04-1.94] 3.05 [1.299-7.17] 0.027 0.010 94% had 24 hr Holter (3,6,12 months) Compliant to HRS Guidelines for definition of success (no AF, AT, Flutter off of AADs) Damiano et al. J Thorac Cardiovasc Surg 2011 The Cox Maze IV for Lone AF: A single center experience in 100 consecutive patients Freedom from ATAs at 12 Months Isthmus lesion Weimar T et al J Interv Card Electrophysiol; 2011 Are the Right Atrial Lesions of the Cox-Maze IV Necessary? Left Atrial Ablation Versus Biatrial Ablation in the Surgical Treatment of Atrial Fibrillation Breda et al Comparison of Bilateral and Unilateral RF Ablation In RF: Early Results Bi-Atrial VS. Left Atrial Barnett SD, Ad N. J Thorac Cardiovasc Surg: 2006;131:1029-30 Surgical Treatment of Atrial Fibrillation in Mitral Valve Disease: Left Atrial Ablation • Meta-analyses have shown significant differences (87 vs 73%, p=.05) between bi-atrial and left lesion set Ad et al. J Thorac Cardiovasc Surg 2006;131:1029 • Results have been very variable with left atrial ablation (range 21-95%) and are dependant on the technology used, the lesion set, and the patient population. • A well designed randomized trial showed only a 44% success rate at 1 year for LA ablation ! Doukas et al. JAMA 2005;294:2323 What are the important lesions of the Cox Maze procedure? Conclusions • All of the left atrial lesions are needed to ensure a success rate of over 80% and to prevent late left atrial flutter. • The right atrial lesion set adds to the overall success rate but may not be necessary in all patients. However, in patients undergoing valve surgery, it takes only 10-15 minutes to perform and adds little morbidity. ABLATE Primary Endpoints • Primary Safety Endpoint – Composite of Death, Stroke, TIA, MI and Excessive Bleeding within 30 days or prior to hospital discharge • Primary Efficacy Endpoint – AF Free (24 hr Holter) and off Class I and III antiarrhythmic drugs at 6 months Left Atrial Lesion Set Checklist Left Atrium Right Antral Pulmonary Vein isolation Left Antral Pulmonary Vein isolation Left Atrial Appendage otomy or excision Left Atrial Appendage to PVI LA roof connecting lesion LA floor connecting lesion Mitral Valve Isthmus lesion Coronary Sinus/MV annulus lesion (epi / endo) Electrical Isolation Testing (Pacing or Sensing) KEY: Blue lines represent typical clamp lesions. Orange line represents typical cryo lesions. Purple line represents surgical incisions. Right Pulmonary Veins Confirmation of Right Antral PVI P / S Confirmation of Left Antral PVI P /S Right Atrial Lesion Set Checklist Connecting lesion along medial walls of RAA toward TV annulus Left Pulmonary Veins KEY: Blue lines represent typical clamp lesions. Orange lines represent typical cryo lesions. Purple oval represents RAA otomy. Right Atrium Right Atrial Appendage Oblique Vertical right atriotomy Connecting lesion from the RAA Oblique to the MEDIAL Tricuspid annulus (10 o’clock position) Connecting lesion from vertical atriotomy to the SVC Connecting lesion from vertical atriotomy to the IVC Connecting lesion from the vertical atriotomy to the MEDIAL Tricuspid annulus (2 o’clock position) ABLATE: Enrolled Patient Disposition 55 Patients Enrolled n=2 Patients expired 53 Patients @ 30 day follow up n=2 Patients expired, n=1 withdrawal 50 Patients @ 6 Months n=2 Patients expired 48 Patients Long-term Median= 21.6 Months ABLATE: Demographics ABLATE (N=55) Age (years) Mean +/-SD Median (Min, Max) Gender Male Ethnic Group Caucasian Black Asian Hispanic 70.5 +/- 9.3 72.0 (45.0, 88.0) % n 58.2 32 90.9 3.6 1.8 3.6 50 2 1 2 ABLATE: Demographics ABLATE (N=55) EF (%) Mean +/-SD Median (Min, Max) LA Size (cm) Mean +/-SD Median (Min, Max) NYHA Classification I II III IV 50.0 +/- 10.3 50.0 (20.0, 70.0) 5.9 +/- 1.0 6.0 (3.9, 7.7) % n 16.4 41.8 40.0 1.8 9 23 22 1 ABLATE: Baseline AF Status ABLATE (N=55) Form of AF Paroxysmal Persistent Long-standing persistent % n 7.3 40.0 52.7 4* 22 29 Duration (months) of AF prior to enrollment Mean +/-SD 61.2 +/- 49.5 Median (Min, Max) 48.6 (1.78, 188.39) Current / Prior failed anti-arrhythmic drugs Paroxysmal Subjects:* LA Size > 5 cm: (3/4); Hx of AF > 12 mos (4/4) 25.5 14 ABLATE Primary Surgical Procedure ABLATE (N=55) Surgery CABG % 18.2 n 10 Mitral Valve 18.2 10 Aortic Valve 21.8 12 Double Valve 16.4 9 CABG & Valve 16.4 9 CABG & Double Valve 9.1 5 ABLATE Primary Safety Endpoint- Results Primary Safety Endpoint Details of Primary Safety Endpoint Operative Mortality (Death) Stroke TIA MI Excessive Bleeding (>2 units with reop) % 9.1 n 5 3.6 1.8 0.0 0.0 2 1 0 0 3.6 2 Primary Safety Endpoint – Major Adverse Event Rate: Non-paroxysmal Population 100.0% 80.0% 60.0% 40.0% 20.0% 0.0% 9.8% 7.8% 0.0% N= (5/51) ABLATE ABLATE AF N= (5/64) Combined Six Month Efficacy: Non-paroxysmal Population Success Rate AF Free off AADs AF Free (Primary Endpoint) (Secondary Endpoint) 100.0% 91% 83% 80.0% 84% 82% 75% 74% 60.0% 40.0% 20.0% N= (34/46) N= (38/46) N= (9/11) N= (10/11) N= (43/57) N= (48/57) 0.0% ABLATE Data on File ABLATE AF Combined Patient Selection & Patient Considerations 2007 HRS Consensus StatementConcomitant Indications • Symptomatic AF patients undergoing other cardiac surgery • Selected asymptomatic AF patients undergoing cardiac surgery in whom the ablation can be performed with minimal risk Reviewing Relevant Patient History • Factors That Influence Decision To Treat and Potential Outcomes of Concomitant Treatment: – Patient Age – Left Atrial Size – Preoperative Duration of AF – Unrelated Co-morbidities – Number of Concomitant Procedures Related to the Patient Cox - Regression Freedom from Late AF Recurrence Stratified by Duration of Preop AF Freedom from Recurrence (%) 100 80 60 1 yr. 5 yrs. 10 yrs. 15 yrs. 20 yrs. 40 20 0 1 2 3 4 p=<0.001 5 6 Time from Surgery (years) 7 8 9 10 Gaynor SL, Damiano RJ; J Thorac Cardiovasc Surg 2005;129:104-11 Post Operative and Post Discharge Patient and Rhythm Management 2007 HRS Guidelines for AF Reporting Outcomes Blanking period • A blanking period of three months should be employed after ablation when reporting outcomes. Definition of success • Freedom from AF/flutter/tachycardia off antiarrhythmic therapy is the primary endpoint of AF ablation. • Freedom from AF at various points following ablation may be a better marker of true benefit and should be considered as a secondary endpoint of ablation. • An episode of AF/flutter/tachycardia detected by monitoring should be considered a recurrence if it has a duration of 30 seconds or more. Postoperative Considerations and Expectations Junctional rhythm occurs quite frequently in post-ablation patients and may be due to some degree of sinus node dysfunction. Pacemaker insertion should not be considered too hastily, and without clear indications. Heart rates in post operative full Maze patient are often in the low 50-60 BPM range. Some patients may be sent home in junctional rhythm. Continued • Patients with junctional rhythm often have extend hospitalization ranging from 7–10 days on average which allows for stabilization of their cardiac rhythm. • Cardioversion may be considered during the early postoperative period if the patient is cardiovascularly unstable or prior to discharge from hospital. Clinical management after surgery for atrial fibrillation focuses on four areas: 1) Fluid retention occur in 12-30% of patients. This may be considered as: – Early 24-36 hrs: Pulmonary congestion – Late: Pleural effusion and weight gain Managed as per standard ICU protocol. 2) Atrial tachyarrhythmias (ATA)– Over 40% of patients experience ATA (AF, Aflutter, AT, SVT) post operatively. – Intraoperative antiarrhythmics/Amiodarone may be administered as per hospital protocol. This may be continued into the postoperative period except for patients with bradycardia or junctional rhythm. Cardioversion may also be considered for these patients as outlined in the previous slide at physician’s discretion. Clinical considerations after surgery : continued 3) Anticoagulation—(At Physician’s Discretion) – Aspirin is usually resumed on POD-1 unless contraindicated. – Coumadin is usually started/restarted on postoperative day (POD)-2. Coumadin should be delayed if the patient experiences a bradycardic rhythm requiring a pace maker. – An INR range of 2.0-2.5 is the recommended level to maintain for patients. – The duration of Coumadin is dependent on physician discretion and may be based upon several factors including, (i) Patient remaining in sinus rhythm (ii) Concomitant procedure performed ie. mechanical valve replacement, and (iii) CHADS2 score. 4) Perioperative sinus/AV dysfunction— (At Physician’s Discretion) – The need for a permanent pacemaker (PPM) is more common in patients with preoperative SA node dysfunction. If the patient develops postoperative bradycardia and/or junctional rhythm, all antiarrhythmics should be discontinued. The patient may be treated conservatively for 7-10 days before a PPM is implanted. Bradycardic rhythms can often resolve within this time period. ABLATE Post Approval Study • Atricure Synergy Ablation Lesions for NonParoxysmal Forms of Atrial Fibrillation Treatment During Concomitant On-Pump Endo/Epicardial Cardiac Surgery Trial Design • Site Selection: – 50 US centers – Up to 10 OUS centers • 3 categories: – ABLATE AF Registry subjects (will be transferred into the ABLATE PAS study); need to be re-consented to participate in PAS – Existing Users – uses Synergy Ablation System, but not part of clinical trial(s) – New Users – new users to the Synergy Ablation System • Certification: – All participating surgeons will have successfully completed the Certification process Trial Design • Enrollment procedures: – All non-paroxysmal subjects presenting with AF and scheduled to undergo a primary open cardiac surgery requiring bypass including valve and/or CABG are eligible – Patients are PRE-SCREENED for eligibility and offered the opportunity to participate Eligibility Criteria Inclusion Criteria • Subject ≥18 • Subject has a history of a non-paroxysmal form of AF as defined by the HRS/EHRA/ECAS Consensus Statement • Persistent AF • Longstanding Persistent AF • Subject agrees to participate in this study by signing the IRB approved informed consent form. • Willing and able to return for scheduled follow-up visits Eligibility Criteria Exclusion Criteria • Stand alone AF without indication(s) for concomitant cardiac surgery. • Need for emergent cardiac surgery (i.e. cardiogenic shock) • Preoperative need for an intra-aortic balloon pump or intravenous ionotropes • Pregnancy or desire to get pregnant for the duration of the study • Enrolled in another clinical trial that could confound the results of this study. Study Outcomes Primary Safety Outcome • Proportion of subjects with any serious adverse events within 30 days post procedure or hospital discharge (whichever is later) considered to be: – device-related or ablation procedure-related – Excluding pacemaker implantation (reviewed separately) • Adjudicated by clinical events committee Study Outcomes Secondary Safety Outcome • Composite major adverse event: – Serious adverse events occurring within 30 days postprocedure or hospital discharge (whichever is later) including: – Death (includes deaths after 30 days or hospital discharge if death is procedure related). – Stroke (resulting in significant permanent disability) – TIA – Myocardial infarction, and – Excessive bleeding (requiring >2 units of blood replacement and surgical intervention). Study Outcomes Primary Efficacy Outcome • The proportion of subjects free from AF while off Class I and III AADs – determined by 48 hour Holter recording at a minimum of 12, 24 and 36 months post operatively • Zio™ Patch or Permanent Pacemaker interrogation can be performed in lieu of 48 hour Holter – Success = AF Free while off of Class I and III AADs • i.e. no episodes lasting >30 continuous seconds of atrial fibrillation, atrial flutter or atrial tachycardia Study Outcomes Secondary Efficacy Outcome • Proportion of patients free from AF, regardless of AAD usage – determined by 48 hour Holter recording at a minimum of 12, 24 and 36 months post operatively • Zio™ Patch or Permanent Pacemaker interrogation can be performed in lieu of 48 hour Holter – Secondary Success = AF Free (regardless of AAD usage) i.e. no episodes lasting >30 continuous seconds of atrial fibrillation, atrial flutter or atrial tachycardia Study Follow-up • 36 month follow-up period • Post-procedure follow up visits at: – – – – – 30 days 4 months 12 months 24 months 36 months Follow-up Assessments 30 day follow-up • Window: +7 days – – – – – – – Physical assessment Medications NYHA Classification 12 Lead ECG AE assessment INR – if anticoagulated Cardioversion if subject is in AF Follow-up Assessments 4 month follow-up • Window: +/- 30 days – – – – – – – Physical assessment NYHA Classification 12 Lead ECG AE assessment Review of medications INR – if anticoagulated Cardioversion if subject is in AF Follow-up Assessments 12 month follow-up • Window: +/- 60 days – – – – – – Physical assessment AE assessment Review of medications INR – if anticoagulated Cardioversion if subject is in AF Primary endpoint evaluation: 48 hour Holter monitor assessment (Zio™ Patch or Pacemaker Interrogation acceptable) Follow-up Assessments 24 month follow-up • Window: +/- 60 days – – – – – – Physical assessment AE assessment Review of medications INR – if anticoagulated Cardioversion if subject is in AF 48 hour Holter monitor assessment (Zio™ Patch or Pacemaker Interrogation acceptable) Follow-up Assessments 36 month follow-up • Window: +/- 60 days – – – – – – Physical assessment AE assessment Review of medications INR – if anticoagulated Cardioversion if subject is in AF 48 hour Holter monitor assessment (Zio™ Patch or Pacemaker Interrogation acceptable) Summary Pathogenesis of AF multifactorial PV responsible in majority LA Substrate modification contributes Maze IV lesion set address multiple mechanisms At least all left atrial lesions RA lesions add to efficacy-minimal cost AF portends to worse long-term outcomes in surgical patients CABG, AVR, MVR Efficacy Rates of near 80% off AAD can be achieved Little extra time and minimal increase in risk NSR improves outcomes in all cardiac surgery patient groups studied Conclusions All patients with atrial fibrillation undergoing cardiac surgery should be considered for concomitant maze procedure utilizing the Cox maze IV lesion set.