Presentation on theme: "Contemporary Surgical Therapy for Atrial Fibrillation"— Presentation transcript:
1 Contemporary Surgical Therapy for Atrial Fibrillation John F. Grehan, M.D., Ph.D.AllinaHealthUnited Heart and Vascular ClinicMinneapolis Heart InstituteGrand RoundsApril 1, 2013
2 ObjectivesProvide a understanding of AF pathophysiology and clinical impact on the surgical populationUnderstand the rationale for the Maze IV lesion setReview preoperative considerations and proper classification of AF patientsUnderstand how to safely and efficiently complete each step of the concomitant Maze IV procedureDiscuss postoperative and post discharge considerations
3 Overview Pathophysiology of Atrial Fibrillaiton Rationale for Concomitant TreatmentChallenges to the Adoption of TreatmentRationale for the Cox Maze IV lesion setABLATE StudyPatient Selection CriteriaPost ABLATE TrialSummaryConclusions
5 Pathogenesis of AF Multiple-wavelet hypothesis1 Focal mechanism with fibrillatory conduction2“Autonomic” hypothesis3For the past 2 – 3 decades it has been appreciated that an important mechanism of AF is multiple loop reentry.More recently it has been recognized that most AF is triggered by rapid firing from the pulmonary veins and that the autonomic ganglia play a role in the initiation of AF.Taken from 2007 HRS GuidelinesMoe GK, Abildskov JA. Am Heart J. 1959;58(1):59-70.Konings KT, et al. Circulation. 1994;89(4):Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):
6 Focal Origin of AFCSFOSVCIVC17316RALA94% of atrial triggers in PVs (45 pts)The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of AFThese foci respond to treatment with RF ablationPulmonary Veins11Studies have revealed that the majority of focal triggers that initiate and maintain PAF arise from the pulmonary veins. Other sites for ectopic activity are the Superior Vena Cava, along the Crista Terminalis, and the posterior left atrium.Hassaiguerre M, NEJM, 1998.
7 Pulmonary Veins Myocardium extends 1–4cm into vein Complex fiber orientationSite of embryological pacemaker tissueExhibits automaticity and triggered activityLower refractory periodsMyocardium extends from the atrium along the pulmonary vein
8 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
9 The Rationale for the Maze IV Lesion Set Script for this developed on the teleprompter. Key message: full biatrial lesion is optimal for NPAF patients although this is entirely subject to patient specific factors such as anatomy, age, comorbidities, primary procedure complexity. The goal is full biatrial lesion set but it is not realistic to think that this can be achieved in all patients.
10 Risks of Untreated AF – Target Population Structural heart disease requiring:Mitral valve surgeryAortic valve surgeryCoronary artery bypassMayo Clinic/Cleveland Clinic Investigations:Compared subjects with Preoperative AF vs. no AFNo AF Ablation surgery performedStatistical matchingIndicationCitationNumber ofPatientsCABGQuader et alAnnals of Thor Surgery 200446984Aortic ValveNgaage et alAnnals of Thor Surgery 20061487Mitral ValveAnnals of Thor Surgery, 20072821It is appropriate to determine the risks of AF in the target group of patients that are undergoing a surgical procedure for their underlying structural heart disease. This provides an assessment of whether the potential added risk of another component to the surgical procedure is necessary. The research conducted at the Mayo Clinic and the Cleveland Clinic reviewed the risks of subjects that had a baseline AF in comparison to those subjects that were AF free at the time of their operation. This case matched series of patients was extensive as highlighted here with the minimum number of patients included, in this case for the Aortic Valve group, of greater than 1400 subjects. These data provide valuable insight into the risks a patient faces of their baseline AF after their structural heart disease is surgically corrected.
11 Risks of Untreated AF in Cardiac Surgery Patients CABG> 20% increase in mortality by 10 yrsIncreased post op morbidity (2 X stroke)Aortic ValveWorse late survival (RR = 1.5)More post op stroke (16% vs. 5%) and CHF (25% vs. 10%)Mitral Valve18% difference in survival by 10 yrsIncrease in late cardiac events/stroke (32% difference)The results of this series of research papers demonstrated the following:There was a greater than 20% increase in mortality by ten years post procedure in the cohort of patients receiving a CABG with baseline AFThere was also a significantly higher level of post op morbidity including a two times greater incidence of stroke. The incidence of this was low however so the potential for this observation being related to chance cannot be ruled out.[CLICK]Layer 2 ADD PACEMAKER RATES…..In the series of subjects receiving a surgical procedure for Aortic Valve disease, the group with AF at baseline was noted to have a 50% higher incidence of late death with a significantly higher risk ratio of 1.5. Further, the incidence of late stroke and CHF was significantly higher in the group with preoperative AF vs. those in baseline sinus rhythmFinally, the study of mitral valve surgery also confirmed a higher late mortality for the patients in AF at baseline with a 18% difference in survival by ten years post op with a significantly higher post operative mortality rate as well. This was coupled with a significantly higher incidence of late cardiac events and stroke of greater than 30%.These data support the need to identify a potential procedure to correct AF in these very sick patients and has been the cornerstone behind the development of the surgical the MAZE procedure and its adoption as standard of care in cardiac surgery today.
12 Midterm survival in patients treated for atrial fibrillation: A propensity-matched comparison to patients without a history of atrial fibrillation3262 consecutive patients with AF and 2449 w/outAF undergoing cardiac surgery April 2004 to April 2009.The American Association for Thoracic Surgerydoi: /j.jtcvs
13 Improved Patient Survival With Concomitant MAZE Procedure Compared With Heart Surgery Alone Conclusions. The restoration of sinus rhythm by a Maze procedure combinedwith heart surgery markedly improved long-term survival in this series.Ann Thorac Surg 2009;87:440-713
14 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.244 patients undergoing mitral surgery with long-standing atrial fibrillation147 maze or PVI v. 97 mitral surgery alonelooking at thromboembolism and rhythm
15 Challenges to Adoption Concomitant AF Treatment
16 25 Years of Surgical AF Treatment 19871st Cut and Sew Maze2002Cox Maze IV Using RF Clamp2012FDA Approval of AtriCure Synergy clamp for AF Treatment (NPAF)Dr. Cox reports high success rates with “Cut and Sew” Maze procedure.Before we talk about the specific training today, let’s spend a moment reviewing the near term timeline of AF treatment….Period of significant trialand error in energy sources and lesion sets to increase adoption and reproducibility.Opportunity to standardize procedure through rigorous training.
17 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
18 The ISMICS Consensus Recommendations Concomitant surgical ablation is recommended to increase the incidence of sinus rhythm both at short- and 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).
19 Under-Treatment by Procedure Note: In 2009 there were 3.5 million U.S. hospital admissions with a primary or secondary diagnosis of AF (ICD-9 code ).(ICD )Source: Agency for Health Care Quality and Research (AHRQ)Cost and Utilization Project Nationwide Inpatient Sample 2009
20 Source: Gammie, Annals 2008;85:909-15 Structural Heart Disease Procedures with Pre- Existing AF DiagnosisUS Concomitant AF Treatment Rates – STS Database67%76%62%48%Source: Gammie, Annals 2008;85:909-15
21 Surgeon Survey, “Why Don’t You Routinely Perform Maze Procedure on Surgical Patients with Pre-Op AF? Based upon a 3rd party survey conducted at the American Association of Thoracic Surgeons annual meeting in 2011, many surgeons report that they perceive the concomitant procedure “adding too much complexity” to their primary procedure. Other extremely important reasons for not routinely treating more of their AF patients was “added pump time”, “not feeling like they could reproduce the results reported by academic centers or those reported in single centered peer review literature”, and “unwillingness to add any patient risks to the procedure”. Finally, a number of surgeons felt like there was very little society consensus on identifying what energy source or lesion set actually provided benefit. All of these concerns can be directly addressed by
22 Do we increase the operative risk by adding the Cox Maze III procedure to aortic valve replacement and coronary artery bypass surgery?485 patients have undergone the Cox Maze III procedure at Inova Heart and Vascular Institute, 95 of whom had a full Cox Maze III with an AVR or CABG (Cox Maze III/AVR = 30; Cox Maze III/CABG = 47; Cox Maze III/AVR/CABG = 18). In addition, 4255 patients with no history of AF underwent AVR or CABG without surgical ablation (AVR = 422; CABG = 3518; AVR/CABG = 315). Data from our CABG, valve, and AF registries were used for analysesCONCLUSIONS:The addition of the Cox Maze III procedure to AVR or CABG did not convey an increase in major morbidity and perioperative risk. Patients who underwent the Cox Maze III procedure demonstrated similar survival over time with improvement in health-related quality of life. The Cox Maze III should not be denied to patients in whom the cardiac surgical procedure does not include atriotomies because of the perceived increased operative risk. The Cox Maze III may significantly improve their outcomeAd et al.J Thorac Cardiovasc Surg Jan 2012
23 Keys to Maze IV Adoption Standardization on concomitant procedureFocus on safety and efficacyProvide reference materials and support throughout the learning curveBuild a substantial body of evidence on durability of outcomes
25 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.
26 Surgical Treatment of Atrial Fibrillation : How about pulmonary vein isolation alone ?
27 PULMONARY VEIN ISOLATION ALONE IS NOT EFFECTIVE IN PATIENTS WITH PERMANENT AF AND VALVULAR HEART DISEASE105 patients with AF undergoing valve surgery were randomly assigned to three groups: “U” or “7” linear cryoablation of left atrium or PV isolationMean ablation time: 18 ± 3, 15 ± 4, 14 ± 4 minutes for U, 7, and PVI respectively.Gaita et al. Circulation 2005;111:
28 Mean follow-up: 41 ± 17 months Successful lesion creation by EAM: 0% (0/17) U lesions65% (11/17) 7 lesions71% (12/17) PVINSR at last follow-up:76% (13/17) U lesions76% (13/17) 7 lesions29% (5/17) PVIGaita et al. Circulation 2005;111:
29 PULMONARY VEIN CRYOABLATION FOR CHRONIC AF 101 pts having concomitant cardiac surgery underwent PVI with spherical cryoprobeMean age: 63 ± 12 yearsMean AF duration 3.4 ± 3.3 yearsNSR at discharge: 75%NSR at last follow up: 53%NSR without AA drugs at last followup: 25%Isobe et al.Circ J 2005;69:
30 Left Atrial Lesions of the Cox-Maze IV SuperiorconnectinglesionInferiorconnectinglesion
31 Right atrial lesion set of the Cox Maze IV The right atrial lesion set of the Cox-Maze procedure IV.
32 CM-IV: Predictors of Late Recurrence Multivariate Analysis (n=282) Months to f/u3612% Freedom from Afib89%93%% Freedom Afib/Off AADs63%79%78%Recurrence VariablesOR, CIp- valueBox lesion set0.38 [ ]0.022LA diameter1.42 [ ]0.027Early ATAs3.05 [ ]0.010-In Gaynor et al, a significant predictive factor for recurrence was duration of preoperative AF. Not so here. May be due to atrial remodeling in MV/hypertensive hearts.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
33 Freedom from ATAs at 12 Months The Cox Maze IV for Lone AF: A single center experience in 100 consecutive patientsFreedom from ATAs at 12 MonthsIsthmus lesionWeimar T et alJ Interv Card Electrophysiol; 2011
34 Are the Right Atrial Lesions of the Cox-Maze IV Necessary?
35 Left Atrial Ablation Versus Biatrial Ablation in the Surgical Treatment of Atrial Fibrillation Breda et alComparison of Bilateral and Unilateral RFAblation In RF: Early Results
36 Bi-Atrial VS. Left Atrial Barnett SD, Ad N. J Thorac Cardiovasc Surg: 2006;131:
37 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 setAd et al. J Thorac Cardiovasc Surg 2006;131:1029Results 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
38 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 minutes to perform and adds little morbidity.
39 ABLATE Primary Endpoints Primary Safety EndpointComposite of Death, Stroke, TIA, MI and Excessive Bleeding within 30 days or prior to hospital dischargePrimary Efficacy EndpointAF Free (24 hr Holter) and off Class I and III antiarrhythmic drugs at 6 monthsTwo primary Endpoints for the study were established to evaluate product and procedure outcomes, one for safety and one for efficacy.The primary safety outcome was a composite MAE rate that consisted of death, stroke, TIA, MI and bleeding within the initial 30 days post procedure or prior to hospital discharge, whichever came latest. It should be noted that all cause death was included in the initial 30 days and any procedural death beyond thirty days that was deemed to be related to the device or procedure. Bleeding was determined to be an endpoint if it required more than two units of blood and required a reoperation. The safety events were reported based on the evaluation performed by an independent physician adjudicator not involved with the company or the study.The primary Efficacy endpoint was defined as Freedom from AF off any antiarrhythmic drugs at six months post procedure as assessed by 24 hour Holter evaluated by an independent core lab. AF Free was defined as AF episodes < 5 min. duration and no more than 1 hr total AF duration in a 24 hr timeframe.
40 Left Atrial Lesion Set Checklist Left AtriumRight Antral Pulmonary Vein isolationLeft Antral Pulmonary Vein isolationLeft Atrial Appendage otomy or excisionLeft Atrial Appendage to PVILA roof connecting lesionLA floor connecting lesionMitral Valve Isthmus lesionCoronary Sinus/MV annulus lesion (epi / endo)Electrical Isolation Testing (Pacing or Sensing)Confirmation of Right Antral PVI P / SConfirmation of Left Antral PVI P /SKEY:Blue lines represent typical clamp lesions.Orange line represents typical cryo lesions.Purple line represents surgical incisions.Right Pulmonary Veins
41 Right Atrial Lesion Set Checklist Connecting lesion along medialwalls of RAA toward TV annulusRight AtriumRight Atrial Appendage ObliqueVertical right atriotomyConnecting lesion from the RAA Oblique to theMEDIAL Tricuspid annulus (10 o’clock position)Connecting lesion from vertical atriotomy to the SVCConnecting lesion from vertical atriotomy to the IVCConnecting lesion from the vertical atriotomy to the MEDIAL Tricuspid annulus (2 o’clock position)Left Pulmonary VeinsKEY:Blue lines represent typical clamp lesions.Orange lines represent typical cryo lesions.Purple oval represents RAA otomy.
42 ABLATE: Enrolled Patient Disposition 55 Patients Enrolledn=2 Patients expired53 30 day follow upn=2 Patients expired, n=1 withdrawal50 6 MonthsA total of 55 subjects were treated in the pivotal study. Two subjects expired in less than 30 days and are accounted for as primary endpoint events resulting in a total of 53 subjects being available for a 30 day assessment. There was one subject that withdrew prior to the 30 day visit on day 21 but it should be noted that at that assessment, he was noted to be free of any safety endpoint event. Two additional subjects expired prior to the six month assessment resulting in a total of 50 evaluable patients at the time of the primary endpoint assessment.The FDA requested that we obtain further long term assessments on the subjects in ABLATE at a time point at or beyond 12 months. Atricure was able to evaluate rhythm status on a total of 48 subjects using 48 hour Holter monitors at a mean follow up of 21.6 months.n=2 Patients expired48 PatientsLong-termMedian= 21.6 Months
43 ABLATE: Demographics ABLATE (N=55) Age (years) Mean +/-SD 70.5 +/- 9.3 Median (Min, Max)72.0 (45.0, 88.0)%nGenderMale58.232Ethnic GroupCaucasian90.950Black3.62Asian1.81HispanicThe subjects in the study had a median age of 72 and is nearly evenly distributed in terms of males and females.
44 ABLATE: Demographics ABLATE (N=55) EF (%) Mean +/-SD 50.0 +/- 10.3 Median (Min, Max)50.0 (20.0, 70.0)LA Size (cm)5.9 +/- 1.06.0 (3.9, 7.7)%nNYHA ClassificationI16.49II41.823III40.022IV1.81In reviewing the demographic characteristics of these 55 patients, note the baseline left atrial size. The median Left Atrial Size in the group was 6 cm underscoring the fact that these are not viable candidates for catheter ablation procedures. Also shown on this table is the break down of NYHA Class which is primarily either Class II or III.
45 ABLATE: Baseline AF Status %nForm of AFParoxysmal7.34*Persistent40.022Long-standing persistent52.729Duration (months) of AF prior to enrollmentMean +/-SD61.2 +/- 49.5Median (Min, Max)48.6 (1.78, )Current / Prior failed anti-arrhythmic drugs25.514Here we show the summary of the baseline AF status as adjudicated. The study enrolled primarily persistent or longstanding persistent AF subjects based on contemporary definitions. These data support the proposed indication of “non-paroxysmal” AF.In addition to the very large left atrial size, it is important to note the duration of AF noted at the time of enrollment. The ABLATE subjects had a median of nearly 50 months of documented AF at baseline. This is an extremely long duration and underscores yet another factor that would characterize them with an intractable form of AF.Paroxysmal Subjects:* LA Size > 5 cm: (3/4); Hx of AF > 12 mos (4/4)
46 ABLATE Primary Surgical Procedure SurgeryABLATE(N=55)%nCABG18.210Mitral ValveAortic Valve21.812Double Valve16.49CABG & ValveCABG & Double Valve9.15When examining the types of procedures that were performed in the group it can be seen that the majority of subjects received a valve operation with many of them being either CABG with valve or double valve.This highlights the primary need for a surgical procedure to correct structural heart disease with the MAZE IV being performed in an effort to try and restore sinus rhythm which can potentially benefit them in the long term.
47 ABLATE Primary Safety Endpoint- Results %nPrimary Safety Endpoint9.15Details of Primary Safety EndpointOperative Mortality (Death)3.62Stroke1.81TIA0.0MIExcessive Bleeding (>2 units with reop)I would like to turn your attention now to the Primary Endpoint results for ABLATE.The safety endpoints include –DeathStrokeTIAMIExcessive bleedingAll events except one were attributed to the primary surgical procedure for structural heart diseaseA total of five primary safety endpoint events have occurred in the study, two deaths, one stroke and two occurrences of bleeding that required blood products with a reoperation.
48 Primary Safety Endpoint – Major Adverse Event Rate: Non-paroxysmal Population The outcomes for ABLATE and ABLATE AF have been combined since these data are being collected under the same IDE with ABLATE AF serving as an extension registry of the ABLATE trial. Upon examination of the combined set of data for ABLATE and ABLATE AF, the MAE rate is actually the lowest of all data experiences.This favorable safety rate supports the overall conclusions of the pivotal ABLATE trial.N= (5/51)N= (5/64)
49 Six Month Efficacy: Non-paroxysmal Population Success Rate(Primary Endpoint)(Secondary Endpoint)The six month efficacy rates for the AblateAF subjects support the outcomes of the ABLATE trial. Note that the Ablate AF continuation study reported greater freedom of AF with lower MAES. This possibly reflects a slightly healthier patient population in Ablate AF as well as investigator experience with the Synergy device and the performance of the complete Maze IV lesion set.N= (34/46)N= (38/46)N= (9/11)N= (10/11)N= (43/57)N= (48/57)Data on File
51 2007 HRS Consensus Statement- Concomitant Indications Symptomatic AF patients undergoing other cardiac surgerySelected asymptomatic AF patients undergoing cardiac surgery in whom the ablation can be performed with minimal risk
52 Reviewing Relevant Patient History Factors That Influence Decision To Treat and Potential Outcomes of Concomitant Treatment:Patient AgeLeft Atrial SizePreoperative Duration of AFUnrelated Co-morbiditiesNumber of Concomitant Procedures Related to the Patient
53 Cox - Regression Freedom from Late AF Recurrence Stratified by Duration of Preop AF 12345678910Time from Surgery (years)20406080100Freedom from Recurrence (%)20 yrs.15 yrs.10 yrs.5 yrs.1 yr.p=<0.001Freedom from late AF recurrence by duration of preoperative AF is demonstrated here in this graph. The duration of preoperative AF was a significant predictor of late AF recurrence. Interestingly patients presenting with a preoperative AF duration of five years shown in green had a 91% freedom from AF recurrence at 10 years following the Cox-Maze procedure. In comparison, those patients with a preoperative AF duration of 20 years shown in purple had only a 72% freedom from AF recurrence at 10 years.Gaynor SL, Damiano RJ; J Thorac Cardiovasc Surg 2005;129:104-11
54 Post Operative and Post Discharge Patient and Rhythm Management
55 2007 HRS Guidelines for AF Reporting Outcomes Blanking periodA blanking period of three months should be employed after ablation when reporting outcomes.Definition of successFreedom 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.
56 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 BPM range. Some patients may be sent home in junctional rhythm.
57 ContinuedPatients 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.
58 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 hrs: Pulmonary congestionLate: Pleural effusion and weight gainManaged 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.
59 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 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.
60 ABLATE Post Approval Study Atricure Synergy Ablation Lesions for Non-Paroxysmal Forms of Atrial Fibrillation Treatment During Concomitant On-Pump Endo/Epicardial Cardiac Surgery
61 Trial Design Site Selection: 3 categories: Certification: 50 US centersUp to 10 OUS centers3 categories:ABLATE AF Registry subjects (will be transferred into the ABLATE PAS study); need to be re-consented to participate in PASExisting Users – uses Synergy Ablation System, but not part of clinical trial(s)New Users – new users to the Synergy Ablation SystemCertification:All participating surgeons will have successfully completed the Certification process
62 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 eligiblePatients are PRE-SCREENED for eligibility and offered the opportunity to participate
63 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 StatementPersistent AFLongstanding Persistent AFSubject agrees to participate in this study by signing the IRB approved informed consent form.Willing and able to return for scheduled follow-up visits
64 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 ionotropesPregnancy or desire to get pregnant for the duration of the studyEnrolled in another clinical trial that could confound the results of this study.
65 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-relatedExcluding pacemaker implantation (reviewed separately)Adjudicated by clinical events committee
66 Study Outcomes Secondary Safety Outcome Composite major adverse event:Serious adverse events occurring within 30 days post-procedure 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)TIAMyocardial infarction, andExcessive bleeding (requiring >2 units of blood replacement and surgical intervention).
67 Study Outcomes Primary Efficacy Outcome The proportion of subjects free from AF while off Class I and III AADsdetermined by 48 hour Holter recording at a minimum of 12, 24 and 36 months post operativelyZio™ Patch or Permanent Pacemaker interrogation can be performed in lieu of 48 hour HolterSuccess = AF Free while off of Class I and III AADsi.e. no episodes lasting >30 continuous seconds of atrial fibrillation, atrial flutter or atrial tachycardia
68 Study Outcomes Secondary Efficacy Outcome Proportion of patients free from AF, regardless of AAD usagedetermined by 48 hour Holter recording at a minimum of 12, 24 and 36 months post operativelyZio™ Patch or Permanent Pacemaker interrogation can be performed in lieu of 48 hour HolterSecondary Success = AF Free (regardless of AAD usage) i.e. no episodes lasting >30 continuous seconds of atrial fibrillation, atrial flutter or atrial tachycardia
69 Study Follow-up 36 month follow-up period Post-procedure follow up visits at:30 days4 months12 months24 months36 months
70 Follow-up Assessments 30 day follow-upWindow: +7 daysPhysical assessmentMedicationsNYHA Classification12 Lead ECGAE assessmentINR – if anticoagulatedCardioversion if subject is in AF
71 Follow-up Assessments 4 month follow-upWindow: +/- 30 daysPhysical assessmentNYHA Classification12 Lead ECGAE assessmentReview of medicationsINR – if anticoagulatedCardioversion if subject is in AF
72 Follow-up Assessments 12 month follow-upWindow: +/- 60 daysPhysical assessmentAE assessmentReview of medicationsINR – if anticoagulatedCardioversion if subject is in AFPrimary endpoint evaluation: 48 hour Holter monitor assessment (Zio™ Patch or Pacemaker Interrogation acceptable)
73 Follow-up Assessments 24 month follow-upWindow: +/- 60 daysPhysical assessmentAE assessmentReview of medicationsINR – if anticoagulatedCardioversion if subject is in AF48 hour Holter monitor assessment (Zio™ Patch or Pacemaker Interrogation acceptable)
74 Follow-up Assessments 36 month follow-upWindow: +/- 60 daysPhysical assessmentAE assessmentReview of medicationsINR – if anticoagulatedCardioversion if subject is in AF48 hour Holter monitor assessment (Zio™ Patch or Pacemaker Interrogation acceptable)
75 Summary AF portends to worse long-term outcomes in surgical patients Pathogenesis of AF multifactorialPV responsible in majorityLA Substrate modification contributesMaze IV lesion set address multiple mechanismsAt least all left atrial lesionsRA lesions add to efficacy-minimal costAF portends to worse long-term outcomes in surgical patientsCABG, AVR, MVREfficacy Rates of near 80% off AAD can be achievedLittle extra time and minimal increase in riskNSR improves outcomes in all cardiac surgery patient groups studied
76 ConclusionsAll patients with atrial fibrillation undergoing cardiac surgery should be considered for concomitant maze procedure utilizing the Cox maze IV lesion set.