A. Marc Gillinov, MD For the Cardiothoracic Surgical Trials Network (CTSN) ACC April 2016

1. RATE VERSUS RHYTHM CONTROL FOR ATRIAL FIBRILLATION AFTER CARDIAC SURGERY A. Marc Gillinov, MD For the Cardiothoracic Surgical Trials Network (CTSN) ACC April 2016

2. Disclosures • Consultant/Speaker • AtriCure • Medtronic • On-X • Edwards • Abbott • Research Funding • St. Jude Medical • Tendyne • Equity Interest • Clear Catheter • Cleveland Clinic • Right to receive royalties from AtriCure for a left atrial appendage occlusion device

3. Importance of Post-Op Atrial Fibrillation • Most common complication after cardiac surgery • Incidence 20-50% • No highly effective preventive strategies • Associated with increased rates of death, complications, hospitalizations, and costs

4. 2014 AHA/ACC/HRS Guidelines Postoperative AF • Based on: • Preventive studies of POAF • Limited clinical data J Am Coll Cardiol. 2014;64(21):2246-80

6. Purpose • Determine effectiveness and safety of rate control versus rhythm control for new-onset atrial fibrillation or atrial flutter after cardiac surgery • AF criteria: onset during index hospitalization (within 7 days of surgery) and either: • AF/Aflutter persisting more than 60 minutes • Recurrent episodes of AF/Aflutter

7. Treatment Interventions • Rhythm control • Amiodarone and/or DC-cardioversion • DCC if AF > 24 hours after initiation of amiodarone • Rate control • Beta blocker, calcium channel blocker, or digoxin • To achieve target heart rate < 100 BPM at rest

8. Anticoagulation • Indication for warfarin • Persistent AF > 48 hours post-randomization • Recurrent AF • Treatment • Target INR 2-3 • Continuous anticoagulation recommended for 60 days • Discontinue at physician’s discretion if NSR maintained > 2 weeks or for complications

9. Primary Endpoint • Total number of hospital days within 60 days of randomization • ED visits • < 24 hours counts as 1 day • > 24 hours count actual time • Short stays < 24 hours • Rehospitalizations

10. Study Design Enrolled Pre-op (n=2109) Enrollment Excluded (n=1586) Randomized (n=523) Allocated to Rate Control (n=262) Allocated Rhythm Control (n=261) Allocation • Withdrawal or lost to follow-up (n=14) • Death (n=3) • Received rhythm control (n=70) • Withdrawal or lost to follow-up (n=13) • Death (n=2) • Discontinued treatment (n=63) Follow-Up Primary Endpoint Analysis (n=262) Primary Endpoint Analysis (n=261) Analysis

11. Patient Characteristics Continuous variables are expressed as mean (SD) or median (IQR) and categorical variables as count (%).

12. Patient Characteristics Continuous variables are expressed as mean (SD) or median (IQR) and categorical variables as count (%).

13. Patient Characteristics Continuous variables are expressed as mean (SD) or median (IQR) and categorical variables as count (%).

14. Surgical Characteristics Continuous variables are expressed as mean (SD) or median (IQR) and categorical variables as count (%). a 505 patients underwent bypass. b 500 patients had aorta cross clamped.

15. Frequency of Post-Op AF

16. Days in Hospital (from randomization) Variables are expressed as median (IQR)

17. Mortality and Serious Adverse Events Variables are expressed as number of events (rate per 100 person-months)

18. Readmissions Variables are expressed as number of events (rate per 100 person-months)

19. Readmissions Variables are expressed as number of events (rate per 100 person-months)

20. Time to Stable non-AF Rhythm

21. AF Status by EKG

22. AF Status from Discharge to 60 Days

23. Reasons and Timing of Non-Adherence

24. Anticoagulation Average duration ~45 days in both groups

25. Limitations • Not powered to detect differences in stroke or serious bleeding • Population limited to new onset AF • AF not continuously monitored post-discharge • Frequent treatment discontinuation • No quality of life assessments

26. Summary • No clear advantage of rate or rhythm control strategy • Equal numbers of hospital days • Similar complication rates • Low rates of persistent AF 60 days after onset • More rhythm control patients free of AF at day 60

27. Clinical Inference • Patient and physician preferences should inform treatment choice • An initial strategy of rate control in hemodynamically stable patients with postoperative AF is reasonable • Avoids toxicity associated with amiodarone • Need to institute rhythm control usually evident during index hospitalization

28. Post Operative AF Centers • Baylor College of Medicine • Baylor Research Institute  • Centre Hospitalier de l'Université de Montréal • Cleveland Clinic Foundation • Columbia University • Duke University • Emory University • Hôpital du Sacré-Coeur de Montréal • Hôpital Laval • Mission Hospital  • Montefiore-Einstein Heart Center • Montreal Heart Institute • Mount Sinai Medical Center • NIH Heart Center at Suburban Hospital • Ohio State University Medical Center • University of Alberta Hospital • University of Maryland  • University of Michigan Health Services • University of Pennsylvania • University of Southern California • University of Virginia • University of Wisconsin