1. Late outcomes of the Cox-Maze IV procedure for atrial fibrillation Matthew C. Henn MD, Timothy S. Lancaster MD, Jacob R. Miller MD, Laurie A. Sinn RN, BSN, Richard B. Schuessler PhD, Marc R. Moon MD, Spencer J. Melby MD, Hersh S. Maniar MD, Ralph J. Damiano, Jr., MD Division of Cardiothoracic Surgery, Department of Surgery Washington University School of Medicine and Barnes-Jewish Hospital St. Louis, Missouri, USA

2. Department of Surgery Division of Cardiothoracic Surgery Background The Cox-Maze IV procedure (CMPIV) is the gold standard for the surgical treatment of atrial fibrillation (AF). Freedom from AF off antiarrhythmic drugs (AADs) of 75- 80% at two years follow up in all patient subgroups. Equivalent freedom from AF as the “cut-and-sew” Cox-Maze III procedure, but with reduced cardiopulmonary bypass time, cross-clamp time, and major morbidity. Lawrance CP, et al. J Thorac Cardiovasc Surg. 2014 Sep;148(3):955-61. Weimar T, et al. Circ Arrhythm Electrophysiol. 2012 Feb;5(1):8-14.

3. Department of Surgery Division of Cardiothoracic Surgery Damiano RJ, et al. J Thorac Cardiovasc Surg. 2011 Jan;141(1):113-21. Freedom from atrial tachyarrhythmias (ATAs) Background: Predictors of recurrence % Freedom from ATAs

4. Department of Surgery Division of Cardiothoracic Surgery VariableOdds Ratio95% CIp value Left atrial size1.421.04 – 1.940.027 Early atrial tachyarrhythmia3.021.07 – 8.4550.010 Left atrial box lesion0.380.167 – 0.8710.022 Background: Predictors of ATA recurrence at one year follow up Damiano RJ, et al. J Thorac Cardiovasc Surg. 2011 Jan;141(1):113-21.

5. Department of Surgery Division of Cardiothoracic Surgery Background There have been very few analyses of late outcomes with the Cox-Maze IV procedure. Important because of questionable long-term durability of radiofrequency and cryothermal ablation lesions, which may influence late treatment success.

6. Department of Surgery Division of Cardiothoracic Surgery Purpose To describe our five year outcomes of the Cox-Maze IV procedure and to analyze risk factors for late recurrence of atrial tachyarrhythmias.

7. Department of Surgery Division of Cardiothoracic Surgery Methods: Study design 576 consecutive patients from January 2002 – Dec 2013 Data were entered prospectively into the STS database and a longitudinal Maze database maintained at our institution. All patients underwent the Cox-Maze IV procedure (n=532) or a left atrial Cox-Maze IV procedure (n=44), either alone or with a concomitant cardiac procedure. 119 patients (21%) underwent a minimally invasive approach via right mini-thoracotomy.

8. Department of Surgery Division of Cardiothoracic Surgery Adapted from Weimar T, et al. J Interv Card Electrophysiol, 2011;31:47-54. Damiano RJ, et al. J Thorac Cardiovasc Surg. 2011 Jan;141(1):113-21. Right Atrial Lesion SetLeft Atrial Lesion Set Methods: Cox-Maze IV procedure Superior connecting lesion Box lesion

9. Department of Surgery Division of Cardiothoracic Surgery 576 Consecutive Patients Concomitant CMPIV: n = 366 (71%) Stand-alone CMPIV: n = 146 (29%) Non-paroxysmal AF n = 193 (53%) Paroxysmal AF n = 170 (47%) Non-paroxysmal AF n = 112 (77%) Non-box lesion: n = 64 (11%) Methods: Patient population Paroxysmal AF n = 34 (23%)

10. Department of Surgery Division of Cardiothoracic Surgery Methods: Study endpoints Efficacy: Freedom from atrial tachyarrhythmias (ATAs) Freedom from ATAs without antiarrhythmic drugs (AADs) Recurrence: any ATA of at least 30 seconds duration Sub-analyses: Paroxysmal AF vs. non-paroxysmal AF Stand-alone vs. concomitant CMPIV Calkins H, et al. Heart Rhythm. 2012 Apr;9(4):632-696.e21.

11. Department of Surgery Division of Cardiothoracic Surgery Demographic Overall (n=576) Paroxysmal AF (n=237, 42%) Non-paroxysmal AF (n=336, 58%) p value Age (yr) 64 ± 1263 ± 1264 ± 12 0.737 Male351/576 (61%)133/237 (56%)119/336 (64%)0.041 Persistent AF66/576 (11%)N/A66/336 (20%)N/A Long-standing persistent AF270/576 (47%)N/A270/336 (80%)N/A Left atrial size (cm) 5.2 ± 1.15.0 ± 1.15.3 ± 1.1 0.006 Preop duration of AF (yr) 5.8 ± 6.94.9 ± 7.16.6 ± 6.8 0.005 Failed catheter ablation117/576 (20%)22/237 (9%)95/336 (28%)< 0.001 Preoperative pacemaker73/576 (13%)30/237 (13%)43/336 (13%)0.961 Results: Preoperative demographics

12. Department of Surgery Division of Cardiothoracic Surgery Results: Follow up Follow up: 89% of patients at any time point 84% of patients at 1 year 58% of patients at 5 years Mean follow up time 3.3 ± 4.7 years Prolonged cardiac monitoring 52% of patients at 5 years

13. Department of Surgery Division of Cardiothoracic Surgery Results: Box vs. no box lesion Freedom from ATAs p = 0.060 p = 0.660 p = 0.630 p = 0.091 p = 0.005

14. Department of Surgery Division of Cardiothoracic Surgery p < 0.001 p = 0.017 p = 0.024 p = 0.068 p = 0.017 Results: Box vs. no box lesion Freedom from ATAs off AADs

15. Department of Surgery Division of Cardiothoracic Surgery p = 0.104 p = 0.052 p = 0.554 p = 0.414 p = 0.949 Results: Paroxysmal vs. non-paroxysmal AF Freedom from ATAs

16. Department of Surgery Division of Cardiothoracic Surgery p = 0.147 p = 0.509 p = 0.394 p = 0.604 p = 0.970 Results: Paroxysmal vs. non-paroxysmal AF Freedom from ATAs off AADs

17. Department of Surgery Division of Cardiothoracic Surgery p = 0.949 p = 0.770 p = 0.442 p = 0.086 p = 0.302 Results: Stand-alone vs. concomitant CMPIV Freedom from ATAs

18. Department of Surgery Division of Cardiothoracic Surgery p = 0.532 p = 0.481 p = 0.090 p = 0.430 p = 0.307 Results: Stand-alone vs. concomitant CMPIV Freedom from ATAs off AADs

19. Department of Surgery Division of Cardiothoracic Surgery Variablep value (1 yr)p value (5 yr) No box lesion<0.0010.008 Early atrial tachyarrhythmia0.0010.013 Preoperative duration of AF0.5680.010 Left atrial size0.0020.547 Preoperative pacemaker0.0030.070 Overall major complications1.0000.045 ICU length of stay0.7970.035 Hospital length of stay0.7230.009 Results: Predictors of recurrence (univariate)

20. Department of Surgery Division of Cardiothoracic Surgery Results: Predictors of recurrence (multivariate) VariableOdds Ratio95% CIp value 1 year follow up: Left atrial size1.291.02 – 1.620.031 Preoperative pacemaker2.491.35 – 4.600.004 No box lesion4.552.36 – 8.78<0.001 5 year follow up: Preoperative duration of AF1.091.02 – 1.160.008 Hospital length of stay1.091.01 – 1.170.026

21. Department of Surgery Division of Cardiothoracic Surgery Probability of ATA or AAD (%) Preoperative AF duration (yr) Results: Effect of preop AF duration on recurrence

22. Department of Surgery Division of Cardiothoracic Surgery Conclusions Freedom from ATAs after the Cox-Maze IV procedure was equivalent for patients with both paroxysmal and non- paroxysmal AF, and for patients undergoing stand-alone or concomitant procedures. Isolation of the posterior left atrium was a critical part of the Maze procedure. If this was not done, the 5 year freedom from ATAs and AADs was less than 35%. The preoperative duration of AF was the most important predictor of late treatment failure. This would argue for earlier intervention in patients with known AF.

23. Department of Surgery Division of Cardiothoracic Surgery Thank you