1. Mechanical PVR Pearls & Pitfalls Joseph A. Dearani, MD Division of Cardiovascular Surgery AATS Seattle April 2015

2. ©2011 MFMER | slide-2 No disclosures

3. ©2011 MFMER | slide-3 Outline Background Which patients, why to consider Old and new literature Techniques of PVR INR management Thrombolysis Summary Background Which patients, why to consider Old and new literature Techniques of PVR INR management Thrombolysis Summary

4. ©2011 MFMER | slide-4 Background Bioprostheses, homografts – most common, require re-re-replacement… Mechanical valves durable but… require anticoagulation The problem… Bioprostheses, homografts – most common, require re-re-replacement… Mechanical valves durable but… require anticoagulation The problem…

5. ©2011 MFMER | slide-5 And the competition…

6. ©2011 MFMER | slide-6

7. ©2011 MFMER | slide-7 Who? PVR Population – Mayo >3,000 Conotruncal Anomalies native PVR – TOF, PS RV - PA conduit PA-VSD, DORV, Truncus, TGA Failed Ross aortic root + PVR Note – mechanical PVR at Mayo…2% of all PVR

8. ©2011 MFMER | slide-8 Why? ACHD Reoperation (n=1,040) Sternotomy #2 3 4 5+ N=630 298 78 34 Early mortality (%)2 5 8 0 Resp failure (%)5 6 6 15 Pacemaker (%)4 4 4 0 Stroke (%)1 2 3 0 Renal failure (%)3 3 5 3 Sternal infect (%)2 1 6 3 Holst et al. Ann Thorac Surg 2011

9. ©2011 MFMER | slide-9 Survival (%) Years #258341531121813980 #3268208152108 7136 #4 67 47 31 25 16 7 5+ 31 19 14 8 6 3 P=0.010 2323 Sternotomy (no.) 4 5+ Late Survival since Last Sternotomy Holst et al. Ann Thorac Surg 2011

10. ©2011 MFMER | slide-10 ACHD Reoperations (n=1,040) Valve*Repair Replace Pulmonary4 423 Aortic22 234 Tricuspid162 144 Mitral71 114 *85% of all operations were valve-related *25% of all operations were multi-valve Holst et al. Ann Thorac Surg 2011

11. ©2011 MFMER | slide-11 No anticoagulation 6/16 failed

12. ©2011 MFMER | slide-12 No anticoagulation 1/4 failed

13. ©2011 MFMER | slide-13 No anticoagulation 3/11 failed

14. ©2011 MFMER | slide-14 With anticoagulation 1/8 failed with inadequate INR

15. ©2011 MFMER | slide-15 October 1965 August 2008 33 21 Age 5 5 66 33 yr n= 54 Mechanical PVR Stulak et al. Ann Thorac Surg 2010

16. ©2011 MFMER | slide-16 #% BAV s/p Ross1222 TOF1019 Truncus Arteriosus815 Carcinoid713 DORV611 PA/VSD59 TGA36 Other36 #% BAV s/p Ross1222 TOF1019 Truncus Arteriosus815 Carcinoid713 DORV611 PA/VSD59 TGA36 Other36 Preop Cardiac Diagnoses

17. ©2011 MFMER | slide-17 #% TV Replacement1528 Aortic root replacement1426 AV replacement1324 TV repair713 MV replacement59 Other1324 #% TV Replacement1528 Aortic root replacement1426 AV replacement1324 TV repair713 MV replacement59 Other1324 Operative Data Concomitant Procedures Operative Data Concomitant Procedures

18. Survival (%) 522511 877 9262241188 522511 877 9262241188 p=0.10 Mechanical Tissue Mechanical Tissue Follow-up (years) Overall Survival Stulak et al. Ann Thorac Surg 2010

19. Freedom from reoperation (%) 522211877 9262241186 522211877 9262241186 p=0.018 Mechanical Tissue Mechanical Tissue Follow-up (years) Freedom from Reoperation Stulak, Dearani et al. Ann Thorac Surg 2010

20. ©2011 MFMER | slide-20 Follow-up Clotting/Bleeding Events – Mechanical PVR Follow-up Clotting/Bleeding Events – Mechanical PVR PE in 1 (INR 1.4)  Successful lytic therapy 8 late bleeding events  Epistaxis in 5  ICH (FH of AVM’s) in 1  Chest wall hematoma in 1  Menorrhagia in 1 PE in 1 (INR 1.4)  Successful lytic therapy 8 late bleeding events  Epistaxis in 5  ICH (FH of AVM’s) in 1  Chest wall hematoma in 1  Menorrhagia in 1

21. ©2011 MFMER | slide-21 Other new literature… N=121 mechanical PVR 70% male, mean age 23 yr Tetralogy of Fallot 90% Mean follow-up 7 years No early, late mortality N=121 mechanical PVR 70% male, mean age 23 yr Tetralogy of Fallot 90% Mean follow-up 7 years No early, late mortality Dehaki et al. Thorac Cardiovasc Surg 2014

22. ©2011 MFMER | slide-22 Other new literature – cont. PVR malfunction 8.3% 9 thrombosis; 8 thrombolysis, 1 reop Mean time 1.7 yr Freedom from…at 1, 5, 10 years Reop100, 99, 98% Thrombosis100, 93, 91% Bleeding (epistaxis)98% PVR malfunction 8.3% 9 thrombosis; 8 thrombolysis, 1 reop Mean time 1.7 yr Freedom from…at 1, 5, 10 years Reop100, 99, 98% Thrombosis100, 93, 91% Bleeding (epistaxis)98% Dehaki et al. Thorac Cardiovasc Surg 2014

23. ©2011 MFMER | slide-23 19 observational studies; N=299 (adult & peds) Mean follow-up 73 months Nonstructural deterioration1.5% Thrombosis2.2% Reoperation0.9% Thrombolysis0.5% 19 observational studies; N=299 (adult & peds) Mean follow-up 73 months Nonstructural deterioration1.5% Thrombosis2.2% Reoperation0.9% Thrombolysis0.5% Mechanical PVR - Meta-Analysis Dunne et al. Ann Thorac Surg 2015

24. ©2011 MFMER | slide-24 Valve Outcomes Warfarin % No Warfarin % Non-structural dysfunction 0.21.5 Thrombosis0.62.2 Surgical reintervention 0.40.9 Thrombolysis0.20.5 Severe bleeding0.10.4 Dunne et al. Ann Thorac Surg 2015

25. ©2011 MFMER | slide-25 Bioprosthetic failure 3 yr %5 yr %10 yr % Homograft124025 - 60 Pericardial11 - 2622 Contegra20 - 27 Medtronic Freestyle 7 - 16 Hancock II4 - 1750 Melody2 - 10 Dunne et al. Ann Thorac Surg 2015

26. ©2011 MFMER | slide-26 Technique Native RVOT and PA Annulus vs proximal PA; tilt toward confluence Patch may not be necessary with dilated PA

27. ©2011 MFMER | slide-27 Intimal Peels in Right-sided Conduits

28. ©2011 MFMER | slide-28 PA RV Bovine Pericardial Conduit Roof No intimal peels

29. ©2011 MFMER | slide-29 Prosthesis Selection

30. Advances Anticoagulation for Valves Advances Low intensity AC for bileaflet aortic prostheses Patient INR self-testing Novel anticoagulants on the way

31. ©2011 MFMER | slide-31 Point-of-Care INR Instruments

32. Time In Range Lafata JE. J Gen Intern Med 2000 89 % 6%6% 5%5% % Time in Range Low Therapeutic High

33. Reduction in AE Rate Thromboembolic Hemorrhage Horstkotte D. J Heart Valve Dis 2004 3.6 % 0.9 % 11 % 4.5 % Percent per pt-yr

34. ©2011 MFMER | slide-34 “ Thrombolysis is the recommended initial treatment for thrombosed right-sided mechanical valves.” JS Alpert JACC 2003 When it happens…

35. Thrombolysis Urokinase, Streptokinase, rt-PA Lytic agent + heparin Temporary pacing with  HR Kao et al. Tex Heart Inst J 2009 Lengyel et al. J Heart Valve Dis 2005 Alpert J Am Coll Cardiol 2003 Manteiga et al. J Thorac Cardiovasc Surg 1998 Keuleers et al. Am J Cardiol 2011 Kogon et al. J Thorac Cardiovasc Surg 2004

36. ©2011 MFMER | slide-36 Anticoagulation for PVR Mayo Clinic Practice Aspirin (81 mg/day) + warfarin Isolated PVRINR 2.5 – 3.0 AVR + PVRINR 3.0 – 3.5

37. ©2011 MFMER | slide-37 Excellent durability Low risk – thrombosis, valve failure Consider in selected patients Multiple prior operations Receiving AC for other reasons, e.g., AVR Premature bioprosthetic degeneration INR self-testing essential Summary – Mechanical PVR

38. Questions & Discussion