1. Role of Interventional Catheterization in Post-Operative TOF Patients Jennifer Rutledge, MD October 25, 2013

2. What is our role? To keep patients with TOF away from the surgeons as long as possible

3. What is our role? Treat / palliate the residual lesions patients may be left with and delay the need for future cardiac surgery Hopefully to improve outcome and quality of life

4. Outline When, Why and How? – Timing of intervention Immediate post-operative versus later – Palliative procedures versus complete repair Shunts Pulmonary arteries Conduits and Valves

5. Timing of Intervention: Early Post-Op Patients who have difficulty recovering after surgery have a higher incidence of residual lesions Diagnostic cath can be performed safely in the early post-op period and often results in the discovery of lesions that require further intervention

6. Timing of Intervention: Early Post-Op Interventional cath has historically been avoided in the immediate post-op period Concerns: – Transport of critically ill patients – Worsening clinical status as a result of the procedure – Fear of disruption (rupture) of fresh suture line

7. Timing of Intervention: Early Post-Op Commonly thought a minimum of 6 weeks of adequate scar tissue formation is required for safe intervention Recent data suggests intervention can be performed safely < 6 weeks Performance of successful catheter intervention can improve survival to discharge

8. Timing of Intervention: Early Post-Op Intervention only considered if the lesion is severe enough to compromise clinical status and repeat surgery is considered to be high risk Requires multidisciplinary team Interventional cath doc Surgeon Intensivist Anesthesiologist Nurses, RT, anesthesia and radiology technicians ECMO team Operating room team including nursing and perfusion

9. Timing of Intervention Timing of catheterization outside of the immediate post-op period is largely based on non-invasive imaging and standard criteria – Significant right ventricular outflow tract obstruction – Branch pulmonary artery stenosis – Severe pulmonary valve regurgitation

10. Types of Intervention: Neonatal Shunts Rarely performed in this population – Anomalous coronary artery – Multiple large VSD’s or TOF/AVSD – Contraindication to bypass Central versus modified Blalock-Taussig shunt

11. Shunts Shunt obstruction can occur 3-20% of cases – Thrombosis, suture line stenosis, intimal proliferation, vascular distortion, ductal tissue constriction – Results in cyanosis of the patient – can be life- threatening – Most often occurs acutely after surgery but can occur late – Risk factors: small shunt and pulmonary artery size, polycythemia, competitive blood flow

12. Shunts Interventional cath options: – Mechanical or pharmacological disruption of clot Goal is to break up the clot and dislodge it distally, improving flow across the shunt Can be achieved manually by using catheters/wires/balloons but only useful for fresh clot May be achieved by local thrombolysis or thrombectomy – Local injection of TPA – often requires prolonged infusions » Not practical for shunts or fresh post-op patients

13. Shunts Shunt thrombosis most often develops in association with a stenosis of the shunt and/or adjacent blood vessel – Balloon dilation or stenting performed to disrupt the clot and treat the stenotic lesion – In the immediate post-op period stenting likely safer More predictable and durable result, less recoil of vessel, smaller balloon/stenosis ratio for effective expansion

14. Shunts

17. Pulmonary Arteries Branch pulmonary artery stenosis is a well- known association in TOF population – Post-surgical: at suture line (shunts, proximal branches), ductal constriction – Native: proximal or distal branches Balloon dilation or stenting – What type of intervention is determined by patient/vessel size and anatomy, timing of surgical intervention (past, present and future)

18. Pulmonary Arteries Lots of toys – Regular balloons – High pressure balloons – Ultra-high pressure balloons – Cutting balloons

19. Pulmonary Arteries Intravascular Stents: – Ideally we like to implant stents that can be further dilated to adult size – Depending on the patient size, this is not always possible Place smaller stents that will then need to be cut across at the time of subsequent surgery

20. Pulmonary Arteries Bergersen L et al. Cardiol Young 2005;15:597-604

21. Pulmonary Arteries Bergersen L et al. Cardiol Young 2005;15:597-604

22. Pulmonary Arteries

24. Angtuaco, M. et al. Cathet Cardiovasc Int. 2011;77:395-399.

25. Pulmonary Artery Growth

26. Conduits Frequently used in patients with TOF at various stages of life Conduits fail due to stenosis and/or regurgitation Freedom from conduit replacement 68-95% at 5 years and 0-59% at 10 years Surgical conduit revision may be delayed in some patients by cath intervention

27. Conduits Balloon dilation alone rarely achieves good result Contraindication to conduit stenting – Anomalous coronary artery positioned behind the conduit Risk of coronary compression

28. Conduits Peng LF et al. Circulation 2006;113:2598-2605. Freedom from conduit surgery

29. Conduits Risk factors for need for earlier re-intervention – Younger age, higher pre-stent RV pressure, diagnosis OTHER than TOF, homograft conduits, conduits ≤ 10 mm Stent fracture seen in 43% – 89% immediately behind the sternum – 82% had compromise of the integrity of the stent Peng LF et al. Circulation 2006;113:2598-2605.

30. Conduits

31. Chronic Pulmonary Regurgitation Any patient with transannular patch repair Majority of patients following conduit or bioprosthetic valve implantation Ultimately all patients with TOF will require therapy (repeated) for chronic PR

32. Transcatheter Valves Developed to treat dysfunctional bioprosthetic valves or conduits and reduce number of and prolong time to next surgical intervention Two current options – Medtronic Melody valve – Edwards Sapien valve

33. Melody Valve Bovine jugular vein; platinum/iridium stent Available in Canada since late 2005; as of May 2013 there have been over 5000 implants in 180 centers in 35 countries – ~50% have underlying diagnosis of TOF

34. Melody Valve Can be considered in patients: – > 30 kg, vessels large enough to accommodate the 22F sheath – Implant site 16-22 (24) mm in diameter – Evidence of conduit/valve dysfunction

35. Melody Valve www.medtronic.com

36. Patients, % US IDE UK German Italian Canadian Melody Valve Courtesy Medtronic

37. Patients, % Baseline Patient Characteristics Conduit Type US IDE UK German Italian Canadian Melody Valve Courtesy Medtronic

38. Long-term Outcomes Pulmonary Valve Competence by Echocardiography 6 months None Trace Mild Moderate Severe Patients, % 1 year None Trace Mild Moderate Severe Patients, % 3 years None Trace Mild Moderate Severe Patients, % Long Term Pulmonary Valve Competence Courtesy Medtronic

39. Melody Valve Freedom from re-operation: – Canada: 91%, 83% and 83% at 12, 24 and 36 months, respectively Freedom from transcatheter intervention – Canada: 91% 1 year, 80% 2 year Courtesy Medtronic

40. Complications Stent Fractures (%) Patients, % 24 28 12 30 7.5 Follow up (months) Melody Valve: Complications Stent fracture in 5-25% – Increased use of pre-stenting of conduits reduces this risk Conduit rupture - ~4% requiring treatment (covered stent/surgery) – <1% “uncontained” rupture but can be fatal Coronary artery compression – Can be seen in ~5% of patients during test evaluation – Can be catastrophic Morray BH et al. Circ Cardio Int;2013:6:535-542

43. Transcatheter Valve Melody valve was expanded the role of interventional cath in post-operative patients Limited size range There are many patients with conduits and valves that are not candidates for a Melody valve

44. Sapien Valve Bovine pericardial valve leaflets hand-sewn into a slotted stainless steel stent Fabric sealing cuff on lower portion of stent Designed for aortic position Can be considered for pulmonary valves/conduits ~21 - 30 mm in diameter, patients > 30-35 kg Shorter stent requires that conduits are fully stented prior to Sapien valve insertion Edwards Lifesciences

45. Sapien Valve

47. Sapien vs. Melody Faza et al. Cathet Cardiovasc Int 2013;82(4):E535-41.

48. Sapien vs. Melody Faza et al. Cathet Cardiovasc Int 2013;82(4):E535-41.

49. Transannular Patch What about the really large RVOT’s? Medtronic Native Outflow Tract Pulmonary Valve Courtesy Medtronic

50. Medtronic’s Early Feasibility Study: Non-randomized, Prospective Primary Objective: – Obtain in vivo data to confirm assumptions on loading conditions for future in vitro frame evaluations Secondary Objectives: – Characterize procedural feasibility, safety & TPV performance Up to 20 subjects - Consented for 5 year follow-up at 3 North American Centers (Implants spring 2014 – F/U to 2019) – The Hospital for Sick Children,Toronto Canada – Dr. Lee Benson – Nationwide Children’s Hospital, Columbus Ohio – Dr. John Cheatham – Children’s Hospital, Boston MA – Dr. Jim Lock Courtesy Medtronic

51. Conclusion Patients with TOF are left with residual lesions Cardiac cath lab procedures can treat or palliate many of these lesions and delay the need for repeat cardiac surgery Future advances will expand the therapeutic options to include a broader range of patient diagnoses and patient sizes