1. Characterization and Outcome of Severe Primary Multi-vessel Pulmonary Vein Stenosis in Low-birth Weight Infants A. Dickens MS, K. Gauvreau ScD, S.P. Prabhu MD, C. Ireland NP, M. Borisuk NP, K.J. Jenkins MD, C.W. Baird MD Departments of Cardiac Surgery, Cardiology and Radiology Boston Children’s Hospital Harvard Medical School

2. Disclosures No disclosures

3. Background  Primary pulmonary vein stenosis (PVS) is the most aggressive form of the disease.  Multi-vessel disease is universally fatal without intervention.  Poor survival even with therapy (Catheter interventions show limited long term relief of stenoses)  On-going need for evaluation of multi-modal treatment (surgical, interventional, and medical)

4. Purpose The purpose of this study was to characterize primary PVS in young pre-mature infants and evaluate outcomes following surgical intervention.

5. Study Design  Retrospective review of Boston Children’s Hospital PVS registry  February 2008 - July 2014  Multi-vessel primary PVS (≥2 veins)  Pre-operative imaging (Perfusion lung scan, echo, CT scan, cardiac cath)

6. Operative Indications 12 (48%), respiratory failure requiring intubation 17 (68%), RV hypertension > 3/4 systemic

7. Operation  Aggressive operation, “modified sutureless” repair  Diseased PVs unroofed and debrided extending to 1st, and occasionally 2nd order branches  Opening of atretic veins  Thickened endocardial fibrous tissue was aggressively resected. Viola, Caldarone. OTCVS, 16(2), 112–121 (2011)

8. Post-operative management  Post-operative care and follow-up  At 7 days, considered for considered for chemotherapeutic based adjuvant inhibition of VEGF  Lung scans and echocardiography every 4-8 weeks  Computed tomography (CT) scan  Low threshold for catheterization and intervention  Lung transplantation considered if indicated

9. Demographics

10. Operative Characteristics

11. Hypertensive right pulmonary artery compressing the right upper PV RPA Right upper PV

12. Mediastinal shift causing a rotational ostial obstruction of left upper PV Left main bronchus Left upper PV ostium Medistinal shift

13. Atelectasis of left lower lung causing rotational shift of cardiac mass and compression of left lower PV Atelectasis Descending Aorta Left lower PV

14. Pulmonary veins Involved % *

15. Atretic Pulmonary veins %

16. Follow-up

17. Survival Survival probably at: 95% CI 30 days96%(75-99%) 60 days88%(66-96%) 90 days88%(66-96%) 120 days74%(51-87%) Probability of Survival

18. Catheterization based re-intervention 100% patients had post-operative catheterization Median 58 days (range, 5-210) 44% had catheterizations prior to discharge 64% multiple catheterizations Median of 3 caths/patient 88% required re-intervention at catheterization Right upper PV had most normal appearance (p=0.03)

19. Freedom from Pulmonary Vein Re-intervention (Cath) Freedom from Re-intervention Probably of re- intervention: 95% CI 30 days88%(66-96%) 60 days33%(16-52%) 90 days17%(5-34%) 120 days17%(5-34%)

20. Pre-operative patient characteristics and predictors of re- intervention

22. Shorter time to re-intervention with 4 PVs involved vs. 2 or 3 PVs (hazard ratio=2.8, p=0.05)

23. Limitations Variation in surgical technique during study period Single center experience Limited number of patients / low power Limited ability to strictly follow surveillance protocols

24. Conclusions Multiple factors contribute to PVS in young infants. Surgical approach requires consideration of ostial obstructions and external surrounding structures. All patients require aggressive post-op surveillance and catheter-based re-interventions.

25. Conclusions Evolving pattern of disease at the individual pulmonary vein level that needs continued evaluation. Aggressive multi-modal treatment including surgery, catheter-based intervention and targeted cell-inhibition have contributed to improved survival in young infants with multi-vessel PVS.