1. Aortic Root Surgery in Marfan Syndrome: comparison of valve-sparing versus total root replacement. A Meta-analysis. Angeloni E, Benedetto U, Refice S, Capuano F, Roscitano A, Sinatra R. University of Rome “La Sapienza” Department of Cardiac Surgery, Ospedale Sant’Andrea, Roma

2. Background For decades total root replacement (TRR) with a valved composite graft was the mainstay therapy for aortic root abnormalities in Marfan (MFS) patients. Complications of TRR: Anticoagulation therapy (thrombo-embolism, hemorrhage) Endocarditis

3. Background Aortic valve sparing techniques (VS), introduced by Yacoub (’79) and David (’88), avoid the need for anticouagulation Potential deterioration of preserved leaflets raises concern over the durability of VS in MFS patients

4. Objective Lack of definitive evidence about durability of VS in MFS 1 on-going, Multi-Center study, but only preliminary results on early outcome are available We conducted a Meta-Analysis on available retrospective series

5. Methods Web-base search engine (PubMed and Ovid) On March 04, 2010, a PubMed and EMBASE search of (Valve sparing OR valve preserving) OR (bentall OR root replacement OR composite valve graft) OR (aortic root surgery) AND (marfan) was conducted, limited to publications about humans. In addition, the entire Cochrane library was searched for (valve sparing) OR (valve preserving) OR (Bentall) OR (composite valve graft) OR (aortic root surgery) AND (marfan) in title, abstract, or key words of publications. Retrieved 530 papers Only 45 papers reported data of aortic root surgery in MFS pts Of those, 33 articles were excluded because one of the following: − Less than 30 patients per arm − Not possible extracting data because of design of the study (eg Dissection vs. Aneurysm) − Data from same Institution in the same period (overlapping)

6. Methods  12 articles included in the study (1434 pts) Both arms of 2 comparative studies Single arms of 4 comparative studies (for which arm updated available in literature) 3 studies reporting data only of VS procedures on MFS patients 3 studies reporting data only of TRR procedures on MFS patients

7. Studies included First Author Pub. Year Op. Period Pts. Procedur e SurgTec(%)Urg., (%) MeanFU, y Age, y Groenink19991984-199843TRRCVG (100)13 (30)8,930 Gott I19991968-1996625TRRCVG (97) or HG (3)NR6,734 Alexiou20011972-199865TRRCVG (95) or HG (5)27 (42)841,7 deOliveira20031979-200144TRRCVG (80) or HG (20)16 (36)6,2534 Karck20041979-200274TRRCVG (100)17 (23)9,535 Zehr20051971-200065TRRCVG (97) or HG (3)NR7,637 Savolainen2005?49TRRCVG (100)10 (20)835 Patel I20081997-200656TRRCVG (100)11 (20)9,538,1 Birks19991979-199982VSRemodelling (100)15 (18)5,4733,9 Gott II19991968-199650VSReimplantation (88) or Remodelling (12)NR6,734 Kallenback20071993-200559VSReimplantation (100)3 (5)4,530 Settepani20072000-200635VSReimplantation (100)2 (6)1,5836 Patel II20081997-200684VSReimplantation (52) or Remodelling (48)2 (2)2,529,2 David20091988-2006103VSReimplantation (75) or Remodelling (25)11 (11)7,337

8. Results Procedure Op.Mort,n (%) Late Mort,%/yRedo, %/yTEE, %/yEndoc, %/y Valve-related compl, %/y Groenink 1999 TRR 7 (16,3)3,1 (1,2-5,1)0,6 (-0,2-1,5)NR 0,6 (-0,2-1,5) Gott MC 1999 I TRR 22 (3,5)3,2 (2,7-3,8)0,2 (0,1-0,4)0,7 (0,4-0,9)0,6 (0,4-0,8)0,5 (0,3-0,7) Alexiou 2001 TRR 4 (6,1)3,9 (2,1-5,6)0,2 (-0,2-0,6)1,0 (0,1-1,9)0,2 (-0,2-0,6)0,5 (-0,1-1,1) deOliveira 2003 TRR 1 (2,3)2,2 (0,4-4,0)1,9 (0,2-3,5)0,7 (-0,3-1,8)1,1 (-0,1-2,4)1,2 (-0,1-2,6) Karck 2004 TRR 5 (6,8)3,5 (2,1-4,9)0,9 (0,2-1,6)0,8 (0,1-1,4)0,3 (-0,1-0,7)0,7 (0,0-1,3) Zehr 2005 TRR 3 (4,6)3,6 (1,9-5,3)0,4 (-0,2-0,6)1,1 (0,1-2,0)0,2 (-0,2-0,6)0,6 (-0,1-1,2) Savolainen 2005 TRR 4 (8,2)1,4 (0,2-2,6)NR Patel 2008 I TRR 0 (0)0,8 (0,0-1,5)0,2 (-0,2-0,6)0,9 (0,1-1,8)0,1 (-0,2-0,4)0,4 (-0,1-0,9) Birks 1999 VSRR 4 (4,9)1,9 (0,6-3,2)2,6 (1,1-4,1)0,2 (-0,2-0,7) 1 (0,1-2,0) Gott MC 1999 II VSRR 0 (0)1,5 (0,2-2,8)0,3 (-0,3-0,9) 0,1 (-0,3-0,6)0,2 (-0,3-0,8) Kallenback 2007 VSRR 0 (0)1,9 (0,2-3,5)2,6 (0,7-4,6)0,4 (-0,4-1,1)0,2 (-0,3-0,7)1,1 (-0,2-2,3) Settepani 2007 VSRR 0 (0)0,9 (-1,6-3,4) 5,4 (-0,7- 11,6) 0,9 (-1,6-3,4)1,8 (-1,7-5,4)2,7 (-1,6-7,0) Patel 2008 II VSRR 0 (0)0,2 (-0,4-0,9)2,4 (0,3-4,5)0,5 (-0,5-1,4)0,2 (-0,4-0,9)1,0 (-0,3-2,4) David 2009 VSRR 1 (0,9)0,8 (0,2-1,5)0,4 (-0,1-0,9) 0,1 (-0,1-0,4)0,3 (-0,1-0,7) Overall TRR 46 (4,5)2,5 (2,1-2,8)0,3 (0,2-0,4)0,7 (0,5-0,9)0,3 (0,2-05)0,5 (0,4-0,7) Overall VSRR 5 (1,2)0,8 (0,4-1,2)0,6 (0,3-1,0)0,3 (0,1-0,6)0,2 (-0,0-0,3)0,4 (0,2-0,7)

9. Results – Heterogeneity Test TRR groupVS groupTotal between Pts, n Operative Mortality, %4.51.2χ2 3.9 (p=0.04) Late Mortality, ppy2.50.8χ2 8.1 (p=0.004) Redo, ppy0.30.6χ2 4.8 (p=0.02) TEE, ppy0.70.3χ2 5.6 (p =0.01) Endocarditis, ppy0.30.2χ2 1.9 (p=NS) Valve-related complications, ppy 0.50.4χ2 10.2 (p=NS)

10. Conclusions VS provides significant advantages in thrombo-embolic events and mortality rates when compared to TRR in MFS patients Overall valve-related complications rates did not differ significantly VS was associated with a significant increase in the rate of reintervention Reintervention rate was lower in those with >70% of pts. receiving David operation Thus far, evidence indicates that is feasible and safe for MFS patients, but concern remains about its durability