Valve-Sparing Aortic Root Replacement in Loeys-Dietz Syndrome

Valve-Sparing Aortic Root Replacement in Loeys-Dietz Syndrome Nishant D. Patel, MD, George J. Arnaoutakis, MD, Timothy J. George, MD, Jeremiah G. Allen, MD, Diane E. Alejo, BA, Harry C. Dietz, MD, Duke E. Cameron, MD, and Luca A. Vricella, MD Johns Hopkins Division of Cardiac Surgery, Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland Background. Loeys-Dietz syndrome (LDS) is a recently recognized aggressive aortic disorder characterized by root aneurysm, arterial tortuosity, hypertelorism, and bifid uvula or cleft palate. The results of prophylactic root replacement using valve-sparing procedures (valvesparing root replacement [VSRR]) in patients with LDS is not known. Methods. We reviewed all patients with clinical and genetic (transforming growth factor- receptor mutations) evidence of LDS who underwent VSRR at our institution. Echocardiographic and clinical data were obtained from hospital and follow-up clinic records. Results. From 2002 to 2009, 31 patients with a firm diagnosis of LDS underwent VSRR for aortic root aneurysm. Mean age was 15 years, and 24 (77%) were children. One (3%) patient had a bicuspid aortic valve. Preoperative sinus diameter was 3.9 0.8 cm (z score 7.0 2.9) and 2 (6%) had greater than 2 aortic insufficiency. Thirty patients (97%) underwent reimplantation procedures using a Valsalva graft. There were no operative deaths. Mean follow-up was 3.6 years (range, 0 to 7 years). One patient required late repair of a pseudoaneurysm at the distal aortic anastomosis, and 1 had a conversion to a David reimplantation procedure after a Florida sleeve operation. No patient suffered thromboembolism or endocarditis, and 1 (3%) patient experienced greater than 2 late aortic insufficiency. No patient required late aortic valve repair or replacement. Conclusions. Loeys-Dietz syndrome is an aggressive aortic aneurysm syndrome that can be addressed by prophylactic aortic root replacement with low operative risk. Valve-sparing procedures have encouraging early and midterm results, similar to those in Marfan syndrome, and are an attractive option for young patients. (Ann Thorac Surg 2011;92:556 61) 2011 by The Society of Thoracic Surgeons Aortic root aneurysms are rare in children; they are usually associated with connective tissue disorders and conotruncal congenital heart disease and may complicate some cardiovascular surgical operations such as the Ross procedure, Norwood procedure, and arterial switch. Aortic root replacement may be indicated in some children to prevent aneurysm rupture, aortic dissection, and valvar incompetence. Traditionally the Bentall procedure [1] has been the operation of choice for aortic root disease and has demonstrated excellent long-term outcomes [2 4]. However an aortic valve with a mechanical prosthesis necessitates long-term anticoagulation and bioprosthetic valves have limited durability in young patients. These considerations make valve-sparing aortic root replacement (VSRR), originally described by Sarsan and Yacoub [5] and David and Feindel [6], an attractive option for children with aortic root aneurysms. Recently Loeys and Dietz described an autosomaldominant inherited syndrome resulting from mutations Accepted for publication April 1, 2011. Presented at the Fifty-seventh Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 3 6, 2010. Address correspondence to Dr Vricella, Johns Hopkins Medical Institutions, 600 N Wolfe St, Blalock 618, Baltimore, MD 21287; e-mail: lvricella@jhmi. edu. in the receptors for transforming growth factor (TGF)- [7]. Loeys-Dietz syndrome (LDS) is characterized by aggressive vascular disease, arterial tortuosity and aneurysm, hypertelorism, and bifid uvula or cleft palate. Patients with LDS experience aortic dissection and rupture at smaller aortic diameters and at a younger age than do patients with Marfan syndrome. We have embarked on a program of early prophylactic aortic root replacement to prevent vascular catastrophe in LDS. This review was conducted to evaluate the safety and early results of this surgical program. Material and Methods Study Design, Patient Selection, and Patient Variables After institutional review board approval, data were collected retrospectively for all patients with LDS who underwent VSRR between 2002 and 2009 at the Johns Hopkins Hospital. Data were obtained from medical and electronic patient records. A waiver for individual consent was granted by our institutional review board. All patients who underwent VSRR had transthoracic echocardiograms to assess preoperative and postoperative aortic valve function. Intraoperative transesophageal echocardiograms were routinely obtained. Echocardiographic data included maximum aortic sinus diameter, 2011 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2011.04.003

Ann Thorac Surg PATEL ET AL 2011;92:556 61 VSRR IN LOEYS-DIETZ SYNDROME 557 sinotubular junction diameter, and annular diameter with respective z scores (number of SDs away from mean for aortic dimensions based on patient body surface area), as well as the degree of aortic insufficiency (0 to 4 ). Clinical follow-up data, including postoperative aortic insufficiency and need for reoperation on the aortic root, were obtained by telephone interviews with the patient, family members, and primary care physicians. Some patients with LDS and aortic root aneurysm/ dissection were not offered VSRR and instead had root replacement with composite grafts. Our relative contraindications for VSRR include marked leaflet fenestration and asymmetry, acute aortic dissection in unstable patients, and a giant root with marked leaflet irregularities. For these patients, a Bentall procedure was performed. In addition, we do not routinely perform VSRR on bicuspid aortic valves with extensive calcification, severe prolapse, marked fenestrations, or a combination of these anomalies. The diagnosis of LDS was confirmed both by genetic analysis and clinical phenotype in collaboration with colleagues in the McKusick Department of Medical Genetics and the Connective Tissue Disorders Clinic at the Johns Hopkins Hospital. Operative Technique Patients underwent a modified David V procedure in which the native aortic valve was resuspended within a Dacron tube graft with prefashioned pseudosinuses (Gelweave Valsalva graft; Vaskutek, Renfrewshire, Scotland, UK). One patient had a reimplantation procedure using a straight Dacron graft because of unavailability of an appropriate small-sized Valsalva graft. Our operative technique has been described in detail elsewhere [8]. All operations are performed through a median sternotomy. Patients are placed on cardiopulmonary bypass using aortic and bicaval venous cannulation. A vent is placed in the left atrium through the right superior pulmonary vein. After aortic clamping and cardioplegic arrest, the aorta is divided above the sinotubular ridge. Using commercial valve sizers, we determine the diameter of the sinotubular junction that provides optimal leaflet apposition and then select a Valsalva graft that is 2 to 3 mm larger because the prosthesis fits outside the aortic valve complex. The base of the aorta is dissected externally down to a subannular level. This is followed by excision of sinus tissue, leaving an approximately 4-mm to 5-mm sinus remnant attached to the annulus. The coronary arteries are mobilized widely. Three 3-0 braided polyester pledgetted horizontal mattress sutures are passed under the annulus at the nadir of each aortic leaflet from inside outward. Our procedure differs from the original David I reimplantation technique in that only 3 subannular sutures are placed. The subannular sutures anchor the graft and ensure that the entire aortic valve complex is within the sinus segment of the Valsalva graft. The proximal collar of the graft is trimmed to 2 rings. The distal end of the graft is usually trimmed to 4 to 5 rings but may be left longer if more extensive replacement of the ascending aorta or arch is necessary. The 3 subannular sutures are passed inside-out through the bottom of the Valsalva graft 120 degrees apart from each other. The stay sutures are drawn up within the graft, which is lowered around the valve complex, and the 3 subannular sutures are tied. The commissures are fixed to the sinotubular junction of the graft using 3 4-0 polypropylene pledgetted mattress sutures. In most patients the commissure height is level with the sinotubular ridge of the graft. In patients with very large roots and tall commissures, fixation can be just above the ridge. The valve is now properly positioned within the graft by the 3 below and the 3 above fixation sutures. Starting at the bottom of each sinus and sewing upward to the commissure tops, continuous 4-0 polypropylene sutures are used to fix the sinus remnant and annulus within the graft. This is the hemostatic suture line. Holes are cut in the graft opposite the coronary artery buttons. We encircle the coronary buttons with polytetrafluoroethylene (Teflon) felt lifesaver pledgets. The left and right coronary anastomoses are completed with 4-0 polypropylene. Finally the distal graft is anastomosed to the aorta using continuous 4-0 polypropylene suture and an external felt strip. Air is evacuated from the heart, the aortic cross-clamp is removed, and the heart is resuscitated. Statistical Analysis Statistical analyses were conducted with Stata version 9.0 software package (Stata Corporation, College Station, TX). Survival and freedom from reoperation of the aortic root were estimated using the Kaplan-Meier method. All continuous variables are presented as mean SD, unless otherwise noted. Results Preoperative Clinical Characteristics A total of 31 patients with a firm diagnosis of LDS underwent VSRR between 2002 and 2009. Preoperative patient characteristics are shown in Table 1. Mean age at operation was 14.6 12.8 years (median, 12.7 years; range, 9 months to 60 years), and 14 (45.2%) were female Table 1. Baseline Clinical Characteristics Variable N 31 (%) Mean age at operation (years) 14.6 12.8 Female patient 14 (45.2) Pediatric ( 18 years) 24 (77.4) Previous cardiac surgery 5 (16.1) Bicuspid aortic valve 1 (3.2) Preoperative maximum sinus 3.9 0.8 (z 7.0 2.9) diameter (cm) Preoperative sinotubular junction 2.8 0.8 (z 4.6 2.5) diameter (cm) Preoperative annular diameter (cm) 2.2 0.5 (z 3.8 2.3) Preoperative 2 aortic 2 (6.5) insufficiency

558 PATEL ET AL Ann Thorac Surg VSRR IN LOEYS-DIETZ SYNDROME 2011;92:556 61 patients. Twenty-four (77.4%) were younger than 18 years of age at the time of operation. One (3.2%) had a bicuspid aortic valve. Five (16.1%) patients had had previous cardiac surgery. All were New York Heart Association class I preoperatively. Preoperative sinus diameter was 3.9 0.8 cm (z score 7.0 2.9), sinotubular junction diameter was 2.8 0.8 cm (z score 4.6 2.5), and annular diameter was 2.2 0.5 cm (z score 3.8 2.3). Two (6.5%) patients had greater than 2 aortic insufficiency on preoperative echocardiography. Operative Data Operative data are displayed in Table 2. One patient (3.2%) underwent David I reimplantation with a straight tube Dacron graft, and 30 (96.8%) patients had reimplantation procedures using a Valsalva graft. Mean cardiopulmonary bypass and cross-clamp times were 144.4 21.7 and 101.3 17.5 minutes, respectively. The most common prosthesis size was 24 mm and was used in 13 (41.9%) patients. Fifteen (48.4%) patients had patent foramen ovale closure at the time of VSRR. Three (9.7%) had concomitant patent ductus arteriosus ligation, 3 (9.7%) had atrial septal defect closure, and 1 (3.2%) had a ventricular septal defect closure. Two (6.5%) patients had concomitant aortic valve repair at the time of VSRR. Survival and Functional Class There were no operative or late deaths. Kaplan-Meier survival was 100% at 7 years. All patients were New York Hospital Association class I at follow-up. In-Hospital Complications Four (12.9%) patients experienced pneumothorax postoperatively. Postoperative infection rates were low. Two (6.5%) patients had postoperative pneumonia. There were no postoperative urinary tract infections or sternal wound infections. Table 2. Operative Data Variable N 31 (%) Mean cross-clamp time (min) 101.3 17.5 Mean cardiopulmonary bypass time (min) 144.4 21.7 Concomitant procedures Aortic valve repair 2 (6.5) Patent foramen ovale closure 15 (48.4) Atrial septal defect 3 (9.7) Ventricular septal defect 1 (3.2) Patent ductus arteriosus ligation 3 (9.7) Table 3. Preoperative and Postoperative Sinus and Annular Diameters Variable Preoperative Postoperative p Value Annulus (cm) 2.2 0.5 2.2 0.4 1.0 Annulus z score 3.8 2.3 2.6 3.1 0.08 Maximum sinus (cm) 3.9 0.8 3.0 0.4 0.001 Maximum sinus z score 7.0 2.9 2.6 2.6 0.001 Late Outcomes Mean follow-up was 3.7 years (range, 0 to 7 years). One 8-year-old female patient who underwent reimplantation with a 24-mm Valsalva graft required repair of a distal pseudoaneurysm 29 months postoperatively. Preoperative and postoperative maximum sinus and annular diameters with respective z scores are shown Table 3. A 1-year-old patient who initially underwent a Florida sleeve procedure experienced a coronary artery button aneurysm and then had a VSRR with the Valsalva graft 4 years later. One patient experienced greater than 2 aortic insufficiency 4.3 years after reimplantation with the Valsalva graft. Freedom from late aortic valve repair or replacement was 100% at 1, 3, and 5 years after reimplantation. No patient experienced thromboembolism or endocarditis at follow-up and no patient had coronary artery anastomotic dehiscence. Comment Aortic root replacement with a mechanical valve has been the gold standard of care for patients with aortic root aneurysms for more than 40 years. It has been a safe, reproducible, and durable operation, but nonetheless results in a low, constant risk of thromboembolism, endocarditis, and anticoagulant-related hemorrhage [2 4]. Implications for lifestyle modification are not insignificant for many patients. For these reasons, we and others have adopted and selectively applied alternative valvepreservation surgical strategies for aortic root replacement over the last 15 years. Low operative mortality and good midterm results have been reported after VSRR in patients with aortic aneurysm [9 18]. In our initial experience, we used the remodeling technique with scalloped Dacron tongues because of the theoretic advantage of preserved sinuses [19 23]. However we observed a trend toward late annular dilatation and aortic insufficiency likely caused by splaying of the Dacron tongues and loss of leaflet apposition height. This has been observed particularly in patients with connective tissue disorders. Our protocol changed to the reimplantation procedure in 2002 when the Gelweave Valsalva graft, a Dacron graft with prefashioned pseudosinuses, became commercially available. We believe that the reimplantation technique using the Valsalva graft preserves sinuses, stabilizes the aortic root below the nadir of the sinuses, and improves hemostasis. Results of VSRR in Marfan syndrome have been reported, but such results are lacking for LDS [24]. LDS results from mutations in the gene coding for receptors for TGF-, which lead to abnormal TGF- signaling and abnormal collagen deposition in the aortic wall. The latter, along with elastin disarray, results in a structurally weak medium that predisposes to aortic aneurysm, dissection, and rupture [24].

Ann Thorac Surg PATEL ET AL 2011;92:556 61 VSRR IN LOEYS-DIETZ SYNDROME 559 Patients with LDS present with a characteristic phenotype of hypertelorism, bifid uvula or cleft palate (or both), and arterial tortuosity [24]. Like their Marfan counterparts, patients with LDS share a predisposition for aneurysm of the aortic root and risk of rupture and dissection, even in childhood. At our institution patients with LDS are referred for surgical intervention at a younger age and smaller aortic root diameters than patients with Marfan syndrome in concordance with the more aggressive vascular phenotype of the former. We reported our initial surgical experience in patients with LDS in 2004 [25]. In that study 14 of the 71 patients with LDS underwent VSRR at 2 separate institutions (Johns Hopkins and University of Ghent). One pediatric patient initially underwent VSRR/arch replacement at Ghent Hospital, required subsequent Bentall operation, and died 11 years after the initial VSRR procedure. This initial experience was instructive in the importance of early prophylactic root replacement and frequent surveillance of the vascular tree. Of the 71 patients, fatal intracerebral and aortic catastrophies occurred in 3 patients younger than 10 years of age. Furthermore, aortic rupture occurred at diameters less than 4.5 cm, which is a rare event in Marfan syndrome. For most adult patients with ascending aortic aneurysm, the threshold for elective aortic root replacement is an aortic diameter of greater than 5.0 cm, rate of aortic root growth greater than 1.0 cm/year, or worsening aortic insufficiency. Indications for VSRR for patients with LDS are not as well defined. Given the much greater risk of aortic catastrophe in LDS, our current threshold for aortic root replacement in adults is an aortic root diameter greater than 4.0 cm or root expansion greater than 0.5 cm/year. For children with severe craniofacial abnormalities (Loeys-Dietz type I) we advise surgery at an aortic root z score greater than 3.0 or an aortic root expansion greater than 0.5 cm/year. For children with mild craniofacial abnormalities (Loeys-Dietz type II), we recommend surgery at an aortic root z score greater than 4.0 or an aortic root that expands greater than 0.5 cm/year. We are also reconsidering our management of the distal ascending aorta and proximal arch at the time of root replacement. None of the patients in this series had an arch or hemiarch replacement because the arch diameters were normal at the time of the valve-sparing procedure. However several patients experienced dilatated distal ascending aortas and proximal arches within a few years postoperatively; this too is an unusual event in Marfan syndrome. Further experience may suggest that more aggressive proximal aortic resection is indicated in some patients with LDS. In this present study all but 1 patient had a reimplantation procedure using the Valsalva graft. A straight Dacron graft was used in that 1 patient because the aortic root diameter was smaller than 24 mm, the smallest commercially available Valsalva graft. The absence of operative and late deaths is encouraging, as is the absence of thromboembolic events or endocarditis at midterm follow-up. However 1 patient experienced greater than 2 aortic insufficiency 4.3 years after reimplantation with the Valsalva graft. At the time of the original operation we noted marked leaflet fenestrations, but these were not considered severe enough to warrant valve replacement. Although this patient will likely require valve replacement in the years ahead, the remainder of the postoperative cohort has enjoyed excellent freedom from significant valve regurgitation or reoperation. Surgeon experience and patient selection are critical for good outcomes. Our operative technique for reimplantation using the Valsalva graft is simple and reproducible. We recommend a Bentall procedure for patients with severe aortic insufficiency who have marked leaflet asymmetry or leaflet fenestrations as well as for patients with bicuspid valves and significant stenosis, thickening, prolapse, or fenestrations. Composite grafts are likely to play a role in the management of patients with LDS; over the time course of this study, 30 patients with LDS had an aortic root replacement with a composite graft. For postoperative surveillance, we recommend that all patients who receive VSRR undergo echocardiography, computed tomography (CT), or magnetic resonance imaging 6 months postoperatively and annually thereafter to monitor aortic root diameter and valve competence. Because of the aggressive nature of LDS and the risk of rupture and dissection at smaller aortic root diameters, we recommend echocardiography every 3 to 6 months for 1 year after surgery and every 6 months thereafter. Given the widespread involvement of the arterial tree in patients with LDS, we also recommend annual head-topelvis body CT scans. Valve-sparing root replacement is a safe and effective surgical option for the management of aortic root aneurysm in patients with LDS. Because of the malignant and aggressive nature of this aortopathy, early recognition of the syndrome by clinical phenotype or genetic analysis is critical. We recommend the reimplantation technique with the Valsalva graft for prophylactic root replacement because of improved stabilization of the annulus, better hemostasis, and preservation of sinuses. Although longterm results are not yet available, midterm outcomes are encouraging. References 1. Bentall HH, De Bono A. A technique for complete replacement of the ascending aorta. Thorax 1968;23:338 9. 2. Gott VL, Greene PS, Alejo DE, et al. Replacement of the aortic root in patients with Marfan s syndrome. N Engl J Med 1999;340:1307 13. 3. Gott VL, Cameron DE, Alejo DE, et al. Aortic root replacement in 271 Marfan patients: a 24-year experience. Ann Thorac Surg 2002;73:438 43. 4. Cameron DE, Alejo DE, Patel ND, et al. Aortic root replacement in 372 Marfan patients: evolution of operative repair over 30 years. Ann Thorac Surg 2009;87: 1344 50. 5. Sarsan MAI, Yacoub M. Remodeling of the aortic valve annulus. J Thorac Cardiovasc Surg 1993;105:435 8. 6. David TE, Feindel CM. An aortic valve-sparing operation for patients with aortic incompetence and aneurysm of the ascending aorta. J Thorac Cardiovasc Surg 1992;103:617 22.

560 PATEL ET AL Ann Thorac Surg VSRR IN LOEYS-DIETZ SYNDROME 2011;92:556 61 7. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006;355:788 98. 8. Cameron DE, Vricella LA. Valve-sparing aortic root replacement in Marfan syndrome. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005;8:103 111. 9. David TE, Ivanov J, Armstrong S, Feindel CM, Webb GD. Aortic valve-sparing operations in patients with aneurysms of the aortic root and ascending aorta. Ann Thorac Surg 2002;74:S1758 61. 10. Kallenbach K, Hagl C, Walles T, et al. Results of valvesparing aortic root reconstruction in 158 consecutive patients. Ann Thorac Surg 2002;74:2026 32. 11. Kallenbach K, Karck M, Pak D, et al. Decade of aortic valve sparing reimplantation: are we pushing the limits too far? Circulation 2005;112(9 suppl ): I253 259. 12. Settepani F, Szeto WY, Pacini D, et al. Reimplantation valve-sparing aortic root replacement in Marfan syndrome using the Valsalva conduit: an intercontinental multicenter study. Ann Thorac Surg 2007;83:S769 73. 13. Patel ND, Williams JA, Barreiro CJ, et al. Valve-sparing aortic root replacement: early experience with the De Paulis Valsalva graft in 51 patients. Ann Thorac Surg 2006;82:548 53. 14. Bethea BT, Fitton TP, Alejo DE, et al. Results of aortic valve-sparing operations: experience with remodeling and reimplantation procedures in 65 patients. Ann Thorac Surg 2004;78:767 72. 15. Pacini D, Settepani F, De Paulis R, et al. Early results of valve-sparing reimplantation procedure using the Valsalva conduit: a multicenter study. Ann Thorac Surg 2006;82:865 71. 16. Patel ND, Weiss ES, Alejo DE, et al. Aortic root operations for Marfan syndrome: a comparison of the Bentall and valve-sparing procedures. Ann Thorac Surg 2008;85:2003 11. 17. de Oliveira NC, David TE, Ivanov J, et al. Results of surgery for aortic root aneurysm in patients with Marfan syndrome. J Thorac Cardiovasc Surg 2003;125:789 96. 18. David TE, Feindel CM, Webb GD, Colman JM, Armstrong S, Maganti M. Aortic valve preservation in patients with aortic root aneurysm: results of the reimplantation technique. Ann Thorac Surg 2007;83:S732 5. 19. Leyh RG, Schmidtke C, Sievers HH, Yacoub MH. Opening and closing characteristics of the aortic valve after different types of valve-preserving surgery. Circulation 1999;100: 2153 60. 20. Bellhouse BJ. Velocity and pressure distributions in the aortic valve. J Fluid Mechanics 1969;37:587 600. 21. Thubrikar MJ, Nolan SP, Aouad J, Deck JD. Stress sharing between the sinus and leaflets of canine aortic valve. Ann Thorac Surg 1986;42:434 40. 22. Grande-Allen KJ, Cochran RP, Reinhall PG, Kunzelman KS. Recreation of sinuses is important for sparing the aortic valve: a finite element study. J Thorac Cardiovasc Surg 2000;119:753. 23. De Paulis R, De Matteis GM, Nardi P, Scaffa R, Bassano C, Chiariello L. Analysis of valve motion after the reimplantation type of valve-sparing procedure (David I) with a new aortic root conduit. Ann Thorac Surg 2002;74:53 7. 24. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005;37:275 81. 25. Williams JA, Loeys BL, Nwakanma LU, et al. Early surgical experience with Loeys-Dietz: a new syndrome of thoracic aortic aneurysm disease. Ann Thorac Surg 2007;83:S757 63. DISCUSSION DR THORALF SUNDT (Rochester, MN): I hate to shake everybody up twice in the same day between the picture of me from earlier this morning in Keith s address and now my appearance in a congenital session, but I appreciate the invitation from the program committee nonetheless. I have a long-standing interest in surgery for congenital heart disease, and the valve-sparing root procedure is one of my favorite operations as well. So congratulations Dr Patel. It was a beautiful presentation. In addition, I should point out that the Tiki Award as originally conceived can be given for outstanding slides as well, and this is one of the most clear, beautiful presentations I have seen in a long time. So I would recommend that the Tiki Committee consider giving the award to somebody who did it right and not always for somebody who did it wrong. Congratulations to you, congratulations to Duke, to Luca, and to Bill for mentoring you and bringing you along. It is critical to the health of our specialty that residents in general surgery be brought along to become interested in this specialty. My first questions for you are, How many patients during this period of time with Loeys-Dietz did not have a valvesparing root operation? What percentage, roughly, of patients with Loeys-Dietz are going to turn out to be candidates for valve-sparing operations? Duke has mentioned before that he has reasonably strict criteria about the amount of leaflet fenestration that he will allow in a patient in whom he will do a valve-sparing root. What percentage of Loeys-Dietz are candidates do you think? DR PATEL: Thank you very much for your comments. Over the eight-year time period, from 2002 to 2009, 31 patients had a valve-sparing operation and 30 had a composite root replacement, so roughly 50:50. DR SUNDT: The next question relates to the uniqueness of this disease, a disease that your group is most familiar with but others are probably less so. It really gets to the question Why write this paper at all? The implication of performing the analysis is that in some way these patients are going to be different from Marfan patients, for example, so share with us more of your thinking today about this disease. Are there some special concerns you think about when you are doing a valvesparing root procedure in Loeys-Dietz syndrome? Given the uniqueness of the tissues and such, do you modify the operation? For example, are you more aggressive with the distal anastomosis? Do you do a hemiarch replacement or even a total arch replacement with the idea that these patients are subject to subsequent aneurysmal dilatation or dissection of the arch? What is your attitude about the leaflets? My experience with some patients with Marfan syndrome is that there is a spectrum of how stretchy the leaflets are. Is this a concern in Loeys- Dietz syndrome? What keeps your group up at night worried about late outcomes. Congratulations on a really beautiful presentation. DR PATEL: Thank you again for those very important questions. With regard to why we did this study and what we were anticipating with the results for this study, we do believe that these patients have very, very malignant tissues. Our initial experience back in 2004, which we reported in the Annals of Thoracic Surgery, was 71 patients we described who had Loeys- Dietz syndrome; roughly half of them were from the University

Ann Thorac Surg PATEL ET AL 2011;92:556 61 VSRR IN LOEYS-DIETZ SYNDROME 561 of Ghent, where Dr Loeys is located, and the other half were from our institution with Hal Dietz. Of those 71 patients, 5 children less than 10 years of age with roots less than 4 cm died of a fatal aortic catastrophe, so given that very early data, we decided to be very aggressive with proceeding with root replacement and monitoring them postoperatively. Typically for Marfan syndrome we will obtain echocardiograms at 6 months and then annually thereafter. These patients are followed every 3 months with echocardiography and then every year with CT imaging from the head all the way down to the pelvis. With regard to replacing the arch, none of the patients in this series have had abnormal arch diameters and none of them have had prophylactic arch replacement, but we have seen some of our composites come back into the clinic with some arch and descending thoracic aneurysms. At this time we are hesitant to replace the arch and proceed with a more aggressive descending thoracic resection because we will be subjecting these patients to a much more difficult operation as well as subjecting their very friable tissues to more suture lines. What we are hoping is that with more long-term data we will be able to identify specific patients who may benefit from a more aggressive surgical intervention. DR ROBERT STEWART (Cleveland, OH): I echo Dr Sundt s compliments on your wonderful presentation. My question relates to a patient with Loeys-Dietz syndrome who requires a cardiac operation for a lesion other than in their aorta. If such a patient has aortic dilatation, but it does not quite meet your criteria for repair, do you feel that continued dilatation is inevitable and if so, would you consider replacing the aortic root when you are fixing the other lesion? DR PATEL: Well, that is interesting in this set of patients because as you saw in my clinical characteristics slide there, there were 2 patients who were fairly elderly when they received their operation; 1 was 60 years of age. We do believe that these patients will eventually have dilatated aortic roots. At present, I would say, from what Dr Cameron and Dr Vricella have told me, that we should proceed with replacing their roots given these very early criteria. These criteria that we have developed aren t based on any data, unfortunately, because we really don t have that data available to us yet. A lot of the natural history of this disease is still unknown. Hopefully with more long-term follow-up with these patients, as well as patients who have not undergone surgery, we will be able to better answer that question.