Valve-Sparing Root Reconstruction Does Not Compromise Survival in Acute Type A Aortic Dissection

Valve-Sparing Root Reconstruction Does Not Compromise Survival in Acute Type A Aortic Dissection Sreekumar Subramanian, MD,* Sergey Leontyev, MD,* Michael A. Borger, MD, PhD, Constanze Trommer, MD, Martin Misfeld, MD, PhD, and Friedrich W. Mohr, MD, PhD Department of Cardiac Surgery, Heart Center Leipzig, Leipzig, Germany; Department of Surgery, University of Arizona Medical Center, Tucson, Arizona; and Department of Cardiothoracic Surgery, Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona Background. The optimal management of the dissected aortic root remains unclear. The purpose of this study was to determine whether aortic valve-sparing root replacement (VSRR) compromises survival in aortic dissection repair and to evaluate the comparative efficacy of 2 types of VSRR procedures. Methods. The Heart Center database (Leipzig, Germany) was reviewed to identify patients who underwent a VSRR for acute type A aortic dissection (AAAD) repair. Patients were classified into 3 groups: Bentall (biological or mechanical valved conduit), Yacoub VSRR, and David VSRR. Intergroup comparisons were performed using the t test and analysis of variance as appropriate. Results. From March 1995 to April 2010, 208/374 patients (56%) undergoing AAAD repair received an aortic root procedure. (n 130) underwent a Bentall operation, group 2 (n 51) underwent a modified Yacoub procedure, and group 3 (n 27) underwent a modified David procedure. Age and logistic European system for cardiac operative risk evaluation (EuroSCORE) as well as cross-clamp, cardiopulmonary bypass, and circulatory arrest times were similar among the groups. Hospital mortality among all 3 groups was similar (group 1, 27%; group 2, 16%; group 3, 15%). At a mean follow-up of 44 months for group 2 and 27 months for group 3, there was no difference in the need for aortic valve replacement for moderate to severe aortic insufficiency (AI) (2/37 survivors in group 2 versus 1/23 survivors in group 3; z score 0.279; p > 0.05). Five-year survival estimates were 66% for group 1, 65% for group 2, and 80% for group 3 (log rank p 0.2). Conclusions. Both the David and Yacoub techniques have similar midterm durability in AAAD repair. When compared with the Bentall procedure, neither technique compromises short-term or midterm survival after AAAD repair. (Ann Thorac Surg 2012;94:1230 4) 2012 by The Society of Thoracic Surgeons Accepted for publication April 26, 2012. *Drs Subramanian and Leontyev contributed equally to this article. Presented at the Poster Session of the Forty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 Feb 1, 2012. Address correspondence to Dr Subramanian, Division of Cardiothoracic Surgery, University of Arizona Medical Center, 1501 N Campbell Ave, No 4402, Tucson, Arizona, 85724; e-mail: ssubramanian@surgery. arizona.edu. The management of aortic insufficiency (AI) in the setting of acute type A aortic dissection (AAAD) remains controversial [1 4]. Although patients with isolated leaflet splaying from a dilatated sinotubular junction may be treated with commissural suspension and an ascending aortic replacement, patients with concomitant aortic sinus pathologic processes require an aortic root intervention. Clearly, those patients with markedly dilatated aortic sinuses and severely damaged aortic valve cusps should be treated with a valved conduit root replacement, which can be performed with excellent results [4, 5]. However for patients with dilatated aortic sinuses and intact valve cusps, valve-sparing root reconstruction (VSRR) is a viable option for selected patients [6 11]. The benefits of valve preservation include the avoidance of anticoagulation and its attendant hemorrhagic complications and a decreased risk of valve-related complications (endocarditis and structural valve deterioration) [8, 10]. VSRR techniques range from external aortic root stabilization (eg, Florida sleeve [12]) and Haverich root stabilization [13] to the David reimplantation [8, 11] and Yacoub remodeling strategies [14]. The latter 2 procedures are the most commonly used and have achieved good results, with the former being preferred in patients with a dilatated aortoventricular junction (eg, patients with Marfan syndrome) [15, 16]. At our center, we have shifted from a Yacoub remodeling strategy to the David reimplantation technique based on surgeon preference, although there are relatively little data available to judge the comparative efficacy and durability of these techniques [17 20]. Although VSRR in the setting of AAAD has been criticized as being too extensive and risky, there are multiple reports demonstrating its safety and efficacy in this setting [20 25]. Given the nature of the disease, a prospective randomized comparison will likely never be performed. Therefore we undertook this retrospective study to evaluate whether valve-sparing root reconstruction in acute type A dissection compromises survival compared 2012 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc http://dx.doi.org/10.1016/j.athoracsur.2012.04.094

Ann Thorac Surg SUBRAMANIAN ET AL 2012;94:1230 4 VALVE-SPARING ROOT IN TYPE A DISSECTION 1231 with the modified Bentall procedure. In addition, we compared the midterm efficacy and durability of the 2 most commonly performed VSRR procedures. Material and Methods Patients From March 1995 to April 2010, 374 patients underwent aortic procedures for AAAD at the Heart Center Leipzig. Of these patients, 208/374 (56%) underwent a formal aortic root procedure. Retrospective chart and operation report review was done to verify the type of aortic root procedure performed, and the patients were classified into 3 groups. (n 130) underwent a modified Bentall operation, group 2 (n 51) underwent a modified Yacoub remodeling VSRR biological glue, and group 3 (n 27) underwent a David reimplantation VSRR. At our center, VSRR is attempted whenever leaflet preservation is feasible, and since 2004 there has been a shift toward the David reimplantation based on surgeon preference. Technique Although there was some variability in surgical technique, the operation performed for AAAD repair involved an ascending aortic and hemiarch replacement to resect the entry site, with a complete arch replacement being performed as necessary, based on reentry tears, arch aneurysms, or tissue quality. A simultaneous antegrade stented or nonstented elephant trunk procedure was performed when a concomitant descending aortic aneurysm was present. Regarding the root strategy, the choice of a valvesparing procedure or a composite root replacement varied among surgeons. In patients who had VSRR, either a David reimplantation or a modified Yacoub remodeling technique was used. The David operations were performed either with a straight tube graft with sizing based on optimal diameter of the aortic root (David I), or with an oversized straight tube graft (4 6 mm larger than the optimal aortic root size), in which the proximal and distal aspects of the prosthesis are plicated down to create aortic neosinuses (David V). Yacoub refers to the strategy whereby 1 to 3 sinuses are excised (most commonly 1 sinus the noncoronary sinus), and the tongues of the ascending aortic prosthesis are sewn to the native aortic wall. Additionally, when required the layers of the preserved sinuses were reapproximated using gelatin-resorcinol-formaldehyde (GRF) biological glue (Cardial Technopole, Sainte-Etienne, France). The modified Bentall procedures were performed using a commercially available mechanical valved conduit or a hand-sewn biological Bentall, in which an appropriately sized tissue valve was sutured to a straight graft and then implanted. Coronary reimplantation was then performed using the button technique. Statistical Analysis Continuous variables are expressed as mean standard deviation and categorical data as proportions. Categorical variables were compared using the 2 test or Fisher s exact test, and independent continuous variables were compared by unpaired Student=s t test, analysis of variance, or Kruskal-Wallis test as appropriate. Event-free survival was calculated by Kaplan-Meier methods with a 95% confidence interval (CI). A p value less than 0.05 was considered statistically significant. All statistical analyses were performed using SPSS, version 17.0 (SPSS, Inc, Chicago, IL). Results Of the 208 patients undergoing a formal aortic root procedure during AAAD repair, 130 were treated with a modified Bentall operation (group 1), and 78 underwent a valvesparing root reconstruction. (n 51) was treated with a modified Yacoub remodeling technique, with the GRF glue being used adjunctively in 13 patients. Thirtyseven of 51 patients had a uni-yacoub, corresponding to only replacement of the noncoronary sinus, 2/51 patients had a bi-yacoub, corresponding to replacement of the noncoronary and right sinuses, and in the remainder only a Yacoub remodeling procedure was noted, without specific mention of the number of sinuses replaced. (n 27) was treated with a David reimplantation technique. Patient demographics are presented in Table 1. Operative details are shown in Table 2. Hospital (including 30-day) mortality among all 3 groups was similar (group 1, 27%; group 2, 16%; group 3, 15%) (p 0.1). Table 3 shows hospital outcomes, all of which were statistically similar in both groups. Follow-up was complete in 97% of patients. The estimated mean survival time was 7.2 0.4 years (range, 0 to 12.3 years) and a total of 554 patient-years. The unadjusted 1-, 3-, 5-, and 8-year survival was 69% 4%, 68% 4%, 66% 5%, and 55% 7%, respectively (Fig 1). Midterm survival was not influenced by type of aortic root procedure (log rank p 0.2). There was no significant difference in the estimated freedom from reoperation between Yacoub (group 2) patients and David (group 3) patients (8.9 0.3 years versus 11.5 0.8 years; log rank p 0.57). Fig 2 shows freedom from root reoperation according to the type of aortic root procedure. Comment Hospital morbidity and mortality remain significant for patients undergoing AAAD repair, but in our series the use of a valve-sparing root reconstruction did not compromise survival when compared with the modified Bentall procedure. Both the modified David and the modified Yacoub VSRR GRF glue procedures had comparable efficacy and midterm durability during AAAD repair. Caveats include appropriate selection of patients (eg, younger age, minimal comorbidities) and valvular pathologic conditions (eg, noncalcified, relatively normal leaflets) for VSRR and significant experience with these techniques in the elective setting before use in AAAD repair [11, 26]. Although both techniques have similar efficacy, several important differences must be noted. The flow profile after the Yacoub technique has been shown to be more physiologic than that after the David reconstruction [18], which may have implications for the development of downstream

1232 SUBRAMANIAN ET AL Ann Thorac Surg VALVE-SPARING ROOT IN TYPE A DISSECTION 2012;94:1230 4 Table 1. Patient Demographics N 208 100% Bentall N 130 62.5% Yacoub N 51 24.5% David N 27 13% p Value Age (y) 57 14 56 14 62 14 53 15 0.02 Men 74 (36%) 45 (35%) 18 (35%) 11 (42%) 0.7 Diabetes 25 (12%) 11(9 %) 13 (26%) 1 (4%) 0.02 Hyperlipidemia 49 (24%) 22 (17%) 20 (39%) 7 (26%) 0.01 COPD 7 (3%) 3 (2%) 3 (6%) 1 (4%) 0.4 Peripheral vascular disease 21 (10%) 7 (5%) 12 (24%) 2 (7%) 0.01 Preoperative LVEF 57 10 58 10 55 10 58 7 0.3 Logistic EuroSCORE 30 18 30 19 31 19 27 15 0.6 Critical preoperative state a 65 (31%) 46 (35%) 12 (24%) 7 (26%) 0.2 Bicuspid aortic valve 24 (12%) 23 (18%) 1 (2%) 0 (0%) 0.04 Marfan syndrome 11 (5%) 9 (7%) 0 (0%) 2 (7%) 0.1 Previous cardiac operation 12 (6%) 6 (5%) 4 (8%) 2 (7%) 0.6 a Critical preoperative state was defined as the need for preoperative ventilation, inotropic support, cardiopulmonary resuscitation, gross hemodynamic instability, or some combination. COPD chronic obstructive pulmonary disease; EuroSCORE European system for cardiac operative risk evaluation; LVEF left ventricular ejection fraction. aortic pathologic processes. The David technique is more appropriate for the dilatated aortoventricular junction, as in Marfan syndrome, whereas either technique may be used in patients with a normal aortoventricular junction.[7,8,16] The Yacoub technique, or more accurately depicted, the uni-yacoub or bi-yacoub technique (depending on the number of sinuses excised), can be performed more quickly than a David reconstruction. In our series, the cross-clamp time required was almost half that required for David reimplantation; therefore it may be more appropriate when multiple concomitant procedures must be performed. In these cases, however, consideration should be given to a composite root replacement because a second pump run for a failed repair is best avoided. Often lack of experience with VSRR is the sole reason for performance of a composite root replacement. However this should not be considered a substandard management, particularly in the setting of an AAAD repair. This is because multiple factors are responsible for decreasing the advantage of VSRR over composite root replacement for acute type A dissection. First, a wellmanaged anticoagulation program has been shown to markedly reduce the incidence of thrombotic and hemorrhagic complications after valved conduit implantation [27]. However the impact of anticoagulation on false lumen thrombosis in the descending aorta can be substantial and can lead to persistent patency of the false lumen, which has been shown to be a risk factor for downstream aortic pathologic processes [28]. Second, the availability of transcatheter techniques for redo aortic valve interventions lessens the impact of recurrent AI after valve repair [29]. This may also be construed as an argument to spare the valve and accept an imperfect result, but we believe that the goal of the operation should be to not only have the patient survive but also to minimize the likelihood of future reintervention. Third, VSRR sometimes must be accompanied by cusp repair to restore aortic valve competence. A recent study evaluating patients after David reimplantation noted that cusp pathologic processes were 1 of the major causes of early and late recurrent AI [30]. Certainly the addition of a potentially complex cusp repair Table 2. Operative Details Bentall Yacoub David P Value Operative time 328 104 342 103 291 108 330 83 0.01 Cardiopulmonary 214 76 221 76 192 81 220 62 0.06 bypass time Cross-clamp time 118 47 126 44 84 38 145 44 0.5 Circulatory arrest time 27 18 28 19 25 16 26 11 0.5 arch 131 (63%) 83 (64%) 31 (61%) 17 (63%) 0.2 replacement Elephant trunk procedure 54 (26%) 38 (29%) 11 (22%) 5 (19%) 0.3

Ann Thorac Surg SUBRAMANIAN ET AL 2012;94:1230 4 VALVE-SPARING ROOT IN TYPE A DISSECTION 1233 Table 3. Hospital Outcomes Bentall Yacoub David P Value Low cardiac output 27 (13%) 17 (13%) 7 (14%) 3 (11%) 0.9 Rethoracotomy for bleeding 55 (26%) 32 (25%) 14 (28%) 9 (33%) 0.6 Sepsis 11 (5%) 6 (5%) 4 (8%) 1 (4%) 0.6 Gastrointestinal complications 22 (11%) 12 (9%) 8 (16%) 2 (7%) 0.6 Dialysis 47 (23%) 32 (25%) 9 (18%) 6 (22%) 0.6 Stroke 36 (18%) 24 (19%) 7 (14%) 5 (19%) 0.7 30-day mortality a 47 (23%) 35 (27%) 8 (16%) 4 (15%) 0.1 a Thirty-day mortality is a composite of hospital and 30-day mortality. to a David reimplantation during an operation for AAAD should be viewed with some skepticism and approached with caution. Despite these factors favoring a composite root replacement, the 1 advantage of VSRR that is unlikely to disappear is the lower risk of endocarditis. A consistent finding in VSRR series in elective and emergency settings is the low (almost 0%) risk of aortic valve endocarditis [8, 11, 26]. Despite a significantly shorter operative time, patients in group 2 had similar operative mortality to patients in group 1 and group 3, perhaps reflective of the older age and increased comorbidities of group 2. Postoperative morbidity, however, was not significantly different between the groups. Interestingly, although survival is comparable in the midterm, the survival difference widens over time. This may simply be a reflection of the older age of the patients undergoing the modified Yacoub procedure or may be due to complications of the chronic type B dissection, which may be related more to the arch/descending aortic pathologic process than to the root procedure. This will be the subject of future studies. The use of GRF glue in group 1 patients represents an important adjunct used widely in Europe for both the proximal and distal aorta [31 33]. The glue is composed of an adhesive (50% gelatin-resorcinol, 1.25% CaCl 2, and 48.75% distilled water) and a hardener (45% glutaraldehyde, 3.6% formaldehyde, 51.4% distilled water). There have been reports of formaldehyde-induced tissue (root) necrosis, and some centers do not use the adhesive for this reason. We noted no cases of root necrosis and believe that proper application of the glue may be the key to preventing this complication [33]. When applying the glue, we have also found it useful to insert gauze into the opened aortic root to minimize contact with the intima. Whether the glue results in a durable repair has been the subject of several studies [32, 33]. Our data indicate that it does not compromise durability, although it was not always clear from the operative reports whether additional sutures were placed to reapproximate the dissected sinuses. Furthermore the patient numbers are too small to draw meaningful conclusions. In addition to freedom from proximal aortic reoperation, freedom from aortic root dilatation is an important metric to assess the success of VSRR and will be the source of future study. Systematic follow-up of these patients is recommended, just as with endovascular aortic procedures, given the potential for proximal or distal aortic reoperations [34]. Limitations of this study include those inherent to a retrospective review. There are certainly patients who un- Fig 1. Survival by aortic root procedure for acute type A aortic dissection. Fig 2. Freedom from root reoperation by aortic root procedure for acute type A aortic dissection.

1234 SUBRAMANIAN ET AL Ann Thorac Surg VALVE-SPARING ROOT IN TYPE A DISSECTION 2012;94:1230 4 derwent composite root replacement during this time frame who may have been candidates for VSRR. The use of VSRR and the specific technique used at our center, like other centers, is dependent on surgeon preference and experience. Serial echocardiographic follow-up was not available to determine conclusively the freedom from AI. Future studies will provide a comparison of VSRR with composite root replacement and will include echocardiographic and computed tomographic scan assessments to determine conclusively the freedom from recurrent AI and proximal aortic dilatation. In conclusion, when used for appropriately selected patients and carried out by experienced surgeons, the use of VSRR in the setting of AAAD does not compromise patient survival when compared with the modified Bentall procedure. Both the David reimplantation technique and the modified Yacoub remodeling technique the use of GRF glue are effective valve preservation strategies in AAAD repair, with comparable durability at midterm follow-up. References 1. Farhat F, Durand M, Boussel L, et al. Should a reimplantation valve sparing procedure be done systematically in type A aortic dissection? Eur J Cardiothorac Surg 2007;31:36 41. 2. Von Segesser LK, Lorenzetti E, Lachat M, et al. Aortic valve preservation in acute type A dissection: is it sound? J Thorac Cardiovasc Surg 1996;111:381 90. 3. Elefteriades JA. What operation for acute type A dissection? J Thorac Cardiovasc Surg 2002;123:201 3. 4. Lai DT, Miller DC, Mitchell RS, et al. Acute type A aortic dissection complicated by aortic regurgitation: composite valve graft versus separate valve graft versus conservative valve repair. J Thorac Cardiovasc Surg 2003;126:1978 86. 5. Halstead JC, Spielvogel D, Meier DM, et al. Composite aortic root replacement in acute type A dissection: time to rethink the indications? Eur J Cardiothorac Surg 2005;27:626 32. 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 21. 7. Erasmi AM, Stierle U, Bechtel JFM, et al. Up to 7 years experience with valve-sparing aortic root remodeling/ reimplantation for acute type a dissection. Ann Thorac Surg 2003;76:99 104. 8. David TE, Feindel CM, Webb GD, Colman JM, Armstrong S, Maganti M. Long-term results of aortic valve-sparing operations for aortic root aneurysm. J Thorac Cardiovasc Surg 2006;132:347 54. 9. Kallenbach K, Oelze, T, Salcher R, et al. Evolving strategies for treatment of acute aortic dissection type A. Circulation 2004;110:II-243 9. 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 33. 11. Leontyev S, Trommer C, Subramanian S, et al. The outcome after aortic valve-sparing (David) operation in 179 patients: a single-centre experience. Eur J Cardiothorac Surg 2012 Feb 9. [Epub ahead of print]. 12. Hess PJ Jr, Klodell CT, Beaver TM, et al. The Florida sleeve: a new technique for aortic root remodeling with preservation of the aortic valve and sinuses. Ann Thorac Surg 2005;80:748 50. 13. Shrestha M, Khaladj N, Hagl C, Haverich A. Valve-sparing aortic root stabilization in acute type A aortic dissection. Asian Cardiovasc Thorac Ann 2009;17:22 4. 14. Sarsam MA, Yacoub M. Remodeling of the aortic valve annulus. J Thorac Cardiovasc Surg 1993;105:435 8. 15. Karck M, Kallenbach K, Hagl C, Rhein C, Leyh R, Haverich A. Aortic root surgery in Marfan syndrome: comparison of aortic valve-sparing reimplantation versus composite grafting. J Thorac Cardiovasc Surg 2004;127:391 8. 16. Volguina IV, Miller DC, LeMaire SA, et al. Valve-sparing and valve-replacing techniques for aortic root replacement in patients with Marfan syndrome: analysis of early outcome. J Thorac Cardiovasc Surg 2009;137:1124 32. 17. Graeter TP, Langer F, Nikoloudakis N, Aicher D, Schäfers HJ. Valve-preserving operation in acute aortic dissection type A. Ann Thorac Surg 2000;70:1460 5. 18. Erasmi AW, Sievers HH, Bechtel JF, Hanke T, Stierle U, Misfeld M. Remodeling or reimplantation for valve-sparing aortic root surgery? Ann Thorac Surg 2007;83:S752 6. 19. Leyh RG, Fischer S, Kallenbach K, et al. High failure rate after valve-sparing aortic root replacement using the remodeling technique in acute type A aortic dissection. Circulation 2002;106(12 Suppl 1):I229 33. 20. Pessotto R, Santini F, Pugliese P, et al. Preservation of the aortic valve in type A aortic dissection complicated by aortic regurgitation. Ann Thorac Surg 1999;67:2010 13. 21. Kallenbach K, Pethig K, Leyh RG, et al. Acute dissection of the ascending aorta: first results of emergency valve-sparing aortic root reconstruction. Eur J Cardiothorac Surg 2002;22:218 22. 22. Casselman FP, Tan ES, Vermeulen FE, et al. Durability of aortic valve preservation and root reconstruction in acute type A aortic dissection. Ann Thorac Surg 2000;70:1227 33. 23. Mazzucotelli JP, Deleuze PH, Baufreton C, et al. Preservation of the aortic valve in acute aortic dissection: long-term echocardiographic assessment and clinical outcome. Ann Thorac Surg 1993;55:1513 7. 24. Geirsson A, Bavaria JE, Swarr D, et al. Fate of the residual distal and proximal aorta after acute type a dissection repair using a contemporary surgical reconstruction algorithm. Ann Thorac Surg 2007;84:1955 64. 25. Leyh RG, Schmidtke C, Bartels C, et al. Valve-sparing aortic root replacement (remodeling/reimplantation) in acute type A dissection. Ann Thorac Surg 2000;70:21 4. 26. Shrestha M, Baraki H, Maeding I, et al. Long-term results after aortic valve-sparing operation (David I). Eur J Cardiothorac Surg 2012;41:56 61; discussion 61 2. 27. Etz CD, Bischoff MS, Bodian C, et al. The Bentall procedure: is it the gold standard? A series of 597 consecutive cases. J Thorac Cardiovasc Surg 2010;140:64 70. 28. Zierer A, Voeller RK, Hill KE, Kouchoukos NT, Damiano RJ Jr, Moon, MR. Aortic enlargement and late reoperation after repair of acute type a aortic dissection. Ann Thorac Surg 2007;84:479 87. 29. Walther T, Dewey T, Borger MA, et al. Transapical aortic valve implantation: step by step. Ann Thorac Surg 2009;87:276 83. 30. Oka T, Okita Y, Matsumori M, et al. Aortic regurgitation after valve-sparing aortic root replacement: modes of failure. Ann Thorac Surg 2011;92:1639 44. 31. Guilmet D, Bachet J, Goudot B, et al. Use of biological glue in acute aortic dissection. Preliminary clinical results with a new surgical technique. J Thorac Cardiovasc Surg 1979;77: 516 21. 32. von Oppell UO, Karani Z, Brooks A, Brink J. Dissected aortic sinuses repaired with gelatin-resorcin-formaldehyde (GRF) glue are not stable on follow up. J Heart Valve Dis 2002;11:249 57. 33. Fukunaga S, Karck M, Harringer W, Cremer J, Rhein C, Haverich A. The use of gelatin-resorcin-formalin glue in acute aortic dissection type A. Eur J Cardiothorac Surg 1999;15:564 570. 34. Moon MR, Sundt TM III, Pasque MK et al. Does the extent of proximal or distal resection influence outcome for type A dissections? Ann Thorac Surg 2001;71:1244 9.