Since the Ross procedure was first described in 1967

Ross-Konno Procedure With Mitral Valve Surgery Norihiko Oka, MD, PhD, Osman Al-Radi, MD, Abdullah A. Alghamdi, MD, Siho Kim, MD, and Christopher A. Caldarone, MD Division of Cardiovascular Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Background. The Ross-Konno procedure has emerged as a complex procedure to address multilevel left ventricular outflow tract obstruction in infants and small children. Significant proportions of patients, however, have concomitant mitral valve disease and require a mitral procedure in addition to the Ross-Konno procedure. Ross-Konno-mitral surgery puts three valves at risk and may be associated with significant morbidity and mortality and, therefore, we sought to characterize midterm clinical outcomes after the Ross-Konno procedures with and without concomitant mitral valve surgery. Methods. We reviewed medical records of 20 consecutive patients who underwent Ross-Konno/Mitral procedures (n 8) or Ross-Konno-nonmitral procedures (eg, without mitral valve repair, n 12) between 1995 and 2007. Results. In Ross-Konno mitral patients (age 326 268 days; range, 1 to 817 days), there were 3 early deaths and 1 late death with a mean follow-up of 1.8 2.5 years. Seven patients had intervention prior to Ross-Konno. Actuarial survival at 5 years was 43.8%. In Ross-Konno nonmitral patients (age, 2,110 2,020 days; range, 3 to 5,563 days), there was one early death with mean follow-up of 2.7 2.6 years. Ten patients had intervention prior to Ross-Konno. Actuarial survival at 5 years was 91.7%. There were significant differences between groups in age, survival rate, intubation time, coronary care unit stay, and hospital stay (Ross-Konno mitral vs Ross- Konno nonmitral: 0.89 0.73 vs 5.8 5.5 years, 43.8 vs 91.7%, 17.0 15.7 vs 2.6 2.7 days, 22.9 22.7 vs 4.1 3.1 days and 28.6 21.2 vs 11.5 7.1 days). Conclusions. The Ross-Konno procedure effectively treats multilevel left ventricular outflow tract obstruction in infants and small children. The requirement for concomitant mitral valve surgery, however, is associated with significantly higher likelihood of mortality. (Ann Thorac Surg 2010;89:1366 70) 2010 by The Society of Thoracic Surgeons Since the Ross procedure was first described in 1967 [1], it has been performed as a treatment for aortic valve disease in growing children, including infants and neonates. For young patients with left ventricular outflow tract obstruction (LVOTO), size mismatch between the aortic and the pulmonary valve frequently precludes a simple Ross procedure. Integration of the Konno procedure into the Ross procedure has emerged as a surgical strategy to manage multilevel left ventricular outflow tract obstruction by enlargement of the LVOT and replacement of the aortic valve with a pulmonary autograft [2 4]. The Ross-Konno procedure allows placement of a size-appropriate aortic prosthesis without requirement for anticoagulation and retaining the potential for growth of the autograft. Despite these desirable characteristics, the procedure has some undesirable characteristics in the relatively high complexity of the procedure and the requirement for placement of a pulmonary valve prosthesis which does not grow and mandates reoperation. Pediatric patients with severe LVOTO frequently have multiple levels of left-sided obstruction, including concomitant mitral valve disease. In this subset of patients, a Ross-Konno procedure may require concomitant mitral Accepted for publication Feb 3, 2010. Address correspondence to Dr Caldarone, Division of Cardiovascular Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada, M5G 1X8; e-mail: christopher.caldarone@sickkids.ca. valve reconstruction. This combination of procedures puts three valves at risk due to a translocation of pulmonary valve to the aortic root, replacement of the native pulmonary valve, and mitral reconstruction. These patients may also have small left ventricles and endocardial fibroelastosis. Thus, concomitant mitral valve disease adds a high level of technical complexity to the Ross- Konno procedure and contemplation of the Ross-Konno/ mitral procedure should be balanced against alternative strategies (eg, abandonment of the left ventricle and single ventricle palliation or transplantation). Because the impact of mitral procedures on the risk profile of Ross-Konno procedures has not been frequently studied, we undertook a retrospective evaluation of the impact of mitral procedures on Ross-Konno procedures. Patients and Methods Twenty consecutive patients underwent Ross-Konno procedures between 1995 and 2007 at The Hospital for Sick Children in Toronto, Canada. Among this group, eight patients had mitral procedures (RKM) and 12 did not require mitral procedures (RK). Demographic, morphologic, and echocardiographic data as well as surgical and postoperative management data were obtained from hospital records. There were 4 hospital deaths and 1 late death. Three patients were lost to follow-up. The mean duration of follow-up was 2.3 2.6 years. The Research 2010 by The Society of Thoracic Surgeons 0003-4975/10/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2010.02.005

Ann Thorac Surg OKA ET AL 2010;89:1366 70 ROSS-KONNO WITH MITRAL VALVE SURGERY 1367 Survival Score As Described By Colan and Colleagues Colan and colleagues [6] reported a scoring system to predict optimal management in neonates with aortic stenosis. Variables include body surface area (BSA), aortic annulus z-score, left ventriclar to heart long-axis ratio, and EFE: PEDIATRIC CARDIAC 10.98 (BSA) 0.56 (aortic annulus z-score) 5.89 (left ventricular to heart long-axis ratio) 0.79 (grade 2 or 3 EFE) 6.78 Outcomes were predicted accurately in 90% of patients with a cutoff of 0.65 (95% of survivors and 80% of events) (Fig 1). Fig 1. Scatter plot showing the discriminant score of Colan and colleagues reference dashed lines show the optimal discriminant cutoffs of 0.65. ( survival; death.) Ethics Board at the Hospital for Sick Children approved the retrospective study and patient consent was waived. Analysis of Data in Context of Previously Published Survival Scores We used two scoring systems to retrospectively examine the initial decision to choose between a one-ventricle and two-ventricle repair. Although these systems were not specifically designed to address the long-term outcomes of Ross-Konno mitral valve procedures, the analysis was undertaken to provide perspective with regard to potentially achievable outcomes if a single-ventricle approach was undertaken in patients with multilevel LVOT obstruction associated with mitral anomalies requiring intervention. Univentricular Survival Advantage Score (UVR-SA Score) The UVR-SA score was developed by the Congenital Heart Surgeons Society and reported by Hickey and colleagues [5]. Variables included in the score are: body weight, height, grade of endocardial fibroelastosis (EFE), the mid aortic arch diameter, Z-score of mitral valve annulus, minimum LVOT diameter, length of apexforming ventricle (from crux of the heart to the apex), presence of moderate or severe tricuspid regurgitation, presence of large ventricular septal defect, and presence of left ventricular dysfunction. A positive value indicates that a patient has greater predicted survival with a univentricular repair (UVR) management strategy. If predicted 5-year survival for UVR is 80% and for biventricular repair is 70%, the UVR-SA value would be 10, indicating a 10% survival difference favoring UVR. On the other hand, if predicted survival for UVR is 50% and biventricular repair is 70%, the UVR-SA value is 20, indicating a 20% survival difference favoring biventricular repair. Statistical Analysis Actuarial survival and freedom from reintervention were evaluated with the Kaplan-Meier method. The p values for differences between distributions were calculated by log-rank test. Differences in age, body weight, grade of EFE, ejection fraction (EF), grade of mitral and aortic valve disease, grade of LVOTO, extracorporeal membrane oxygenation requirement, mean length of intubation, coronary care unit stay, and hospital stay between groups were analyzed by t test (Table 1). Results Ross-Konno With Mitral Valve Surgery (RKM) In group RKM (n 8, mean age, 326 268 days; range, 1 to 817 days, male:female 6:2), there were 3 hospital Table 1. Perioperative Data Variables Ross-Konno\ Mitral Ross-Konno p Value Age at operation (days) 326 268 2,110 2,020 0.01 Body weight (kg) 6.94 2.72 20.96 15.6 0.01 Grade of the EFE 1.1 1.1 0.3 0.9 0.03 EF 0.7829 0.097 0.70 0.217 0.18 Grade of MS 1.6 1.1 0.5 0.5 0.006 Grade of MR 1.6 0.7 0.6 0.5 0.0008 Grade of AS 2.5 0.5 2.5 0.8 0.45 Grade of AR 1.8 1.1 1.8 1.1 0.40 Pressure gradient at 78.3 9.7 70 21.7 0.18 LVOT (mm Hg) Intubation period 17 15.7 2.6 2.7 0.005 (days) CCU stay (days) 22.9 22.7 4.1 3.1 0.01 Hospital stay (days) 28.6 21.2 11.5 7.1 0.01 Grade of EFE: 0 no endocardial fibroelastosis; 1 endocardial fibroelastosis on the mitral valve papillary muscles only; 2 endocardial fibroelastosis on the papillary muscles and some involvement of the endocardial surface of the left ventricle; 3 extensive endocardial involvement. Grade of valve stenosis and regurgitation: 0 none, 1 mild, 2 moderate, 3 severe. AR aortic valve regurgitation; AS Aortic valve stenosis; CCU coronary care unit; EF ejection fraction; EFE endocardial fibroelastosis; LVOT left ventricular outflow tract; MR mitral valve regurgitation; MS mitral valve stenosis.

1368 OKA ET AL Ann Thorac Surg ROSS-KONNO WITH MITRAL VALVE SURGERY 2010;89:1366 70 Fig 2. Kaplan-Meier curves illustrating the probabilities of freedom from death. deaths and 1 late death with a mean follow-up of 1.8 2.5 years. Seven patients had interventions prior to the Ross-Konno procedure (6 balloon valvuloplasty, 1 open mitral valvotomy and ASD closure, 1 mitral valvotomy and sub-aortic resection, 1 aortic arch and mitral valve repair). Table 2 shows types of mitral valve surgery for each patient. Mean length of intubation, coronary care unit stay, and hospital stay were 17.0 15.7, 22.9 22.7 and 28.6 21.2 days, respectively. Three patients needed postoperative extracorporeal membrane oxygenation support in the coronary care unit after Ross-Konno procedure. Actuarial survival at 5 years was 43.8% (Fig 2). Three patients required reintervention. Freedom from reintervention or death at 5 years was 37.5% (Fig 3). Ross-Konno Without Mitral Valve Surgery (RK) In group RK (n 12, mean age, 2,110 2,020 days; range, 3 to 5,563 days; male:female 5:7), there was one hospital death. There were no late deaths with mean follow-up of 2.7 2.6 years. Ten patients had interventions prior to the Ross-Konno procedure (8 balloon valvuloplasty; 6 coarctation repair; 4 sub-aortic stenosis resection;1 modified Konno, ventricular septal defect closure and aortic valve commissurotomy; 1 coarctation repair and pulmonary banding, 1 atrioventricular septal defect repair, 1 homograft replacement of aortic valve). Mean length of intubation, coronary care unit stay, and hospital stay were 2.6 2.7, 4.1 3.1 and 11.5 7.1 days, respectively. Actuarial survival at 5 years is 91.7% (Fig 2). Two patients required reintervention. Freedom from reintervention or death at 5 years was 65.2% (Fig 3). There were significant differences between two groups in age and body weight at surgery. There were significant differences in postoperative intubation time (17.0 15.7 vs 2.6 2.7 days, p 0.005), coronary care unit stay (22.9 22.7 vs 4.1 3.1 days, p 0.01), and hospital stay (28.6 21.2 vs 11.5 7.1 days, p 0.01). Survival after the Ross-Konno procedure differed between groups (43.8% vs 91.7% survival at 5 years for RKM and RK groups, respectively, p 0.05). Analysis of Scores Using Published Survival Scoring Systems The UVR-SA scores in the RKM group ranged from 36.1 to 18.8 with a median of 16.0. The mean values were 13.5 22.1, indicating that two-ventricle repair was predicted to offer superior long-term survival in comparison with a single-ventricle repair. Similarly, the Fig 3. Kaplan-Meier curves illustrating the probabilities of freedom from failure (death or reintervention).

Ann Thorac Surg OKA ET AL 2010;89:1366 70 ROSS-KONNO WITH MITRAL VALVE SURGERY Table 2. Characteristics of Patients With Mitral Valve Surgery Patient Age (Days) MS MR UVR-SA Colan Score [Ref 6] Mitral valve surgery Status Patient 1 69 Severe Mild 36.1 1.5 Papillary muscle splitting, Anterior H.D. leaflet extension Patient 2 357 Moderate Mild 18.8 2.5 Papillary muscle splitting L.D. Patient 3 385 None Moderate 32.3 3.0 Annuloplasty Alive Patient 4 535 Moderate Moderate 13.6 3.2 Cleft repair, Annuloplasty Alive Patient 5 817 Moderate Mild 18.0 0.63 Mitral valve replacement H.D. Patient 6 119 Moderate Mild 18.3 0.28 Papillary muscle splitting Alive Patient 7 325 None Moderate 9.1 0.20 Commissuroplasty Alive Patient 8 1 None Severe 35.3 0.35 Mitral valve replacement H.D. 1369 PEDIATRIC CARDIAC H.D. hospital death; L.D. late death; MR mitral valve regurgitation; MS mitral valve stenosis; UVR-SA univentricular survival advantage score. scoring system of Colan and colleagues [6] ranged from 2.9 to 3.2 with a median value of 0.28. The mean value was 0.42 1.95. These values also predict more favorable outcomes for two-ventricle repairs for this group of patients. However, in the RKM, 2 of 3 patients who died had positive UVR-SA values, indicating that we could have had better outcome with univentricular repair. Comment Palliation of infants with multilevel LVOTO is a challenge and a wide array of procedures can be considered in these patients. Among these considerations, surgical management of aortic and mitral valve disease is often an important clinical objective and the Ross-Konno procedure with or without concomitant mitral valve surgeries directly address these objectives. In 1995, Calhoon and Bolton [2] reported two cases of the Ross-Konno procedure and Reddy and colleagues [3] reported experience of 11 patients with the Ross-Konno procedure in 1996. Since then, the Ross-Konno procedure has been applied as a treatment for the patients with severe LVOTO with favorable midterm outcomes [7 9]. Nevertheless, there are drawbacks to the Ross-Konno procedure that are clinically relevant to this discussion. The pulmonary valve in the aortic position is vulnerable to undergo dilatation with or without aortic valve insufficiency after Ross [10 12] and Ross-Konno procedures [13, 14]. Pathologic abnormalities in translocated dilated pulmonary autograft have been characterized by focal interruption of the media of the graft wall with total absence of elastin fibers and intimal proliferation with fibrosis [15]. After the Ross-Konno procedure, there is potential for heart block associated with the septal ventriculoplasty which occurred in one patient in our series. Severe LVOTO may be associated with mitral valve pathology and the combination of LVOTO and mitral lesions is associated with poor outcomes [16, 17]. Treatment of isolated congenital mitral valve stenosis itself is a major challenge [18 20]. Shone and colleagues [21] described the group of patients with four defects of the systemic circulation: supraannular mitral ring, subaortic stenosis, parachute mitral valve deformity, and coarctation of the aorta. Subsequent reports [22, 23] have described surgical outcomes for patients with multiple levels of left-heart obstruction including mitral valve involvement and concluded that increasing severity of the mitral valve obstruction was associated with worsening long-term outcome. A Ross-Konno procedure with concomitant mitral surgery puts three valves (aortic autograft, pulmonary conduit, and mitral valve) at risk for postoperative complications. In patients with extensive LVOTO including valvar pathology, the outcome after creation of three-valve pathology must be balanced against potential outcomes attainable with a univentricular repair. The common perception that biventricular physiology is superior to univentricular physiology has led to a bias favoring biventricular repair. Inappropriate pursuit of biventricular repair for critical LVOTO in borderline candidates is more frequent and more consequential in survival terms than is inappropriate pursuit of univentricular repair [23]. The UVR-SA score has been proposed as a decision aid in choosing between univentricular and biventricular repairs. In the RKM group, there were 3 hospital deaths and 1 late death. Two of these patients had positive UVR-SA values, indicating that we could have had better outcome with univentricular repair. The other 2 patients, however, had negative UVR-SA values suggesting that the biventricular repair option was appropriate. It should be noted, however, that the UVR-SA score and the scoring system of Colan and colleagues [6] are not sensitive to the influence of mitral valve pathology, which may be a result of selection bias in the datasets on which the scores are based. In addition to preselection bias which may have limited the spectrum of mitral pathology seen in both systems, neither system includes detailed morphologic criteria describing mitral papillary, chordal, or leaflet pathology which may have an important influence in clinical outcomes. Four patients in the RKM group died after aggressive mitral valve surgery including papillary splitting and mitral valve replacement. None of the RKM patients with mitral procedures limited to annuloplasty or commissuroplasty of the mitral valve died. These data are consistent with previous reports that describe worsening outcomes associated with increasing severity of mitral valve involvement.

1370 OKA ET AL Ann Thorac Surg ROSS-KONNO WITH MITRAL VALVE SURGERY 2010;89:1366 70 In conclusion, the Ross-Konno procedure is an important surgical strategy for patients with severe LVOTO. However, the requirement for concomitant aggressive mitral valve surgery is associated with significantly higher mortality. In patients with severe mitral pathology requiring the Ross-Konno procedure, heart transplant, and univentricular repair management should be considered. References 1. Ross DN. Replacement of the aortic and mitral valve with pulmonary autograft. Lancet 1967;2:956 8. 2. Calhoon JH, Bolton JWR. Ross/Konno procedure for critical aortic stenosis in infancy. Ann Thorac Surg 1995;60(6 suppl): S597 9. 3. Reddy VM, Rajasinghe HA, Teitel DF, Haas GS, Hanley FL. Aortoventriculoplasty with the pulmonary autograft: the Ross-Konno procedure. J Thoracic Cardiovasc Surg 1996; 111:158 67. 4. Konno S, Imai Y, Iida Y, Nakajima M, Tatsuno K. A new method for prosthetic valve replacement in congenital aortic stenosis associated with hypoplasia of the aortic valve ring. J Thorac Cardiovasc Surg 1975;70:909 17. 5. Hickey EJ, Caldarone CA, Blackstone EH, et al. Critical left ventricular outflow tract obstruction: the disproportionate impact of biventricular repair in borderline cases. J Thorac Cardiovasc Surg 2007;134:1429 37. 6. Colan SD, McElhinney DB, Crawford EC, Keane JF, Lock JE. Validation and re-evaluation of a discriminant model predicting anatomic suitability for biventricular repair in neonates with aortic stenosis. J Am Coll Cardiol 2006;47: 1858 65. 7. Najm HK, Coles JG, Black MD, Benson L, Williams WG. Extended aortic root replacement with aortic allografts or pulmonary autografts in children. J Thorac Cardiovasc Surg 1999;118:503 9. 8. Lacour-Gayet F, Sauer H, Ntalakoura K, et al. Ross-Konno procedure in neonates: report of three patients. Ann Thorac Surg 2004;77:2223 5. 9. Brown JW, Ruzmetov M, Vijay P, Rodefeld MD, Turrentine MW. The Ross-Konno procedure in children: outcomes, autograft and allograft function, and reoperations. Ann Thorac Surg 2006;82:1301 7. 10. David TE, Omran A, Ivanov J, et al. Dilatation of the pulmonary autograft after the Ross procedure. J Thorac Cardiovasc Surg 2000;119:210 20. 11. Elkins RC, Lane MM, McCue C. Ross operation in children: late results. J Heart Valve Dis 2001;10:736 41. 12. Laudito A, Brook MM, Suleman S, et al. The Ross procedure in children and young adults: a word of caution. J Thoracic Cardiovasc Surg 2001;122:147 53. 13. Ohye RG, Gomez CA, Ohye BJ, Goldberg CS, Bove EL. The Ross/Konno procedure in neonates and infants: intermediate-term survival and autograft function. Ann Thorac Surg 2001;72:823 30. 14. Nemoto S, Sudarshan C, Brizard C. Successful aortic root remodeling for repair of a dilated pulmonary autograft after a Ross-Konno procedure in early childhood. Ann Thorac Surg 2004;78:e45 7. 15. Takkenberg JJM, Zondervan PE, van Herwerden LA. Progressive pulmonary autograft root dilation and failure after Ross procedure. Ann Thorac Surg 1999;67:551 4. 16. Zias EA, Mavroudis C, Backer CL, Kohr LM, Gotteiner NL, Rocchini AP. Surgical repair of the congenitally malformed mitral valve in infants and children. Ann Thorac Surg 1998;66:1551 9. 17. Coles JG, Williams WG, Watanabe T, et al. Surgical experience with reparative techniques in patients with congenital mitral valvular anomalies. Circulation 1987;76(suppl III):III- 117 22. 18. Serraf A, Zoghbi J, Belli E, et al. Congenital mitral stenosis with or without associated defects: an evolving surgical strategy. Circulation 2000;102(suppl III):III-166 71. 19. Yoshimura N, Yamaguchi M, Oshima Y, et al. Surgery for mitral valve disease in the pediatric age group. J Thorac Cardiovasc Surg 1999;118:99 106. 20. McCarthy JF, Neligan MC, Wood AE. Ten years experience of an aggressive reparative approach to congenital mitral valve anomalies. Eur J Cardiothorac Surg 1996;10:534 9. 21. Shone JD, Sellers RD, Anderson RC, Adams P Jr, Lillehei CW, Edwards JE. The developmental complex of parachute mitral valve, supravalvular ring of left atrium, subaortic stenosis, and coarctation of aorta. Am J Cardiol 1963;6:714 25. 22. Bolling SF, Iannettoni MD, Dick M 2nd, Rosenthal A, Bove EL. Shone s anomaly: operative results and late outcome. Ann Thorac Surg 1990;49:887 93. 23. Brauner RA, Laks H, Drinkwaster DC Jr, et al. Multiple left heart obstructions (Shone s anomaly) with mitral valve involvement: long-term surgical outcome. Ann Thorac Surg 1997;64:721 9.