Hemodynamic Assessment After Complete Repair of Pulmonary Atresia With Major Aortopulmonary Collaterals

Hemodynamic Assessment After Complete Repair of Pulmonary Atresia With Major Aortopulmonary Collaterals Richard D. Mainwaring, MD, V. Mohan Reddy, MD, Lynn Peng, MD, Calvin Kuan, MD, Michal Palmon, BS, MPH, and Frank L. Hanley, MD Divisions of Pediatric Cardiac Surgery, Pediatric Cardiology, and Pediatric Anesthesiology, Lucile Packard Children s Hospital/ Stanford University, Stanford, California Background. Pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals (PA/VSD/ MAPCAs) is a complex form of congenital heart defect. There are limited data regarding late hemodynamics of patients after repair of PA/VSD/MAPCAs. This study evaluated the hemodynamics of patients who underwent complete repair of PA/VSD/MAPCSs and subsequently returned for a conduit change. Methods. This was a retrospective review of 80 children undergoing a right ventricle (RV)-to-pulmonary artery conduit replacement after complete repair of PA/VSD/ MAPCAs. All patients underwent preoperative cardiac catheterization to define the cardiac physiology. Patients were an average age of 6.5 1.2 years, and the average interval between complete repair and conduit change was 4.5 1.1 years. Results. The preoperative cardiac catheterization demonstrated an average RV right peak systolic pressure of 70 22 mm Hg and pulmonary artery pressure of 38 14 mm Hg. This pressure gradient of 32 mm Hg reflects the presence of conduit obstruction. After conduit change, the intraoperative RV systolic pressure was 34 8mm Hg, similar to 36 9 mm Hg at the conclusion of the previous complete repair. The corresponding RV/aortic pressure ratios were 0.36 0.07 and 0.39 0.09, respectively. Conclusions. The data demonstrate that patients who underwent complete repair of PA/VSD/MAPCAs had nearly identical pulmonary artery pressures when they returned for conduit change some 4.5 years later. This finding indicates that the growth and development of the unifocalized pulmonary vascular bed is commensurate with visceral growth. We would hypothesize that complete repair, along with low RV pressures, will confer a long-term survival advantage. (Ann Thorac Surg 2013;95:1397 402) 2013 by The Society of Thoracic Surgeons Pulmonary atresia with ventricular septal defect (PA/ VSD) and major aortopulmonary collaterals (MAPCAs) is a complex and highly variable form of congenital heart disease. The natural history of PA/VSD/ MAPCAs is quite poor, with 10-year and 20-year survival estimated at 50% and 20%, respectively [1, 2]. The development of the midline unifocalization approach has been shown to significantly affect the prognosis for these patients [3, 4]. Numerous groups have adopted the midline unifocalization approach [5 11] and have confirmed the success of this surgical algorithm relative to the untreated natural history. Thus, one of the last forms of congenital heart disease, which had been lacking a successful strategy, has now given way to a surgical approach with a significant effect. Although the short-term and intermediate-term outcomes of patients undergoing a unifocalization approach to PA/VSD/MAPCAs have been well documented, there is currently a paucity of data evaluating late outcomes, as Accepted for publication Dec 21, 2012. Address correspondence to Dr Mainwaring, Stanford University School of Medicine, 300 Pasteur Dr, Falk CVRC, Stanford, CA 94305; e-mail: mainwaring@stanford.edu. summarized in Table 1. This lack of long-term outcome data is understandable for a variety of reasons. First, when new techniques are introduced, the initial focus tends to be the evaluation of short-term results. It is only after an approach matures that there is an effort to evaluate longer-term outcomes. Second, the unifocalization approach was introduced relatively recently, and thus, there has not been the opportunity to document outcomes in large cohorts over an extended period of time. The late results will inevitably be influenced by short-term factors (ie, surgical mortality) and also longer-term factors, such as the degree to which physiologic variables are normalized, such as the right ventricle (RV)/left ventricle (LV) pressure ratio. The effects of these latter factors may take years or even decades to manifest. To date, the existing literature has focused on factors affecting short and intermediate outcomes and has not attempted to address determinants of late outcome. The present study was conceived to address the lack of follow-up physiologic data in patients who have undergone a unifocalization approach for the management of PA/VSD/MAPCAs. One opportunity to access complete 2013 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc http://dx.doi.org/10.1016/j.athoracsur.2012.12.066

1398 MAINWARING ET AL Ann Thorac Surg HEMODYNAMIC ASSESSMENT 2013;95:1397 402 Table 1. Review of Literature on Hemodynamics After Unifocalization and Complete Repair First Author Year Total Pts (No.) Pts With Complete Repair (No.) Post-op RV/LV Ratio Pts With Late Assessment (No.) Late RV/LV Ratio Time to Assessment (y) Mainwaring Current 80 80 0.39 80 0.36 4.5 d Udekem [12] 2005 82 53... 22 0.62 1.4 Ishibashi [9] 2007 113 91...... 0.70 0.3 Carotti [7] 2010 90 55 0.48 35 0.53 8 Liava a [13] 2012 20 12... 9 0.64 1.1 Griselli [5] 2004 164 113 0.60......... Song [11] 2009 40 15 0.57......... Amark [8] 2006 53 21............ Mumtaz [10] 2008 40 25............ Davies [6] 2009 216 158............ LV left ventricle; Pts patients; RV right ventricle. hemodynamic data is at the time that failure of the RV-to-pulmonary artery conduit replacement develops. Our institutional policy has been to perform cardiac catheterization in all patients before conduit change, and we also routinely measure RV pressures intraoperatively after completion of the operation. The purpose of the present study was to review the results of these hemodynamic data in the follow-up of patients who have undergone complete repair after a unifocalization procedure. Material and Methods The Institutional Review Board at Stanford University approved this study. The study period was from April 2002 (when the surgical team moved to Stanford) to February 2012. Patients were identified through the cardiac database, and their medical records were subsequently reviewed. The current study summarizes the hemodynamic assessment of 80 patients (48 boys and 32 girls) undergoing a RV-to-pulmonary artery conduit change after complete repair of PA/VSD/MAPCAs. These 80 patients underwent cardiac catheterization before the RV-to-pulmonary artery conduit change to establish a complete assessment of their hemodynamic variables. Indications for cardiac catheterization were conduit stenosis in 74 and conduit insufficiency in 62. During the cardiac catheterization, 14 patients underwent 16 interventions, including balloon dilation or stent of the conduit in 8, dilation of peripheral stenoses in 6, and occlusion of residual MAPCAs in 2. Calculation of pulmonary vascular resistance was performed using pressure measurements from the central pulmonary arterial confluence. The operative records for the RV-to-pulmonary artery conduit change were reviewed. Patients were an average age at this operation of 6.5 1.2 years (range, 1.1 to 13.8 years), and the average weight was 22.0 4.4 kg (range, 5.5 to 58.6 kg). The RV pressure was measured by placing a needle directly into the RV through the proximal suture line. The RV/aortic peak systolic pressure measurements were recorded after separation from cardiopulmonary bypass. The operative records for the previous complete repair were reviewed for all patients. At the conclusion of all complete repair procedures, we routinely place a transthoracic pressure catheter through the free wall of the right atrium and advance this line across the tricuspid valve for monitoring of RV pressures in the postoperative period. A representative measurement of the RV and aortic peak systolic pressure measurements were recorded in the operative note. The average interval between complete repair and conduit change was 4.5 2.0 years. The original pulmonary artery anatomy included 66 of 80 patients (82%) with intrapericardial branch pulmonary arteries present at birth. In this group, 59 had confluent and 7 had nonconfluent central branch pulmonary arteries. Central branch pulmonary arteries were completely absent in 14 patients (18%). Statistical results are reported as the mean standard deviation. Comparison of different temporal points was performed with a paired t test analysis. Results The hemodynamic results of the cardiac catheterization performed before conduit change demonstrated an average RV peak systolic pressure of 70 22 mm Hg, a pulmonary artery peak systolic pressure of 38 14 mm Hg, and a LV peak systolic pressure of 90 18 mm Hg (Fig 1). These values reflect the presence of conduit obstruction in 74 and conduit insufficiency in 62 of the 80 patients. The average peak systolic gradient from the RV to the pulmonary artery was 32 15 mm Hg. Calculation of the pulmonary vascular resistance revealed an average of 2.35 0.40 Woods units. A ratio of peak systolic RV and pulmonary artery pressures to LV pressures was calculated from the pressure measurements for each patient, as shown in Figure 2. The average RV/LV peak systolic pressure ratio was 0.75 0.16. The average peak systolic pressure ratio

Ann Thorac Surg MAINWARING ET AL 2013;95:1397 402 HEMODYNAMIC ASSESSMENT 1399 Table 2. Concomitant Procedures Performed at the Time of Right Ventricle-to Pulmonary Artery Conduit Replacement Procedure No. Augmentation of central confluence 4 Repair of patent foramen ovale 4 Repair aortic valve 1 Repair of coronary artery 1 Fig 1. Hemodynamic assessment at cardiac catheterization demonstrates peak systolic pressures in the right ventricle (RV), pulmonary artery (PA), and left ventricle (LV). The error bars show the standard deviation. comparing the central pulmonary arterial/lv pressure ratio was 0.41 0.08. These ratios were statistically different from one another (p 0.005). Ten of the 80 (13%) patients underwent concomitant procedures, as summarized in Table 2. The conduit replacement in 76 patients was done without the need for an aortic cross-clamp. The average length of time on cardiopulmonary bypass was 92 44 minutes (median, 77 minutes; range, 52 to 224 minutes). The average RV peak systolic pressure was 34 8mm Hg after conduit replacement, with a simultaneous aortic peak systolic pressure of 94 10 mm Hg. Therefore, the calculated RV/aortic peak systolic pressure ratio after replacement of the conduit was 0.36 0.07 (Fig 3). The distribution of the intraoperative pressure ratios for the 80 individuals is shown in Figure 4. Data for the patients at the time of the previous complete repair are summarized in Figure 5. The average RV/aortic peak systolic pressure ratio was 0.39 0.09, or an average of 0.03 higher than that recorded after conduit replacement. This difference was not statistically significant. Three of the 80 patients demonstrated an increase in RV/aortic peak systolic pressure ratios of more than 0.05 when the measurements from complete repair were compared with those after conduit replacement. The 80 patients have been monitored for an average of 4.3 2.0 years (range, 1 month to 9.5 years) after conduit change. Fourteen have undergone a second conduit change, and 6 have had a third conduit change. In addition, a number of patients have undergone transcatheter insertion of a Melody valve (Medtronic Heart Valves Inc, Santa Ana, CA) since its approval by the U.S. Food and Drug Administration in 2010. No surgical deaths have occurred related to these subsequent procedures. There was one late death unrelated to the operation. Comment This report summarizes the hemodynamic measurements in 80 patients who had previously undergone complete repair of PA/VSD/MAPCAs and subsequently returned for conduit replacement. We chose conduit replacement as a definitive event because all patients would have a complete hemodynamic assessment at this time. The results of this study demonstrated an average Fig 2. Peak systolic pressure ratios are shown at cardiac catheterization for the right ventricle (RV) and pulmonary artery (PA) compared with the left ventricle (LV). The error bars show the standard deviation. Fig 3. Peak systolic pressure ratios are shown after conduit replacement, with data from the cardiac catheterization presented for reference. The error bars show the standard deviation. (Ao aorta; LV left ventricle; PA pulmonary artery; RV right ventricle.)

1400 MAINWARING ET AL Ann Thorac Surg HEMODYNAMIC ASSESSMENT 2013;95:1397 402 Fig 4. Bar graph demonstrates the distribution of right ventricle/aortic (RV/Ao) peak systolic pressure ratios at the conclusion of conduit replacement. RV/aortic peak systolic pressure ratio of 0.36 0.07, which was identical to the pressure ratio of 0.39 0.09 obtained at the conclusion of the previous complete repair. These findings indicate that the growth and development of the unifocalized pulmonary vascular bed is commensurate with visceral growth. To date, very limited hemodynamic data have been reported after complete repair of PA/VSD/MAPCAs. We could identify only three published reports that provided these data, with a total of 66 patients, as summarized in Table 1. The current study essentially doubles the number of patients with late hemodynamic data. Solid hemodynamic data are not available in most patients after complete repair because most programs (including ours) do not routinely perform cardiac catheterizations after the repair. It is for this reason that we chose conduit replacement as our end point because we do perform cardiac catheterizations before conduit operations and this provided an opportunity to obtain exact hemodynamic measurements. We acknowledge that the number of patients with PA/VSD/MAPCA who have undergone conduit replacements at our institution is a small fraction compared with the number who have undergone complete repair of PA/VSD/MAPCAs. There are a number of reasons for this disparity. First, by virtue of the Health Insurance Protection and Privacy Act enacted in 2003, we no longer have access to many of the medical records from our previous institution. In addition, although we receive referrals from a large geographic area for the initial treatment of PA/VSD/MAPCAs, many of these centers are comfortable performing the subsequent conduit replacements. Finally, the Melody valve has reduced the total number of conduit replacements that we perform since its approval 2 years ago. Thus, although this report provides data for only 80 patients, this is the entirety of patients who fulfilled the entry requirement of undergoing both a complete repair and conduit replacement at Stanford since the year 2002. The long-term outcome of patients with tetralogy of Fallot who undergo definitive repair has been directly linked with the residual pressure load on the RV [14 16]. Patients with normal RV pressures after repair have a predicted life expectancy approaching normal. In contrast, patients with elevated RV pressures have a high attrition rate. This experience with tetralogy of Fallot demonstrated an inflection point for RV/LV pressure ratio of 0.67 to determine favorable vs unfavorable longterm outcomes. The physiologic importance of RV pressures in tetralogy of Fallot has become universally accepted in the past several decades. Our previous reports indicate that 90% of patients achieve complete repair, with an average RV/LV pressure ratio of 0.41 0.12 immediately postoperatively and 0.36 0.11 at 7 years of follow-up [17]. The RV/LV pressure ratios in the current study are congruent with these previously reported data. We developed and use an intraoperative flow study to facilitate the decision making in patients undergoing complete repair [18]. Our current criteria include a flow rate of 3 L/min/m 2 to the reconstructed pulmonary arteries, with an acceptable pulmo- Fig 5. Peak systolic pressure ratios at the time of previous complete repair are compared with data after conduit replacement. The error bars show the standard deviation. (Ao aorta; LV left ventricle; PA pulmonary artery; RV right ventricle.)

Ann Thorac Surg MAINWARING ET AL 2013;95:1397 402 HEMODYNAMIC ASSESSMENT 1401 nary artery pressure of 25 mm Hg. These parameters will correspond to a postoperative RV/LV pressure ratio of approximately 0.40. The distribution of RV/aortic pressure ratios after conduit replacement is shown in Figure 4, with an average RV/aortic pressure ratio of 0.36 and no patient exceeding 0.60. Only 3 patients had a significant increase in RV/aortic pressure ratios after complete repair compared with the same measurements after conduit replacement. These data would suggest that pulmonary artery pressures and resistance across the reconstructed pulmonary vascular bed remain remarkably constant over time. Our group has not identified the original pulmonary artery anatomy to be a significant predictor of long-term outcome in most circumstances. Of the patients included in this study, central branch pulmonary arteries were present in 82% and were completely absent in 18%. In this latter group, complete repair relies entirely on unifocalization of collaterals, which in our hands has proven to have an equal rate of success. The one exception to this rule appears to be patients with confluent central pulmonary arteries that have normal arborization, share dual blood supply with MAPCAs, and present with cyanosis [19]. We recently demonstrated that this subgroup of patients had a lower rate of single-stage complete repair and ultimate complete repair. We believe this seemingly paradoxic result is more attributable to the growth and development of the pulmonary vascular bed in patients who present with the combination of dual supply and cyanosis than to the central branch pulmonary artery anatomy. Numerous groups have now reported their results for the surgical treatment of PA/VSD/MAPCAs [5 13, 20]. Surprisingly, only a few studies have provided data on RV/LV pressure ratios after complete repair (as summarized in Table 1), and just one study provided early and late hemodynamics [7]. The RV/LV pressure ratios reported in the literature are quite divergent, with averages ranging anywhere from 0.48 to 0.70. By definition, some of these patients would have RV/LV pressure ratios in excess of 0.67 and thus exceed the critical value determined for long-term success in tetralogy of Fallot. That the relationship between RV/LV pressure ratios and long-term survival has yet to be proven for PA/VSD/ MAPCAs is principally because it has yet to be evaluated. It is reasonable to presume that the physiologic principles that have been proven for tetralogy of Fallot will ultimately be shown to be applicable to patients with PA/VSD/MAPCAs as well. Liava a and colleagues [13] recently published their series of 25 patients in whom they managed PA/VSD/ MAPCAs without unifocalization of any MAPCAs. This approach resulted in complete repair in 12 patients, with 6 additional patients awaiting repair. The average RV/LV pressure ratio after complete repair was 0.64 (range, 0.54 to 0.91) at a median of 8 months. The authors concluded that their approach provides encouraging results with excellent early survival. We recognize that this approach may have a valid role in the treatment of the specific subset of patients who have confluent central pulmonary arteries with normal arborization and share dual supply with the MAPCAs (ie, the group of patients for whom we advocate initial treatment with an aortopulmonary window). However, this subgroup represents only 7% of all patients with PA/VSD/MAPCAs. Furthermore, 1 in 5 patients with PA/VSD/MAPCAs do not have any intrapericardial branch pulmonary arteries and thus are not treatable using their algorithm. This may account for the finding that 5 of the 25 patients in their study did not qualify for pulmonary artery rehabilitation and were managed with an alternative technique. We would raise concern that the relatively high RV/LV pressure ratios achieved by this philosophic approach will not provide satisfactory long-term results. There is one evident limitation in the interpretation of the current study. By definition, the patients included in this study were those who underwent a complete repair and a conduit replacement. This potentially may have a preselection bias in favor of those patients with the best physiology. However, the goal of this study was to evaluate the hemodynamic data in the same patient from complete repair to conduit replacement and was never intended to be representative of all patients enrolling for treatment. The study excluded all children in whom a complete repair was never achieved, which invariably is due to adverse physiology. This circumstance accounts for about 10% of the entire cohort of patients with PA/VSD/MAPCAs at our center. In addition, patients who have undergone complete repair and subsequently die before their conduit replacement would not be participants in this study. Although interim death is relatively rare in our experience, one potential explanation for this could be the presence of higher RV/LV pressure ratios. Thus, we would acknowledge that the patients included in this study are the survivors and likely represent somewhat more favorable cardiac and pulmonary physiology. In summary, the results of this study demonstrate that patients with PA/VSD/MAPCAs who return for conduit change have nearly identical RV pressures compared to when they originally underwent their complete repair. These data imply that the unifocalized pulmonary vascular bed has adequate growth potential to keep pace with visceral growth. The data also indicate that it is possible to achieve very acceptable RV pressures in the short-term and in the longer-term. We would hypothesize that complete repair and low RV pressures will prove to be the two most important prognostic indicators for long-term survival in PA/VSD/MAPCAs. References 1. Bull K, Somerville J, Spiegelhalter D. Presentation and attrition in complex pulmonary atresia. JACC 1995;25:491 9. 2. Leonard H, Derrick G, O Sullivan J, Wren C. Natural and unnatural history of pulmonary atresia. Heart 2000;84:499 503. 3. Reddy VM, Liddicoat JR, Hanley FL. Midline one-stage complete unifocalization and repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. J Thorac Cardiovasc Surg 1995;109:832 45.

1402 MAINWARING ET AL Ann Thorac Surg HEMODYNAMIC ASSESSMENT 2013;95:1397 402 4. Reddy VM, McElhinney DB, Amin Z, et al. Early and intermediate outcomes after repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: Experience with 85 patients. Circulation 2000;101:1826 32. 5. Griselli M, McGuirk SP, Winslaw DS, et al. The influence of pulmonary artery morphology on the results of operations for major aortopulmonary collateral arteries and complex congenital heart defects. J Thorac Cardiovasc Surg 2004;127: 251 8. 6. Davies B, Mussa S, Davies P, et al. Unifocalization of major aortopulmonary collateral arteries in pulmonary atresia with ventricular septal defect is essential to achieve excellent outcomes irrespective of native pulmonary artery morphology. J Thorac Cardiovasc Surg 2009;138:1269 75. 7. Carotti A, Albanese SB, Filleppelli S, et al. Determinants of outcome after surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2010;140:1092 103. 8. Amark KM, Karamlou T, O Carroll A, et al. Independent risk factors associated with mortality, reintervention, and achievement of complete repair in children with pulmonary atresia with ventricular septal defect. J Am Coll Cardiol 2006;47:1448 56. 9. Ishibashi N, Shin oka T, Ishiyama M, Sakamoto T, Kurosawa H. Clinical results of staged repair with complete unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Eur J Cardiothorac Surg 2007;32:202 8. 10. Mumtaz MA, Rosenthal G, Qureshi A, et al. Melbourne shunt promotes growth of diminutive central pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and systemic-to-pulmonary collateral arteries. Ann Thorac Surg 2008;85:2079 84. 11. Song SW, Park HK, Park YH, Cho BK. Pulmonary atresia with ventricular septal defects and major aortopulmonary collateral arteries. Circ J 2009;73:516 22. 12. d Udekem Y, Alphonso N, Norgaard MA, et al. Pulmonary atresia with ventricular septal defects and major aortopulmonary collateral arteries: Unifocalization brings no longterm benefits. J Thorac Cardiovasc Surg 2005;130:1496 502. 13. Liava a M, Brizard CP, Konstantinov IE, et al. Pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals: Neonatal pulmonary artery rehabilitation without unifocalization. Ann Thorac Surg 2012;93:185 92. 14. Kirklin JW, Blackstone EH, Shimazaki Y, et al. Survival, functional status, and reoperations after repair of tetralogy of Fallot with pulmonary atresia. J Thorac Cardiovasc Surg 1988;96:102 16. 15. Katz NM, Blackstone EH, Kirklin JW, Pacifico AD, Bargeron LM Jr. Late survival and symptoms after repair of tetralogy of Fallot. Circulation 1982;62:403 10. 16. Kirklin JW, Blackstone EH, Jonas RA, et al. Morphologic and surgical determinants of outcome events after repair of tetralogy of Fallot and pulmonary stenosis. A two-institution study. J Thorac Cardiovasc Surg 1992;103:706 23. 17. Malhotra SP, Hanley FL. Surgical management of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: a protocol-based approach. Semin Thorac Cardiovasc Surg Pediatr Card Surg Ann 2009;12:145 51. 18. Reddy VM, Petrossian E, McElhinney DB, Moore P, Teitel DF, Hanley FL. One-stage complete unifocalization in infants: When should the ventricular septal defect be closed? J Thorac Cardiovasc Surg 1995;109:832 45. 19. Mainwaring RD, Reddy VM, Perry SB, Peng L, Hanley FL. Late outcomes in patients undergoing aortopulmonary window for pulmonary atresia/stenosis and major aortopulmonary collaterals. Ann Thorac Surg 2012;94:842 8. 20. Norgaard MA, Alphonso N, Cochrane AD, Menaham S, Brizard CP, d Udekem Y. Major aorto-pulmonary collateral arteries of patients with pulmonary atresia and ventricular septal defect are dilated bronchial arteries. Eur J Cardiothorac Surg 2006;29:653 8.