Neither age at repair nor previous palliation affects outcome in tetralogy of Fallot repair

Transcription

1 European Journal of Cardio-Thoracic Surgery 45 (2014) doi: /ejcts/ezt307 Advance Access publication 12 June 2013 ORIGINAL ARTICLE a b c Neither age at repair nor previous palliation affects outcome in tetralogy of Fallot repair Branko Mimic a,b,katel.brown a, Nilesh Oswal a, Jacob Simmonds a, Tain-Yen Hsia a, Victor T. Tsang a, Marc R. De Leval c and Martin Kostolny a, * Cardiothoracic Surgery Department, Great Ormond Street Hospital, London, UK Cardiac Surgery Department, University Children s Hospital, Belgrade, Serbia Cardiothoracic Surgery Department, Harley Street Clinic, London, UK * Corresponding author. Cardiothoracic Surgery Department, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK. Tel: ; fax: ; kostom@gosh.nhs.uk (M. Kostolny). Received 18 December 2012; received in revised form 16 April 2013; accepted 29 April 2013 Abstract OBJECTIVES: The study aimed to evaluate the results following complete repair of tetralogy of Fallot (TOF) in relation to age at surgery and to assess the role of palliation in the current era. METHODS: A retrospective review of 251 consecutive patients with TOF repaired between 2003 and 2011 at the Great Ormond Street Hospital was performed. Children were divided into two groups: Group A, younger than 6 months (n = 78) and B, older than 6 months (n = 173). Early clinical outcomes and reoperation/reintervention rates were studied as well as indication for a palliation. RESULTS: There was 1 (0.4%) early and 1 (0.4%) late death after a median follow-up time of 4.5 years. Forty-three patients (17%) underwent repair after initial palliation with inter-stage mortality of 5%. Groups A and B were similar in terms of surgical approach, postoperative complications and length of stay. Significant differences were found in terms of more frequent use of a transannular patch (P = 0.05), longer surgeries (P = 0.02) and a greater proportion of palliated patients (P = 0.002) in older patients. There was no difference in rates of reoperation/reintervention between groups and following both primary and staged repair. Palliated patients were more symptomatic (duct-dependent pulmonary blood flow; P < 0.01, cyanotic spells; P < 0.01), had more extracardiac/genetic anomalies (P < 0.01), coronary anomalies (P = 0.015) and significantly smaller pulmonary annulus, right pulmonary artery (RPA) and left pulmonary artery (LPA) Z-scores (P < 0.01 for all). CONCLUSION: Age at complete repair was not linked to early clinical outcome or reoperation/reintervention rate. Palliative procedures postponed the timing of complete repair, but did not increase the reintervention rate. Keywords: Tetralogy of Fallot Palliation Primary repair INTRODUCTION Although the history of tetralogy of Fallot (TOF) repair extends over six decades, controversy concerning the optimal technique and timing of the corrective surgery still remains. In the current era, primary surgical repair in infants continues to gain increasing acceptance [1, 2]. Proponents of primary neonatal repair in symptomatic patients cite factors such as prevention of time-related end-organ damage from cyanosis, removal of stimulus for right ventricular (RV) hypertrophy and improved lung development to support this policy [3 5]. In addition, this approach avoids the risks of shunt-related complications, namely shunt thrombosis, congestive heart failure, pulmonary hypertension and pulmonary arterial distortion. However, a number of surgeons undertaking a neonatal TOF repair use a trans-ventricular approach [1, 6] and deep hypothermic circulatory arrest [6]. Furthermore, transannular Presented at the 26th Annual Meeting of the European Association for Cardio- Thoracic Surgery, Barcelona, Spain, October patch (TAP) reconstruction of the right ventricular outflow tract (RVOT) was reported to be used more frequently in neonates and young infants [1, 7], with possible deleterious effects of long-term pulmonary regurgitation (PR) [8]. Some have advocated palliating symptomatic neonates to avoid TAP and preserve the pulmonary valve function at the time of complete repair [9, 10]. We have taken the approach of elective primary repair of infants without severe cyanosis around the age of 6 months and staged repair of symptomatic neonates and young infants with unfavourable anatomy. In this study, the relationship between age at corrective surgery and outcome was assessed, and the indications for a staged rather than primary repair were explored. MATERIALS AND METHODS Patient population All patients undergoing either palliation or complete repair of TOF between 1 January 2003 and 1 April 2011 were identified from The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery 93 our institution patient database. Data were obtained from medical records and echocardiographic, surgical and catheterization reports. Patients with pulmonary atresia, absent pulmonary valve, major systemic to pulmonary collaterals, double outlet right ventricle with aortic-mitral discontinuity, associated atrioventricular septal defect and those who required concomitant tracheal surgery were excluded. TOF with pulmonary stenosis was diagnosed by trans-thoracic echocardiography and occasionally supplemented by cardiac catheterization to further delineate the anatomy of the pulmonary arteries and/or define the presence of major systemic to pulmonary collaterals. Cardiac catheterization was utilized more often in patients who had previous palliation (49 vs 18%; P = 0.02). Based on age at repair, children were divided into two groups: Group A, younger than 6 months (n = 78, median age 132 days; range , mean weight 5.6 ± 1.0 kg) and Group B, >6 months (n = 173, median age 315 days; range , mean weight 8.4 ± 2.8 kg). Palliation was reserved for symptomatic neonates with sustained cyanosis (saturations <70%), cyanotic spells and ductdependent pulmonary blood flow and those who had unfavourable anatomy such as branch pulmonary artery (PA) hypoplasia or coronary anomalies. Severe non-cardiac anomalies or syndromes might have been a contributing factor in decision-making. This study was registered and approved by the Research & Development office at the Institute of Child Health, London with ethical approval for the use of retrospective, anonymized data. Surgical technique Primary repairs were performed on moderate hypothermia cardiopulmonary bypass (CPB) with aortic and bicaval cannulation and intermittent, antegrade blood cardioplegia. A vent was routinely inserted through the right upper pulmonary vein into the left atrium. The transatrial/transpulmonary approach was the preferred method of repair. The RVOT inspection, and excision/transection of obstructive parietal and septal bundles began through the tricuspid valve. After completion of the infundibular myectomy, the diameters of the RVOT and the pulmonary valve were assessed with Hegar dilators and if found less than the two standard deviations (SDs) for the patient s age and weight [11], the main PA was opened longitudinally. Further RVOT obstruction (RVOTO) relief was performed by additional muscle bundles transection and/or pulmonary valvotomy. If the infundibulum had a long tunnel-like stenosis, a small infundibular incision was performed without incising the pulmonary valve ring. If necessary (Z-score < 3), the pulmonary arteriotomy was extended proximally and a TAP was inserted. Branch pulmonary arterioplasty was performed if indicated either by a separate patch or by extension of main PA (MPA) patch. The ventricular septal defect (VSD) was closed through the tricuspid valve in all but 5 patients. Interatrial communications were routinely closed in 238 (95%) patients. After the coming of CPB, the adequacy of the repair was assessed by measuring the peak RV/left ventricle (LV) pressure ratio in 210 of 251 (84%) patients. An RV/LV pressure ratio of <0.75 was considered as acceptable. Transoesophageal echocardiography was routinely used to assess the repair. If the residual obstruction was demonstrated at the level of the annulus with RV/LV pressure ratio of >0.75, then a TAP was inserted. Residual obstruction at the sub-valvular level was managed by either further muscle bundle resection or ventriculotomy with the placement of infundibular patch. This was required in 31 patients (12%). Outcome was evaluated in March 2012 in terms of patient survival using the survival status recorded in the UK care record service, and the occurrence of any reinterventions including surgical or catheter based was noted since all such procedures are recorded in the database. The follow-up echocardiograms were reviewed on 180/251 (72%) with the mean follow-up time of 2.64 years (range, ). Missing echocardiographic data were those from patients under remote follow-up either abroad or at distant locations in the UK. Statistical analysis Variables are expressed as the mean ± SD or median and range as appropriate. Continuous variables were compared with twotailed, unpaired Student s t-test or Mann Whitney U-test, as applicable. Categorical data were compared with two-tailed Pearson χ 2 test or Fisher s exact test, as applicable. For all analyses, a P-value of <0.05 was considered statistically significant. Freedoms from time-related events (reoperation and reintervention) were analysed using the Kaplan Meier method and for the analysis of differences in the course of survival, the log-rank test was used. Multivariate Cox regression analysis was used to define independent predictors for reoperation and reintervention. RESULTS Demographic and operative results The study included 251 consecutive patients with TOF (138 males, 55%) who underwent complete repair. Extracardiac malformations were found in 37 (15%) patients and a congenital or genetic syndrome was diagnosed in 36 (14%). The median age at repair was 248 days (range, ) and the median weight was 7.2 kg (range ), with the oldest patient having immigrated to the UK shortly before repair was undertaken. Forty-three patients (17%) underwent corrective repair after initial palliation. The demographic and operative data for all patients and the comparison between age groups A and B are depicted in Table 1. The older patients received a TAP more frequently (A: 44 vs B: 57%; P = 0.05) and required longer cross clamp (A: 49.8 ± 19.2 vs B: 55.9 ± 20.6; P = 0.02) and CPB time (A: 96.6 ± 34.5 vs B: ± 35.6; P = 0.03). More patients from age group B had previous palliation (A: 6 vs B: 22%; P = 0.002). The majority in both groups received a right ventriculotomy to further enlarge the RVOT (A: 64 vs B: 72%; P = 0.23). Higher TAP and increased right ventriculotomy rate in patients repaired after 6 months did not result in significantly different RV/LV pressure ratio immediately after correction (A: 0.58 vs B: 0.56; P = 0.14). Different types of PA plasty at the time of complete repair were equally distributed between groups (A: 9 vs B: 15%; P = 0.19). Early outcomes There was 1 (0.4%) early (hospital) death in a child with dysmorphic features who underwent complete repair with a TAP at the age of 19 months and had a major conal branch crossing the RVOT. The patient died of cardiac failure and multiorgan dysfunction on CONGENITAL

3 94 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery Table 1: Demographic and operative data and comparison between Groups A and B Variable analysed Group A (n = 78) Group B (n = 173) Overall (n = 251) P-value Preoperative data Male/female 45/33 93/80 138/ χ 2 Age (months), median (range) 4.4 ( ) 10.5 ( ) 8.3 ( ) <0.01 MW Weight (kg), mean ± SD 5.6 ± ± ± 2.7 <0.01 T Right aortic arch, n (%) 11 (14) 20 (12) 31 (12) 0.57 χ 2 Associated cardiac anomalies, n (%) 9 (12) 27 (16) 36 (14) 0.39 χ 2 Associated non-cardiac anomalies, n (%) 9 (12) 26 (15) 37 (15) 0.39 χ 2 Syndromes, n (%) 8 (10) 28 (16) 36 (14) 0.21 χ 2 All coronary anomalies, n (%) 5 (6) 17 (10) 22 (9) 0.47 χ 2 Previous palliation, n (%) 5 (6) 38 (22) 43 (17) χ 2 Operative data (complete repair) TAP plasty, n (%) 34 (44) 98 (57) 132 (53) 0.05 χ 2 Non-TAP with ventriculotomy, n (%) 16 (21) 27 (15) 43 (17) 0.34 χ 2 Non-TAP without ventriculotomy, n (%) 28 (35) 48 (28) 76 (30) 0.25 χ 2 Branch pulmonary arterioplasty, n (%) 7 (9) 26 (15) 33 (13) 0.19 χ 2 Bypass time (min), mean ± SD 96.6 ± ± ± MW AXCT (min), mean ± SD 49.8 ± ± ± MW RV/LV pressure ratio, mean ± SD 0.58 ± ± ± MW TAP: transannular patch; AXCT: aortic cross-clamp time; RV/LV: right ventricle/left ventricle; MW: Mann Whitney U-test; χ 2 : Pearson χ 2 test; F: Fisher s exact test; T: Student s t-test. Bold figures indicate statistically significant differences. Table 2: Postoperative data following complete repair and comparison between groups Variable analysed Group A (n = 78) Group B (n = 173) Overall (n = 251) P-value Number of patients (%) Number of patients (%) Number of patients (%) Hours intubated, median (range) 22 (0 520) 23 (0 714) 23 (0 714) 0.63 MW ICU stay, median hours (range) 68 (22 713) 51 (0 9682) 55.5 ( ) 0.09 MW Early reoperation/reintervention 1 (1) 8 (5) 9 (4) 0.28 F Early death 0 (0) 1 (0.6) 1 (0.4) 1.00 F Delay sternal closure 4 (5) 5 (3) 9 (4) 0.46 F Major bleeding required re-exploration 2 (3) 11 (6) 13 (5) 0.35 F Pleural drainage 4 (5) 9 (5) 13 (5) 0.97 F ECMO 2 (3) 2 (1) 4 (2) 0.59 F Peritoneal dialysis 14 (18) 28 (16) 42 (17) 0.73 χ 2 JET 12 (15) 27 (16) 39 (15) 0.79 χ 2 Amiodaron 10 (13) 22 (13) 32 (13) 0.98 χ 2 Temporary pacing 14 (18) 39 (23) 53 (21) 0.29 χ 2 LCOS 8 (10) 11 (6) 19 (8) 0.28 χ 2 Sepsis 1 (1) 4 (2) 5 (2) 1.00 F Chylothorax 4 (5) 6 (3) 10 (4) 0.51 F NO 2 (3) 6 (3) 8 (3) 1.00 F NEC 1 (1) 1 (0.6) 2 (1) 0.52 F Brain infarct 1 (1) 0 (0) 1 (0.4) 0.31 F PM implantation 0 (0) 2 (1) 2 (1) 1.00 F Diaphragm plication 1 (1) 2 (1) 3 (1) 1.00 F ECMO: extracorporeal membrane oxygenation; JET: junctional ectopic tachycardia; LCOS: low cardiac output syndrome; NO: nitric oxide; NEC: necrotizing enterocolitis; PM: pace maker; MW: Mann Whitney U-test; F: Fisher s exact test; χ 2 : Pearson χ 2 test. the sixth postoperative day. The entire cohort had a median duration of mechanical ventilator support of 23 h (range, 0 714), and a median postoperative intensive care unit (ICU) stay of 55.5 h (range, ), with no observed differences between Groups A and B. Postoperative complications (Table 2) were also similar between Groups A and B. Nine of 251 patients required at total of 11 early reoperations and 1 reintervention in the catheter lab during the same admission. Six patients had reintervention(s) for a residual RVOTO or branch PA stenosis, 1 patient had a residual VSD, 1 had a repair of ruptured tricuspid valve chordae and 1 had a closure of residual patent ductus arteriosus. Late outcomes There was 1 (0.4%) late (after discharge) death in an ex-premature baby with DiGeorge syndrome who underwent primary repair with a TAP at the age of 15 months with prolonged ICU stay (8

4 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery 95 Table 3: Indication for and type of late reoperation and reintervention Reoperations Number of reoperations Reinterventions Number of reinterventions RVOTO relief with muscle bundles resection or TAP plasty 3 Balloon dilatation of LPA and RPA stenosis 4 RV-PA conduit insertion for residual RVOTO and/or pulmonary arteries 9 Balloon dilatation of LPA stenosis 3 stenosis RV-PA conduit insertion for free PR and RV dilatation 3 Balloon dilatation of RPA stenosis 0 RV-PA conduit replacement for conduit obstruction 2 Balloon dilatation of RVOT 3 Aortopexy 1 Balloon dilatation of RPA stent 2 Vascular ring repair 1 Balloon dilatation of LPA stent 4 Balloon dilatation of Hanckok conduit 1 stenosis Stenting of RPA and LPA stenosis 2 Stenting of LPA stenosis 7 Stenting of RPA stenosis 2 ASD device closure 1 PA band dilatation 1 Total RVOTO: right ventricle outflow tract obstruction; RV: right ventricle; PR: pulmonary regurgitation; TAP: transannular patch; RV-PA: right ventricle to pulmonary artery; RPA: right pulmonary artery; LPA: left pulmonary artery; PA: pulmonary artery. days). The echocardiography before discharge showed grossly impaired RV function and the child died at home after a sudden event 18 months postoperatively. Twenty-nine patients underwent 19 late reoperations and 30 late catheter based reinterventions after a median time of 18 (range, 1 61) and 10 months (range, ), respectively. Indications for and types of surgical and catheter reintervention are given in Table 3. Both 5-year freedom from reoperation and freedom from any reoperation and reintervention were not significantly different between the 2 patient groups (Fig. 1). Univariate Cox regression models for the hazard of a first reintervention are given in Table 4: age group, palliations and congenital syndromes did not increase the risk of reintervention. Univariate analysis indicated the hazard was greater with TAP (P = 0.04), a second run of bypass (P =0.03) and arterioplasty of branch pulmonary arteries at the time of complete repair (P < 0.01). A Cox multiple regression model indicated that only pulmonary arterioplasty was significant when all factors were considered together (P < 0.01). At a median echocardiographic follow-up of 2.6 years, the mean peak RVOT velocity in Groups A and B was similar at 2.23 ± 0.74 and 2.23 ± 0.73 m/s, respectively (P = 0.846). The mean value of PR grade (coded as follows: none-0, mild-1; moderate-2; severe-3; free-4) was estimated as severe or free in 50% of patients. TAP was associated with significantly more severe PR: 75% of these had severe or free vs 24% of those without TAP, P < Despite finding older patients to be more likely to receive a TAP, the proportion with severe PR was not significantly greater in Group B than A (severe or free PR 54 vs 43%, respectively; P = 0.33). All but 14 patients had either normal or mildly impaired RV function at the last follow-up; however, there was no significant difference between Groups A and B in terms of RV function. The palliated group During the study period, 47 patients underwent palliation initially, of whom 43 underwent complete repair (2 patients died interstage and 2 were awaiting repair at the time of study closure). Figure 1: Actuarial freedom from any late reoperation and reintervention and comparison between age groups. Eight of these 43 had at least one shunt palliation performed at another institution. There were 35 surgical and 4 interventional palliations performed at our institution (Table 5). For shunt palliation, a sternotomy was the preferred approach (29/34 shunts). At the shunt operation, 3 of 34 had a patch enlargement of the proximal LPA. Indications for palliation were one or a combination of following factors: sustained cyanosis (<70%), cyanotic spells, ductdependent pulmonary blood flow, hypoplastic branch pulmonary arteries (right pulmonary artery (RPA) and/or left pulmonary artery (LPA) Z-score < 2), weight <3 kg, prematurity and anomalous coronary (LAD/RCA) crossing RVOT. The median age at palliation was 27 days (range, 1 296), median weight 3.3 kg (range, ). Thirty-seven of 39 (95%) had two and more indications for palliation. Three of 4 patients who underwent shunt palliation due to major coronary anomaly (LAD/RCA) crossing the RVOT were >3 months old at the time of palliation. A comparison CONGENITAL

5 96 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery Table 4: Cox regression model for the hazard of a first reintervention of any type Univariate Cox regression Hazard ratio for first reintervention = surgery + catheter (95% CI) P-value Group A vs B 0.87 (0.44, 1.75) 0.70 Palliated vs non-palliated 1.41 (0.64, 3.11) 0.38 Syndromic vs non-palliated 1.43 (0.62, 3.25) 0.40 TAP 2.12 (1.04, 4.33) 0.04 Monocusp valve 0.67 (0.09, 4.95) 0.70 Pulmonary arterioplasty 7.14 (3.69, 13.81) <0.001 CPB second run 2.35 (1.07, 5.17) 0.03 RVOT patch 0.47 (0.14, 1.53) 0.21 MPA patch 0.76 (0.32, 1.84) 0.55 Multiple Cox regression, including the three significant factors CPB second run 1.54 (0.68, 3.45) 0.30 TAP 1.27 (0.60, 3.44) 0.53 Pulmonary arterioplasty 6.09 (2.96, 12.54) <0.001 TAP: transannular patch; RVOT: right ventricle outflow tract; PA: pulmonary artery; CPB: cardiopulmonary bypass. Bold figures indicate risk factors for a reintervention. Table 5: Palliative procedures performed at our institution Palliation type No of patients Age (days) at palliation, median (range) Surgical Right modified BT shunt 24 Left modified BT shunt 4 Right modified BT shunt + LPA 3 27(1 296) plasty Central systemic to pulmonary 3 shunt RVOT patch 1 61 Overall surgical palliation (1 296) Interventional Balloon pulmonary valvotomy 2 9 (4 14) Stenting of RVOT (13 58) Overall interventional palliation (4 58) BT: Blalock Taussig; LPA: left pulmonary artery; RVOT: right ventricle outflow tract. between patients who underwent primary and staged repair at our institution is given in Table 6. Patients who required staged repair were more symptomatic (duct-dependent pulmonary blood flow 29 vs 0%; P < 0.01, cyanotic spells 34 10%; P < 0.01) and had significantly more extracardiac anomalies, syndromes (43 vs 20%; P < 0.01), and coronary anomalies (20 vs 7%; P = 0.015). Furthermore, they represent the subset of children with less favourable anatomy characterized by significantly smaller pulmonary annulus, RPA and LPA Z-scores (P < 0.01 for all). A palliative procedure increased the age at complete repair, with median time from palliation to repair of 375 days (range ). Only 5 palliated patients had complete repair before 6 months of age. Although palliated patients had more TAP (83 vs 48%; P < 0.01) at the time of corrective surgery than those who underwent primary repair, they did not experience a significantly higher reoperation/reintervention rate (Fig. 2). There was 1 early shunt-related death and 1 late death in a child with VACTERL association and severely hypoplastic pulmonary arteries who died of a non-cardiac reason 1 year after palliation. There were five major complications after surgical palliation. One right shunt occlusion and infection, which required taking down of the shunt followed by left shunt insertion, extracorporeal membrane oxygenation (ECMO) support and stenting of the RPA. There were 3 mediastinal explorations due to major bleeding and 1 cardiac arrest. DISCUSSION This study reviews a single-centre experience with the surgical treatment of TOF over the most recent era ( ). Inclusion of patients for study was based on a diagnosis of TOF rather than the operative procedure, in order to optimally elucidate important mortalities and morbidities at all stages, and thus reflect on our practice. During the study period, elective primary repair was considered for all patients 6 months of age. Staged repair was reserved for symptomatic neonates with sustained cyanosis and duct-dependent pulmonary blood flow. Unfavourable coronary anatomy, hypoplastic branch pulmonary arteries, associated extracardiac anomalies and genetic syndromes also affected our decision in favour of initial palliation. Optimal age at repair The elective repair of an asymptomatic infant with TOF has been proposed as optimally timed between 3 and 12 months of age. It has been shown that infants undergoing primary repair before 3 months of age experienced greater morbidity than older infants; more frequent need for peritoneal drainage, longer times to extubation and longer stays in the ICU [12, 13]. Bove et al. [14] have shown that decreasing the age at repair, at least to the age of 3 months, does not affect the early clinical outcome. Furthermore, they proposed complete repair between 3 and 6 months of age, irrespective of symptomatic status or previous palliation. They believe this age range enhances the opportunity of relieving the hypoplastic RVOT with minimal transannular incision, with the risk of revision being required later, but highlight the long-term protective effect of restrictive physiology on RV function. These conclusions are in keeping with our study, which demonstrated that children undergoing primary repair before the age of 6 months had equivalent mid-term results in terms of recurrent RVOTO and RV function. Furthermore, younger age at repair was not linked to any increased perioperative morbidity measure, nor was it linked to the risk of reinterventions. Whether repair at a younger age increases the need for the use of a TAP remains uncertain [12, 15, 16]. The higher incidence of TAP in the older patients in our series might be explained by progressive right ventricle hypertrophy and reduced PA development leading to more aggressive RVOTO relief at the time of complete repair. However, it is more likely that this finding is the result of our policy to correct the anatomically and physiologically favourable patients while palliating the others. The fact that palliation postponed complete repair with a median inter-stage period of 375 days (all but 5 palliated patients underwent complete repair

6 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery 97 Table 6: Comparison between patients that underwent primary and staged repair (palliated patients that referred from other institutions were excluded; Z-scores for palliated patients were collected before palliation) Variable analysed Staged repair (n = 35) Primary repair (n = 208) P-value Preoperative data Spells, n (%) 12 (34) 21 (10) <0.01 (χ 2 ) DAP dependant pulmonary circulation, n (%) 10 (29) 0 (0) <0.01 (F) Prematurity, n (%) 8 (23) 24 (12) 0.07 (χ 2 ) Extracardiac anomalies/syndromes, n (%) 15 (43) 42 (20) <0.01 (χ 2 ) All coronary anomalies, n (%) 7 (20) 15 (7) (χ 2 ) (LAD from RCA/RCA from LCA) (3/1) (2/0) Pulmonary annulus Z-score, mean ± SD 4.34 ± ± 3.01 <0.01 (T) RPA Z-score, mean ± SD 2.27 ± ± 1.24 <0.01 (T) LPA Z-score, mean ± SD 2.09 ± ± 1.58 <0.01 (T) Catheterization prior complete repair, n (%) 21 (60) 32 (15) <0.01 (χ 2 ) Operative data (complete repair) TAP, n (%) 29 (83) 99 (48) <0.01 (χ 2 ) Bypass time (min), mean ± SD ± ± (MW) AXCT (min), mean ± SD 54.9 ± ± (MW) Branch PA plasty, n (%) 8 (23) 24 (12) 0.07 (χ 2 ) Follow-up data Reoperation and/or reintervention, n (%) 6 (17) 23 (11) 0.45 (χ 2 ) DAP: ductus arteriosus persistens; LAD: left anterior descending; RCA: right coronary artery; TAP: transannular patch; AXCT: aortic cross-clamp time; RPA: right pulmonary artery; LPA: left pulmonary artery; MW: Mann Whitney U-test; χ 2 : Pearson χ 2 test; F: Fisher s exact test.; T: Student s t-test. Bold figures indicate statistically significant differences. Figure 2: Actuarial freedom from any late reoperation/reintervention and comparison between primary and staged repair. after the age of 6 months) and that palliated patients need significantly more TAP than those undergoing primary repair (83 vs 48%) suggest that the severity of RVOTO, rather than age at repair in isolation, determines the frequency with which TAP is used. This finding correlates with other studies that have suggested that age at repair does not influence the incidence of use of TAP [17] and that palliated patients required more TAP [9]. Significantly longer cross clamp and CPB times in the older age group in our series might be the result of similar factors. Staged vs primary repair The management of the symptomatic neonates and young infants under 3 months of age is more controversial. Options for these children include surgical or interventional palliation or early primary repair. Kanter et al. [18] have recently shown an early mortality of 1/17 in the shunted group and no mortality among 20 primary repaired neonates. In the same study, the actuarial freedom from death or reoperation at 5 years was 69% for the primary repaired and 77% for the shunted neonates. A multiinstitutional report from 2002 [19] showed that for patients 3 months of age or less, the mortality for a shunt vs a repair was similar (6.2 vs 8.0%). Knott-Craig et al. [20] demonstrated a relatively high mortality rate of 11% for staged repair, whereas Sfyridis et al.[21] showed zero operative and inter-stage mortality in shunted patients. Our overall inter-stage mortality of 5% (2/39) is consistent with other reports showing relatively low mortality rates with staged repair of TOF [21, 22]. Furthermore, our strategy is in accordance with authors who advocate an individualized approach rather than primary repair in all TOF patients [7, 10, 13]. The different types of surgical and interventional palliation utilized in our institution express an effort to offer an optimal palliation to each patient, based on their clinical condition, weight and underlying anatomy. Symptomatic neonates with branch pulmonary arteries of relatively reasonable size (>3 mm) were more likely to receive right or left shunt palliation, whereas those with severely hypoplastic pulmonary arteries underwent either a central systemic to pulmonary shunt or RVOT patch. A RVOT stent has recently become a possible alternative for symptomatic neonates with critical PV stenosis [23]. Reoperation and reintervention Freedom from surgical or catheter reintervention after TOF repair in early infancy in published series [16, 24, 25] ranges from 79 to 96% at 20 years. Bove et al. [14] demonstrated a 3-year freedom from reoperation for residual or recurrent RVOTO of 86%. Tamesberger et al. [1] has shown that the majority of CONGENITAL

7 98 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery reintervention (75%) is due to stenotic LPA. The 5-year freedom from reoperation and reintervention for any cause of 86% (equivalent between palliated and primary repair groups, and unrelated to age at repair) in our series appears comparable to other published data [13, 16, 21]. Twenty of 30 (66%) reinterventions in our series occurred because of a LPA stenosis, which contributed as an indication for reoperation or reintervention in 21 of 29 patients. Furthermore, branch pulmonary arterioplasty at the time of complete repair regardless of the technique employed was the strongest predictor of reintervention and reoperation in our experience. Correction with a TAP did not influence late reoperation/reintervention rate in our series. This correlates with the study by Alexiou et al. [16], which demonstrated that the use of a TAP is not a significant factor for any further operation and intervention for pulmonary valve replacement (PVR). Only three patients received an RV-PA conduit for free PR associated with significant RV dilatation. On the other hand, a relatively high proportion of PVR in our patients undergoing reoperation (12/15) might be a result of RVOTO at multiple levels (from infundibulum to proximal branch pulmonary arteries), usually combined with free PR in children who had received a TAP. However, further follow-up is mandatory to assess effect of TAP on long-term RV function and the necessity for PVR. Limitations This study is limited by its retrospective nature. Echocardiographic follow-up data are incomplete with relatively short median followup time. Patients were divided into two groups with a cut-off age at repair of 6 months being rather arbitrary. Since the palliated group represents the subset of patients with less favourable anatomy and physiology often associated with extracardiac or coronary anomalies, we are not able to compare the outcome of palliation and early primary repair. Consequently, we do not know what the outcome would have been if we had done repair instead of palliation for these high-risk patients. Our strategy and conclusions Currently, for symptomatic patients, primary repair is considered in the absence of coronary anomalies, small pulmonary arteries and major extracardiac problems irrespective of age. For asymptomatic patients, a repair is undertaken ideally between 4 and 6 months of age. Age at complete repair was not linked to early clinical outcomes or reoperation/reintervention rate. Palliation postponed the timing of complete repair, and palliated patients were more likely to receive a TAP, however, this was unrelated to the reintervention rate. Our strategy to selectively palliate patients results in as good an outcome as primary repair. Primary repair at an age <6 months gave good mid-term results in patients with favourable anatomy. It is possible to operate earlier and leave staged repair for the subset of symptomatic patients with the most unfavourable anatomy. Conflict of interest: none declared. REFERENCES [1] Tamesberger MI, Lechner E, Mair R, Hofer A, Sames-Dolzer E, Tulzer G. Early Primary Repair of Tetralogy of Fallot in Neonates and Infants Less Than Four Months Of Age. Ann Thorac Surg 2008;86: [2] Pigula FA, Khalil PN, Mayer JE, del Nido PJ, Jonas RA. Repair of tetralogy of Fallot in neonates and young infants. Circulation 1999;100:II [3] Rabinovitch M, Herrera-deLeon V, Castaneda AR, Reid L. Growth and development of the pulmonary vascular bed in patients with tetralogy of Fallot with or without pulmonary atresia. Circulation 1981;64: [4] Derby CD, Pizarro C. 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Tetralogy of Fallot: surgical management individualized to the patient. Ann Thorac Surg 2001;71: [11] Rowlatt JF, Rimoldi HJ, Lev M. The quantitative anatomy of the normal child s heart. Pediatr Clin North Am 1963;10: [12] Van Arsdell GS, Maharaj GS, Tom J, Rao VK, Coles JG, Freedom RM et al. What is the optimal age for repair of tetralogy of Fallot? Circulation 2000; 102 (19 suppl 3):III [13] Ooi A, Moorjani N, Baliulis G, Keeton BR, Salmon AP, Monro JL et al. Medium term outcome for infant repair in tetralogy of Fallot: Indicators for timing of surgery. Eur J Cardiothorac Surg 2006;30: [14] Bové T, François K, Van De Kerckhove K, Panzer J, De Groote K, De Wolf D et al. Assessment of a right-ventricular infundibulum-sparing approach in transatrial-transpulmonary repair of tetralogy of Fallot. Eur J Cardiothorac Surg 2012;41: [15] Vobecky SJ, Williams WG, Trusler GA, Coles JG, Rebeyka IM, Smallhorn J et al. 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8 B. Mimic et al. / European Journal of Cardio-Thoracic Surgery 99 APPENDIX. CONFERENCE DISCUSSION Dr G. Sarris (Athens, Greece): The authors report their entire last eight years experience with surgery for tetralogy of Fallot including all patients, palliations as well as repairs, and achieved truly excellent results with an early mortality of 0.4%, which is in keeping with the best results that are published in the literature. There were, however, some reoperations, including 11 early reoperations during the same hospitalization and a not-insignificant rate of late reoperations for the right ventricular outflow tract. Of the patients who were palliated, 35 had their palliation at the authors institution, and only eight were referred there with a previous palliative procedure. Therefore, of the 78 patients who comprised the early repair group, only 5% had a prior palliative procedure. But of the 173 patients who comprised the late group, 20% had shunts at the authors institution. One could therefore say that the group of patients who had later repair was burdened by these patients who were deemed to be unfavourable enough in terms of anatomy and clinical situation that they were shunted. And conversely, the group of patients who were subjected to early repair was relieved of the higher risk patients because those high-risk patients were shunted and therefore had their repair postponed. The authors question was is there a relationship between age at surgery and outcome? and they concluded that age at repair does not seem to affect clinical outcome. My comment is that this conclusion is not true for all of this group of patients, but only for the subgroup of patients who do not need early palliative help. Therefore, following this comment, I have two questions. The first one is: based on your analysis of this experience, have you changed your policy of selective shunting? And do you still offer, therefore, selective shunting to your patients based on these criteria that you have outlined? Dr Mimic: It is a quite difficult question. I think that we have changed our policy a little bit recently. So definitely there is still a group of patients who require some kind of palliation, actually different types of palliation. We offered in our institution, actually expressed our wish to offer the best possible palliation to the child regarding underlying anatomy, clinical condition, and weight at that time. Probably still there is still room for shunt palliation and also other types of palliation, but we think that the preferable age for complete repair is between four and six months of age. Dr Sarris: My follow-up question, then, pertains to the situation of a child with tetralogy, a newborn who might present to your unit without symptoms and without any of the listed indications for shunting. What would your recommendation for repair be for these patients? Would it be neonatal repair? Dr Mimic:Definitely we still do not do early neonatal repair in asymptomatic patients. Probably the best age, as I already mentioned, is between four and six months of age. But in symptomatic neonates with unfavourable anatomy, most likely we would offer a palliation. CONGENITAL