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Systemic-Pulmonary Shunt Facilitates the Growth of the Pulmonary Valve Annulus in Patients With Tetralogy of Fallot
Systemic-Pulmonary Shunt Facilitates the Growth of the Pulmonary Valve Annulus in Patients With Tetralogy of Fallot Byung Kwon Chong, MD, Jae Suk Baek, MD, Yu-Mi Im, PhD, Chun Soo Park, MD, Jeong-Jun Park, MD, and Tae-Jin Yun, MD, PhD Divisions of Pediatric Cardiac Surgery and Pediatric Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul; and Seoul Women’s College of Nursing, Seoul, Republic of Korea
Background. Transannular patching (TAP) frequently accompanies primary repairs (PRs) in symptomatic neonates with tetralogy of Fallot (TOF). If a systemicpulmonary shunt (SPS) facilitates the growth of the pulmonary valve annulus (PVA), patients with a marginally small PVA could benefit from a staged repair in terms of lowering the risk of TAP. Methods. Among 216 infants with TOF who underwent surgical intervention between January 2004 and December 2013, 29 infants underwent SPS with a subsequent repair (SPS group), whereas 187 infants received a PR (PR group). Median age and the Z-score of the PVA (PVA [Z]) at SPS were 32 days and L3.5, respectively. There was one late death and one follow-up loss after SPS, and preservation of the PVA was achieved on repair in 16 patients (16 of 29; 55%). Results. Multiple regression analysis showed that performance of SPS was the only indicator of the increase
in the PVA (Z) in the entire cohort (n [ 216). On mixed linear regression, the PVA (Z) increased significantly after the placement of an SPS (L3.6 D 0.2*duration in months, p [ 0.001), whereas the prerepair changes in the PVA (Z) were not statistically significant in the PR group (p [ 0.7), with a significant intergroup difference (p < 0.001). Receiver operating characteristic curve analysis showed that placement of TAP is expected when the preshunt PVA (Z) is smaller than L4.2 (area under the curve: 0.82; 95% confidence interval: 0.62 to 1.00; sensitivity, 100%; specificity, 73%). Conclusions. SPS facilitates outgrowth of the PVA over somatic growth in patients with TOF. However, preservation of the PVA may not be achieved on staged repair if the initial PVA is too small.
D
[1]. Although our indications for shunt were not different from those of other investigators, we have inferred that the pulmonary valve annulus (PVA) growth rate is higher than that of somatic growth after an SPS, based on the coincidental findings that we have been able to preserve the PVA with a staged repair strategy in patients whose PVA had been deemed too small to be preserved at the time of SPS. Given the collinearity of the dimensions of the right ventricular outflow tract [7, 8], symptomatic young patients with severe infundibular stenosis tend to have a marginally small PVA. This is why PR for neonatal symptomatic TOF is associated with a higher risk of transannular patching (TAP) [9–15]. If performance of an SPS allows outgrowth of the PVA over somatic growth, patients with a marginally small PVA may benefit from staged repair strategy in terms of lowering the risk of TAP. In this study, we sought to determine whether an SPS facilitates growth of the PVA.
espite the excellent survival after the repair of tetralogy of Fallot (TOF), the optimal surgical management for symptomatic neonates and young infants has remained controversial. Even though primary repair (PR) is thought to be the procedure of choice in this setting [1], the systemic-pulmonary shunt (SPS) is still not infrequently performed in many pediatric cardiac programs [2–6]. It is still under debate whether PR is always superior to a staged repair. Because fetal echocardiography is more frequently used and precise prenatal diagnoses can be made in most of the patients, we tend to encounter more seriously symptomatic neonates with TOF who may need early surgical intervention. Current consensus indications for an SPS in patients with TOF are severely hypoplastic pulmonary arteries and extracardiac conditions precluding PR (eg, sepsis, viral respiratory infection, intracranial hemorrhage, and other organ dysfunction)
(Ann Thorac Surg 2016;-:-–-) Ó 2016 by The Society of Thoracic Surgeons
Accepted for publication May 17, 2016. Presented at the Fifty-second Annual Meeting of The Society of Thoracic Surgeons, Phoenix, AZ, Jan 23–27, 2016. Address correspondence to Dr Yun, Division of Pediatric Cardiac Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons Published by Elsevier
Patients and Methods Patients Between January 2004 and December 2013, 360 patients with TOF (excluding TOF with pulmonary atresia, TOF with absent pulmonary valve syndrome, and TOF with 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.05.064
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atrioventricular septal defect) underwent surgical intervention during infancy. The types of surgical intervention performed for these patients were PR (319 of 360; 89%), SPS (33 of 360; 9%), and palliative procedures other than SPS (ie, right ventricular outflow tract relief with TAP or stenting) (8 of 360; 2%). To determine the impact of SPS on the growth of the PVA, 216 patients with serial echocardiographic examinations before repair were selected, and these patients constituted the study cohort. Of these patients, 187 patients underwent PR (187 of 216; 87%; PR group), and 29 patients received an SPS (29 of 216; 13%; SPS group). Baseline characteristics including sex, gestational age, birth weight, frequency of prematurity, or the rate of prenatal diagnosis were not different between the two groups, but age at repair was significantly older in the SPS group, presumably the result of deferment of repair once the patients were stabilized by SPS (Table 1). Placement of an SPS was performed at a median age of 32 days (range, 5 to 319 days). Distal anastomoses of the modified Blalock-Taussig shunt were made to the right pulmonary artery in 15 patients, to the main pulmonary artery in 11 patients, and to the left pulmonary artery in 3 patients. Indications for an SPS were bilateral pulmonary artery hypoplasia in 13 patients, severe hypoxemia and marginally small pulmonary artery necessitating an emergency operation in 10 patients, severe juxtaductal stenosis with unilateral pulmonary artery hypoplasia in 5 patients, and multiple cardiac rhabdomyomas associated with tuberous sclerosis precluding PR in 1 patient [16]. Patients’ characteristics of the SPS group are detailed in Table 2. There was one late death 5 months after SPS, which was attributed to septic shock from necrotizing enterocolitis. Complications after SPS included shunt occlusion necessitating shunt revision or additional palliation (n ¼ 4), contralateral pulmonary artery hypoplasia necessitating a contralateral side SPS (n ¼ 1), and phrenic nerve paralysis on the ipsilateral side of SPS necessitating diaphragmatic plication (n ¼ 1).
Echocardiographic Measurement Echocardiographic images were obtained using a Vivid 7 Vantage machine equipped with 7- and 5-MHz transducers (GE Vingmed, Horten, Norway). All recordings of two-dimensional, M-mode, and Doppler images were obtained according to the recommendations of the American Society of Echocardiography [17]. All serial echocardiographic data before the repair were used except for echocardiograms repeated within 7 days. On average, 2.54 echocardiographic examinations per patient were conducted. All echocardiographic examinations were reviewed by a single cardiologist through offline analysis using Image-Arena software (version 4.6; TomTec Imaging Systems, Unterschleissheim, Germany). The Z-score of the PVA (PVA [Z]) was calculated using the formula described by Pettersen and colleagues [18]. The DPVA (Z) was defined as the difference of the PVA (Z) between the first and the last echocardiograms before repair.
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Statistical Analysis Data are presented as frequencies, medians with ranges for nonparametric data, or means with standard deviations for parametric data. Comparison of patients’ characteristics between the groups was performed using Fisher’s exact test or the c2 test for categorical variables and the Mann-Whitney U test or Student’s t test for continuous variables. To identify the variable that induces a larger DPVA (Z) in the entire cohort (n ¼ 216), a multiple regression analysis was performed including the following variables: sex, prematurity, birth weight, type of ventricular septal defect, interval between the dates of the first and the last echocardiography, and the performance of an SPS. To evaluate and compare the changes in the PVA (Z) as time passed, a mixed linear regression analysis was conducted to handle correlated data with unequal numbers of repetitions [19]. Thus, the impact of older age at repair (ie, longer follow-up period before repair) in the SPS group was adjusted by putting the variable “interval between the dates of the first and the last echocardiography” into multiple regression analysis and by mixed linear regression analysis. A receiver operating characteristics curve analysis was performed in the SPS group to determine the value of the preshunt PVA (Z) above which preservation of the PVA (AP) is expected on later repair. Statistical analyses were performed using SPSS 21 (SPSS Korea Data Solution, Seoul, South Korea) and R package “stats” version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria: http://www.R-project.org). Statistical differences were defined as significant by a two-sided test with a p value less than 0.05.
Results Repair of TOF was performed at a median age of 194 days (14 to 352 days) in the PR group and 255 days (85 to 1,590 days) in the SPS group (p < 0.001). Echocardiographic findings in both groups are listed in Table 3. Although the median PVA (Z) in the SPS group was significantly smaller than that in the PR group on the initial echocardiographic examination (3.5 vs 1.8; p < 0.001), PVA (Z) on the last echocardiographic examination before repair (2.6 2.2 vs 2.1 1.2; p ¼ 0.2) and the proportion of the patients with AP at repair (55% vs 73%; p ¼ 0.5) were comparable between the two groups. When the PVA (Z) on the last echocardiographic examination was compared with that of the initial echocardiographic examination in each group, there was a significant increase in the PVA (Z) after the placement of an SPS (p < 0.001) but no statistically significant changes in the PVA (Z) in PR group (p ¼ 0.29). Multiple regression analysis showed that performance of an SPS was the only indicator of outgrowth of the PVA over somatic growth (ie, larger D PVA [Z]) in the entire cohort (n ¼ 216) (Table 4). On mixed linear regression, the PVA (Z) increased significantly after the placement of an SPS (3.6 þ 0.2 duration in months; p ¼ 0.001), whereas the prerepair changes in the PVA (Z) were not statistically significant in the PR group (2.0 to
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Table 1. Patient-Related Characteristics and Operative Profile All Patients (n ¼ 216)
Variable Female sex Gestational age (days) Birth weight (kg) Prematurity (<37 weeks) Prenatal diagnosis Repair age (days) AP on repair
96 268 3.1 28 173 196 152
AP ¼ pulmonary annulus preservation;
SPS Group (n ¼ 29)
(44%) (179 w 293) (1.2 w 4.1) (13%) (80%) (14 w 1590) (70%)
16 268 3.0 6 22 255 16
PR ¼ primary repair;
PR Group (n ¼ 187)
(55%) (179 w 293) (2.3 w 4.1) (21%) (76%) (85 w 1590) (55%)
80 268 3.1 22 151 194 136
p Value
(43%) (240 w 280) (1.2 w 4.0) (12%) (81%) (14 w 352) (73%)
0.2 0.7 0.5 0.2 0.6 <0.001 0.5
SPS ¼ systemic-pulmonary shunt.
0.03 duration in months; p ¼ 0.7), with a significant intergroup difference (p < 0.001) (Figs 1, 2). Even though growth of the PVA outpaced somatic growth after an SPS in most of the patients, the growth of the PVA after an SPS was not sufficient to allow AP when the initial PVA was too small. For instance, AP was eventually achieved
in 16 of 19 patients (84%) with a PVA (Z) equal to or greater than 4.0 on initial preshunt echocardiographic imaging, whereas all patients with a PVA (Z) less than 4.0 received TAP (Fig 3). Receiver operating characteristics curve analysis showed that placement of TAP was expected on repair when the preshunt PVA (Z) was
Table 2. Patient-Related Characteristics of the Systemic-Pulmonary Shunt Group No.
Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
M M F F M F M M M F M M F F F M F F F F F M F F F M M M F
a
Shunt Age (days) 10 22 32 16 15 5 33 39 39 50 35 15 36 22 29 14 9 15 24 50 95 40 18 190 321 246 185 22 119
Shunt Type RMBT Central RMBT Central RMBT Central LMBT RMBT Central RMBT RMBT RMBT RMBT LMBT Central RMBT RMBT Central Central Central RMBT Central RMBT RMBT Central RMBT RMBT Central LMBT
Shunt Size (mm)
Age 1 (Z) (days)
PVA1 (Z)
Age 2 (days)
PVA2 (Z)
3 3.5 3.5 3.5 3.5 3.5 3.5 4 3.5 3.5 3 3.5 3.5 3.5 3.5 4 3.5 3.5 3.5 3.5 3.5 4 4 4 5 4 4 3.5 4
0 22 29 0 0 1 23 38 22 45 31 0 30 18 0 12 0 1 1 44 89 40 1 185 319 1 180 1 0
1.3 6.3 4.8 5.5 1.4 2.2 2.4 3.4 4.0 6.8 3.3 2.6 4.0 3.9 5.2 1.3 4.7 1.8 4.0 2.0 4.4 3.7 3.9 3.3 6.6 2.9 3.2 2.1 3.5
282 255 199 346 772 40 1536 135 404 209 483 20 133 193 159 98 174 78 358 154 255 302 147 685 434 1,007 354 126 202
0.4 6.4 3.8 4.3 0.9 1.6 3.3 2.3 0.6 4.9 2.7 1.0 0.7 3.5 4.6 0.5 5.5 1.4 0.6 3.7 2.7 3.2 0.8 5.5 5.6 0.7 3.1 0.1 1.9
RVOTR AP TAP TAP TAP AP NAa TAP AP AP TAP AP NAa AP AP TAP AP TAP TAP AP AP TAP AP AP TAP TAP AP AP AP AP
Patient No. 6 died of necrotizing enterocolitis before repair, and patient No. 12 was lost to follow-up.
Age 1 ¼ age at initial echocardiography; Age 2 ¼ age at the last echocardiography before repair; AP ¼ pulmonary valve annulus preservation; F ¼ female; M ¼ male; LMBT ¼ left modified Blalock-Taussig shunt; NA ¼ not applicable; PVA1 (Z) ¼ pulmonary valve annulus Z-score at initial echocardiography; PVA2 (Z) ¼ pulmonary valve annulus Z-score at the last echocardiography before repair; RMBT ¼ right modified Blalock-Taussig shunt; RVOTR ¼ right ventricular outflow tract reconstruction; TAP ¼ transannular patching.
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Table 3. Initial and Final Echocardiographic Data in the Systemic-Pulmonary Group and the Primary Repair Group Variable
All Patients (n ¼ 216)
SPS Group (n ¼ 29)
Initial echocardiographic findings Age (days) 1 (0 w 319) Body weight (kg) 3.2 (1.6 w 8.3) 130 (47 w 565) PAI (mm2/m2) PVA (mm) 5.7 (3.0 w 11.0) PVA (Z) 2.1 (6.8 w 1.0) Final echocardiographic findings before repair Age (days) 122 (7 w 1,536) Interval (days) 109 (4 w 1,534) Body weight (kg) 6.5 1.7 180 (94 w 487) PAI (mm2/m2) PVA (mm) 6.8 (3.8 w 14.6) PVA (Z) 2.2 1.4 PAI ¼ pulmonary artery index; PR ¼ primary repair; annulus; SPS ¼ systemic-pulmonary shunt.
18 3.2 87 4.4 3.5
(0 w 319) (2.4 w 8.3) (47 w 159) (3.0 w 6.6) (6.8 w 1.3)
209 (20 w 1536) 172 (21 w 1534) 7.5 2.3 319 (96 w 399) 6.1 (4.1 w 14.6) 2.6 2.2 PVA ¼ pulmonary valve annulus;
smaller than 4.2 (area under the curve: 0.82; 95% confidence interval: 0.62 to 1.00; sensitivity, 100%; specificity, 73%) (Fig 4).
Comment The optimal surgical strategy for symptomatic neonates with TOF is still under debate. Although PR has been thought to be an ideal approach in this setting [1], palliation seems to be favored more in practice. In the multicenter analysis encompassing 342 patients with TOF who were registered in The Society of Thoracic Surgeons database after various neonatal surgical interventions, palliation was more frequently performed than repair (ie, palliation in 178 and PR in 152) [2]. Given that the proportion of palliation for symptomatic neonates and young infants with TOF does not exceed 50% in large-volume centers [4, 20], it seems plausible to state that a subset
PR Group (n ¼ 187)
p Value
(0 w 203) (1.6 w 7.4) (49 w 565) (3.0 w 11.0) (6.7 w 1.0)
0.008 0.1 <0.001 <0.001 <0.001
117 (7 w351) 106 (4 w 354) 6.3 1.6 177 (94 w 487) 7.0 (3.8 w 12.2) 2.1 1.2
<0.001 <0.001 <0.001 0.7 0.2 0.2
1 3.1 135 5.8 1.8
PVA (Z) ¼ Z-score of the pulmonary valve
of patients who received palliation according to the aforementioned statistics would have undergone PR. Furthermore, an SPS has been reported to be associated with a several complications, including shunt occlusion, pulmonary artery distortion, and pulmonary overcirculation resulting in congestive heart failure. This study also showed that the placement of an SPS was associated with a significantly higher risk of interstage death and shunt-related morbidities. Because of the advances in surgical techniques and postoperative care, early outcomes of PR in infants with TOF are excellent, with a less than 3% early mortality rate [12, 20, 22, 24]. In the contemporary series, PR is advocated regardless of symptoms if patients are older than 3 months of age [21–23]. However, information pertaining to the actual benefits of PR over SPS for neonates is sparse. Given that the incidence of TAP is consistently high (71% to 100%) in the reported series of PRs for TOF in neonates and young infants [2, 4, 9–15, 20, 22], one may argue that the long-term disadvantages of TAP on right
Table 4. Multiple Regression Analysis to Identify Predictors for Larger Difference in the Z-Score of the Pulmonary Valve Annulus Diameter on Initial and Prerepair Echocardiography in the Entire Cohort (N ¼ 216) Multiple Regression Analysis Variables Sex Prematurity (<37 weeks) Birth weight (kg) VSD type Interval (months)a Performance of SPS
B
SE
p Value
0.29 0.18 0.07 0.06 0.01 1.07
0.18 0.30 0.19 0.25 0.21 0.26
0.11 0.58 0.97 0.82 0.56 0.001
a Interval between the first postnatal echocardiography and the last echocardiography before repair.
DPVA (Z) ¼ difference in B ¼ unstandardized regression coefficient; the Z-score of the pulmonary valve annulus diameter on initial and prerepair echocardiography; SE ¼ standard error; SPS ¼ systemicpulmonary shunt; VSD ¼ ventricular septal defect.
Fig 1. Postnatal changes of the Z-score of the pulmonary valve annulus diameter (PVA [Z]) in the primary repair group.
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Fig 2. Postnatal changes of the Z-score of the pulmonary valve annulus diameter (PVA [Z]) in the systemic-pulmonary shunt group.
ventricular size and function undermine the potential benefits of early repair in this subset of patients. Although several reports asserted that TAP does not adversely affect long-term outcomes with regard to further reintervention or mortality rates [14, 15], it is generally accepted that avoidance of TAP is desirable to prevent right ventricular dilatation necessitating pulmonary valve implantation [25–27]. The growth of the PVA after SPS placement has been implied in several studies [5, 6, 8, 24]. If placement of an SPS allows outgrowth of the PVA over somatic growth, patients with a marginally small PVA could benefit from a staged repair strategy in terms of lowering the risk of TAP. However, direct comparison between the SPS group and the PR group in terms of the incidence of AP is usually inappropriate because the two groups are different in the dimensions of the right ventricular outflow tract [5]. If the initial PVA is too small, the growth
Fig 3. Postnatal changes of the Z-score of the pulmonary valve annulus diameter (PVA [Z]) according to the types of right ventricular outflow tract reconstruction on repair in the systemic-pulmonary shunt group. PVA preservation was eventually achieved in 16 of 19 patients (84%) with a PVA (Z) equal to or greater than 4.0 on initial preshunt echocardiography, whereas all patients with PVA (Z) less than 4.0 received transannular patching.
Fig 4. Receiver operating characteristics curve analysis to determine the value of the initial Z-score of the pulmonary valve annulus diameter (PVA [Z]) above which PVA preservation is predicted on repair after a systemic-pulmonary shunt. (AUC ¼ area under the curve; CI ¼ confidence interval; Sens ¼ sensitivity; Spec ¼ specificity.)
of the PVA may not be sufficient for AP at the time of repair [5], as indicated in this study. If the initial PVA is sizable, PR may be the better surgical option than palliation. Thus, we would presume that the portion of the patients with TOF who would benefit from a staged repair for outgrowth of a marginally small PVA may be small. With respect to the types of ventricular septal defect, patients with infundibular septal deficiency (ie, subarterial or total conal defect ventricular septal defect) would benefit more from a staged repair strategy because this subgroup of patients with TOF may have a higher risk of developing right ventricular outflow tract obstruction after repair [7]. This study is subject to the limitations inherent to a single-institution, nonrandomized retrospective research. Although we were able to quantify the growth of the PVA after an SPS, it was difficult to isolate the effect of applying an SPS from the effects of other factors that may have contributed to outgrowth of the PVA. The changes in the PVA (Z) in the PR group were compared with those in the SPS group because one may argue that increase in the PVA (Z) is a time-related natural process, which turned out to be false in this study. Even though surgical mortality and morbidity rates of the SPS group were apparently higher than those of the PR group, we did not intend to compare the clinical outcomes of the two groups because the initial anatomic disposition was entirely different between the two groups. Despite the drawbacks of the staged repair, potential growth in the PVA after SPS may allow a valve-sparing repair in a subset of patients with a small PVA. Randomized controlled clinical trials are thus desirable for the accurate assessment of the benefits of an SPS over PR in a selected subset of patients.
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References 1. Van Arsdell G, Yun TJ. An apology for primary repair of tetralogy of Fallot. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005:128–31. 2. Al Habib HF, Jacobs JP, Mavroudis C, et al. Contemporary patterns of management of tetralogy of Fallot: data from The Society of Thoracic Surgeons database. Ann Thorac Surg 2010;90:813–9. 3. Fraser CD, McKenzie ED, Cooley DA. Tetralogy of Fallot: surgical management individualized to the patient. Ann Thorac Surg 2001;71:1556–63. 4. Kanter KR, Kogon BE, Kirshbom PM, Carlock PR. Symptomatic neonatal tetralogy of Fallot: repair or shunt? Ann Thorac Surg 2010;89:858–63. 5. Nakashima K, Itatani K, Oka N, et al. Pulmonary annulus growth after the modified Blalock-Taussig shunt in tetralogy of Fallot. Ann Thorac Surg 2014;98:934–40. 6. Stewart RD, Backer CL, Young L, Mavroudis C. Tetralogy of Fallot: results of a pulmonary valve–sparing strategy. Ann Thorac Surg 2005;80:1431–9. 7. Lim JY, Jhang WS, Kim YH, et al. Tetralogy of Fallot without the infundibular septum–restricted growth of the pulmonary valve annulus after annulus preservation may render the right ventricular outflow tract obstructive. J Thorac Cardiovasc Surg 2011;141:969–74. 8. Ross ET, Costello JM, Backer CL, Brown LM, Robinson JD. Right ventricular outflow tract growth in infants with palliated tetralogy of Fallot. Ann Thorac Surg 2015;99: 1367–72. 9. Di Donato RM, Jonas RA, Lang P, Rome JJ, Mayer JE Jr, Castaneda AR. Neonatal repair of tetralogy of Fallot with and without pulmonary atresia. J Thorac Cardiovasc Surg 1991;101:126–37. 10. Godart F, Rey C, Prat A, et al. Early and late results and the effects on pulmonary arteries of balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. Eur Heart J 1998;19:595–600. 11. Walsh EP, Rockenmarcher S, Keane JF, Hougen TJ, Lock JE, Castaneda AR. Late results in patients with tetralogy of Fallot repaired during infancy. Circulation 1988;77:1062–7. 12. Pigula FA, Khalil PN, Mayer JE, del Nido PJ, Jonas RA. Repair of tetralogy of Fallot in neonates and young infants. Circulation 1999;100(Suppl):II157–61. 13. Hirsch JC, Mosca RS, Bove EL. Complete repair of tetralogy of Fallot in the neonate: results in the modern era. Ann Surg 2000;232:508–14. 14. d’Udekem Y, Ovaert C, Grandjean F, et al. Tetralogy of Fallot: transannular and right ventricular patching equally
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affect late functional status. Circulation 2000;102(Suppl 3): III116–22. Bacha EA, Scheule AM, Zurakowski D, et al. Long-term results after early primary repair of tetralogy of Fallot. J Thorac Cardiovasc Surg 2001;122:154–61. Jhang WK, Jung HS, Ko JK, Yun TJ. Repair of tetralogy of Fallot after the regression of multiple rhabdomyomas in a patient with tuberous sclerosis. J Thorac Cardiovasc Surg 2010;139:e135–6. Quinones MA, Otto CM, Stoddard M, et al. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 2002;15: 167–84. Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. J Am Soc Echocardiogr 2008;21: 922–34. Dean CB, Nielsen JD. Generalized linear mixed models: a review and some extensions. Lifetime Data Anal 2007;13: 497–512. Hennein HA, Mosca RS, Urcelay G, Crowley DC, Bove EL. Intermediate results after complete repair of tetralogy of Fallot in neonates. J Thorac Cardiovasc Surg 1995;109:332–42. Van Arsdell GS, Maharaj GS, Tom J, et al. What is the optimal age for repair of tetralogy of Fallot? Circulation 2000;102(Suppl 3):III123–9. Tamesberger MI, Lechner E, Mair R, Hofer A, SamesDolzer E, Tulzer G. Early primary repair of tetralogy of Fallot in neonates and infants less than four months of age. Ann Thorac Surg 2008;86:1928–35. Parry AJ, McElhinney DB, Kung GC, Reddy VM, Brook MM, Hanley FL. Elective repair of acyanotic tetralogy of Fallot in early infancy: overall outcome and impact on the pulmonary valve. J Am Coll Cardiol 2000;36:2279–83. Sousa Uva M, Lacour-Gayet F, Komiya T, et al. Surgery for tetralogy of Fallot at less than six months of age. J Thorac Cardiovasc Surg 1994;107:1291–300. Kim GS, Han SB, Yun TJ. Pulmonary annulus preservation lowers the risk of late postoperative pulmonary valve implantation after the repair of tetralogy of Fallot. Pediatr Cardiol 2015;36:402–8. Karl TR, Sano S, Pornviliwan S, Mee RB. Tetralogy of Fallot: favorable outcome of nonneonatal transatrial, transpulmonary repair. Ann Thorac Surg 1992;54:903–7. Giannopoulos NM, Chatzis AK, Karros P, et al. Early results after transatrial/transpulmonary repair of tetralogy of Fallot. Eur J Cardiothorac Surg 2002;22:582–6.
DISCUSSION DR RICHARD KIM (Los Angeles, CA): I think that this paper again goes to show that there is a lot that we do not know about pulmonary artery growth and differential pulmonary artery growth. I am not sure I completely agree with you that the retrograde blood flow through a shunt would be sufficient to create a growth stimulus upon the annulus. It seems to me that there would not be any increase of flow across the annulus itself. This would perhaps increase pulmonary artery size but not necessarily the annulus. Would you have any other potential reasons or theories on how that annulus can grow? DR CHONG: Well, there are a couple of hypotheses that the increased left ventricular end-diastolic volume through the shunt makes more forward flow. And there is another theory that not actual blood flow but pressure of the pulmonary valve annulus may facilitate the growth of pulmonary valve annulus. I think
further studies are required, like echocardiogram or angiography or something. DR CHRISTOPHER CALDARONE (Toronto, ON, Canada): It is a very intriguing study. It is interesting today we have seen two different techniques that both are reported to increase pulmonary valve size, one placing an internal pulmonary artery band that decreases flow through the valve but may increase the pressure on the arterial side of the valve leaflets, and this technique as well, which, as you pointed out, does not really increase flow through the valve but is associated with catch-up growth. So it suggests that the flow through the valve is not really the signal we need to create, it is the pressure on the valve itself. It is a quite intriguing thought. One question I wanted to ask though, among the valves in which you saw this catch-up growth when you went to the
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operating room, although you were able to preserve the annulus, can you tell us about the competence of the valves and the appearance of the valve leaflets?
with marginally small PVA in the ToF spectrum may benefit from the placement of systemic pulmonary shunt in terms of increasing the probability of the later annulus preservation.
DR CHONG: Well, I did not look at it, but I presume that better morphology may lead to better growth of pulmonary valve annulus.
DR CALDARONE: Thanks for clarifying that, Dr Yun.
DR CALDARONE: Was the pulmonary valve competent after the repair when you preserved the annulus? DR YUN: Can I answer the question on his behalf? Well, it depends on the morphology of the pulmonary valve. Thus, regardless of the performance of systemic pulmonary shunt, competence of the pulmonary valve is determined by the morphology of the pulmonary valve at the time of repair. In some patients, the pulmonary valve is fibrotic and thickened at the time of systemic-pulmonary shunt. You may manage to preserve the annulus for these patients at the time of repair, but valve function may be unsatisfactory. On the other hand, some patients have very thin, mobile, albeit small, pulmonary valves at the time of shunt. If the PVA grows properly thanks to the shunt, their valve competency would be good after annulus preservation. Regarding the question of why the PVA grows after shunt, we did not try to verify the mechanism of the growth of the pulmonary valve annulus. We just saw it and just tried to compare shunt group with primary repair group in terms of the growth of the annulus. Maybe 5% or 10% of the patients
DR SHUNJI SANO (Okayama, Japan): We have a very similar result. We have repaired more than 300 [cases of] tetralogy of Fallot, the shunt ratio is around 8%, and we have had no deaths after the shunt. The main pulmonary artery grows as well as the pulmonary valve annulus after the shunt. But these findings are not always seen. As you said, the pulmonary valve annulus does not grow if the pulmonary valve itself is very thick and fibrotic. But growth of the pulmonary annulus is seen in many patients with tetralogy of Fallot. Therefore, we can preserve the pulmonary valve as much as we can. We used to repair tetralogy of Fallot with a mini-transannular patch less than 5 mm from the annulus. However, during 10 to 20 years’ time, many of these patients had mild to moderate pulmonary competence, and their left ventricular end-diastolic volume increased a little bit. Therefore, exercise tolerance became much less. So we changed the policy to try to preserve the pulmonary valve annulus as much as possible and then the pulmonary incompetence became much less in these patients. Now we can preserve the pulmonary valve in more than 80% of [cases of] tetralogy of Fallot. This strategy might be similar to that of Dr Chong’s group. DR CHONG: Thanks for the comment.
Background. Transannular patching (TAP) frequently accompanies primary repairs (PRs) in symptomatic neonates with tetralogy of Fallot (TOF). If a systemicpulmonary shunt (SPS) facilitates the growth of the pulmonary valve annulus (PVA), patients with a marginally small PVA could benefit from a staged repair in terms of lowering the risk of TAP. Methods. Among 216 infants with TOF who underwent surgical intervention between January 2004 and December 2013, 29 infants underwent SPS with a subsequent repair (SPS group), whereas 187 infants received a PR (PR group). Median age and the Z-score of the PVA (PVA [Z]) at SPS were 32 days and L3.5, respectively. There was one late death and one follow-up loss after SPS, and preservation of the PVA was achieved on repair in 16 patients (16 of 29; 55%). Results. Multiple regression analysis showed that performance of SPS was the only indicator of the increase
in the PVA (Z) in the entire cohort (n [ 216). On mixed linear regression, the PVA (Z) increased significantly after the placement of an SPS (L3.6 D 0.2*duration in months, p [ 0.001), whereas the prerepair changes in the PVA (Z) were not statistically significant in the PR group (p [ 0.7), with a significant intergroup difference (p < 0.001). Receiver operating characteristic curve analysis showed that placement of TAP is expected when the preshunt PVA (Z) is smaller than L4.2 (area under the curve: 0.82; 95% confidence interval: 0.62 to 1.00; sensitivity, 100%; specificity, 73%). Conclusions. SPS facilitates outgrowth of the PVA over somatic growth in patients with TOF. However, preservation of the PVA may not be achieved on staged repair if the initial PVA is too small.
D
[1]. Although our indications for shunt were not different from those of other investigators, we have inferred that the pulmonary valve annulus (PVA) growth rate is higher than that of somatic growth after an SPS, based on the coincidental findings that we have been able to preserve the PVA with a staged repair strategy in patients whose PVA had been deemed too small to be preserved at the time of SPS. Given the collinearity of the dimensions of the right ventricular outflow tract [7, 8], symptomatic young patients with severe infundibular stenosis tend to have a marginally small PVA. This is why PR for neonatal symptomatic TOF is associated with a higher risk of transannular patching (TAP) [9–15]. If performance of an SPS allows outgrowth of the PVA over somatic growth, patients with a marginally small PVA may benefit from staged repair strategy in terms of lowering the risk of TAP. In this study, we sought to determine whether an SPS facilitates growth of the PVA.
espite the excellent survival after the repair of tetralogy of Fallot (TOF), the optimal surgical management for symptomatic neonates and young infants has remained controversial. Even though primary repair (PR) is thought to be the procedure of choice in this setting [1], the systemic-pulmonary shunt (SPS) is still not infrequently performed in many pediatric cardiac programs [2–6]. It is still under debate whether PR is always superior to a staged repair. Because fetal echocardiography is more frequently used and precise prenatal diagnoses can be made in most of the patients, we tend to encounter more seriously symptomatic neonates with TOF who may need early surgical intervention. Current consensus indications for an SPS in patients with TOF are severely hypoplastic pulmonary arteries and extracardiac conditions precluding PR (eg, sepsis, viral respiratory infection, intracranial hemorrhage, and other organ dysfunction)
(Ann Thorac Surg 2016;-:-–-) Ó 2016 by The Society of Thoracic Surgeons
Accepted for publication May 17, 2016. Presented at the Fifty-second Annual Meeting of The Society of Thoracic Surgeons, Phoenix, AZ, Jan 23–27, 2016. Address correspondence to Dr Yun, Division of Pediatric Cardiac Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons Published by Elsevier
Patients and Methods Patients Between January 2004 and December 2013, 360 patients with TOF (excluding TOF with pulmonary atresia, TOF with absent pulmonary valve syndrome, and TOF with 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.05.064
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atrioventricular septal defect) underwent surgical intervention during infancy. The types of surgical intervention performed for these patients were PR (319 of 360; 89%), SPS (33 of 360; 9%), and palliative procedures other than SPS (ie, right ventricular outflow tract relief with TAP or stenting) (8 of 360; 2%). To determine the impact of SPS on the growth of the PVA, 216 patients with serial echocardiographic examinations before repair were selected, and these patients constituted the study cohort. Of these patients, 187 patients underwent PR (187 of 216; 87%; PR group), and 29 patients received an SPS (29 of 216; 13%; SPS group). Baseline characteristics including sex, gestational age, birth weight, frequency of prematurity, or the rate of prenatal diagnosis were not different between the two groups, but age at repair was significantly older in the SPS group, presumably the result of deferment of repair once the patients were stabilized by SPS (Table 1). Placement of an SPS was performed at a median age of 32 days (range, 5 to 319 days). Distal anastomoses of the modified Blalock-Taussig shunt were made to the right pulmonary artery in 15 patients, to the main pulmonary artery in 11 patients, and to the left pulmonary artery in 3 patients. Indications for an SPS were bilateral pulmonary artery hypoplasia in 13 patients, severe hypoxemia and marginally small pulmonary artery necessitating an emergency operation in 10 patients, severe juxtaductal stenosis with unilateral pulmonary artery hypoplasia in 5 patients, and multiple cardiac rhabdomyomas associated with tuberous sclerosis precluding PR in 1 patient [16]. Patients’ characteristics of the SPS group are detailed in Table 2. There was one late death 5 months after SPS, which was attributed to septic shock from necrotizing enterocolitis. Complications after SPS included shunt occlusion necessitating shunt revision or additional palliation (n ¼ 4), contralateral pulmonary artery hypoplasia necessitating a contralateral side SPS (n ¼ 1), and phrenic nerve paralysis on the ipsilateral side of SPS necessitating diaphragmatic plication (n ¼ 1).
Echocardiographic Measurement Echocardiographic images were obtained using a Vivid 7 Vantage machine equipped with 7- and 5-MHz transducers (GE Vingmed, Horten, Norway). All recordings of two-dimensional, M-mode, and Doppler images were obtained according to the recommendations of the American Society of Echocardiography [17]. All serial echocardiographic data before the repair were used except for echocardiograms repeated within 7 days. On average, 2.54 echocardiographic examinations per patient were conducted. All echocardiographic examinations were reviewed by a single cardiologist through offline analysis using Image-Arena software (version 4.6; TomTec Imaging Systems, Unterschleissheim, Germany). The Z-score of the PVA (PVA [Z]) was calculated using the formula described by Pettersen and colleagues [18]. The DPVA (Z) was defined as the difference of the PVA (Z) between the first and the last echocardiograms before repair.
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Statistical Analysis Data are presented as frequencies, medians with ranges for nonparametric data, or means with standard deviations for parametric data. Comparison of patients’ characteristics between the groups was performed using Fisher’s exact test or the c2 test for categorical variables and the Mann-Whitney U test or Student’s t test for continuous variables. To identify the variable that induces a larger DPVA (Z) in the entire cohort (n ¼ 216), a multiple regression analysis was performed including the following variables: sex, prematurity, birth weight, type of ventricular septal defect, interval between the dates of the first and the last echocardiography, and the performance of an SPS. To evaluate and compare the changes in the PVA (Z) as time passed, a mixed linear regression analysis was conducted to handle correlated data with unequal numbers of repetitions [19]. Thus, the impact of older age at repair (ie, longer follow-up period before repair) in the SPS group was adjusted by putting the variable “interval between the dates of the first and the last echocardiography” into multiple regression analysis and by mixed linear regression analysis. A receiver operating characteristics curve analysis was performed in the SPS group to determine the value of the preshunt PVA (Z) above which preservation of the PVA (AP) is expected on later repair. Statistical analyses were performed using SPSS 21 (SPSS Korea Data Solution, Seoul, South Korea) and R package “stats” version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria: http://www.R-project.org). Statistical differences were defined as significant by a two-sided test with a p value less than 0.05.
Results Repair of TOF was performed at a median age of 194 days (14 to 352 days) in the PR group and 255 days (85 to 1,590 days) in the SPS group (p < 0.001). Echocardiographic findings in both groups are listed in Table 3. Although the median PVA (Z) in the SPS group was significantly smaller than that in the PR group on the initial echocardiographic examination (3.5 vs 1.8; p < 0.001), PVA (Z) on the last echocardiographic examination before repair (2.6 2.2 vs 2.1 1.2; p ¼ 0.2) and the proportion of the patients with AP at repair (55% vs 73%; p ¼ 0.5) were comparable between the two groups. When the PVA (Z) on the last echocardiographic examination was compared with that of the initial echocardiographic examination in each group, there was a significant increase in the PVA (Z) after the placement of an SPS (p < 0.001) but no statistically significant changes in the PVA (Z) in PR group (p ¼ 0.29). Multiple regression analysis showed that performance of an SPS was the only indicator of outgrowth of the PVA over somatic growth (ie, larger D PVA [Z]) in the entire cohort (n ¼ 216) (Table 4). On mixed linear regression, the PVA (Z) increased significantly after the placement of an SPS (3.6 þ 0.2 duration in months; p ¼ 0.001), whereas the prerepair changes in the PVA (Z) were not statistically significant in the PR group (2.0 to
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Table 1. Patient-Related Characteristics and Operative Profile All Patients (n ¼ 216)
Variable Female sex Gestational age (days) Birth weight (kg) Prematurity (<37 weeks) Prenatal diagnosis Repair age (days) AP on repair
96 268 3.1 28 173 196 152
AP ¼ pulmonary annulus preservation;
SPS Group (n ¼ 29)
(44%) (179 w 293) (1.2 w 4.1) (13%) (80%) (14 w 1590) (70%)
16 268 3.0 6 22 255 16
PR ¼ primary repair;
PR Group (n ¼ 187)
(55%) (179 w 293) (2.3 w 4.1) (21%) (76%) (85 w 1590) (55%)
80 268 3.1 22 151 194 136
p Value
(43%) (240 w 280) (1.2 w 4.0) (12%) (81%) (14 w 352) (73%)
0.2 0.7 0.5 0.2 0.6 <0.001 0.5
SPS ¼ systemic-pulmonary shunt.
0.03 duration in months; p ¼ 0.7), with a significant intergroup difference (p < 0.001) (Figs 1, 2). Even though growth of the PVA outpaced somatic growth after an SPS in most of the patients, the growth of the PVA after an SPS was not sufficient to allow AP when the initial PVA was too small. For instance, AP was eventually achieved
in 16 of 19 patients (84%) with a PVA (Z) equal to or greater than 4.0 on initial preshunt echocardiographic imaging, whereas all patients with a PVA (Z) less than 4.0 received TAP (Fig 3). Receiver operating characteristics curve analysis showed that placement of TAP was expected on repair when the preshunt PVA (Z) was
Table 2. Patient-Related Characteristics of the Systemic-Pulmonary Shunt Group No.
Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
M M F F M F M M M F M M F F F M F F F F F M F F F M M M F
a
Shunt Age (days) 10 22 32 16 15 5 33 39 39 50 35 15 36 22 29 14 9 15 24 50 95 40 18 190 321 246 185 22 119
Shunt Type RMBT Central RMBT Central RMBT Central LMBT RMBT Central RMBT RMBT RMBT RMBT LMBT Central RMBT RMBT Central Central Central RMBT Central RMBT RMBT Central RMBT RMBT Central LMBT
Shunt Size (mm)
Age 1 (Z) (days)
PVA1 (Z)
Age 2 (days)
PVA2 (Z)
3 3.5 3.5 3.5 3.5 3.5 3.5 4 3.5 3.5 3 3.5 3.5 3.5 3.5 4 3.5 3.5 3.5 3.5 3.5 4 4 4 5 4 4 3.5 4
0 22 29 0 0 1 23 38 22 45 31 0 30 18 0 12 0 1 1 44 89 40 1 185 319 1 180 1 0
1.3 6.3 4.8 5.5 1.4 2.2 2.4 3.4 4.0 6.8 3.3 2.6 4.0 3.9 5.2 1.3 4.7 1.8 4.0 2.0 4.4 3.7 3.9 3.3 6.6 2.9 3.2 2.1 3.5
282 255 199 346 772 40 1536 135 404 209 483 20 133 193 159 98 174 78 358 154 255 302 147 685 434 1,007 354 126 202
0.4 6.4 3.8 4.3 0.9 1.6 3.3 2.3 0.6 4.9 2.7 1.0 0.7 3.5 4.6 0.5 5.5 1.4 0.6 3.7 2.7 3.2 0.8 5.5 5.6 0.7 3.1 0.1 1.9
RVOTR AP TAP TAP TAP AP NAa TAP AP AP TAP AP NAa AP AP TAP AP TAP TAP AP AP TAP AP AP TAP TAP AP AP AP AP
Patient No. 6 died of necrotizing enterocolitis before repair, and patient No. 12 was lost to follow-up.
Age 1 ¼ age at initial echocardiography; Age 2 ¼ age at the last echocardiography before repair; AP ¼ pulmonary valve annulus preservation; F ¼ female; M ¼ male; LMBT ¼ left modified Blalock-Taussig shunt; NA ¼ not applicable; PVA1 (Z) ¼ pulmonary valve annulus Z-score at initial echocardiography; PVA2 (Z) ¼ pulmonary valve annulus Z-score at the last echocardiography before repair; RMBT ¼ right modified Blalock-Taussig shunt; RVOTR ¼ right ventricular outflow tract reconstruction; TAP ¼ transannular patching.
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Table 3. Initial and Final Echocardiographic Data in the Systemic-Pulmonary Group and the Primary Repair Group Variable
All Patients (n ¼ 216)
SPS Group (n ¼ 29)
Initial echocardiographic findings Age (days) 1 (0 w 319) Body weight (kg) 3.2 (1.6 w 8.3) 130 (47 w 565) PAI (mm2/m2) PVA (mm) 5.7 (3.0 w 11.0) PVA (Z) 2.1 (6.8 w 1.0) Final echocardiographic findings before repair Age (days) 122 (7 w 1,536) Interval (days) 109 (4 w 1,534) Body weight (kg) 6.5 1.7 180 (94 w 487) PAI (mm2/m2) PVA (mm) 6.8 (3.8 w 14.6) PVA (Z) 2.2 1.4 PAI ¼ pulmonary artery index; PR ¼ primary repair; annulus; SPS ¼ systemic-pulmonary shunt.
18 3.2 87 4.4 3.5
(0 w 319) (2.4 w 8.3) (47 w 159) (3.0 w 6.6) (6.8 w 1.3)
209 (20 w 1536) 172 (21 w 1534) 7.5 2.3 319 (96 w 399) 6.1 (4.1 w 14.6) 2.6 2.2 PVA ¼ pulmonary valve annulus;
smaller than 4.2 (area under the curve: 0.82; 95% confidence interval: 0.62 to 1.00; sensitivity, 100%; specificity, 73%) (Fig 4).
Comment The optimal surgical strategy for symptomatic neonates with TOF is still under debate. Although PR has been thought to be an ideal approach in this setting [1], palliation seems to be favored more in practice. In the multicenter analysis encompassing 342 patients with TOF who were registered in The Society of Thoracic Surgeons database after various neonatal surgical interventions, palliation was more frequently performed than repair (ie, palliation in 178 and PR in 152) [2]. Given that the proportion of palliation for symptomatic neonates and young infants with TOF does not exceed 50% in large-volume centers [4, 20], it seems plausible to state that a subset
PR Group (n ¼ 187)
p Value
(0 w 203) (1.6 w 7.4) (49 w 565) (3.0 w 11.0) (6.7 w 1.0)
0.008 0.1 <0.001 <0.001 <0.001
117 (7 w351) 106 (4 w 354) 6.3 1.6 177 (94 w 487) 7.0 (3.8 w 12.2) 2.1 1.2
<0.001 <0.001 <0.001 0.7 0.2 0.2
1 3.1 135 5.8 1.8
PVA (Z) ¼ Z-score of the pulmonary valve
of patients who received palliation according to the aforementioned statistics would have undergone PR. Furthermore, an SPS has been reported to be associated with a several complications, including shunt occlusion, pulmonary artery distortion, and pulmonary overcirculation resulting in congestive heart failure. This study also showed that the placement of an SPS was associated with a significantly higher risk of interstage death and shunt-related morbidities. Because of the advances in surgical techniques and postoperative care, early outcomes of PR in infants with TOF are excellent, with a less than 3% early mortality rate [12, 20, 22, 24]. In the contemporary series, PR is advocated regardless of symptoms if patients are older than 3 months of age [21–23]. However, information pertaining to the actual benefits of PR over SPS for neonates is sparse. Given that the incidence of TAP is consistently high (71% to 100%) in the reported series of PRs for TOF in neonates and young infants [2, 4, 9–15, 20, 22], one may argue that the long-term disadvantages of TAP on right
Table 4. Multiple Regression Analysis to Identify Predictors for Larger Difference in the Z-Score of the Pulmonary Valve Annulus Diameter on Initial and Prerepair Echocardiography in the Entire Cohort (N ¼ 216) Multiple Regression Analysis Variables Sex Prematurity (<37 weeks) Birth weight (kg) VSD type Interval (months)a Performance of SPS
B
SE
p Value
0.29 0.18 0.07 0.06 0.01 1.07
0.18 0.30 0.19 0.25 0.21 0.26
0.11 0.58 0.97 0.82 0.56 0.001
a Interval between the first postnatal echocardiography and the last echocardiography before repair.
DPVA (Z) ¼ difference in B ¼ unstandardized regression coefficient; the Z-score of the pulmonary valve annulus diameter on initial and prerepair echocardiography; SE ¼ standard error; SPS ¼ systemicpulmonary shunt; VSD ¼ ventricular septal defect.
Fig 1. Postnatal changes of the Z-score of the pulmonary valve annulus diameter (PVA [Z]) in the primary repair group.
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Fig 2. Postnatal changes of the Z-score of the pulmonary valve annulus diameter (PVA [Z]) in the systemic-pulmonary shunt group.
ventricular size and function undermine the potential benefits of early repair in this subset of patients. Although several reports asserted that TAP does not adversely affect long-term outcomes with regard to further reintervention or mortality rates [14, 15], it is generally accepted that avoidance of TAP is desirable to prevent right ventricular dilatation necessitating pulmonary valve implantation [25–27]. The growth of the PVA after SPS placement has been implied in several studies [5, 6, 8, 24]. If placement of an SPS allows outgrowth of the PVA over somatic growth, patients with a marginally small PVA could benefit from a staged repair strategy in terms of lowering the risk of TAP. However, direct comparison between the SPS group and the PR group in terms of the incidence of AP is usually inappropriate because the two groups are different in the dimensions of the right ventricular outflow tract [5]. If the initial PVA is too small, the growth
Fig 3. Postnatal changes of the Z-score of the pulmonary valve annulus diameter (PVA [Z]) according to the types of right ventricular outflow tract reconstruction on repair in the systemic-pulmonary shunt group. PVA preservation was eventually achieved in 16 of 19 patients (84%) with a PVA (Z) equal to or greater than 4.0 on initial preshunt echocardiography, whereas all patients with PVA (Z) less than 4.0 received transannular patching.
Fig 4. Receiver operating characteristics curve analysis to determine the value of the initial Z-score of the pulmonary valve annulus diameter (PVA [Z]) above which PVA preservation is predicted on repair after a systemic-pulmonary shunt. (AUC ¼ area under the curve; CI ¼ confidence interval; Sens ¼ sensitivity; Spec ¼ specificity.)
of the PVA may not be sufficient for AP at the time of repair [5], as indicated in this study. If the initial PVA is sizable, PR may be the better surgical option than palliation. Thus, we would presume that the portion of the patients with TOF who would benefit from a staged repair for outgrowth of a marginally small PVA may be small. With respect to the types of ventricular septal defect, patients with infundibular septal deficiency (ie, subarterial or total conal defect ventricular septal defect) would benefit more from a staged repair strategy because this subgroup of patients with TOF may have a higher risk of developing right ventricular outflow tract obstruction after repair [7]. This study is subject to the limitations inherent to a single-institution, nonrandomized retrospective research. Although we were able to quantify the growth of the PVA after an SPS, it was difficult to isolate the effect of applying an SPS from the effects of other factors that may have contributed to outgrowth of the PVA. The changes in the PVA (Z) in the PR group were compared with those in the SPS group because one may argue that increase in the PVA (Z) is a time-related natural process, which turned out to be false in this study. Even though surgical mortality and morbidity rates of the SPS group were apparently higher than those of the PR group, we did not intend to compare the clinical outcomes of the two groups because the initial anatomic disposition was entirely different between the two groups. Despite the drawbacks of the staged repair, potential growth in the PVA after SPS may allow a valve-sparing repair in a subset of patients with a small PVA. Randomized controlled clinical trials are thus desirable for the accurate assessment of the benefits of an SPS over PR in a selected subset of patients.
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References 1. Van Arsdell G, Yun TJ. An apology for primary repair of tetralogy of Fallot. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005:128–31. 2. Al Habib HF, Jacobs JP, Mavroudis C, et al. Contemporary patterns of management of tetralogy of Fallot: data from The Society of Thoracic Surgeons database. Ann Thorac Surg 2010;90:813–9. 3. Fraser CD, McKenzie ED, Cooley DA. Tetralogy of Fallot: surgical management individualized to the patient. Ann Thorac Surg 2001;71:1556–63. 4. Kanter KR, Kogon BE, Kirshbom PM, Carlock PR. Symptomatic neonatal tetralogy of Fallot: repair or shunt? Ann Thorac Surg 2010;89:858–63. 5. Nakashima K, Itatani K, Oka N, et al. Pulmonary annulus growth after the modified Blalock-Taussig shunt in tetralogy of Fallot. Ann Thorac Surg 2014;98:934–40. 6. Stewart RD, Backer CL, Young L, Mavroudis C. Tetralogy of Fallot: results of a pulmonary valve–sparing strategy. Ann Thorac Surg 2005;80:1431–9. 7. Lim JY, Jhang WS, Kim YH, et al. Tetralogy of Fallot without the infundibular septum–restricted growth of the pulmonary valve annulus after annulus preservation may render the right ventricular outflow tract obstructive. J Thorac Cardiovasc Surg 2011;141:969–74. 8. Ross ET, Costello JM, Backer CL, Brown LM, Robinson JD. Right ventricular outflow tract growth in infants with palliated tetralogy of Fallot. Ann Thorac Surg 2015;99: 1367–72. 9. Di Donato RM, Jonas RA, Lang P, Rome JJ, Mayer JE Jr, Castaneda AR. Neonatal repair of tetralogy of Fallot with and without pulmonary atresia. J Thorac Cardiovasc Surg 1991;101:126–37. 10. Godart F, Rey C, Prat A, et al. Early and late results and the effects on pulmonary arteries of balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. Eur Heart J 1998;19:595–600. 11. Walsh EP, Rockenmarcher S, Keane JF, Hougen TJ, Lock JE, Castaneda AR. Late results in patients with tetralogy of Fallot repaired during infancy. Circulation 1988;77:1062–7. 12. Pigula FA, Khalil PN, Mayer JE, del Nido PJ, Jonas RA. Repair of tetralogy of Fallot in neonates and young infants. Circulation 1999;100(Suppl):II157–61. 13. Hirsch JC, Mosca RS, Bove EL. Complete repair of tetralogy of Fallot in the neonate: results in the modern era. Ann Surg 2000;232:508–14. 14. d’Udekem Y, Ovaert C, Grandjean F, et al. Tetralogy of Fallot: transannular and right ventricular patching equally
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DISCUSSION DR RICHARD KIM (Los Angeles, CA): I think that this paper again goes to show that there is a lot that we do not know about pulmonary artery growth and differential pulmonary artery growth. I am not sure I completely agree with you that the retrograde blood flow through a shunt would be sufficient to create a growth stimulus upon the annulus. It seems to me that there would not be any increase of flow across the annulus itself. This would perhaps increase pulmonary artery size but not necessarily the annulus. Would you have any other potential reasons or theories on how that annulus can grow? DR CHONG: Well, there are a couple of hypotheses that the increased left ventricular end-diastolic volume through the shunt makes more forward flow. And there is another theory that not actual blood flow but pressure of the pulmonary valve annulus may facilitate the growth of pulmonary valve annulus. I think
further studies are required, like echocardiogram or angiography or something. DR CHRISTOPHER CALDARONE (Toronto, ON, Canada): It is a very intriguing study. It is interesting today we have seen two different techniques that both are reported to increase pulmonary valve size, one placing an internal pulmonary artery band that decreases flow through the valve but may increase the pressure on the arterial side of the valve leaflets, and this technique as well, which, as you pointed out, does not really increase flow through the valve but is associated with catch-up growth. So it suggests that the flow through the valve is not really the signal we need to create, it is the pressure on the valve itself. It is a quite intriguing thought. One question I wanted to ask though, among the valves in which you saw this catch-up growth when you went to the
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CHONG ET AL SHUNT-RELATED PULMONARY VALVE ANNULUS GROWTH
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operating room, although you were able to preserve the annulus, can you tell us about the competence of the valves and the appearance of the valve leaflets?
with marginally small PVA in the ToF spectrum may benefit from the placement of systemic pulmonary shunt in terms of increasing the probability of the later annulus preservation.
DR CHONG: Well, I did not look at it, but I presume that better morphology may lead to better growth of pulmonary valve annulus.
DR CALDARONE: Thanks for clarifying that, Dr Yun.
DR CALDARONE: Was the pulmonary valve competent after the repair when you preserved the annulus? DR YUN: Can I answer the question on his behalf? Well, it depends on the morphology of the pulmonary valve. Thus, regardless of the performance of systemic pulmonary shunt, competence of the pulmonary valve is determined by the morphology of the pulmonary valve at the time of repair. In some patients, the pulmonary valve is fibrotic and thickened at the time of systemic-pulmonary shunt. You may manage to preserve the annulus for these patients at the time of repair, but valve function may be unsatisfactory. On the other hand, some patients have very thin, mobile, albeit small, pulmonary valves at the time of shunt. If the PVA grows properly thanks to the shunt, their valve competency would be good after annulus preservation. Regarding the question of why the PVA grows after shunt, we did not try to verify the mechanism of the growth of the pulmonary valve annulus. We just saw it and just tried to compare shunt group with primary repair group in terms of the growth of the annulus. Maybe 5% or 10% of the patients
DR SHUNJI SANO (Okayama, Japan): We have a very similar result. We have repaired more than 300 [cases of] tetralogy of Fallot, the shunt ratio is around 8%, and we have had no deaths after the shunt. The main pulmonary artery grows as well as the pulmonary valve annulus after the shunt. But these findings are not always seen. As you said, the pulmonary valve annulus does not grow if the pulmonary valve itself is very thick and fibrotic. But growth of the pulmonary annulus is seen in many patients with tetralogy of Fallot. Therefore, we can preserve the pulmonary valve as much as we can. We used to repair tetralogy of Fallot with a mini-transannular patch less than 5 mm from the annulus. However, during 10 to 20 years’ time, many of these patients had mild to moderate pulmonary competence, and their left ventricular end-diastolic volume increased a little bit. Therefore, exercise tolerance became much less. So we changed the policy to try to preserve the pulmonary valve annulus as much as possible and then the pulmonary incompetence became much less in these patients. Now we can preserve the pulmonary valve in more than 80% of [cases of] tetralogy of Fallot. This strategy might be similar to that of Dr Chong’s group. DR CHONG: Thanks for the comment.