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Effect of Endovascular Stenting of Right Ventricle to Pulmonary Artery Conduit Stenosis in Infants With Hypoplastic Left Heart Syndrome on Stage II Outcomes
Effect of Endovascular Stenting of Right Ventricle to Pulmonary Artery Conduit Stenosis in Infants With Hypoplastic Left Heart Syndrome on Stage II Outcomes Robert G. Gray, MDa,*, L. Luann Minich, MDa, Hsin Yi Weng, MPHb, Mason C. Heywood, BSb, Phillip T. Burch, MDc, and Collin G. Cowley, MDa There is growing awareness that the Norwood procedure with the Sano modification is prone to early right ventricular to pulmonary artery (RV–PA) conduit stenosis resulting in systemic oxygen desaturation, increased interstage morbidity, and death. We report our experience with endovascular stent placement for conduit stenosis and compare the outcomes at stage II surgery between stented and nonstented infants. The medical records of all patients with hypoplastic left heart syndrome who received an RV–PA conduit at Norwood palliation from May 2005 to January 2010 were reviewed. The preoperative anatomy, demographics, operative variables, and outcomes pertaining to the Norwood and subsequent stage II surgeries were obtained and compared between stented and nonstented infants. The pre- and post-stent oxygen saturation, stenosis location, type and number of stents implanted, concomitant interventions, procedure-related complications, and reinterventions were collected. Of the 66 infants who underwent the Norwood procedure with RV–PA conduit modification, 16 (24%) received stents. The anatomy, demographics, and outcome variables after the Norwood procedure were similar between the stented and nonstented infants. The age at catheterization was 93 ⴞ 48 days, and the weight was 4.9 ⴞ 1.2 kg. The oxygen saturation increased from 66 ⴞ 9% before intervention to 82 ⴞ 6% immediately after stenting (p <0.0001). No interstage surgical shunt revisions were performed in either group. Age, weight, pre-stage II echocardiographic variables, oxygen saturation, and operative and outcome variables, including mortality, were similar between the 2 groups. In conclusion, endovascular stent placement for RV–PA conduit stenosis after the Norwood procedure leads to improved systemic oxygen levels and prevents early performance of stage II surgery without compromising stage II outcomes. © 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:118 –123) The mortality associated with the Norwood procedure in infants with hypoplastic left heart syndrome (HLHS) remains the greatest among the congenital heart procedures.1–5 One strategy for providing pulmonary blood flow involves the placement of a right ventricular to pulmonary artery (RV–PA) conduit instead of the traditional modified Blalock-Taussig (mBT) shunt.6 There is a growing awareness, however, that the RV–PA conduit is prone to early stenosis, leading to systemic oxygen desaturation and contributing to increased interstage morbidity and death.3,7,8 In an effort to manage this progressive cyanosis, some centers have advocate performing the stage II surgery as early as 2 months of age,9,10 and others have opted to surgically revise the RV–PA conduit or to replace it with a mBT shunt.7,11,12 Recently, transcatheter stent placement within the RV–PA conduit has been reported to improve systemic oxygen saturation.13–18 To date, the effects of endovascular RV–PA conduit stent implantation on the acute outcomes at the a Division of Pediatric Cardiology, bDepartment of Pediatrics, and cDivision of Cardiothoracic Surgery, University of Utah, Salt Lake City, Utah. Manuscript received January 4, 2012; revised manuscript received and accepted February 26, 2012. *Corresponding author: Tel: (801) 662-5400; fax: (801) 662-5404. E-mail address: [email protected] (R.G. Gray).
0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2012.02.060
stage II surgery have not been fully investigated. Therefore, we sought to determine the risks and effectiveness of endovascular stent placement for the treatment of RV–PA conduit stenosis and to compare the stage II surgical outcomes between the infants who underwent conduit stenting and those who did not. The institutional review boards of the University of Utah and Primary Children’s Medical Center approved this retrospective study under a waiver of informed consent. The pediatric cardiovascular surgery database was searched for all patients with HLHS who had undergone the Norwood procedure with the Sano modification from May 2005 to January 2010. The medical records were reviewed for gender, gestational age, and underlying cardiac diagnosis. The variables related to the Norwood surgery included age and weight at surgery, RV–PA conduit diameter at implantation, duration of cardiopulmonary bypass (CPB), aortic crossclamping, circulatory arrest and days of mechanical ventilation, chest tube use, intensive care unit length of stay (LOS), hospital LOS, and discharge oxygen saturation. The interstage period was defined as the interval after Norwood discharge until admission for stage II surgery. The variables related to stage II surgery included age and weight at surgery, prestage II oxygen saturation, CPB duration, days of mechanical ventilation, chest tube use, intensive care unit www.ajconline.org
Congenital Heart Disease/Stage II Outcomes After Conduit Stent
119
Figure 1. Angiographic example of distal RV–PA conduit stenosis (arrow) using right anterior oblique caudal angulation before (A) and after stent placement (B). Table 1 Cardiac anatomy, demographics, and outcome variables at initial Norwood procedure Variable
Conduit Stent (n ⫽ 16)
No Conduit Stent (n ⫽ 50)
6 6 1 2 1 38.1 ⫾ 1.8 7.4 ⫾ 4.0 3.2 ⫾ 0.6
17 16 13 1 3 38.1 ⫾ 1.3 5.8 ⫾ 2.0 3.0 ⫾ 0.5
15 1 0 0
44 5 1 0
1.00
11 5 0 0 5.2 ⫾ 0.4 144 ⫾ 25 57 ⫾ 12 6⫾3 20 ⫾ 18 25 ⫾ 18 32 ⫾ 23 42 ⫾ 24 78 ⫾ 5
34 16 0 0 5.0 ⫾ 0.3 156 ⫾ 48 55 ⫾ 14 6⫾5 16 ⫾ 19 19 ⫾ 19 24 ⫾ 22 31 ⫾ 22 78 ⫾ 4
0.96
Anatomic subtype Aortic atresia/mitral atresia Aortic stenosis/mitral stenosis Aortic atresia/mitral stenosis Aortic stenosis/mitral atresia Hypoplastic left heart syndrome variant* Gestational age (weeks) Age at Norwood (days) Birth weight (kg) Echocardiographic systolic function (n) Normal Mildly decreased Moderately decreased Severely decreased Echocardiographic atrioventricular valve regurgitation (n) None/trace Mild Moderate Severe Right ventricular–pulmonary artery conduit diameter† (mm) Cardiopulmonary bypass time (minutes) Aortic cross-clamp (minutes) Circulatory arrest (minutes) Mechanical ventilation (days) Chest tube use (days) Intensive care unit stay (days) Total hospital stay (days) Discharge oxygen saturation (%)
p Value 0.22
0.51 0.34 0.17
0.06 0.63 0.50 0.15 0.31 0.09 0.10 0.09 0.99
* HLHS variant was double outlet right ventricle with mitral atresia (n ⫽ 4). Diameter at surgical implantation.
†
LOS, and hospital LOS. All deaths were recorded up to discharge after stage II surgery. The echocardiographic reports were reviewed for right ventricular systolic function and grade of tricuspid regurgitation before the Norwood and stage II surgeries. Right ventricular function was subjectively graded as normal or mildly, moderately, or severely decreased, and tricuspid regurgitation was graded as none/trace, mild, moderate, or severe.6,19
All catheterization procedures were performed with the patient under general anesthesia. A femoral venous approach was preferred whenever possible. Routinely, a 4F glide catheter (Terumo, Somerset, New Jersey) with a JB1 curve was used with a 0.035-in. glide wire to access the proximal conduit and perform manual angiography. The patients underwent stent placement if angiographic conduit narrowing was identified in the setting of concurrent severe
120
Table 2 Characteristics of patients undergoing conduit stenting Patient Number
Age at Stenting (d)
Weight (kg)
Access Site
Long Venous Sheath
1 2 3 4 5 6 7
5 5 6 5 5 5 5
104 84 51 118 131 150 80
5.0 5.6 4.9 4.3 6.6 4.8 4.5
F F F F F F F
Present Present Present Absent Absent Absent Absent
8 9 10
6 6 5
101 208 42
6.5 5.9 3.1
IJ F F
11
5
72
3.5
12
5
11
13
5
14 15 16
Stent Location
Stent Size (mm)
Concomitant Interventions
Reintervention Type (Age at Catheterization)
Age at Stage II (days)
Proximal Proximal Proximal Proximal Proximal Proximal Proximal
7 ⫻ 16 7 ⫻ 16 8 ⫻ 26 5 ⫻ 12 7 ⫻ 12 Two 8 ⫻ 12 7 ⫻ 12
Distal conduit angioplasty Bilateral PA angioplasty ND ND Right PA angioplasty ND ND
129 107 187 209 158 235 132
Absent Present Present
Distal Proximal Distal
6 ⫻ 16 Two 7 ⫻ 16 6 ⫻ 16
Aortic angioplasty ND ND
IJ
Absent
Two 6 ⫻ 16
ND
3.8
F
Present
Proximal and distal Distal
ND ND ND ND ND ND Retrieval of embolized stent, repeat proximal stent (81 days) ND ND Proximal conduit stents (137 days) ND
6 ⫻ 12
ND
99
4.4
IJ
Absent
5
33
2.6
F
5 5
94 103
6.0 5.2
F F
Two 6 ⫻ 16
ND
Absent
Proximal and distal Distal
6 ⫻ 16
ND
Absent Absent
Proximal Proximal
6 ⫻ 16 5 ⫻ 12
ND Pulmonary vein stent
* RV–PA conduit diameter at implantation. F ⫽ femoral vein; IJ ⫽ internal jugular vein; ND ⫽ not done; OHTx ⫽ orthotopic heart transplantation; PA ⫽ pulmonary artery.
134 OHTx (347 days) 140 210
Proximal and distal conduit stents (13 days) ND
Died (15 days)
Proximal conduit stent (208 days) ND Distal conduit stent (110 days)
Died (219 days)
166
227 Died (161 days)
The American Journal of Cardiology (www.ajconline.org)
Conduit Size* (mm)
Congenital Heart Disease/Stage II Outcomes After Conduit Stent
hypoxemia (Figure 1). Initially, the stents were hand-mounted on low-profile balloons and deployed within the conduit using a long venous sheath. However, after low-profile, premounted stents became commercially available, they were used exclusively, and, in most cases, a 0.018-in. Roadrunner wire (Cook Medical, Bloomington, Indiana) was positioned in a distal branch pulmonary artery.13,18 In most cases, premounted Formula 418 stents (Cook Medical) were implanted without the use of a long guide sheath, using anatomic landmarks to guide stent placement. The stent size was based on the conduit diameter and was typically ⱕ1 mm larger than the conduit diameter recorded at surgical implantation and was not based on the stenotic diameter. The oxygen saturation was recorded before and after stent placement under similar hemodynamic conditions and inhaled oxygen concentrations. Resolution of conduit stenosis was confirmed on post-stent angiograms and improvement in systemic oxygen saturation. All catheterization records were reviewed for age and weight at catheterization, pre- and post-stent oxygen saturation, location of conduit stenosis, vascular access site, type of venous sheath, type and number of stents implanted, and concomitant interventions performed. All procedure-related complications and catheterbased reinterventions were noted. The patients were divided into 2 groups: those with endovascular stent implantation, and those without stenting of the conduit. The variables collected from both groups at all designated intervals were analyzed. Comparisons between groups and independent predictors of stent placement were made using the Wilcoxon rank sum tests, Fisher exact tests, or chi-square tests, as appropriate. Multivariate logistic regression analysis was performed to identify the effects of anatomic subtype on overall mortality. Data are expressed as mean ⫾ SD, unless otherwise specified. p Values of ⬍0.05 were considered significant. During the study period, 66 (86%) of 77 infants with HLHS, or a related variant, underwent the Norwood procedure with Sano modification and formed the study group (7 patients with mBT shunt, and 4 patients with bilateral PA bands and ductal stents were excluded). Of these 66 infants with RV–PA conduits, 16 (24%) received stents. The cardiac anatomy, demographics, initial echocardiographic findings, and outcome variables after Norwood palliation were similar between those with and without conduit stents (Table 1). The potential risk factors for conduit stenting were investigated. Gestational age, birth weight, age at Norwood, anatomic subtype, RV–PA conduit diameter, pre-Norwood RV systolic function and tricuspid valve regurgitation grade, CPB duration, aortic cross-clamping duration, circulatory arrest and days of mechanical ventilation, chest tube use, intensive care unit LOS, hospital LOS, and post-Norwood discharge oxygen saturation were entered into the univariate model. None of these variables was associated with using conduit stents. The demographics, stent type and location, and concomitant interventions or reinterventions performed for the 16 infants who received ⱖ1 RV-PA conduit stent are summarized in Table 2. Patient age at catheterization was 93 ⫾ 48 days (range 11 to 208), and weight was 4.9 ⫾ 1.2 kg (range 2.6 to 6.6). Stents were placed in the proximal conduit in 10 infants, distal conduit in 4, and both proximal and distal conduit in 2. The median oxygen saturation increased from 66 ⫾ 9% before intervention to 82 ⫾ 6% immediately after stent
121
Table 3 Variables associated with stage II surgery Variable
Conduit Stent (n ⫽ 12)
No Conduit Stent (n ⫽ 40)
p Value
Age at stage II (days) Weight at stage II (kg) Echocardiographic systolic function (n) Normal Mildly decreased Moderately decreased Severely decreased Echocardiographic atrioventricular valve regurgitation (n) None/trace Mild Moderate Severe Preoperative oxygen saturation (%) Cardiopulmonary bypass (minutes) Mechanical ventilation (days) Chest tube use (days) Intensive care unit stay (days) Total hospital stay (days)
170 ⫾ 43 6.2 ⫾ 1.0
159 ⫾ 35 6.0 ⫾ 0.9
0.57 0.53
9 3 0 0
24 12 2 2
0.30
5 5 2 0 80 ⫾ 6 122 ⫾ 50
12 18 9 1 78 ⫾ 5 99 ⫾ 33
0.69
0.40 0.09
4⫾5 8 ⫾ 12 15 ⫾ 18 21 ⫾ 20
4⫾7 6⫾6 6⫾8 11 ⫾ 10
0.48 0.48 0.13 0.13
Table 4 Transplant-free survival Variable
Conduit Stent (n ⫽ 16)
No Conduit Stent (n ⫽ 40)
p Value
Overall survival Survival to Norwood discharge Interstage survival
12/16 (75%) 15/16 (94%)
40/50 (80%) 42/50 (84%)
0.73 0.43
12/15 (80%)
40/42 (95%)
0.11
Data are presented as n (%).
placement (p ⬍0.0001). There were 5 concomitant interventions performed: 2 proximal branch pulmonary artery angioplasties, 1 conduit angioplasty, 1 aortic arch angioplasty, and 1 pulmonary vein stent. Repeat cardiac catheterization with additional conduit stenting was performed in 5 (31%) of 16 infants at a median of 7 ⫾ 83 days (range 1 to 189) after the first intervention. Narrowing of the opposite end of the previously stented conduit (2 proximal, 1 distal) developed in 3 infants (Table 2). In 1 infant, acute hypoxemia was noted during anesthesia induction immediately before his pre-stage II catheterization. He was found to have severe proximal conduit stenosis, which was stented, resulting in resolution of his hypoxemia. His stage II surgery was performed uneventfully 3 days later, as previously scheduled. The other 2 patients, however, were deemed unsuitable for additional surgical palliation because of progressive lung disease in 1 and progressive pulmonary vein stenosis in the other. Overall, 2 stent-related complications occurred. A proximal RV–PA conduit stent embolized to the transverse aortic arch on the day after stent placement in 1 infant. During retrieval of the embolized stent in the catheterization laboratory, he experienced cardiac arrest and was successfully resuscitated. The proximal conduit was successfully rest-
122
The American Journal of Cardiology (www.ajconline.org)
Figure 2. Angiographic example of distal RV–PA conduit stenosis (arrow) using various camera angulations after proximal conduit stent placement (asterisk). Left anterior oblique cranial (A) and lateral (B) angulations might allow for underestimation of distal conduit stenosis, which was better profiled using left anterior oblique caudal angulation, before (C) and after intervention (D).
ented, and he underwent stage II surgery 51 days later. Another infant, who had undergone urgent stent implantation in the distal conduit on postoperative day 7, developed a thrombus in the conduit with recurrence of profound cyanosis within 24 hours. During conduit angioplasty, he experienced cardiac arrest and was ultimately unable to wean from support and died. Additional workup revealed that the patient was heterozygous for both MTHFR and factor V Leiden gene mutations. Stage II surgery was performed in 52 (79%) of 66 infants. No interstage surgical shunt revisions were performed in either group. No demographic, clinical, or outcome variables were significantly different between the stented and nonstented groups (Table 3). The overall transplant-free survival rate through the stage II surgery was 79% (52 of 66) and was similar between the stented and nonstented groups (Table 4). No deaths during or immediately after the stage II surgery occurred in either group. The present study has shown that endovascular RV–PA conduit stent placement in infants with HLHS allows those infants with significant conduit stenosis to undergo stage II surgery at a similar age and weight as those without stents and, importantly, without a negative effect on stage II outcomes. The recent Pediatric Heart Network prospective,
multicenter trial randomizing patients to undergo the Norwood procedure with either an RV–PA conduit or mBT shunt demonstrated that patients who received an RV–PA conduit had a greater rate of 12-month transplant-free survival.6 However, they also demonstrated that infants with RV–PA conduits underwent more unintended endovascular interventions, largely attributed to the greater rates of balloon dilation or stent placement of either the RV–PA conduit or the branch pulmonary arteries. In total, 41% of those who received an RV–PA conduit required unplanned catheter-based interventions before stage II surgery.6 This was greater than our reported experience at 24%, likely because the investigators included all interventions and did not specifically report on conduit stenting alone. Previous singlecenter, retrospective studies focusing only on stent implantation for RV–PA conduit stenosis reported implantation rates of 9% to 23%.7,13,18 Intervention for early stenosis of a shunt-dependent circulation is indicated to prevent progressive hypoxemia and pulmonary artery growth compromise, both of which are risk factors for greater morbidity and mortality and increased resource utilization before and during stage II completion. Several strategies can be used to treat shunt stenosis. Some centers have performed an “early” stage II surgery
Congenital Heart Disease/Stage II Outcomes After Conduit Stent
in infants with severe hypoxemia (⬍3 months of age) with similar survival probabilities but requiring increased resource utilization compared to infants undergoing the procedure at an older age.9,10 Other centers have embraced surgical shunt revision but have reported an associated increase in infection rates, extracorporeal membrane oxygenation use, hospital mortality, and resource utilization with this strategy.11 Transcatheter therapy offers an attractive alternative to these approaches, particularly when intervention is required very early after the Norwood procedure. Infants in the present series who underwent stent placement had a significant and immediate increase in their oxygen saturation, allowing the stage II surgery to be performed at the same age and weight as for nonstented infants. Importantly, stent placement did not significantly increase the CPB times, days of mechanical ventilation, chest tube use, or intensive care unit or hospital LOS. Certainly, although the long-term effects of the use of endovascular stents in the treatment of severe hypoxemia remain unknown, the shortterm results are encouraging. There are lessons to be learned from this early experience. Our reintervention rate after initial stent placement was significant, with 31% requiring additional RV–PA conduit stent placement before their stage II surgery. Additional stenotic areas of the conduit not addressed with the initial stent placement accounted for 60% of the cases requiring repeat stenting (Figure 2). This underscores the importance of angiographic evaluation using multiple camera angulations to identify all significant stenoses throughout the conduit. It is possible that the newer angiographic equipment and techniques becoming available, such as 3-dimensional rotational angiography, might assist in the procedural evaluation of conduit stenoses in the future.20 Investigators have reported complications of heart block and systemic hypotension with conduit stenting,13 but these were not routinely encountered in our patient cohort. This might have been related to the use of low-profile, premounted stents with the avoidance of a long venous sheath whenever possible.18,21 Our single case of stent embolization occurred early in our experience with a relatively short stent (12 mm in length). Subsequently, longer stents were used to treat proximal conduit stenoses, without additional complications. The present study was limited by being retrospective with a relatively small sample size. The limited power might account for the failure to identify predictors for the need for RV–PA conduit stenting. The small numbers also prevented comparisons of endovascular stenting to other treatment options such as surgical reintervention or balloon angioplasty alone. 1. Azakie A, Martinez D, Sapru A, Fineman J, Teitel D, Karl TR. Impact of right ventricle to pulmonary artery conduit on outcome of the modified Norwood procedure. Ann Thorac Surg 2004;77:1727–1733. 2. Mahle WT, Cuadrado AR, Tam VK. Early experience with a modified Norwood procedure using right ventricle to pulmonary artery conduit. Ann Thorac Surg 2003;76:1084 –1089. 3. Tabbutt S, Dominguez TE, Ravishankar C, Marino BS, Gruber PJ, Wernovsky G, Gaynor JW, Nicolson SC, Spray TL. Outcomes after the stage I reconstruction comparing the right ventricular to pulmonary artery conduit with the modified Blalock-Taussig shunt. Ann Thorac Surg 2005;80:1582–1590, 1581. 4. Sano S, Ishino K, Kado H, Shiokawa Y, Sakamoto K, Yokota M, Kawada M. Outcome of right ventricle-to-pulmonary artery shunt in
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first-stage palliation of hypoplastic left heart syndrome: a multiinstitutional study. Ann Thorac Surg 2004;78:1951–1958. Pizarro C, Malec E, Maher KO, Januszewska K, Gidding SS, Murdison KA, Baffa JM, Norwood WI. Right ventricle to pulmonary artery conduit improves outcome after stage I Norwood for hypoplastic left heart syndrome. Circulation 2003;108(Suppl 1):II155–II160. Ohye RG, Sleeper LA, Mahony L, Newburger JW, Pearson GD, Lu M, Goldberg CS, Tabbutt S, Frommelt PC, Ghanayem NS, Laussen PC, Rhodes JF, Lewis AB, Mital S, Ravishankar C, Williams IA, DunbarMasterson C, Atz AM, Colan S, Minich LL, Pizarro C, Kanter KR, Jaggers J, Jacobs JP, Krawczeski CD, Pike N, McCrindle BW, Virzi L, Gaynor JW; Pediatric Heart Network Investigators. Comparison of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med 2010;362:1980 –1992. Desai T, Stumper O, Miller P, Dhillon R, Wright J, Barron D, Brawn W, Jones T, DeGiovanni J. Acute interventions for stenosed right ventriclepulmonary artery conduit following the right-sided modification of Norwood-Sano procedure. Congenit Heart Dis 2009;4:433– 439. Pruetz JD, Badran S, Dorey F, Starnes VA, Lewis AB. Differential branch pulmonary artery growth after the Norwood procedure with right ventricle-pulmonary artery conduit versus modified BlalockTaussig shunt in hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 2009;137:1342–1348. Petrucci O, Khoury PR, Manning PB, Eghtesady P. Outcomes of the bidirectional Glenn procedure in patients less than 3 months of age. J Thorac Cardiovasc Surg 2010;139:562–568. Ghanayem NS, Tweddell JS, Hoffman GM, Mussatto K, Jaquiss RD. Optimal timing of the second stage of palliation for hypoplastic left heart syndrome facilitated through home monitoring, and the results of early cavopulmonary anastomosis. Cardiol Young 2006;16(Suppl 1):61– 66. O’Connor MJ, Ravishankar C, Ballweg JA, Gillespie MJ, Gaynor JW, Tabbutt S, Dominguez TE. Early systemic-to-pulmonary artery shunt intervention in neonates with congenital heart disease. J Thorac Cardiovasc Surg 2011;142:106 –112. Hsia TY, Migliavacca F, Pennati G, Balossino R, Dubini G, de Leval MR, Bradley SM, Bove EL. Management of a stenotic right ventriclepulmonary artery shunt early after the Norwood procedure. Ann Thorac Surg 2009;88:830 – 838. Muyskens S, Nicolas R, Foerster S, Balzer D. Endovascular stent placement for right ventricle to pulmonary artery conduit stenosis in the Norwood with Sano modification. Congenit Heart Dis 2008;3:185–190. Januszewska K, Kozlik-Feldmann R, Dalla-Pozza R, Greil S, Abicht J, Netz H, Reichart B, Malec E. Right ventricle-to-pulmonary artery shunt related complications after Norwood procedure. Eur J Cardiothorac Surg 2011;40:584 –590. Kaestner M, Handke RP, Photiadis J, Sigler M, Schneider MB. Implantation of stents as an alternative to reoperation in neonates and infants with acute complications after surgical creation of a systemicto-pulmonary arterial shunt. Cardiol Young 2008;18:177–184. Eicken A, Genz T, Sebening W. Stenting of stenosed shunts in patients after a Norwood-Sano operation. Catheter Cardiovasc Interv 2006;68: 301–303. Petit CJ, Gillespie MJ, Kreutzer J, Rome JJ. Endovascular stents for relief of cyanosis in single-ventricle patients with shunt or conduitdependent pulmonary blood flow. Catheter Cardiovasc Interv 2006; 68:280 –286. Dähnert I, Riede FT, Razek V, Weidenbach M, Rastan A, Walther T, Kostelka M. Catheter interventional treatment of Sano shunt obstruction in patients following modified Norwood palliation for hypoplastic left heart syndrome. Clin Res Cardiol 2007;96:719 –722. Helbing WA, Bosch HG, Maliepaard C, Rebergen SA, van der Geest RJ, Hansen B, Ottenkamp J, Reiber JH, de Roos A. Comparison of echocardiographic methods with magnetic resonance imaging for assessment of right ventricular function in children. Am J Cardiol 1995; 76:589 –594. Glatz AC, Zhu X, Gillespie MJ, Hanna BD, Rome JJ. Use of angiographic ct imaging in the cardiac catheterization laboratory for congenital heart disease. J Am Coll Cardiol Imaging 2010;3:1149 –1157. Pass RH, Hsu DT, Garabedian CP, Schiller MS, Jayakumar KA, Hellenbrand WE. Endovascular stent implantation in the pulmonary arteries of infants and children without the use of a long vascular sheath. Catheter Cardiovasc Interv 2002;55:505–509.
0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2012.02.060
stage II surgery have not been fully investigated. Therefore, we sought to determine the risks and effectiveness of endovascular stent placement for the treatment of RV–PA conduit stenosis and to compare the stage II surgical outcomes between the infants who underwent conduit stenting and those who did not. The institutional review boards of the University of Utah and Primary Children’s Medical Center approved this retrospective study under a waiver of informed consent. The pediatric cardiovascular surgery database was searched for all patients with HLHS who had undergone the Norwood procedure with the Sano modification from May 2005 to January 2010. The medical records were reviewed for gender, gestational age, and underlying cardiac diagnosis. The variables related to the Norwood surgery included age and weight at surgery, RV–PA conduit diameter at implantation, duration of cardiopulmonary bypass (CPB), aortic crossclamping, circulatory arrest and days of mechanical ventilation, chest tube use, intensive care unit length of stay (LOS), hospital LOS, and discharge oxygen saturation. The interstage period was defined as the interval after Norwood discharge until admission for stage II surgery. The variables related to stage II surgery included age and weight at surgery, prestage II oxygen saturation, CPB duration, days of mechanical ventilation, chest tube use, intensive care unit www.ajconline.org
Congenital Heart Disease/Stage II Outcomes After Conduit Stent
119
Figure 1. Angiographic example of distal RV–PA conduit stenosis (arrow) using right anterior oblique caudal angulation before (A) and after stent placement (B). Table 1 Cardiac anatomy, demographics, and outcome variables at initial Norwood procedure Variable
Conduit Stent (n ⫽ 16)
No Conduit Stent (n ⫽ 50)
6 6 1 2 1 38.1 ⫾ 1.8 7.4 ⫾ 4.0 3.2 ⫾ 0.6
17 16 13 1 3 38.1 ⫾ 1.3 5.8 ⫾ 2.0 3.0 ⫾ 0.5
15 1 0 0
44 5 1 0
1.00
11 5 0 0 5.2 ⫾ 0.4 144 ⫾ 25 57 ⫾ 12 6⫾3 20 ⫾ 18 25 ⫾ 18 32 ⫾ 23 42 ⫾ 24 78 ⫾ 5
34 16 0 0 5.0 ⫾ 0.3 156 ⫾ 48 55 ⫾ 14 6⫾5 16 ⫾ 19 19 ⫾ 19 24 ⫾ 22 31 ⫾ 22 78 ⫾ 4
0.96
Anatomic subtype Aortic atresia/mitral atresia Aortic stenosis/mitral stenosis Aortic atresia/mitral stenosis Aortic stenosis/mitral atresia Hypoplastic left heart syndrome variant* Gestational age (weeks) Age at Norwood (days) Birth weight (kg) Echocardiographic systolic function (n) Normal Mildly decreased Moderately decreased Severely decreased Echocardiographic atrioventricular valve regurgitation (n) None/trace Mild Moderate Severe Right ventricular–pulmonary artery conduit diameter† (mm) Cardiopulmonary bypass time (minutes) Aortic cross-clamp (minutes) Circulatory arrest (minutes) Mechanical ventilation (days) Chest tube use (days) Intensive care unit stay (days) Total hospital stay (days) Discharge oxygen saturation (%)
p Value 0.22
0.51 0.34 0.17
0.06 0.63 0.50 0.15 0.31 0.09 0.10 0.09 0.99
* HLHS variant was double outlet right ventricle with mitral atresia (n ⫽ 4). Diameter at surgical implantation.
†
LOS, and hospital LOS. All deaths were recorded up to discharge after stage II surgery. The echocardiographic reports were reviewed for right ventricular systolic function and grade of tricuspid regurgitation before the Norwood and stage II surgeries. Right ventricular function was subjectively graded as normal or mildly, moderately, or severely decreased, and tricuspid regurgitation was graded as none/trace, mild, moderate, or severe.6,19
All catheterization procedures were performed with the patient under general anesthesia. A femoral venous approach was preferred whenever possible. Routinely, a 4F glide catheter (Terumo, Somerset, New Jersey) with a JB1 curve was used with a 0.035-in. glide wire to access the proximal conduit and perform manual angiography. The patients underwent stent placement if angiographic conduit narrowing was identified in the setting of concurrent severe
120
Table 2 Characteristics of patients undergoing conduit stenting Patient Number
Age at Stenting (d)
Weight (kg)
Access Site
Long Venous Sheath
1 2 3 4 5 6 7
5 5 6 5 5 5 5
104 84 51 118 131 150 80
5.0 5.6 4.9 4.3 6.6 4.8 4.5
F F F F F F F
Present Present Present Absent Absent Absent Absent
8 9 10
6 6 5
101 208 42
6.5 5.9 3.1
IJ F F
11
5
72
3.5
12
5
11
13
5
14 15 16
Stent Location
Stent Size (mm)
Concomitant Interventions
Reintervention Type (Age at Catheterization)
Age at Stage II (days)
Proximal Proximal Proximal Proximal Proximal Proximal Proximal
7 ⫻ 16 7 ⫻ 16 8 ⫻ 26 5 ⫻ 12 7 ⫻ 12 Two 8 ⫻ 12 7 ⫻ 12
Distal conduit angioplasty Bilateral PA angioplasty ND ND Right PA angioplasty ND ND
129 107 187 209 158 235 132
Absent Present Present
Distal Proximal Distal
6 ⫻ 16 Two 7 ⫻ 16 6 ⫻ 16
Aortic angioplasty ND ND
IJ
Absent
Two 6 ⫻ 16
ND
3.8
F
Present
Proximal and distal Distal
ND ND ND ND ND ND Retrieval of embolized stent, repeat proximal stent (81 days) ND ND Proximal conduit stents (137 days) ND
6 ⫻ 12
ND
99
4.4
IJ
Absent
5
33
2.6
F
5 5
94 103
6.0 5.2
F F
Two 6 ⫻ 16
ND
Absent
Proximal and distal Distal
6 ⫻ 16
ND
Absent Absent
Proximal Proximal
6 ⫻ 16 5 ⫻ 12
ND Pulmonary vein stent
* RV–PA conduit diameter at implantation. F ⫽ femoral vein; IJ ⫽ internal jugular vein; ND ⫽ not done; OHTx ⫽ orthotopic heart transplantation; PA ⫽ pulmonary artery.
134 OHTx (347 days) 140 210
Proximal and distal conduit stents (13 days) ND
Died (15 days)
Proximal conduit stent (208 days) ND Distal conduit stent (110 days)
Died (219 days)
166
227 Died (161 days)
The American Journal of Cardiology (www.ajconline.org)
Conduit Size* (mm)
Congenital Heart Disease/Stage II Outcomes After Conduit Stent
hypoxemia (Figure 1). Initially, the stents were hand-mounted on low-profile balloons and deployed within the conduit using a long venous sheath. However, after low-profile, premounted stents became commercially available, they were used exclusively, and, in most cases, a 0.018-in. Roadrunner wire (Cook Medical, Bloomington, Indiana) was positioned in a distal branch pulmonary artery.13,18 In most cases, premounted Formula 418 stents (Cook Medical) were implanted without the use of a long guide sheath, using anatomic landmarks to guide stent placement. The stent size was based on the conduit diameter and was typically ⱕ1 mm larger than the conduit diameter recorded at surgical implantation and was not based on the stenotic diameter. The oxygen saturation was recorded before and after stent placement under similar hemodynamic conditions and inhaled oxygen concentrations. Resolution of conduit stenosis was confirmed on post-stent angiograms and improvement in systemic oxygen saturation. All catheterization records were reviewed for age and weight at catheterization, pre- and post-stent oxygen saturation, location of conduit stenosis, vascular access site, type of venous sheath, type and number of stents implanted, and concomitant interventions performed. All procedure-related complications and catheterbased reinterventions were noted. The patients were divided into 2 groups: those with endovascular stent implantation, and those without stenting of the conduit. The variables collected from both groups at all designated intervals were analyzed. Comparisons between groups and independent predictors of stent placement were made using the Wilcoxon rank sum tests, Fisher exact tests, or chi-square tests, as appropriate. Multivariate logistic regression analysis was performed to identify the effects of anatomic subtype on overall mortality. Data are expressed as mean ⫾ SD, unless otherwise specified. p Values of ⬍0.05 were considered significant. During the study period, 66 (86%) of 77 infants with HLHS, or a related variant, underwent the Norwood procedure with Sano modification and formed the study group (7 patients with mBT shunt, and 4 patients with bilateral PA bands and ductal stents were excluded). Of these 66 infants with RV–PA conduits, 16 (24%) received stents. The cardiac anatomy, demographics, initial echocardiographic findings, and outcome variables after Norwood palliation were similar between those with and without conduit stents (Table 1). The potential risk factors for conduit stenting were investigated. Gestational age, birth weight, age at Norwood, anatomic subtype, RV–PA conduit diameter, pre-Norwood RV systolic function and tricuspid valve regurgitation grade, CPB duration, aortic cross-clamping duration, circulatory arrest and days of mechanical ventilation, chest tube use, intensive care unit LOS, hospital LOS, and post-Norwood discharge oxygen saturation were entered into the univariate model. None of these variables was associated with using conduit stents. The demographics, stent type and location, and concomitant interventions or reinterventions performed for the 16 infants who received ⱖ1 RV-PA conduit stent are summarized in Table 2. Patient age at catheterization was 93 ⫾ 48 days (range 11 to 208), and weight was 4.9 ⫾ 1.2 kg (range 2.6 to 6.6). Stents were placed in the proximal conduit in 10 infants, distal conduit in 4, and both proximal and distal conduit in 2. The median oxygen saturation increased from 66 ⫾ 9% before intervention to 82 ⫾ 6% immediately after stent
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Table 3 Variables associated with stage II surgery Variable
Conduit Stent (n ⫽ 12)
No Conduit Stent (n ⫽ 40)
p Value
Age at stage II (days) Weight at stage II (kg) Echocardiographic systolic function (n) Normal Mildly decreased Moderately decreased Severely decreased Echocardiographic atrioventricular valve regurgitation (n) None/trace Mild Moderate Severe Preoperative oxygen saturation (%) Cardiopulmonary bypass (minutes) Mechanical ventilation (days) Chest tube use (days) Intensive care unit stay (days) Total hospital stay (days)
170 ⫾ 43 6.2 ⫾ 1.0
159 ⫾ 35 6.0 ⫾ 0.9
0.57 0.53
9 3 0 0
24 12 2 2
0.30
5 5 2 0 80 ⫾ 6 122 ⫾ 50
12 18 9 1 78 ⫾ 5 99 ⫾ 33
0.69
0.40 0.09
4⫾5 8 ⫾ 12 15 ⫾ 18 21 ⫾ 20
4⫾7 6⫾6 6⫾8 11 ⫾ 10
0.48 0.48 0.13 0.13
Table 4 Transplant-free survival Variable
Conduit Stent (n ⫽ 16)
No Conduit Stent (n ⫽ 40)
p Value
Overall survival Survival to Norwood discharge Interstage survival
12/16 (75%) 15/16 (94%)
40/50 (80%) 42/50 (84%)
0.73 0.43
12/15 (80%)
40/42 (95%)
0.11
Data are presented as n (%).
placement (p ⬍0.0001). There were 5 concomitant interventions performed: 2 proximal branch pulmonary artery angioplasties, 1 conduit angioplasty, 1 aortic arch angioplasty, and 1 pulmonary vein stent. Repeat cardiac catheterization with additional conduit stenting was performed in 5 (31%) of 16 infants at a median of 7 ⫾ 83 days (range 1 to 189) after the first intervention. Narrowing of the opposite end of the previously stented conduit (2 proximal, 1 distal) developed in 3 infants (Table 2). In 1 infant, acute hypoxemia was noted during anesthesia induction immediately before his pre-stage II catheterization. He was found to have severe proximal conduit stenosis, which was stented, resulting in resolution of his hypoxemia. His stage II surgery was performed uneventfully 3 days later, as previously scheduled. The other 2 patients, however, were deemed unsuitable for additional surgical palliation because of progressive lung disease in 1 and progressive pulmonary vein stenosis in the other. Overall, 2 stent-related complications occurred. A proximal RV–PA conduit stent embolized to the transverse aortic arch on the day after stent placement in 1 infant. During retrieval of the embolized stent in the catheterization laboratory, he experienced cardiac arrest and was successfully resuscitated. The proximal conduit was successfully rest-
122
The American Journal of Cardiology (www.ajconline.org)
Figure 2. Angiographic example of distal RV–PA conduit stenosis (arrow) using various camera angulations after proximal conduit stent placement (asterisk). Left anterior oblique cranial (A) and lateral (B) angulations might allow for underestimation of distal conduit stenosis, which was better profiled using left anterior oblique caudal angulation, before (C) and after intervention (D).
ented, and he underwent stage II surgery 51 days later. Another infant, who had undergone urgent stent implantation in the distal conduit on postoperative day 7, developed a thrombus in the conduit with recurrence of profound cyanosis within 24 hours. During conduit angioplasty, he experienced cardiac arrest and was ultimately unable to wean from support and died. Additional workup revealed that the patient was heterozygous for both MTHFR and factor V Leiden gene mutations. Stage II surgery was performed in 52 (79%) of 66 infants. No interstage surgical shunt revisions were performed in either group. No demographic, clinical, or outcome variables were significantly different between the stented and nonstented groups (Table 3). The overall transplant-free survival rate through the stage II surgery was 79% (52 of 66) and was similar between the stented and nonstented groups (Table 4). No deaths during or immediately after the stage II surgery occurred in either group. The present study has shown that endovascular RV–PA conduit stent placement in infants with HLHS allows those infants with significant conduit stenosis to undergo stage II surgery at a similar age and weight as those without stents and, importantly, without a negative effect on stage II outcomes. The recent Pediatric Heart Network prospective,
multicenter trial randomizing patients to undergo the Norwood procedure with either an RV–PA conduit or mBT shunt demonstrated that patients who received an RV–PA conduit had a greater rate of 12-month transplant-free survival.6 However, they also demonstrated that infants with RV–PA conduits underwent more unintended endovascular interventions, largely attributed to the greater rates of balloon dilation or stent placement of either the RV–PA conduit or the branch pulmonary arteries. In total, 41% of those who received an RV–PA conduit required unplanned catheter-based interventions before stage II surgery.6 This was greater than our reported experience at 24%, likely because the investigators included all interventions and did not specifically report on conduit stenting alone. Previous singlecenter, retrospective studies focusing only on stent implantation for RV–PA conduit stenosis reported implantation rates of 9% to 23%.7,13,18 Intervention for early stenosis of a shunt-dependent circulation is indicated to prevent progressive hypoxemia and pulmonary artery growth compromise, both of which are risk factors for greater morbidity and mortality and increased resource utilization before and during stage II completion. Several strategies can be used to treat shunt stenosis. Some centers have performed an “early” stage II surgery
Congenital Heart Disease/Stage II Outcomes After Conduit Stent
in infants with severe hypoxemia (⬍3 months of age) with similar survival probabilities but requiring increased resource utilization compared to infants undergoing the procedure at an older age.9,10 Other centers have embraced surgical shunt revision but have reported an associated increase in infection rates, extracorporeal membrane oxygenation use, hospital mortality, and resource utilization with this strategy.11 Transcatheter therapy offers an attractive alternative to these approaches, particularly when intervention is required very early after the Norwood procedure. Infants in the present series who underwent stent placement had a significant and immediate increase in their oxygen saturation, allowing the stage II surgery to be performed at the same age and weight as for nonstented infants. Importantly, stent placement did not significantly increase the CPB times, days of mechanical ventilation, chest tube use, or intensive care unit or hospital LOS. Certainly, although the long-term effects of the use of endovascular stents in the treatment of severe hypoxemia remain unknown, the shortterm results are encouraging. There are lessons to be learned from this early experience. Our reintervention rate after initial stent placement was significant, with 31% requiring additional RV–PA conduit stent placement before their stage II surgery. Additional stenotic areas of the conduit not addressed with the initial stent placement accounted for 60% of the cases requiring repeat stenting (Figure 2). This underscores the importance of angiographic evaluation using multiple camera angulations to identify all significant stenoses throughout the conduit. It is possible that the newer angiographic equipment and techniques becoming available, such as 3-dimensional rotational angiography, might assist in the procedural evaluation of conduit stenoses in the future.20 Investigators have reported complications of heart block and systemic hypotension with conduit stenting,13 but these were not routinely encountered in our patient cohort. This might have been related to the use of low-profile, premounted stents with the avoidance of a long venous sheath whenever possible.18,21 Our single case of stent embolization occurred early in our experience with a relatively short stent (12 mm in length). Subsequently, longer stents were used to treat proximal conduit stenoses, without additional complications. The present study was limited by being retrospective with a relatively small sample size. The limited power might account for the failure to identify predictors for the need for RV–PA conduit stenting. The small numbers also prevented comparisons of endovascular stenting to other treatment options such as surgical reintervention or balloon angioplasty alone. 1. Azakie A, Martinez D, Sapru A, Fineman J, Teitel D, Karl TR. Impact of right ventricle to pulmonary artery conduit on outcome of the modified Norwood procedure. Ann Thorac Surg 2004;77:1727–1733. 2. Mahle WT, Cuadrado AR, Tam VK. Early experience with a modified Norwood procedure using right ventricle to pulmonary artery conduit. Ann Thorac Surg 2003;76:1084 –1089. 3. Tabbutt S, Dominguez TE, Ravishankar C, Marino BS, Gruber PJ, Wernovsky G, Gaynor JW, Nicolson SC, Spray TL. Outcomes after the stage I reconstruction comparing the right ventricular to pulmonary artery conduit with the modified Blalock-Taussig shunt. Ann Thorac Surg 2005;80:1582–1590, 1581. 4. Sano S, Ishino K, Kado H, Shiokawa Y, Sakamoto K, Yokota M, Kawada M. Outcome of right ventricle-to-pulmonary artery shunt in
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