Management and Outcomes of Heterotaxy Syndrome Associated With Pulmonary Atresia or Pulmonary Stenosis Vinod A. Sebastian, MD, Javier Brenes, MD, Raghav Murthy, MD, Surendranath Veeram Reddy, MD, V. Vivian Dimas, MD, Alan Nugent, MBBS, Thomas Zellers, MD, Rong Huang, MS, Kristine J. Guleserian, MD, and Joseph M. Forbess, MD Division of Pediatric Cardiothoracic Surgery, Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center; Division of Pediatric Cardiology, University of Texas Southwestern Medical Center and Children’s Medical Center; and Research Department, Children’s Medical Center Dallas, Dallas, Texas
Background. Historic outcomes of patients with heterotaxy and pulmonary atresia or pulmonary stenosis (PA/ PS) have been poor and in the current era are incompletely described. We reviewed our management of these patients and associated risk factors for death. Methods. We retrospectively reviewed the records of all patients with heterotaxy and PA/PS treated in our institution from January 1, 2002, to August 31, 2012. Death data were also confirmed with the Social Security Death Index. The log-rank test was done to assess six risk factors for death. Results. We identified 42 patients with heterotaxy and PA/PS. Median age at the first operation was 6.5 days, and median follow-up was 3.5 years. Death data were complete for all patients. Overall mortality was 19% (8 of 42).
The 30-day, 1-year, and 5-year mortality estimation was 4.76%, 12.3%, and 19.1% respectively, as determined by the Kaplan-Meier method. The log-rank test showed total anomalous pulmonary venous return (TAPVR) (p < 0.05) and obstructed TAPVR requiring an operation at less than 30 days (p [ 0.001) were significant risk factors for death. Conclusions. In the current era, surgical treatment of heterotaxy and PA/PS can result in good outcomes. Associated TAPVR and obstructed TAPVR requiring neonatal correction were noted to be risk factors for death.
T
Patients
he management of newborns with heterotaxy syndrome can be challenging due to the frequent combination of severe cardiac and noncardiac anomalies. Patients with heterotaxy syndrome associated with pulmonary atresia or significant pulmonary stenosis (PA/PS) are an especially difficult subset, because they often require single-ventricle palliation and their outcomes have been disappointing. We reviewed all of the heterotaxy patients presenting to Children’s Medical Center Dallas with associated PA/PS.
Patients and Methods Approval for this study was obtained from the Institutional Review Board at Children’s Medical Center Dallas and the University of Texas Southwestern Medical Center. Accepted for publication Feb 20, 2014. Oral presentation at the Thirty-ninth Annual Meeting of the Western Thoracic Surgical Association, Coeur d’Alene, Idaho, June 26–29, 2013. Address correspondence to Dr Sebastian, 1935 Medical District Dr, Ste C3.211, Dallas, TX 75235; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2014;-:-–-) Ó 2014 by The Society of Thoracic Surgeons
Between January 1, 2002, and August 31, 2012, 42 patients with heterotaxy syndrome and PA/PS were treated at Children’s Medical Center Dallas. We performed a retrospective review of the medical records of all patients with heterotaxy and PA/PS. Death data were also confirmed with the Social Security Death Index. The duration of follow-up was calculated from the first operation to the last clinical encounter with a cardiologist at our institution. Heterotaxy syndrome was defined as a complex of anomalies of visceral-cardiac relations in association with intracardiac pathology [1]. After the initial discharge, most of these patients were managed on a singleventricle palliation pathway, with the final destination being a Fontan circulation. Follow-up after completion of the Fontan circulation was done at the discretion of the patient’s cardiologist. Patients with associated total anomalous pulmonary venous return (TAPVR) underwent neonatal pulmonary vein repair if they had two or more of the following: clinical signs of obstructed pulmonary veins, chest radiographic evidence of obstructed pulmonary veins, or echocardiography/catheter based evidence of obstructed pulmonary veins. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.02.076
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Table 1. Heterotaxy With Pulmonary Atresia/Pulmonary Stenosis Variable Patients Sex Male Female Pulmonary atresia Pulmonary stenosis Unilateral/bilateral discontinuous PAs TAPVR AVSD DORV Interrupted inferior vena cava AVSD ¼ atrioventricular septal defect; ventricle; PA ¼ pulmonary arteries; pulmonary venous return.
No.
Percentage of Total
42
100
19 23 25 17 7 13 33 11 8
45.24 54.76 59.5 40.5 16.67 31 78.6 26.2 19
DORV ¼ double-outlet right TAPVR ¼ total anomalous
Statistical Analysis The log-rank test was performed to assess the following variables as risk factors for death: discontinuous pulmonary arteries, TAPVR, obstructed TAPVR requiring surgical intervention at an age of less than 30 days, TAPVR requiring surgical intervention at an age of greater than 30 days, and PS vs PA. Kaplan-Meier survival curves were created for those risk factors.
Fig 1. Algorithm for management of heterotaxy with pulmonary atresia/pulmonary stenosis. (TAPVR ¼ total anomalous pulmonary venous return.)
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Results We identified 42 patients with heterotaxy and PA/PS. Concomitant diagnoses included unilaterally or bilaterally discontinuous pulmonary arteries, TAPVR, atrioventricular septal defect, and double-outlet right ventricle (DORV). Patient demographics and associated diagnoses are listed in Table 1. Figure 1 shows the algorithm we use in the treatment of these patients, and Figure 2 summarizes the subgroups within our entire patient cohort. The median age at the first operation was 6.5 days (range, 1 to 277 days), and median follow-up was 3.5 years (range, 0.06 to 18.5 years). Death data were complete for all patients. The Society of Thoracic Surgeons (STS) mortality for the entire cohort was 11.9% (5 of 42 patients) and overall mortality was 19% (8 of 42 patients). The Kaplan-Meier survival curves in Figure 3 show 30-day, 1-year, and 5-year survival of 95.24%, 87.7%, and 80.9%, respectively. Among the variables analyzed by log-rank test, the risk factors for death among the entire cohort were the presence of TAPVR and the presence of obstructed TAPVR requiring surgery at less than 30 days of age (Figs 4, 5). Three patients underwent biventricular repair. Biventricular repair was undertaken in the presence of 2 ventricles of adequate volume and function, as well as a septatable atrioventricular valve with adequate inlet to each ventricle and venoatrial connections.
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Fig 2. Clinical management of heterotaxy with pulmonary atresia/pulmonary stenosis. (TAPVR ¼ total anomalous pulmonary venous return.)
Three patients transitioned from single-ventricle palliation to the transplant list for failing single-ventricle physiology. Only 1 of these 3 patients received a transplant. The remaining patients have been taken down the single-ventricle palliation pathway with the addition of a
Fig 3. Kaplan-Meier survival curve (blue line) is shown with the 95% confidence limits (range bars), with circles indicating censored patients.
TAPVR repair if the pulmonary veins appear obstructed based on chest roentgenogram, clinical examination, and echocardiographic or catheterization diagnosis of obstruction.
Fig 4. Survival comparison is shown between heterotaxy patients with pulmonary atresia/pulmonary stenosis with total anomalous pulmonary venous return (TAPVR; dashed red line; red circles indicating censored patients) and those without TAPVR (solid blue line, blue circles indicating censored patients). Log-rank test showed significantly worsened survival in the TAPVR group (p ¼ 0.038). The range bars show the 95% confidence limits.
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Unplanned Intervention in the Operating Room or Catheterization Suite Eleven patients required unplanned reintervention in the operating room or in the catheterization laboratory. The diagnoses, intervention, indication for intervention, and current disposition are listed in Table 2.
Ductal Stent Ductal stenting was considered in 5 patients and was completed in 2. Three patients did not have favorable ductal anatomy to allow ductal stenting and underwent systemic-to-pulmonary artery shunt placements. In the remaining 2 patients, ductal stenting was performed, followed by TAPVR repair at 8 and 9 months, respectively. Fig 5. Survival comparison is shown between heterotaxy patients with pulmonary atresia (PA)/pulmonary stenosis (PS) with total anomalous pulmonary venous return (TAPVR) who underwent operations at less than 30 days of age (solid red line; red circles indicating censored patients) vs the remaining patients in the cohort (dashed blue line, blue circles indicating censored patients). The logrank test showed significant difference in survival between the two groups (p ¼ 0.001). The range bars show the 95% confidence limits.
Discontinuous Pulmonary Arteries Seven patients had discontinuous pulmonary arteries, of which 5 had bilateral discontinuous pulmonary arteries. Three of 5 had unifocalization with central pulmonary artery reconstruction, of whom 1 patient had ductal stents as a neonate. One of these patients, who also had a neonatal TAPVR repair with unifocalization to a modified Blalock-Taussig shunt, died in the perioperative period
Table 2. Unplanned Intervention in the Operating Room or Catheterization Suite Diagnosis Complete AVSD, TAPVR, bilateral SVC, pulmonary atresia Dextrocardia with unbalanced AVSD, discontinuous pulmonary arteries, TAPVR, bilateral SVC, pulmonary atresia Unbalanced AVSD, pulmonary atresia, interrupted IVC Dextrocardia with unbalanced AVSD, pulmonary stenosis
Unplanned reintervention
Indication Inflow stenosis
Disposition
Revision of systemic to pulmonary artery shunt Pre Glenn LPA stent
Diffusely hypoplastic LPA Awaiting Fontan
LPA stent
Ductal coarctation
Awaiting Fontan
Stenting of right modified BT shunt Pericardial window Pulmonary patch arterioplasty Sternal exploration Pleurodesis
Completed Fontan circulation
Shunt thrombosis Pericardial effusion Cyanosis after Glenn Sternal infection Pleural effusion
Complete AVSD with pulmonary atresia, ECMO for respiratory insufficiency Respiratory insufficiency obstructed TAPVR Unbalanced AVSD, d-malposed great AV valve repair AV valve regurgitation arteries, pulmonary atresia, bilateral SVC Pulmonary atresia, right aortic arch ECMO Postoperative ventricular fibrillation Dextrocardia, DORV with pulmonary ECMO and shunt thrombectomy Shunt thrombosis stenosis, bilateral cavae, obstructed TAPVR, right aortic arch Shunt revision and arterioplasty Right pulmonary artery Dextrocardia with AVSD, bilateral SVC, pulmonary atresia, right aortic arch stenosis Unbalanced AVSD with pulmonary Pulmonary vein repair Right lower pulmonary stenosis, obstructed TAPVR vein stenosis DORV, d-malposed great vessels, bilateral ECMO and stenting of shunt Shunt thrombosis SVC, interrupted IVC, pulmonary stenosis
Awaiting Glenn
Death Completed Fontan circulation Death Death
Completed Fontan circulation Awaiting transplant Completed 2-ventricle repair
AV ¼ atrioventricular; AVSD ¼ atrioventricular septal defect; BT ¼ Blalock-Taussig; DORV ¼ double-outlet right ventricle; extracorporeal membrane oxygenation; IVC ¼ inferior vena cava; LPA ¼ left pulmonary artery; SVC ¼ superior vena cava; total anomalous pulmonary venous return.
ECMO ¼ TAPVR ¼
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from morbidity related to malignant supraventricular tachycardia. Of the remaining 2 in the unifocalization group, both underwent superior cavopulmonary connection and are awaiting completion of Fontan circulation. The remaining 2 patients with discontinuous PAs underwent creation of “classic-style” autologous systemic-to-pulmonary shunts with subclavian and unilateral carotid artery turndowns to the ipsilateral pulmonary artery, and both have undergone completion of superior cavopulmonary connection and are awaiting Fontan completion (Figures 6 and 7).
Pulmonary Stenosis PS was present in 17 patients (40.5%) rather than PA. This did not confer a survival benefit in the log-rank test. Twelve of 17 PS patients underwent systemic-topulmonary artery shunts to supplement pulmonary artery blood flow. Of these, 4 had additional control of antegrade pulmonary blood flow with pulmonary artery ligation (n ¼ 1) and pulmonary artery banding (n ¼ 3) after performance of a shunt. We have a low threshold to perform mechanical restriction of antegrade pulmonary blood at the time of systemic-to-pulmonary artery shunt to optimize systemic perfusion. Four patients with PS did not have an initial systemic-to-pulmonary artery shunt.
Fig 7. Surgical reconstruction is shown in a patient with left aortic arch and bilaterally discontinuous pulmonary arteries. After ductal resection, the right subclavian artery and left carotid artery are used to reconstruct right and left pulmonary artery respectively.
Two of these had primary bidirectional Glenn, and the other two had TAPVR repair, followed by bidirectional Glenn, without the need for an intervening procedure for additional pulmonary blood flow.
Total Anomalous Pulmonary Venous Return Associated TAPVR was present in 13 patients, comprising 5 supracardiac, 4 infracardiac, and 4 cardiac-level TAPVR. Of the 5 supracardiac TAPVR patients, 3 had a vertical vein to a right sided superior vena cava, 1 to the innominate, and 1 to a left-sided superior vena cava. Five presented with obstruction and were repaired at less than 30 days of age. Another 4 patients underwent repair at greater than 30 days of age. Of these 4 who underwent delayed pulmonary vein intervention, three had presented with some signs of obstruction but were selected for observation and delayed pulmonary vein repair according to our selection criteria mentioned in Patients and Methods. Obstruction has not developed in 4 patients, all of whom had cardiac level TAPVR, and they have not required any intervention. Only 1 patient has required surgical reintervention for pulmonary vein stenosis.
Comment Fig 6. Drawing shows a patient with a left aortic arch and bilaterally discontinuous pulmonary arteries (PAs). (Ao ¼ aorta; RA ¼ right atrium; RPA ¼ right pulmonary artery; RV ¼ right ventricle; SVC ¼ superior vena cava.)
To the best of our knowledge, this is the first report dedicated to an analysis of patients with heterotaxy syndrome and PA/PS. Our therapy for these patients has evolved over time. More recently, we have started evaluating these patients for the use of a ductal stent as the
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initial neonatal intervention, especially in those with associated TAPVR. We have also adopted a different approach to TAPVR diagnosed in the neonatal period in patients with heterotaxy and PA or PS. A broad-based diagnostic evaluation is performed in neonates with associated TAPVR, looking at the pulmonary vein echocardiographic characteristics or appearance in the catheterization laboratory, chest radiographic findings of pulmonary vein obstruction, and clinical examination findings of pulmonary vein obstruction. Neonatal TAPVR repair was, in general, performed in the presence of two or more factors suggesting obstruction. None of the cardiac-level TAPVR patients required any pulmonary vein interventions. The extracardiac TAPVR patients who were not repaired in the neonatal period continued to have mild degree of pulmonary vein obstruction beyond the neonatal period. Single-ventricle physiology was present in most of these patients with extracardiac TAPVR and so they underwent pulmonary vein repair to maintain an optimal pulmonary vascular bed. Other series have reported heterotaxy syndrome in association with univentricular repair [2, 3], biventricular repair [4], TAPVR repair [5, 6] and right atrial isomerism or left atrial isomerism [7–10]. Right atrial isomerism has been associated with worse survival than left atrial isomerism [7–10]. We did not use atrial isomerism to subclassify our patient population, although we did look at the association with TAPVR, discontinuous pulmonary arteries, PA vs PS, and univentricular or biventricular repair. Historical outcomes with heterotaxy syndrome and congenital heart disease have been unsatisfactory. Sadiq and colleagues [7] reported 45% overall survival in 20 patients with right atrial isomerism, and only 9 patients were eventual Fontan candidates. Hashmi and colleagues [8] reported a 69% mortality rate for children with right atrial isomerism, and another study from the same institution reported 44% mortality in children born with left atrial isomerism [9]. In 2009, Anagnostopoulos and colleagues [10] reported improved surgical outcomes in heterotaxy patients. In patients with right and left atrial isomerism, 3-year survival was 79% and 94%, respectively. The incidence of sinus node dysfunction was higher in the patients with left atrial isomerism. The risk factors for death in patients with right atrial isomerism were the presence of obstructed TAPVR and greater than moderate atrioventricular valve regurgitation. The incidence of single-ventricle palliation was 85% in that series, which is highly comparable to the 93% incidence in our patient cohort. We have found similar risk factors for increased death—the presence of TAPVR and obstructed TAPVR requiring surgical intervention at less than 30 days of age. Ota and colleagues [11] reported their surgical outcomes in patients with right atrial isomerism and also found neonatal palliative intervention to be a risk factor for early death. Morales and colleagues [6] compared the outcomes of TAPVR repair in patients with and without heterotaxy. With a mean follow-up of 2.6 years, they reported 5
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deaths in 84 TAPVR patients without heterotaxy and 7 deaths in 38 patients with TAPVR and heterotaxy. However, this mortality difference was not statistically significant. They noted a 9.8% reoperation rate after TAPVR repair, but 58% of the reoperations for pulmonary vein stenosis were in heterotaxy patients compared with nonheterotaxy patients. Foerster and colleagues [12] reported a higher 47% restenosis rate after TAPVR repair in heterotaxy patients. Only one patient in our cohort of heterotaxy syndrome, PA/PS, and TAPVR, has required reintervention for pulmonary vein stenosis. Morales and colleagues [6] found no statistically significant difference in survival between TAPVR in heterotaxy and nonheterotaxy patients but did report PA and the need for systemic-to-pulmonary shunt to be risk factors for death among their entire cohort. Three patients in our series underwent two ventricle repairs. These patients were initially palliated with a systemic-to-pulmonary artery shunt, and then a Rastelli pathway was used to connect the morphologic left ventricle to the aorta. At this time, right ventricle to pulmonary artery continuity was established using a Contegra conduit in all 3 patients. Stent angioplasty of the ductus arteriosus can be performed for ductal-dependent pulmonary or systemic circulation. When we use ductal stents for neonates with heterotaxy and ductal-dependent pulmonary circulation, our institutional policy is to use a stent 4 mm or lesser in diameter, due to concern for diastolic run off physiology leading to systemic malperfusion and necrotizing enterocolitis. For ducts larger than 4 mm in diameter, prostaglandins are stopped a few hours before ductal stenting to allow the use of an appropriately sized stent for the patient’s body weight. We have avoided ductal stenting for tortuous ducts (with curvature greater than 180 degrees). Ductal stenting is performed using a prograde approach (femoral venous access), retrograde approach (femoral arterial access), or by carotid artery cutdown approach. Immediately after ductal stenting, an intravenous heparin drip is started and aspirin is given for 48 hours. Anticoagulation is continued with low-molecularweight heparin and aspirin. At the time of discharge, these patients are enrolled in our Safe-at-Home program for interstage monitoring of single-ventricle patients. Close monitoring of saturations and serial echocardiograms is done to evaluate for ductal stent obstruction due to thrombosis or in-stent restenosis. At our institution, ductal stents are typically evaluated in the catheterization laboratory 3 to 4 months after implantation. We are encouraged by the early results obtained with less traditional methods, such as primary ductal stenting or the use of bilateral autologous systemicto-pulmonary artery shunts, that allow for avoiding on-cardiopulmonary bypass systemic-to-pulmonary artery shunting with or without neonatal pulmonary artery unifocalization. Heterotaxy is often associated with multiple intracardiac lesions, and when subgroups of cardiac lesions or interventions are examined within the study
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group, the subanalyses is often underpowered. This is an inherent limitation of our study. For example, we cannot make statistically significant inferences about the subgroup where ductal stenting was attempted. In patients with discontinuous pulmonary arteries that are not amenable to ductal stenting, our preferred technique of reconstruction has been with the subclavian artery and carotid artery with a “turn down” flap that connects it to the ipsilateral discontinuous pulmonary artery in the form of a “classic shunt” (Figures 6 and 7). We perform this technique without cardiopulmonary bypass, and it has allowed us the versatility to treat the discontinuous pulmonary arteries in heterotaxy with its positional anomalies such as dextrocardia or right aortic arch (Figures 8 and 9). This technique has also allowed us the maximal use of autologous vascular tissue for centralization of pulmonary arteries at a later stage. We have performed bidirectional Glenn on both of the patients that underwent a classic shunt for discontinuous pulmonary arteries and no significant distal vascular ischemia has occurred with the use of these autologous tissue shunts. A third patient with discontinuous pulmonary arteries underwent bilateral ductal stents and delayed centralization of the pulmonary arteries. The remaining 2 patients with bilaterally discontinuous pulmonary arteries underwent neonatal centralization of the pulmonary arteries, and the patient that underwent simultaneous TAPVR repair died. Currently, we use primary ductal stenting as our
Fig 8. Drawing shows patient with right aortic arch and bilaterally discontinuous pulmonary arteries (LPA ¼ left pulmonary artery; RPA ¼ right pulmonary artery.)
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Fig 9. Surgical reconstruction is shown in a patient with a right aortic arch and bilaterally discontinuous pulmonary arteries. After ductal resection, the right carotid artery and left subclavian artery are used to reconstruct right and left pulmonary artery respectively.
preferred treatment modality for stabilization of pulmonary blood flow in patients with heterotaxy, pulmonary atresia, and TAPVR with or without discontinuous pulmonary arteries. Thirteen patients in our entire cohort had associated TAPVR. We believe that careful selection of TAPVR patients for nonsurgical intervention in the neonatal period is possible and likely beneficial. In our institution, every neonatal patient with heterotaxy and PA/PS with TAPVR is assessed carefully according to the appearance of the pulmonary veins on echocardiography or in the catheterization laboratory, chest radiographic findings, and clinical examination. We use a combination of all these factors to decide on the need for neonatal surgical intervention for TAPVR in heterotaxy and PA/PS. For example, an acyanotic TAPVR patient with PA, a large patent ductus arteriosus, clear chest roentgenogram, and stable hemodynamics would not be treated with neonatal TAPVR repair in our institution. We have speculated that moderate or more sonographic flow acceleration in the pulmonary venous pathway should be expected in this patient with excessive pulmonary blood flow and, if all other clinical indicators are favorable, that this is a patient who does not require urgent primary TAPVR repair. Jonas and colleagues [13] have also recommended selective TAPVR surgical intervention in patients with heterotaxy syndrome. The mortality rate for neonatal TAPVR repair in singleventricle heterotaxy patients with PA tends to be very high. We have observed that this death can often be
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the result of associated morbid propensities in these patients, such as postoperative arrhythmias, significant common atrioventricular valve regurgitation, and marginal single-ventricle performance after a lengthy TAPVR repair, pulmonary artery unifocalization, or a systemicto-pulmonary artery shunt placement with resultant volume overload. We have, therefore, used echocardiographic, catheterization, radiographic criteria, and clinical presentation to carefully define the group that requires neonatal TAPVR repair. Heterotaxy patients also have associated noncardiac malformations, including intestinal malrotation, that can cause significant morbidity and death. Surgical management of malrotation with the Ladd procedure can also be associated with significant cardiac morbidity and death. So we prefer to perform the Ladd procedure on these patients after the second-stage palliation with bidirectional Glenn. We only recommend an earlier Ladd procedure for patients who have clinical evidence of obstruction with bilious vomiting before the second-stage palliation [14]. In conclusion, this series represents our recent experience of heterotaxy patients with associated PA or PS. This remains a challenging and very heterogeneous group. The presence of TAPVR remains a risk factor for death in heterotaxy patients with PA or PS. We are continuing to modify and refine our techniques for the management of these patients. We are encouraged by the early results obtained with less traditional methods, such as ductal stenting or classic bilateral systemic-to-pulmonary artery shunts, that allow for creation or stabilization of pulmonary blood flow without the use of cardiopulmonary bypass. We believe that careful selection of TAPVR patients for delayed pulmonary vein repair beyond the neonatal period is also possible and likely beneficial. We are sufficiently encouraged to maintain this as our current strategy. We thank Rebekah Dodson for the illustrations provided in Figures 6, 7, 8, and 9.
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References 1. Hancock Friesen CL, Zurakowski D, Thiagarajan RR, et al. Total anomalous pulmonary venous connection: an analysis of current management strategies in a single institution. Ann Thorac Surg 2005;79:596–606. 2. Bartz PJ, Driscoll DJ, Dearani JA, et al. Early and late results of the modified Fontan operation for heterotaxy syndrome: 30 years of experience in 142 patients. J Am Coll Cardiol 2006;48:2301–5. 3. Stamm C, Friehs I, Duebner LF, et al. Improving results of the modified Fontan operation in patients with heterotaxy syndrome. Ann Thorac Surg 2002;74:1967–78. 4. Lim HG, Bacha EA, Marx GR, et al. Biventricular repair in patients with heterotaxy syndrome. J Thorac Cardiovasc Surg 2009;137:371–9. 5. Gaynor JW, Collins MH, Rychik R, Gaughan JP, Spray TL. Long-term outcome of infants with single ventricle and total anomalous pulmonary venous connection. J Thorac Cardiovasc Surg 1999;117:506–14. 6. Morales DL, Scully PT, Braud BE, et al. Heterotaxy patients with total anomalous pulmonary venous return: improving surgical results. Ann Thorac Surg 2006;82:1621–8. 7. Sadiq M, Stumper O, De Giovanni JV. Management and outcome of infants and children with right atrial isomerism. Heart 1996;75:314–9. 8. Hashmi A, Abu-Sulaiman R, McCrindle BW, Smallhorn JF, Williams WG, Freedom RM. Management and outcomes of right atrial isomerism: a 26-year experience. J Am Coll Cardiol 1998;31:1120–6. 9. Gilljam T, McCrindle BW, Smallhorn JF, Williams WG, Freedom RM. Outcomes of left atrial isomerism over a 28-year period at a single institution. J Am Coll Cardiol 2000;36:908–16. 10. Anagnostopoulos PV, Pearl JM, Octave C, et al. Improved current era outcomes in patients with heterotaxy syndrome. J Thorac Cardiovasc Surg 2009;35:871–8. 11. Ota N, Fujimoto Y, Murata M, et al. Improving outcomes of the surgical management of right atrial isomerism. Ann Thorac Surg 2012;93:832–9. 12. Foerster SR, Gauvreau K, McElhinney DB, Geva T. Importance of totally anomalous pulmonary venous connection and postoperative pulmonary vein stenosis in outcomes of heterotaxy syndrome. Pediatr Cardiol 2008;29:536–44. 13. Jonas RA. Surgical management of the neonate with heterotaxy and long-term outcomes of heterotaxy. World J Pediatr Congenit Heart Surg 2011;2:264–74. 14. Sharma MS, Guleserian KJ, Forbess JM. Ladd’s procedure in functional single ventricle and heterotaxy syndrome: does timing affect outcome? Ann Thorac Surg 2013;95: 1403–7.
Background. Historic outcomes of patients with heterotaxy and pulmonary atresia or pulmonary stenosis (PA/ PS) have been poor and in the current era are incompletely described. We reviewed our management of these patients and associated risk factors for death. Methods. We retrospectively reviewed the records of all patients with heterotaxy and PA/PS treated in our institution from January 1, 2002, to August 31, 2012. Death data were also confirmed with the Social Security Death Index. The log-rank test was done to assess six risk factors for death. Results. We identified 42 patients with heterotaxy and PA/PS. Median age at the first operation was 6.5 days, and median follow-up was 3.5 years. Death data were complete for all patients. Overall mortality was 19% (8 of 42).
The 30-day, 1-year, and 5-year mortality estimation was 4.76%, 12.3%, and 19.1% respectively, as determined by the Kaplan-Meier method. The log-rank test showed total anomalous pulmonary venous return (TAPVR) (p < 0.05) and obstructed TAPVR requiring an operation at less than 30 days (p [ 0.001) were significant risk factors for death. Conclusions. In the current era, surgical treatment of heterotaxy and PA/PS can result in good outcomes. Associated TAPVR and obstructed TAPVR requiring neonatal correction were noted to be risk factors for death.
T
Patients
he management of newborns with heterotaxy syndrome can be challenging due to the frequent combination of severe cardiac and noncardiac anomalies. Patients with heterotaxy syndrome associated with pulmonary atresia or significant pulmonary stenosis (PA/PS) are an especially difficult subset, because they often require single-ventricle palliation and their outcomes have been disappointing. We reviewed all of the heterotaxy patients presenting to Children’s Medical Center Dallas with associated PA/PS.
Patients and Methods Approval for this study was obtained from the Institutional Review Board at Children’s Medical Center Dallas and the University of Texas Southwestern Medical Center. Accepted for publication Feb 20, 2014. Oral presentation at the Thirty-ninth Annual Meeting of the Western Thoracic Surgical Association, Coeur d’Alene, Idaho, June 26–29, 2013. Address correspondence to Dr Sebastian, 1935 Medical District Dr, Ste C3.211, Dallas, TX 75235; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2014;-:-–-) Ó 2014 by The Society of Thoracic Surgeons
Between January 1, 2002, and August 31, 2012, 42 patients with heterotaxy syndrome and PA/PS were treated at Children’s Medical Center Dallas. We performed a retrospective review of the medical records of all patients with heterotaxy and PA/PS. Death data were also confirmed with the Social Security Death Index. The duration of follow-up was calculated from the first operation to the last clinical encounter with a cardiologist at our institution. Heterotaxy syndrome was defined as a complex of anomalies of visceral-cardiac relations in association with intracardiac pathology [1]. After the initial discharge, most of these patients were managed on a singleventricle palliation pathway, with the final destination being a Fontan circulation. Follow-up after completion of the Fontan circulation was done at the discretion of the patient’s cardiologist. Patients with associated total anomalous pulmonary venous return (TAPVR) underwent neonatal pulmonary vein repair if they had two or more of the following: clinical signs of obstructed pulmonary veins, chest radiographic evidence of obstructed pulmonary veins, or echocardiography/catheter based evidence of obstructed pulmonary veins. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.02.076
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Table 1. Heterotaxy With Pulmonary Atresia/Pulmonary Stenosis Variable Patients Sex Male Female Pulmonary atresia Pulmonary stenosis Unilateral/bilateral discontinuous PAs TAPVR AVSD DORV Interrupted inferior vena cava AVSD ¼ atrioventricular septal defect; ventricle; PA ¼ pulmonary arteries; pulmonary venous return.
No.
Percentage of Total
42
100
19 23 25 17 7 13 33 11 8
45.24 54.76 59.5 40.5 16.67 31 78.6 26.2 19
DORV ¼ double-outlet right TAPVR ¼ total anomalous
Statistical Analysis The log-rank test was performed to assess the following variables as risk factors for death: discontinuous pulmonary arteries, TAPVR, obstructed TAPVR requiring surgical intervention at an age of less than 30 days, TAPVR requiring surgical intervention at an age of greater than 30 days, and PS vs PA. Kaplan-Meier survival curves were created for those risk factors.
Fig 1. Algorithm for management of heterotaxy with pulmonary atresia/pulmonary stenosis. (TAPVR ¼ total anomalous pulmonary venous return.)
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Results We identified 42 patients with heterotaxy and PA/PS. Concomitant diagnoses included unilaterally or bilaterally discontinuous pulmonary arteries, TAPVR, atrioventricular septal defect, and double-outlet right ventricle (DORV). Patient demographics and associated diagnoses are listed in Table 1. Figure 1 shows the algorithm we use in the treatment of these patients, and Figure 2 summarizes the subgroups within our entire patient cohort. The median age at the first operation was 6.5 days (range, 1 to 277 days), and median follow-up was 3.5 years (range, 0.06 to 18.5 years). Death data were complete for all patients. The Society of Thoracic Surgeons (STS) mortality for the entire cohort was 11.9% (5 of 42 patients) and overall mortality was 19% (8 of 42 patients). The Kaplan-Meier survival curves in Figure 3 show 30-day, 1-year, and 5-year survival of 95.24%, 87.7%, and 80.9%, respectively. Among the variables analyzed by log-rank test, the risk factors for death among the entire cohort were the presence of TAPVR and the presence of obstructed TAPVR requiring surgery at less than 30 days of age (Figs 4, 5). Three patients underwent biventricular repair. Biventricular repair was undertaken in the presence of 2 ventricles of adequate volume and function, as well as a septatable atrioventricular valve with adequate inlet to each ventricle and venoatrial connections.
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Fig 2. Clinical management of heterotaxy with pulmonary atresia/pulmonary stenosis. (TAPVR ¼ total anomalous pulmonary venous return.)
Three patients transitioned from single-ventricle palliation to the transplant list for failing single-ventricle physiology. Only 1 of these 3 patients received a transplant. The remaining patients have been taken down the single-ventricle palliation pathway with the addition of a
Fig 3. Kaplan-Meier survival curve (blue line) is shown with the 95% confidence limits (range bars), with circles indicating censored patients.
TAPVR repair if the pulmonary veins appear obstructed based on chest roentgenogram, clinical examination, and echocardiographic or catheterization diagnosis of obstruction.
Fig 4. Survival comparison is shown between heterotaxy patients with pulmonary atresia/pulmonary stenosis with total anomalous pulmonary venous return (TAPVR; dashed red line; red circles indicating censored patients) and those without TAPVR (solid blue line, blue circles indicating censored patients). Log-rank test showed significantly worsened survival in the TAPVR group (p ¼ 0.038). The range bars show the 95% confidence limits.
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Unplanned Intervention in the Operating Room or Catheterization Suite Eleven patients required unplanned reintervention in the operating room or in the catheterization laboratory. The diagnoses, intervention, indication for intervention, and current disposition are listed in Table 2.
Ductal Stent Ductal stenting was considered in 5 patients and was completed in 2. Three patients did not have favorable ductal anatomy to allow ductal stenting and underwent systemic-to-pulmonary artery shunt placements. In the remaining 2 patients, ductal stenting was performed, followed by TAPVR repair at 8 and 9 months, respectively. Fig 5. Survival comparison is shown between heterotaxy patients with pulmonary atresia (PA)/pulmonary stenosis (PS) with total anomalous pulmonary venous return (TAPVR) who underwent operations at less than 30 days of age (solid red line; red circles indicating censored patients) vs the remaining patients in the cohort (dashed blue line, blue circles indicating censored patients). The logrank test showed significant difference in survival between the two groups (p ¼ 0.001). The range bars show the 95% confidence limits.
Discontinuous Pulmonary Arteries Seven patients had discontinuous pulmonary arteries, of which 5 had bilateral discontinuous pulmonary arteries. Three of 5 had unifocalization with central pulmonary artery reconstruction, of whom 1 patient had ductal stents as a neonate. One of these patients, who also had a neonatal TAPVR repair with unifocalization to a modified Blalock-Taussig shunt, died in the perioperative period
Table 2. Unplanned Intervention in the Operating Room or Catheterization Suite Diagnosis Complete AVSD, TAPVR, bilateral SVC, pulmonary atresia Dextrocardia with unbalanced AVSD, discontinuous pulmonary arteries, TAPVR, bilateral SVC, pulmonary atresia Unbalanced AVSD, pulmonary atresia, interrupted IVC Dextrocardia with unbalanced AVSD, pulmonary stenosis
Unplanned reintervention
Indication Inflow stenosis
Disposition
Revision of systemic to pulmonary artery shunt Pre Glenn LPA stent
Diffusely hypoplastic LPA Awaiting Fontan
LPA stent
Ductal coarctation
Awaiting Fontan
Stenting of right modified BT shunt Pericardial window Pulmonary patch arterioplasty Sternal exploration Pleurodesis
Completed Fontan circulation
Shunt thrombosis Pericardial effusion Cyanosis after Glenn Sternal infection Pleural effusion
Complete AVSD with pulmonary atresia, ECMO for respiratory insufficiency Respiratory insufficiency obstructed TAPVR Unbalanced AVSD, d-malposed great AV valve repair AV valve regurgitation arteries, pulmonary atresia, bilateral SVC Pulmonary atresia, right aortic arch ECMO Postoperative ventricular fibrillation Dextrocardia, DORV with pulmonary ECMO and shunt thrombectomy Shunt thrombosis stenosis, bilateral cavae, obstructed TAPVR, right aortic arch Shunt revision and arterioplasty Right pulmonary artery Dextrocardia with AVSD, bilateral SVC, pulmonary atresia, right aortic arch stenosis Unbalanced AVSD with pulmonary Pulmonary vein repair Right lower pulmonary stenosis, obstructed TAPVR vein stenosis DORV, d-malposed great vessels, bilateral ECMO and stenting of shunt Shunt thrombosis SVC, interrupted IVC, pulmonary stenosis
Awaiting Glenn
Death Completed Fontan circulation Death Death
Completed Fontan circulation Awaiting transplant Completed 2-ventricle repair
AV ¼ atrioventricular; AVSD ¼ atrioventricular septal defect; BT ¼ Blalock-Taussig; DORV ¼ double-outlet right ventricle; extracorporeal membrane oxygenation; IVC ¼ inferior vena cava; LPA ¼ left pulmonary artery; SVC ¼ superior vena cava; total anomalous pulmonary venous return.
ECMO ¼ TAPVR ¼
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from morbidity related to malignant supraventricular tachycardia. Of the remaining 2 in the unifocalization group, both underwent superior cavopulmonary connection and are awaiting completion of Fontan circulation. The remaining 2 patients with discontinuous PAs underwent creation of “classic-style” autologous systemic-to-pulmonary shunts with subclavian and unilateral carotid artery turndowns to the ipsilateral pulmonary artery, and both have undergone completion of superior cavopulmonary connection and are awaiting Fontan completion (Figures 6 and 7).
Pulmonary Stenosis PS was present in 17 patients (40.5%) rather than PA. This did not confer a survival benefit in the log-rank test. Twelve of 17 PS patients underwent systemic-topulmonary artery shunts to supplement pulmonary artery blood flow. Of these, 4 had additional control of antegrade pulmonary blood flow with pulmonary artery ligation (n ¼ 1) and pulmonary artery banding (n ¼ 3) after performance of a shunt. We have a low threshold to perform mechanical restriction of antegrade pulmonary blood at the time of systemic-to-pulmonary artery shunt to optimize systemic perfusion. Four patients with PS did not have an initial systemic-to-pulmonary artery shunt.
Fig 7. Surgical reconstruction is shown in a patient with left aortic arch and bilaterally discontinuous pulmonary arteries. After ductal resection, the right subclavian artery and left carotid artery are used to reconstruct right and left pulmonary artery respectively.
Two of these had primary bidirectional Glenn, and the other two had TAPVR repair, followed by bidirectional Glenn, without the need for an intervening procedure for additional pulmonary blood flow.
Total Anomalous Pulmonary Venous Return Associated TAPVR was present in 13 patients, comprising 5 supracardiac, 4 infracardiac, and 4 cardiac-level TAPVR. Of the 5 supracardiac TAPVR patients, 3 had a vertical vein to a right sided superior vena cava, 1 to the innominate, and 1 to a left-sided superior vena cava. Five presented with obstruction and were repaired at less than 30 days of age. Another 4 patients underwent repair at greater than 30 days of age. Of these 4 who underwent delayed pulmonary vein intervention, three had presented with some signs of obstruction but were selected for observation and delayed pulmonary vein repair according to our selection criteria mentioned in Patients and Methods. Obstruction has not developed in 4 patients, all of whom had cardiac level TAPVR, and they have not required any intervention. Only 1 patient has required surgical reintervention for pulmonary vein stenosis.
Comment Fig 6. Drawing shows a patient with a left aortic arch and bilaterally discontinuous pulmonary arteries (PAs). (Ao ¼ aorta; RA ¼ right atrium; RPA ¼ right pulmonary artery; RV ¼ right ventricle; SVC ¼ superior vena cava.)
To the best of our knowledge, this is the first report dedicated to an analysis of patients with heterotaxy syndrome and PA/PS. Our therapy for these patients has evolved over time. More recently, we have started evaluating these patients for the use of a ductal stent as the
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initial neonatal intervention, especially in those with associated TAPVR. We have also adopted a different approach to TAPVR diagnosed in the neonatal period in patients with heterotaxy and PA or PS. A broad-based diagnostic evaluation is performed in neonates with associated TAPVR, looking at the pulmonary vein echocardiographic characteristics or appearance in the catheterization laboratory, chest radiographic findings of pulmonary vein obstruction, and clinical examination findings of pulmonary vein obstruction. Neonatal TAPVR repair was, in general, performed in the presence of two or more factors suggesting obstruction. None of the cardiac-level TAPVR patients required any pulmonary vein interventions. The extracardiac TAPVR patients who were not repaired in the neonatal period continued to have mild degree of pulmonary vein obstruction beyond the neonatal period. Single-ventricle physiology was present in most of these patients with extracardiac TAPVR and so they underwent pulmonary vein repair to maintain an optimal pulmonary vascular bed. Other series have reported heterotaxy syndrome in association with univentricular repair [2, 3], biventricular repair [4], TAPVR repair [5, 6] and right atrial isomerism or left atrial isomerism [7–10]. Right atrial isomerism has been associated with worse survival than left atrial isomerism [7–10]. We did not use atrial isomerism to subclassify our patient population, although we did look at the association with TAPVR, discontinuous pulmonary arteries, PA vs PS, and univentricular or biventricular repair. Historical outcomes with heterotaxy syndrome and congenital heart disease have been unsatisfactory. Sadiq and colleagues [7] reported 45% overall survival in 20 patients with right atrial isomerism, and only 9 patients were eventual Fontan candidates. Hashmi and colleagues [8] reported a 69% mortality rate for children with right atrial isomerism, and another study from the same institution reported 44% mortality in children born with left atrial isomerism [9]. In 2009, Anagnostopoulos and colleagues [10] reported improved surgical outcomes in heterotaxy patients. In patients with right and left atrial isomerism, 3-year survival was 79% and 94%, respectively. The incidence of sinus node dysfunction was higher in the patients with left atrial isomerism. The risk factors for death in patients with right atrial isomerism were the presence of obstructed TAPVR and greater than moderate atrioventricular valve regurgitation. The incidence of single-ventricle palliation was 85% in that series, which is highly comparable to the 93% incidence in our patient cohort. We have found similar risk factors for increased death—the presence of TAPVR and obstructed TAPVR requiring surgical intervention at less than 30 days of age. Ota and colleagues [11] reported their surgical outcomes in patients with right atrial isomerism and also found neonatal palliative intervention to be a risk factor for early death. Morales and colleagues [6] compared the outcomes of TAPVR repair in patients with and without heterotaxy. With a mean follow-up of 2.6 years, they reported 5
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deaths in 84 TAPVR patients without heterotaxy and 7 deaths in 38 patients with TAPVR and heterotaxy. However, this mortality difference was not statistically significant. They noted a 9.8% reoperation rate after TAPVR repair, but 58% of the reoperations for pulmonary vein stenosis were in heterotaxy patients compared with nonheterotaxy patients. Foerster and colleagues [12] reported a higher 47% restenosis rate after TAPVR repair in heterotaxy patients. Only one patient in our cohort of heterotaxy syndrome, PA/PS, and TAPVR, has required reintervention for pulmonary vein stenosis. Morales and colleagues [6] found no statistically significant difference in survival between TAPVR in heterotaxy and nonheterotaxy patients but did report PA and the need for systemic-to-pulmonary shunt to be risk factors for death among their entire cohort. Three patients in our series underwent two ventricle repairs. These patients were initially palliated with a systemic-to-pulmonary artery shunt, and then a Rastelli pathway was used to connect the morphologic left ventricle to the aorta. At this time, right ventricle to pulmonary artery continuity was established using a Contegra conduit in all 3 patients. Stent angioplasty of the ductus arteriosus can be performed for ductal-dependent pulmonary or systemic circulation. When we use ductal stents for neonates with heterotaxy and ductal-dependent pulmonary circulation, our institutional policy is to use a stent 4 mm or lesser in diameter, due to concern for diastolic run off physiology leading to systemic malperfusion and necrotizing enterocolitis. For ducts larger than 4 mm in diameter, prostaglandins are stopped a few hours before ductal stenting to allow the use of an appropriately sized stent for the patient’s body weight. We have avoided ductal stenting for tortuous ducts (with curvature greater than 180 degrees). Ductal stenting is performed using a prograde approach (femoral venous access), retrograde approach (femoral arterial access), or by carotid artery cutdown approach. Immediately after ductal stenting, an intravenous heparin drip is started and aspirin is given for 48 hours. Anticoagulation is continued with low-molecularweight heparin and aspirin. At the time of discharge, these patients are enrolled in our Safe-at-Home program for interstage monitoring of single-ventricle patients. Close monitoring of saturations and serial echocardiograms is done to evaluate for ductal stent obstruction due to thrombosis or in-stent restenosis. At our institution, ductal stents are typically evaluated in the catheterization laboratory 3 to 4 months after implantation. We are encouraged by the early results obtained with less traditional methods, such as primary ductal stenting or the use of bilateral autologous systemicto-pulmonary artery shunts, that allow for avoiding on-cardiopulmonary bypass systemic-to-pulmonary artery shunting with or without neonatal pulmonary artery unifocalization. Heterotaxy is often associated with multiple intracardiac lesions, and when subgroups of cardiac lesions or interventions are examined within the study
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group, the subanalyses is often underpowered. This is an inherent limitation of our study. For example, we cannot make statistically significant inferences about the subgroup where ductal stenting was attempted. In patients with discontinuous pulmonary arteries that are not amenable to ductal stenting, our preferred technique of reconstruction has been with the subclavian artery and carotid artery with a “turn down” flap that connects it to the ipsilateral discontinuous pulmonary artery in the form of a “classic shunt” (Figures 6 and 7). We perform this technique without cardiopulmonary bypass, and it has allowed us the versatility to treat the discontinuous pulmonary arteries in heterotaxy with its positional anomalies such as dextrocardia or right aortic arch (Figures 8 and 9). This technique has also allowed us the maximal use of autologous vascular tissue for centralization of pulmonary arteries at a later stage. We have performed bidirectional Glenn on both of the patients that underwent a classic shunt for discontinuous pulmonary arteries and no significant distal vascular ischemia has occurred with the use of these autologous tissue shunts. A third patient with discontinuous pulmonary arteries underwent bilateral ductal stents and delayed centralization of the pulmonary arteries. The remaining 2 patients with bilaterally discontinuous pulmonary arteries underwent neonatal centralization of the pulmonary arteries, and the patient that underwent simultaneous TAPVR repair died. Currently, we use primary ductal stenting as our
Fig 8. Drawing shows patient with right aortic arch and bilaterally discontinuous pulmonary arteries (LPA ¼ left pulmonary artery; RPA ¼ right pulmonary artery.)
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Fig 9. Surgical reconstruction is shown in a patient with a right aortic arch and bilaterally discontinuous pulmonary arteries. After ductal resection, the right carotid artery and left subclavian artery are used to reconstruct right and left pulmonary artery respectively.
preferred treatment modality for stabilization of pulmonary blood flow in patients with heterotaxy, pulmonary atresia, and TAPVR with or without discontinuous pulmonary arteries. Thirteen patients in our entire cohort had associated TAPVR. We believe that careful selection of TAPVR patients for nonsurgical intervention in the neonatal period is possible and likely beneficial. In our institution, every neonatal patient with heterotaxy and PA/PS with TAPVR is assessed carefully according to the appearance of the pulmonary veins on echocardiography or in the catheterization laboratory, chest radiographic findings, and clinical examination. We use a combination of all these factors to decide on the need for neonatal surgical intervention for TAPVR in heterotaxy and PA/PS. For example, an acyanotic TAPVR patient with PA, a large patent ductus arteriosus, clear chest roentgenogram, and stable hemodynamics would not be treated with neonatal TAPVR repair in our institution. We have speculated that moderate or more sonographic flow acceleration in the pulmonary venous pathway should be expected in this patient with excessive pulmonary blood flow and, if all other clinical indicators are favorable, that this is a patient who does not require urgent primary TAPVR repair. Jonas and colleagues [13] have also recommended selective TAPVR surgical intervention in patients with heterotaxy syndrome. The mortality rate for neonatal TAPVR repair in singleventricle heterotaxy patients with PA tends to be very high. We have observed that this death can often be
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the result of associated morbid propensities in these patients, such as postoperative arrhythmias, significant common atrioventricular valve regurgitation, and marginal single-ventricle performance after a lengthy TAPVR repair, pulmonary artery unifocalization, or a systemicto-pulmonary artery shunt placement with resultant volume overload. We have, therefore, used echocardiographic, catheterization, radiographic criteria, and clinical presentation to carefully define the group that requires neonatal TAPVR repair. Heterotaxy patients also have associated noncardiac malformations, including intestinal malrotation, that can cause significant morbidity and death. Surgical management of malrotation with the Ladd procedure can also be associated with significant cardiac morbidity and death. So we prefer to perform the Ladd procedure on these patients after the second-stage palliation with bidirectional Glenn. We only recommend an earlier Ladd procedure for patients who have clinical evidence of obstruction with bilious vomiting before the second-stage palliation [14]. In conclusion, this series represents our recent experience of heterotaxy patients with associated PA or PS. This remains a challenging and very heterogeneous group. The presence of TAPVR remains a risk factor for death in heterotaxy patients with PA or PS. We are continuing to modify and refine our techniques for the management of these patients. We are encouraged by the early results obtained with less traditional methods, such as ductal stenting or classic bilateral systemic-to-pulmonary artery shunts, that allow for creation or stabilization of pulmonary blood flow without the use of cardiopulmonary bypass. We believe that careful selection of TAPVR patients for delayed pulmonary vein repair beyond the neonatal period is also possible and likely beneficial. We are sufficiently encouraged to maintain this as our current strategy. We thank Rebekah Dodson for the illustrations provided in Figures 6, 7, 8, and 9.
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References 1. Hancock Friesen CL, Zurakowski D, Thiagarajan RR, et al. Total anomalous pulmonary venous connection: an analysis of current management strategies in a single institution. Ann Thorac Surg 2005;79:596–606. 2. Bartz PJ, Driscoll DJ, Dearani JA, et al. Early and late results of the modified Fontan operation for heterotaxy syndrome: 30 years of experience in 142 patients. J Am Coll Cardiol 2006;48:2301–5. 3. Stamm C, Friehs I, Duebner LF, et al. Improving results of the modified Fontan operation in patients with heterotaxy syndrome. Ann Thorac Surg 2002;74:1967–78. 4. Lim HG, Bacha EA, Marx GR, et al. Biventricular repair in patients with heterotaxy syndrome. J Thorac Cardiovasc Surg 2009;137:371–9. 5. Gaynor JW, Collins MH, Rychik R, Gaughan JP, Spray TL. Long-term outcome of infants with single ventricle and total anomalous pulmonary venous connection. J Thorac Cardiovasc Surg 1999;117:506–14. 6. Morales DL, Scully PT, Braud BE, et al. Heterotaxy patients with total anomalous pulmonary venous return: improving surgical results. Ann Thorac Surg 2006;82:1621–8. 7. Sadiq M, Stumper O, De Giovanni JV. Management and outcome of infants and children with right atrial isomerism. Heart 1996;75:314–9. 8. Hashmi A, Abu-Sulaiman R, McCrindle BW, Smallhorn JF, Williams WG, Freedom RM. Management and outcomes of right atrial isomerism: a 26-year experience. J Am Coll Cardiol 1998;31:1120–6. 9. Gilljam T, McCrindle BW, Smallhorn JF, Williams WG, Freedom RM. Outcomes of left atrial isomerism over a 28-year period at a single institution. J Am Coll Cardiol 2000;36:908–16. 10. Anagnostopoulos PV, Pearl JM, Octave C, et al. Improved current era outcomes in patients with heterotaxy syndrome. J Thorac Cardiovasc Surg 2009;35:871–8. 11. Ota N, Fujimoto Y, Murata M, et al. Improving outcomes of the surgical management of right atrial isomerism. Ann Thorac Surg 2012;93:832–9. 12. Foerster SR, Gauvreau K, McElhinney DB, Geva T. Importance of totally anomalous pulmonary venous connection and postoperative pulmonary vein stenosis in outcomes of heterotaxy syndrome. Pediatr Cardiol 2008;29:536–44. 13. Jonas RA. Surgical management of the neonate with heterotaxy and long-term outcomes of heterotaxy. World J Pediatr Congenit Heart Surg 2011;2:264–74. 14. Sharma MS, Guleserian KJ, Forbess JM. Ladd’s procedure in functional single ventricle and heterotaxy syndrome: does timing affect outcome? Ann Thorac Surg 2013;95: 1403–7.
