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Ann Thorac Surg 2007;83:173-178
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Surgery for Transposition of the Great Arteries in Neonates Weighing Less Than 2,000 Grams: A Consecutive Series of 25 Patients

Régine Roussin, MD*, Emre Belli, MD, Jacqueline Bruniaux, MD, Serge Demontoux, MD, Anita Touchot, MD, Claude Planché, MD, Alain Serraf, MD, PhD

Hôpital Marie Lannelongue, Le Plessis Robinson, France

Accepted for publication July 18, 2006.

* Address correspondence to Dr Roussin, Hôpital Marie Lannelongue 133, Avenue de la Résistance, 92350 Le Plessis Robinson, France (Email: rroussin{at}ccml.com).

Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 
BACKGROUND: The arterial switch operation (ASO) is the optimal option for neonates with transposition of the great arteries (TGA). Low birth weight (LBW) and prematurity were considered as risk factors for poor outcome in early corrective surgery for cardiac defects. This retrospective study was undertaken to evaluate early and midterm results in infants with TGA weighing less than 2,000 grams who underwent surgical procedure in the neonatal period.

METHODS: Among the 1,505 patients who underwent surgical procedure for TGA at our institution, 25 (0.02%) had a birth weight less than 2,000 grams and constituted the study group. Median age at operation was 19 days and median weight was 1,930 grams. Prior to surgery, all were in the intensive care unit. Eleven (48%) with TGA and intact interventricular septum had an ASO but one had a Senning operation. Among 13 patients (52%) with complex TGA, 9 had anatomic repair and 4 had palliation.

RESULTS: Operative mortality was 16%. Age at operation greater than 30 days and palliation were risks factors for early death. At postoperative 43 months, actuarial survival rate was 71% and freedom from reoperation rate was 73%. All survivors were considered to have good cardiac status; 95% joined the normal curve for LBW infants without heart defects.

CONCLUSIONS: These data support that delaying repair in LBW neonates with simple or complex TGA does not confer any benefit and is associated with higher morbidity.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Discussion
 References
 
Since Jatene and colleagues performed the first anatomical repair for transposition of the great arteries-ventricular septal defect (TGA-VSD), the arterial switch operation (ASO) has become the optimal treatment for children with TGA in either simple or complex form with excellent survival rate and quality of life [1]. Low birth weight (LBW) or prematurity are known as risk factors for poor outcome in early corrective surgery for many cardiac defects. Although most cardiovascular malformations are often associated with LBW and intrauterine growth retardation, TGA was not demonstrated per se responsible for prematurity or LBW [2]. Premature or LBW newborns with TGA are very rare, only 0.02% of the 1,505 TGA operated at our institution. The indication for early anatomic repair remains under debate, particularly in the presence of associated defects. On the other hand, this population will eventually increase because of most frequent maternal pathology, progress in pregnancy induction, prenatal diagnosis, and improvement in the management of premature or LBW neonates. The aim of the present study was to evaluate surgical experience in a retrospective and consecutive series of 25 patients who underwent surgical management of TGA with or without associated defect.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Discussion
 References
 
This study was approved by the Ethics Committee of Marie Lannelongue Hospital. As it was a retrospective study, individual consent was waived by the Ethics Committee.

Patient Characteristics
Between 1990 and 2003, among 1,140 patients who underwent surgery for transposition of the great arteries, 25 (0.02%) had a birth weight less than 2,000 grams. Before 1990, these babies were denied surgery. Nineteen patients (76%) were born prematurely and 20 patients (80%) were hypotrophic for the gestational age. The median weight at birth was 1,790 grams (range, 950 to 2,000 grams). Prenatal diagnosis was available in 13 patients (52%). A placental insufficiency as cause of prematurity and hypotrophy was documented in 18 patients (72%).

Preoperative Clinical Condition
All the patients were in the intensive care unit (ICU). Cerebral echography was carried out for all patients. Preoperative clinical data is summarized in Table 1. Median age and median weight at the operation were 19 days (range, 5 to 90 days) and 1,930 grams (range, from 1,400 to 2,800 grams). Only one patient had association with extracardiac (renal and orthopedic) malformations. Twenty patients received prostaglandin infusion preoperatively; they received the lowest dose of prostaglandin to maintain the ductus open. We started the treatment with a dose of 0.0125 microgram per kilogram per minute and increased the dose if necessary until 0.0250 micrograms per kilogram per minute. Seven patients with membrane hyaline disease received surfactant preoperatively. We did not use, systematically, surfactant before, during, or after the surgery in this group of patients.


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  		Table 1. Preoperative Morbidity
 
Cardiac Diagnosis
The cardiac defects were diagnosed exclusively by two-dimensional echocardiography and color flow Doppler studies. The diagnosis included simple TGA (n = 12 patients [48%]) and complex TGA (13 patients [52%]) (Table 2). The coronary patterns in Marie Lannelongue classification were the following: type I, n = 19; type II, n = 3; type III, n = 3 [1].


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  		Table 2. Diagnosis and Surgical Procedure
 
Surgical Procedure
Four patients with complex TGA had palliative surgery: one patient, with TGA and multiple VSD, had pulmonary artery banding and atrial septectomy; the second, with TGA and large VSD, had pulmonary artery banding (PAB); the third, with TGA-VSD and aortic arch interruption, had PAB and aortic arch reconstruction with a 5 mm polytetrafluoroethylene conduit; the fourth, with TGA-VSD and aortic coarctation, had PAB and aortic arch repair. Twenty-one patients (84%) had anatomical repair (Table 2). All repairs were performed through median sternotomy and under cardiopulmonary bypass (CPB). Patient monitoring and anesthetic protocol were similar to those used in neonates and children weighing more than 2,000 grams at operation. Standard neonatal CPB was used, with aortic and bicaval venous cannulation, and full-flow perfusion (150 mL/Kg/min) at moderate hypothermia at 25°C. The median duration of cardiopulmonary bypass was 160 minutes (range, 35 to 418) for the entire series and 179 minutes (range, 35 to 300) for complex TGA patients. The median aortic cross-clamp time was 79 minutes (range, 53 to 144). A period of deep hypothermic total circulatory arrest was used in 3 patients at earlier experience. To avoid extra edema after CPB, the patients received furosemide postoperatively in the ICU during the first 48 hours after the operation. All simple TGA patients but one underwent anatomical repair by ASO. This patient had a Senning procedure; his birth weight was 1,500 grams, he was operated on in 1990, he was 60 days old, and the surgery was delayed. Now, we operate on such a patient by an ASO below three weeks of age.

Data Collection and Analysis
Perioperative data were obtained through retrospective review of hospital records. Outcome analysis included operative mortality (defined as death during the hospitalization) and morbidity. Confidence intervals (95%, confidence limits [CL]) were stated. Follow-up, including clinical status, weight evolution, psychomotor development, reintervention rate, and late survival was available for all patients.

StatView 5.0 software (SAS Institute, Inc, Cary, NC) was used for data analysis. Data were expressed as median value and range. Univariate analyses of continuous variables were performed with the Student t test. Univariate comparisons for categoric variables were performed with the 2-tailed {chi}2 test or, when necessary, the Fischer exact test. Every univariate parameter that reached significance (p < 0.05) was then tested in a multivariate logistic regression model. Time-related events were examined by the actuarial method.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Discussion
 References
 
Hospital Mortality
Hospital mortality occurred in four patients (16%; CL 5% and 36%). One patient with TGA-VSD died after an ASO, from liver injury at chest tube placement. The unique patient presenting with TGA-interventricular septum (IVS), who underwent a Senning procedure, died because of hemorrhage under circulatory support initiation by extracorporeal membrane oxygenation consequent to severe cardiac failure. The third patient, with TGA-IVS, for whom the operation was delayed until 45 days of age, died because of postoperative pulmonary infection. The fourth patient, presenting with TGA-VSD, underwent urgent palliative procedure (surgical atrial septectomy and PAB) after failure of a balloon atrial septostomy at 35 days of age; he died because of abdominal hemorrhage secondary to femoral artery puncture failure. Table 3 represents risk factor analysis for death.


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  		Table 3. Statistical Analysis
 
Early Morbidity
Our strategy for sternum closure at the end of the procedure was the same as that for patients with TGA operated on with an ASO and weighing more than 2 kg. The chest was left open electively, because of hemodynamic instability or complex procedure, 14 times. Chest closure was performed 1 to 13 days (median, 2 days) after the initial procedure. The early morbidity is presented in Table 4. The median duration of mechanical ventilation was 8 days (range, 3 to 43). The median time of ICU stay was 10 days (range, from 0 to 45). Duration of mechanical ventilation and length of ICU stay were similar for the study group patients and others. One patient with TGA-VSD coarctation repair presented with residual coarctation 28 days later; he had a catheter exploration and during the procedure the right coronary artery was dissected and stented. Two patients with palliative procedure had balloon atrial septostomy. Postoperative neurologic complication was observed in one patient.


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  		Table 4. Early Morbidity
 
Late Mortality
There were three late deaths (14%; CL, 3% and 36%). One patient died suddenly two months after surgery; the autopsy revealed a right coronary thrombosis. The second patient died from cardiac failure two months later. The third patient, with a two-stage procedure, died 14 months after repair from inferior vena cava thrombosis. The actuarial survival, including operative mortality, was 75% and 71% at 1 and 5 years, respectively (Fig 1).


Figure 1
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  		Fig 1. Actuarial survival and freedom from reoperation. ({diamondsuit} = actuarial survival; {blacksquare} = freedom from reoperation.)

 
Clinical Assessment
The median follow-up was 43 months (range, 1 to 156 months) and was 100% complete. All survivors were considered to have good cardiac status and were in sinus rhythm. They joined the normal curve for LBW infants not affected by a congenital heart malformation. Regarding the clinical neurodevelopmental status, obvious mental and motor retardation were observed in two patients; one patient had presented cerebral hemorrhage before operation, the second patient suffered from cerebral infarction during a reoperation for pulmonary stenosis.

Late Reinterventions
Four patients required five reoperations (19%; CL, 5% and 42%). Two patients with two-stage procedure had repair two and eight months after palliation. Two patients were reoperated on for pulmonary stenosis two and six years after initial repair. Actuarial freedom from reintervention was 94% at 1 year and 73% at 5 years (Fig 1).


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Discussion
 References
 
Low birth weight neonates with congenital heart disease often have the characteristic problems of premature or small for gestational age neonates related to the inadequate maturation of organ systems. These problems include metabolic disturbances (such as electrolyte imbalances, hypothermia, and hypoglycemia), pulmonary disease (such as apnea, hyaline membrane disease, bronchopulmonary dysplasia, and pulmonary hemorrhage), and others including intraventricular hemorrhage, necrotizing enterocolitis, and renal insufficiency. The management of these neonates is still under debate; when do we operate and what is the better approach, one step surgical repair or first palliation. Previous reports [3] have suggested that age and weight are risk factors for poor outcome of corrective operations for many with congenital heart disease (CHD). Considerable progress has been made in achieving total repair of heart disease in the neonatal period. Application of this strategy to the LBW has pointed out that surgery can be achieved in such cases with acceptable risk [4–8]. Different studies [4, 5, 7, 8] reported on surgical management of LBW with miscellaneous CHD, the early death varied from 22% to 15%. None of these reports focused on neonates with TGA. With particular attention to the sporadic cases of TGA reported on in these studies, the mortality rate varied from 17% to 67% for patients under 2,000 grams. Prêtre and colleagues [9] published lower weight as a risk for death in a large TGA series of neonates who underwent ASO. In our series, the overall hospital mortality was 16% and only 9% for the TGV-IVS group. There was no statistically significant difference in terms of early mortality between the study group and the institutional global TGA series. In light of these results, one can conclude that the prematurity and the LBW did not influence the early outcome, and early repair can be performed in LBW neonates with an acceptable risk [5, 7, 8].

Patients older than 30 days at operation were a significant risk factor in our series. If these patients stayed in ICU to achieve further weight gain they contracted infection, ventilatory dependency, failure to thrive, chronic pulmonary disease, necrotizing enterocolitis, and acute renal failure. Chang and colleagues [10] reported on a series of 100 LBW neonates with CHD who were managed with different protocols. Among patients operated on early the mortality rates were 18% with corrective procedures and 22% with palliative procedures, and in the group of delayed intervention the mortality was 23% [10]. In one patient in our series, with isolated TGA and for whom the operation was delayed solely for the purpose of somatic growth, ASO was performed at 45 days; he died of severe pulmonary infection two days after the operation. Delaying repair of CHD did not confer any benefit and was associated with higher preoperative morbidity [4, 10]. However, the importance of obtaining cardiovascular stability and allowing for the recovery of major organ system insults before surgery are now well-accepted philosophies [5]. An ASO is the operation of reference for the surgical treatment of TGA [1, 11–13]. The left ventricle ability to sustain a systemic function slowly decreases after two weeks of age [14]. Wernovsky and colleagues [13], in a series of 470 patients, reported that older age at repair was a risk factor in patients with TGA-IVS. In our series, a patient with TGA-IVS, operated on at 60 days old with a Senning procedure, died of cardiac output. The more we delayed operation, the more the left ventricle would be able to sustain a systemic function. We can conclude that the ASO operation is the operation of choice in the LBW neonate with TGA. The essential to success, in particular for TGA for which ASO is the operation of choice, was prompt and early operation before clinical deterioration occurs.

Some of the most important developments have been in the area of cardiopulmonary bypass (CPB) techniques. Equipment has been streamlined to diminish hemodilution and priming volume in small infants. Cardiopulmonary bypass time, cross-clamping time, and circulatory arrest were reported to be risk factors for early outcome [4, 5, 7, 8]. In our series these factors were not significant, especially circulatory arrest. Only three patients at the beginning of the study had circulatory arrest. Now, circulatory arrest has been abandoned, when necessary, for aortic arch repair; we used continuous cerebral perfusion. However, CPB may be contraindicated in the presence of certain medical conditions such as intraventricular hemorrhage; such patients will require surgical palliation.

Palliative surgery or delaying open heart repair in select low weight neonates with CHD does not confer any benefit [4, 5, 10]. It is logical to assume that restoration of cardiovascular physiology should normalize the clinical status of these children. In particular in our series of homogenous CHD, for which we can propose an initial repair, palliation was a significant risk factor of early mortality. In TGA-VSD neonatal repair is recommended to minimize the adverse systemic effects of prolonged cyanosis or congestive heart failure and to decrease the likelihood of pulmonary vascular disease, in the same way pulmonary artery banding my have some deleterious effects at different levels [11, 13]. In our series, 13 patients had complex TGA, nine patients had initial repair, and among the four patients with palliation three died. Early repair of either simple or complex TGA was the best option. We reserved palliation for patients with complex intracardiac anomalies or for those with CPB contraindicated (cerebral hemorrhage).

The majority of the surviving neonates were clinically doing well after early operation [4, 5, 7]. All the survivors were considered to have good cardiac status and were in sinus rhythm in our series. Regarding the clinical neurodevelopment state, obvious mental retardation was observed in two patients. The majority of these patients joined the normal curve for LBW neonates not affected by a CHD. We find the same causes of late death in this population of LWB neonates as in all the patients with TGA operated on in our institution. Losay and colleagues [12] reported that the primary cause of death was coronary related; death occurred secondary to pulmonary stenosis. In our series, two patients were reoperated on for pulmonary stenosis, two and six years after the primary repair. The LBW with TGA and complete repair during the neonatal period, when they have turned the initial operative challenge, have the same future in terms of survival and late reoperation as the patients with a birth weight more than 3,000 grams operated on for TGA [15].

Early repair with one step anatomical repair for neonates with transposition of the great arteries and under 2 kg is associated with an acceptable risk. We recommend palliation for complex intracardiac anomalies or if cardiopulmonary bypass is not mandatory.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
References
 
DR CHARLES D. FRASER, JR (Houston, TX): Thank you for that very nice presentation and we’re all indebted to you for sharing this large experience, which helps us understand how to manage this difficult group of patients.

I would personally say of babies presenting less than 2 kg, patients with transposition are often more amenable to aggressive repair than some of our other lesions. And if I understood your data correctly, the mean weight at presentation was around 1,400 grams and the mean weight at the time of surgery was around 2 kg. And there was a range; I believe the smallest baby at the time of presentation was around 950 grams and at the time of surgery was just over 1,400 grams. So, presumably the decision was made in some of these babies to grow them a bit before surgery. And we find that sometimes that’s a mistake. And I wonder if you could help us tease out the issues that would help you decide which babies to let grow and which babies just to go ahead and decide to operate on. Because sometimes we find that even in the very small babies that are small for gestational age, we can’t get them to grow and we just have to go ahead and operate. So how do you decide about that?

DR ROUSSIN: Every time it was a discussion between the neonatologist and the cardiologist and the surgeon. But for the patient between 1,500 grams and 2 kg, we don’t wait for the operation, we operate the baby even if it was hypotrophic for the gestational age, we operate as soon as possible.

DR ERLE H. AUSTIN III (Louisville, KY): Is there a weight below which your surgeons will not operate?

DR ROUSSIN: No. As you can see in our series, a patient was operated and had an arterial switch operation at 45 days. And now we operate left ventricular mass and volume. And if a patient was referred to our institution later, we have defined ratio, left ventricular mass, and left ventricular volume; if this ratio is more than 2.5, we make arterial switch operation even if the patient is more than one month old.

DR AUSTIN: I was more interested about the early presentation, such as the child who presented at 950 grams. Would your surgeons operate at 950 grams? Why did you wait until 1,400 grams?

DR ROUSSIN: I don’t understand your question.

DR ALAIN SERRAF (Le Plessis Robinson, France): As a coauthor of this paper I’ll try to answer some of your questions.

The smallest patient who received an arterial switch weighed 1.2 kilo. By now, I think that we would allow patients below 1 kg to grow a little bit. At that level I am not sure that the effects of cardiopulmonary bypass are more deleterious than surgery because of immaturity of the tissue and the membranes.

DR AUSTIN: So what is the lowest weight at which you will operate?

DR SERRAF: 1.2 kilogram.

DR EMILE M. BACHA (Chicago, IL): Just a clarification. I think that complex TGA are actually easier to take care of postop if they have a complete anatomical repair versus a palliation in the form of a PA [pulmonary artery] band. So I’m not sure what you said, but for complex TGA, ie, TGA with VSD, I think that a complete anatomical repair makes more sense in the less than 2 kilo patients. Do you agree or not?

DR ROUSSIN: Yes, I agree.

DR MARCO RICCI (Miami, FL): More than the absolute weight, one could also be concerned about the gestational age, particularly as it relates to pulmonary vascular resistance. In some of these babies that are very premature, the pulmonary vascular resistance might be elevated. That goes back a little bit to Dr Fraser’s point. I wonder whether it would be more beneficial to wait maybe a few weeks in these patients to avoid the period of maximally elevated pulmonary resistance, which could complicate significantly the postoperative course. I am somewhat surprised to see that in your series, which is quite large, you haven’t had any problems in terms of elevated pulmonary resistance requiring, for instance, mechanical support.

DR SERRAF (Les Plessis Robinson, France): If you don’t mind, I will answer this question too. Although pulmonary hypertension is theoretically prone to develop in this subset of patients, we never have to face uncontrolled pulmonary hypertensive crisis, even in those very immature patients. Indeed, nitric oxide was always effective in these patients and we never have to regret to do this operation as early as we can do it.

DR FRANÇOIS LACOUR-GAYET (Denver, CO): Just a short question. We are seeing in this series that only three patients had circulatory arrest. Could you elaborate on the strategy of doing bicaval cannulation and full flow even in these very small weights.

DR ROUSSIN: Actually we don’t use circulatory arrest, never, because we use full flow perfusion even if the aortic arch needs to be repaired.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 

  1. Serraf A, Lacour Gayet F, Bruniaux J, et al. Anatomic correction of transposition of the great arteries in neonates J Am Coll Cardiol 1993;22:193-200.[Abstract]
  2. Rosenthal GL, Wilson DP, Permutt T, Bougham JA, Ferencz C. Birth weight and cardiovascular malformations: a population based studyThe Baltimore-Washington Infant Study. Am J Epidemiol 1991;133:1273-1281.[Abstract/Free Full Text]
  3. Pawade A, Waterson K, Laussen P, Karl TR, Mee RB. Cardiopulmonary bypass in neonates weighing less than 2.5 kg: analysis of the risk factors for early and late mortality J Card Surg 1993;8:1-8.[Medline]
  4. Reddy VM, Mc Elhinney DB, Sagrado T, Parry AJ, Teitel DF, Hanley FL. Results of 102 cases of complete repair of congenital heart defects in patients weighing 700 to 2500 grams J Thorac Cardiovasc Surg 1999;117:324-331.[Abstract/Free Full Text]
  5. Rossi FR, Seiden HS, Sadeghi AM, et al. The outcome of cardiac operations in infants weighing two kilograms or less J Thorac Cardiovasc Surg 1998;116:28-32.[Abstract/Free Full Text]
  6. Beyens T, Biarent D, Bouton JM, et al. Cardiac surgery with extracorporeal circulation in 23 infants weighing 2500 g or less: short and intermediate term outcome Eur J Cardiothorac Surg 1998;14:165-172.
  7. Bové T, François K, De Groote K, et al. Outcome analysis of major cardiac operation in low weight neonates Ann Thorac Surg 2004;78:181-187.[Abstract/Free Full Text]
  8. Oppido G, Napelone CP, Formigari R, et al. Outcome of cardiac surgery in low birth weight and premature infants Eur J Cardiothorac Surg 2004;26:44-53.[Abstract/Free Full Text]
  9. Prêtre R, Tamisier D, Bonhoeffer P, et al. Results of the arterial switch operation in neonates with transposed great arteries Lancet 2001;357:1826-1830.[Medline]
  10. Chang AC, Hanley FL, Lock JE, Castaneda AR, Wessel DL. Management and outcome of low birth weight neonates with congenital heart disease J Pediatr 1994;124:461-466.[Medline]
  11. Serraf A, Comas JV, Lacour Gayet F, Bruniaux J, Bouchart F, Planche C. Neonatal anatomic repair of transposition of the great arteries and ventricular septal defect Eur J Cardiothorac Surg 1992;6:630-634.[Abstract]
  12. Losay J, Touchot A, Serraf A, et al. Late outcome after arterial switch operation for transposition of the great arteries Circulation 2001;104(suppl I):I121-I126.
  13. Wernovsky G, Mayer JE, Jonas RA, et al. Factors influencing early and late outcome of the arterial switch operation for transposition of the great arteries J Thorac Cardiovasc Surg 1995;109:289-302.[Abstract/Free Full Text]
  14. Lacour Gayet F, Piot D, Zoghbi J, et al. Surgical management and indication of left ventricular retraining in arterial switch for transposition of the great arteries with intact ventricular septum Eur J Cardiothorac Surg 2001;20:824-829.[Abstract/Free Full Text]
  15. Serraf A, Roux D, Lacour Gayet F, et al. Reoperation after the arterial switch operation for transposition of the great arteries J Thorac Cardiovasc Surg 1995;110:892-899.[Abstract/Free Full Text]



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