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Click here to read this article as a CME activity
a Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
b Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei, Taiwan
Accepted for publication August 11, 2008.
* Address correspondence to Dr Sano, Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan (Email: s_sano{at}cc.okayama-u.ac.jp).
Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.
| Pediatric cardiac surgery:
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Methods: Between February 1998 and June 2007, 62 patients with HLHS underwent a Norwood procedure by using right ventricle to pulmonary artery conduit (median age, 9 days [range, 1 to 57]; median body weight 2.7 kg [range, 1.6 to 3.9 kg]). The subsequent 47 patients underwent a bidirectional Glenn procedure (stage 2). Thirty-two patients underwent a modified Fontan procedure (stage 3). Follow-up was complete (median, 32 months; range, 1 to 101).
Results: Hospital mortality after the Norwood procedure was 8% (5 of 62 patients). Between stages, 9 patients died, 3 before stage 2 and 6 before stage 3. There was 1 late death after stage 3. Overall survival was 76% (47 of 62). The estimated 1-year and and 5-year survival rates were 80% and 73%, respectively. Using the any-mortality as the endpoint, prematurity (gestational age <37 weeks), body weight less than 2.5 kg at stage 1 operation, and tricuspid regurgitation 2+ or more were associated with mortality. Using Cox regression analysis, body weight less than 2.5 kg and tricuspid regurgitation 2+ or more were two independent factors associated with midterm survival.
Conclusions: From 9 years of experience, despite good early survival after Norwood stage 1 palliation, low body weight and tricuspid valve regurgitation were still associated with worse outcome. More efforts should be made to improve the late results for patients with hypoplastic left heart syndrome.
Hypoplastic left heart syndrome (HLHS) was a fatal disease until only a recent quarter century ago. About 95% of affected infants died within the first month of life without early intervention [1]. The development of Norwood stage palliation [2] greatly improved the outcome of the patients with HLHS. However, with the significant improvement in surgical intervention, the Norwood procedure is a technical challenge and still carries significant mortality and morbidity.
Many authors have previously reported risk factors for the Norwood procedure, including anatomical diagnosis, aortic atresia, smaller ascending aortic diameter, prematurity, low birth weight, additional cardiac anomalies, noncardiac anomalies, chromosomal abnormalities, lower preoperative pH, initial operations after 14 or 30 days, fetal diagnosis, longer circulatory arrest or cardiopulmonary bypass time, and the presence of significant tricuspid regurgitation (TR); however, most of these reports are focused on the early postoperative mortality and are usually not consistent from study to study [3–6].
Furthermore, these reports were concerned with the Norwood stage 1 palliation (S1P) with a systemic to pulmonary shunt as the source of pulmonary blood flow. Recent modification of S1P using a right ventricle to pulmonary artery (RV-PA) shunt provided stable hemodynamics characterized by a higher diastolic pressure [3, 4] and led to an excellent early survival [3–6]. We previously reported that RV-PA shunt will avoid pulmonary overflow after S1P, which should be beneficial especially for low body weight infants. Although the low body weight was identified as a risk factor for mortality even in large centers with good results [7, 8], whether the same risk factor applied for the modification of S1P with the use of the RV-PA shunt is not clear yet.
The current study was undertaken to evaluate a single institution's 9-year experiences with the Norwood S1P using the RV-PA shunt, and to try to identify the factors associated with the outcome.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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The medical, operative records, and angiographic and echocardiographic data for all patients were reviewed. Anatomic diagnosis was based on review of echocardiography and operative findings. Follow-up status was determined by review of the medical records and contact with the referring cardiologists. Follow-up was complete for all patients.
Operative Procedure
Most of the procedure with the PV-PA shunt was performed as previously described; however, there were some modifications in our technique during 9-year time period [3, 4].
Initially, an arterial cannula was inserted into a 3.5-mm expanded polytetrafluoroethylene (ePTFE) tube (Gore-Tex; W. L. Gore & Associates, Flagstaff, AZ) that was anastomosed to the innominate artery (Fig 1A). To perfuse the whole body as much as possible, this single arterial cannula was soon changed to a dual arterial cannula. Another arterial cannula was inserted into the descending aorta through the ductus arteriosus. Therefore, most of the cardiopulmonary bypass was established by dual arterial perfusion and single atrial or bicaval drainage. After insertion of a venous cannula into the right atrium, cardiopulmonary bypass was commenced at a flow rate of 150 to 180 mL · min–1 · kg–1. During the cooling phase, the ductus arteriosus was ligated and divided (proximal to the cannulation site). Then a better operative field was obtained, and the descending thoracic aorta was extensively mobilized by blunt dissection as far distally as possible.
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Another important technical modification is reconstruction of neoaorta. Under selective cerebral perfusion through the innominate artery, the aortic arch was opened inferiorly and this incision was extended down into the ascending aorta to the level of the transected end of the main PA (Fig 1B). The aortic arch and ascending aorta just opposite the site of the innominate artery were sutured inferiorly to extend the width of aortic arch and shortened the neoaortic suture line (proximal arch plasty). This modification shifted the proximal aortic arch inferiorly. The technical modification of distal neoaortic reconstruction was the application of Brawn's modification (distal arch plasty; Fig 1C) [3–6]. Combined with proximal arch plasty and distal arch plasty, the neoaorta was reconstructed directly in most of the patients without any patch material.
Right ventriculotomy was also an important technical point. Initially, the ventricular hole was created by scissors or knife, which was changed to coronary puncher to create a small hole constantly and to prevent late obstruction at the shunt anastomosis. It was also important to punch out a piece of RV muscle underlying the ventriculotomy. The size of the ventricular hole was approximately 1 mm bigger than the ePTFE graft. The RV-PA shunt was placed to the left of the neoaorta in all patients, and was anastomosed to the right ventriculotomy during rewarming using 6-0 polypropylene suture. Modified ultrafiltration was routinely used after weaning from cardiopulmonary bypass.
Delayed sternal closure was performed routinely except in 1 patient, who died of tamponade. A bidirectional Glenn (BDG) procedure (stage 2 palliation) was performed with or without cardiopulmonary bypass after a mean interval of 5.5 months. A Hegar dilator sized 4 to 5 mm was inserted into the left PA through the right PA before establishment of the BDG procedure. If the RV-PA graft was short, the same size ePTFE graft was interposed to the graft of the RV-PA shunt. The RV-PA was left open as an additional pulmonary blood supply if there was no significant tricuspid valve regurgitation.
The Fontan procedure (stage 3 procedure) was performed at approximately 2 years of age. A lateral tunnel cavopulmonary connection was constructed by means of an ePTFE patch or a right atrial flap if the patients were small. Extracardiac cavopulmonary connection using an ePTFE graft was chosen if the body weight of the patients was more than 10 kg. Heart transplantation was not a realistic option at any stage because of the strict regulation in our country.
Statistical Analysis
The medical records, operative reports, and angiographic and echocardiographic results for all patients were reviewed. Follow-up was complete for all patients.
The primary outcomes of this study were the mortality after Norwood S1P and the late mortality during the follow-up period. Patient and operative variables were assessed as potential predictors of stage 1 mortality and overall mortality. Data are presented as means ± SD for medians and ranges as indicated. Differences between the two groups were determined with the Fisher exact test, Mann-Whitney rank-sum test, or Student t test, as appropriate. Survival estimates were obtained from the Kaplan-Meier model. For analyzing the factors associated with survival function, the log-rank test was used. The Cox proportional hazards model was used for comparing the risk factors for mortality.
Data were analyzed using SPSS 11.5 (SPSS, Chicago, Illinois). Any p value less than 0.05 was considered to have statistical significance. Not significant (NS) indicates statistical insignificance.
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Results |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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During the study period, 7 patients received bilateral PA banding as the first palliation procedure (because of intact atrial septum, n = 3; low birth weight, n = 1; shock, n = 1; congenital complete heart block, n = 1; and PA banding at other institution, n = 1), and these patients were not included in this study.
The extracardiac diagnosis and chromosomal abnormalities are summarized in Table 1.
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Operative Mortality With Stage 1 Palliation
There were 5 hospital deaths. The cause of death included sudden death (n = 2), heart failure due to hypertrophic cardiomyopathy (n = 1), tamponade (n = 1), and methicillin-resistant Streptococcus aureus sepsis (n = 1). Therefore, the hospital mortality among 62 patients who underwent S1P with the RV-PA shunt was 8%. There were 3 late deaths due to shunt obstruction (n = 2) and suffocation due to milk aspiration (n = 1). Four patients underwent additional systemic-pulmonary artery shunt for future biventricular repair.
Follow-Up
Among the survivors, 47 patients received bidirectional cavopulmonary shunt (BDG). There were 2 hospital deaths, due to heart failure (n = 1) and heparin-induced thrombocytopenia (n = 1). Three patients died late after the BDG procedure, 1 of heart failure, 1 of severe TR, and 1 of pneumonia. One patient required take-down of his BDG owing to high central venous pressure and died eventually. In summary, there were 6 patients who died after stage 2, and 4 of them had poor heart function before operation. Thirty-two patients underwent the Fontan procedure. There was 1 late death after the Fontan procedure. Two patients received biventricular repair, and 2 are waiting for biventricular repair. Therefore, the overall survival to 9 years was 76%. The outcome of these patients is summarized in Figure 2.
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Intraoperative variables including duration of cardiopulmonary bypass, duration of myocardial ischemic time, duration of descending aortic cross clamp time were not significantly different between the survivors and nonsurvivors for Norwood S1P (Table 2).
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For patients with either one of the three factors (prematurity, body weight <2.5 kg, TR 
2), the overall mortality was 48% (13 of 27); and for patients with none of the three factors, the overall mortality was 7% (2 of 35) in this cohort.
Using the whole cohort for Kaplan-Meier survival analysis, the estimated 1-year survival rate and 5-year survival rates were 80% and 73%, respectively (Fig 3).
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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There was a significant improvement in the mortality associated with the Norwood procedure in recent years. Mahle and coworkers [9] reported outcomes of 840 patients who underwent the Norwood procedure for HLHS between 1984 and 1999. The overall 1-year survival was 51%; however, later year of surgery was associated with significantly improved survival. Operative survival for the period 1995 to 1998 was 71.4%. Gaynor and colleagues [8] reported that 158 patients received the Norwood procedure between 1998 and 2001; the operative survival was 77%, and 1-year survival was 66%. A more recent experience in Ann Arbor reported the operative survival was 79% for 111 patients who received the operation between 2001 and 2003 [7]. The operative survival of our series (92%) also showed good early results.
Since we modified the Norwood S1P using an RV-PA shunt, our results showed a marked improvement and excellent early survival [3–6]. We think that the RV-PA shunt provided advantages of hemodynamics characterized by a higher diastolic pressure, improved coronary perfusion, and less volume load on the RV [3, 4], which led to an excellent early survival [3–6]. The midterm survival in this report is also quite promising, with 1-year survival of 80% and 5-year survival of 73%, compared with other series at 40% to 60% survival at 5 years [9–12]. In the recent series at Childrens' Hospital of Philadelphia, the estimated 3-year survival was 73% in the RV-PA shunt group [13].
Factors Associated With Outcomes
There were some variables that have been shown as risk factors for operative mortality. Prematurity is a risk factor for operative mortality as reported by Daebritz and colleagues [12]. Significant TR was known as a poor prognostic factor in previous reports [14, 15]. Low body weight at the time of Norwood S1P also has been identified as a predictor of mortality [11, 16]. At Children's Hospital of Philadelphia, operative mortality after the Norwood procedure for 67 patients weighing less than 2.5 kg at the time of surgery between 1990 and 1997 was 51%, and this figure improved to 38% between 1998 and 2001 [3–6].
In this study, the prematurity, body weight less than 2.5 kg, TR 2+ or greater were not associated with operative mortality at S1P; however, these were significantly associated with the late mortality. All the 4 premature babies died later, even though all were early survivors. The early operative mortality was only 16% for the 18 patients (3 of 18) weighing less than 2.5 kg at S1P, but 7 early survivors died in the late stage, with the overall mortality increased to 55% (10 of 18).
Many authors suggested that the management of pulmonary blood flow is problematic in these low body weight infants. The traditional modified Blalock-Taussig shunt using 3.5-mm graft resulted in pulmonary overcirculation and systemic malperfusion, and a 3.0-mm graft leaves little room for technical error and increases risk of thrombosis. In our series, the 5-mm RV-PA shunt was used in the majority of patients, but a 4-mm graft was used in 6 patients including low body weight infants (3 patients were less than 2.0 kg). The patients with a 4-mm RV-PA shunt all survived initially, but the late mortality rate was 66% (4 of 6), including 2 sudden shunt occlusions. We think the management of low body weight patients with a small RV-PA shunt (4 mm) could only improve short-term outcome, and possibly we need to modify the treatment strategy after S1P to prevent late mortality.
Significant TR is also a risk factor for mortality, and some may suggest heart transplantation is the choice for these patients. In this series, more than half (7 of 13; 54%) of the patients with TR 2+ or greater died before Fontan operation, including 2 patients with tricuspid valve plasty and 1 with valve replacement. The finding that a failing right ventricle in systemic circulation is not compatible with life is not surprising, and unfortunately, heart transplantation is not a realistic management option in our country.
The anatomic subtypes of HLHS [9, 17–19], especially aortic atresia, have been considered as a risk factor for poor outcome. Our data did not show significant difference in the anatomic subtypes, possibly because of limited sample size.
The other traditional risk factors such as bypass time, age more than 14 days at operation, and small ascending aortic diameter were not associated with mortality, similar to a recent report from Ann Arbor [7]. The chromosomal abnormalities, noncardiac anomalies were also reported risk factors associated with the outcome [7], but we did not demonstrate their association with outcome in this study.
These findings imply that we could successfully manage the patients in the early perioperative and postoperative stages, but substantial late mortality occurred; and the risk factors (low body weight, TR) were similar to the previously reported risk factors for early mortality.
Late Mortality
The persistent incidence of interstage death is of great concern, especially during the first year of life among patients who survived the initial hospitalization. Gaynor and colleagues [8] reported that 12% of the survivors of the initial procedure died before 1 year of age, mostly before superior cavopulmonary connection. These deaths are usually sudden and often unexplained. Mahle and associates [9] evaluated the incidence of unexpected death among 536 patients with HLHS who survived the Norwood procedure. Unexpected death occurred in 4.1% of this large group of patients (22 of 536) at a median age of 79 days. In their reports, perioperative arrhythmias and earlier era of surgical procedure were associated with an increased risk for unexpected death. No anatomic subtypes were found to be risk factors for death. Multiple factors may be responsible for the unexplained deaths, including coronary insufficiency, arrhythmia, ventricular dysfunction, residual arch obstruction, PA distortion, restrictive atrial septal defect, and inadequate pulmonary blood flow.
In this study, the interstage mortality is still substantial: 9 (16%) of the early survivors died before Fontan completion. The literature discussing the prevention of late mortality is relatively limited. Recently, intense surveillance after discharge was suggested by Ghanayem and associates [20], and decrease of interstage mortality was shown. Heart transplantation for high-risk patients with HLHS has been suggested [3–6]; however, it was associated with a 27.8% mortality rate and not feasible in our country.
RV-PA Conduit Versus Modified Blalock-Taussig Shunt in Stage 1 Palliation
The study to compare RV-PA conduit and modified Blalock-Taussig shunt for stage 1 palliation is ongoing in United States. In the report from Philadelphia by Ballweg and coworkers [13], there is no difference in survival at 3 years (RV-PA conduit: 73% [59% to 83%] versus modified Blalock-Taussig shunt: 69% [59% to 77%]; p = 0.6). Before stage 2, the RV-PA group had younger age, lower arterial saturation, and higher diastolic blood pressure. At stage 3, there was a tendency toward more ventricular dysfunction, atrioventricular valve regurgitation, and neoaortic valve regurgitation in the RV-PA group. This finding raises the concern about the impact of right ventricular incision on late outcome, although the survival was not different. However, in the report [13, 21], more patients with aortic atresia received an RV-PA conduit, and this variant of HLHS will be likely to receive a modified Blalock-Taussig shunt. Whether anatomic variation, such as aortic atresia (with small aorta and possible coronary circulation compromise) could also have an impact on ventricular function is not well understood. Given that overall survival was not different at the current report, we need more long-term follow-up data from the randomized study, which was supported by the National Insitutes of Health and is still in progress, to understand which surgical strategy will be better, or more suitable for which subset of patients.
Study Limitation
The study spans a long duration, and its retrospective nature and too-small number of patients to perform meaningful subgroup analysis should be recognized as a limitation of this study, although our database collects data prospectively for all the operations. The effect of general improvement in surgical technique and perioperative care as experience accumulated could not be analyzed in the study. Heart transplantation is a choice for HLHS patients with poor right ventricular function, but it is not possible in our country because of a prohibition on pediatric heart transplantation.
In conclusion, with the use of an RV-PA shunt and refinement of surgical technique, the traditional risk factors for Norwood S1P mortality had less impact on early results; however, low body weight and significant TR still had a negative impact on midterm survival. More efforts should be made to improve the long-term results for patients with hypoplastic left heart syndrome.
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Discussion |
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So there are three questions basically: One, neoaortic insufficiency, which I did not see reported in your series. Two, was the tricuspid insufficiency due to the ventriculotomy? And three, did you see any ventricular arrhythmias in the follow-up period?
DR SANO: The answer to the first question, so far we have no neoaortic regurgitation, so far, and they had no repair at all. Number two, tricuspid regurgitation due to ventriculotomies is unknown. We have a few patients, I think there are 4 or 5 patients, who required tricuspid valve repair, but I don't know whether it's due to the tricuspid regurgitation from the ventriculotomy or not. And 1 patient, the late death after the Fontan, who had a tricuspid valve repair twice, and finally, I did the tricuspid replacement and then the sudden death. And that's also the worry to me, the heart failure and tricuspid regurgitation. One patient who had the late death after the Glenn, and I wonder whether it's due to the ventriculotomy or not. I don't know the answer.
DR MAVROUDIS: No arrhythmias?
DR SANO: Ventricular arrhythmia is so far in no patient.
DR MAVROUDIS: So far. Thank you very much.
DR EMILE M. BACHA (Boston, MA): One quick technical question. When you talked about cuffed PTFE, do you mean the ringed Gore-Tex graft? And I'm curious whether you take a piece of a ringed conduit, and use that to close the PA opening, which I think would be a very nice way to deal with the closure of the branch PAs? That's the first question.
The second question is also about tricuspid regurgitation. And I wonder whether you know your incidence. How often do you do tricuspid valvuloplasty either during the first stage or during the second stage? We've had the exact same findings in terms of tricuspid regurgitation being a factor in late survival, and we've become much more aggressive at treating tricuspid valve regurgitation either at the first stage or the second stage.
DR SANO: The answer to the first question, the cuffed Gore-Tex graft is made from just ordinary 5-mm Gore-Tex graft, not ring Gore-Tex. So the same graft, you cut the Gore-Tex and open up, like this, and then in the middle you punch out and then anastomose the actual graft. So this worked like a cuff. And it's very easy to have it hemodilate, or for the interventionist put the balloon to dilate. So out of 62 patients, we only had 1 patient who required patchplasty of the pulmonary arteries.
In answer to the second question, tricuspid regurgitation, I also worried about the tricuspid regurgitation. We have now 4 or 5 patients who had tricuspid valve repair at the time of bidirectional Glenn. I know 1 patient had a dysplastic tricuspid valve, another 3 or 4 had like a normal dilated annulus. So we repaired with autologous pericardium like a ring, patch ring, to enforce, and still have tricuspid regurgitation. And then at the Fontan, we repair again. I don't know whether it's due to ventriculotomy or not, because 80% or more of the patients have no tricuspid regurgitation increased, only some. But there is definitely some patients whose annulus dilates.
DR CHRISTOPHER A. CALDARONE (Toronto, Ontario, Canada): Doctor Sano, one small point: I noticed in the manuscript that you said that if your perception was that the shunt was small, that you would leave the shunt in place at the time of cavopulmonary anastomosis. Could you comment on how often you left the shunt intact at the time of cavopulmonary anastomosis what repercussions there might be doing so.
DR SANO: The reason why I leave the shunt open at the second stage is to increase the blood flow, especially to the left lung. So the left pulmonary artery is closed more and the saturations are little bit more. But if the patient had tricuspid regurgitation, I don't want to have it volume loaded. These patients, I ligate. If the patient has trivial or no tricuspid regurgitation, we usually leave the shunt open. That is on more than 80% of our series.
DR CALDARONE: That's interesting.
DR RODOLFO NEIROTTI (Geneva, Switzerland): I would like to call your attention to the use of biodegradable annuloplasty rings to treat tricuspid valve incompetence. These rings allow the growth of the tricuspid annulus in children and also preserve the normal three-leaflet configuration of the native tricuspid valve.
DR SANO: Thank you. I haven't used this ring, but I'm very interested in it.
DR CALDARONE: Just out of curiosity from the audience, there have been reports on putting the shunt to the right or to the left of the reconstructed aortic arch. Just for interest, by show of hands, how many surgeons would route the shunt to the right versus the left of the reconstructed aortic arch? [Hands raised in audience.] It seems like about twice as many surgeons would leave the shunt to the left. Thank you very much, Dr Sano.
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Acknowledgments |
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