First-stage palliation for hypoplastic left heart syndrome

Comparison of Norwood Shunt Types: Do the Outcomes Differ 6 Years Later? Eric M. Graham, MD, Sinai C. Zyblewski, MD, Jacob W. Phillips, MD, Girish S. Shirali, MBBS, Scott M. Bradley, MD, Geoffery A. Forbus, MD, Varsha M. Bandisode, MD, and Andrew M. Atz, MD Divisions of Pediatric Cardiology and Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina Background. A modification to the Norwood procedure involving a right ventricle-to-pulmonary artery (RV-PA) shunt may improve early postoperative outcomes. Concerns remain about the effect of the right ventriculotomy required with this shunt on long-term ventricular function. Methods. Between January 2000 and April 2005, 76 patients underwent the Norwood procedure, 35 with a modified Blalock-Taussig shunt (mbts) and 41 with a RV-PA shunt. Patients were monitored until death or September 1, 2009, with an average follow-up of 6.8 years. Cardiac catheterization, echocardiograms, perioperative Fontan courses, and need for cardiac transplantation were compared between groups. Results. Cumulative survival was 63% (22 of 35) in the mbts group vs 78% (32 of 41) in the RV-PA group (p 0.14). Pre-Fontan echocardiography revealed poorer ventricular function in RV-PA patients (p 0.03). Cardiac transplantation was required in 6 of 32 (19%) patients with a prior RV-PA shunt vs 1 of 23 (4%) in the mbts group (p 0.06). This results in an almost identical cumulative transplant-free survival between groups; 60% (21 of 35) in the mbts group and 63% (26 of 41) in the Conclusions. Neither shunt offers a clear survival advantage through an average follow-up of 6.8 years. The RV-PA shunt results in impaired late ventricular function that may result in an increased need for cardiac transplantation. (Ann Thorac Surg 2010;90:31 5) 2010 by The Society of Thoracic Surgeons First-stage palliation for hypoplastic left heart syndrome (HLHS) remains a challenging surgical intervention. The right ventricle to pulmonary artery (RV-PA) shunt is a recent modification with potential advantages compared to the modified Blalock-Taussig shunt (mbts) [1 6]. These advantages may include more balanced systemic, pulmonary, and coronary blood flow, with an improved resistance to physiologic insults such as cardiac arrest [7]. Several institutions have reported favorable early outcomes, including decreased surgical mortality and interstage death, for patients undergoing a Norwood procedure with an RV-PA shunt [8 12]. Despite reports of favorable early outcomes, three different single-institution series have failed to show a significant advantage of one shunt type over the other through stage 2 palliation [13 15]. Concerns remain about the required ventriculotomy after the RV-PA shunt and its long-term effects on ventricular function. The objectives of this study were to compare the clinical course and outcomes of the two shunts at the time of Fontan completion and to determine whether either shunt offered an advantage with longer follow-up. Material and Methods Approval of the study and a waiver of the need for parental consent were obtained from the Institutional Review Board of Medical University of South Carolina. Accepted for publication March 16, 2010. Address correspondence to Dr Graham, Medical University of South Carolina, 165 Ashley Ave, MSC 915, Charleston, SC 29425; e-mail: grahamem@musc.edu. Study Patients From January 2000 to April 2005, Norwood procedures were performed in 80 consecutive patients with a systemic right ventricle and aortic arch obstruction. Patients were not included after this date due to our participation in the Pediatric Heart Network s Single Ventricle Reconstruction Trial [16]. Hypoplastic left heart syndrome was present in 70 patients, and right ventricle-dominant unbalanced atrioventricular septal defect with aortic arch hypoplasia in 10. Four patients were excluded due to conversions between the two shunts and the potentially confounding effects of both shunt types in a single patient. Of the 76 remaining patients, 35 underwent a mbts and 41 a RV-PA shunt. The two types of shunt were not used concurrently: all patients with a RV-PA shunt, but only 3 patients with a mbts were operated on after May 2002. Patient characteristics before Norwood palliation were similar between groups, including the presence of an intact atrial septum in 5 (3 mbts, 2 RV-PA), gestational age at birth (38.2 weeks mbts, 38.3 weeks RV-PA) and the presence of extracardiac or genetic defects in 7 (4 mbts, 3 RV-PA). The early outcomes from initial Norwood palliation through the second-stage palliation in this cohort have previously been reported [15]. Patient Courses Patient courses were reviewed and compared between the two groups from the initial Norwood palliation through September 1, 2009. The groups were compared for suitability for and outcome after Fontan completion, 2010 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2010.03.078

32 GRAHAM ET AL Ann Thorac Surg NORWOOD SHUNT TYPES: 6 YEARS LATER 2010;90:31 5 deaths, and listing for or receiving a cardiac transplant. Our institutional practice is to perform a complete pre- Fontan echocardiogram and cardiac catheterization at age 30 to 36 months and to proceed with Fontan completion at age 36 to 42 months (typically a fenestrated extracardiac conduit). At the time of pre-fontan assessment, right ventricular systolic function was qualitatively graded on an ordinal scale from 1 (normal) to 4 (severe dysfunction), and tricuspid regurgitation severity was qualitatively graded from 1 (none) to 4 (severe). Given the predominately noncontemporaneous groups, blinded assessment was not possible. Standard 12-lead surface electrocardiograms at the time of pre-fontan admission were reviewed for maximal QRS duration. The occurrence of intraventricular conduction delay, defined as a QRS duration exceeding the 98th percentile for age, was recorded. Patient records were reviewed for ventricular rhythm abnormalities requiring therapy. Determination of Fontan Suitability Surviving patients who had not undergone Fontan completion or cardiac transplantation by September 1, 2009, were categorized into two groups: those anticipating Fontan completion and those in whom Fontan completion was intentionally being delayed in lieu of consideration for cardiac transplant. Those in the latter category included patients listed for cardiac transplantation, as well as patients not yet listed but deemed inappropriate Fontan candidates. Survival information was complete in all patients. Three patients whose Fontan completion was performed at another institution were not included in the perioperative Fontan description (2 patients in the mbts group and 1 patient in the RV-PA group). Statistical Analyses Data are presented as median (range) and mean standard deviation, as appropriate. Groups were compared using the Fisher s exact test, 2 analysis, Kaplan- Meier survival analysis, and the log-rank test, Mann- Whitney rank sum test, or the unpaired t-test assuming unequal variance, as appropriate. Statistical significance was defined as p 0.05. Results Patient Courses Hospital morbidity and mortality after the Norwood procedure, interstage mortality, and outcome after stage 2 palliation did not differ between the two groups, as previously described (Fig 1) [15]. The courses of the 23 patients in the mbts group and 33 patients in the RV-PA group who survived stage 2 palliation are shown in Figure 2. Average length of follow-up for survivors in the entire group was 6.8 years (range, 4.4 to 9.7 years). Follow-up was 8.3 1.0 years in the mbts group vs 5.7 0.8 years in the RV-PA group (p 0.0001). Pre-Fontan Assessment Unblinded qualitative echocardiographic assessment revealed significantly poorer ventricular function in the RV-PA group; the median echocardiographic score was 1 (range, 1 to 2) for mbts vs 2 (range, 1 to 4) for RV-PA (p 0.03). The degree of tricuspid regurgitation was similar between groups. The median echocardiographic score was 2 (range, 1 to 4) in both groups (p 0.96). There were no differences in hemodynamic data derived from cardiac catheterization between groups, other than an unexplained lower diastolic and mean systemic arterial blood pressure in the RV-PA group (Table 1). Fig 1. Postoperative and interstage mortality after the Norwood procedure. a p 0.75; b p 0.13 of hospital survivors; c 34 of 41 patients (83%) who underwent a right ventricle-to-pulmonary artery (RV- PA) shunt survived to stage 2 palliation vs 23 of 35 patients (66%) who underwent a modified Blalock-Taussig shunt (mbts; p 0.14).

Ann Thorac Surg GRAHAM ET AL 2010;90:31 5 NORWOOD SHUNT TYPES: 6 YEARS LATER 33 Fig 2. Clinical courses after stage 2 palliation in patients undergoing modified Blalock-Taussig shunt (mbts) and right ventricle-topulmonary artery (RV-PA) shunt. Fontan Hospital Course At the time of Fontan completion, there was no difference between the two groups in age, weight, time on mechanical ventilation, intensive care unit length of stay, or total hospital length of stay (Table 2). One patient in the mbts group died in the hospital on postoperative day 11 secondary to multiorgan failure. Electrocardiograms at the time of pre-fontan admission revealed no difference between groups in median QRS duration: 90 msec (range, 78 to 120 msec) in mbts vs 96 Table 1. Pre-Fontan Cardiac Catheterization Data Variable mbts (n 21) Mean SD RV-PA (n 26) Mean SD p Value Arterial blood pressure, Systolic 95 13 88 14 0.06 Diastolic 51 7 44 6 0.0007 Mean 70 9 61 9 0.002 Left atrial pressure, 8 5 8 3 0.67 Mean PA pressure, 12 4 12 4 0.65 Transpulmonary 4 1 4 2 0.77 gradient, Ventricular EDP, 8 3 8 4 0.83 Oxygen saturation, % Systemic 84 5 83 4 0.31 Superior vena cava 64 4 64 6 0.81 Qp/Qs 0.7 0.2 0.7 0.2 0.97 PVR, units m 2 1.7 0.9 1.5 0.8 0.65 Nakata index, mm 2 /m 2 272 57 272 69 0.99 EDP end diastolic pressure; mbts modified Blalock-Taussig shunt; PVR pulmonary vascular resistance; RV-PA right ventricle-to-pulmonary artery shunt; SD standard deviation. msec (range, 76 to 126 msec) in RV-PA (p 0.21). Intraventricular conduction delay, defined as exceeding 72 msec ( 98th percentile for age appropriate normal [17]) was present in all patients regardless of previous shunt type. Two patients in each group required therapy for ventricular rhythm abnormalities at any time (p 0.99). Survival and Outcomes One patient in the RV-PA group died between the second-stage palliation and Fontan completion (Fig 2). Cumulative survival from initial Norwood palliation through September 1, 2009, was 63% (22 of 35) in the mbts group and 78% (32 of 41) in the RV-PA group (p 0.14; Fig 3). Despite an average 2.6-year shorter follow-up period in the RV-PA group, a trend was shown in these patients toward an increased need for cardiac transplantation. One patient in the mbts group required cardiac transplantation compared with 6 in the RV-PA group (4 before and 2 after Fontan palliation; p 0.06). All cardiac transplantations were required secondary to some combination of myocardial failure and atrioventricular valve Table 2. Fontan Hospitalization Data Variable a mbts (n 16) RV-PA (n 20) p Value Age, y 3.7 1.0 3.6 1.1 0.98 Weight, kg 14.3 1.2 14.7 2.7 0.50 Mechanical ventilation, h 25 (5 38) 19 (11 412) 0.17 Length of stay, d Intensive care unit 2.8 (1.8 11.0) 2.0 (1.0 27.8) 0.15 Hospital 12 (7 44) 11 (8 38) 0.52 Hospital death. No. 1 0 0.46 a Continuous data are reported as mean standard deviation or median (range), as appropriate. mbts modified Blalock-Taussig shunt; RV-PA right ventricle to pulmonary artery shunt.

34 GRAHAM ET AL Ann Thorac Surg NORWOOD SHUNT TYPES: 6 YEARS LATER 2010;90:31 5 Fig 3. Kaplan-Meier plot shows survival after Norwood palliation with a modified Blalock-Taussig shunt (mbts, solid line) and right ventricle-to-pulmonary artery shunt (RV-PA, dashed line). regurgitation. Four additional patients in the RV-PA group are currently under consideration for cardiac transplantation, one of whom is currently listed (Fig 2). When the two outcomes of death and cardiac transplantation are combined, there appears to be a potential early survival advantage of the RV-PA that is offset over time by an increased requirement for cardiac transplantation (Fig 4). This results in an almost identical cumulative transplant-free survival at 6 years between groups: 60% (21 of 35) in the mbts group and 63% (26 of 41) in the Regardless of whether there is an early survival benefit associated with the RV-PA shunt, concerns remain about the required ventriculotomy and its effects on long-term RV function and the potential for ventricular dysrhythmias. Once the superior cavopulmonary connection is completed and the shunt is removed, any physiologic advantages of one shunt type over the other are presumably removed; however, the deleterious effects of a ventriculotomy may persist. We found any potential early survival advantage with the RV-PA shunt in our series was offset over time by an increased requirement for cardiac transplantation, resulting in an almost identical cumulative transplant-free survival between groups of 60% (21 of 35) in the mbts group and 63% (26 of 41) in the The RV-PA shunt results in unique ventricular physiology in which there is no period of isovolumic relaxation or contraction [19, 20]. Although not specifically evaluated in single-ventricle physiology, the importance of the isovolumic phase has been demonstrated in biventricular physiology [21]. Conflicting results regarding RV function after the RV-PA shunt have also been reported [14, 22]. Complicating the interpretation of these results is that there is no uniformly accepted method for quantifying systemic RV function. Nonetheless, qualitative assessment of systolic RV function has been demonstrated to be a predictor of survival [23]. In our cohort of patients, we previously found no difference in RV systolic function at the time of superior cavopulmonary anastomosis [15]. Despite this, systolic ventricular function at the time of Fontan completion was qualitatively worse in patients who had received an RV-PA shunt. It is unclear if the declining function in the RV-PA group is secondary to Additional Analysis Further analyses were performed based on the intention to treat. The 4 patients who underwent conversion from a RV-PA to a mbts were included and the data were reanalyzed. There was no change in the results. Of these 4 patients, 2 died before stage 2 palliation and the remaining 2 underwent Fontan completion and are transplant-free survivors. Comment In an effort to improve postoperative outcomes, numerous institutions have revisited the use of a RV-PA shunt in patients undergoing the Norwood procedure. Despite the theoretic advantages of the RV-PA shunt and some favorable early clinical reports, the current literature fails to consistently demonstrate a survival advantage over the mbts [9 15, 18]. These differences could be explained by the hypothesis that the RV-PA shunt offers an early survival advantage only in some institutions or in some patient populations that may not be present uniformly across institutions. Fig 4. Kaplan-Meier plot shows of freedom from death or cardiac transplant after Norwood palliation with a modified Blalock-Taussig shunt (mbts, solid line) and right ventricle-to-pulmonary artery shunt (RV-PA, dashed line).

Ann Thorac Surg GRAHAM ET AL 2010;90:31 5 NORWOOD SHUNT TYPES: 6 YEARS LATER the ventriculotomy, the change in ventricular loading conditions with the reinstitution of the isovolumic phases, or both. Despite echocardiographic evidence of worse ventricular function in the RV-PA group, hemodynamic data derived from cardiac catheterization and postoperative Fontan courses were essentially identical between the two groups. Nonetheless, ventricular dysfunction likely had some effect in the trend towards cardiac transplantation in patients who received a RV-PA shunt, and we documented a trend towards cardiac transplantation in patients that have undergone a Norwood procedure with a RV-PA shunt. This may be due to our institutional preference to complete Fontan palliation at age 36 to 42 months. This time frame is later than some institutions, and thus provides the opportunity for longer follow-up before proceeding with Fontan palliation. This underscores the importance of not only a larger multiinstitutional study but also of longer follow-up. Limitations of this study are its relatively small sample size, its retrospective, nonrandomized design, and the inherit biases associated with the use of predominately historical controls. Although there were no significant changes during the study period in support strategy or postoperative management, subtle changes undoubtedly occurred. As discussed, qualitative assessment of RV function, especially when unblinded, has the potential for bias. In conclusion, neither the RV-PA shunt nor the mbts offers a clear survival advantage through an average follow-up of 6.8 years. The RV-PA shunt results in impaired late ventricular function that may lead to an increased need for cardiac transplantation, resulting in an almost identical cumulative transplant-free survival between groups. References 1. Sano S, Ishino K, Kawada M, et al. 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