Randomized Controlled Trial

. 2018 May 22;137(21):2246-2253.

doi: 10.1161/CIRCULATIONAHA.117.029375. Epub 2018 Feb 1.

Transplant-Free Survival and Interventions at 6 Years in the SVR Trial

Jane W Newburger¹, Lynn A Sleeper², J William Gaynor³, Danielle Hollenbeck-Pringle⁴, Peter C Frommelt⁵, Jennifer S Li^{6

7

8}, William T Mahle⁹, Ismee A Williams¹⁰, Andrew M Atz¹¹, Kristin M Burns¹², Shan Chen⁴, James Cnota¹³, Carolyn Dunbar-Masterson², Nancy S Ghanayem⁵, Caren S Goldberg¹⁴, Jeffrey P Jacobs¹⁵, Alan B Lewis¹⁶, Seema Mital¹⁷, Christian Pizarro¹⁸, Aaron Eckhauser¹⁹, Paul Stark⁴, Richard G Ohye¹⁴; Pediatric Heart Network Investigators

Affiliations

¹ Boston Children's Hospital and Harvard Medical School, MA (J.W.N., L.A.S., C.D.-M.). jane.newburger@cardio.chboston.org.
² Boston Children's Hospital and Harvard Medical School, MA (J.W.N., L.A.S., C.D.-M.).
³ Children's Hospital of Philadelphia and University of Pennsylvania Medical School, Philadelphia (J.W.G.).
⁴ New England Research Institutes, Watertown, MA (D.H.-P., S.C., P.S.).
⁵ Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee (P.C.F., N.S.G.).
⁶ North Carolina Consortium, Duke University, Durham (J.S.L.).
⁷ East Carolina University, Greenville, NC (J.S.L.).
⁸ Wake Forest University, Winston-Salem, NC (J.S.L.).
⁹ Children's Healthcare of Atlanta and Emory University, GA (W.T.M.).
¹⁰ Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia College of Physicians and Surgeons, NY (I.A.W.).
¹¹ Medical University of South Carolina, Charleston (A.M.A.).
¹² National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (KM.B.).
¹³ Cincinnati Children's Medical Center, OH (J.C.).
¹⁴ University of Michigan Medical School, Ann Arbor (C.S.G., R.G.O.).
¹⁵ Congenital Heart Institute of Florida, St. Petersburg (J.P.J.).
¹⁶ Children's Hospital Los Angeles, CA (A.B.L.).
¹⁷ Hospital for Sick Children, Toronto, Ontario, Canada (S.M.).
¹⁸ Nemours Cardiac Center, Wilmington, DE (C.P.).
¹⁹ Primary Children's Hospital and the University of Utah, Salt Lake City (A.E.).

PMID: 29437119
PMCID: PMC5963989
DOI: 10.1161/CIRCULATIONAHA.117.029375

Randomized Controlled Trial

Transplant-Free Survival and Interventions at 6 Years in the SVR Trial

Jane W Newburger et al. Circulation. 2018.

. 2018 May 22;137(21):2246-2253.

doi: 10.1161/CIRCULATIONAHA.117.029375. Epub 2018 Feb 1.

Authors

Affiliations

¹ Boston Children's Hospital and Harvard Medical School, MA (J.W.N., L.A.S., C.D.-M.). jane.newburger@cardio.chboston.org.
² Boston Children's Hospital and Harvard Medical School, MA (J.W.N., L.A.S., C.D.-M.).
³ Children's Hospital of Philadelphia and University of Pennsylvania Medical School, Philadelphia (J.W.G.).
⁴ New England Research Institutes, Watertown, MA (D.H.-P., S.C., P.S.).
⁵ Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee (P.C.F., N.S.G.).
⁶ North Carolina Consortium, Duke University, Durham (J.S.L.).
⁷ East Carolina University, Greenville, NC (J.S.L.).
⁸ Wake Forest University, Winston-Salem, NC (J.S.L.).
⁹ Children's Healthcare of Atlanta and Emory University, GA (W.T.M.).
¹⁰ Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia College of Physicians and Surgeons, NY (I.A.W.).
¹¹ Medical University of South Carolina, Charleston (A.M.A.).
¹² National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (KM.B.).
¹³ Cincinnati Children's Medical Center, OH (J.C.).
¹⁴ University of Michigan Medical School, Ann Arbor (C.S.G., R.G.O.).
¹⁵ Congenital Heart Institute of Florida, St. Petersburg (J.P.J.).
¹⁶ Children's Hospital Los Angeles, CA (A.B.L.).
¹⁷ Hospital for Sick Children, Toronto, Ontario, Canada (S.M.).
¹⁸ Nemours Cardiac Center, Wilmington, DE (C.P.).
¹⁹ Primary Children's Hospital and the University of Utah, Salt Lake City (A.E.).

PMID: 29437119
PMCID: PMC5963989
DOI: 10.1161/CIRCULATIONAHA.117.029375

Abstract

Background: In the SVR trial (Single Ventricle Reconstruction), 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups.

Methods: Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial.

Results: Transplant-free survival for the RVPAS versus modified Blalock-Taussig shunt groups did not differ at 6 years (64% versus 59%, P=0.25) or with all available follow-up of 7.1±1.6 years (log-rank P=0.13). The RVPAS versus modified Blalock-Taussig shunt treatment effect had nonproportional hazards (P=0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before stage II surgery (HR, 0.66; 95% confidence interval, 0.48-0.92). The effect of shunt type on death or transplant was not statistically significant between stage II to Fontan surgery (HR, 1.36; 95% confidence interval, 0.86-2.17; P=0.17) or after the Fontan procedure (HR, 0.76; 95% confidence interval, 0.33-1.74; P=0.52). By 6 years, patients with RVPAS had a higher incidence of catheter interventions (0.38 versus 0.23/patient-year, P<0.001), primarily because of more interventions between the stage II and Fontan procedures (HR, 1.72; 95% confidence interval, 1.00-3.03). Complications did not differ by shunt type; by 6 years, 1 in 5 patients had had a thrombotic event, and 1 in 6 had had seizures.

Conclusions: By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS versus modified Blalock-Taussig shunt groups. Children assigned to the RVPAS group had 5% higher transplant-free survival, but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Keywords: Norwood procedure; cardiac surgery; congenital heart defect; congenital heart disease; single ventricle.

PubMed Disclaimer

Conflict of interest statement

DISCLOSURES

No relevant conflicts to disclose.

Figures

**Figure 1**
Comparison of the assigned shunt types in their freedom from the composite end point of death or cardiac transplantation (ie, transplantation-free survival). RVPAS indicates right ventricle–to–pulmonary artery shunt; and MBTS, modified Blalock-Taussig shunt.

**Figure 2**
Comparison of the assigned shunt types in their freedom from any catheter interventions. RVPAS indicates right ventricle–to–pulmonary artery shunt; and MBTS, modified Blalock-Taussig shunt.

**Figure 3**
Kaplan-Meier estimates of the proportion of patients with stroke (Panel A), 6-year incidence for RVPAS *vs.* MBTS, 10% *vs.* 7%; Thrombotic events (Panel B), 6-year incidence RVPAS *vs.* MBTS, 19% *vs.* 21%; Seizures (Panel C), 6-year incidence for RVPAS *vs.* MBTS, 18% *vs.* 15%; and PLE = protein losing enteropathy (Panel D), 6-year incidence for RVPAS *vs.* MBTS, 7% *vs.* 3%. RVPAS indicates right ventricle–to–pulmonary artery shunt; and MBTS, modified Blalock-Taussig shunt.

See this image and copyright information in PMC

Comment in

Surgical Palliation for Hypoplastic Left Heart Syndrome: For Now, Just Keep Doing What You Do Best.
Fraser CD Jr. Fraser CD Jr. Circulation. 2018 May 22;137(21):2254-2255. doi: 10.1161/CIRCULATIONAHA.118.033689. Circulation. 2018. PMID: 29784679 No abstract available.
On rough road of hypoplastic left heart syndrome after Norwood procedure.
Marrone C, Galletti L. Marrone C, et al. J Thorac Dis. 2019 Mar;11(Suppl 3):S465-S467. doi: 10.21037/jtd.2018.11.27. J Thorac Dis. 2019. PMID: 30997249 Free PMC article. No abstract available.
Single-ventricle reconstruction 2.0: A closer look at our understanding of care for infants undergoing the Norwood procedure.
Karamlou T, Meza JM, Najm HK, Nigro JJ, Hill KD. Karamlou T, et al. J Thorac Cardiovasc Surg. 2019 Sep;158(3):837-842.e5. doi: 10.1016/j.jtcvs.2018.12.121. Epub 2019 Apr 17. J Thorac Cardiovasc Surg. 2019. PMID: 31101343 No abstract available.

References

1. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart syndrome: experience with palliative surgery. Am J Cardiol. 1980;45:87–91. - PubMed
1. Sano S, Ishino K, Kawada M, Arai S, Kasahara S, Asai T, Masuda Z, Takeuchi M, Ohtsuki S. Right ventricle-pulmonary artery shunt in first-stage palliation of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg. 2003;126:504–509. - PubMed
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1. Newburger JW, Sleeper LA, Frommelt PC, Pearson GD, Mahle WT, Chen S, Dunbar-Masterson C, Mital S, Williams IA, Ghanayem NS, Goldberg CS, Jacobs JP, Krawczeski CD, Lewis AB, Pasquali SK, Pizarro C, Gruber PJ, Atz AM, Khaikin S, Gaynor JW, Ohye RG Pediatric Heart Network I. Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial. Circulation. 2014;129:2013–2020. - PMC - PubMed
1. www.pediatricheartnetwork.org/ForResearchers/PHNPublicUseDatasets.PHN Public Use Datasets website.

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Transplant-Free Survival and Interventions at 6 Years in the SVR Trial

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Transplant-Free Survival and Interventions at 6 Years in the SVR Trial

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