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Commentary: Unicorns and leprechauns

  • Christopher E. Mascio
    Correspondence
    Address for reprints: Christopher E. Mascio, MD, Division of Pediatric Cardiothoracic Surgery-Department of Surgery, Children's Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, 3401 Civic Center Blvd, Suite 8574, Philadelphia, PA 19104.
    Affiliations
    Division of Pediatric Cardiothoracic Surgery-Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, Pa
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa
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Open ArchivePublished:December 21, 2019DOI:https://doi.org/10.1016/j.jtcvs.2019.12.017
      The best initial therapy for hypoplastic left heart syndrome remains controversial. There is no clear winner between transplantation and palliation. A paradigm-shifting breakthrough is needed.
      See Article page 1451.
      Stackhouse and colleagues
      • Stackhouse K.A.
      • McCrindle B.W.
      • Blackstone E.H.
      • Rajeswaran J.
      • Kirklin J.K.
      • Bailey L.L.
      • et al.
      Surgical palliation or primary transplantation for aortic valve atresia.
      report on the cohort of patients with aortic atresia (read: hypoplastic left heart syndrome [HLHS]) enrolled from 1994 to 2000 in the Congenital Heart Surgeons' Society study comparing outcomes of different initial management strategies. The focus of this manuscript is on the 2 most common initial interventions—surgical palliation and listing for primary cardiac transplantation. The authors discovered that survival with primary transplantation, including waitlist mortality, was superior to surgical palliation. They also evaluated quality-of-life and found that those undergoing primary transplantation reported fewer symptoms but equivalent quality of life.
      This is a significant paper, as it both compares medium/longer-term outcomes between the 2 most common initial therapies for HLHS and prompts continued debate and investigation about what the best initial therapy should be for this challenging lesion. As mentioned, the major strength of this manuscript is the continued follow-up through adolescence of patients intervened in as neonates. However, the cohort is historical, and only 2 of the 26 participating centers regularly performed primary transplantation. I wonder if the findings would be the same if the cohort was more recent. Results have improved drastically since 1994 for surgical palliation. We discovered that our in-hospital mortality after surgical palliation was halved (28.7% to 14.9%) when comparing the late 1990s with the early 2000s.
      • Mascio C.E.
      • Irons M.L.
      • Ittenbach R.F.
      • Gaynor J.W.
      • Fuller S.M.
      • Kaplinski M.
      • et al.
      Thirty years and 1663 consecutive Norwood procedures: has survival plateaued?.
      And, for the lowest-risk patients, those with 0 to 2 risk factors, mortality was 5% to 10% in the most recent era.
      • Mascio C.E.
      • Irons M.L.
      • Ittenbach R.F.
      • Gaynor J.W.
      • Fuller S.M.
      • Kaplinski M.
      • et al.
      Thirty years and 1663 consecutive Norwood procedures: has survival plateaued?.
      Better early survival would certainly improve medium/longer-term survival. Others report that primary neonatal heart transplantation has a waitlist mortality up to 34%.
      • John M.
      • Bailey L.L.
      Neonatal heart transplantation.
      And, with operative mortality being reported around 10%, it is hard to champion primary heart transplantation as drastically superior when more than 40% die before transplantation or shortly after.
      • Shah S.
      • Asante-Korang A.
      • Ghazarian S.R.
      • Stapleton G.
      • Herbert C.
      • Decker J.
      • et al.
      Risk factors for survival after heart transplantation in children and young adults: a 22-year study of 179 transplants.
      Even if transplantation was clearly better, the problem of donor organ shortage persists.
      With neither therapy a dominant winner, where do we turn for answers? Mythical creatures seem absurd to mention at this writing, but many would categorize xenotransplantation and the perfect ventricular assist device in the same family as unicorns and leprechauns. Xenotransplantation is often described as forever the future of heart transplantation. However, given recent advances in genetic engineering and immunobiology, some have called for increased efforts to try pig-to-human neonatal heart transplantation. The scientific rationale includes immunologically privileged neonates and the following: inducing B-cell tolerance (elimination of major pig antigens along with the immature B-cell response in neonates) and thymectomy at time of operation along with pig thymus transplantation to blunt the neonatal T-cell response.
      • Cleveland D.
      • Adam Banks C.
      • Hara H.
      • Carlo W.F.
      • Mauchley D.C.
      • Cooper D.K.C.
      The case for cardiac xenotransplantation in neonates: is now the time to reconsider xenotransplantation for hypoplastic left heart syndrome?.
      It is also well described and experienced that durable mechanical support in neonates with HLHS is nearly uniformly fatal. Hemorrhage, thromboembolism, and size constraints continue to limit widespread, long-term application of this therapy to our smallest, most complex patients. We all sit and hope that a new, miniaturized device with a blood-friendly surface will become available. Until there is a paradigm-shifting breakthrough, we continue for surgical palliation for low-risk patients and hybrid stage 1 palliation as a bridge to transplantation for greater-risk patients.

      References

        • Stackhouse K.A.
        • McCrindle B.W.
        • Blackstone E.H.
        • Rajeswaran J.
        • Kirklin J.K.
        • Bailey L.L.
        • et al.
        Surgical palliation or primary transplantation for aortic valve atresia.
        J Thorac Cardiovasc Surg. 2020; 159: 1451-1461.e7
        • Mascio C.E.
        • Irons M.L.
        • Ittenbach R.F.
        • Gaynor J.W.
        • Fuller S.M.
        • Kaplinski M.
        • et al.
        Thirty years and 1663 consecutive Norwood procedures: has survival plateaued?.
        J Thorac Cardiovasc Surg. 2019; 158: 220-229
        • John M.
        • Bailey L.L.
        Neonatal heart transplantation.
        Ann Cardiothorac Surg. 2018; 7: 118-125
        • Shah S.
        • Asante-Korang A.
        • Ghazarian S.R.
        • Stapleton G.
        • Herbert C.
        • Decker J.
        • et al.
        Risk factors for survival after heart transplantation in children and young adults: a 22-year study of 179 transplants.
        World J Pediatr Congenit Heart Surg. 2018; 9: 557-564
        • Cleveland D.
        • Adam Banks C.
        • Hara H.
        • Carlo W.F.
        • Mauchley D.C.
        • Cooper D.K.C.
        The case for cardiac xenotransplantation in neonates: is now the time to reconsider xenotransplantation for hypoplastic left heart syndrome?.
        Pediatr Cardiol. 2019; 40: 437-444

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