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Innovation associated with the treatment of patients with congenital and pediatric cardiac disease

Volume 19 - Supplement S2 - November 2009
Contents

Original Article

  • Innovation in Basic Science: Stem Cells and their role in the treatment of Paediatric Cardiac Failure – Opportunities and Challenges

  • Sunjay Kaushal, Jeffrey Phillip Jacobs, Jeffrey G. Gossett, Ann Steele, Peter Steele, Craig R. Davis, Elfriede Pahl, Kalpana Vijayan, Alfred Asante-Korang, Robert J. Boucek, Carl L. Backer, Loren E. Wold
  • Published online by Cambridge University Press:
    01 November 2009, pp. 74-84

  • Heart failure is a leading cause of death worldwide. Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration.

    A stem cell is defined as a cell with the properties of being clonogenic, self-renewing, and multipotent. In response to intercellular signalling or environmental stimuli, stem cells differentiate into cells derived from any of the three primary germ layers: ectoderm, endoderm, and mesoderm, a powerful advantage for regenerative therapies. Meanwhile, a cardiac progenitor cell is a multipotent cell that can differentiate into cells of any of the cardiac lineages, including endothelial cells and cardiomyocytes.

    Stem cells can be classified into three categories: (1) adult stem cells, (2) embryonic stem cells, and (3) induced pluripotential cells. Adult stem cells have been identified in numerous organs and tissues in adults, including bone-marrow, skeletal muscle, adipose tissue, and, as was recently discovered, the heart. Embryonic stem cells are derived from the inner cell mass of the blastocyst stage of the developing embryo. Finally through transcriptional reprogramming, somatic cells, such as fibroblasts, can be converted into induced pluripotential cells that resemble embryonic stem cells.

    Four classes of stem cells that may lead to cardiac regeneration are: (1) Embryonic stem cells, (2) Bone Marrow derived stem cells, (3) Skeletal myoblasts, and (4) Cardiac stem cells and cardiac progenitor cells. Embryonic stem cells are problematic because of several reasons: (1) the formation of teratomas, (2) potential immunologic cellular rejection, (3) low efficiency of their differentiation into cardiomyocytes, typically 1% in culture, and (4) ethical and political issues. As of now, bone marrow derived stem cells have not been proven to differentiate reproducibly and reliably into cardiomyocytes. Skeletal myoblasts have created in vivo myotubes but have not electrically integrated with the myocardium. Cardiac stem cells and cardiac progenitor cells represent one of the most promising types of cellular therapy for children with cardiac failure.

  • The Gerbode Defect: The Significance of a Left Ventricular to Right Atrial Shunt*

  • Angela M. Kelle, Luciana Young, Sunjay Kaushal, C. Elise Duffy, Robert H. Anderson, Carl L. Backer
  • Published online by Cambridge University Press:
    01 November 2009, pp. 96-99
  • Background

    The so-called Gerbode ventriculo-atrial defect is a rare defect that permits shunting from the left ventricle to the right atrium. It takes 2 forms, either a deficiency of the atrioventricular membranous septum, or shunting initially through a ventricular septal defect, with atrial shunting occurring through a deficiency in the septal leaflet of the tricuspid valve. In this review, we describe the natural history and outcomes of surgical repair for the variant with shunting through a deficiency at the site of the atrioventricular membranous septum.

    Methods

    From 1990 to 2008, we identified 6 patients from our departmental database who had undergone surgical closure of a congenital defect of the atrioventricular component of the membranous septum. Median age at repair was 1.6 years, with a range, from 0.4 to 19 years. All patients were symptomatic, with 3 having congestive cardiac failure, 2 failing to thrive, and 2 having intolerance to exercise. All had a dilated right atrium demonstrated by echocardiogram, with a mean preoperative gradient measured by echocardiogram to be 109 millimetres of mercury, with a range from 65 to 150 millimetres of mercury.

    Results

    There was no operative or late mortality. The mean size of the defect was 6.2 ± 2.0 millimetres, with a range from 4 to 8 millimetres. All were closed by insertion of a patch. The mean period of cardiopulmonary bypass was 90.5 ± 11.3 minutes, the mean time of aortic cross-clamping 54.8 ± 6.9 minutes, and the mean length of stay in hospital 4.3 ± 1.0 days. No patient had a residual defect, and only trivial regurgitation of the tricuspid valve was evident by postoperative echocardiography. There were no complications or reoperations.

    Conclusion

    The membranous ventriculo-atrial defect can be recognized echocardiographically on the basis of dilation of the right atrium in the setting of an unusually high Doppler echocardiogram gradient compared to the ventricular septal defect with shunting only at ventricular level. Since all patients in our series were symptomatic, we recommend surgical closure of all these defects.

Abstracts

Front Cover (OFC, IFC) and matter

  • CTY volume 19 issue S2 Cover and Front matter

  • Published online by Cambridge University Press:
    01 November 2009, pp. f1-f10
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Back Cover (OBC, IBC) and matter

  • CTY volume 19 issue S2 Cover and Back matter

  • Published online by Cambridge University Press:
    01 November 2009, pp. b1-b4
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