Regenerative Medicine Strategies for Hypoplastic Left Heart Syndrome

Abstract

Hypoplastic left heart syndrome (HLHS), the most severe and common form of single ventricle congenital heart lesions, is characterized by hypoplasia of the mitral valve, left ventricle (LV) and all LV outflow structures. While advances in surgical technique and medical management have allowed survival into adulthood, HLHS patients have severe morbidities, decreased quality of life and a shortened lifespan. The single right ventricle (RV) is especially prone to early failure because of its vulnerability to chronic pressure-overload, a mode of failure distinct from ischemic cardiomyopathy encountered in acquired heart disease. As these patients enter early adulthood, an emerging epidemic of RV failure has become evident. Regenerative medicine strategies may help preserve or boost RV function in children and adults with HLHS by promoting angiogenesis and mitigating oxidative stress. Rescuing a RV in decompensated failure may also require the creation of new, functional myocardium. Although considerable hurdles remain before their clinical translation, stem cell therapy and cardiac tissue engineering possess revolutionary potential in the treatment of pediatric and adult patients with HLHS who currently have very limited long-term treatment options.