Congenital heart disease affects 1/100 live births and is one of the most common congenital abnormalities. Patients with congenital heart disease often have extracardiac abnormalities, likely secondary to genetic syndromes such as Trisomy 21, Noonan's syndrome, and Turner Syndrome. The relationship between congenital heart disease and lymphatic abnormalities and/or dysfunction is well documented and can be grossly divided into syndromic and non-syndromic etiologies. In patients with genetic syndromes (as examples listed above), there are known primary abnormal lymphatic development leading to a large pleiotropic manifestation of lymphatic dysfunction from lymphedema, chylothorax, ascites, protein losing enteropathy, to severe multicompartment lymphatic dysfunction. With further understanding of the genetic underpinnings of some syndromes, i.e., Noonan's syndrome, there have been advances in medical therapies that allow for direct targeting of abnormal signaling pathways in these rasopathies. Trametinib, a MEK1/2 inhibitor, has been successfully used in growing numbers of Noonan's patients with underlying lymphatic dysfunction1, 2, 3. Non-syndromic patients, or those without clear genetic etiologies for the lymphatic dysfunction, are often thought to be secondary to physiologic abnormalities as sequelae of congenital heart disease and palliative surgeries.

Single ventricle heart disease is the population at highest risk of developing lymphatic abnormalities with as high as 20% of patients developing clinical lymphatic dysfunction over their lifetime. With the advancement in surgical techniques, patients with single ventricle heart disease are now able to survive beyond the neonatal period and with further palliative procedures can survive into adulthood. As a consequence of this staged palliation, the univentricular heart is maintained as the systemic pumping chamber while the pulmonary blood flow becomes passive with redirection of central veins (SVC, IVC) directly to the pulmonary arteries (Superior cavopulmonary connection and Total cavopulmonary connection (SVC+IVC). Given the lack of a subpulmonary ventricle, this physiology results in an obligate increase in central venous pressure that is often 2-3x normal central venous pressures. As a result, the lymphatic system is secondarily affected, causing first an increase in afterload (Superior cavopulmonary connection) and lymphatic hypertension. Second, with the incorporation of the IVC (TCPC), there is an increased generation of lymphatic fluid (primarily from the liver) that now results in increased preload. The combination of these effects can have profound effects on lymphatic system function (Figure 1).

With the secondary effects occurring in the lymphatic system due to the increased central venous pressure, there are also anatomic and functional changes within the central lymphatics that, while compensatory in nature, can also result in significant clinical abnormalities. The most common abnormalities associated are chylothorax (CTX), plastic bronchitis (PB), protein losing enteropathy (PLE), and multicompartment lymphatic failure. In the sections below, we will describe the findings associated with the diseases and our current treatment strategies within the congenital heart disease population.