Invited commentary

Abstract

Suda and colleagues have produced an intriguing investigation of the relationship of vascular endothelial growth factor (VEGF) in patients with cyanosis and the palliative or reparative operations that these patients receive. The topic is an important one, in that VEGF has been hypothesized to play at least a contributory role in the pathophysiology of pulmonary arteriovenous malformations (PAVM). Because PAVM are known to regress in many, if not all, patients who undergo Fontan procedures, the failure of VEGF levels to normalize after the Fontan may at first be taken to undermine the theory that VEGF is a causative factor in PAVM formation and persistence. Although that may indeed be the case, it would be premature to exclude VEGF as an actor in this process. It is known that PAVM occur in a significant proportion of patients with unidirectional or bidirectional cavopulmonary connections over a sufficient period of time; however PAVM do not occur in all such patients. It is much more likely that it is a combination of hemodynamic and humoral factors that determine the presence of PAVM and their likelihood of dilatation (which may in fact be a greater variable than their presence). Accordingly, it is possible that elevation of serum VEGF is a necessary but not sufficient condition for PAVM that attain a clinical degree of significance. Likewise, it is a fascinating observation that VEGF levels normalize after biventricular repairs. Here, as well, caution should be exercised in interpreting these data. The underlying anatomy is so profoundly different in hearts for which biventricular repair is possible as opposed to those for which Fontan palliation remains the best acceptable option that comparisons of vascular derived growth factors may be of little relevance. Furthermore, the observations are at relatively few points in time, thus opening a very narrow window on a process that evolves over many years. Despite these reservations, Suda and colleagues have explored an important avenue that improves our understanding of a poorly understood clinical problem.