Congenital cardiac, aortic arch, and vascular bed anomalies in PHACE syndrome (from the International PHACE Syndrome Registry)

Abstract

PHACE syndrome represents the association of large infantile hemangiomas of the head and neck with brain, cerebrovascular, cardiac, ocular, and ventral or midline defects. Cardiac and cerebrovascular anomalies are the most common extracutaneous features of PHACE, and they also constitute the greatest source of potential morbidity. Congenital heart disease in PHACE is incompletely described, and this study was conducted to better characterize its features. This study of the International PHACE Syndrome Registry represents the largest central review of clinical, radiologic, and histopathologic data for cardiovascular anomalies in patients with PHACE to date. Sixty-two (41%) of 150 subjects had intracardiac, aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian artery was the most common cardiovascular anomaly (present in 31 (21%) of 150 subjects). Coarctation was the second most common anomaly, identified in 28 (19%) of 150 subjects, and can be missed clinically in patients with PHACE because of the frequent association of arch obstruction with aberrant subclavian origin. Twenty-three (37%) of 62 subjects with cardiovascular anomalies required procedural intervention. A greater percentage of hemangiomas were located on the left side of the head and neck in patients with coarctation (46% vs 39%); however, hemangioma distribution did not predict the presence of cardiovascular anomalies overall. In conclusion, PHACE is associated with a high risk of congenital heart disease. Cardiac and aortic arch imaging with detailed assessment of arch patency and brachiocephalic origins is essential for any patient suspected of having PHACE. Longitudinal investigation is needed to determine the long-term outcomes of cardiovascular anomalies in PHACE.

Figure 1

Flowchart demonstrating subject inclusion process and cardiovascular anomaly frequencies. Individual subjects may have more than 1 anomaly. Values are expressed as percent of total eligible registry population (n=150). PFO, patent foramen ovale; PDA, patent ductus arteriosus; SCA, subclavian artery; VSD, ventricular septal defect.

Figure 2

Three dimensional MRI aortic reconstruction in this PHACE patient with severe coarctation with multiple areas of narrowing and aneurysms in the transverse arch (as outlined by arrows in 2A). Both subclavian arteries arise distal to areas of obstruction (arrows in 2B), and the right subclavian artery has an aberrant origin.

Figure 3

Low power H&E of aortic coarctation tissue from a PHACE patient demonstrating intimal hyperplasia and large arcuate zones with loss of smooth muscle and elastic tissue. Inset shows elastin stain.