Background—The high incidence of aortic disease in subjects with congenital aortic valve malformations suggests a causative relationship between these 2 conditions. The histological observation in aortic dilatation/aneurysm/dissection is Erdheim cystic medial necrosis (CMN), a noninflammatory loss of smooth muscle cells (SMCs), fragmentation of elastic fibers, and mucoid degeneration.

Methods and Results—To examine whether apoptosis is 1 of the mechanisms underlying CMN and aortic medial layer SMC loss, ascending aortic wall specimens from 32 patients were collected at cardiothoracic surgery and examined by histochemical staining and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling. From echocardiography results, 4 groups of patients were identified: bicuspid valve carriers with (bi/dil) or without (bi/0) aortic dilatation and tricuspid valve carriers with (tri/dil) or without (tri/0) aortic dilatation. Massive focal apoptosis was observed in the medial layers of bi/dil (mean apoptotic index [mAI], 8.1±6.0) and tri/dil (mAI, 8.1±8.3) compared with tri/0 (mAI, 0.9±1.2; P=0.0079 and P=0.037). In bi/0 (mAI, 9.1±5.7) compared with tri/0 (mAI, 0.9±1.2), rates of medial SMC apoptosis were increased (P=0.0025). Bi/dil (mean age, 40.6±15.7 years) were significantly younger than tri/dil (mean age, 56.4±12.8 years) undergoing the same operation (P=0.0123).

Conclusions—Premature medial layer SMC apoptosis could be part of a genetic program underlying aortic disease in patients with aortic valve malformations.