Mechanisms underlying aortic dilatation in congenital aortic valve malformation

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/d issection is Erdheim cystic medial necrosis (CMN), a noninflammatory loss o f smooth muscle cells (SMCs), fragmentation of elastic fibers, and mucoid d egeneration. Methods aad Results-To examine whether apoptosis is 1 of the mechanisms und erlying CMN and aortic medial layer SMC loss, ascending aortic wall specime ns from 32 patients were collected at cardiothoracic surgery and examined b y 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/di l) or without (bi/0) aortic:dilatation and tricuspid valve carriers with (t ri/dil) or without (tri/0) aortic dilatation,Massive focal apoptosis was ob served 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 (mea n 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 malformati ons.