The bicuspid aortic valve : studies on valve morphology and pathology in relation to ascending aortic dilatation and coronary artery disease

Abstract

The prevalence of bicuspid aortic valve (BAV) is 1-2% and is thereby the most common cardiac malformation. BAV is highly associated with valvular dysfunction and aortic conditions such as ascending aortic aneurysm and aortic dissection. Of BAV individuals, 25-50% will develop indications for surgical intervention. The underlying molecular mechanisms of BAV formation and the reason for the high prevalence of ascending aortic aneurysm in these patients are unknown.

The overall aim of this thesis was to characterise morphological, molecular and clinical aspects of BAV disease in adult patients undergoing cardiac surgery due to aortic valve and/or ascending aortic pathology. In the study population of this thesis more than 50% of the patients had a BAV. BAV patients were approximately 10 years younger than patients with tricuspid aortic valves (TAV) at the time of surgery. Patients that had additional coronary artery disease were older than patients that did not, regardless of whether they had a BAV or a TAV. Ascending aortic aneurysm was substantially more common in BAV patients than in TAV patients while aortic ectasia was equally common regardless of valve morphology. In patients with ascending aortic dilatation, aortic valve stenosis was almost exclusively associated with BAV whereas aortic valve regurgitation was associated with either BAV or TAV.

Study I assessed the morphology of the aortic root and ascending aorta in relation to valve morphology and BAV phenotype (n = 300). BAV patients had larger dimensions of the left ventricular outflow tract and annulus than TAV patients regardless of aortic morphology. The relative distribution of aortic aneurysm or ectasia was not related to BAV phenotype.

Study II investigated a possible association between severity of valve pathology and morphology of the aortic root and ascending aorta (n = 500). The combination of aortic valve stenosis and ascending aortic aneurysm was common in BAV patients but was virtually non-existent in TAV patients. Increasing severity of valve pathology was associated with smaller aortic dimensions. The distribution of valve pathology did not differ with the various BAV phenotypes. Study III evaluated a possible correlation between ascending aortic dilatation and dilatation of the distal aorta (n = 97). BAV patients with ascending aortic aneurysms had smaller dimensions of the distal aorta than the corresponding group of TAV patients. Concomitant dilatation of the descending aorta was predominantly found in TAV patients.

Study IV analysed the occurrence of matrix degrading proteases in the media of the aortic wall (n = 109). Expression of matrix metalloproteinase 14 and 19 was associated with ascending aortic dilatation in TAV patients, but not BAV patients.

Study V evaluated patient characteristics in relation to valve morphology, valve pathology, aortic morphology and coronary artery disease (n = 702). BAV patients with aortic valve pathology and/or ascending aortic dilatation rarely had concomitant coronary artery disease. Ascending aortic dilatation and coronary artery disease seldom co-existed regardless of valve morphology.