Characterization of differences in clinical parameters and extracellular matrix composition between bicuspid and tricuspid aortic valves: How this can be used to predict outcome and to develop new treatment strategies

Bicuspid aortic valve (BAV) is the most common congenital heart disease with an estimated prevalence of 0.5-1.4% in the general population. The condition increases the risk of a number of complications, with aortic stenosis (AS) being the most common, and close to 70% of all patients with a BAV require aortic valve replacement (AVR) during their lifetime. In study I, 271 consecutive patients (152 BAV AS and 119 tricuspid aortic valve (TAV) AS) with severe AS underwent surgical AVR (SAVR). Preoperative echocardiography revealed that BAV AS patients had more pronounced preoperative systolic and diastolic dysfunction, despite being younger and having less comorbidities than tricuspid aortic valve (TAV) AS patients. Furthermore, the incidence of postoperative HF was higher BAV AS patients, while all-cause mortality during follow-up was similar for BAV AS and TAV AS patients. In study II, 227 consecutive patients (133 BAV AS and 94 TAV AS) with severe AS underwent SAVR. The incidence of postoperative atrial fibrillation (POAF) and its association to preoperative left atrial (LA) reservoir strain was investigated. The incidence of POAF was similar for BAV AS and TAV AS patients, but there was a significant interaction between aortic valve morphology and LA reservoir regarding POAF. Furthermore, BAV AS patients had a higher incidence of persisting POAF and cumulative ischemic stroke incidence during follow-up after SAVR. In study III, the incidence of new-onset conduction disturbances (new-onset third-degree atrioventricular (AV) block or new-onset left bundle-branch block (LBBB)) was retrospectively investigated in 1147 patients (589 BAV AS and 558 TAV AS) with severe AS that underwent SAVR. The incidence of new-onset conduction disturbances was higher in BAV AS patients. New-onset LBBB was associated with a worse long-term prognosis after SAVR. Bicuspid patients with fusion of the right- and the non-coronary cusps were at greatest risk of developing postoperative conduction disturbances. In study IV, aortic valve tissue was collected from 88 patients who underwent aortic valve surgery. Proteomic analyses of the excised valves showed that the extracellular matrix (ECM) composition in BAV and TAV patients differs significantly. The ECM of BAV patients is abundant with fibrosis markers, while the ECM of TAV patients is abundant with inflammatory markers. In conclusion, this thesis demonstrates that BAV AS and TAV AS patients are two distinct patient categories w