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

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 co
nditions
such as ascending aortic aneurysm and aortic dissection. 
Of BAV 
individuals, 
25
-
50% 
will 
develop
indication
s
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 o
f this thesis was to characteris
e 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 ha
d
a BAV. 
BAV patients were approxim
ately 10 years younger than 
patients 
with tricuspid aortic valves (TAV) 
at the time of surgery
.
P
atients 
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 w
ith 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 ha
d
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. Increasin
g severity of valve pathology 
was
associated with smaller aortic dimensions. The distribution of valve pathology d
id
not 
differ with the various BAV 
phenotypes.




Study III
evaluated a possible correlation between ascending aortic dilatation and 
dilatation o
f the distal 
aorta 
(n = 97). 
BAV patients with ascending aortic aneurysm
s
ha
d 
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 m
atrix 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 ha
d
concomitant 
coronary artery disease. A
scending aortic dilatation and coronary artery disease seldom 
co
-
exis
ted
regardless of valve morphology