5 DISCUSSION
To our knowledge, this is the first report of the FLS technique being
applied in treating severe aortic valve calcification. Compared with the
conventional technique, the FLS technique was associated with: (1)
shorter cross-clamp time, CPB time and operative time, (2) shorter
hospital stay, and (3) superior hemodynamic performance of the
bioprosthetic aortic valves.
The incidence of calcific AS increases with age, with an average of
0.2% in patients of 50-59 years old and 9.8% in patients of 80-89
years old.17 Calcific AS occurs 10-15 years earlier in
population with congenital bicuspid aortic valves than normal
controls.18 Calcification of the aortic valve is
progressive and involves multiple mechanisms, including lipoprotein
deposition, chronic inflammation, mineralization, osteoblastic
transition of interstitial cells and active leaflet
calcification.10-11 Pathological analysis of diseased
valves revealed that fibrocalcific changes predominantly occur in the
fibrosa layer and extend to the aortic side of the valve, which maybe
associated with the spatial distribution of several anti-osteogenic
genes expressed by endothelium. The endothelium covering the aortic side
of leaflets shows lower expression of anti-osteogenic genes than that on
the ventricular side.10 Based on these pathological
characteristics of calcified aortic valve, we designed the new technique
that thoroughly removes calcified tissue by stripping the fibrosa layer
of the diseased valve and the annulus, namely, the FLS technique.
Our study showed that the FLS technique reduced cross-clamp time, CPB
time and operation time in MIAVR. This can be attributed to two factors:
(1) the FLS technique requires significantly shorter time to remove
calcified tissue, (2) the FLS technique causes less damage to the aortic
annulus and leaves less residual calcified tissue, which allows use of
continuous sutures that takes less
time. MIAVR offers several advantages over full sternotomy AVR,
including reduced trauma and pain, shorter ICU and hospital stay,
improved cosmesis, and lower rate of atrial fibrillation. However, the
cross-clamp time and CPB time are prolonged in MIAVR than full
sternotomy AVR,19-20 which is associated with
increased mortality and mobility.21-22 By implementing
the FLS technique, we have overcome these limitations and promoted the
application of MIAVR in treating severe AS.
In current study, 1 patient had severe, 2 patients had moderate and 1
patient had mild PVL postoperation in conventional group but only 1
patient in FLS group had mild PVL. However, there was no significant
difference between groups regarding the incidence and constituent ratio
of the degree of PVL. Conventional methods of mechanically crushing
calcified tissue can destroy the normal fibrous tissue in the annulus
and reduce its strength and tensile force, which causes the annulus to
be damaged by sutures. Moreover, calcified tissue in the aortic annulus
and residual valve is also difficult to be completely cleared by
conventional method, which may also contribute to PVL.
The prevalence of cerebrovascular
events varies from 1% to 17% among patients with calcific AS who
underwent AVR.23-24 Leker RR et.al reported that the
risk factors for cerebrovascular events after AVR include longer bypass
duration, older age, and larger pre-existing lesion
burdens.25 Moreover, debris produced by mechanical
crushing of calcified tissue is easy to fall into the left ventricle and
hidden in intricate muscle bundles, which may enter the arterial system
through left ventricular ejection and induce cerebro-arterial embolism.
In this study, the incidence of cerebrovascular events and permanent
strokes were 20.7% and 6.9% in conventional group in per-protocol
analysis, while that in FLS group were 7.1% and 0 respectively.
However, there was no differences between the two groups, probably due
to the small number of enrolled patients and the fact that we only
performed the neurological examinations on symptomatic patients, thus
silent cerebral events may have been missed.26
Patients in FLS group obtained a
significantly larger indexed EOA postoperatively than conventional group
whether analyzed by intention-to-treat or per-protocol. The reason maybe
that leaflets and annular
calcification can be completely
removed by FLS technology, so diameter and elasticity of aortic annular
can be restored to normal state. Therefore, we can implant a aortic
bioprothesis of optimal annulus size but not an undersized. However,
small aortic root has remained a challenge. Small aortic root was
observed in 17% of asymptomatic patients with mild to moderate AS, who
had a significantly smaller annulus diameter in comparison with those
with a normal aortic root. Enlargement is necessary to increase the
indexed EOA during AVR for patients with small aortic annular. However,
only 5% of patients received an annular enlargement procedure during
AVR due to increased operative mortality and major
morbidity.27 The residual calcification on aortic
annulus or valve is the main cause for aborted annular enlargement
during AVR, especially when the calcium extends down into the left
ventricular outflow tract or the mitral valve. In this study, all
patients with small aortic root in the FLS group received annular
enlargement before implantation of a proper sizing of the prosthetic
valve. In contrast, 2 patients with small aortic root in the
conventional group did not receive concomitant annular enlargement due
to the residual calcified tissue. As a result, oversized bioprostheses
were implanted in order to avoid
prosthesis-patient mismatch
(PPM). Compared with annular
enlargement, bioprosthesis oversizing can only increase a very limited
valve size. In addition, oversizing alters aortic annular configuration
and valvular hemodynamics, which leads to decreased EOA and increased
pressure gradients.28 Therefore we conclude that using
FLS technique in annular enlargement should be conducted on more
patients with small aortic root in order to achieve better hemodynamic
performance and patient outcome.
There remain several limitations in
current study. First, it is a single-center trial with a small cohort
size. Second, Patients are limited to bioprosthetic valve replacement,
so most of them are frail elderly who have higher average age and more
comobidities than the real world, which may cause selection bias. Third,
all operations were performed by one surgeon who may have more
experience with the FLS technique than the conventional technique.
Fourth, we only followed up for one year, and long-term effect has not
be established. Therefore, long-term safety and efficacy study of FLS in
a larger cohort of patients is needed in the future.