Discussion
Of the 144 patients who underwent mitral valve surgery in this center,
25 patients progressed to significant AVD, which was similar to the
results obtained by Kim DJ [8] in a retrospective analysis of 1231
patients (13.2%).
The filling of the left ventricle in patients with MVD is often
abnormal, masking the actual hemodynamic effect of the left ventricle,
which is easy to misestimate the severity of AVD and actual peak
velocity of the aortic valve by transthoracic echocardiography. Zitink
RS [13] pointed out that for patients with severe MS complicated
with mild to moderate AVD, the only certain method of quantitative
evaluation to determine the degree of AVD is left heart catheterization,
with simultaneous measurement of transvalvular pressure differences and
blood flow. Besides, the presence of AVD before surgery means that the
valve and its adjacent structures have shown pathological changes, so
these patients are more likely to have further progress than patients
without aortic valve involvement. As well as suggested by Choudhary SK
[5] and Kim DJ [8] et al, the presence of mild to moderate AVD
before the operation was a powerful risk factor for the progression of
AVD.
Compared with aortic valve replacement, the hemodynamic changes of
mitral valve replacement were more complex. Once the MVD is corrected,
the blood flow from the left atrium to the left ventricle may be
significantly increased(Especially for MS), leaving the left ventricle
in a higher preload than before. It also changes the flow
characteristics near the aortic valve as a result of changes in blood
jet direction from the prosthetic mitral valve [6, 14]. This means
that the mechanical environment of the aortic valve will be changed. The
mechanical environment of the aortic valve is complex, including shear
stress, pressure, stretch force, and bending force. Some animal
experiments and clinical observations have confirmed that there is a
correlation between mechanical stress and heart valve biology. These
mechanical changes cause a large number of biological responses,
containing gene expression, protein activation, and phenotypic
characteristics changes of valvular interstitial cells (VICs), thus
regulating the tissue structure of the aortic valve [15-17]. For
example, the elevated pressure of the aortic valve can lead to cellular
dysfunction and extracellular matrix remodeling [18]. Specifically,
it can change the phenotypic characteristics of aortic VICs, including a
proportional increase in collagen synthesis, downregulation of the
α-smooth muscle actin, vimentin, and calponin, further lead to
pathological changes such as valve thickening and calcification
[19-21]. Under physiological conditions, the aortic valve can be
extended by about 10% during diastole, and the tissue extensibility of
the valve decreases with age. The reason may be that the continuous
formation of collagen fibril increases the diameter of some fibers and
reduces the compliance of valvular tissue, so the greater tensile force
will be needed to produce the same extension. Batten et al reported that
stretch force could regulate collagen synthesis in VICs through
phenotypic transformation [22]. VICs synthesize collagen to change
the stiffness of the valve to adapt to the stretch force, and the
stiffness of the valve plays an important role in regulating the
calcification of the valve [23]. Other studies have found that
elevated pressure can increase the expression of vascular cell adhesion
molecule-1 to induce inflammation [24].
Moreover, we found that prosthesis size is correlated with the
progression of AVD in this study. The disease has a certain regional
correlation in our center. In the south of China, most of the patients
undergoing MV surgery are thin and elderly women, and the Implantation
of an oversized prosthesis valve may be prone to cause valve mismatch
(patient-prosthesis mismatch, PPM), which is more likely to lead to the
progress of AVD. However, the clinical significance of mitral valve PPM
has still been controversial. Ozyalcin S, Lam B [25-26], et al
believed that PPM was related to long-term survival and recommended the
implantation of a larger prosthesis. Nevertheless, other studies showed
that PPM did not affect long-term survival [27]. According to the
results of multivariable analysis, the implantation of a smaller size
mitral prosthesis is a protective factor only in terms of the effect on
the progression of AVD, which may also be related to increased left
ventricular preload after surgery. Bolman RM [28] also suggested the
implantation of smaller prosthetic valves in elderly, thin patients.
Hence, it would seem that the aortic valve area should not be used as
the single criterion for determining who is a candidate for aortic valve
operation [11].
Heller SJ believes that in patients with chronic MVD, part of the
myocardium is in a state of disuse due to long-standing underfilling of
the left ventricle, resulting in its atrophy. It is considered that this
is an adaptive change of left ventricle to preload reduction, which may
be related to the function of cardiomyocytes and left ventricular
remodeling in patients [29]. Although this state of atrophy is often
reversible, due to the destruction of the structure of the mitral valve
and left ventricle caused by surgery, coupled with intraoperative
ischemia and reperfusion injury, it takes a long time for the left
ventricle to recover to withstand blood from the left atrium, which also
confirms the relationship between the endpoint event and the left
ventricular size in the conclusion of our study. From the above view,
for patients with smaller LVD before the operation, the replacement of
the larger size prosthesis means that the left ventricle, which was in a
state of enduring atrophy, will bear relatively more blood flow from the
left atrium after the operation. It will make the left ventricle in a
state of high preload for a long period after the operation, which may
be one of the reasons for promoting the progression of AVD. Mentias et
al [8] discovered from their large matched cohort studies that
ventricular size criteria for prognosis were related to outcome
“paradoxically” because those with larger volumes were more likely to
be sent to life-prolonging surgery than those with smaller volumes.
Although the authors did not report more detailed data.
According to another result of this study, tricuspid ring annuloplasty
should be performed simultaneously during mitral valve surgery. Although
there is just mild to moderate tricuspid regurgitation (TR) before the
operation, it may quickly lead to the progression of TR and AVD if not
treated. The occurrence of TR is mainly due to dilation of the annulus
and enlargement of the right ventricle, which is usually secondary to
the left heart failure, an overload of the right ventricle volume and
pressure, and enlargement of the heart chamber caused by myocardial or
valvular lesions. However, the interdependence of the left and right
ventricles is extremely important for the function of the heart. In
addition to having a common interventricular septum, their muscle fibers
are continuous and can play a role as a mechanical complex. Furthermore,
the two ventricles share a mutual biochemical environment, improving the
function of both ventricles by improving both systemic and local
concentrations of neurohormones [30]. Antunes MJ believed that
untreated or recurrent TR can cause the right ventricle to dilate and
the interventricular septum to move toward the left ventricle during
diastole, results in a rise in pulmonary venous pressure and left
ventricular diastolic pressure. These interrelated ventricular cavity
pressure and volume alterations are called “restriction-dilatation
syndrome” [31]. Therefore, it may be argued that simultaneous
implantation of a tricuspid artificial ring can delay the progress of
AVD by improving the right ventricular function.