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.