Aortic valve replacement (AVR) is currently the mainstay of treatment for aortic valve pathology, including stenosis and/or insufficiency, and the primary goal of AVR is to reduce the volume and/or pressure load on the left ventricle and to promote left ventricular remodeling and recovery of left heart function. Therefore, ideally, the aortic transvalvular pressure difference should be close to or even zero after AVR. However, in the vast majority of patients, especially those with small aortic annuli, a significant transvalvular pressure difference is still present after AVR. Therefore, Rahimtoola first introduced the concept of prosthesis-patient mismatch (PPM) in 1978. This article provides a brief review of the clinical research progress of PPM. In Rahimtoola’s definition, PPM is a condition in which the effective orifice area (EOA) of the implanted prosthetic heart valve is smaller than that of a normal person and the relative stenosis of the aortic valve remains after surgery, resulting in a series of complications or potential risks [1]. The normal human aortic valve opening area is 3.0-4.5 cm2, and the clinical application of either mechanical or biological valves is difficult to achieve this standard. Currently, most scholars define PPM using the effective opening area index (EOA index, EOAI) of the prosthetic heart valve, EOAI = EOA/body surface area (BSA). The more clinically used classification of PPM is generally divided into three categories [2]: if EOAI > 0.85 cm2/m2, it is considered that there is no or only mild PPM with no clinical significance; moderate PPM, 0.65 < EOAI ≤ 0.85 cm2/m2; and severe PPM, EOAI ≤ 0.65 cm2/m2. However, the criteria for defining PPM are not uniform, and a few scholars define EOAI < 0.75 cm2/m2 as PPM [3], while the criteria for severe PPM are defined as EOAI ≤ 0.6 cm2/m2 [4, 5]. 2. the incidence of PPM and its causes Most foreign studies have shown that the incidence of PPM after AVR is quite high. walther et al. studied 4131 AVR patients (1856 with replacement of bilobed mechanical valves and 2275 with replacement of allograft bioprosthetic valves with stents) and the incidence of postoperative moderate PPM was 26.7% and the incidence of severe PPM was 2.4% [6]. Moon et al [3] studied 1400 patients with AVR (467 with replacement mechanical valves and 933 with bioprosthetic valves) and the incidence of postoperative PPM was 11% (mechanical valves) and 51% (bioprosthetic valves), respectively; Eichinger et al [7] even reported 100% postoperative PPM in patients with replacement 19 mm bioprosthetic valves, unless the patient had a small body surface area or an aortic annulus The risk of widening surgery is high and the use of 19 mm bioprosthetic valves (including bovine pericardial and porcine aortic valves) is not recommended clinically. Compared with Westerners, Chinese patients are low in height and weight, which corresponds to a significantly smaller body surface area; moreover, rheumatic valve disease still predominates in heart valve disease in China, and aortic valve lesions are mostly stenosis combined with incomplete closure, and patients with simple aortic stenosis are rare, making it possible to implant a relatively large prosthetic valve during surgery. The Japanese, who are also located in East Asia, are similar in size to China, and Hashimoto retrospectively analyzed 181 patients with AVR, and only 4% of elderly patients (65 years or older) with intraoperative replacement of a 19-mm Carpentier-Edwards Perimount bovine pericardial bioprosthesis developed PPM after surgery [8], suggesting that a 19-mm bioprosthesis is a reliable option for elderly patients with small aortic annuli Japanese is a reliable option. In contrast, we have not been able to report a large number of cases on whether a high percentage of PPM is present in the national population after AVR, which warrants our study. There are two main causes of PPM after AVR: (1) Patients with aortic valve lesions often have calcification and/or fibrosis of the aortic annulus with varying degrees of left ventricular hypertrophy, and the above pathological changes can cause a reduction in the aortic valve annular diameter, which clinically forces the implantation of relatively small-sized prosthetic valves. (2) The surgically implanted prosthetic heart valve has its own support structure, and its opening area is necessarily smaller than that of a normal valve with the same annular diameter; moreover, the support structure of the prosthetic heart valve more or less affects the geometry of the left ventricular outflow tract and causes a relative narrowing of the left ventricular outflow tract [9]. This is precisely the reason why the EOA is larger with a stentless bioprosthetic valve than with a stented bioprosthetic valve. In addition, for technical reasons, surgeons implanting small-sized valves for surgical safety can also lead to the postoperative PPM phenomenon. The effect of PPM on hemodynamics and left ventricular hypertrophy has been extensively studied by Pibarot and Dumesnil, and the results of one of their studies showed that the mean transvalvular pressure difference was 33±2 mmHg in patients with an EOAI ≤0.65 cm2/m2 after AVR and 22±8 mmHg in patients with an EOAI ≤0.85 cm2/m2. transvalvular pressure difference was 22±8 mmHg, whereas in patients without PPM (EOAI>0.85 cm2/m2), the mean transvalvular pressure difference was only 15±6 mmHg [10]. In their other group of 396 AVR patients with stented bioprosthetic valves, stentless bioprosthetic valves, and homogeneous aortic or pulmonary artery with valve tubing applied to replace the aortic valve, the patients who developed PPM postoperatively were all those with stented bioprosthetic valves replaced and had a higher measured mean transvalvular pressure difference, whereas the stentless and homogeneous valves had a larger EOAI and a relatively lower mean transvalvular pressure difference after implantation [11]. The high transvalvular pressure difference caused by PPM is theoretically equivalent to the presence of aortic stenosis or left ventricular outflow tract obstruction even after aortic valve replacement, which prevents the patient from improving postoperative hemodynamics and increases left ventricular afterload, ultimately resulting in the failure to reduce or incomplete reduction of preoperative left ventricular hypertrophy and even an increase in left ventricular weight. Left ventricular hypertrophy is considered an independent predictor of decreased systolic and diastolic function of the left ventricle, and is even a risk factor for decreased exercise tolerance and increased long-term mortality in patients. Del Rizzo et al [12] observed 1103 AVR patients for 3 years and found that the decrease in LV weight was lower in those with EOAI <0.8 cm2/m2 than in those with EOAI >0.8 cm2/m2 (4.5% vs. 23.0%, P=0.0001). The study by Ruel et al [13] also demonstrated that PPM after AVR affects the reduction of LV hypertrophy and LV weight loss, which in turn affects the recovery of left heart function in patients. Coronary flow reserve (CFR) is an important parameter that affects the long-term survival of patients after AVR. Bakhtiary et al [14] studied 48 patients with AVR and measured CFR by magnetic resonance imaging before surgery, 5 days after surgery and 6 months after surgery. However, patients in the PPM group (EOAI ≤ 0.85 cm2/m2) had significantly lower CFR than those in the non-PPM group. It can be seen that PPM not only leads to high residual transvalvular pressure difference after surgery, which affects the recovery of left ventricular hypertrophy, but also affects coronary blood flow, which leads to insufficient blood supply to myocardial cells and further aggravates myocardial damage. 4. clinical significance of PPM PPM is not directly associated with valve-related complications after AVR (e.g., bleeding, thrombosis, valve failure, reoperation, etc.) [10], but the effect of PPM on hemodynamics and coronary blood flow leads to the persistence of postoperative left ventricular hypertrophy, which affects the recovery of cardiac function and quality of life of patients after surgery.PPM and postoperative NYHA cardiac function classification is strongly associated with [10], is an independent risk factor for late persistent or recurrent congestive heart failure after AVR [15], and PPM also leads to an increased incidence of postoperative syncope, pulmonary edema, and angina [16]. The relationship between PPM and AVR mortality has been a hot topic of research in recent years.Blais et al. studied 1266 AVR patients, and the relative risk of immediate postoperative mortality was 2.1 times higher when the EOAI was between 0.65 cm2/m2 and 0.85 cm2/m2; and the risk was 11.4 times higher when the EOAI was below 0.65 cm2/m2 [ Walther et al. showed that PPM significantly increased both near-term (within 30 days postoperatively) and long-term mortality after AVR. The immediate postoperative mortality rate was 10.6% in patients with moderate PPM compared with 6.9% in patients without PPM (P = 0.018); the 5-year and 8.5-year postoperative survival rates were 79.6 ± 1.3% and 76.8 ± 1.7% in patients with PPM compared with 84.9 ± 0.7% and 81.4 ± 1.0% in patients without PPM, respectively (P < 0.01) [6].Moon et al. found that that PPM after AVR affects survival in younger patients (under 60 years of age) and less in older patients [3].Studies by Mohan [17] and Mohty-Echahidi [4] also confirmed that severe PPM after surgery affects long-term survival of patients. However, there has been controversy regarding the clinical significance of PPM. Many studies have shown that PPM after AVR does not affect patients' NYHA cardiac function class, degree of left ventricular hypertrophy, survival, complication rate, etc. Koch et al. studied 1108 patients with AVR and concluded that the recovery of patients' postoperative function is similar for different valve sizes and that the main factor affecting patients' recovery is their age, and they even pointed out that the current criteria for PPM, namely EOAI ≤0.85 cm2/m2 is not associated with the development of heart failure in patients after AVR [18].Hanayama et al. studied 1129 AVR patients with EOAI <0.6 cm2/m2 as a criterion for severe PPM, and the results showed that NYHA cardiac function class, left ventricular weight index, and survival of patients with PPM at 7 years after surgery were not significantly different from those without PPM, and they concluded that PPM was not associated with recovery of cardiac function and intermediate and long-term survival after AVR.19] The results of Howell et al. also showed that severe PPM (EOAI <0.6 cm2/m2) did not affect in-hospital mortality and intermediate mortality after AVR [20]. The diametrically opposed findings on the clinical significance of PPM may be related to the different criteria for PPM applied in different studies and the different number of cases, and a multicenter, large-sample collaboration is needed in future studies to adopt uniform PPM criteria. It is well known that aortic valve replacement should be performed with a prosthetic valve of as large a diameter as possible to reduce the possibility of postoperative PPM. In the second step, the EOA of the prosthetic valve needed to achieve an EOAI >0.85 cm2/m2 is calculated based on the patient’s body surface area; in the third step, the appropriate prosthetic valve is selected based on the results of the second step. In this article, the authors also list the minimum EOA of prosthetic valves that should be implanted in patients with different body surface areas to achieve an EOAI >0.85 cm2/m2 and the EOA of commonly used brands and models of prosthetic valves to facilitate the search. For patients with small aortic annulus, new prosthetic heart valves have been introduced clinically, mainly including stentless bioprosthesis and supra-annular aortic valve. Compared with conventional prosthetic valves, newer valves such as stentless bioprosthesis and supra-annular aortic valve have better hemodynamics and lower transvalvular pressure difference, which can significantly reduce the incidence of postoperative PPM and promote the recovery of left ventricular hypertrophy and improvement of cardiac function [21,22]. In addition to the application of new prosthetic heart valves, the following methods can be applied to prevent and treat the occurrence of PPM after AVR: (1) aortic valve replacement surgery with an enlarged aortic annulus. The surgical approach to enlarge the aortic annulus includes Manouguian, Nicks, and Konno methods, but enlarging the aortic annulus prolongs the operative time, tends to cause bleeding, and increases the risk of the procedure; therefore, Sakamoto et al. used enlarging the aortic annulus surgery as the first choice for the prevention of PPM in patients under 65 years of age, while it was not chosen for high-risk patients over 65 years of age surgery [23]. (ii) Application of homogeneous allogeneic valves for aortic root replacement. (iii) Application of autologous pulmonary valve for Ross procedure. The latter two methods are difficult to perform, and both have the disadvantage of difficult valve sources and the need for secondary surgery, and are not much used clinically. 6. Problems in PPM research Although much progress has been made in the study of PPM after AVR, many problems still exist, and it is these problems that may lead to the controversy of the clinical significance of PPM. Specifically, they include the following aspects: ① The lack of uniform criteria for the definition of PPM has led to different results for the same study. Therefore, there is an urgent need to define a unified definition of PPM. ②The methods used to determine EOA of prosthetic valves are not uniform. The prosthetic valve EOA used in some studies is based on the data provided by the manufacturer [6], which is calculated from the diameter of the inner edge of the prosthetic valve suture ring. The EOA of the actual prosthetic valve after implantation is often less than the data provided by the manufacturer. Some studies have also applied two-dimensional echocardiography and echodoppler techniques to determine prosthetic valve EOA in vivo [24]. Due to the influence of the prosthetic valve material, the ultrasound beam of 2D echocardiography has difficulty penetrating the mechanical valve manufacturing material, and artifacts such as shadows and multiple reflections appear in the valve orifice and its posterior area, which affect the accuracy of the measurement; the echodoppler technique is considered the primary noninvasive method for evaluating prosthetic heart valve function, but it can only measure EOA indirectly, and its accuracy is affected by several factors. Three-dimensional echocardiography can arbitrarily select and display the section of interest within the acquired three-dimensional imaging data, ensuring that the image used when measuring the EOA of the mechanical valve is in the true short-axis section of the prosthetic valve, which may become one of the main tools to study the phenomenon of PPM after AVR in the future. The EOA of the prosthetic valve can be reduced by the growth of fibrous tissue along the annulus after implantation of the mechanical valve, so Rahimtoola advocated that the EOA of the prosthetic valve should be measured again at 6 and 12 months after AVR [25]. (4) Many studies simply calculate mortality during follow-up, without analyzing the causes of death of patients after AVR, especially whether the cause of death of patients in the distant future is cardiac-related and whether the cardiac-related death of patients is related to PPM [26]. All these issues need to be addressed one by one in future clinical studies to truly understand the clinical significance of PPM after AVR.