Seventeen-millimeter St. Jude Medical Regent valve in patients with small aortic annulus: dose moderate prosthesis-patient mismatch matter?

Dealing with a small aortic root of less than 19 mm during aortic valve replacement (AVR) remains a challenging scenario for the cardiac surgeons with regard to operative techniques and selection of appropriate prosthesis [1–4]. As implantation of a smaller prosthetic valve without adequate effective orifice area index (EOAi) may predispose to unfavorable outcomes, several strategies at the time of operation have been developed to avoid the feared prosthesis-patient mismatch (P-PtM, defined as EOAi ≤ 0.85 cm²/m²) [5–8], including the use of aortic root enlargement/replacement procedures with a larger prosthesis (eg. a stentless bioprosthesis or a new generation of stented bioprosthesis) or modern bileaflet mechanical valve implanted in the supra-annular position. However, these strategies are technically more difficult, require longer cardiopulmonary bypass times, and fail to point uniformly toward an improved clinical outcome [2, 3].

The 17-mm St. Jude Medical Regent (SJMR) valve with an improved hemodynamic profile is regarded as a valid option for patients who have small aortic roots [9, 10]. Although the Regent valves offer a larger EOA than that of conventional prosthetic valves, the occurrence of P-PtM in patients with 17-mm SJMR valves is reported as high as 31%-94.1% [1, 2, 9–11]. The main hemodynamic consequence of P-PtM, especially the severe P-PtM (EOAi ≤ 0.65 cm²/m²), is to generate higher than expected transvalvular gradients, which is responsible for incomplete left ventricular mass (LVM) regression, increased valve-related complications and postoperative mortality [6, 7, 12–15]. However, controversies still exist as to the impacts of early postoperative moderate P-PtM (0.65 cm²/m² < EOAi ≤ 0.85 cm²/m²) on late outcomes [5–7, 12–15]. Moreover, reported experience with 17-mm Regent valves in a large series of patients are rare. Thus, the objective of this study was to evaluate the effects of moderate P-PtM on midterm outcomes after isolated AVR with a 17-mm SJMR valve and to determine if these effects are modulated by patient’s confounding variables.

The present study demonstrated satisfactory outcomes of AVR with 17-mm SJMR valve in terms of midterm survival, physical capacity and hemodynamic performances. The data of our study corroborate with previous studies indicating the presence of moderate P-PtM early after surgery was not a risk factor of intermediate mortality. However, in our subgroup analysis, moderate P-PtM was associated with a significant decrease in overall survival in patients with impaired LV systolic function. These findings emphasize the importance of a prospective strategy for selection of appropriate AVR candidate and operative methods to achieve satisfactory results in patients with small aortic annulus.

Although the 17-mm SJMR valve is a new generation of aortic prosthesis with an improved hemodynamic profile, the beneficial effects of implanting this mechanical valve in patients with small aortic roots remain unclear, particularly in young patients and in the mid- to long-term. Okamura group reported a cohort of elderly patients (mean age >70 years) demonstrating satisfactory clinical improvement and regression of LVM after AVR with the 17-mm SJMR [2, 10, 11]. Similarly, a series of studies demonstrated favorable clinical outcomes, as well as improved hemodynamic performance both at rest and under an exercise load [2, 8–11, 18, 19], after AVR with a 17-mm SJMR valve. However, these studies are mostly presented with a small number of elderly patients during a relatively short follow-up period. As the moderate P-PtM frequently occurred after implantation of a small aortic Regent valve [1, 2, 9–11], its potential adverse effects on postoperative outcomes are not well characterized. Therefore, we need to investigate furtherly into the safety and effectiveness of the 17-mm SJMR in a large number of patients of all ages.

Apart from its improved hemodynamic performances, the 17-mm SJMR valve was applied in this population for several other reasons. First, our patients presented with a relatively high-risk characteristics [high proportion of female patients (74.5%), NYHA class III/IV (50.9%), LVEF < 50% (55.7%), and concomitant coronary surgery (34.9%)], and therefore a “quick and simple” procedure was required to reduce myocardial ischemic time. It is clinically evident that a prolonged aortic cross-clamp time is one of the most important risk factors for post-AVR adverse events [3, 4, 6, 7]. Although aortic root enlargement procedures or stentless prosthesis implantation are feasible options for patients with small aortic annulus, these procedures are technically more difficult and time consuming, and may result in higher morbidity than simple valve replacement, particularly in our patients who often have a severe calcified aortic root due to rheumatic and degenerative etiologies (81.1%). Moreover, a series of studies have clearly indicated that a better hemodynamic outcome early after surgery in patients underwent aortic root enlargement and AVR could not translate into an improved postoperative survival compared with patients with isolated AVR [2–4].

An important finding of this study is that moderate P-PtM is associated with increased postoperative mortality in patients with LVEF < 50%, but with normal prognosis in those with preserved ventricular function. Since patients with impaired LV function are more vulnerable to the excessive afterload imposed by P-PtM, it is reasonable to find in our series that the follow-up mortality are significantly increased in patients with a combination of moderate P-PtM and impaired LV systolic function. Studies from several groups also clearly indicated that the influential role of moderate P-PtM on late survival is more important in patients with reduced ventricular reserve than in those with preserved LV function [12, 13]. On the contrary, however, some others failed to identify the moderate P-PtM as an independent predictor of valve-related complication and mortality after AVR [15, 19]. These compelling evidence may be partially explained by the fact that investigators used different parameters (eg. projected, geometric or in vivo measured EOAi) to identify P-PtM and quantify its severity. As demonstrated in the present study, using the projected EOAi in predicting P-PtM in patients with LVEF < 50% has a lower accuracy; therefore, the projected EOAi to determine prediction and outcomes of P-PtM is of limited value. Also, differences in baseline characteristics and prevalence of moderate versus severe P-PtM in the patient population, as well as the diversity of the implanted prosthesis and surgical approaches are believed to contribute.

Previous studies have demonstrated that the influence of P-PtM on postoperative outcomes is an age-dependent phenomenon. As reported by Mohty et al. [12] and Moon et al. [20], moderate -to- severe P-PTM was detrimental to survival in young patients (<60 or 70 years of age), but its impacts on older patients are negligible. These findings might be related to the fact that younger patients are generally more physically active and they indeed have greater cardiac output requirements in relation to body size. However, in our series, younger age (<65 years) was not identified as an independent risk factor of increased midterm mortality and valve-related complications in patients with moderate P-PtM. A possible explanation could be that the proportion of patients with bioprosthetic valve in previous studies was as high as 67%-77.8% [12, 13]. As P-PtM is a significant risk factor for accelerated degeneration of bioprosthetic heart valves [21], and bioprosthesis in younger patients may expose to the progression of valvular degeneration for a longer period of time, it seems very likely that the impact of moderate P-PtM on postoperative outcomes is more pronounced in younger patients than in older ones. In addition, our insignificant result might be owing to the limited numbers of the subgroup populations.

Some could argue that the use of mechanical prostheses in AVR may potentially increase mortality and morbidity compared with the use of bioprosthesis, particularly due to anticoagulation–related complications [22]. However, in the present study, which employed strict control of PT-INR within a range of 1.5-2.0, only three patients experienced anticoagulation-related adverse events, accounting for a linearized rate of 0.2% per patient-year. These complication rates are comparable to other reports of patients who underwent bioprostheses implantation [2, 12, 13, 15]. According to the American College of Chest Physicians guidelines [23], our anticoagulant level is lower but is proved efficient in Chinese patients with mechanical heart valve prostheses [24, 25]. Similarly, investigators from other Asian countries have demonstrated low incidence of thrombosis and hemorrhage complications with low intensity anticoagulant strategy, suggesting that mechanical valves are not a risk factor for postoperative adverse events with good control of PT-INR levels (1.8-2.2) [2, 9].

Moderate P-PtM after implantation of a small mechanical prosthesis at aortic position is associated with increased midterm mortality and valve-related complications in patients with pre-existing LV dysfunction. Selected patients with small aortic annulus can experience satisfactory clinical results and midterm survival after isolated AVR with a 17-mm SJMR valve.