Aortic valve replacement in patients over 60: Real‐world surgical outcomes

With the advent of transcatheter aortic valve implantation (TAVI) has come an expectation that there will be a decline in surgical aortic valve replacement (SAVR). This has been fueled by trials comparing outcomes between TAVI and SAVR in lower‐risk patients. The aim of this study was to examine outcomes following SAVR in patients over the age of 60.

One question that remains surrounds long-term outcomes of TAVI, which is clearly of relevance to the younger and lower-risk cohort as the majority of trials to date report early-or mid-term outcomes, over which little structural valve degeneration (SVD) is observed in either cohort. 5 Although long-term data is lacking for TAVI in lower surgical risk patients, longer-term outcomes following SAVR are very well established. 6 In elderly patients, the lifespan of a SAVR biologic prosthesis is estimated to be in excess of 15 years. 7 A recent study with a median follow-up of 10 years reported an incidence of clinically relevant SVD of only 6.6%. 6 In anticipation of the increased investigation of TAVI in lower surgical risk cohorts, the aim of this study was to examine contemporary outcomes following SAVR in patients ≥60 years at a high-volume center.

| Patient population
All patients ≥60 years that had SAVR between January 1st, 2015 and December 31st, 2018, at the Royal Papworth Hospital, Cambridge, UK, were identified. Patients who had undergone previous cardiac surgery or had SAVR with concomitant procedures were excluded.
The study was approved by the Royal Papworth Hospital Research and Development clinical ethics department. Consent of patients was waived. A Heart team discussion occurs for all urgent cases while elective cases are referred directly by the Cardiology team. Of these, patients with multiple comorbidities are discussed at valve (and when appropriate TAVI) multidisciplinary team meetings.
Patients were divided into low risk and high risk by European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (<4 and ≥4), as defined in the EACTS Guidelines for the management of valvular heart disease. 8 The cohorts were also divided by age (60-69, 70-79, ≥80) for further comparisons.

| Outcomes
Demographic, intra-procedure and post-procedure data, including incidence of complications, length of hospital, and intensive care unit (ICU) stay were retrieved from our surgical and ICU databases. Mortality information was obtained from the UK national patient administration system and was available for all patients. Acute Kidney Injury (AKI) grade was calculated using the Acute Kidney Injury Network classification. 9 The diagnosis of chest infection was based on documentation in the notes of a patient and/or administration of a course of antibiotics with chest documented as the indication. This did not require a positive sputum culture or clear chest radiographic evidence.

| Statistical analysis
Statistical analysis was performed using GraphPad Prism 9.0.0 (GraphPad Software, Inc.), and R 3.6.1 (R Core Team). We have presented categorical variables as numbers (percentages) and continuous variables as median (IQR, interquartile range), as all continuous variables recorded were not deemed to have a normal distribution using the D'Agostino-Pearson test and Shapiro-Wilk test. All variables were compared using nonparametric tests. The categorical variables were analyzed using the χ 2 or Fisher's exact test within the age and EuroSCORE II groups. Continuous variables were compared using the Mann-Whitney U test or the Kruskal-Wallis test.
The Kaplan-Meier method was used to plot the patient survival rates, with the log-rank (Mantel-Cox) test used to compare groups. p < .05 was considered statistically significant.

| RESULTS
Over the 5-year period of study, 1005 patients ≥60 years underwent SAVR at our center. For the purpose of comparison, they were divided based on EuroSCORE II, <4 (n = 857) and ≥4 (n = 148).

| Patient characteristics
Patient demographics are summarized in Table 1. The median age of patients was 75 years and the median EuroSCORE II was 1.6.
There was a higher proportion of females (p = .03) and older age (p < .001) patients in the high surgical risk cohort. As would be predicted, patients in the higher score cohort suffered greater comorbidityspecifically hypertension (p = .01), chronic pulmonary disease (p < .001), neurological disease (p < .001), diabetes (p = .003), and peripheral vascular disease (p < .001). They also had higher NYHA scores (p < .001).

| Intraoperative characteristics
Intraoperative characteristics are summarized in Table 2. In this cohort, 19.2% of operations were performed on an urgent or emergent basis. The vast majority were performed through a median sternotomy (98.2%) and used a bioprosthetic valve (97.5%). The median cardiopulmonary bypass (CPB) time was 68 min and the aortic cross-clamp time of 51 min.
There was a significant increase in the proportion having urgent operations (p < .001) and receiving bioprosthesis (p = .04) between the surgical risk groups. There was a reduction in cross-clamp time (p < .001) with increasing EuroSCORE II, but no significant reduction in CPB time in the higher-risk group (p = .42). In keeping with this observation, a statistically significant trend was observed with a decreased proportion of procedures being performed by non-consultant grade surgeons (p = .005).

| Patient outcomes
Patient outcomes are summarized in Table 3. The incidence of reexploration for bleeding was 3.7%. The incidence of AKI was 20.8%, and SUMAL ET AL.

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39.0% experienced fast atrial fibrillation. Three additional patients returned to theater for other complications: two required coronary artery bypass grafting, and one underwent repair of type A aortic dissection. The incidence of cerebrovascular accident (CVA) for the cohort was 1.2% and pacemaker implantation 3.6%. The median ICU and hospital lengths of stay were 24.1 h and 8.2 days, respectively. In all, 85.8% of patients were discharged home and 14.2% were transferred to a local hospital or for further rehabilitation before discharge home. The overall 30-day mortality was 1.7%; for elective patients, this was 1.1%.
In the higher surgical risk group, a higher proportion required blood transfusion (p < .001), and more units of blood were transfused (p = .008).
There was a greater incidence of AKI with the higher surgical risk  hospital (p < .001) stays. However, 30-day mortality was also significantly higher in the high-risk group (p = .007).

| Age groups
Patient demographics and intraoperative details stratified by age are shown in Tables S1 and S2. Key outcomes are shown in Table 4.
Noteworthy outcomes include a significant proportion of older patients incurring AKI (p < .001) and having significantly prolonged ICU (p < .001) and hospital (p = .002) stays. Furthermore, there was an increase in the proportion transferred for ongoing care rather than being discharged home. Longer-term patient survival was significantly reduced with age ( Figure 1B; p < .001).

| DISCUSSION
In this study, we report outcomes following SAVR in 1005 patients ≥60 years old at a high-volume center over a 5-year period. We observed overall 30-day mortality of 1.7%. In the elective cohort, it was just 1.1%.
SAVR has long been established as the gold-standard treatment option for patients with aortic valve disease. 10 Over recent years there has been significant interest in the potential of TAVI as a less invasive alternative treatment option for these patients. 13 As such it is time to evaluate "real-world" outcomes following surgery to enable clinicians to offer patients the best treatment option. For TAVI to become an established treatment option for intermediate-and low-risk patients, it will be necessary to demonstrate that TAVI is comparable to surgery both in short-term and perhaps more importantly in longer-term outcomes.
This study includes patients operated on an urgent and emergent basis (representing 19.2% of our cohort) and surgery for infective endocarditis, to present "real-world" practice. We observed a stroke rate of We observed a significant reduction in aortic cross-clamp time with increased surgical risk. We believe that this relates to a reduced likelihood for a consultant to train on higher-risk cases. The need for blood transfusion significantly increased with surgical risk (and patient age). This may relate to a higher incidence of anemia with age. 14 For the higher-risk patients, 38.5% were discharged to their local hospital or for convalescence. This reflects these patients' older age and consequent longer postsurgical recovery. 15 There are other studies that have examined outcomes following SAVR. Thourani et al. 16  To date, TAVI remains a relatively new treatment and data regarding longer-term durability continues to be sought. However, an incidence of SVD of 30% at 5 years was reported in one study. 21 A recent meta-analysis by Ler et al. 22 focussed on SVD including data from large multicentre trials. They report higher 1-year, 2-3 years, and 5-year rates of paravalvular regurgitation, moderate or severe aortic regurgitation, and reintervention in the TAVI group compared to SAVR.
A similar review of TAVI valve durability concluded that long-term durability remains unclear, limited by the currently available data. 23 In keeping with this, the UK TAVI registry reported an incidence of moderate to severe SVD of 9.1% between 5 and 10 years follow-up, however, in this series only 18% had reached 8 years of follow-up. 24 The significance of TAVI valve durability has recently been questioned. Tam et al. 25 have shown through discrete event simulation modeling that valve durability may be unlikely to result in reduced life expectancy other than in younger low-risk patient cohorts.
As such, much attention has focused on comparing short-term outcomes between TAVI and SAVR. Numerous multicentre rando- superiority of TAVI in early outcomes. 4,26,27 It is important to highlight that there has been much written in the literature questioning the methodology of these industry-sponsored trials, designed to favor TAVI through strict patient selection criteria. 28,29 To offer some balance to this argument, we have demonstrated, in patients ≥60 years, that excellent outcomes can be achieved following SAVR.
Despite these questions on TAVI durability, it is clear that TAVI is having an impact on surgical practice. It would appear that with increased durability of modern valves, bioprostheses are being implanted in patients of younger age than in the past-also in anticipation of a future valve-in-valve procedure (rather than a redo surgery), also removing the requirement for therapeutic anticoagulation and its associate risks. 30 Even valve manufacturers are evolving-such as the Edwards Inspiris Resilia prosthesis which has been designed specifically with valve-in-valve TAVI in mind with an expandable ring. 2-year mortality of 17% also compare unfavorably with our outcomes.
The low-risk PARTNER 3 trial included patients with STS PROM < 4% (mean STS PROM of 1.5%; mean age of 73 years). 4 In this trial, the 30-day mortality following SAVR was 1.1%, which was similar to our patients undergoing elective surgery. However, the incidence of stroke at 2.4% was double our experience. The NOTION trial similarly compared TAVI with SAVR in a lower-risk cohort. 26 The mean EuroSCORE II of the cohort was 2.0% with a mean age of 79 years, and 81% of patients were considered low risk. They reported a 30-day mortality of 3.7% and stroke incidence of 3.0%, both notably higher than our series.
These three large studies clearly show that the surgical arm outcomes do not reflect that which can be achieved at high-volume surgical centers and should be considered when interpreting the trial outcomes. It is also worth considering the outcomes for the TAVI populations in these studies (summarized in Table 5). It can be seen that our surgical outcomes are generally superior to those of TAVI. There is a notable advantage when it comes to stroke and the requirement for permanent pacemaker implantation. However, TAVI remains superior in several other outcomes, notably the length of hospitalization. 4,26,31 In addition, the PARTNER 3 trial reported much higher rates of patients discharged home/self-care in their TAVI cohort compared to SAVR (95.8% vs. 73.1%). 4 The less invasive nature of TAVI likely explains the reduced length of stay.
It is clear from our series that outcomes are inferior with older age, particularly in those ≥80 years. Therefore, in view of the higher morbidity associated with SAVR and significantly faster recovery from TAVI, it would seem reasonable for the option of TAVI to be carefully considered in patients ≥80 years, particularly those with higher surgical risk.

| Limitations
This is a single center, retrospective study which has inherent limitations; however, our prospectively maintained databases and clinical records allow for accurate data collection. We have analyzed a recent cohort of patients to present a contemporary analysis, which prevents us from examining the longer-term outcomes of these patients. There remained the challenge of comparing this with our realworld TAVI data as in the UK TAVI is recommended for high-surgical risk patients and in those not suitable for SAVR. 32 Stratifying based on predictive-risk models is also inherently limited as there are factors impacting on the outcome not accounted for within these models. Furthermore, some of the multicentre randomized trials have used the STS score rather than EuroSCORE II for stratification. Unfortunately, we lacked data to retrospectively calculate the STS score for patients in our cohort.

| CONCLUSIONS
SAVR can be performed in patients ≥60 years with excellent outcomes. We report 30-day mortality for all-comers of 1.7% and 1-year survival of 94.3%, which compare favorably with outcomes from TAVI trials, with their highly selected patient cohorts. SAVR remains a reliable, tried and tested, treatment option in these patients and can be performed with low risk.