CARDIOTHORACIC

Background: Given the ageing population and uptake of transcatheter approaches for treating aortic stenosis (AS), a renewed evaluation of outcomes after surgical aortic valve replacement (SAVR) is warranted. With guidelines recommending age-based indications for surgical and transcatheter approaches, this study critically evaluates outcomes in age-based subgroups, with the aim to re ﬁ ne management of AS in the elderly, where there is often no clear consensus. Methods: Six hundred and thirteen consecutive patients who underwent SAVR in an Australian tertiary cardiac centre between 1 June 2014 and 13 January 2022 were retrospectively analysed. Of these, 70.31% were <75 years (Group 1) and 29.69% were ≥ 75 years (Group 2). Groups were compared with respect to early and long-term outcomes. Logistic regression, Kaplan – Meier survival estimates and Cox proportional hazards


Background
Aortic stenosis (AS) is the most common valvular disorder in the Western world, affecting 1 in 8 individuals over 75 years old. 1 Surgical aortic valve replacement (SAVR) is the gold standard treatment for patients with symptomatic severe AS who are surgical candidates.Over the last two decades, the emergence of transcatheter aortic valve replacement (TAVR) has challenged the role of SAVR, as a less invasive alternative with benefits of shorter hospital stay and less morbidity associated with open heart surgery.Despite this, a recent meta-analysis showed that the protective effect of TAVR runs out after 1 year, with increased rehospitalization after 6 months and all-cause mortality after 2 years. 2 SAVR remains the definitive treatment for AS, offering long-term survival comparable to age-and sex-matched peers without AS. 3 Septuagenarians and octogenarians are an age group of interest for assessing surgical candidacy.They are considered a high-risk group due to the frequent presence of frailty and multiple comorbidities. 4Recent guidelines provide age-based indications, with the European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines recommending TAVR for patients older than 75 years and American Heart Association recommending TAVR for octogenarians. 5,6The concern arises when a proportion of elderly patients who could benefit from SAVR are denied based on age.While conventional risk scores are often used to assess surgical candidacy, its impact depends strongly on age, with up to one third of patients being denied SAVR based solely on age, irrespective of their estimated surgical risk. 7,8he evolving landscape in the treatment of AS and the increasing relevance for an ageing population justifies a renewed evaluation of SAVR outcomes in the elderly.As such, this study sought to examine the short-and long-term outcomes after SAVR, comparing allcause mortality and complication rates between patients less than 75 years and patients 75 years or older, to evaluate the validity of age-based guideline recommendations in the local context.

Methods
This retrospective, single-institutional cohort study was approved by the Gold Coast Hospital and Health Service Human Research and Ethics Committee (Reference Number: LNR/2022/QGC/84135), in accordance with the principles set out by the Declaration of Helsinki.Data were collected retrospectively from the Gold Coast University Hospital Cardiothoracic Surgery Database.All consecutive patients who underwent SAVR at the Gold Coast University Hospital from 1 June 2014 to 13 January 2022 were included.Patients with concurrent aortic or valve procedures were excluded.
The local database corresponds to the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Cardiac Surgery Database, for consistency of data definitions as follows. 9Operative mortality was defined as death within 30 days postoperatively.New renal insufficiency was defined as an increased serum creatinine to >200 μmol per litre and a doubling in creatinine over baseline preoperative value or a new requirement for dialysis or hemofiltration.Arrhythmia includes any of atrial or ventricular origin or requirement for pacemaker insertion.Permanent stroke was defined as a central neurological deficit persisting for more than 72 h.Anticoagulation complications were defined as any bleeding, haemorrhage and/or embolic events related to anticoagulant therapy.
All statistical analyses were conducted using Stata 17 Statistics software (College Station, Texas, USA).For this study, patients are grouped into those who were <75 years (Group 1) and ≥75 years (Group 2).Demographic and clinical variables were summarized using descriptive statistics.Continuous variables were described with the mean and standard deviation or median and interquartile range depending on normality, which was assessed by the Shapiro-Wilk test.Categorical variables were summarized as frequencies and proportions.Risk ratios were calculated to demonstrate the effect of age group on outcomes.To assess the effect of age group and other potential covariates on dichotomous outcomes (overall mortality, mortality at 30 days, 1 year and 5 years), logistic

Preoperative variables and operative data
Demographic and operative characteristics are presented in Tables 1  and 2 respectively.Of 613 patients, 70.31% were <75 years (Group 1) and 29.69% were ≥75 years of age (Group 2).The mean age of Group 1 was 62.86 AE 10.45 years compared with 79.38 AE 3.17 years in Group 2. Group 1 patients were more likely to be male and less likely to have hypercholesterolemia, hypertension, and previous arrhythmia.Group 1 underwent more isolated SAVR than Group 2 (P = 0.01).Group 1 had a higher frequency of urgent and emergency surgery, and lower frequency of elective and salvage surgery compared with Group 2 (P = 0.002).The duration of cardiopulmonary bypass and crossclamping were similar between groups (P = 0.86 and P = 0.58 respectively).

Long term outcomes
The all-cause mortality was higher in Group 1 compared to Group 2 at both 1 and 5 years postoperatively (3.94% versus 2.75%, P = 0.47; 7.66% versus 6.59%, P = 0.65).Age ≥ 75 was not found to be an independent predictor of 1-year, 5-year or overall mortality.

Temporal trends
The temporal trend in operative mortality, return to theatre, new renal failure, readmission within 30 days and prolonged ventilation are illustrated in Figure 2. The incidence of prolonged ventilation and return to theatre were numerically higher in 2021 compared to the preceding seven-years mean but neither reached statistical significance (14.00% versus 8.00%, P = 0.26, and 22.22% versus 15.28%, P = 0.42, respectively).The temporal trend of operative mortality, new renal failure and readmission within 30 days remain consistently low over 7 years.

Discussion
Severe AS carries a two-fold increase in mortality without intervention. 10More than half of these patients will die within 5 years.Aortic valve replacements are therefore considered lifesaving, returning expected survival to that comparable to their unaffected age-and sex-matched peers. 11Despite consensus on the survival benefit of valve replacement, a recent study revealed that 20% of patients with AS who fulfilled Class I recommendation for intervention according to the EACTS/ESC guidelines were denied intervention, with older age and comorbidities particularly influencing decision-making. 113][14] We reported an operative mortality of 2.12% for the entire cohort and 1.28% for the AS-only subgroup.This compares favourably with the existing literature, with operative mortality rates ranging from 2% to 9.6%, including the ANZSCTS study from over a decade ago. 3 This may represent a better understanding of frailty and thereby, improved patient selection.Over the last decade, frailty has been recognized as an important predictor of survival that is not captured in conventional risk scores such as the Society of Thoracic Surgeons (STS) score and EuroScore II. 15Despite measures developed to assess frailty, there is inconsistent uptake of validated tools across health services, limiting its impact as an adjunct to assessing surgical candidacy.With no difference in long-term mortality between age groups and low operative mortality, the results reinforce the consistency of favourable outcomes after SAVR in our tertiary cardiac centre.
Concerns about stroke risk with TAVR have been raised and remain a controversial area of discussion.A recent meta-analysis showed that although TAVR was protective periprocedurally, the advantage reverses after 1 year and becomes a risk factor for allcause mortality and stroke after 2 years. 2 Consistent with our findings, Wang et al. found no difference in the incidence of stroke after SAVR between septuagenarians and octogenarians. 16he development of renal insufficiency is a recognized complication after both SAVR and TAVR.A national study found that octogenarians had a higher incidence of renal failure post-SAVR compared to those aged less than 80 (11.70% versus 4.20% respectively, P < 0.001). 3However, this was not illustrated in our results, which showed that patients less than 75 years had a higher incidence of renal failure (P = 0.02).This may in part be explained by the difference in age-based selectivity, where elderly patients are more likely to be denied surgery compared to younger patients, due to presumed frailty.This highlights the potential ways in which age-based recommendations can be problematic as it casts assumptions on operability.Importantly, age was not found to be a predictor for mortality at 30 days, 1 year or 5 years.This was true for other variables including hypertension, pre-existing arrhythmias, dyslipidaemia, NYHA class and ejection fraction.Reassuringly, the short-and long-term survival demonstrated in both the overall cohort and the AS-only subgroup suggests that SAVR achieves excellent outcomes regardless of valvular pathology.
While outcomes post-SAVR have been well published, this contemporary study is one of few that provides age-based analysis as a response to the most recent guidelines for AS treatment.While the literature often reports outcomes of all patients undergoing SAVR, this study included AS-specific subgroup analyses, to ensure the applicability of results to AS patients.The main limitations are its retrospective nature and selection bias.Despite the regional nature of this study, it will serve as a useful comparison for benchmarking with cardiac centres across Australia.
With the imminent expansion of TAVR indications in Australia, this contemporary study adds to the evidence that SAVR should not be withheld based on age alone, despite age-based guidelines.SAVR remains an effective treatment for AS with long-term survivorship, even in selected elderly patients.

Fig. 1 .
Fig. 1.Kaplan-Meier survival curve comparing survival estimates stratified by age for (a) all patients who underwent SAVR and (b) patients with AS who underwent SAVR.

Fig. 2 .
Fig. 2. Temporal trends in early outcomes after SAVR in a single tertiary cardiac centre.

Table 1
Patient characteristics stratified by age regression was performed.Univariate analyses were first performed.Normally distributed variables were compared with Student's t-test, while non-normally distributed continuous variables were compared using the Mann-Whitney U test.Categorical variables were compared using a Chi-square or Fisher's exact test.Variables found to have a P < 0.1 on univariate analysis and those that were clinically important (age group, hypercholesterolaemia, congestive heart failure, New York Heart Association Class, and concomitant coronary artery bypass graft) were tested in the logistic regression model.Variables were retained if P < 0.05 or if the odds ratio (OR) was considered clinically important (>3 or < 0.3).Age ≥ 75 was always included.Time-to-event analyses were performed on long term mortality data obtained via automatic linkage with the Births, Deaths and Marriages registry.The census date was 22nd February 2022.Kaplan-Meier survival curves were constructed, and log-rank tests used to assess the effect of each dichotomous variable.A Cox proportional hazards model identified independent predictors for time-to-mortality.The analyses were performed in the overall cohort and for the AS-specific subgroup.

Table 2
Operative characteristics of all patients who underwent SAVR

Table 3
Outcomes within 30 days postoperatively for patients with AS