Aortic stenosis (AS) is the most prevalent heart valve disease, causing significant morbidity and mortality in the elderly due to aging of the population [1, 2, 3]. Its prevalence exceeds 10% in individuals aged over 65 in US and European populations [4, 5, 6], although the prevalence in China may be lower, according to the results of a single-centre retrospective study of the echocardiographic data of 287,556 patients [7]. The initial stages of the disease are characterized by the progression of valvular lesions, involving endothelial cell damage, infiltration with lipids and macrophages, lipid oxidation, and subsequent fibrosis and calcification, which ultimately leads to obstruction of the aortic valve [6, 8].

To date, due to the lack of specific medications for treating or preventing the progression of AS, aortic valve replacement (AVR) which includes surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) is recommended for patients with severe symptomatic disease [9, 10].

EuroSCORE II is a logistic risk model developed in 2011 from 22,381 patients in 22 European centers and weights 18 peri-operative variables (age, renal function, cardiac status, etc.) [11]. It was originally developed for perioperative risk stratification in cardiac surgery [11, 12], but had also been validated for predicting in-hospital mortality and short-to-medium-term mortality after AVR [13], coronary artery bypass grafting (CABG) [14]. However, there are limited studies assessing the long-term prognostic value of EuroSCORE II for patients with moderate-to-severe AS, regardless of whether they undergo AVR (SAVR or transcatheter aortic valve replacement (TAVR)), especially in Chinese patients.

This study aimed to explore the relationships between EuroSCORE II, AVR status, and all-cause mortality in patients with moderate-to-severe AS, and to identify the optimal EuroSCORE II cut-off value for prognostic use in patients without AVR.

A growing body of evidence demonstrates that patients with symptomatic severe AS have a poor prognosis if they do not undergo surgery, with a mean survival time of 4 years [8]. Therefore, AVR is widely recommended for the treatment of such patients [17]. EuroSCORE II, originally developed for perioperative risk stratification in cardiac surgery, incorporates variables such as age, renal function, and extracardiac arteriopathy, which are also implicated in the progression of calcific aortic valve disease [6].

The study found that high-risk group (EuroSCORE II $\ge$4%) was associated with higher risk of all-cause mortality. Our baseline results revealed that a high EuroSCORE II reflects not only heart disease severity but also broader end-organ damage, including key factors like kidney dysfunction, anemia, liver congestion from heart failure, and malnutrition.

It is this comprehensive physiological decline that renders patients too vulnerable to withstand the persistent hemodynamic stress of untreated severe aortic stenosis, ultimately leading to the observed extremely high mortality [18]. The pathophysiological overlap between cardiovascular risk factors and AS progression—particularly the roles of chronic inflammation, endothelial dysfunction, and calcification [19]—suggests that EuroSCORE II may be used for not only surgical risk but also underlying disease severity and systemic vascular health.

While the STS score is another widely used risk model, a meta-analysis of 22 studies involving 145,592 cardiac surgery procedures showed that the overall discriminatory ability of the EuroSCORE II is good and similar to that of the STS risk score. However, the STS risk score has shown a suboptimal calibration in some validation studies, particularly in European cardiac surgical populations [20]. Future studies directly comparing these models in Chinese patients with AS would be valuable.

In this context, our study extends the utility of EuroSCORE II beyond the perioperative setting, demonstrating its prognostic value for long-term mortality within the past 10 years in Chinese patients with moderate-to-severe AS, regardless of AVR status. We found that patients in the high-risk group (EuroSCORE II $\ge$4%), irrespective of whether they underwent AVR, exhibited a significantly higher risk of all-cause mortality compared to those in the low-risk group, which was align with previous studies linking EuroSCORE II to outcomes in TAVI patients [16, 21, 22]. A retrospective study of 350 patients with moderate-to-severe AS undergoing TAVI found that 30-day mortality was associated with higher EuroSCORE II (12.6 $\pm$ 1.8% vs. 7.5 $\pm$ 0.3%, p 0.001) and an AUC of 0.70, indicating its predictive value for short-term mortality [16]. Another study of 59 patients with severe symptomatic AS who underwent TAVI between 2010 and 2014 also showed that EuroSCORE II predicts in-hospital and 30-day mortality [23]. However, the short duration of follow-up in these studies limits their relevance to clinical practice. In contrast, a long-term retrospective study by Fan et al. [24] categorized 332 patients with low-gradient severe AS and preserved LVEF into high-risk (EuroSCORE II $\ge$4%, N = 115) and low-risk (EuroSCORE II 4%, N = 208) groups and followed them for 2 years [25]. Unlike these reports that were limited to follow-up time, our long-term follow-up offers similar insights that the high-risk group had significantly poorer cumulative survival compared to the low-risk group when using 4% as a cut-off value.

Moreover, moderate-to-severe aortic stenosis patients with a low-risk EuroSCORE II (4%) were also recommended to undergo AVR, as it significantly reduced the risk by 77% of all-cause mortality, which was similar to some major trials in low-risk patients.

Notably, the PARTNER2 study [26] and the SURTAVI study [27] using TAVR in low-risk patients performed by the American College of Cardiology (ACC), including the PARTNER 3 study (using the SAPIEN-3 ultra transcatheter heart valve) and the Evolut Low Risk Trial study (using the self-expanding Evolute R valve) [28] showed TAVR’s non-inferiority or superiority to SAVR in short to medium-term outcomes. After 5 years of follow-up, the PARTNER 3 study revealed similar annual rates of cardiovascular mortality, stroke, and re-hospitalization for both TAVR and SAVR (approximately 1%, 1%, and 3%, respectively). These findings support recommending either procedure for low EuroSCORE II patients, offering benefits such as shorter hospital stays and lower mortality risks [29]. Therefore, surgical or transcatheter AVR (SAVR/TAVI) is recommended for low-risk patients to achieve a clear survival benefit, aligning with international guidelines and providing real-world validation in a Chinese population. Our study confirms that SAVR and TAVI have similar outcomes for moderate-to-severe AS. The prospective NOTION trial (N = 280) showed no significant differences in 2-year all-cause (8.0% vs. 9.8%; p = 0.54) or cardiovascular mortality (6.5% vs. 9.1%; p = 0.40) between TAVR and SAVR [30]. Moreover, the NOTION trial’s extended data revealed no significant all-cause mortality difference over 8 years [15]. The 2021 ESC/EACTS guidelines recommend SAVR for patients under 75, and TAVR for those over 75, high-risk (STS-PROM or EuroSCORE II $>$8%), or ineligible for surgery (class I) [9]. Despite guidelines, numerous randomized clinical trials show TAVR is at least as effective as SAVR for short- to medium-term results [31, 32].

A key validation study demonstrated EuroSCORE II’s inaccuracies in predicting mortality for cardiac surgery patients, either underestimating for high-risk or overestimating for low-risk groups [32]. Our ROC analysis identified a EuroSCORE II cut-off of 2.23% (AUC, 0.675) for moderate-to-severe AS patients without AVR, validated by Kaplan-Meier (log-rank p 0.001) and Cox analyses (HR 2.111, 95% CI 1.069–4.166, p = 0.031). This threshold, more accurate than the traditional 4%, may enhance clinical detection, treatment response, and prognosis for these patients. Notably, the original 4% value applied broadly to AS patients, regardless of surgery, whereas our 2.23% value is specific to those with moderate-to-severe AS who have not undergone AVR.

The study’s strengths include its multi-centre observational design with verifiable external validity, a 9-year follow-up period, and robust adjustment for confounders, confirming the significant association between EuroSCORE II and all-cause mortality in moderate-to-severe AS patients. These findings enrich the clinical utility of EuroSCORE II in predicting AS outcomes, potentially improving patient outcomes and reducing disease burden.

Our study has the following strengths: firstly, our research uniquely examines the predictive value of EUROSCORE II for both moderate and severe aortic stenosis (AS) patients, expanding the scope beyond the commonly studied severe AS population and providing insights into a broader spectrum of disease severity. Secondly, our study is based on multi-center data sourced from three centers within a database jointly collected by multiple Chinese valve centers, ensuring the diversity and representativeness of the sample. Additionally, our study benefits from a long follow-up period of up to 9.09 years, with a wide-ranging span that enhances the stability and reliability of our conclusions. Importantly, we innovatively propose modifying the EUROSCORE II cut-off value to 2.23% for moderate-to-severe AS patients without AVR surgery, addressing a gap in the literature and offering a novel perspective on risk stratification.

However, limitations exist. This study is a Chinese-based retrospective cohort which has its inherent selection bias and our sample size was relatively limited, thus lacking generalization and necessitating external validation. Additionally, the applicability of EuroSCORE II is limited by etiological differentiation (e.g., degenerative calcific vs. rheumatic) for aortic stenosis due to lacking historical records data. Moreover, echocardiographic and laboratory parameters were static, risking bias from measurement errors or inter-center criteria differences.

Finally, though EuroSCORE II was associated with mortality without AVR, its modest accuracy demands supplementation with clinical and imaging data for reliable risk stratification.

In conclusion, both the EuroSCORE II (cut-off value 4%) and AVR status were independently associated with the long-term prognosis of patients with moderate-to-severe AS. Patients with a low-risk EuroSCORE II (4%) should be recommended to undergo AVR (either SAVR or TAVI). Furthermore, our analysis identified an exploratory, lower EuroSCORE II cutoff value of 2.23% for risk stratification in patients who did not undergo AVR. However, this novel threshold is derived from retrospective data and requires prospective validation before any clinical application can be considered.

EuroSCORE II, European System for Cardiac Operative Risk Evaluation; SBP, systolic blood pressure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HB, haemoglobin; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; TG, triglyceride; Cr, creatinine; CC, creatinine clearance; TBIL, total bilirubin; LVEF, left ventricular ejection fraction; AV-Vmax, maximum velocity of blood flow through the aortic valve; AV-MG, mean gradient across the aortic valve; AVA, aortic valve area; PAH, pulmonary arterial hypertension; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker.

Our heart valvular disease intervention center construction unit from The Second Affiliated Hospital of Shantou University Medical College is part of the National Clinical Medical Research Center for Radiology and Therapy, Interventional Center for Valvular Disease, Dongfang Huaxia Cardiovascular Health Institute, Suzhou Industrial Park. Our data were from Three heart valve centers, which are derived from a database called Aortic Valve Diseases RISk facTOr assessmenT and Prognosis modeL Construction (ARISTOTLE). The datasets used and analyzed during the current study are available from the corresponding authors upon reasonable request.

XC and DH contributed to the manuscript equally. They are responsible for studying conceptualization, data curation, data analysis and writing the original draft. BY and JC are responsible for formal analysis, accessing and verifying the data and writing editing. WL, YL and RL are responsible for investigation, software, data curation and editing. JY, JS and ST are responsible for investigation, software, data curation and editing. XH and BX are responsible for investigation, software, data curation and methodology. XZ, JC and JL are responsible for conceptualization and data curation. JL is also responsible for conceptualization and writing reviews or editing. All authors reviewed the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was carried out in accordance with the guidelines of the Declaration of Helsinki and approved by the Ethics Review Committee of the Second Affiliated Hospital of Shantou University Medical College (ERB number: 2024-23). Patient follow-up was conducted via telephone contact, with verbal informed consent approved by the institutional ethics committee.

We thank Mark Cleasby, PhD from Liwen Bianji (Edanz) for editing the language of a draft of this manuscript.

This research received no external funding.

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM42757.