Previous studies have validated the favorable effect of complete revascularization (CR) on the prognoses of patients with complex coronary artery disease (CAD) [1, 2, 3]. The COMPLETE trial, which compared CR versus culprit-only revascularization strategies for treating multivessel disease after early percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), demonstrated that CR was better than culprit-lesion-only PCI in lowering the risk of adverse cardiovascular events in individuals affected by STEMI and multivessel CAD [4]. Additionally, renal function impairment has been associated with rapid plaque progression, potentially contributing to the vulnerability of coronary plaques and increasing the risk of CAD [5, 6]. Furthermore, the Grand Drug-Eluting Stent (Grand-DES) registry, which included five multicenter national Korean registries, reported that CR leads to improved clinical results in individuals with chronic kidney disease (CKD) compared to incomplete revascularization (IR) [7]. Therefore, the complexity and severity of coronary disease and renal function determine the PCI strategy for CR or IR in clinical settings. Hence, risk stratification and evaluation of residual disease should be performed for the long-term prognosis of individuals with complex CAD and chronic renal insufficiency (CRI) after PCI.

The development of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS), also known as the pre-PCI SS, was aimed at evaluating the anatomic complexity of angiographic stenoses and facilitating decision-making for the optimal revascularization approach in individuals with complex CAD [8]. However, previous research has revealed the association of SS with mortality and adverse cardiovascular events in acute coronary syndrome (ACS) [9, 10]. Despite its usefulness, the lack of clinical variables in SS has been identified as a limitation by European and United States revascularization guidelines [11, 12]. To overcome these limitations, the SYNTAX score II (SS-II) was developed, which combines anatomical factors (SS and unprotected left main coronary artery (ULMCA) disease) with six clinical variables (age, creatinine clearance, left ventricular ejection fraction (LVEF), sex, chronic obstructive pulmonary disease (COPD), and peripheral vascular disease). Compared to SS, SS-II has shown a gradually increasing predictive value for long-term mortality in individuals with complex CAD undergoing PCI [13]. Head et al. [1] reported that IR was associated with unfavorable clinical outcomes after PCI in a 3-year SYNTAX trial, and the post-PCI SYNTAX score, such as the residual SYNTAX score (rSS), was developed to evaluate the predictive value of IR after PCI in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, quantifying the residual burden of anatomical coronary disease [2]. The high-rSS group was associated with an elevated risk of clinical comorbidity and a disease characterized by more anatomical complications compared to low-rSS groups [3]. Additionally, previous studies have shown that rSS is relevant to poorer clinical outcomes both during the in-hospital period and the subsequent long-term period after discharge [14, 15]. Recently, the post-PCI SS-II, such as the residual SS-II (rSS-II), has been validated for predicting long-term outcomes in individuals with ACS [16, 17]. However, no prior studies have evaluated the predictive value of rSS-II in patients with complex CAD and CRI. Therefore, the main objective of this research was to validate the prognostic value of rSS-II in individuals with complex CAD and CRI after PCI.

Several important findings were observed in this study: (1) rSS-II was able to predict long-term prognosis over a median follow-up time of 37 months in individuals with complex CAD and CRI after PCI. (2) Compared to rSS and SS-II, rSS-II showed improved calibration, higher net benefit for clinical performance, and better discriminative capacity. (3) rSS-II was able to independently predict long-term prognoses and effectively stratify patients based on their risks of ACM and CM after PCI in individuals with complex CAD and CRI.

Despite Généreux et al.’s [2] claim that post-PCI residual coronary stenosis is a nidus of new events, the treatment of non-culprit vessels and the timing of PCI have been questionable until recently. The SYNTAX trial showed that IR has a negative effect on long-term clinical outcomes and is a surrogate biomarker of significant coronary complexity and clinical comorbidity [26]. The COMPLETE trial reported that CR during the index hospitalization is linked to a clear clinical benefit compared to culprit-lesion-only PCI in individuals with STEMI and multivessel CAD [4]. Several studies have also shown that CR improves the prognosis of individuals receiving PCI for ACS with CKD [7, 26]. However, in the CKD population, Kim et al. [27] found no therapeutic benefit of angiographic CR compared to IR. In this study, first-generation DES was used by about 60% of patients, while second-generation DES has been reported to have a protective impact on clinical outcomes in CKD-affected individuals [28].

The Grand-DES investigation found that CKD-affected individuals who underwent multivessel PCI during the index hospitalization had a reduced incidence of death and cardiovascular events for up to three years after the procedure [7]. However, due to high adverse event rates and low procedural success rates, only a small proportion (3.4%) of patients received CR in this study. The findings of this research are consistent with those reported by the IR group of the trial, indicating that a higher residual disease burden, equivalent to a higher rSS-II, increases unfavorable cardiovascular outcomes in individuals with complex CAD and CRI after PCI.

A previous study demonstrated that rSS, which quantifies the residual burden of anatomical coronary disease, evaluated the predictive value of IR after PCI [2]. Farooq et al. [3] indicated that rSS was capable of independently predicting 5-year ACM in individuals affected by complex CAD after PCI using drug-eluting stents in the SYNTAX trial. However, the application of rSS in clinical practices is limited due to the absence of clinical variables, which has led to the establishment and validation of rSS-II for predicting the prognosis of individuals receiving PCI. Boukhris et al. [29] demonstrated that rSS-II could anticipate midterm outcomes in patients with complex ACS. Bortnick et al. [16] further suggested that rSS-II was associated with long-term ACM using Cox regression analysis in a post-STEMI cohort from the Montefiore STEMI registry (HR: 2.46, 95% CI: 1.51–3.99, p 0.001), which is consistent with the findings of this research. However, the main distinction is that the registry did not stratify different risk outcomes based on rSS-II for patients with STEMI. Risk stratification is important for identifying individuals at a higher risk of a particular health condition in order to offer proven interventions. In comparison, patients in the SHINANO registry were classified into two categories based on the cut-off value calculated using ROC analysis for ACM [17], showing that the incidence of ACM in the high-score group was significantly higher than in the low-score group (38.0% vs. 5.7%, p 0.01). In this research, patients were classified into three categories based on rSS-II. Compared to the low- and medium-rSS-II groups, the high-rSS-II group had a significantly higher incidence of ACM and CM.

In the SHINANO registry, Kashiwagi et al. [17] indicated that rSS-II might be a crucial tool in predicting long-term mortality in individuals with ACS and multivessel disease following PCI. The AUC of rSS-II for predicting ACM (AUC = 0.82, 95% CI: 0.74–0.91) was significantly better compared to that of rSS (AUC = 0.54, 95% CI: 0.1–0.67) (p 0.001). Although the AUC of rSS-II showed an increasing trend compared to SS II (0.82 [0.74–0.91] vs. 0.80 [0.71–0.90], p = 0.089), it was not statistically significant. Furthermore, this research demonstrated a similar discriminative power of rSS-II compared to the original rSS and SS-II in predicting ACM in individuals with complex CAD and CRI following PCI. However, the main differences existed in the sub analysis performed using data from the SHINANO registry, which recruited only 120 patients, and the validation of rSS-II was based solely on its discriminative power, lacking calibration and evaluation of clinical utility.

Discrimination, calibration, and clinical utility are well-established components of a predictive model. Steyerberg et al. [30] emphasized that decision-analytic measures should be reported prior to applying the prediction model for clinical decision-making. This approach can potentially assist physicians in evaluating the significance of information by using a risk assessment tool to compare potential risks and benefits. In this research, the advantage of rSS-II over rSS and SS-II for clinical applications was determined through DCA, given that rSS and SS-II were already being used in clinical research and practices. The rSS-II demonstrated acceptable net benefits across various threshold probabilities for long-term prognoses compared to rSS and SS-II.

There are certain limitations to this study. Firstly, it was a retrospective, single-center study. Therefore, further prospective studies and multicenter datasets are necessary to assess the generalizability and validity of rSS-II. Secondly, pre-PCI creatinine clearance and LVEF were used in the study. However, a previous study reported that creatinine clearance and left LVEF in SS II should be modified using PCI [29] and used as post-PCI in rSS-II. Hence, further studies including postoperative creatinine clearance and LVEF are needed to validate the performance of rSS-II in predicting the prognosis of individuals with complex CAD and CRI after PCI. Finally, rSS-II was validated only in the Chinese population. Therefore, additional studies with larger population samples are required to further validate its performance.

The present study provides favorable evidence for the precise use of rSS-II in predicting long-term clinical outcomes in individuals with complex CAD and CRI after PCI. Over a median follow-up of 37 months, rSS-II demonstrated good discriminatory power for risk prediction of ischemic outcomes. Furthermore, it can identify patients who may benefit from further revascularization.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

SYZ, YML, and LQY provided the conception of the idea for the study. SYZ, YML, and JFC contributed to the development of the methodology and wrote the manuscript. SYZ, YML, JFC, YCW, HTL, NG, YFW, and XFC were responsible for the interpretation of statistical results. LQY revised 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 Ethics Committee of Cangzhou Central Hospital, Hebei Medical University had approved the study protocol (ID: 2017-006-01), which was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent could be successfully provided by all cases.

We are grateful to all of the study participants whose work made this study possible.

This work was supported by the Special Project for Clinical and Basic Sci & Tech Innovation of Guangdong Medical University (GDMULCJC2024112) and the Natural Science Foundation of Hebei Province, China (H2021110008).

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/RCM26962.