Impacts of Residual SNYTAX Score on The Clinical Outcomes Following Percutaneous Coronary Intervention in Chronic Coronary Syndrome Patients

Background : The residual SYNTAX score (RSS) can be used to measure the residual stenosis severity and complexity. The prognostic role of RSS in CCS patients is still unknown. We purposed to investigate the impact of RSS on the clinical outcomes following PCI in CCS patients. Methods : A prospective cohort study was performed. Based on the residual SYNTAX score, patients were divided into three groups: RSS 0, RSS 0 to 9.5, and RSS >9.5. The primary outcome was patient-oriented composite endpoint (POCE), including repeat revascularization, myocardial infarction, and all-cause mortality. Results : After 1-year follow-up period, patients in RSS >9.5 group revealed the greater POCE (4.3% vs. 6.4% vs. 23.9%; p = 0.016) than others. The repeat revascularization rate also was greater in the RSS >9.5 group (0.0% vs. 6.4% vs. 19.6%; p = 0.012). However, the hospitalization due to angina rates in all groups was not significantly different (4.3% vs. 4.2% vs. 4.3%; p = 1.000). The multivariate analysis revealed that RSS >9.5 was the strong predictor for repeat revascularization during 1 year follow-up (Odds ratio [OR] = 9.605; 95% confidence interval [CI] = 1.207 - 76.458; p = 0.033). Conclusion : The greater RSS was associated with the higher 1-year POCE and repeat revascularization rate in CCS patients. The high RSS was also the strong predictor for 1-year repeat revascularization for CCS patients.

Coronary artery disease (CAD) is a chronic disease due to atherosclerotic plaque generation in the epicardial coronary arteries. 1,2 Globally, CAD has been recognized as the number one cause of death. 2,3 Every year, at least 470,000 Indonesian people are estimated to die due to stroke or CAD. 4 The dynamic nature of CAD manifests as the various clinical presentation. Acute coronary syndromes (ACS) and chronic coronary syndromes (CCS) are the clinical manifestations of CAD.1 The CCS is a new terminology that replaces "stable CAD." It is a progressive atherosclerotic plaque accumulation process accompanied by functional changes in the epicardial coronary artery. 1 Myocardial revascularization through coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) are the cornerstones of the CCS treatment strategy. 1,5 Complete revascularization has to be achieved during conducting PCI or CABG. However, in a particular circumstance, complete revascularization cannot be achieved by PCI because of several reasons. 6 The severity and complexity of coronary artery lesions can be assessed using the SYNTAX score. 7,8 The residual SYNTAX score (RSS) can be used to measure the residual stenosis severity and complexity by calculating the SYNTAX score from post-PCI angiography. 9 The ACUITY trial revealed that in non-ST elevation myocardial infarction (NSTEMI), the RSS >8 could independently predict 1-year ischemic events and mortality. 10 A study from Altekin et al. demonstrated that in ST-elevation myocardial infarction (STEMI), the higher RSS was associated with the greater ischemic cardiac events. 11 The prognostic role of RSS in CCS patients is still unknown. In this prospective study, we purposed to investigate the impact of RSS on the clinical outcomes following PCI in CCS patients.

Study design and participants
We conducted a prospective cohort study in dr. Saiful Anwar General Hospital Malang, East Java, Indonesia in 2016. This cohort study conformed with the declaration of Helsinki principles and was recognized by the local research ethics board. Before collecting data, 20 Original Article patients or their family members had signed the informed consent.
In this study, we included: (1) all CCSs patient who underwent PCI, (2) aged >40 years; (3) previous history of myocardial infarction (MI) or positive exercise stress test result; (4) treated with optimal medical treatment based on guideline; and (5) good adherence to the medication. The exclusion criteria were: (1) lost to follow-up; (2) incomplete data; (3) disability to conduct physical activities; (4) myocardial infarction within two weeks following PCI procedure; and (5) psychiatric disorders. All essential data regarding clinical, angiographic, and procedural characteristics data were collected from the direct interview and medical record. Our study flowchart was displayed in figure 1

Statistical analysis
The IBM Statistical Package for Social Science (SPSS version 25.0) was used in processing data. The number and percentage were used to show the categorical data. Mean and standard deviation (SD) were used to describe continuous data with normal distribution. On the other hand, median and interquartile range (IQR: the 25th percentile [0.25 quantile] and the 75th percentile [0.75 quantile]) were used to show continuous data with the abnormal distribution. We used the Shapiro-Wilk test and the Kolmogorov-Smirnov test to evaluate continuous data normality. The analysis of variance (ANOVA) or Kruskal Wallis tests were used to compare continuous data with or without normal distribution, respectively. The Chi-squared test and Kolmogorov-Smirnov test were used to compare categorical data. The p-value was less than 0.05 was considered statistically significant.

Clinical outcomes
All patients for whom the loss of follow-up was not included in the data analysis. After 1-year follow-up period, patients in RSS >9.5 Figure 1. Study flowchart. CCS = chronic coronary syndromes; PCI = percutaneous coronary intervention. Table 1. Baseline characteristics ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BMS = bare metal stent; CAD = coronary artery disease; CTO = chronic total occlusion; DES = drug-eluting stent; LAD = left anterior descending; PCI = percutaneous coronary intervention; RCA = right coronary artery; RWMA = regional wall motion abnormality. data in Indonesian population with no loss of follow-up. We evaluated the severity of incomplete revascularization using RSS and its effect on the clinical outcomes in CCS patients. Several essential findings were obtained from this prospective cohort study. First, the greater RSS was associated with the higher 1-year POCE and repeat revascularization rate in CCS patients. Second, in CCS patients, the high RSS (RSS >9.5) was the strong predictor for 1-year repeat revascularization.
Atherosclerosis formation is the key pathogenesis in CAD. It is slowly progressing for several decades. The atherosclerosis risk factors including, male sex, genetics, dyslipidemia, obesity, hypertension, diabetes mellitus, or sedentary lifestyle induce a low-grade inflammation. That low-grade inflammation has the critical role in the atherosclerosis process acceleration. In CCS, this slowly progressive group revealed the greater POCE (4.3% vs. 6.4% vs. 23.9%; p = 0.016) than others. The repeat revascularization rate also was greater in the RSS >9.5 group (0.0% vs. 6.4% vs. 19.6%; p = 0.012). However, the hospitalization due to angina rates in all groups was not significantly different (4.3% vs. 4.2% vs. 4.3%; p = 1.000). Only one patient in RSS >9.5 group passed away during the follow-up period. The summary of the outcomes is presented in Table 2. The multivariate analysis revealed that RSS >9.5 was the strong predictor for repeat revascularization during 1 year follow-up (Odds ratio [OR] = 9.605; 95% confidence interval [CI] = 1.207 -76.458; p = 0.033)

Discussion
This prospective cohort study represented the real-world

Clinical characteristics
Some important lessons can be drawn from our current research. First, our research provided the data about the benefit of complete revascularization (RSS 0) in reducing 1-year POCE and repeat revascularization in CCS patients who underwent PCI. Second, incomplete revascularization with high RSS was the strong predictor for 1-year repeat revascularization. However, our current research had some limitations. First, this study was a single-center study. Second, our present study included small number of patients compared to the previous studies. 10,11,13,24 Third, even though we conducted multivariate analysis to overcome significant confounders, we cannot manage the other confounders that may bring the significant impact on the study results. Fourth, we did not compare the prognostic value of RSS with the novel SYNTAX-II score, which includes clinical and angiographic parameters. 25 Because of those several drawbacks, a randomized controlled trial (RCT) with better design, larger study population, and longer follow-up is required.

Conclusion
Our study demonstrated that the greater RSS was associated with the higher 1-year POCE and repeat revascularization rate in CCS patients. The high RSS was the strong predictor for 1-year repeat revascularization for CCS patients. The RSS can be used to guide the level of revascularization determination and the next revascularization strategy.

Ethics Approval and Consent to participate
This study was approved by local Institutional Review Board, and all participants have provided written informed consent prior to involve in the study.

Consent for publication
Not applicable.

Availability of data and materials
Data used in our study were presented in the main text.

Competing interests
Not applicable.
6.5. Funding source Not applicable.

Authors contributions
Idea/concept: WKA. Design: WKA. Control/supervision: MSR, HM, PS, CTT, YW. Data collection/processing: WKA. Extraction/Analysis/ atherosclerotic process results in coronary artery inner layer thickening. The final result of this process was coronary artery lumen narrowing with diverse severity. 14 The coronary artery stenosis severity can be assessed non-invasively using computed tomography angiography (CTA) or invasively using coronary angiography (CAG). However, until now, the CAG is still the gold standard tool in evaluating coronary artery stenosis severity. 15 In determining the vessel wall and atherosclerotic plaque morphology, other imaging modalities including, optical coherence tomography (OCT) and intravascular ultrasound (IVUS), are required. 16,17 In certain conditions, myocardial ischemia occurs because the stenotic blood vessels fails to compensate the raised myocardial oxygen demand. 18,19 The compensatory vasodilation is not helpful if the coronary artery lumen stenosis is greater than 80% of lumen diameter. Endothelial disfunction, microvessel disease, or vascular spasm may increase the ischemia. 19 Complete revascularization with PCI is recognized to be beneficial because it can significantly improve myocardial infarction and cardiovascular death. 20 However, around 59% of patients have incomplete revascularization following PCI procedure. 21 SYNTAX score has been developed to determine coronary artery lesions' complexity or severity. The higher SYNTAX score represents a more complex and more severe coronary artery lesion. It is also correlated with bad prognosis in CAD patients receiving PCI. 7,8 For CAD patients with complex lesions such as three-vessel disease or multivessel CAD, the high SYNTAX was a strong predictor for major adverse cardiovascular events (MACE) or mortality. 22,23 The residual SYNTAX score can be calculated from post-PCI angiography to assess the complexity and severity of the residual stenotic lesion. 9 It is important to stratify the patients and prepare the next revascularization strategy.
Our results supported the findings of the prior studies. In the EXCELLENT registry, the higher RSS (RSS >7) was associated with increased 1-year POCE and repeat revascularization. Moreover, in that study, the high RSS was recognized as the significant predictor for 1-year POCE. 13 A study from Yan et al. revealed that incomplete revascularization (RSS >8) increased the risk of MACE, MI, cardiac mortality, all-cause mortality, repeat revascularization, and stroke. 24 Both studies included all ACS and CCS patients. However, our current study only included CCS patients. In the ACS setting, two previous studies revealed that RSS had an excellent performance in predicting the poor prognosis. The ACUITY trial revealed that in NSTEMI, the RSS >8 could independently predict 1-year ischemic events and mortality. 10 Altekin et al. demonstrated that the higher RSS (RSS >7) was associated with the greater ischemic cardiac events in STEMI patients. 11 This study demonstrated that higher RSS was not associated with higher rehospitalization because of angina. This finding was not reported in the prior studies. 10,11,13,24 In theory, complete revascularization (RSS 0) can provide better clinical outcomes regarding angina or rehospitalization because of angina. However, our finding failed to prove it. It could