Study Design and Population
This is a single-center, prospective observational cohort study conducted in Assiut University Heart Hospital (AUHH).
Patient Population
All adult patients admitted to Assiut University Heart hospitals diagnosed with acute coronary syndrome (ACS), including patients with acute ST-segment Elevation Myocardial Infarction (STEMI) or Non-ST-segment Acute Coronary Syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) in the setting of multi-vessel disease (MVD), which was defined as significant coronary artery stenosis in two or more segments of the coronary artery tree, in the period between July 1, 2018, to December 31, 2019.
Patients were excluded either if they received fibrinolytic therapy, presented with cardiogenic shock, underwent CABG, or had severe renal impairment.
Within the previously mentioned criteria, 185 patients were surveyed, of which 149 patients were included, one patient refused to participate in the study, and 35 patients had crucial missing data. Of the 149 enrolled patients, 114 of them (76.5%) were either successfully followed up or met the primary endpoint of the study, and 35 patients (23.5% of the total enrolled patients) were lost to follow-up due to the constraints imposed by the COVID-19 pandemic.
Sample size estimation
Considering the primary endpoint of the study (In-Hospital MACE rate of 28%) (17), the estimated sample size of the population, based on the power of 85%, and alpha= 5%, was calculated to be = 108 patients. The sample size was calculated using the OpenEpi sample size calculator available here: https://www.openepi.com/SampleSize/SSCohort.htm.
Diagnosis of ACS
Patients were diagnosed with ACS based on the latest guidelines of diagnosing STEMI and NSTE-ACS published by the European Society of Cardiology (ESC) in the years 2015 and 2020 for NSTE-ACS diagnosis (13,18) and in 2017 for STEMI diagnosis (11).
Angiographic Analysis
Angiographic analysis was performed in two orthogonal views according to the local protocols used in Assiut University Heart Hospital. The patients’ angiographic views were reviewed, and the bSS and rSS were calculated using a web-based calculator (www.syntaxscore2020.com). All the parameters and stenoses were assessed visually. The rSS was determined as the SS remaining after completion of PCI. In the case of staged-PCI procedures (defined as a second planned PCI procedure after the initial intervention), the final planned procedure was used as the entry point for this study.
Procedural Data
All patients who underwent PCI received 300 mg of aspirin and a 600-mg loading dose of clopidogrel or 180 mg of ticagrelor. Heparin was administered throughout the procedure according to standardized protocols. PCI was performed via femoral or radial approach according to operator’s decision. Glycoprotein IIb/IIIa inhibitors were used at the discretion of the operator. After the procedure, all patients received 75-100 mg/day of aspirin indefinitely, as well as 150 mg for two weeks and then 75 mg/day of clopidogrel or 90 mg b.i.d. of ticagrelor for at least 12 months. Standard post-intervention care was implemented. All patients consented to the procedure.
Angiographic scores:
Residual SYNTAX Score
The baseline SYNTAX (bSS) score and the residual SYNTAX score (rSS) were calculated by summing up the individual scores for each lesion with diameter stenosis ≥50% in vessels with a diameter ≥ 1.5 mm in the angiography obtained before and after the procedure. The SYNTAX algorithm of scoring is fully described elsewhere. (19)
SYNTAX Revascularization Index
The SYNTAX Revascularization Index (SRI), representing the proportion of CAD burden treated by PCI, was calculated using the following formula: SRI= (1-[rSS/bSS]) ×100. (20)
The bSS and rSS were calculated using both the original SYNTAX Score Calculator currently found on http://syntaxscore.org, and the web version of the updated SYNTAX Score 2020 Calculator, which is found on http://syntaxscore2020.com. The results from both calculators were used for test-retest reliability analysis, while the results from the updated edition was used for the remainder of the data analysis. In addition, inter-rater reliability was assessed with the help of two of our colleagues at the Department of Cardiology, who calculated baseline and residual SYNTAX I scores for ten randomly selected patients.
Patients’ follow up and data collection
Patient data, including contact information, PCI reports, discharge reports, and any other relevant data sources, were obtained from the AUHH database. Coronary angiography imaging data and loops were obtained from the AUHH coronary catheterization lab imaging database and Assiut University Hospitals’ Paxera® Picture Archiving and Communication Servers (PACS). Patients with missing reports or imaging data were excluded from the analysis. Patient follow-up has been performed by outpatient clinic visits. Patients who were lost to follow-up were excluded as well from the follow-up analysis process, including survival analysis.
Major Adverse Cardiac Outcomes (MACE), including in-hospital and up to 2-years follow-up, represented a composite of cardiac death (including periprocedural), non-fatal myocardial infarction, heart failure (HF), unplanned revascularization including target vessel revascularization (TVR), target lesion revascularization (TLR) and Coronary artery bypass graft (CABG).
For surviving patients, the initial time limit for follow-up was one year after the date of the coronary intervention. However, due to logistic delays in the study, an additional twelve-month follow-up was introduced to benefit from the added time for qualified patients.
Endpoints of the study and their definitions:
Primary endpoint: The primary endpoint of the study was the in-hospital major adverse cardiac events (MACE)
Secondary endpoint: Included the individual components of the primary endpoint, as well as ACUITY defined major bleeding(21) and acute kidney injury (AKI). Also, the secondary endpoint included up to 2-year MACE and its individual components.
An event was characterized as periprocedural death if it occurred within 24 hours of PPCI. Pre-specified definitions of recurrent MI and bleeding were the same as those used in the ACUITY trial (21). HF was defined as symptoms of dyspnea attributed to pulmonary congestion resulting in administration of oxygen and/or intravenous diuretics amongst other ant-failure treatments. AKI was described as a 25% relative or 0.5mg/dL (44.2μmol/L) absolute increase in presenting serum creatinine after PPCI. (22)
In the case of staged PCI procedures (defined as a second planned PCI procedure after the initial intervention) (23), the final planned procedure was used as the entry point for this study. If there was any event between the procedures, we used the first planned procedure as the reference. The rSS and SRI were calculated after the completion of all staged/planned PCI procedures unless an event occurred between the procedures, then we used the initial scores.
Ethics Statement
This study complied with the Declaration of Helsinki and was reviewed and approved by the ethics committee of the Faculty of Medicine, Assiut University (Institutional Review Board Approval No. 17100078). All patients were informed about the technique, and informed consent was obtained from them.
Statistical Analysis:
All statistical analyses were performed using IBM® Statistical Package for Social Sciences (SPSS) ® Statistics version 25 (SPSS Inc., Chicago, IL, USA) and MedCalc® Statistical Software version 20.013 (MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc.org; 2021). Categorical data were presented as frequencies and percentages, and Chi-square tests were used for comparisons between groups. Continuous data were reported as means ± standard deviations and medians (interquartile range), which were tested for normality using the Shapiro-Wilk test. Where continuous data were normally distributed, the Student's T-test and One-way ANOVA were used for comparisons between groups; where data were non-normally distributed, the Mann-Whitney U and Kruskal-Wallis H test were used. Regression analyses were performed using the binary logistic regression test. The diagnostic accuracy of the angiographic and clinical scores was assessed with the area under the curve (AUC) analysis of receiver operating characteristic (ROC) curves. Regression models were further evaluated for their discrimination power using the concordance index (C-index). Patients were stratified into three tertiles according to their rSS and SRI values, based on the percentiles of both scores.
For survival analysis, the outcome was tested related to time from the admission until death/endpoint along the follow-up period. The Kaplan–Meier survival curves were performed, differences in MACE rates were analyzed by log-rank test, and pairwise comparisons were performed using the Mantel-Cox test. Univariate Cox regression analyses were conducted to detect the hazard ratio (HR) of MACE, and potentially relevant factors were included in a multivariate Cox regression model and adjusted for confounding patient factors. In all statistical tests, p-value <0.05 was considered statistically significant.