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Association of SYNTAX score with myocardial injury in STEMI patients: a cardiac magnetic resonance study

SYNTAX score (SS) is positively correlated with postprocedural myocardial injury identied by high sensitivity cardiac troponin in patients undergone elective coronary artery intervention, evidences about the association of SS with myocardial injury in STEMI patients were still scarce. A total of 149 consecutive patients within 24 h of STEMI were enrolled in the study. Both angiography and cardiac magnetic resonance (CMR) were performed during hospitalization. The time was 7.05 h (4.44,95.91, IQR) from symptom to angiography and 7.31 ± 2.60 days from symptom to CMR. The total median SS was 17(9–25, IQR). In terms of myocardial injury parameters, there was a positive correlation between SS and infarct size (IS) (p < 0.001, Spearman r = 0.292), and negative correlation between SS and myocardial salvage index (MSI) (p < 0.001, Spearman r=-0.314). There was no signicant correlation between SS and area at risk, microvascular obstruction or intramyocardial hemorrhage. According to SS, patients were divided into low SS (< 22) (LSS)(n = 96) or mediate-high SS ( ≥ 22) (MHSS)(n = 53) group. In the multivariable model, after adjustment for important known predictors of IS, MHSS was signicantly associated with high IS ( ≥ mean 35.43) (odd ratio = 2.245, 95% condence interval [1.002–5.053], p = 0.048), as a continuous variate, SS was also signicant associated with high IS (odd ratio = 1.053, 95% condence interval [1.014–1.095], p = 0.008). The areas under the receiver operating characteristic curves of SS for high IS and low MSI were 0.664 and 0.610. Conclusion: of STEMI patients who presented to hospital within 24h from symptom onset, SS was positively related with IS and negatively with MSI. SS was an independent predictor of IS after adjusting for important covariates.


Introduction
It was well established that in acute myocardial infarction patients, high infarct size (IS) and intramyocardial hemorrhage (IMH) were closely related to bad prognosis [1,2]. Microvascular obstruction (MVO) is the underlying cause for the no-re ow phenomenon in ST-segment elevation myocardial infarction (STEMI). The presence and extent of MVO measured by cardiovascular magnetic resonance imaging (CMR) after primary percutaneous coronary intervention (PCI) in STEMI are strongly associated with mortality and hospitalization for heart failure within 1 year and might be a better predictor of longterm major cardiovascular adverse events than IS [3,4].All these parameters, re ecting severity of myocardial injury, were typical indexes of CMR, which has emerged as a robust imaging modality for assessing patients after acute myocardial injury [5]. It is important to identify patients with severe myocardial injury so as to initiate intense care at early phase.
The anatomical Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score is an important instrument that can help clinicians to establish the optimum revascularization approach in patients with complex coronary artery disease (CAD) [6][7][8][9]. Previous studies found that SYNTAX score (SS) correlated signi cantly with cardiac troponin releases after elective PCI and could predicts peri-procedural myocardial injury de ned as elevated troponin I at 6-24 h post-PCI [10,11]. Therefore, it may be reasonable to assume that the complexity of CAD represented by SS is the surrogate of myocardial injury.
The objective of this study was to investigate the association of SS with myocardial injury identi ed by CMR in STEMI patients.

Method Participants
We conducted a single-center retrospective observational study at Cangzhou central hospital-a tertiary care hospital. We identi ed 276 STEMI patients undergone angiography between October 2018 and September 2020. The inclusion criteria were as follow: (1) electrocardiography (ECG) features consistent with acute STEMI (ST-segment elevation ≥1 mm in ≥2 limb leads or ≥2 mm in ≥2 contiguous precordial leads); (2) time duration within 24h from typical chest pain to hospitalization; (3) undergone CMR within 3~10 days from symptom onset. A total of 127 patients were excluded for the following reasons: declined CMR for personal reasons(n=16); old myocardial infarction history(n=8); unstable clinical station(n=39); claustrophobia(n=3); undergone CMR over10 days from symptom onset(n=10); hospitalization over 24h from symptom onset(n=51). Finally, 149 patients were enrolled for the analysis ( Fig.1). The present study was approved by the ethical committee at Cangzhou Central Hospital. Requirement for informed consent was waived, because of the observational nature of the study.

SYNTAX score
The score calculator is available on the SS website (www.SYNTAXscore.com). Our analysis was performed by two independent operators. Every signi cant inter-observer difference required a recalculation.
Laboratory tests, echocardiography and CMR [12,13] Blood samples were taken immediately after hospitalization, and ultrasound was performed 7±3 days after PCI. CMR was performed using a 3.0-T scanner (GE Discovery MR750w; GE Healthcare, Milwaukee, WI, USA) with electrocardiographic-gated image acquisition. MRI parameters were measured on shortaxis images covering the entire left ventricle (8-/0-mm slice thickness/slice gap) with the following sequences: a steady-state free precession (SSFP) cine sequence to determine the left ventricular (LV) function, mass and volume and a short-tau inversion recovery T2-weighted (T2-STIR) sequence to determine the area at risk (AAR) of myocardial infarction. Late gadolinium enhancement (LGE) images were acquired approximately 10~15 min after the intravenous administration of gadolinium-based contrast medium (0.2 mmol/kg, Magnevist, gadopentetate dimeglumine injection, Bayer) to determine the IS.
Analysis was performed using dedicated software (cmr42 version 5.11.3, Circle Cardiovascular Imaging, Calgary, Alberta, Canada). Images were anonymized, batched, and analyzed in a blinded fashion by two experienced operators. The AAR was de ned as high-signal myocardial edema mass/LV mass ratio. The IS was de ned as the hyperenhanced myocardium on the LGE images and is expressed as the infarcted LV mass/LV mass ratio. MVO was de ned as dark areas surrounded by hyperenhanced myocardium on the LGE images. The presence of intramyocardial hemorrhage (IMH) was de ned as hypointense areas within the brighter edematous zone on T2-STIR images. The papillary muscles were included in the LV cavity volume. The regions of interest (ROIs) for the volumes of AAR, IMH, IS, and MVO were created by manually drawing the lesion contours, while the LV volume was calculated by the semiautomated drawing of endocardial and epicardial contours for the whole LV myocardium on each slice. Myocardial edema was described as areas with a signal intensity >5 SD that of remote normal myocardium. The IS was calculated using the >5 SD method. Discordant cases were reviewed and reconciled with superior imaging specialists.
Statistical methods SPSS was used for statistical analysis. Categorical data are presented as numbers and percentages, and continuous data are presented as the mean (standard deviation) or median (interquartile range). Continuous variables with normal distributions were compared using the t-test. Continuous parameters that were not normally distributed were compared using the Mann-Whitney test. Categorical variables were compared using the chi-squared test (or Fisher's exact test when the expected value was <5). Independent predictors of high IS and low MSI were determined in a multivariate binary logistic regression model adjusted for all baseline variables found to be signi cant in the univariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the usefulness of SS to discriminate high IS and low MSI. All statistical analyses were performed using SPSS version 20 (SPSS Inc, Chicago, IL, USA) and graphs produced using GraphPad Prism version 8.0 (GraphPad Software, La Jolla, CA, USA). A p value of < 0.05 was regarded as statistically signi cant.

Patient characteristics
Of a total 149 patients, mean age was 59.89±10.86 years, 72.5% were male. The overall median SS was 17(IQR:9-25). According to SS, patients were divided into low SS (LSS)(n=96) or mediate-high SS (MHSS) (n=53) group. Patient characteristics between two groups are shown in Table 1. Compared with LSS group, MHSS group had higher age and APOB, lower body weight index and creatinine clearance rate and a higher prevalence of multivessel disease, initial TIMI ow grade 0/1, and initial TIMI thrombus grade 4/5 (all p<0.05).

TTE and CMR parameters
All TTE parameters were comparable (  Fig.2).

Correlations between SS and CMR parameters
Correlations between SS and CMR parameters are presented in Fig.3. SS had a positive correlation with IS(%LV) (r=0.292, p<0.001) and negative with MSI (r=-0.314, p<0.001). An example is illustrated in Fig.4.  .6).

Discussion
The present study is, to the best of our knowledge, the rst report on the relationship between SS and myocardial injury in STEMI patients presenting to hospital within 24h from symptom onset. We identi ed three major ndings:(1) there was a signi cant positive correlation between SS and IS and negative correlation between SS and MSI (Fig. 3).
(2) compared with LSS group, MHSS group has lower LVEF deprived by CMR and higher LVESV, but LVEDV was comparable between groups. (3) according to the univariate and multivariate logistic models, SS (both as categorical variable and continuous variable) was the independent predictor of high IS after adjusted for confounders (Fig. 6).
In the CvLPRIT study [14], patients treated with a staged complete revascularization (CR) had higher SS  15,16], in patients undergone CABG or PCI, SS was not only positively related to peri-procedural myocardial injury (deprived by elevated cardiac troponin and CKMB 6h after operation), but also an independent predictor of it. The increase in release of cardiac biomarkers after selective PCI was signi cantly associated with the extent of atherosclerosis identi ed by the SS [17]. These ndings were consistent with those of our study.
Furthermore, in our study, there was no signi cant relationship between SS and AAR was detected, thus, the negative correlation between SS and MSI might be interpreted by the positive correlation between SS and IS. This study has a few limitations. First, the proportion of patients with speci c SS group (< 22, n = 96; 22≤&<32, n = 36;>32, n = 17) in our population was too small to allow conclusions in all 3 groups. Consequently, tests of interaction were underpowered, especially when adjusted for covariates. Therefore, bias from residual confounding factors could still be present. Second, although all patients were enrolled consecutively, part of them declined CMR for personal reasons or unstable clinical station, for example, severe heart failure; on the other hand, only patients presented to hospital within 24h from symptom onset were included in our study population, thus it should be very cautious to interpretate the conclusions in the speci c patients.
In conclusion, of STEMI patients within 24h from symptom onset, SS was positively related with IS and negatively with MSI. SS was an independent predictor of IS after adjusting for important covariates.

Declarations Funding None
Compliance with ethical standards Con ict of interest The authors declare that they have no con icts of interest.