Prediction of microvascular obstruction by coronary artery angiography score after acute ST-segment elevation myocardial infarction：a single-center retrospective observational study

doi:10.21203/rs.3.rs-1540506/v1

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Prediction of microvascular obstruction by coronary artery angiography score after acute ST-segment elevation myocardial infarction：a single-center retrospective observational study

https://doi.org/10.21203/rs.3.rs-1540506/v1

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Background: Some coronary artery angiography scores are associated with no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). However, quality evidence about the association between coronary artery angiography score and microvascular injury is still needed. Our study aimed to validate the ability of coronary artery angiography score in predicting microvascular obstruction (MVO) detected by cardiac magnetic resonance (CMR) imaging.

Methods: From October 2020 to October 2021, 141 consecutive patients with acute STEMI who underwent primary PCI and CMR were reviewed retrospectively. CMR were performed between 3 to 7 days after PCI. Patients were divided into MVO group and non-MVO group based on the CMR results. Two coronary artery angiography scores (SYNTAX score and Gensini score) were used to assess the severity of coronary artery atherosclerotic burden.

Results: A total of 122 patients were included (mean age 60.6 ± 12.8 years). MVO occurred in 51 (41.8%) patients. Patients with MVO had higher SYNTAX scores (p < 0.001) and Gensini scores (p < 0.001) than those without MVO. Gensini score (r =0.580, p < 0.001) showed relative stronger correlation with infarction size than SYNTAX score (r =0.521, p < 0.001). The areas under the receiver operator characteristic curves of SYNTAX score and Gensini score for predicting MVO patients were 0.726 and 0.805. In multivariable regression analysis, peak troponin I (odd ratio [OR] = 1.196, p = 0.001), left ventricular ejection fraction (LVEF) (OR = 0.915, p = 0.021) and Gensini score (OR = 17.567, p = 0.016) were identified as independent predictors of MVO.

Conclusions: In patients with acute STEMI undergoing primary PCI treatment, Gensini score showed relative stronger correlation with infarction size than SYNTAX score and Gensini score may be an independent predictor of MVO.

Cardiac magnetic resonance

Acute ST-segment elevation myocardial infarction

Microvascular occlusion

SYNTAX score

Gensini score

Early percutaneous coronary intervention (PCI) treatment has been reported to significantly reduce mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) [1]. However, the consequent improvement in the myocardial perfusion post-PCI is not universal. About 50% of patients undergoing primary PCI shows delayed myocardial perfusion [2, 3]. This phenomenon is called as microvascular obstruction (MVO) and is related to structural and functional damage at the microvascular level by PCI revascularization [4, 5]. Previous studies have shown a significant increase in the incidence of major adverse cardiac events in patients with MVO [3].

Cardiac magnetic resonance (CMR) is a non-invasive imaging tool with high spatial resolution, has been widely used to detect and quantify the extent of MVO [6, 7, 8]. However, the long time breath-holding requirements make it difficult for STEMI patients to cooperate and excessive dosage of gadolinium contrast agent also increases the risk of renal failure.

Some coronary artery angiography scores have been used to assess the coronary artery atherosclerotic burden, such as SYNTAX score [9] and Gensini score [10]. More recently, it has been shown that the SYNTAX score and the Gensini score were associated with no-reflow phenomenon (TIMI blood flow < 3 or myocardial color grade < 2) after PCI [11, 12]. However, quality evidence about the association between coronary artery angiography score and microvascular injury in acute STEMI patients is still needed. Therefore, our study aimed to validate the ability of coronary artery angiography score in predicting MVO detected by CMR imaging.

Study population

This retrospective single-centre cohort study enrolled 141 consecutive patients with acute STEMI who underwent primary PCI and CMR at Lianyungang First People's Hospital from October 2020 to October 2021. STEMI was defined as a combination of chest pain suggested that the duration of myocardial ischemia was > 30min. The electrocardiography (ECG) indicated ST segment elevation > 2mm on at least two precordial leads or limb leads and troponin levels significantly increased beyond double the normal upper limit. The inclusion criteria were as follows: (1) Diagnosis of STEMI; (2) PCI was performed within 12 hours from symptom onset; (3) Coronary angiography was performed before and immediately after PCI; (4) CMR was performed between 3 to 7 days after PCI. The exclusion criteria were as follows: (1) Age < 18 years; (2) Previous history of myocardial infarction or revascularization (n = 11); (3) Incomplete coronary angiography image (n = 6) or poor CMR image quality (n = 3). Finally, 122 patients were enrolled (mean age 60.6 ± 12.8 years old; 72.1% was male).

PCI and Coronary artery angiography

PCI treatment was performed by Seldinger's method in all chest pain patients with a median time of 4.5 h, using 5F contrast catheter, 6F guide catheter and 0.014-inch guide wire. A total of 100 ml nonionic contrast agent (Ultravist 370; Bayer AG, Berlin ,German) was injected. Heparin used bivalirudin, injected intravenously at 7.5 ml and maintained intravenously at 17.5 ml/h. Drug-eluting stents were used in all patients. All stents were implanted directly whenever possible, or balloon predilation angioplasty (8–10 atmospheric pressure) was performed in the remaining cases. Thrombolysis in myocardial infarction (TIMI) blood flow grades before and after PCI were recorded.

Coronary artery angiography score

Based on the results of coronary artery angiography before PCI, two coronary artery angiography scores (SYNTAX score and Gensini score) were used to assess the severity of coronary artery atherosclerotic burden by two uninformed cardiologists. The SYNTAX score was calculated using the SYNTAX score online calculator (http://www.SYNTAXscore.com), evaluating all coronary lesions with diameter stenosis > 50% and vessels with diameter > 1.5 mm [13]. The SYNTAX score for the degree of coronary stenosis were 2 for 50–99%, 5 for 100%. The Gensini score was calculated based on the product of the degree scoring of coronary stenosis and the location score of the lesion [10]. The Gensini score for the degree of coronary stenosis were 1 for 1–25%, 2 for 26–50%, 4 for 51–75%, 8 for 76–90%, 16 for 91–99%, 32 for 100%. The culprit artery was defined as the target artery treated by PCI treatment.

Cardiac magnetic resonance

CMR examinations were performed in all patients after PCI with a median time of 5.2 days. CMR were conducted with a 1.5T MR scanner (Magnetom Aera XJ, Siemens, Erlangen, Germany) using an 12-element phased-array coil equipped with ECG-gated. Scan sequences were as follows: The cardiac cine imaging was performed by steady-state free precession sequence (SSFP) sequence; slice gap 0 mm; slice thickness 8 mm; repetition time, 37 ms; echo time, 1.2 ms; field of view 340 × 340 mm². The T2-weighted imaging was performed by short time inversion recovrey (STIR) sequence with the same prescription of cine images. Late gadolinium enhancement (LGE) imaging was performed by phase sensitive inversion recovery (PSIR) sequence; slice gap 0 mm; slice thickness 8 mm; echo time, 1.3 ms; inversion time, 300-340ms; field of view 340 × 340 mm².

All images were evaluated on the CMR dedicated post-processing software (cvi42 v5.13, Circle Cardiovascular Imaging, Calgary, Canada). The CMR images were interpreted by two uninformed radiologists and consensus was reached when opinions were different. The left ventricular ejection fraction (LVEF) were calculated on the cine images. The area at risk (AAR) was defined as the high signal region (> 2 standard deviations [SD] of the normal myocardial signal) on the T2-weighted images. T2-weighted images with poor image quality or unrecognizable AAR area were removed. The infarction size (IS) was quantified on the LGE images 10 minutes after gadolinium (Jiadexian, Hengrui, Lianyungang, China) injection. The signal threshold for the IS was set to > 5 SD of the normal myocardial signal. The myocardial salvage index (MSI) was calculated as: MSI = (AAR − IS) / AAR × 100. The MVO was defined as the hypoenhanced region within LGE area. The AAR and IS were recorded as the percentage of overall left ventricular (LV) myocardial mass.

Statistical analysis

Statistical analyses was performed using IBM SPSS 26.0 software (IBM Corp, Chicago, IL, USA). Continuous variables are expressed as mean ± SD or median (25th to 75th percentile) and were compared using independent sample t-tests or Mann-Whitney U-tests for nonmormal data. Categorical data are expressed as n (%) and were compared using Chi-squared tests. Spearman correlation analysis was used to assess the correlation between coronary scores and IS (%LV). Area under the curve (AUC) in the receiver operating characteristic (ROC) analysis was used to assess predictive performance and the optimal cutoff value were identified by the Youden Index. The binary logistic regression analysis was performed to assess the coronary score for the prediction of MVO (results were expressed as odds ratio [OR] and 95% confidence interval [CI]). Coronary scores were converted into categorical variables based on the cutoff value. The variables of p < 0.1 in the univariable analysis were included in the multivariate tests. All tests were two-tailed and p < 0.05 was considered as statistically significant.

characteristics of patients

A total of 122 patients with acute STEMI were enrolled, including 51 (41.8%) in the MVO group and 71 (58.2%) in the non-MVO group. Typical examples (with and without MVO) of patients are shown in Fig. 1. In the data comparison between the two groups, there were no statistically significant differences in age, gender, heart rate, systolic blood pressure, diastolic blood pressure, hypertension, diabetes, current Smoker, dyslipidemia, GRACE score, Killip class, time from symptom onset to PCI, time from PCI to CMR, culprit artery left circumflex artery (LCX), number of diseased arteries and final TIMI flow grade (all p > 0.05). Compared with the non-MVO group, MVO group had higher peak Troponin I, higher peak creatine kinase (CK), higher peak creatine kinase isoenzyme (CK-MB), higher pro-B-type natriuretic peptide (PRO-BNP), more culprit artery left anterior descending artery (LAD), less culprit artery right coronary artery (RCA), more initial TIMI 0/1 flow, lower LVEF, larger AAR (%LV), larger and IS (%LV), lower MSI, higher SYNTAX scores and higher Gensini scores (all p < 0.05) (Table 1).

Table 1

characteristics of patients
Parameters	Total Population (n = 122)	Non-MVO group (n = 71)	MVO group (n = 51)	p-Value
Age (years)	60.6 ± 12.8	61.1 ± 14.1	59.8 ± 10.9	0.593
Male, n (%)	88 (72.1)	49 (69.0)	39 (76.5)	0.365
Heart rate (bpm)	79.8 ± 13.7	76.8 ± 12.9	82.9 ± 18.5	0.154
Systolic blood pressure (mmHg)	133.5 ± 20.7	133.0 ± 23.9	134.2 ± 15.5	0.733
Diastolic blood pressure (mmHg)	81.6 ± 14.1	80.6 ± 14.7	83.0 ± 13.2	0.345
Hypertension, n (%)	58 (47.5)	36 (50.7)	22 (43.1)	0.409
Diabetes, n (%)	32 (26.2)	17 (23.9)	15 (29.4)	0.498
Current Smoker, n (%)	27 (22.1)	13 (18.3)	14 (27.5)	0.230
Dyslipidemia, n (%)	16 (13.1)	10 (14.1)	6 (11.8)	0.708
GRACE score, n (%)	141.8 ± 29.0	133.2 ± 23.9	140.1 ± 31.2	0.188
Peak Troponin I (ng/ml)	23.7 (13.7 to 30.0)	15.8 (9.8 to 28.6)	30.0 (23.7 to 30.0)	< 0.001
Peak CK (U/L)	2748.5 (1432.5 to 3817.5)	1925.5 (1138.5 to 3053.0)	3505.0 (2708.5 to 6920.3)	< 0.001
Peak CK-MB (U/L)	270.0 (202.0 to 404.0)	211.0 (163.0 to 276.0)	346.0 (274.0 to 473.0)	< 0.001
PRO-BNP (pg/mL)	815.0 (432.5 to 1996.5)	683.5 (427.8 to 933.0)	987.0 (515.8 to 3205.3)	0.026
Heart failure Killip class, n (%)
I	91 (74.6)	55 (77.5)	36 (70.6)	0.389
≥ II	31 (15.4)	16 (12.5)	15 (29.4)
Time from symptom onset to PCI (h)	6.2 (4.5 to 9.3)	6.0 (5.0 to 9.0)	6.2 (4.0 to 11.3)	0.545
Culprit artery, n (%)
LAD	66 (54.1)	28 (39.4)	38 (74.5)	< 0.001
LCX	9 (7.4)	6 (8.5)	3 (5.9)	0.592
RCA	47 (38.5)	37 (52.1)	10 (19.6)	< 0.001
Number of diseased arteries, n (%)
Single-artery	64 (52.5)	34 (47.9)	30 (58.8)	0.233
Multi-artery	58 (47.5)	37 (42.1)	21 (41.2)
Initial TIMI flow grade, n (%)
0/1	95 (77.9)	48 (67.6)	47 (92.2)	0.001
2/3	27 (67.6)	23 (32.4)	4 (7.8)
Final TIMI flow grade, n (%)
0/1	112 (91.8)	67 (94.4)	45 (88.2)	0.223
2/3	10 (8.2)	4 (5.6)	6 (11.8)
Time from PCI to CMR (days)	5.2 (4.3 to 6.4)	5.1 (3.8 to 6.2)	5.2 (4.5 to 6.9)	0.275
LVEF (%)	36.7 ± 10.2	40.7 ± 9.7	31.2 ± 8.4	< 0.001
AAR (% LV)	28.3 (22.5 to 34.8)	25.3 (20.4 to 29.3)	34.8 (28.2 to 37.8)	< 0.001
IS (% LV)	22.3 (15.6 to 32.5)	18.4 (13.2 to 22.3)	27.3 (23.8 to 33.1)	< 0.001
MSI (%)	22.3 (13.9 to 37.2)	25.7 (14.9 to 44.8)	16.3 (8.8 to 22.2)	< 0.001
SYNTAX score	17.8 (11.0 to 22.0)	16.0 (10.0 to 18.0)	20.0 (15.8 to 22.3)	< 0.001
Gensini score	53.0 (36.0 to 80.0)	44.0 (32.0 to 58.0)	74.0 (50.5 to 81.5)	< 0.001
Note: Values are mean ± SD, number (%) or median (25th to 75th percentile). Abbreviations: MVO microvascular obstruction; GRACE the Global Registry of Acute Coronary Events; CK creatine kinase; CK-MB creatine kinase isoenzyme; PRO-BNP pro-B-type natriuretic peptide; PCI percutaneous coronary intervention; LAD left anterior descending coronary artery; LCX left circumflex coronary artery; RCA right coronary artery; TIMI thrombolysis in myocardial infarction; CMR cardiac magnetic resonance; LVEF left ventricular ejection fraction; AAR area at risk; IS infarct size; MSI myocardial salvage index

Correlations between coronary scores and IS

In the correlation analysis, the two coronary scores were all positively correlated with IS (%LV). Among them, Gensini score (r = 0.567, p < 0.001) showed relative stronger correlation with IS (%LV) than SYNTAX score (r = 0.521, p < 0.001) (Fig. 2).

ROC curve analysis

The ROC curve analysis of the two coronary scores predicted MVO were shown in Table 2. Among them, Gensini score showed the larger area under the curve (AUC = 0.807, 95% CI: 0.730-0.884, p < 0.001) than SYNTAX score (AUC = 0.726, 95% CI: 0.634-0.818, p < 0.001). At the optimal cutoff value of 61, the Gensini score predicted MVO sensitivity and specificity were 76.5% and 77.5%. At the optimal cutoff value of 17.5, the SYNTAX score predicted MVO sensitivity and specificity were 74.5% and 67.6% (Fig. 3).

Univariable and multivariable analysis

In the univariable analysis for predicting MVO, variables including peak troponin I, peak CK, Peak CK-MB, culprit artery LAD, culprit artery RCA, Initial TIMI flow 0/1, LVEF, AAR, IS, MSI, SYNTAX score and Gensini score had a p-value < 0.1 After adjustment for other potential confounders including PRO-BNP, AAR, IS and MSI, the multivariable analysis showed that peak troponin I (OR = 1.196, 95% CI: 1.075-1.330, p = 0.001), LVEF (OR = 0.915, 95% CI: 0.849-0.987, p = 0.021) and Gensini score (OR = 17.567, 95% CI: 1.691-182.515, p = 0.016) were identified as independent predictors of MVO (Table 2).

Table 2 Univariable and multivariable regression analysis for MVO

Variable	OR	95% CI	p-Value
Univariable analysis
Peak Troponin I	1.153	1.089 - 1.220	< 0.001
Peak CK	1.000	1.000 - 1.001	< 0.001
Peak CK-MB	1.003	1.001 - 1.005	0.005
PRO-BNP	1.001	1.001 - 1.006	0.006
Culprit artery LAD	4.489	2.039 - 9.885	< 0.001
Culprit artery RCA	0.224	0.097 - 0.516	< 0.001
Initial TIMI flow 0/1	5.630	1.809 - 17.524	0.003
LVEF (%)	0.895	0.854 - 0.939	< 0.001
AAR (% LV)	1.107	1.043 - 1.175	0.001
IS (% LV)	1.221	1.138 - 1.311	< 0.001
MSI (%)	0.927	0.885 - 0.971	0.001
SYNTAX score	6.100	2.735 - 13.607	< 0.001
Gensini score	11.172	4.758 - 26.231	< 0.001
Multivariable analysis
Peak Troponin I	1.196	1.075 - 1.330	0.001
LVEF (%)	0.915	0.849 - 0.987	0.021
Gensini score	17.567	1.691 - 182.515	0.016

Abbreviations: MVO microcirculation obstruction;OR odd ratio; CI confidence interval; CK creatine kinase; CK-MB creatine kinase isoenzyme; PRO-BNP pro-B-type natriuretic peptide; LAD left anterior descending coronary artery; RCA right coronary artery; TIMI thrombolysis in myocardial infarction; LVEF left ventricular ejection fraction; AAR area at risk; IS infarction size

In the present study, we investigated the association between coronary artery angiography score and MVO in patients with acute STEMI after PCI treatment. We found that (1) patients with MVO had higher Gensini score and SYNTAX score than those without MVO; (2) Gensini score showed relative stronger correlation with IS than Gensini score; (3) peak troponin I, LVEF and Gensini score were independent associated with MVO after adjustment for potential confounders.

Coronary artery angiography score is widely used to assess extent and severity of coronary atherosclerotic disease (CAD) burden [14]. Previous studies proved that the SYNTAX score and the Gensini score were able to predict no-reflow phenomenon defined by TIMI flow or myocardial color grade post-PCI [11,12]. However, multiple evidences showed TIMI flow or myocardial color grade underestimated the prevalence of microvascular injury [2,15]. CMR is an excellent imaging tool to detect MVO with high sensitivity and specifificity and recent expert consensus recommends 3 to 7 days post-PCI as the preferred CMR imaging time point to evaluate MVO [16]. Therefore, evaluating the association between angiography score and MVO can provide higher quality evidence for early identification of patients with microvascular injury. Our study showed that patients with MVO had significantly higher angiography scores than those without MVO.

MVO is a severe marker of microvascular blood flow dysfunction. The development of MVO depends on several factors: (1) The shedding of atherosclerotic or thrombotic debris caused by PCI [17], (2) vasospasm caused by the release of vasoconstrictor factors such as endothelin and thromboxane [18], (3) activation of platelets and coagulation factors in microvascular caused by endothelial cell injury and [4], (4) inflammatory response to progressive leukocyte accumulation in the infarct area [19]. Previous studies proved that those STEMI patients with MVO are more likely to have reduced reduced LV function and a poor follow-up outcome [5]. Our study showed that patients with MVO has significantly larger IS (%LV) and lower LVEF than those without MVO.

The SYNTAX score is a comprehensive angiography score and widely used to predict prognosis in patients after PCI [20,21]. However, our results showed that the Gensini score had larger AUC in predicting MVO than the SYNTAX score and was an independent predictor of MVO. Although both scores were grading the severity of CAD, there are many differences between them. In SYNTAX score algorithm, the percent diameter stenosis is not carefully differentiated and only taking non occlusive (50-99% diameter stenosis) and occlusive (100% diameter stenosis) lesion into consideration. In addition, excessive morphologic scores also weakened the effect of thrombotic load in patients with acute STEMI. In Gensini score algorithm, the percent diameter stenosis is carefully differentiated from 25% to 100% and the severity score of lesion stenosis is geometrically increasing, which reinforced the effect of thrombotic load in patients with acute STEMI. Therefore, these differences may explain the association between MVO and the Gensini score rather than SYNTAX score.

The coronary artery angiography score has also been associated with the magnitude of myocardial injury. Several studies have shown that the SYNTAX score correlated signifcantly with biomarkers of cardiac injury [22,23]. In a CMR study, Gao et al. [24] observed SYNTAX score was signifcant positive correlation with IS and was the independent predictor of high IS (≥ mean 35.43 %LV). These findings were consistent with those of our study. Furthermore, in our study, Gensini score showed relative stronger correlation with IS (%LV) than other scores. Previous studies showed that Gensini score was correlated with atherosclerotic plaque burden assessed by intracoronary ultrasound [25]. Therefore, the Gensini score could be a more simple and effective tool for infarct severity assessment post-STEMI.

The study had several limiations. First, this was a single-center study with a small sample size. A multi-center studies with larger sample size would be required reconfirm our results. Second, The observational retrospective design of this study may have resulted in bias in information selection. Finally, this study used angiography-based visual scoring to predict MVO and the results may be affected by observer subjective factors.

In patients with acute STEMI undergoing primary PCI treatment, Gensini score showed relative stronger correlation with infarction size than SYNTAX score and Gensini score may be an independent predictor of MVO.

STEMI: ST-segment elevation myocardial infarction; PCI: Percutaneous coronary intervention; MVO: Microvascular obstruction; CMR: Cardiac magnetic resonance; ECG: Electrocardiography; TIMI: Thrombolysis in myocardial infarction; SSFP: Steady-state free precession; STIR: Short time inversion recovrey; LGE: Late gadolinium enhancement; PSIR: Phase sensitive inversion recovery; LVEF: Left ventricular ejection fraction; AAR: Area at risk; SD: Standard deviations; IS: Infarct size; MSI: Myocardial salvage index; LV: Left ventricular; AUC: Area under the curve; ROC: Receiver operating characteristic; OR: Odds ratio; CI: Confidence interval; CK: Creatine kinase; CK-MB: Creatine kinase isoenzyme; PRO-BNP: Pro-B-type natriuretic peptide; LCX: Left circumflex coronary artery; LAD: Left anterior descending artery; RCA: Right coronary artery; CAD: Coronary artery disease.

Acknowledgements

Not applicable.

Authors’ contributions

Ziwen L and Hongbin Y conceived and supervised the study; Ziwen L and Dehua W designed experiments; Ziwen L, Hongbin Y, Dehua W, Yayun Z, Yongli F, Yi Z and Ying Z performed experiments; Yayun Z and Yongli F analyzed data; Ziwen L wrote the manuscript; Yi Z and Ying Z made manuscript revisions. All authors reviewed the results and approved the final version of the manuscript.

Funding

This study has received funding by the SKY Imaging Research Fund of China Foundation for International Medical Exchange (ID:Z-2014-07-2101).

Availability of data and materials

The data set supporting the results of this article are included within the article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The present study was approved by the ethical committee of Lianyungang First People's Hospital (KY-20211030001-01) and received informed consent from the patients. Patient data were completely anonymized. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Author details

¹Department of Radiology, Lianyungang First People's Hospital, Clinical Medical College, Nanjing Medical University. ²Department of Radiology, Lianyungang First People's Hospital, Clinical Medical College, Jinzhou Medical University. ³Department of Radiology, the First Affiliated Hospital of Kangda College Nanjing Medical University. ⁴Department of Cardiology, Lianyungang First People's Hospital, Lian Yungang, Jiangsu Province, China.

*Correspondence: [email protected]

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No competing interests reported.

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Prediction of microvascular obstruction by coronary artery angiography score after acute ST-segment elevation myocardial infarction：a single-center retrospective observational study

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Abstract

Figures

Background

Methods

Study population

PCI and Coronary artery angiography

Coronary artery angiography score

Cardiac magnetic resonance

Statistical analysis

Results

characteristics of patients

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1