The Relationship of Coronary Thrombus Burden and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Score in Patients With ST-Segment Elevation Myocardial Infarction

Abstract

Background

The anticoagulation and risk factors in atrial fibrillation (ATRIA) score is associated with adverse cardiovascular events. However, its relationship with coronary thrombus burden is unclear. Therefore, we aimed to investigate the relationship between the ATRIA score and thrombus burden in patients with ST-segment elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI).

Materials and Methods

The study was designed as a prospective cross-sectional observational study. Our study included 319 patients who were prospectively admitted with STEMI between January 2021 and April 2022. Patients were divided into 2 groups with low thrombus burden (LTB) (grade <3) and high thrombus burden (HTB) (grade ≥3). ATRIA score was calculated and recorded for all patients. ATRIA scores of both groups were compared.

Results

In our study, 58.9% (n = 188) of patients in the LTB group and 41% (n = 131) of patients in the HTB group. The ATRIA risk score (p < .001) was significantly higher in the HTB group. In multivariate logistic regression analysis, ATRIA score, glomerular filtration rate, hypertensıon, abciximab usage, and no-reflow were found to be independent predictors of HTB in STEMI patients undergoing primary PCI. In receiver operating characteristic analysis, ATRIA score >4 had a sensitivity of 66.2% and specificity of 95.2%, and ATRIA score >8 sensitivity of 98% and specificity of 100% predicted HTB.

Conclusion

In this study, we found that thrombus burden may be associated with ATRIA risk score in patients presenting with STEMI.

Keywords

ATRIA score thrombus burden ST-segment elevation myocardial infarction

Introduction

Coronary artery occlusion due to atherosclerotic plaque rupture and intracoronary thrombus formation are the main pathophysiological mechanisms of ST-segment elevation myocardial infarction (STEMI).¹ High thrombus burden (HTB) in the coronary artery (infarct-related artery [IRA]) responsible for STEMI is associated with distal embolism, stent thrombosis, no-reflow phenomenon, and larger infarct size as well as a significant determinant of long-term cardiovascular mortality and morbidity. The level of intracoronary thrombus burden detected during primary percutaneous coronary intervention (PCI) in STEMI patients has a central role in the follow-up and management of these patients.^2–6 Despite improved mechanical and pharmacologic treatment procedures, the clinical management of intracoronary thrombus burden remains complex. Therefore, the prediction of thrombus burden in STEMI patients is critical for optimizing the treatment process and improving clinical outcomes.⁷

The anticoagulation and risk factors in atrial fibrillation (ATRIA) risk score is a practical scoring system used to predict the risk of thromboembolism in patients with atrial fibrillation (AF), which is inexpensive and easy to apply.⁸ Moreover, the predictive efficiency of the ATRIA score for thromboembolism in AF patients has been shown to be better than traditional scoring systems such as CHADS2 and CHA2DS2-VASc.^8–10 Each of the parameters in the ATRIA risk scoring system is generally associated with thromboembolic events. Recent studies have shown that the ATRIA risk score is associated with adverse clinical outcomes in patients with acute coronary syndrome (ACS).^11–13

This study aimed to evaluate the effectiveness of the ATRIA score in predicting intracoronary thrombus burden in STEMI patients.

Material and Methods

Study Population and Clinical Evaluations

This study was designed as a prospective, cross-sectional, and observational study. A total of 500 consecutive patients admitted to the emergency department of Düzce University Training and Research Hospital between January 2021 and April 2022 who underwent primary PCI due to STEMI diagnosis were prospectively evaluated. The cardiology clinic where the study was conducted serves as a high-volume tertiary cardiac center in the Western Black Sea Region (>2000 PCI per year).

Exclusion criteria were: previous coronary artery bypass graft (CABG) surgery, stent thrombosis or restenosis, thrombolytic therapy within the last 48 h, presence of active infection including COVID-19, presence of preprocedural AF, recent major surgical procedures or major trauma, presence of known chronic inflammatory disease, history of malignancy, presence of myeloproliferative disease, end-stage liver failure, receiving any antithrombotic therapy and refusal to participate in the study. No upper or lower age limit was used. A total of 500 patients were evaluated as part of the study. One hundred and twenty-seven patients were excluded because they fulfilled at least one of the exclusion criteria. Fifty-four patients were excluded from the study because of inaccurate laboratory results and incorrect or missing data recording. Ultimately, 319 patients were included in the study. The study was approved by the Institutional Ethics Committee.

Patients with STEMI who presented within the first 12 h after the onset of typical chest pain and had diagnostic electrocardiography (ECG) findings were included in the study. Diagnostic ECG findings were as follows: (i) presence of ST-segment elevation in at least 2 consecutive leads, (ii) ST-segment elevation in leads V2–V3 ≥ 2.5 mm in men younger than 40 years, ≥2 mm in men 40 years and older, (iii) ≥1.5 mm in women of all ages, and/or (iv) ≥1 mm in other leads. In addition, (iv) ST-segment elevation >0.5 mm in leads V7–V9 with isolated ST-segment depression when the terminal T wave was positive in leads V1–V3, or (v) the presence of newly developed left bundle branch block.

After a detailed medical history and physical examination, all patients’ age, gender, history of hypertension (HT), diabetes, dyslipidemia, smoking status, history of ischemic or hemorrhagic stroke, previous PCI or CABG, family history of coronary artery disease (CAD), and body mass index (BMI) were noted. Additionally, blood pressure, heart rate, Killip class, and the presence of cardiogenic shock were recorded. Antecubital venous blood samples were taken from all patients included in the study at the time of admission to the emergency department. Cardiac biomarkers, complete lipid profile, high-sensitivity C-reactive protein (hsCRP), complete blood count, urea, creatinine, and hepatic aminotransferases were analyzed. Glomerular filtration rate (GFR) was calculated using the Cockcroft–Gault equation. Periprocedural factors include an IRA, time of onset of chest pain, time of the first presentation to the emergency department, duration of chest pain, time of coronary balloon inflation, stent diameter, length, and characteristics were noted. All patients were evaluated with transthoracic echocardiography at the 48th hour after PCI. Left ventricular ejection fraction (LVEF) was calculated using the modified biplane Simpson's method.

Scores

The ATRIA score was developed from the ATRIA study cohort. It was calculated by adding 1 point for each of the following factors: female sex, diabetes mellitus (DM), congestive heart failure, HT, proteinuria, and renal dysfunction (ie, estimated GFR <45 mL/min/1.73 m² or end-stage renal disease) and by adding 0 to 9 points depending on the specific score weighting of patients age according to the presence or absence of prior ischemic stroke.⁸ All parameters of scoring are summarized in Table 1. The CHA2DS2-VASc risk score was calculated by assigning a score of 1 point for each of the following conditions: congestive heart failure (ejection fraction < 40%), HT, age between 65 and 74 years, DM, vascular disease (myocardial infarction or peripheral arterial disease), and female gender; a score of 2 points for the following conditions: history of stroke or transient ischemic attack (TIA) and age >75 years.¹⁴

Table 1.

ATRIA Score.

Risk factor	Points without Prior Stroke (Points)	Points with Prior Stroke (Points)
Age, years
>85	6	9
75–84	5	7
65–74	3	7
<65	0	0
Female gender	1	1
Diabetes mellitus	1	1
Congestive heart failure	1	1
Hypertension	1	1
eGFR < 45 or ESRD	1	1

Abbreviations: ATRIA, anticoagulation and risk factors in atrial fibrillation; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease.

Angiographic Analyses

Coronary angiography (CAG) via radial or femoral access was performed for each patient. Iodiksanol (Visipaque®) was used as a contrast agent during CAG in all subjects. All patients were given oral aspirin (300 mg) and oral clopidogrel (600 mg) or ticagrelor (180 mg) at the time of admission and intravenous heparin 100 IU/kg just before catheterization. Abciximab was routinely used in our center as a glycoprotein (Gp) IIb/IIIa receptor blocker. Balloon predilatation was not performed in cases suitable for direct stenting. In other cases, stenting was performed after balloon predilatation. Whenever possible, drug-eluting stents were preferred to bare metal stents. Glycoprotein IIb/IIIa receptor blocker use, balloon, and stent selection were left to the operator's discretion. A coronary thrombus aspiration catheter is not used in our center. We did not administer thrombolytic therapy to any patient. Patients referred to our center after thrombolysis were taken directly to the angiography laboratory without waiting time and underwent primary PCI. Patients who had received thrombolytic therapy were not included in the study. Angiography images were evaluated by 2 different cardiologists who had no knowledge of the patients’ clinical data. Thrombus burden in the infarct-related lesion was calculated in five grades based on the classification thrombolysis in myocardial infarction (TIMI) study group.¹⁵ Thrombus burden was classified as: grade 0, no thrombus; grade 1, possible thrombus; grade 2, the greatest dimension of the thrombus is <1/2 vessel diameter; grade 3, largest dimension >1/2 to <2 vessel diameter; grade 4, greatest dimension >2 vessel diameter; grade 5, total vascular occlusion due to thrombus. Grade 5 patients were reclassified after success of flow with guidewire passage or small balloon passage or dilation.¹⁶ Then, final thrombus grades were divided into 2 classes: low thrombus burden (LTB) (grade <3) and HTB (grade ≥3).¹⁷ An additional subgroup analysis of thrombus grade ≥4 or <4 was also performed. Flow in the post-PCI vessel was evaluated with the TIMI flow grade before and after the procedure.^18,19 Despite successful dilation and the absence of mechanical complications after completion of the procedure, blood flow in the IRA was considered no-reflow if TIMI ≤2 flow.^18,19 The complexity of CAD was evaluated using the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score, which was prospectively calculated using the SYNTAX score algorithm on the baseline diagnostic angiogram.²⁰ The current online version was used in the calculation of the SYNTAX scores.²¹ The Global Registry of Acute Coronary Events (GRACE) score (derived from the GRACE registry) was calculated by using the online calculator during hospital admission.²² Target vessel diameter and characteristics of the lesion, TIMI frame count, thrombus burden grade, preprocedural TIMI flow rate, postprocedural TIMI flow rate, SYNTAX score, and the procedure used were recorded. Angiography images of the study patients were evaluated by 2 experienced interventional cardiologists who were unaware of the patient's laboratory measurements, clinical status, and ATRIA score. A third cardiologist was consulted when there was inconsistency between the 2 observers.

Statistical Analyses

Mean, standard deviation, median minimum, maximum, frequency, and ratio values were used in the descriptive statistics of the data. The distribution of variables was measured with the Kolmogorov–Smirnov test. Independent sample t-test, Kruskal–Wallis test, and Mann–Whitney U test were used to analyze quantitative independent data. The chi-square test was used to analyze qualitative independent data, and the Fischer test was used when chi-square test conditions were not met. Effect level and cut-off value were investigated with the receiver operating characteristic (ROC) curve. The effect level was investigated by univariate and multivariate logistic regression. Statistical analyses were performed using SPSS software (version 27.0; SPSS Inc., Chicago, IL, USA).

Results

The mean age of the patients was 66.2 ± 9.6 years and 234 (73.3%) of them were male. The HTB group consisted of 131 patients (mean age 66.2 ± 12.8 years, n = 92 [69.2%] male), and the LTB group consisted of 188 patients (mean age 65.9 ± 6.7 years, n = 142 [76.3%] male). The baseline characteristics and laboratory results of the groups are summarized in Table 2.

Table 2.

Baseline Characteristics and Laboratory Results of Study Groups.

Variables	Low Thrombus Burden (n = 188)	High Thrombus Burden (n = 131)	P Value
Age, years	61.3 ± 6.7	70.2 ± 12.8	.003
Male, n (%)	142 (76.3%)	92 (69.2%)	.153
BMI, kg/m²	27.7 ± 3.9	27.9 ± 4.3	.801
Smoking, n (%)	57 (30.6%)	79 (59.4%)	<.001
Diabetes mellitus, n (%)	30 (16.1%)	48 (36.1%)	<.001
Hypertension, n (%)	52 (28.0%)	93 (69.9%)	<.001
Hyperlipidemia, n (%)	47 (25.3%)	39 (29.3%)	.421
Chronic kidney disease, n (%)	13 (7.0%)	21 (15.8%)	.012
Previous history of PCI, n (%)	31 (16.7%)	28 (21.1%)	.320
Family history of CAD, n (%)	40 (21.5%)	28 (21.1%)	.922
History of stroke/TIA, n (%)	1 (0.5%)	6 (4.5%)	.039
Heart rate (beats/min)	81.7 ± 16.7	85.1 ± 22.6	.298
Systolic BP, mmHg	126.1 ± 24.6	121.0 ± 27.9	.082
Diastolic BP, mmHg	78.8 ± 16.7	74.4 ± 17.6	.024
White Blood Cell count, 103/mL	12.1 ± 4.1	12.1 ± 3.8	.626
Hemoglobin, g/dL	14.1 ± 1.8	13.7 ± 1.8	.044
Platelet count, 103 /mL	247.5 ± 71.2	260.5 ± 75.2	.196
Urea, mg/dL	37.4 ± 22.8	36.3 ± 14.8	.760
Creatinine, mg/dL	0.97 ± 0.29	1.4 ± 0.55	.000
GFR, mL/min/1.73 m²	81.5 ± 21.7	73.1 ± 23.6	.028
Glucose, mg/dL	164.8 ± 84.2	165.6 ± 88.2	.992
hsCRP, mg/dL	1.95 ± 7.58	1.89 ± 4.04	.255
Troponin, ng/L	9.55 ± 11.04	9.14 ± 10.57	.734
CK-MB, mg/L	109.7 ± 133.7	128.4 ± 170.6	.869
Triglyceride, mg/dL	152.2 ± 122.5	172.7 ± 157.5	.182
LDL-C, mg/dL	111.5 ± 36.8	116.7 ± 37.8	.220
HDL-C, mg/dL	40.0 ± 11.3	38.5 ± 9.6	.557

Abbreviations: BMI, body mass index; PCI, percutaneous coronary intervention; CAD, coronary artery disease; TİA, transient ischemic attack; BP, blood pressure; hsCRP, high-sensitivity C-reactive protein; CK-MB, creatine kinase-MB; GFR, glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.

Study groups were similar with regard to age, sex, BMI, dyslipidemia, previous history of PCI, and family history of CAD (P = .583, .153, .801, .421, .320, and .922, respectively). Also, no significant differences were observed in heart rate and systolic blood pressure between the groups (P = .298 and .082, respectively). White blood cell count and platelet count were similar between the groups (P = .626 and .196, respectively). Glucose, hsCRP, cardiac troponin, serum creatine kinase-MB (CK-MB), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride were not significantly different between the groups (P = .992, .255, .734, .869, .220, .557, and .182, respectively).

A comparison of the baseline angiographic and procedural characteristics of the two groups is shown in Table 3. There was no significant difference between both groups' infarct-related artery and periprocedural cardiac rhythm. There was no significant difference between both groups' door-balloon time, radial approach, stent diameter, stent length, anterior myocardial infarction, balloon predilatation, TIMI before intervention, and LVEF at 48th hour (P = .905, .255, .244, .491, .496, .541, .588, .163, .999, and .056, respectively).

Table 3.

Angiographic and Procedural Characteristics of Study Groups.

Variables		Low Thrombus Burden (Grade <3) (n = 188)	High Thrombus Burden (Grade ≥3) (n = 131)	P Value
Chest pain duration		234.5 ± 159.1	308.2 ± 248.2	.001
Pain-ballon time		237.2 ± 159.9	312.0 ± 251.5	.002
Door-ballon time		58.0 ± 30.4	58.0 ± 26.3	.905
CAG duration		24.7 ± 11.9	27.7 ± 11.9	.003
Radial approach		92	57	.244
Femoral approach		98	78	.291
IRA	LMCA	1	0	1.000
	LAD	84	55	.499
	CX	31	18	.444
	RCA	67	58	.171
Stent diameter		3.02 ± 0.53	3.03 ± 0.43	.491
Stent length		24.4 ± 77	23.7 ± 7.1	.496
Contrast volume		243.2 ± 79.6	262.2 ± 90.0	.036
History of stroke		0	2	.042
Periprocedural cardiac rhythm	NSR	179	123	.141
	AF	10	7	.141
	VF–VT	13	12	.505
	AV block	2	1	1.000
Killip class	I	148	80	<.001
	II	24	29
	III	9	5
	IV	5	19
Anterior myocardial infarction		84	56	.588
Nonanterior myocardial infarction		101	77	.524
Balloon angioplasty		153	117	.163
DES usage		139	79	.004
BMS usage		39	42	.032
Abciximab Usage		69	84	.000
TIMI before intervention	0	124	88
	I	22	16	.999
	II	37	27
	III	3	2
TIMI after intervention	0	1	7
	I	4	5	<.001
	II	3	16
	III	174	105
No-reflow		8	28	<.001
İn-hospital mortality		3	15	<.001
48th hour LVEF (%)		44.9 ± 9.0	40.8 ± 12.2	.056

Abbreviations: CAG, coronary angiography; IRA, infarct-related artery; LMCA, left main coronary artery; LAD, left anterior descending; Cx, circumflex artery; RCA, right coronary artery; MI, myocardial infarction; TIA, transient ischemic attack; NSR, normal sinus rhythm; AF, atrial fibrillation; VT, ventricular tachycardia; VF, ventricular fibrillation; AV, atrioventricular; DES, drug-eluting stent; BMS, bare-metal stent; TIMI, thrombolysis in myocardial infraction; LVEF, left ventricular ejection fraction.

Patients with high-thrombus burden had higher smoking (P < .001), DM (P < .001), HT (P < .001), Cronıc renal failıre (CRF) (P = .012), history of stroke (P < .001), chest pain duration (P = .001), pain-balloon time (P = .002), CAG duration (P = .003), Killip class (P < .001), abciximab usage (P = .000), contrast volume (P = .036), TIMI after intervention (P < .001), and no-reflow (P < .001). The GFR (P = .028), hemoglobin value (P < .001), and diastolic blood pressure (P = .024) were significantly lower in the HTB group. While drug-eluting stent (DES) (P = .004) usage was significantly higher in the LTB group, bare-metal stent (BMS) (P = .032) usage was significantly higher in HTB. In the follow-up of the patients, in-hospital mortality (P < .001) was found to be significantly higher in the HTB group.

The ATRIA risk score (P < .001) was significantly higher in the HTB group. Also, the SYNTAX score (P = .032), CHA2DS2-VASc score (P < .001), and GRACE score (P < .001) were significantly higher in the HTB group (Table 4).

Table 4.

Clinical Scores.

Variables	Low Thrombus Burden (n = 188)	High Thrombus Burden (n = 131)	P Value
ATRIA score	1.35 ± 1.64	4.98 ± 2.99	< . 001
CHA2DS2-VASc score	1.41 ± 1.08	3.11 ± 1.49	< . 001
SYNTAX score	16.2 ± 8.4	18.9 ± 10.1	. 032
GRACE score	110.5 ± 27.9	136.7 ± 40.1	< . 001

Abbreviations: ATRIA, anticoagulation and risk factors in atrial fibrillation; GRACE, Global Registry of Acute Coronary Events.

In multivariate logistic regression analysis, ATRIA score (odds ratio [OR]: 1.672; 95% confidence interval [CI]: 1.460–1.914; P = .000), GFR (OR: 2.13; 95% CI: 1.985–2.316; P = .004), HT (OR: 1.948; 95% CI: 1.044–3.633; P = .036), abciximab usage (OR: 2.34; 95% CI: 1.304–4.200; P = .004) and no-reflow (OR: 1.75; 95% CI: 1.503–1.942; P = .000) were found to be independent predictors of HTB in STEMI patients undergoing primary PCI (Table 5).

Table 5.

Univariate and Multivariate Predictors of Coronary Thrombus Burden in Patients with STEMI.

Variables	Univariate Model			Multivariate Model
Variables	OR	95% CI	P Value	OR	95% CI	P Value
Age	1.007	1.030–1.110	.001	1.09	1.030–1.140	.001
Smoking	0.302	0.190–0.481	.000
Hemoglobin	1.885	1.452–2.170	.003
Serum creatinine	1.007	1.030–1.110	.001
GFR	2.544	2.107–2.955	.000	2.130	1.985–2.316	.004
ATRIA score	1.891	1.583–2.028	.000	1.672	1.460–1.914	.000
SYNTAX score	1.032	1.007–1.059	.012
CHA2DS2-VASc score	2.758	2.188–3.477	.000
GRACE score	1.024	1.016–1.032	.000
Chest pain duration	1.002	1.001–1.003	.003
Pain-ballon time	1.002	1.001–1.003	.000
CAG duration	1.021	1.002–1.041	.031
Diabetes mellitus	2.936	1.733–4.975	.000
Hypertension	5.991	3.671–9.778	.000	1.948	1.044–3.633	.036
History of stroke	25.299	3.311–193.31	.002
Killip class	1.715	1.310–2.246	.000
Abciximab usage	2.907	1.833–4.610	.000	2.340	1.304–4.200	.004
DES usage	0.495	0.306–0.798	.004
BMS usage	1.740	1.046–2.896	.033
No-reflow	7.772	3.304–18.28	.000	1.750	1.503–1.942	.000

Abbreviations: GFR, glomerular filtration rate; CAG, coronary angiography; DES, drug-eluting stent; BMS, bare-metal stent; STEMI, ST-segment elevation myocardial infarction; GRACE, Global Registry of Acute Coronary Events.

The ability of the ATRIA score to predict HTB was evaluated by ROC curve analysis. The area under curve (AUC) value of this analysis is presented in Figure 1 (AUC = 0.836 (0.788–0.884, P = .000)). The ATRIA score >4 (sensitivity 66.2% and specificity 95.2%) and ATRIA score >8 (sensitivity 98% and specificity 100%) were the cutoff of the scores predicting HTB. One of the most important findings was that the thrombus burden increased proportionally as the ATRIA score increased (Figure 2).

Figure 1.

Receiver operating characteristics curves of anticoagulation and risk factors in atrial fibrillation (ATRİA) score in predicting thrombus burden.

Figure 2.

Probability of high thrombus burden according to anticoagulation and risk factors in atrial fibrillation (ATRIA) score.

Discussion

To our knowledge, this is the first study to evaluate the validity of the ATRIA score in predicting HTB in patients with STEMI. The main new finding of the current study was that STEMI patients with an HTB in the IRA had significantly higher ATRIA scores compared to STEMI patients with an LTB. We also demonstrated that as the cut-off value of the ATRIA score increases in these patients, the thrombus burden in the artery associated with infarction might also increase. Moreover, HT, abciximab usage, no-reflow, and low GFR were additional independent predictors of HTB.

Significant advances have been made in the treatment and management of STEMI over the last three decades. These advances have been made possible by demonstrating the critical role of thrombus formed by coronary plaque rupture in coronary occlusion and the resulting myocardial ischemia/infarction.²³ Revascularization based on primary PCI is the central component of the treatment in patients with STEMI. Primary PCI aims to restore patency of the IRA and ultimately myocardial perfusion as early as possible. However, distal embolization of thrombus is common even in primary PCI performed in the most experienced centers. Almost a third of patients have impaired microvascular area perfusion despite TIMI-3 flow in infarct-related coronary arteries.²⁴ Increasing the thrombus burden further impairs the reperfusion of the microvascular area and increases the risk of complications that may arise. Intracoronary HTB may complicate up to 70% of STEMI cases.²⁵ In addition, HTB correlates with larger myocardial infarct size and coronary no-reflow associated with distal embolization, increased risk of stent thrombosis, with subsequent increase in mortality and major adverse cardiac events (MACEs).^4,6,26–28 In this context, intracoronary thrombus burden appears to be the primary prognostic marker for MACEs in STEMI patients.

Originally, the ATRIA score was used for thromboembolic ischemic stroke risk stratification in patients with AF. The ATRIA score was created to better identify AF patients at high risk of stroke than conventional thromboembolism scores.^8,29 The ATRIA score combines renal dysfunction with the CHADS2 score and considers age categories in detail. Age and previous ischemic stroke appear to be the most important factors in ATRIA scoring. These two characteristics account for a large proportion of stroke risk prediction. Advanced age is a dominant risk factor for both cardiovascular and cerebrovascular disease. It is also an independent predictor of poor outcomes in acute myocardial infarction.^30–32 The score was validated in the ATRIA–Cardiovascular Research Network cohort comprising about 35 000 patients with AF. It has been revealed that the ATRIA score outperformed the CHADS2 and CHA2DS2-VASc scores regarding c-index and net reclassification improvement for predicting stroke and thromboembolism.²⁹ These 3 scoring systems were also compared in more than 60 000 AF patients in the UK Clinical Practice Research Datalink cohort. The ATRIA score was better at identifying low thrombosis-risk AF patients who had been classified as high thrombosis-risk by the CHA2DS2-VASc score.⁹ All these studies revealed that the ATRIA score performed better than the CHADS2 and CHA2DS2-VASc scores in predicting ischemic stroke in AF patients, especially in the low thromboembolic risk group.^8,9,33 Studies in different patient cohorts and a recent meta-analysis also support these results. A subsequent meta-analysis supported these results.^10,34

Considering that the parameters in the ATRIA score are directly related to coronary artery diseases, it would be a reasonable hypothesis to think that the ATRIA score can be used to evaluate coronary thrombotic processes. In this context, studies have recently emerged investigating whether the ATRIA score can be used to evaluate early and long-term adverse events caused by CAD. Çetinkal et al¹¹ suggested that the ATRIA score can predict long-term adverse events in myocardial infarction patients and prognostic assessment can be made with the ATRIA score. Abacıoğlu et al¹³ have shown that the ATRIA score may predict no-reflow in patients undergoing primary PCI and may be associated with microvascular dysfunction. Another recent study suggested that the ATRIA score might be useful in predicting contrast-induced nephropathy (CIN) in STEMI patients who underwent primary PCI and that patients at high risk for CIN could be detected by using the ATRIA score in these patients.³⁵ In the present study, we evaluated the effectiveness of the ATRIA score in predicting thrombus burden during the acute atherothrombotic process in STEMI patients. We found that STEMI patients with HTB had a higher ATRIA score and that thrombus burden increased dramatically as the ATRIA score increased. Furthermore, serum creatinine which is indirectly involved in ATRIA scoring, and HT which is directly involved in ATRIA scoring were significantly higher in patients with HTB even outside the scoring. In this context, the presence of HT and renal dysfunction seems to have a significant effect on the results of the present study. Age was the predominant factor in applying the ATRIA score. Researchers have designed this score keeping in mind the increased risk of ischemic stroke in elderly patients. This situation probably increases the diagnostic accuracy of the ATRIA score in a patient with AF. Especially when the ATRIA score is calculated in patients with a previous stroke, age becomes even more critical. We hypothesize that the age distribution of the patients significantly influenced the results of this study, while a history of previous ischemic stroke had a weak contribution. Another parameter in ATRIA scoring is gender. Since the female gender represents 1 point on the ATRIA score, gender distribution might have impacted this study's results. Previously, it has been shown that female patients have a higher risk for poor outcomes in acute myocardial infarction than male patients.³⁶ In the present study, the share of the female gender among patients with HTB was 29.7%, while the share of the female gender among patients with LTB was only 24.4%. Although the difference was not statistically significant, this may have contributed to the higher ATRIA score in high-thrombus burden patients.

Thrombus burden has previously been reported to be an important determinant of coronary microembolization. HTB is associated with an increased risk of procedural complications such as no-reflow, stent malapposition, and stent thrombosis. In addition, HTB has been associated with increased infarct size due to impaired postprocedural epicardial and myocardial perfusion and distal embolization in patients with STEMI undergoing primary PCI.³⁷ To minimize the risk of no-reflow, current guidelines recommend the use of glycoprotein IIb/IIIa inhibitors in patients with an HTB.⁷ In our study, the no-reflow rate and Gp IIb-IIIa antagonist use in HTB patients was significantly higher than in LTB patients

In the current study, HT was more common in STEMI patients with HTB. This result suggests that HT may be associated with more severe prothrombotic processes in STEMI patients. In a recent meta-analysis, HT was identified as the only predictor of STEMI, while DM, dyslipidemia, and advanced age were predictors for non-ST-elevation myocardial infarction and unstable angina pectoris.³⁸ Furthermore, HT is associated with an increased incidence of cardiovascular risk factors and directly contributes to the atherosclerotic process.³⁹ However, it is also a controversial clinical situation, as HT facilitates the action of other factors causing endothelial dysfunction.⁴⁰ It has been suggested that coronary occlusion in patients with preexisting HT might be associated with more extensive myocardial injury, more significant myocardial dysfunction, and consequently, adverse clinical outcomes.^41,42 Lots of clinical evidence supports the existence of a prothrombotic process in patients with HT. This situation may be due to hypertensive end-organ damage paradoxically activating some coagulation factors such as fibrinogen.⁴³ In patients with HT, mean platelet volume and mean platelet mass are higher, and mean platelet granularity is lower. In addition, catecholaminergic discharge and renin-angiotensin-aldosterone system activation trigger platelet aggregation and activation in hypertensive patients.⁴⁴ Our data are partially consistent with these previous findings and may at least explain the high incidence of HT in STEMI patients with an HTB.

Our study has some limitations. First, this is a single-center study with a relatively small study population. Second, the thrombus grade was calculated by evaluating only angiographic images. We did not use intravascular imaging techniques such as intravascular ultrasound and optical coherence tomography. Third, since only STEMI patients were included, the results might not be expanded to all ACS patients. Studies with larger samples are required to confirm our results.

Conclusions

In this study, we have shown that an increase in the ATRIA score correlates with an increase in coronary thrombus burden in STEMI patients undergoing primary PCI. Therefore, the identification of STEMI patients with HTB undergoing primary PCI using this simple scoring system may help to select the best treatment strategy and to take measures to reduce the rate of no-reflow. Further studies are needed to determine the association of the ATRIA score with HTB in STEMI patients.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article

ORCID iD

Osman Kayapinar

References

Silvain

Collet

Nagaswami

, et al. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol. 2011;57(12):1359-1367.

Fukuda

Tanaka

Shimada

Nishida

Kawarabayashi

Yoshikawa

. Predicting angiographic distal embolization following percutaneous coronary intervention in patients with acute myocardial infarction. Am J Cardiol. Feb 2003 15;91(4):403-407.

Sianos

Papafaklis

Daemen

, et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol. 2007;50(7):573-583.

Ndrepepa

Tiroch

Fusaro

, et al. 5-year Prognostic value of noreflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010;55(21):2383-2389.

Yip

Chen

Chang

, et al. Angiographic morphologic features of infarct-related arteries and timely reperfusion in acute myocardial infarction: predictors of slow-flow and no-reflow phenomenon. Chest. 2002;122(4):1322-1332.

Vecchio

Varani

Chechi

, et al. Coronary thrombus in patients undergoing primary PCI for STEMI: prognostic significance and management. World J Cardiol. 2014;6(6):381-392.

Ibanez

James

Agewall

, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology. Eur Heart J. 2018;39:119-177.

Singer

Chang

Borowsky

, et al. A new risk scheme to predict ischemic stroke and other thromboembolism in atrial fibrillation: the ATRIA study stroke risk score. J Am Heart Assoc. 2013;2(3):e000250.

van den Ham

Klungel

Singer

Leufkens

HGM

van Staa

. Comparative performance of ATRIA, CHADS2, and CHA2DS2-VASc risk scores predicting stroke in patients with atrial fibrillation: results from a National Primary Care Database. J Am Coll Cardiol. 2015;66:1851-1859.

10.

Aspberg

Chang

Atterman

Bottai

Singer

. Comparison of the ATRIA, CHADS2, and CHA2DS2-VASc stroke risk scores in predicting ischaemic stroke in a large Swedish cohort of patients with atrial fibrillation. Eur Heart J. 2016;37:3203-3210.

11.

Çetinkal

Koçaş

, et al. Comparative performance of AnTicoagulation and risk factors in atrial fibrillation and global registry of acute coronary events risk scores in predicting long-term adverse events in patients with acute myocardial infarction. Anatol J Cardiol. 2018;20(2):77.

12.

Yildirim

Kucukosmanoglu

Yavuz

, et al. Comparison of the ATRIA, CHA2DS2-VASc, and modified scores ATRIA-HSV, CHA2DS2-VASc-HS, for the prediction of coronary artery disease severity. Angiology. 2021;72(7):664-672.

13.

Abacıoglu

Yildirim

Koyunsever

Kilic

. The ATRIA and modified-ATRIA scores in evaluating the risk of no-reflow in patients with STEMI undergoing primary percutaneous coronary intervention. Angiology. 2021;33197211026420.

14.

Hindricks

, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498.

15.

Gibson

de Lemos

Murphy

, et al. Combination therapy with Abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation. 2001;103:2550-2554.

16.

Sianos

Papafaklis

Serruys

. Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J Invasive Cardiol. 2010;22(Suppl 10):6B-14B.

17.

Jolly

, et al. Thrombus aspiration in patients with high thrombus burden in the TOTAL trial. J Am Coll Cardiol. 2018;72(14):1589-1596.

18.

Niccoli

Burzotta

Galiuto

Crea

. Myocardial no-reflow in humans. J Am Coll Cardiol. 2009;54:281-292.

19.

Gibson

, et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation. 2000;101(2):125-130.

20.

Sianos

Morel

Kappetein

, et al. The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005;1(2):219-227.

21.

SYNTAX Working Group. SYNTAX score calculator. 2007 . Accessed February 2012, http://www.syntaxscore.com

22.

Granger

Goldberg

Dabbous

, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163:2345-2353.

23.

Nabel

Braunwald

. A tale of coronary artery disease and myocardial infarction. N Engl J Med. 2012;366:54-63.

24.

Jaffe

, et al. Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation. 2008;117:3152-3156.

25.

Xiao

Wang

, et al. Effects of different strategies on high thrombus burden in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary catheterization. Coron Artery Dis. 2019;30:555-563.

26.

Agarwal

. Role of intracoronary fibrinolytic therapy in contemporary PCI practice. Cardiovas Revasc Med. 2019;20:1165-1171.

27.

Lee

Kim

Shin

. A case of successful reperfusion through a combination of intracoronary thrombolysis and aspiration thrombectomy in STsegment elevation myocardial infarction associated with an ectatic coronary artery. BMC Cardiovasc Disord. 2017;17:94.

28.

Napodano

Dariol

Al Mamary

, et al. Thrombus burden and myocardial damage during primary percutaneous coronary intervention. Am J Cardiol. 2014;113:1449-1456.

29.

Jagadish

Kabra

. Stroke risk in atrial fibrillation: beyond the CHA2DS2-VASc score. Curr Cardiol Rep. 2019;21(9):95.

30.

Roffi

Patrono

Collet

, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267-315.

31.

Rosengren

Wallentin

Simoons

, et al. Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey. Eur Heart J. 2006;27:789-795.

32.

Dai

Busby-Whitehead

Alexander

. Acute coronary syndrome in the older adults. J Geriatr Cardiol. 2016;13:101-108.

33.

Deering

. Incorporating stroke and bleeding risk stratification tools into atrial fibrillation management making sense of the alphabet soup. J Atr Fibrillation. 2017;9:1497.

34.

Zhu

Ding

, et al. Meta-analysis of ATRIA versus CHA2DS2-VASc for predicting stroke and thromboembolism in patients with atrial fibrillation. Int J Cardiol. 2017;227:436-442.

35.

Aksoy

Bagcı

. Predictive value of ATRIA risk score for contrast-induced nephropathy after percutaneous coronary intervention for ST-segment elevation myocardial infarction. Rev Assoc Med Bras. 2019;65(11):1384-1390.

36.

Kedev

Sukmawan

Kalpak

, et al. Transradial versus transfemoral access for female patients who underwent primary PCI in STEMI: two years follow-up data from acute STEMI interventional registry. Int J Cardiol. 2016;217(Suppl):S16-S20.

37.

Tanboga

Topcu

Aksakal

Kalkan

Sevimli

Acikel

. Determinants of angiographic thrombus burden in patients with ST-segment elevation myocardial infarction. Clin Appl Thromb Hemost. 2014;20:716-722.

38.

Iannaccone

Quadri

Taha

, et al. Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis. Eur Heart J Cardiovasc Imaging. 2016;17(10):1128-1137.

39.

Rakugi

Kamitani

, et al. Links between hypertension and myocardial infarction. Am Heart J. 1996;132:213-221.

40.

Bolad

Delafontaine

. Endothelial dysfunction: its role in hypertensive coronary disease. Curr Opin Cardiol. 2005;20:270-274.

41.

Chen

Hemmelgarn

Alhaider

Quan

Campbell

Rabi

. Metaanalysis of adverse cardiovascular outcomes associated with antecedent hypertension after myocardial infarction. Am J Cardiol. 2009;104:141-147.

42.

Pedrinelli

Ballo

Fiorentini

, et al. Hypertension and acute myocardial infarction: an overview. J Cardiovasc Med. 2012;13:194-202.

43.

Catena

Colussi

Brosolo

Sechi

. A prothrombotic state is associated with early arterial damage in hypertensive patients. J Atheroscler Thromb. 2012;19:471-478.

44.

El Haouari

Rosado

. Platelet function in hypertension. Blood Cells Mol Dis. 2009;42:38-43.