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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 1  |  Page : 8-13

Incidence of myocardial infarction with nonobstructive coronary arteries in patients with acute coronary syndrome


1 Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, National Heart Institute, Cairo, Egypt
3 Department of Cardiology, Ministry of Health, National Heart Institute, Cairo, Egypt

Date of Submission28-Sep-2020
Date of Decision12-Jan-2021
Date of Acceptance18-Jan-2021
Date of Web Publication18-Apr-2022

Correspondence Address:
Ahmed M Abdel Aal
43 Studiomasr Street, Al Haram, Al Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_331_20

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  Abstract 


Objective
To estimate the incidence of myocardial infarction with nonobstructive coronary arteries (MINOCA) among Egyptian cases with acute myocardial infarction (AMI) and to evaluate the role of neutrophilic elastase in AMI cases.
Background
Previous research studies have declared that MINOCA is a syndrome with angiographic normal or near-normal coronary arteries but had evidence of MI clinically, which has many causes.
Patients and methods
To reach the goal of this research, a group study was designed. A total of 627 cases admitted at Cardiology Department of Faculty of Medicine Menoufia University and National Heart Institute in the period from February 2019 to July 2019 were included. Cases were divided into two groups: group 1 included AMI cases with obstructive coronary artery disease group, and group 2 included AMI cases with nonobstructive coronary artery disease (MINOCA group). All cases were subjected to (a) full history taking; (b) clinical examination; (c) laboratory investigations, such as serum HbA1C, cardiac enzymes (total creatine kinase, creatine kinase-myocardial band, and troponin), and serum neutrophil elastase; and (d) other investigations, including ECG and coronary angioplasty.
Results
There were 627 acute coronary syndrome cases, and 49 cases were diagnosed as MINOCA. Regarding the risk factors, diabetes mellitus and smoking showed a significant difference in-between both studied groups (P = 0.038 and 0.014, respectively).
Conclusion
Our study concluded that ~7.8% of the Egyptian cases that presented with AMI for primary percutaneous coronary intervention have MINOCA.
High serum neutrophilic elastase concentration is a sensitive marker, suggesting the existence of complex atheromatous plaques in AMI cases.

Keywords: acute coronary syndrome, primary percutaneous coronary intervention, nonobstructive coronary artery, serum neutrophil elastase


How to cite this article:
El Shafey WE, Aziz WF, Kamal El-Din AM, Abdel Aal AM. Incidence of myocardial infarction with nonobstructive coronary arteries in patients with acute coronary syndrome. Menoufia Med J 2022;35:8-13

How to cite this URL:
El Shafey WE, Aziz WF, Kamal El-Din AM, Abdel Aal AM. Incidence of myocardial infarction with nonobstructive coronary arteries in patients with acute coronary syndrome. Menoufia Med J [serial online] 2022 [cited 2022 Aug 11];35:8-13. Available from: http://www.mmj.eg.net/text.asp?2022/35/1/8/343116




  Introduction Top


In cases with normal coronary arteries by angiography, the etiology and pathogenesis of myocardial infarction (MI) are still unclear [1]. Acute myocardial infarction (AMI) is acute myocardial injury evidenced by clinical manifestations, with the rise and/or fall of cardiac troponin (cTn), with at least one value more than the 99th percentile URL, and with manifestations of myocardial ischemia or new changes of ischemia in ECG. Recently, the definition of MI was updated by the fourth (last) Universal Definition of MI Expert Consensus Document owing to the high usage of high-sensitivity cTn [2].

To implement immediate treatment (e.g. reperfusion therapy), it is common to identify (a) 'ST elevation MI' (STEMI) as MI cases with discomfort in chest or other manifestations of ischemia with ST elevation in two consecutive ECG leads, (b) 'non-ST elevation MI as MI cases with no elevation in ST segment in ECG, and (c) unstable angina as cases with no elevation in values of biomarkers. The last clinical definition of MI in 2018 required abnormal cardiac biomarkers to confirm the injury of myocardial ischemic [3].

Unstable angina is diagnosed when these biomarkers are not detected in the blood hours after the initial onset of ischemic chest pain. Unstable angina exhibits one or more of three principal presentations: (a) rest angina (usually lasting >20 min), (b) new-onset (<2 months previously) severe angina, and (c) a crescendo pattern of occurrence (increasing in intensity, duration, frequency, or any combination of these factors) [4].

In response to acute inflammation as a result of AMI, neutrophil elastase is released, which is a subfamily of serine proteases that are stored in azurophilic granule, with other proteases such as cathepsin G and proteinase 3. Neutrophil elastase degrade not only elastin but also fibronectin, laminar, and collagens III, IV, and VI. NE swings the proteolytic balance in favor of matrix breakdown by activation of matrix metalloproteinase enzyme [5]. Cases with AMI have been shown to have higher neutrophil elastase levels compared with those with stable angina, independent of cardiovascular risk factors [6].

Al-Hadi and Fox[7] reported that creatine kinase-myocardial band (CK-MB) exists in a large quantity in heart muscle but is not totally cardiac specific and exists also in skeletal muscles and other tissues. Approximately 15–40% of the total creatine kinase (CK) activity of heart muscle is due to CK-MB. CK was introduced in 1965 as a biochemical marker for myocardial damage, and it is one of the oldest markers in this field. It has a clinical sensitivity for the diagnosis of AMI of 90%. It is released within 12 h after symptom onset of AMI, peaks in serum at 24–36 h, and returns to normal in 48–72 h. As a result of these release kinetics, measurement of total CK is not suitable for the early diagnosis (within 6 h) of AMI. The aim of this study was to estimate the incidence of myocardial infarction with nonobstructive coronary arteries (MINOCA) among Egyptian cases with AMI and to evaluate the role of neutrophilic elastase in AMI cases.


  Patients and methods Top


After approval of the Local Institutional Ethical Committee of Menoufia University Hospital and after taking a written consent from the participants, this cross-sectional study was conducted on 627 cases admitted at Cardiology Department at Faculty of Medicine, Menoufia University, and National Heart Institute in the period from February 2019 to July 2019.

Inclusion criteria

The following were the inclusion criteria:

  1. Both males and females.
  2. First-ever manifestation of acute coronary syndrome (ACS).
  3. No contraindication for coronary angiography such as contrast allergy and renal impairment.


Exclusion criteria

The following were the exclusion criteria:

  1. Prior history of ischemic heart disease.
  2. Prior MI.
  3. Prior percutaneous coronary intervention.
  4. Prior coronary artery bypass graft.


The cross-sectional study was carried out through two stages:

  1. Stage I: all cases admitted with first-ever manifestation of ACS in determined period of research were included, representing 627 cases, and then the cases were grouped into two groups:


    1. Group 1: AMI cases with obstructive coronary artery (OCA group), representing 578 cases.
    2. Group 2: AMI case with non-OCA (MINOCA group), representing 49 cases.


  2. Stage II: a random sample selection of 49 cases from group 1 (OCA group) was done who were sex and age matched with 49 cases of group 2 (MINOCA group) to assess difference between matched cases in both groups regarding serum neutrophil elastase.


For all cases, the following was done:

  1. Complete history taking:


  2. Thorough history taking was done for all cases, with special stress on the following:

    1. Personal history: age and sex.
    2. Past history of symptoms of pulmonary congestion or symptoms of systemic congestion
    3. Family history of coronary artery disease (CAD), hypertension (HTN), diabetes mellitus (DM), and smoking.


  3. Clinical examination

    Clinical examination was done for all cases with special stress on the following:


    1. Complete general examination: pulse and blood pressure.
    2. Symptoms of systemic congestion such as lower limb edema, abdominal pain, and ascites.
    3. Pulmonary congestion symptoms such as dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.


Laboratory investigations

  1. Serum hemoglobin A1C and cardiac enzymes (CK-MB and troponin):


    1. Samples are collected at the time of case presentation.
    2. cTnI was considered positive if it exceeds normal reference (above 0.02 ng/ml).


  2. Neutrophil elastase: blood sampling was done before angioplasty from guiding catheter (RT. or LT. according to the culprit lesion site).

    A 5 ml blood sample was drawn from patients who agreed to participate in this study. The samples were separated and stored at −20°C. An enzyme-linked immunosorbent assay kit was used to assay human neutrophil elastase in the sample according to the manufacturer's instructions (Product No.: ab270204; Abcam Co. Ltd, Cambridge, UK).
  3. Other investigations included the following:


    1. ECG:

      For diagnosis of ACS, ECG was performed on admission at emergency room triage at a paper speed of 25 mm/s and amplification of 10 mm/mv, with special stress on the ST segment elevation.

      MI was diagnosed by ECG when there is new ST-segment elevation at the J point of at least two contiguous leads of more than or equal to 2 mm (≥0.2 mV) in men or more than or equal to 1.5 mm (0.1 mV) in women in leads V2 and V3 or more than or equal to 1 mm in any other contiguous precordial leads or the limb leads for either sex. New left bundle branch block ST depression in more than or equal to 2 precordial leads (V1–V4) may indicate a posterior STEMI [8], which can happen concurrent with inferior ST elevation or in isolation (isolated posterior infarct); this diagnosis can be confirmed by the presence of more than or equal to 1 mm ST elevation in the posterior (V7–V9) leads.


    2. Coronary angioplasty:

      All cases were transferred directly to catheter laboratory in a timely fashion in accordance with guidelines, time to hospital (from onset of chest pain to diagnosis). All cases received chewable aspirin 300 mg and clopidogrel 600 mg before the procedure.


Left-sided cardiac catheterization was done using retrograde percutaneous trans-femoral technique. After preparing both inguinal regions with antiseptic solution, the femoral artery was punctured using an 18-G needle, through which a J-wire was inserted. Then, the femoral sheath was placed over the wire and left in place through which catheters were inserted.

A 100-cm-long Judkin catheter was used for examination of the left (through femoral sheath) and right coronary systems within different views to visualize it. Heparin (10 000 IU) was administered only when percutaneous coronary intervention was decided for cases with OCA. The coronary lesion is initially crossed with an 0.014-inch-diameter coronary wire. Then the stent is introduced and inflated either directly or after predilatation.


  Results Top


A total of 672 AMI cases were enrolled at this study, including 578 cases (413 males and 165 females) had OCA and 49 cases (40 males and nine females) diagnosed as MINOCA. Male cases were 81.6% MINOCA and 71.5% OCA and female cases were 55.1% MINOCA and 52.1% OCA. The mean age for MINOCA cases was 49.27 ± 6.94 years and for OCA cases was 53.03 ± 9.10 years. Regarding risk factors, DM, family history, and smoking showed significant difference when comparing the two studied groups (P < 0.001 and 0.014, respectively), but HTN and dyslipidemia showed no significant difference when comparing the two studied groups (P > 0.05) [Table 1].
Table 1: Anthropometric measures and risk factors of the study groups

Click here to view


Regarding cardiac biomarkers, we found that CK-MB showed significant increase in MINOCA cases (P < 0.001) [Table 2].
Table 2: Clinical presentation, investigations for cardiac biomarkers; TIMI flow after primary percutaneous coronary intervention, and ECG finding for the study groups

Click here to view


Regarding CK-MB, a CK-MB cutoff point in cases of more than 59.5 ng/ml is more likely to diagnose MINOCA, as 73.5% of MINOCA cases have CK-MB cut-off level more than 59.5 ng/ml (sensitivity), and 51.8% of OCA cases have CK-MB cut-off level more than 59.5 ng/ml (specificity) [Table 3].
Table 3: Receiver operating characteristic curve to estimate cut off levels for chest pain and creatine kinase-myocardial band in myocardial infarction with nonobstructive coronary arteries patients

Click here to view


Regarding serum level of elastase in cases with OCA and in MINOCA cases, we found that median serum level of elastase is statistically significant higher in obstructive CAD group (median = 891.0 pg/ml) than in MINOCA group (median = 73.0 pg/ml) (P < 0.001) [Table 4].
Table 4: The serum level of elastase in patients with obstructive coronary artery disease and in patients with myocardial infarction with nonobstructive coronary arteries

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Receiver operating characteristic curve to estimate cut off levels of CK-MB is shown in [Figure 1].
Figure 1: ROC curve to estimate cutoff levels of CK-MB. CK-MB, creatine kinase-myocardial band; ROC, receiver operating characteristic.

Click here to view



  Discussion Top


MI in the absence of OCA disease (MINOCA) occurs in 5–6% of AMI cases (range reported between 5 and 15%). Diagnosis of MINOCA should be made according to the Fourth Universal Definition of MI, in the absence of obstructive CAD (no lesion ≥50%). The diagnosis of MINOCA should exclude (a) other overt causes for elevated troponin (e.g. pulmonary embolism and sepsis), (b) overlooked obstructive coronary disease (e.g. distal stenosis or occluded small branches), and (c) nonischemic causes for myocyte injury (e.g. myocarditis) [9].

Nonobstructive coronary disease by coronary angiography should be differentiated between patients with normal coronary arteries and minimal luminal irregularities (<30% stenosis) and mild to moderate coronary atherosclerosis (30 to <50%). FFR can be useful. In this study, we discuss the incidence of MINAOCA in cases presented with AMI within 6 months and determine whether changes in concentration of serum neutrophilic elastase level could suggest the angiographically finding [10].

In our study, 627 ACS cases were included that were divided into 49 cases diagnosed as MINOCA and 578 cases as OCA. Male cases were 81.6% MINOCA and 71.5% obstructive ACS, and female cases were 55.1% MINOCA and 52.1% obstructive ACS. The mean age for MINOCA cases was 49.27 ± 6.94 years and for obstructive ACS cases was 53.03 ± 9.10 years. Risk factors, such as DM, family history, and smoking, showed significant difference when comparing the two studied groups (P < 0.001, 0.197, and 0.014, respectively), with higher in OCA case, but HTN and dyslipidemia showed no significant difference when comparing the studied groups.

This is in agreement with Williams et al. [11], who reported that 897 (10.8%) from 8305 cases with MI were MINOCA. In comparison with OCA cases, MINOCA cases had lower mean age (63.1 ± 12.5 vs. 65.1 ± 12.0 years, P < 0.001), female predominance (54.3 vs. 27.5%, P < 0.001), higher prevalence of smoking (46 vs. 42.1%, P = 0.04), higher prevalence of DM (84.3 vs. 77.3%, P < 0.01), higher systolic blood pressure (143.3 ± 27.2 vs. 141 ± 27.2 mmHg, P = 0.021), lower TC/HDL (3.81 ± 1.43 vs. 4.42 ± 2.17, P < 0.001), and lower levels of LDL (2.53 ± 1.15 vs. 2.72 ± 1.25 mmol/l, P < 0.001). A study by Pasupathy et al.[12] reported that 36 (8.2%), from a total of 440 AMI cases in the Queen Elizabeth Hospital, were diagnosed as MINOCA cases. Of which, cases that had HTN were 60% followed by DM, as 24%, and 24% were smokers.

We found a significant difference between the two groups regarding CK-MB (dl/ml) and ECG finding. This is in accordance with Collste et al. [13], who reported that acute pulmonary embolism may mimic AMI, presenting with chest pain, CK-MB, and the associated acute right heart strain, producing ECG changes and an increase in troponin levels. Thus, a diagnosis of acute pulmonary embolism needs to be considered in MINOCA, but the merits of routinely screening for this diagnosis are less clear. In addition, Nordenskjöld et al.[14] found that, early mortality for STEMI cases without obstructive CAD is reported at 0.6%, which is significantly lower than the early mortality in those with obstructive CAD (2.8%)

We found that regarding CK-MB, a CK-MB cutoff point of more than 59.5 ng/ml in cases is more likely to diagnose MINOCA, as 73.5% of MINOCA cases have CK-MB cutoff level more than 59.5 ng/ml (sensitivity), and 51.8% of OCA have CK-MB cutoff level more than 59.5 ng/ml (specificity).

This goes with Hong and Oh [15], who reported that CK-MB activity [cut-off value 16 U/l, and relative index (CK-MB 100/total CK) 4–25%] and cTnT (cut-off value 0.1 ng/ml) were detected in serum within 3 h after onset of chest pain, and cTnT persisted for longer times than CK-MB activity. Sensitivity of cTnT (69.6%) is not statistically different from CK-MB activity (72.9%) within 24 h of chest pain but more sensitive after 24 h of symptom. Specificity (87.9%) and negative predictive value (91.2%) of cTnT were superior to that of CK-MB activity within 24 h of chest pain. Their receiver operating characteristic curve analysis demonstrated the following: cutoff, sensitivity, and specificity for cTnT were 0.13 ng/ml, 76.7%, and 100%, respectively, and CK-MB activity had 14 U/l, 84.7, and 71.0%, respectively. Measurement of cTnT was useful for late-admitted AMI cases and together with CK-MB could improve the detection of MI.

On relation between serum level of elastase in cases with OCA and in MINOCA cases, it is obviously clear that OCA cases have been shown to have higher neutrophil elastase levels compared with MINOCA cases, independent of cardiovascular risk factors.

In agreement with us, Amaro Cendon et al.[16] found in a study done on 95 cases that underwent coronary angiography during investigation of chest pain and/or heart valve disease that 38 had normal coronary arteriograms (group 1) and 57 had coronary lesions (group 2). They reported that the concentration of elastase was higher in group 2 compared with group 1 (41 ± 21 vs. 27 ± 14 μg/l) (P < 0.001), and higher in cases with complex plaque compared with cases with simple plaque (53 ± 27 vs. 33 ± 12 μg/l) (P < 0.001).

Cases with ACS express cytokines and chemoattractants such as tumor necrosis factor-α and interleukin-8, which activate neutrophil elastase that are trapped behind atheromatous plaque for hemolysis. Cases with ACS have lower level of NE than OCA case, which may be owing to consumption of this enzyme and washed out with macrophage after spontaneous recanalization or early presentation before well-formed thrombus.


  Conclusion Top


  1. The results obtained in our study support that in cases undergoing coronary angiography, MINOCA is uncommon but problematic.
  2. Cases with MINOCA were younger and more often women.
  3. Regarding cardiovascular risk factors, cases with DM, HTN, and family history of CAD were lower in MINOCA group. Hyperlipidemia shows nonsignificant difference between the two groups.
  4. High levels of neutrophil elastase were associated with severe atheromatous plaque.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018; 72:2231–2264.  Back to cited text no. 1
    
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Yang Q, Wang Y, Liu J, Liu J, Taubert K. Invasive management strategies and antithrombotic treatments in patients with non–ST-segment–elevation acute coronary syndrome in China: findings from the improving CCC project (care for cardiovascular disease in China). Circ Cardiovasc Interv 2017; 10:e004750.  Back to cited text no. 3
    
4.
Kaya Ç, Altay S. An extreme case of vasospastic angina mimicking acute STEMI: severe three-vessel disease with critical stenoses. Anatol J Cardiol 2019; 21:347–349.  Back to cited text no. 4
    
5.
Wen G, An W, Chen J, Maguire EM, Chen Q, Yang F, et al. Genetic and pharmacologic inhibition of the neutrophil elastase inhibits experimental atherosclerosis. J Am Heart Assoc 2018; 7:e008187.  Back to cited text no. 5
    
6.
Kurup R, Patel S. Neutrophils in acute coronary syndrome. EMJ Cardiol 2017; 5:79–87.  Back to cited text no. 6
    
7.
Al-Hadi H, Fox K. Cardiac markers in the early diagnosis and management of patients with acute coronary syndrome. Sultan Qaboos Univ Med J 2009; 9:231–246.  Back to cited text no. 7
    
8.
Bhave P, McCabe J, Armstrong E, Kulkarni A, Hoffmayer K, Kinlay S. Prevalence and factors associated with false-positive ST-segment elevation myocardial infarction diagnoses at primary percutaneous coronary intervention–capable centers: a report from the Activate-SF registry. Arch Intern Med 2012; 172:864–871.  Back to cited text no. 8
    
9.
Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation 2015; 131:861–870.  Back to cited text no. 9
    
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Scalone G, Niccoli G, Crea F. Editor's Choice-pathophysiology, diagnosis and management of MINOCA: an update. Eur Heart J 2019; 8:54–62.  Back to cited text no. 10
    
11.
Williams M, Barr P, Lee M, Poppe K, Kerr A. Outcome after myocardial infarction without obstructive coronary artery disease. Heart 2019; 105:534–530.  Back to cited text no. 11
    
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Pasupathy S, Rodgers S, Tavella R, McRae S, Beltrame JF. Risk of thrombosis in patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA). TH Open 2018; 2:e167–e172.  Back to cited text no. 12
    
13.
Collste O, Sörensson P, Frick M, Agewall S, Hofman-Bang C. Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study. J Intern Med Suppl 2013; 273:189–196.  Back to cited text no. 13
    
14.
Nordenskjöld A, Baron T, Eggers K, Jernberg T, Lindahl B. Predictors of adverse outcome in patients with myocardial infarction with non-obstructive coronary artery (MINOCA) disease. Int J Cardiol 2018; 261:18–23.  Back to cited text no. 14
    
15.
Hong G, Oh K. Clinical usefulness of the CK-MB activity and cardiac troponin T as markers for detection of acute myocardial infarction. Korean J Clin Pathol 2000; 20:24–29.  Back to cited text no. 15
    
16.
Amaro Cendon A, González-Juanatey JR, Sampedro Gude F, Iglesias Carreno C, Fernandez Vazquez F, Lamela Virgos A, Garcia Acuna JM, Gil de la Pena M. Activity of leukocyte elastase in coronary disease diagnosed by coronarography. Rev Esp Cardiol 1994; 47:523–528.  Back to cited text no. 16
    


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    Tables

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