The relation between percutaneous coronary intervention (PCI) and subsequent myocardial injury has been reported for many years . Its incidence ranges from 10% to 40% and depends on several factors such as angiographic, procedural characteristics and the biomarker used for its detection . This injury is usually related to procedural complications such as side branch occlusion, distal embolization of thrombus or plaque, poor flow, and coronary dissection [2,3]. However, periprocedural myocardial infarction (PMI) may happens after apparently uncomplicated procedures .
The definition of periprocedural myocardial infarction is debatable and varies in clinical trials. The consensus definition of myocardial infarction (MI) including periprocedural myocardial infarction that was published in 2000, was any rise and fall in cardiac biomarkers above the upper limit of normal (ULN) . In 2007, the American College of Cardiology (ACC) defined periprocedural myocardial infarction as an increase of biomarkers greater than 3 times ULN and considered elevations of cardiac biomarkers between 1and 3 times ULN as periprocedural myocardial necrosis (PMN) and not infarction .
The adjusted mortality risk at 6months was significantly increased for periprocedural myocardial infarction, but was not increased for periprocedural myocardial necrosis (RR, 2.82; P=0.03) . Another analysis from Cornell Angioplasty Registry showed that after elective PCI, troponin I elevation greater than 5 times ULN were associated with a 1.8-fold increase of long-term (2-year) mortality . The importance of PMN is frequently dismissed because there is little or no evidence for an independent risk of poor prognosis from these small biomarker elevations .
The aim of this study is to assess the impact of periprocedural myocardial necrosis (diagnosed by elevation of cardiac biomarkers (CK, CK-MB and troponin) between 1 and 5 times ULN on short term prognosis (in hospital and 3months follow up) and to determine its possible risk factors.
The Current study was conducted as a prospective observational study on 100 patients admitted to critical care department, Cairo university with non ST elevation acute coronary syndrome (During the period between January 2011 and January 2012); and scheduled to undergo coronary angiography and requiring PCI. Patients with renal impairment, disseminated malignancy, or who develop PMI diagnosed by elevation of cardiac biomarkers greater than 5 times ULN were excluded. Written informed consent were taken from all patients or their 1st degree relatives. The study was approved from our local ethical committee. All patients were subjected to: detailed history taking including their Canadian Cardiovascular Society grading of angina pectoris , full general and systemic examination, standard 12-lead ECG, echocardiographic assessment, kidney function tests, coagulation and lipid profile. Cardiac enzymes (CK, CK-MB, and quantitative Troponin I) were done before coronary angiography and every 8h for 24h after the procedure.
The studied patients were divided into 2 groups according to results of Cardiac Biomarkers after PCI into:
- Group I: patients who had 1–5 times ULN elevation of any cardiac biomarkers (CK, CK-MB, and/or quantitative Troponin I) within 24h after PCI. (30 patients)
- Group II: patients who did not have elevated cardiac biomarkers. (70 patients)
Medical treatment for all patients before and after PCI included Aspirin and Clopidogrel. After PCI, the dose of clopidogrel was 75mg twice daily for one month then 75mg once daily during the whole study period. All PCIs were performed by right trans-femoral approach.
Angiographic data: The extent and severity of coronary artery disease was assessed using modified Gensini score (MGS) , all other data including: the culprit vessel; lesion type and length; stent type, diameter and length; number of PCI vessels as well as any procedural complications were reported.
Prognosis and outcome: patients were followed for 3months to detect the occurrence of major adverse cardiac events (MACE):
- 1- Arrhythmias that require pharmacological or interventional treatment.
- 2- Readmission by recurrent myocardial ischemia either unstable angina or MI.
- 3- Need for target vessel revascularization either by PCI or CABG.
- 4- Heart failure defined by symptoms and sings of pulmonary congestion requiring the use of specific therapy as diuretics, vasodilators, and inotropic supports.
- 5- Death.
Statistical Analysis: Data were prospectively collected and coded prior to analysis using the professional statistical Package for Social Science (SPSS version 21). All data were expressed as mean and standard deviation (SD). Frequency tables for all categorical data and descriptive statistics for quantitative data has been performed. Student t-test and chi-square test after checking normality for all continuous data. Mean values were compared and statistical significance was defined as P<0.05.
3.1. Baseline clinical and demographic data
The two studied groups showed significant difference regarding their age and prevalence of diabetes mellitus, and hypertension. Also, the number of patients who had history of CHF was significantly higher in Group I compared to Group II. Table 1 Apart from significant higher incidence of previous Q wave infarction in group I compared to group II (76.7% versus 11.4%, P value <0.001), both groups showed no significant difference regarding their baseline and follow up ECG findings.
3.2. Angiographic and procedural data
In the studied patients, 122 vessels were subjected to PCI in 100 patients where RCA constituted 42% (52), LAD constituted 38% (46) and LCX constituted 20% (24). It was found that there was no significant correlation between type of the treated vessel and elevation of cardiac biomarkers. However, lesions in group I were significantly longer and more complex compared to group II, (25.9±6.5 vs 22.5±5.2, P value <0.001), (86.7% vs 10%, P value <0.001) respectively. Multivessel PCIs were more in group I compared to group II (33% vs 16%, with p value 0.01). Thirty three patients were identified to have complex lesions as follows (20 CTO, 5 heavy calcifications, 5 long lesions & 3 bifurcational lesions) all of them were in group I apart from 7 patients with CTO lesions.
Incidence of side branch occlusion was significantly higher in group I compared to group II (3.3% vs 0% with p value 0.008). While the incidence of edge dissection and vessel perforation were insignificantly higher in group I compared to group II (13.3% vs 4% with p value 0.106 and 3.3% vs 0% with p value 0.513 respectively) Table 2.
Patients in Group I had higher incidence of early (in hospital) and late (3months) post intervention MACE compared to patients in Group II Table 3.
Patients who experienced procedural complications as edge dissection, perforation, distal embolization, acute stent thrombosis, slow, or no reflow had higher incidence of early but not late (3months) post intervention MACE compared with uncomplicated patients Table 4.
Multivariate logistic regression analysis was used to develop a model of predicting periprocedural myocardial necrosis and procedural complications. It was found that previous MI, diabetes mellitus, complex lesions rendered periprocedural myocardial necrosis 54, 47, 11 times more likely with P value 0.003, 0.002, 0.027, respectively. MGS was an independent predictor of procedural complications, as each unit increase in MGS, increased odds of procedural complications 1.2 times, (P value 0.046) which in turn increased odds of early post intervention MACE 5.7 times, (P value 0.003).
This study shows that older, diabetic, heart failure, and previously infracted patients are more likely to develop periprocedural myocardial necrosis which in turn lead to poor short term prognosis after PCI. MGS was an independent predictor of procedural complications which in turn increased odds of early post intervention MACE. This was supported with our results that showed that patients in group I patients were significantly older compared to group II (59.3±12.1yrs vs 54.2±10.2yrs with p value 0.03) and this goes hand in hand with Nageh et al.  who enrolled 316 consecutive patients with stable symptoms & native coronary artery disease undergoing elective PCI. They found that age was a significant predictor for elevated cardiac biomarker post PCI (p value: 0.01). Claudio Cavillini  et al., proved the same concept, as he reported that PMN occurs more in patients with high cardiovascular risks as advanced age, unfavorable coronary anatomy, and in patients with renal failure that were excluded from our study.
The same concept was proved by Feldman et al.  who enrolled 1601 patients undergoing PCI. Of them, 831 patients (52%) had myocardial injury proven by elevated cardiac biomarkers and their mean age was significantly higher compared to patients who had not. (67.3±11.4yrs vs 65.9±11.8yrs, with p value 0.02).
On analyzing risk factors, we observed that group I patients had a significant higher incidence of diabetes mellitus compared to group II patients (96.7% vs 11.4% respectively with p value <0.001). On the contrary Cantor et al.  found that diabetes mellitus is an insignificant predictor of periprocedural myocardial injury after elective PCIs, (14.8% vs 20.3% with p value >0.05). Also, Feldman et al.  stated that there was insignificant impact of diabetes mellitus on the periprocedural myocardial injury, (30.2% vs 34.4% respectively, with p value 0.077). This difference between our results and their results may be due to poor control of diabetes mellitus in our subjects and hence the aggressive detrimental effect of diabetes mellitus.
Congestive heart failure (CHF) was found to be a significant predictor of PMN in the present work (30% in group I vs 4.3% in group II with p value<0.001). Parallel to our results, Feldman et al.  had identified CHF as a significant predictor of elevated cardiac biomarkers after elective PCI (8.9% vs 6.2% respectively, with p value 0.048).
In the current study, previous history of MI was found to be a significant predictor of periprocedural myocardial necrosis (76.7% in group I vs 11.4% in group II with p value<0.001). In contrast to our results, previous MI had not been considered a significant predictor of periprocedural myocardial injury according to Feldman et al. study  (33.9% vs 31.6% respectively with p value 0.338) and Cantor et al.  (18.1% vs 23.1% respectively with p value >0.05). This could be explained by small sample size in our study compared to their studies.
This study also showed that the severity and extent of the coronary artery disease and the occurrence of procedural complications were significant risk factors of periprocedural myocardial necrosis which in turn lead to poor short term prognosis. As we found that longer and more complex lesions were significant predictors of periprocedural myocardial necrosis (p value<0.05). Using multivariate analysis, MGS was found to be an independent predictor for procedural complications, as each unit increase in MGS increased odds of procedural complications 1.2 times, (P value 0.046) which in turn increased odds of early post intervention MACE 5.7 times, (P value 0.003). Ellias B et al. , mentioned the same idea when he reported that there is direct relation between the amount of atherosclerotic plaque burden and periprocedural myocardial infarction, and hence the significance of atheroembolic process in the pathophysiology of periprocedural myocardial infarction. They postulated that plaque disruption releases prothrombotic biofactors leading to platelet activation, microvascular thrombosis, inflammation and release of reactive oxygen species that will end in myocardial injury.
Regarding procedural complications, side branch occlusion was found to be a significant predictor of periprocedural myocardial necrosis (10% in group I vs 0% in group II with p value 0,008). This goes hand in hand with Nageh et al. , and Cantor et al.  studies who found that significant relationship between procedural complications and myocardial injury. Xavier Muschart et al.,  mentioned the same concept, as they found that 60% of their patients who developed periprocedural myocardial infarction were related to procedural complications as side branch occlusion, distal embolization, prolonged ischemia, and stent thrombosis.
Compared to group II, group I patients had higher incidence of developing early post intervention (during the hospital) MACE (43.3% in group I vs 12.9% in group II with p value<0.001). This goes hand in hand with Nageh et al.  who found that cardiac biomarkers elevation is associated with worse post intervention outcome. Again, Cantor et al.  and Stone et al.  found that cardiac biomarkers elevation was significantly correlated with early post intervention MACE. In 2013, Park et al.,  reported that cardiac enzyme elevation post PCI was associated with significant and clinically meaningful increased risk of mortality. The mechanism that led to poor prognosis cannot be explained by the degree of myocardial damage which was limited in periprocedural myocardial necrosis patients. The possible mechanisms may be the extent of coronary artery disease or occurrence of procedural complications.
In our study, patients who had procedural complications experienced higher incidence of early (in hospital) MACE (P value <0.001) and this goes hand to hand with Cantor et al.  and Nageh et al.  results.
Also, we found that group I patients had higher incidence of developing MACE after 3months compared to group II patients, (66.7% vs 14.3%, with p value<0.001). This was supported by Cantor et al.  study, as they found that incidence of MACE was more in patients who had periprocedural myocardial injury. (P value: 0.007).
5. Conclusions and recommendations
Periprocedural myocardial necrosis is associated with poor short term prognosis. Periprocedural myocardial necrosis is more likely in older, diabetic, heart failure, infracted patients and those who have complex lesions. Modified Gensini Score was an independent predictor of procedural complications and hence short term major advance cardiac events. Small sample size and relatively short follow up period are limitations of this study.
We recommend to routinely measure cardiac biomarkers before and after elective percutaneous intervention. Any elevation of cardiac biomarkers should be considered and these patients should be closely followed.
The current study was self funding one & there were no conflicting interests.
 Prasad Abhiram, Rihal Charanjit S, Lennon Ryan J, et al. Significance of periprocedural myonecrosis on outcomes after percutaneous coronary intervention. Circ: Cardiovasc Intervention 2008;1:10-19.
 Herrmann J. Peri-procedural myocardial injury. Eur Heart J 2005;26:2493-2519.
 Hassan Pervais M, Sood Poornima, Soodhir Krishnankutty, et al. Circ: Cardiovasc Intervention 2012;5:142-145.
 Mehran R, Dangas G, Mintz GS, et al. Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions: intravascular ultrasound study of 2256 patients. Circulation 2000;101:604-610.
 Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-969.
 Thygesen K, Alpert JS, White HD. Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal Definition of Myocardial Infarction. ESC/ACCF/AHA/WHF Expert Consensus Document. J Am Coll Cardiol 2007;50:2173-2195.
 Roe MT, Mahaffey KW, Kilaru R, et al. Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes. Eur Heart J 2004;25:313-321.
 Feldman DN, Minutello RM, Bergman G, et al. Relation of troponin I levels following non emergent percutaneous coronary intervention to short-and long-term outcomes. Am J Cardiol 2009;104:1210-1215.
 Lansky Alexandra J, Stone Gregg W. Advances in interventional cardiology: periprocedural myocardial infarction prevalence, prognosis, and prevention. Circ: Cardiovasc Interventions 2010;3:602-610.
 Kaul Padma, Naylor C David, Armstrong Paul W, et al. Can J Cardiol 2009;25(7):225-231.
 Heffernan KS, Patvardhan EA, Kapur NK, et al. Peripheral augmentation index as a biomarker of vascular aging: an invasive hemodynamics approach. Eur J Appl Physiol 2012;112(8):2871-2879.
 Nageh T, Thomas MR, Sherwood RA, et al. Direct stenting may limit myocardial injury during percutaneous coronary intervention. J Invasive Cardiol 2003;15:115-118.
 Cavallini Claudio, Verdeccheia Paolo, Savonitto Stefano, et al. Circ: Cardiovasc Interventions 2010;3:431-435.
 Cantor WJ, Newby LK, Christenson, et al. Prognostic significance of elevated troponin I after percutaneous coronary intervention. J Am Coll Cardiol 2002;39:1738-1744.
 Elias B, Hanna Hennebry Thomas A. Periprocedural myocardial infarction: review and classification. Clin Cardiol 2010;33(8):476-483.
 Muschart Xavier, Slimani Alisson, Jamart Jacques, et al. The different mechanisms of periprocedural myocardial infarction and their impact on in hospital outcome. J Invasive Cardiol 2012;24(12):655-660.
 Stone GW, Mehran R, Dangas G, et al. Differential impact on survival of electrocardiographic Q-wave versus enzymatic myocardial infarction after percutaneous intervention: a device-specific analysis of 7147 patients. Circulation 2001;104:642-647.
 Park D-W, Kim Y-H, Yun S-C, et al. Frequency, causes, predictors, and clinical significance of peri-procedural myocardial infarction following percutaneous coronary intervention. Eur Heart J 2013;34:1662-1669.