Impact of periprocedural myocardial necrosis on short term clinical outcome

The Egyptian Journal of Critical Care Medicine xxx (2017) xxx–xxx

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Original article

Impact of periprocedural myocardial necrosis on short term clinical outcome Yosef Haggag, Mohamed Saleh ⇑, Mahmoud Khaled, Amr Elhadidy Critical Care Medicine Department, Cairo University, Egypt

a r t i c l e

i n f o

Article history: Received 21 January 2016 Revised 15 July 2016 Accepted 16 March 2017 Available online xxxx Keywords: Periprocedural myocardial necrosis PCI Modified Gensini score

a b s t r a c t Background: No reliable data whether periprocedural myocardial necrosis (PPN) has same poor prognostic value as periprocedural myocardial infarction (PMI) or not. We aimed to assess the impact of PPN on short term clinical outcome. Methods: 100 patients admitted with non ST elevation acute coronary syndrome and underwent PCI were enrolled. Patients were grouped according to the occurrence of PPN into 2 groups, and were followed for 3 months. Patients with PMI were excluded. Results: 30 patients (30%) had PPN and were associated with higher risks of major adverse cardiac events (MACE) during the hospital and 3 months follow up (43.3% and 66.7% vs. 12.9% and 14.3% respectively; p < 0.001). PPN was more likely to occur in older, diabetic, previously infracted, and heart failure patients (p value: <0.05), in addition to patients who had lengthy and more complex lesions (p value 0.006 and <0.001 respectively). Each unit increase in Modified Gensini Score (MGS) increased odds of procedural complications 1.2 times, (P value 0.046), which in turn increased odds of short term MACE 5.7 times, (P value 0.003). Conclusions: PPN are associated with poor short term prognosis. PPN occurs more in diabetic, heart failure, infracted patients and those who have complex lesions. Ó 2017 The Egyptian College of Critical Care Physicians. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction The relation between percutaneous coronary intervention (PCI) and subsequent myocardial injury has been reported for many years [1]. Its incidence ranges from 10% to 40% and depends on several factors such as angiographic, procedural characteristics and the biomarker used for its detection [2]. 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 [4].

Peer review under responsibility of The Egyptian College of Critical Care Physicians.

Production and hosting by Elsevier ⇑ Corresponding author. E-mail addresses: [email protected] (Y. Haggag), mohamedhs138@gmail. com (M. Saleh), [email protected] (M. Khaled), [email protected] (A. Elhadidy).

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) [5]. 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 [6]. The adjusted mortality risk at 6 months was significantly increased for periprocedural myocardial infarction, but was not increased for periprocedural myocardial necrosis (RR, 2.82; P = 0.03) [7]. 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 longterm (2-year) mortality [8]. 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 [9].

http://dx.doi.org/10.1016/j.ejccm.2017.03.002 2090-7303/Ó 2017 The Egyptian College of Critical Care Physicians. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Haggag Y et al. Impact of periprocedural myocardial necrosis on short term clinical outcome. Egypt J Crit Care Med (2017), http://dx.doi.org/10.1016/j.ejccm.2017.03.002

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Y. Haggag et al. / The Egyptian Journal of Critical Care Medicine xxx (2017) xxx–xxx

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 3 months follow up) and to determine its possible risk factors. 2. Methods 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 [10], 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 8 h for 24 h 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 24 h 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 75 mg twice daily for one month then 75 mg once daily during the whole study period. All PCIs were performed by right transfemoral approach. Angiographic data: The extent and severity of coronary artery disease was assessed using modified Gensini score (MGS) [11], 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 3 months 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. Results 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. 3.3. Prognosis Patients in Group I had higher incidence of early (in hospital) and late (3 months) 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 (3 months) 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

Table 1 Baseline demographic data. Data are presented as Mean ± SD or number (percentage %). All patients

Group I (N = 30)

Group II (N = 70)

P value

Age Gender ($) Diabetes Mellitus Hypertension FH of CAD Dyslipidaemia Current Smoking Canadian Score Hyperuricemia History of CHF History of CVAs COPD Liver Cirrhosis FS% EF%

59.3 ± 12.1 8 (26.7%) 29 (96.7%) 26 (86.7%) 21 (70%) 28 (93.3%) 19 (63.3%) 1.6 ± 0.9 18 (60%) 9 (30%) 17 (56%) 1 (3.3%) 1 (3.3%) 29.9 ± 6.3 56.2 ± 9.5

54.2 ± 10.2 17 (24.3%) 8 (11.4%) 38 (54.3%) 35 (50%) 57 (81.4%) 41 (58.6%) 1.4 ± 0.8 46 (65.7%) 3 (4.3%) 21 (24.2%) 1 (1.4%) 1 (1.4%) 31.0 ± 5.7 56.2 ± 9.2

0.034 0.493 <0.001 0.001 0.051 0.107 0.414 0.189 0.372 <0.001 0.521 0.5121 0.5121 0.374 0.983

Please cite this article in press as: Haggag Y et al. Impact of periprocedural myocardial necrosis on short term clinical outcome. Egypt J Crit Care Med (2017), http://dx.doi.org/10.1016/j.ejccm.2017.03.002

Y. Haggag et al. / The Egyptian Journal of Critical Care Medicine xxx (2017) xxx–xxx Table 2 Angiographic and procedural data. Data are presented as Mean ± SD or number (percentage %).

Average length (mm) Average diameter (mm) Complex lesions DES BMS Direct stenting Predilatation Single vessel intervention Multivessel intervention Edge dissection Perforation Slow flow Distal embolization Stent thrombosis Side Branch. Occ. No reflow

Group I (N = 30) Mean ± SD

Group II (N = 70) Mean ± SD

P value

25.9 ± 6.5

22.5 ± 5.2

0.006

3.1 ± 0.4

3.2 ± 0.4

0.533

26 (86.7%) 23 (57.5%) 17 (42.5%) 7 (17.5%) 33 (82.5%) 20 (66.66%)

7 (10%) 50 (60.9%) 32 (39.1%) 10 (12.2%) 72 (87.8%) 59 (84%)

<0.001 0.025 0.20 0.15 0.25 0.521

10 (33.33%)

11 (16%)

0.01

4 1 5 0 0 3 0

3 (4%) 0 (0%) 18 (25.7%) 0 (0%) 0 (0%) 0 (0%) 0

0.106 0.513 0.642 1.000 1.000 0.008 1.000

(13.3%) (3.3%) (16.6%) (0%) (0%) (3.3%)

Table 3 Early (in hospital) and late (3 months) post intervention MACE. Data are presented as number (%). MACE

Group I (30 pts)

Group II (70 pts)

P value

Early (In hospital) Late (3 months)

13 (43.3%) 20 (66.7%)

9 (12.9%) 10 (14.3%)

<0.001 <0.001

Table 4 Early and late post intervention MACE in relation to procedural complications. Data are presented as number (%). MACE

Procedural complications N(%)

No procedural complications N(%)

P value

Early (In hospital) Late (3 months)

15 (46.9%) 12 (37.5%)

7 (10.6%) 18(27.3%)

<0.001 0.273

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). 4. Discussion 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 ± 12.1 yrs vs 54.2 ± 10.2 yrs with p value 0.03) and this goes hand in hand with Nageh et al. [12] 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 [13] et al., proved the same concept, as he reported that PMN occurs more in patients with high cardio-

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vascular 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. [8] 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 ± 11.4 yrs vs 65.9 ± 11.8 yrs, 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. [14] 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. [8] 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. [8] 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 [8] (33.9% vs 31.6% respectively with p value 0.338) and Cantor et al. [14] (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. [15], 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. [12], and Cantor et al. [14] studies who found that significant relationship between procedural complications and myocardial injury. Xavier Muschart et al., [16] 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

Please cite this article in press as: Haggag Y et al. Impact of periprocedural myocardial necrosis on short term clinical outcome. Egypt J Crit Care Med (2017), http://dx.doi.org/10.1016/j.ejccm.2017.03.002

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Y. Haggag et al. / The Egyptian Journal of Critical Care Medicine xxx (2017) xxx–xxx

(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. [12] who found that cardiac biomarkers elevation is associated with worse post intervention outcome. Again, Cantor et al. [14] and Stone et al. [17] found that cardiac biomarkers elevation was significantly correlated with early post intervention MACE. In 2013, Park et al., [18] 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. [14] and Nageh et al. [12] results. Also, we found that group I patients had higher incidence of developing MACE after 3 months compared to group II patients, (66.7% vs 14.3%, with p value < 0.001). This was supported by Cantor et al. [14] 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. Disclaimer The current study was self funding one & there were no conflicting interests.

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Please cite this article in press as: Haggag Y et al. Impact of periprocedural myocardial necrosis on short term clinical outcome. Egypt J Crit Care Med (2017), http://dx.doi.org/10.1016/j.ejccm.2017.03.002