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Impact of periprocedural biomarker elevation on mortality in stable angina pectoris patients undergoing elective coronary intervention: a systematic review and meta-analysis including 24 666 patients
Mohamad Soud,
aAlexandre Hideo-Kajita,
aGavin Ho,
aOmar Yacob,
aFares Alahdab,
bFred King,
aRon Waksman,
aEugène P. McFadden
cand Hector M. Garcia-Garcia
aBackground Uncertainty remains regarding the exact prognostic impact of biomarker elevation following percutaneous coronary intervention in patients with stable angina pectoris and the subsequent risk of death. We sought, therefore, to evaluate the effect of periprocedural myocardial infarction on the subsequent mortality risk following percutaneous coronary intervention in patients with stable angina pectoris and normal preprocedural cardiac biomarkers level.
Methods After a systematic literature search was done in PubMed and EMBASE, we performed a meta-analysis of studies with post-procedural cardiac biomarkers data.
All-cause mortality and cardiac death were evaluated in subjects with stable angina pectoris who underwent an elective coronary intervention.
Results Fourteen studies with 24 666 patients were included. The mean age was 64.2 years ± 9.8 with about 3-quarters (74.9%) of these patients being men. The mean duration of follow-up was 18.1 months ± 14.3.
Periprocedural myocardial infarction, based on study- specific biomarker criteria, occurred in 14.3% of the patients. Periprocedural myocardial infarction conferred a statistically significant increase in the risk of all-cause
mortality (odds ratio, 1.62; 95% confidence interval, 1.30–2.01; P < 0.0001; I2 = 0%); where reported separately, cardiac death was also significantly increase (odds ratio, 2.77; 95% confidence interval, 1.60–4.80; P = 0.0003;
I2 = 0%).
Conclusion The occurrence of periprocedural myocardial infarction after an elective percutaneous coronary intervention in patients with stable angina pectoris is associated with a statistically significant increase in subsequent all-cause mortality and cardiac mortality. Coron Artery Dis XXX: 000–000 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Coronary Artery Disease 2019, XXX:000–000
Keywords: cardiac biomarker, periprocedural myocardial infarction, stable angina pectoris
aRutgers New Jersey Medical School, Newark, New Jersey, bMayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA and cInterventional Cardiology, Cork University Hospital, Cork, Ireland Correspondence to Hector M. Garcia-Garcia, MD, PhD, Interventional Cardiology, MedStar Washington Hospital Center, 110 Irving St NW, Washington, DC 20010, USA
Tel: (202) 877 7754; fax (202) 877 2715;
e-mail: [email protected] Received 27 June 2019 Accepted 25 August 2019
INTRODUCTION
Percutaneous coronary intervention (PCI) is commonly performed in stable angina patients (SAP) for symptom relief. PCI is increasingly performed in high-risk patients with complex lesions. Innovations in stent technology have impacted procedural success [1]. Nevertheless, even in the era of new drug-eluting stents and antiplate- let pretreatment, elevated cardiac biomarkers occur in 20–40% of patients after nonemergent PCIs [2–5].
Despite the abundance of data that have evaluated the relationship of this cardiac biomarker elevation after PCI, uncertainty remains regarding the exact prognostic
impact of such elevation and its association with mortal- ity [2,6,7].
We sought, therefore, to evaluate the effect of periproce- dural biomarker elevation on mortality following PCI in patients with stable angina pectoris and normal pre- procedural cardiac enzymes in a systematic review and meta-analysis.
Methods
Inclusion criteria
Eligible studies would have fulfilled all of the follow- ing inclusion criteria: (1) randomized controlled trials or observational studies (cohort, cross-sectional, or case-con- trol studies) published as original articles or conference abstracts that evaluated and compared the effect of post-procedural cardiac biomarker elevation in patients
with SAP; (2) normal cardiac biomarkers level at base- line; (3) scheduled PCI for nonemergent procedure; (4) post-procedural enzymes level assessment; (5) a refer- ence group composed of patients who did not experience a significant post-procedural biomarker elevation; and (6) complete reporting of follow-up mortality rates. The outcomes of interest were all-cause mortality and cardiac death after PCI.
Search strategy
With the help of an experienced librarian (F.K.), the search was carried out in PubMed/Medline, and Embase databases until December 2018. The predefined search terms were as follows: ‘myocardial infarction’
or ‘periprocedural myocardial infarction’ and ‘percuta- neous coronary intervention’ or ‘troponin’ or ‘creatine kinase-MB.’ Further details regarding the search strategy and search terms used are detailed in the Supplementary Table 1, Supplemental digital content 1, http://links.lww.
com/MCA/A286.
In addition, conference abstracts and presentations were considered using the Google search engine to ensure fur- ther that pertinent articles were not missed. The refer- ence lists of included studies were screened as well for any eligible studies. This search was not limited by any language filters.
Data extraction and outcome measures
All included abstracts and full-text articles were assessed between three reviewers (M.S., G.H., and A.H.J), such that two people independently reviewed each submis- sion. Disagreements were resolved by consensus includ- ing the third reviewer.
In the case that the same study was reported in more than one article, only the most complete (i.e. in sample size and outcomes reported) version of that study was included.
For each included study, the following data variables were extracted: first author, article title, study design, year of publication, type of PCI that was performed, post-PCI assessment time, follow-up duration, cardiac enzymes tested, and the specific cutoff that was used in each study to define periprocedural myocardial infarction (PMI).
Reflecting the absence of a consensus definition of PMI, different cardiac markers and values were used by indi- vidual studies to define PMI. We accepted these individ- ual protocol definitions of PMI and did not attempt to retrospectively recategorize them.
In the included studies, the blood samples were taken before and within 24–48 hours after the procedure to assay cardiac enzymes with few exceptions. Additional determinations were performed if any patient developed post-procedural symptoms suggestive of myocardial ischemia. Details regarding the different cutoffs used to define PMI as well as the timing of post-PCI assessment are described in Table 1.
Dichotomous variables were reported as percentages, whereas continuous variables were reported as mean ± SD.
Quality of evidence and risk of bias assessment
The risk of bias in the included studies was assessed by two reviewers independently based on the modified Newcastle-Ottawa-scale (NOS) in this meta-analysis [20].
Modified NOS uses a rating system to determine the risk of bias in studies based on several domains, which include a selection of participants, comparability between groups, and assessment of exposure and outcome. Modified NOS is widely used and is recommended by the Cochrane col- laboration to assess the quality of nonrandomized studies especially in cohort and case-control studies.
We intended to assess publication bias using funnel plot technique, Begg’s rank test, and Egger’s regression
Table 1 The different cutoffs used to define periprocedural myocardial infarction along with the timing of post-percutaneous coronary intervention assessment of different cardiac biomarkers
Study Year Cardiac biomarker(s) PMI definition Post-PCI assessment time
Saadeddin et al.8 2002 cTnI CK-MB 2.0 μg/L 24 IU/L 24 h
Gravning et al.9 2008 cTnI > 2.5 × ULN 12–18 h
Gómez-Hospital et al.10 2009 cTnI 3 × ULN 12 and 24 h
Lindsey et al.6 2009 CK-MB 3 × ULN Every 8 h for a minimum of 2 samples
De Labriolle et al.11 2009 cTnI 3 × ULN 6–8 h and 12–24 h
Cavallini et al.12 2010 CK-MB cTnI 1 × URL 3 × URL 12–24 h
Mitsuba et al.13 2012 cTnT 3 × ULN After 24 h
Legrand et al.14 2014 cTn 3 × URL 8 and 24 h
Ndrepepa et al.23 2016 hs-cTnT 1 × URL 6, 12, and 24 h
Jang et al.15 2016 CK-MB 3 × ULN Every 8 h within 48 h
Zhang et al.16 2016 CK-MB 3 × ULN 12–24 h
Koskinas et al.17 2018 hs-cTnT 5 × ULN Within 6 h and daily collections until
48 h or discharge
Kang et al.18 2018 cTnI 5 × ULN Within 24 h
Zeitouni et al.19 2018 hs-cTnT 1–5 × ULN with evidence of ischemia
5 × ULN (isolated) Within 48 h
CK-MB, creatine kinase-MB; hs-cTn, high-sensitivity cardiac troponin; PCI, percutaneous coronary intervention; PMI, periprocedural myocardial infarction; ULN, upper limit normal; URL, upper reference limit.
test, as appropriate given the known limitations of these methods.
Statistical analysis
The meta-analysis was conducted in accordance with Reporting Items for Systematic Reviews and Meta- Analyses guidelines [21].
The findings were evaluated descriptively based on the information provided by each of the included studies.
Quantitative study results were expressed as odds ratios (OR) with 95% confidence interval (CI).
We assessed heterogeneity in the included body of evi- dence using χ2 tests (P > 0.1 showed no significant heter- ogeneity among studies) and I2 statistic (I2 > 25, > 50, and
> 75% showed low, moderate, and high heterogeneity, respectively). All values are 2-tailed, and P < 0.05 was set as the threshold for statistical significance.
The statistical package used was RevMan 5—Review Manager Version 5.3. Copenhagen: The Nordic Cochrane Center [22].
Results
Search results and patient characteristics
We identified 487 abstracts from our initial search, result- ing in 61 articles for full-text review to assess eligibility with Fourteen studies [6,8–19,23] met the full inclusion criteria (Fig. 1). Most of the studies were performed in Europe [9,10,12,14,17,19,23], while five were conducted in Asia [8,13,15,16,18], and two were performed in North America [6,11].
These comprised 24 666 patients who had undergone PCI and in whom cardiac enzymes were measured before and after the coronary intervention. The mean age was 64.2 years ± 9.8 with about 3-quarters (74.9%) of these patients being men. The mean duration of follow-up was 18.1 ± 14.3 months.
Although stent implantation was used in all included publi- cations, data regarding the type of stent (whether drug-elut- ing or bare-metal) was available for only nine studies. The complete patients’ baseline and procedural characteristics of all the studies are summarized in Tables 2 and 3.
Fig. 1
Flow diagram of the meta-analysis with the algorithm for the literature search results and inclusion into the study.
Table 2Clinical features in the overall population StudySaadeddin et al.8Gravning et al.9
Gómez- Hospital et al.10Lindsey et al.6De Labriolle et al.11Cavallini et al.12Mitsuba et al.13Legrand et al.14Ndrepepa et al.23Jang et al.15Zhang et al.16Koskinas et al.17Kang et al.18Zeitouni et al.19 Year20022008200920092009201020122014201620162016201820182018 RegionAsiaEuropeEuropeUnited StatesUnited StatesEuropeAsiaEuropeEuropeAsiaAsiaEuropeAsiaEurope DesignProspectiveRetrospectiveProspectiveProspectiveRetrospectiveProspectiveProspectiveProspectiveRetrospectiveRetrospectiveRetrospectiveRetrospectiveRetrospectiveProspective Sample size9619475759613200236246891346356062949231971387 Follow-up, month2412141212246115.54212125512 Age ± SD, year55 ± 1260.5 ± 7.563 ± 1064.7 ± 1164.5 ± 1162.5 ± 1564.9 ± 2.566.2 ± 10.868.6 ± 13.162.1 ± 9.864.7 ± 11.870.5 ± 1366.2 ± 9.666.9 ± 0.3 Male, %7573.274.967.56579.780.475.97683.382.976.459.479.2 HTN, %5225.855.679.883.9-82.664.87662.99175.662.462.3 HLD, %84.313.468.475.888.86171.772.68131.438.678.417.863.6 DM, %57.310.332.135.433.818.241.324.827.450.632.73033.535.7 LVEF, %--60-51.857.764.2-6056.25955.75855.7 BMI, kg/m2---29.9--23.828.5-26.8-27.224.526.7 Smoker, %39.6-59.622.754.8-73.922.714.931.442.115.724.424.1 Previous MI, %--29.23223.149.815.225.830.821.425.328.5-- Previous PCI, %--21.838.931.876.7-40.2-18.57.8--- Previous CABG, %
---2314.910.5-10.511.5-1.313.5-8.1 BMI, body mass index; CABG, coronary artery bypass grafting; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention.
Quality of evidence and risk of bias assessment
Eight items relevant to the evaluation of quality were applied to this meta-analysis (Supplementary Table 2, Supplemental digital content 1, http://links.lww.com/MCA/
A286).
We were unable to assess the publication bias as there were insufficient studies to properly assess a funnel plot or more advanced regression-based assessments.
Evidence synthesis of study outcomes
PMI, as defined in the reported studies, occurred in 14.3% of the total population. PMI conferred a statisti- cally significant increase in the risk of all-cause mortality (OR, 1.62; 95% CI, 1.30–2.01; P < 0.0001; I2 = 0%) (Fig. 2).
Only six studies reported cardiac death as a discrete out- come. In these studies, cardiac death was increased in
individuals with elevated post-procedural cardiac bio- markers (OR, 2.77; 95% CI, 1.60–4.80; P = 0.0003; I2 = 0%) (Fig. 3). There was no evidence of significant heter- ogeneity among the included studies.
Analysis of studies where both outcomes of interests (i.e.
all-cause mortality as well as cardiac death) were reported showed similar results with a significantly larger rise in cardiac death as compared to all-cause mortality [2.60 (1.24–5.41) and 2.02 (1.07–3.81), respectively] (Fig. 4).
Subgroup analysis
To determine whether the study outcomes changed with different cardiac biomarkers that had been used in the individual publications, we assessed subgroups of studies according to periprocedural cardiac enzymes utilized to define PMI.
Table 3 Lesion and procedural characteristics
Study Lesion number
Target vessel, %
Stent diameter, mm Stent length, mm
Stent/scaffold type, %
POBA, %
LM LAD LCX RCA DES BMS BVS
Saadeddin et al.8 - - 50 17.7 29.2 - - - - - 25.1
Gravning et al.9 - - 28.3 20.9 26.7 - - - - - -
Gómez-Hospital et al.10 - - - - - - 20.5 - 91.3 - 8.7
Lindsey et al.6 - 2.1 41.2 26.1 35.5 3.1 24.2 92.2 7.8 0 -
De Labriolle et al.11 5759 1.7 40.3 24.4 33.2 3.1 20.2 - - - -
Cavallini et al.12 - - - - - - - 76.7 - - -
Mitsuba et al.13 46 0 45.7 15.2 39.1 - 19.7 71.6 - - -
Legrand et al.14 - 2.1 39.5 24.7 31.7 - 29.6 - - - -
Ndrepepa et al.23 - 4 42.6 23.3 28.5 - 23.9 94.4 - - -
Jang et al.15 - 0 43.1 30.9 50.5 - - 100 0 0 0
Zhang et al.16 - - 53.1 10.8 36.4 - - 100 0 0 0
Koskinas et al.17 13415 3.5 42.1 23.5 28.4 - 26.3 92.2 2. 3.1 0
Kang et al.18 - - - - - 3.3 41 100 0 0 0
Zeitouni et al.19 - 4.7 - - - 2.9 28.8 80.6 10.8 - 3.5
BMS, bare metal stent; BVS, bioresorbable vascular scaffold; DES, drug-eluting stent; LAD, left anterior descending artery; LCX, left circumflex; LM, left main coronary artery; RCA, right coronary artery.
Fig. 2
Forest plot for all-cause mortality in individuals with elevated post-procedural cardiac biomarkers group compared to those with normal enzymes following percutaneous coronary intervention. Heterogeneity across trials was evaluated with I2 statistic. Because the heterogeneity was low, a fixed-effect model was used. CI, confidence interval; M-H, Mantel–Haenszel model.
In studies that have used cardiac troponin (cTn), PMI was associated with a statistically significant increase in all-cause mortality as well as cardiac death [OR, 1.49 (95% CI, 1.15–1.94; P = 0.003; I2 = 0%) and OR, 3.20 (95% CI, 1.64–6.25, P = 0.0007; I2 = 0%); respectively].
There were only three studies that evaluated the prog- nosis of periprocedural biomarker elevation have used creatine kinase-MB (CK-MB) [6,15,16]. In those studies, the occurrence PMI did confer a statistically significant increase in the risk of all-cause mortality but not in car- diac death (Figs. 5 and 6).
In the included studies, the shortest length of follow-up was 1 month, while the longest was 45.5 years. These var- iable lengths of follow-up could influence the accuracy for estimating the risk of mortality. To determine whether the overall results would change with different follow-up periods, we stratified studies to subgroups according to follow-up length. The results demonstrated a higher inci- dence of all-cause mortality in individuals with elevated post-PCI cardiac biomarkers regardless of the duration of follow-up. Cardiac death was significantly higher in those studies with a 1-year follow-up period (Supplementary
Fig. 4
Funnel plot for the studies where both outcomes of interests (i.e. all-cause mortality as well as cardiac death) were reported. CI, confidence inter- val; M-H, Mantel–Haenszel model; STIB, Stent Thrombosis In Belgium trial.
Fig. 3
Forest plot for cardiac death in individuals with elevated post-procedural cardiac biomarkers group compared to those with normal enzymes following percutaneous coronary intervention. Heterogeneity across trials was evaluated with I2 statistic. Because the heterogeneity was low, a fixed-effect model was used. CI, confidence interval; M-H, Mantel–Haenszel model.
Figure 1a–b, Supplemental digital content 1, http://links.
lww.com/MCA/A286). Additionally, excluding studies with a follow-up duration of fewer than 6 months (Legrand et al. [14]) did not change the overall results.
Discussion
We demonstrated in this analysis that, in SAP patients who underwent an elective coronary intervention, PMI was associated with nearly 60% higher all-cause mortality rate with even a drastically greater risk for cardiac death when compared to those with normal post-procedural cardiac enzymes.
In the first universal definition of myocardial infarction, the routine measurement of cardiac enzymes before and after PCI was strongly encouraged [24]. The bio- marker historically used for this purpose has been CK-MB initially as a measure of myocardial damage with early studies have shown a proportional relation- ship between the rise in CK-MB and 6-month all-cause mortality [25,26].
CK-MB has been largely replaced by highly sensitive cTn (T or I) as the biomarkers of choice due to both higher sensitivity and specificity for myocardial necrosis [27,28].
The prognostic implications of either of these biomark- ers’ elevation after PCI and the occurrence of PMI have been the subject of conflicting conclusions in the litera- ture. A major factor may relate to the multiplicity of defi- nitions that have been employed.
While early small studies with relatively short follow-up found no increased mortality risk [29], subsequent large prospective trials have suggested that there is a threshold elevation of specific myocardial necrosis markers after PCI that is clinically relevant [4,30,31].
However, many of these studies enrolled populations where several confounding factors may obscure the rela- tion between PMI and mortality. Many included patients with acute coronary syndrome or elevated baseline car- diac biomarkers and did not consider variables such as overall atherosclerosis burden, presence of diabetes, the success of stent implantation, ejection fraction, or adher- ence to evidence-based therapies such as dual antiplate- let therapy or statins that have been shown to affect prognosis.
Gravning et al. [9] suggested that post-PCI troponin elevation predicted 1-year adverse outcome in patients with acute coronary syndromes but not in those with stable CAD. Along the same line, Christensen et al. [32]
Fig. 5
Funnel plot for all-cause mortality incidence in individuals with elevated post-procedural cardiac biomarkers group compared to those with normal enzymes following percutaneous coronary intervention. Summary meta-estimates presented grouped by type of the cardiac biomarker used. All summary meta-estimate calculations based on random-effects model analysis. CI, confidence interval; CK.MB, creatine kinase-MB; cTn, cardiac troponin; M-H, Mantel–Haenszel model.
demonstrated the independent prognostic value for both cardiac biomarkers of any cutoff showed no statistical significance for all-cause mortality in patients with SAP, whereas the combined endpoint of all-cause mortality or new-onset heart failure were ambiguous in both the short- and long-term follow-ups.
In the light of these contradictory results, some authors have suggested that long-term prognosis after PCI might be related more to the preprocedural biomarkers val- ues rather than to any additional biomarker elevation following PCI [2,33–35]. Hence, differences in clinical presentation and baseline biomarkers levels are strong confounders that affect the association between PMI and clinical outcome.
In order to account for this observation, we aimed in our analysis to only include individuals with SAP patients and normal preprocedural cardiac enzymes and we excluded patients if the primary indication for PCI was the treat- ment of acute coronary syndrome or if baseline cardiac biomarkers levels were elevated.
Nonetheless, even in the cohort of patients with SAP with normal baseline cardiac biomarkers, some studies have suggested no significant relationship between PMI and long-term outcomes [11,36] whereas, others have reported a nonlinear relationship in which mortality was associated with the occurrence of a threshold biomarker elevation post-PCI [37,38].
Another factor that might explain the conflicting conclu- sions regarding the prognostic value of PMI was the use of different biomarkers in different studies. While only a few studies have used CK-MB compared to cTn, our subgroup analysis demonstrated a significant increase of all-cause mortality in those with post-PCI elevation of either of these enzymes. This observation was not seen in the risk of cardiac death in the studies that used CK-MB alone (Figs. 5 and 6).
With the arrival of the higher sensitivity troponin assays (hs-cTn), several studies have evaluated its prognos- tic role in predicting outcomes after PCI despite not yet being integrated into the most recent definitions of PMI [28]. In our study, we included three studies that have evaluated the relationship between hs-cTn and post-procedural death in SAP patients [17,19,23]. The subgroup analysis of these studies demonstrated that the PCI-related elevation of hs-cTn did not offer prognos- tic information concerning the all-cause mortality but was associated with significantly increased risk of cardiac death (Figs. 5 and 6).
Limitations
Our study has several evident limitations. First, inherent to all meta-analyses is the potential for heterogeneity among selected studies. However, heterogeneity testing did not indicate significant heterogeneity for the over- all odds ratios of death. Second, our analysis included
Fig. 6
Funnel plot for cardiac death in individuals with elevated post-procedural cardiac biomarkers compared to those with normal enzymes following percutaneous coronary intervention. Summary meta-estimates presented grouped by type of the cardiac biomarker used. All summary meta-es- timate calculations based on random-effects model analysis. CI, confidence interval; CK-MB, creatine kinase-MB; cTn, cardiac troponin; M-H, Mantel–Haenszel model.
studies with different threshold values to define PMI reflecting the ongoing divergence on the most appro- priate definition. However, we tried to take this param- eter into account by performing subgroup analyses. The results did not show any effect on mortality. Another lim- itation of the present meta-analysis is that the evaluation of the cardiac enzymes’ elevation was not performed at the same time across the included studies which might have different effects on PMI occurrence. Despite that, we included studies with variable follow-up durations;
a sensitivity analysis after excluding studies with a fol- low-up duration of fewer than 6 months did not change the overall results. Finally, we used the outcome events reported in the included studies to integrate the results of this study. Hence, we cannot assess whether differ- ent baseline characteristics that were not analyzed in this meta-analysis (such as older age, hypertension, dia- betes, or renal insufficiency, as well as medical pretreat- ment, stent length, stent type, or number of vessels with lesions) would have had different effects on the progno- sis of the included patients.
Conclusion
This meta-analysis, of all the published studies to date, demonstrated that the occurrence of PMI after elective coronary stenting is associated with a statistically and clinically significant increase in the subsequent risk of death in patients with SAP and normal baseline cardiac biomarkers.
Our results aim to inform the interventional community that PMI remains relatively common even in the contem- porary era and has prognostic value. We cannot, however, conclude whether PMI, as defined in the reported stud- ies, has a causal association with mortality. Similarly, it is not possible to conclude PMI is an indirect reflection of elevated baseline risk, comprising atherosclerosis burden, and other factors such as ejection fraction or subsequent adherence to dual antiplatelet therapy or other guideline supported recommendations. Further large randomized trials are needed to further define the relative contribu- tion of biomarker elevation in conjunction with clinical and other relevant variables to prognosis after PCI and to help develop new strategies to minimize the risk of death or other cardiac events following PCI.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
References
1 Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al.; Task Force Members; ESC Committee for Practice Guidelines;
Document Reviewers. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34:2949–3003.
2 Prasad A, Rihal CS, Lennon RJ, Singh M, Jaffe AS, Holmes DR Jr. Significance of periprocedural myonecrosis on outcomes after
percutaneous coronary intervention: an analysis of preintervention and postintervention troponin T levels in 5487 patients. Circ Cardiovasc Interv 2008; 1:10–19.
3 Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G.
Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (antiplatelet therapy for reduction of myocardial damage during angioplasty) study. Circulation 2005;
111:2099–2106.
4 Ellis SG, Chew D, Chan A, Whitlow PL, Schneider JP, Topol EJ. Death following creatine kinase-MB elevation after coronary intervention: iden- tification of an early risk period: importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy. Circulation 2002; 106:1205–1210.
5 Iantorno M, Lipinski MJ, Garcia-Garcia HM, Forrestal BJ, Rogers T, Gajanana D, et al. Meta-analysis of the impact of strut thickness on outcomes in patients with drug-eluting stents in a coronary artery. Am J Cardiol 2018; 122:1652–1660.
6 Lindsey JB, Marso SP, Pencina M, Stolker JM, Kennedy KF, Rihal C, et al.; EVENT Registry Investigators. Prognostic impact of periprocedural bleeding and myocardial infarction after percutaneous coronary intervention in unselected patients: results from the EVENT (evaluation of drug-elut- ing stents and ischemic events) registry. JACC Cardiovasc Interv 2009;
2:1074–1082.
7 Kini A, Marmur JD, Kini S, Dangas G, Cocke TP, Wallenstein S, et al.
Creatine kinase-MB elevation after coronary intervention correlates with diffuse atherosclerosis, and low-to-medium level elevation has a benign clinical course: implications for early discharge after coronary intervention. J Am Coll Cardiol 1999; 34:663–671.
8 Saadeddin SM, Habbab MA, Sobki SH, Ferns GA. Biochemical detection of minor myocardial injury after elective, uncomplicated, successful percuta- neous coronary intervention in patients with stable angina: clinical outcome.
Ann Clin Biochem 2002; 39:392–397.
9 Gravning J, Ueland T, Mørkrid L, Endresen K, Aaberge L, Kjekshus J.
Different prognostic importance of elevated troponin I after percutaneous coronary intervention in acute coronary syndrome and stable angina pecto- ris. Scand Cardiovasc J 2008; 42:214–221.
10 Gómez-Hospital JA, Cequier A, Valero J, González-Costello J, Mañas P, Iràculis E, et al. Minor myocardial damage during percutaneous coronary intervention does not affect long-term prognosis. Rev Esp Cardiol 2009;
62:625–632.
11 De Labriolle A, Lemesle G, Bonello L, Syed AI, Collins SD, Ben-Dor I, et al.
Prognostic significance of small troponin I rise after a successful elective percutaneous coronary intervention of a native artery. Am J Cardiol 2009;
103:639–645.
12 Cavallini C, Verdecchia P, Savonitto S, Arraiz G, Violini R, Olivari Z, et al.;
Italian Atherosclerosis, Thrombosis and Vascular Biology and Society for Invasive Cardiology–GISE Investigators. Prognostic value of isolated tro- ponin I elevation after percutaneous coronary intervention. Circ Cardiovasc Interv 2010; 3:431–435.
13 Mitsuba N, Teragawa H, Hata T, Nishioka K, Fujii Y, Mikami S, et al. Deep echo attenuation without calcification increases the risk of periprocedural myonecrosis after elective percutaneous coronary intervention in patients with coronary artery disease. Intern Med 2012; 51:691–698.
14 Legrand V, Cuisset T, Chenu P, Vrolix M, Martinez C, Dens J, et al. Platelet reactivity and cardiovascular events after percutaneous coronary interven- tion in patients with stable coronary artery disease: the stent thrombosis in belgium (STIB) trial. Eurointervention 2014; 10:204–211.
15 Jang WJ, Yang JH, Choi SH, Song YB, Hahn JY, Kim WS, et al. Association of periprocedural myocardial infarction with long-term survival in patients treated with coronary revascularization therapy of chronic total occlusion.
Catheter Cardiovasc Interv 2016; 87:1042–1049.
16 Zhang Q, Hu J, Yang ZK, Ding FH, Zhang JS, Du R, et al. Correlates and outcomes related to periprocedural myocardial injury during percutaneous coronary intervention for chronic total occlusion: results from a prospective, single center PCI registry. Catheter Cardiovasc Interv 2016; 87 (suppl 1):616–623.
17 Koskinas KC, Ndrepepa G, Räber L, Karagiannis A, Kufner S, Zanchin T, et al. Prognostic impact of periprocedural myocardial infarction in patients undergoing elective percutaneous coronary interventions. Circ Cardiovasc Interv 2018; 11:e006752.
18 Kang MG, Kang Y, Jang HG, Kim K, Koh JS, Park JR, et al. Coronary artery calcium score in predicting periprocedural myocardial infarction in patients undergoing an elective percutaneous coronary intervention. Coron Artery Dis 2018; 29:589–596.
19 Zeitouni M, Silvain J, Guedeney P, Kerneis M, Yan Y, Overtchouk P, et al.;
ACTION Study Group. Periprocedural myocardial infarction and injury in elective coronary stenting. Eur Heart J 2018; 39:1100–1109.
20 Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P.
The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonran- domised studies in meta-analyses 2014. Available from: http://www.ohri.ca/
programs/clinical_epidemiology/oxford.asp.
21 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-anal- yses of studies that evaluate health care interventions: explanation and elaboration. Plos Med 2009; 6:e1000100.
22 Review Manager (RevMan) [Computer program].Version 5.3. Copenhagen:
The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
23 Ndrepepa G, Braun S, Cassese S, Mayer K, Lohaus R, Lahmann AL, et al. Prognostic value of high-sensitivity troponin T after percutaneous cor- onary intervention in patients with stable coronary artery disease. Revista espanola de cardiologia (English ed) 2016; 69:746–753.
24 Antman E, Bassand JP, Klein W, Ohman M, Lopez Sendon JL, Rydén L, 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: The Joint European Society of Cardiology/ American College of Cardiology Committee**A list of contrib- utors to this ESC/ACC Consensus Document is provided in Appendix B. J Am Coll Cardiol 2000; 36:959–969.
25 Akkerhuis KM, Alexander JH, Tardiff BE, Boersma E, Harrington RA, Lincoff AM, Simoons ML. Minor myocardial damage and prognosis: are sponta- neous and percutaneous coronary intervention-related events different?
Circulation 2002; 105:554–556.
26 Tardiff BE, Califf RM, Tcheng JE, Lincoff AM, Sigmon KN, Harrington RA, et al. Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. IMPACT-II investigators. Integrilin (eptifibatide) to minimize platelet aggregation and coronary thrombosis-II. J Am Coll Cardiol 1999; 33:88–96.
27 Moussa ID, Klein LW, Shah B, Mehran R, Mack MJ, Brilakis ES, et al.
Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the society for cardiovascular angiography and interventions (SCAI). J Am Coll Cardiol 2013; 62:1563–1570.
28 Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018; 72:2231–2264.
29 Oh JK, Shub C, Ilstrup DM, Reeder GS. Creatine kinase release after suc- cessful percutaneous transluminal coronary angioplasty. Am Heart J 1985;
109:1225–1231.
30 Harrington RA, Lincoff AM, Califf RM, Holmes DR Jr, Berdan LG, O’Hanesian MA, et al. Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the coro- nary angioplasty versus excisional atherectomy trial (CAVEAT). J Am Coll Cardiol 1995; 25:1693–1699.
31 Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG. Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions. Circulation 1996; 94:1528–1536.
32 Christensen MK, Huang H, Torp-Pedersen C, Trydal T, Ravkilde J.
Incidence and impact on prognosis of peri-procedural myocardial infarction in 2760 elective patients with stable angina pectoris in a historical prospective follow-up study. BMC Cardiovasc Disord 2016;
16:140.
33 Miller WL, Garratt KN, Burritt MF, Lennon RJ, Reeder GS, Jaffe AS.
Baseline troponin level: key to understanding the importance of post-PCI troponin elevations. Eur Heart J 2006; 27:1061–1069.
34 Jeremias A, Kleiman NS, Nassif D, Hsieh WH, Pencina M, Maresh K, et al.;
Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) Registry Investigators. Prevalence and prognostic significance of preprocedural car- diac troponin elevation among patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the evaluation of drug eluting stents and ischemic events registry. Circulation 2008;
118:632–638.
35 Zanchin T, Raber L, Koskinas KC, Piccolo R, Juni P, Pilgrim T, et al.
Preprocedural high-sensitivity cardiac troponin T and clinical outcomes in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention. Circ Cardiovasc Interv 2016;
9:e003202.
36 Ndrepepa G, Colleran R, Braun S, Cassese S, Hieber J, Fusaro M, et al.
High-sensitivity troponin T and mortality after elective percutaneous coro- nary intervention. J Am Coll Cardiol 2016; 68:2259–2268.
37 Olivier CB, Sundaram V, Bhatt DL, Leonardi S, Lopes RD, Ding VY, et al.; CHAMPION PLATFORM and CHAMPION PCI Investigators.
Definitions of peri-procedural myocardial infarction and the association with one-year mortality: insights from CHAMPION trials. Int J Cardiol 2018;
270:96–101.
38 Lindsey JB, Kennedy KF, Stolker JM, Gilchrist IC, Mukherjee D, Marso SP, et al. Prognostic implications of creatine kinase-MB elevation after percu- taneous coronary intervention: results from the evaluation of drug-eluting stents and ischemic events (EVENT) registry. Circ Cardiovasc Interv 2011;
4:474–480.
