International Journal of Cardiology 178 (2015) 181–183
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
The cardioprotection of ischemic postconditioning in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention Bao-Shan Liu a,b,c,d,1, Feng Xu a,b,c,d,1, Jia-Li Wang a,b,c,d, Cheng Zhang a, Yun Zhang a, Pan-Pan Hao a,⁎, Yu-Guo Chen a,b,c,d,⁎ a
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China c Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China d Department of Emergency, Qilu Hospital, Shandong University, Jinan, China b
a r t i c l e
i n f o
Article history: Received 18 October 2014 Accepted 21 October 2014 Available online 24 October 2014 Keywords: Ischemic postconditioning Myocardial infarction Percutaneous coronary intervention Meta-analysis
Ischemic postconditioning (IPoC) was defined as inflation and deflation of the angioplasty balloon after reopening of the criminal coronary artery in patients with acute ST-segment elevation myocardial infarction (STEMI) [1]. Some studies reported IPoC exerted cardioprotection [2,3]. But others observed negative results [4–7]. A previous metaanalysis demonstrated a significant benefit of IPoC over standard care for the reduction of myocardial infarct size as determined by peak creatine kinase (CK) release and left ventricular ejection fraction (LVEF), however, the effects of IPoC on clinical outcomes remain to be determined [8]. Hence, we performed an updated meta-analysis to ascertain whether IPoC reduced adverse clinical endpoints and improved cardiac function in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). We searched relevant reports through PubMed, EMBASE, the China National Knowledge Internet, and the grey literature databases. Our search was not restricted to articles in English. Literatures were searched
⁎ Corresponding authors at: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, 250012 Jinan, China. E-mail addresses: [email protected] (P.-P. Hao), [email protected] (Y.-G. Chen). 1 The first two authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ijcard.2014.10.097 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
in PubMed with the terms (“ischemic postconditioning” (MeSH Terms) OR (“ischemic” (All Fields) AND “postconditioning” (All Fields)) OR “ischemic postconditioning” (All Fields)) AND (“percutaneous coronary intervention” (MeSH Terms) OR (“percutaneous” (All Fields) AND “coronary” (All Fields) AND “intervention” (All Fields)) OR “percutaneous coronary intervention” (All Fields)) with no restriction on subheadings. Similar and adapted search terms were used for the other literature databases or search engines. The reference lists of all retrieved literatures were checked for other potentially relevant citations, and studies not included in the above electronic sources were searched manually. Studies were included if they (i) covered ischemic postconditioning in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI); (ii) were prospective randomized controlled trials (RCTs) or observational studies; and (iii) contained sufficient information for the observed outcomes for estimating the pooled weighted mean difference (WMD) or the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI). Studies were excluded if two articles reported results of the same study (the article with more complete and recent data was included). The methodological quality of enrolled studies was assessed with criteria adapted from guidelines for the evaluation of articles on prognosis [9]. RevMan 5.2.11 software (developed by the Cochrane Collaboration) was used for meta-analysis. Fig. 1 summarizes the selection of reports of eligible clinical trials. We identified 808 potentially eligible literature citations, all of which were reviewed as full articles. A total of 22 full articles were enrolled in the meta-analysis, and the interobserver agreement for the study selection was excellent (κ = 0.95). The detailed characteristics of the 22 studies are given in Supplementary Table 1. The sample sizes ranged from 17 to 700 participants. These trials included an aggregate of 2313 patients: 1705 Caucasian and 608 Chinese. The mean ages ranged from 56 to 69.17 years and the percentage of males is 78.08%. The methodological quality of the included studies was in general good, with 17 of 22 reports describing 3 or more of the 4 quality criteria (Supplementary Table 2). Reports for all studies clearly defined the inception cohort, and loss to follow-up was reported as N 10% in only two reports, although in 12 reports it was unclear whether patient enrollment was selective, and for only 11 studies was outcome assessment blinded.
182
B.-S. Liu et al. / International Journal of Cardiology 178 (2015) 181–183
Fig. 1. Flowchart of literature selection process.
We found IPoC significantly reduced the incidence of heart failure (4.20% vs. 8.28%) with an OR of 0.47 (95% CI, 0.29–0.78; P = 0.003; Table 1). We found IPoC had a better performance in lowering the incidence of serious arrhythmia compared with the control group (7.14% vs. 15.93%) with an OR of 0.34 (95% CI, 0.13–0.90; P = 0.03; Table 1). But our analyses showed that IPoC didn't reduce the incidence of major adverse cardiovascular events (MACE) (8.60% vs. 8.99%; OR, 0.96; 95% CI, 0.64–1.44; P = 0.85), death (3.80% vs. 2.82%; OR, 1.36; 95% CI, 0.79–2.36; P = 0.27), stent thrombosis (1.80% vs. 1.79%; OR, 1.01; 95% CI, 0.40–2.56; P = 0.99) or reinfarction (1.65% vs. 0.82%; OR, 3.11; 95% CI, 0.62–15.63; P = 0.17) (Table 1). IPoC significantly improved wall motion score index (WMSI) with a WMD of −0.12 (95% CI, −0.16-0.08; P = b 0.00001). But IPoC didn't reduce area at risk (WMD, 0.38; 95% CI, − 2.54–3.30; P = 0.80) or improve myocardial blush grades (MBG) (WMD, 1.18; 95% CI, 0.92–1.52; P = 0.20; Table 1). The between-study heterogeneity was explained in part by ethnicity, postconditioning protocols, follow-up duration, and multicenter
design (Supplementary Table 3). IPoC improved LVEF in 3 months but not in 6 or 12 months, in Asians but not in Caucasians, and in 90s or 120 s protocol but not in 180 s or 240 s protocol. IPoC reduced CK-MB peak in Caucasians but not in Asians, in multicenter studies but not in monocenter studies, and in 180 s or 240 s protocol but not in 90s or 120 s protocol. IPoC reduced CK peak in Asians rather than Caucasians, and in 90s or 120 s protocol rather than 180 s or 240 s protocol. IPoC improved corrected TIMI frame count (CTFC) in Asians but not in Caucasians, and in 90s or 120 s protocol but not in 180 s or 240 s protocol. We calculated the fail-safe number (Nfs) for each comparison as Nfs = (εZ/1.64)2 − κ, where κ was the number of reports of studies included in the meta-analysis. Any calculated Nfs value smaller than the number of retrieved reports of studies indicated publication bias. The Nfs values for CK peak, CK-MB peak, troponin I (TnI) peak, LVEF, infarct size, acute coronary syndromes (ACS), heart failure, CTFC, WMSI, complete ST segment resolution, MBG, myocardial savage index (MSI) and MACE were greater than the number of studies included in the metaanalysis. However, the Nfs value for area at risk, death, stent thrombosis,
Table 1 The effect of IPoC on clinical outcomes in patients with STEMI undergoing PPCI. Outcomes after PPCI
sample size (IPoC/control)
Heterogeneity
WMD or OR
95% CI
P value
Heart failure Serious arrhythmia LVEF(N = 3 months) WMSI Death Stent thrombosis Reinfarction ACS MACE LVEF in acute phase CTFC CK peak CK-MB peak TnI peak Infarct size Area at risk Complete ST segment resolution MBG MSI
753/752 112/113 307/316 206/219 818/815 444/446 405/406 486/486 605/612 670/713 164/216 293/341 566/619 96/100 172/171 101/100 664/716 725/725 107/113
0 0 70% 14% 0 0 0 58% 26% 77% 58% 93% 95% 99% 84% 0 76% 25% 81%
0.47 0.34 0.03 −0.12 1.36 1.01 3.11 0.53 0.96 0.02 −3.96 −255.66 −21.29 56.81 −0.70 0.38 1.58 1.18 −3.83
0.29 to 0.78 0.13 to 0.90 0.01 to 0.05 −0.16 to −0.08 0.79 to 2.36 0.40 to 2.56 0.62 to 15.63 0.06 to 4.72 0.64 to 1.44 −0.01 to 0.04 −6.85 to −1.06 −745.22 to 231.89 −65.55 to 22.98 −48.24 to 161.85 −6.23 to 4.83 −2.54 to 3.30 0.78 to 3.17 0.92 to 1.52 −20.12 to 12.48
0.003 0.03 0.004 b0.00001 0.27 0.99 0.17 0.57 0.85 0.19 0.007 0.30 0.35 0.29 0.80 0.80 0.20 0.20 0.65
LVEF, left ventricular ejection fraction; WMSI, wall motion score index; MACE, major adverse cardiovascular events; CTFC, corrected TIMI frame count; CK, creatine kinase; CK-MB, creatine kinase-MB; TnI, Troponin I; MBG, myocardial blush grades; MSI, myocardial savage index. WMD, weighted mean difference; OR, odd ratio.
B.-S. Liu et al. / International Journal of Cardiology 178 (2015) 181–183
reinfarction and serious arrhythmia was smaller than the number of retrieved studies, which were possibly consistent with small-studyrelated bias. Our results indicated that IPoC might improve cardiac function and reduce the incidence of heart failure and serious arrhythmia in patients with STEMI undergoing PPCI. More high-quality multicenter RCTs focusing on MACE are warranted. Acknowledgment The study was supported by the National Natural Science Foundation of China (81400284, 81170136, 81100147, 81300103, 81300219, 81400284), the Specialized Research Fund for the Doctoral Program of Higher Education (20130131110048), and the Grant from the Department of Science and Technology of Shandong Province (2011GSF11806). Appendix A. Supplementary data Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2014.10.097.
183
References [1] F.J. Bernink, L. Timmers, A.M. Beek, et al., Progression in attenuating myocardial reperfusion injury: an overview, Int. J. Cardiol. 170 (2014) 261–269. [2] H. Thibault, C. Piot, P. Staat, et al., Long-term benefit of postconditioning, Circulation 117 (2008) 1037–1044. [3] P. Staat, G. Rioufol, C. Piot, et al., Postconditioning the human heart, Circulation 112 (2005) 2143–2148. [4] V. Bodi, J.M. Ruiz-Nodar, E. Feliu, et al., Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine, Int. J. Cardiol. 175 (2014) 138–146. [5] J. Lønborg, L. Holmvang, H. Kelbæk, et al., ST-Segment resolution and clinical outcome with ischemic postconditioning and comparison to magnetic resonance, Am. Heart J. 160 (2010) 1085–1091. [6] G. Tarantini, E. Favaretto, M.P. Marra, et al., Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial, Int. J. Cardiol. 162 (2012) 33–38. [7] J.Y. Hahn, Y.B. Song, E.K. Kim, et al., Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction (POST) randomized trial, Circulation 128 (2013) 1889–1896. [8] P.R. Hansen, H. Thibault, J. Abdulla, Postconditioning during primary percutaneous coronary intervention: a review and meta-analysis, Int. J. Cardiol. 144 (2010) 22–25. [9] S. McRae, H. Tran, S. Schulman, et al., Effect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis, Lancet 368 (2006) 371–378.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
The cardioprotection of ischemic postconditioning in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention Bao-Shan Liu a,b,c,d,1, Feng Xu a,b,c,d,1, Jia-Li Wang a,b,c,d, Cheng Zhang a, Yun Zhang a, Pan-Pan Hao a,⁎, Yu-Guo Chen a,b,c,d,⁎ a
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China c Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China d Department of Emergency, Qilu Hospital, Shandong University, Jinan, China b
a r t i c l e
i n f o
Article history: Received 18 October 2014 Accepted 21 October 2014 Available online 24 October 2014 Keywords: Ischemic postconditioning Myocardial infarction Percutaneous coronary intervention Meta-analysis
Ischemic postconditioning (IPoC) was defined as inflation and deflation of the angioplasty balloon after reopening of the criminal coronary artery in patients with acute ST-segment elevation myocardial infarction (STEMI) [1]. Some studies reported IPoC exerted cardioprotection [2,3]. But others observed negative results [4–7]. A previous metaanalysis demonstrated a significant benefit of IPoC over standard care for the reduction of myocardial infarct size as determined by peak creatine kinase (CK) release and left ventricular ejection fraction (LVEF), however, the effects of IPoC on clinical outcomes remain to be determined [8]. Hence, we performed an updated meta-analysis to ascertain whether IPoC reduced adverse clinical endpoints and improved cardiac function in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). We searched relevant reports through PubMed, EMBASE, the China National Knowledge Internet, and the grey literature databases. Our search was not restricted to articles in English. Literatures were searched
⁎ Corresponding authors at: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, 250012 Jinan, China. E-mail addresses: [email protected] (P.-P. Hao), [email protected] (Y.-G. Chen). 1 The first two authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ijcard.2014.10.097 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
in PubMed with the terms (“ischemic postconditioning” (MeSH Terms) OR (“ischemic” (All Fields) AND “postconditioning” (All Fields)) OR “ischemic postconditioning” (All Fields)) AND (“percutaneous coronary intervention” (MeSH Terms) OR (“percutaneous” (All Fields) AND “coronary” (All Fields) AND “intervention” (All Fields)) OR “percutaneous coronary intervention” (All Fields)) with no restriction on subheadings. Similar and adapted search terms were used for the other literature databases or search engines. The reference lists of all retrieved literatures were checked for other potentially relevant citations, and studies not included in the above electronic sources were searched manually. Studies were included if they (i) covered ischemic postconditioning in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI); (ii) were prospective randomized controlled trials (RCTs) or observational studies; and (iii) contained sufficient information for the observed outcomes for estimating the pooled weighted mean difference (WMD) or the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI). Studies were excluded if two articles reported results of the same study (the article with more complete and recent data was included). The methodological quality of enrolled studies was assessed with criteria adapted from guidelines for the evaluation of articles on prognosis [9]. RevMan 5.2.11 software (developed by the Cochrane Collaboration) was used for meta-analysis. Fig. 1 summarizes the selection of reports of eligible clinical trials. We identified 808 potentially eligible literature citations, all of which were reviewed as full articles. A total of 22 full articles were enrolled in the meta-analysis, and the interobserver agreement for the study selection was excellent (κ = 0.95). The detailed characteristics of the 22 studies are given in Supplementary Table 1. The sample sizes ranged from 17 to 700 participants. These trials included an aggregate of 2313 patients: 1705 Caucasian and 608 Chinese. The mean ages ranged from 56 to 69.17 years and the percentage of males is 78.08%. The methodological quality of the included studies was in general good, with 17 of 22 reports describing 3 or more of the 4 quality criteria (Supplementary Table 2). Reports for all studies clearly defined the inception cohort, and loss to follow-up was reported as N 10% in only two reports, although in 12 reports it was unclear whether patient enrollment was selective, and for only 11 studies was outcome assessment blinded.
182
B.-S. Liu et al. / International Journal of Cardiology 178 (2015) 181–183
Fig. 1. Flowchart of literature selection process.
We found IPoC significantly reduced the incidence of heart failure (4.20% vs. 8.28%) with an OR of 0.47 (95% CI, 0.29–0.78; P = 0.003; Table 1). We found IPoC had a better performance in lowering the incidence of serious arrhythmia compared with the control group (7.14% vs. 15.93%) with an OR of 0.34 (95% CI, 0.13–0.90; P = 0.03; Table 1). But our analyses showed that IPoC didn't reduce the incidence of major adverse cardiovascular events (MACE) (8.60% vs. 8.99%; OR, 0.96; 95% CI, 0.64–1.44; P = 0.85), death (3.80% vs. 2.82%; OR, 1.36; 95% CI, 0.79–2.36; P = 0.27), stent thrombosis (1.80% vs. 1.79%; OR, 1.01; 95% CI, 0.40–2.56; P = 0.99) or reinfarction (1.65% vs. 0.82%; OR, 3.11; 95% CI, 0.62–15.63; P = 0.17) (Table 1). IPoC significantly improved wall motion score index (WMSI) with a WMD of −0.12 (95% CI, −0.16-0.08; P = b 0.00001). But IPoC didn't reduce area at risk (WMD, 0.38; 95% CI, − 2.54–3.30; P = 0.80) or improve myocardial blush grades (MBG) (WMD, 1.18; 95% CI, 0.92–1.52; P = 0.20; Table 1). The between-study heterogeneity was explained in part by ethnicity, postconditioning protocols, follow-up duration, and multicenter
design (Supplementary Table 3). IPoC improved LVEF in 3 months but not in 6 or 12 months, in Asians but not in Caucasians, and in 90s or 120 s protocol but not in 180 s or 240 s protocol. IPoC reduced CK-MB peak in Caucasians but not in Asians, in multicenter studies but not in monocenter studies, and in 180 s or 240 s protocol but not in 90s or 120 s protocol. IPoC reduced CK peak in Asians rather than Caucasians, and in 90s or 120 s protocol rather than 180 s or 240 s protocol. IPoC improved corrected TIMI frame count (CTFC) in Asians but not in Caucasians, and in 90s or 120 s protocol but not in 180 s or 240 s protocol. We calculated the fail-safe number (Nfs) for each comparison as Nfs = (εZ/1.64)2 − κ, where κ was the number of reports of studies included in the meta-analysis. Any calculated Nfs value smaller than the number of retrieved reports of studies indicated publication bias. The Nfs values for CK peak, CK-MB peak, troponin I (TnI) peak, LVEF, infarct size, acute coronary syndromes (ACS), heart failure, CTFC, WMSI, complete ST segment resolution, MBG, myocardial savage index (MSI) and MACE were greater than the number of studies included in the metaanalysis. However, the Nfs value for area at risk, death, stent thrombosis,
Table 1 The effect of IPoC on clinical outcomes in patients with STEMI undergoing PPCI. Outcomes after PPCI
sample size (IPoC/control)
Heterogeneity
WMD or OR
95% CI
P value
Heart failure Serious arrhythmia LVEF(N = 3 months) WMSI Death Stent thrombosis Reinfarction ACS MACE LVEF in acute phase CTFC CK peak CK-MB peak TnI peak Infarct size Area at risk Complete ST segment resolution MBG MSI
753/752 112/113 307/316 206/219 818/815 444/446 405/406 486/486 605/612 670/713 164/216 293/341 566/619 96/100 172/171 101/100 664/716 725/725 107/113
0 0 70% 14% 0 0 0 58% 26% 77% 58% 93% 95% 99% 84% 0 76% 25% 81%
0.47 0.34 0.03 −0.12 1.36 1.01 3.11 0.53 0.96 0.02 −3.96 −255.66 −21.29 56.81 −0.70 0.38 1.58 1.18 −3.83
0.29 to 0.78 0.13 to 0.90 0.01 to 0.05 −0.16 to −0.08 0.79 to 2.36 0.40 to 2.56 0.62 to 15.63 0.06 to 4.72 0.64 to 1.44 −0.01 to 0.04 −6.85 to −1.06 −745.22 to 231.89 −65.55 to 22.98 −48.24 to 161.85 −6.23 to 4.83 −2.54 to 3.30 0.78 to 3.17 0.92 to 1.52 −20.12 to 12.48
0.003 0.03 0.004 b0.00001 0.27 0.99 0.17 0.57 0.85 0.19 0.007 0.30 0.35 0.29 0.80 0.80 0.20 0.20 0.65
LVEF, left ventricular ejection fraction; WMSI, wall motion score index; MACE, major adverse cardiovascular events; CTFC, corrected TIMI frame count; CK, creatine kinase; CK-MB, creatine kinase-MB; TnI, Troponin I; MBG, myocardial blush grades; MSI, myocardial savage index. WMD, weighted mean difference; OR, odd ratio.
B.-S. Liu et al. / International Journal of Cardiology 178 (2015) 181–183
reinfarction and serious arrhythmia was smaller than the number of retrieved studies, which were possibly consistent with small-studyrelated bias. Our results indicated that IPoC might improve cardiac function and reduce the incidence of heart failure and serious arrhythmia in patients with STEMI undergoing PPCI. More high-quality multicenter RCTs focusing on MACE are warranted. Acknowledgment The study was supported by the National Natural Science Foundation of China (81400284, 81170136, 81100147, 81300103, 81300219, 81400284), the Specialized Research Fund for the Doctoral Program of Higher Education (20130131110048), and the Grant from the Department of Science and Technology of Shandong Province (2011GSF11806). Appendix A. Supplementary data Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2014.10.097.
183
References [1] F.J. Bernink, L. Timmers, A.M. Beek, et al., Progression in attenuating myocardial reperfusion injury: an overview, Int. J. Cardiol. 170 (2014) 261–269. [2] H. Thibault, C. Piot, P. Staat, et al., Long-term benefit of postconditioning, Circulation 117 (2008) 1037–1044. [3] P. Staat, G. Rioufol, C. Piot, et al., Postconditioning the human heart, Circulation 112 (2005) 2143–2148. [4] V. Bodi, J.M. Ruiz-Nodar, E. Feliu, et al., Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine, Int. J. Cardiol. 175 (2014) 138–146. [5] J. Lønborg, L. Holmvang, H. Kelbæk, et al., ST-Segment resolution and clinical outcome with ischemic postconditioning and comparison to magnetic resonance, Am. Heart J. 160 (2010) 1085–1091. [6] G. Tarantini, E. Favaretto, M.P. Marra, et al., Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial, Int. J. Cardiol. 162 (2012) 33–38. [7] J.Y. Hahn, Y.B. Song, E.K. Kim, et al., Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction (POST) randomized trial, Circulation 128 (2013) 1889–1896. [8] P.R. Hansen, H. Thibault, J. Abdulla, Postconditioning during primary percutaneous coronary intervention: a review and meta-analysis, Int. J. Cardiol. 144 (2010) 22–25. [9] S. McRae, H. Tran, S. Schulman, et al., Effect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis, Lancet 368 (2006) 371–378.
