Staged Revascularization for Chronic Total Occlusion in the Non-IRA in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: An Updated Systematic Review and Meta-analysis

Abstract

Objectives: Meta-analysis was performed to evaluate the effect of staged revascularization with concomitant chronic total occlusion (CTO) in the non-infarct-associated artery (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (p-PCI).

Methods: Various electronic databases were searched for studies published from inception to June, 2021. The primary endpoint was all-cause death, and the secondary endpoint was a composite of major adverse cardiac events (MACEs). Odds ratios (ORs) were pooled with 95% confidence intervals (CIs) for dichotomous data.

Results: Seven studies involving 1540 participants were included in the final analysis. Pooled analyses revealed that patients with successful staged revascularization for CTO in non-IRA with STEMI treated with p-PCI had overall lower all-cause death compared with the occluded CTO group (OR, 0.46; 95% CI, 0.23–0.95), cardiac death (OR, 0.43; 95% CI, 0.20–0.91), MACEs (OR, 0.47; 95% CI, 0.32–0.69) and heart failure (OR, 0.57; 95% CI, 0.37–0.89) compared with the occluded CTO group. No significant differences were observed between groups regarding myocardial infarction and repeated revascularization.

Conclusions: Successful revascularization of CTO in the non-IRA was associated with better outcomes in patients with STEMI treated with p-PCI.

Main article text

Significance Statement

This analysis of 1540 participants from seven studies is the most recent and largest meta-analysis assessing the efficacy of successful revascularization for CTO in the non-IRA in patients with STEMI. Successful revascularization for CTO in the non-IRA in patients with STEMI treated with p-PCI was associated with a lower composite endpoint of MACEs. These findings might aid in clinical decision-making regarding interventional therapy for CTO in the non-IRA in patients with STEMI.

Introduction

Acute ST-segment elevation myocardial infarction (STEMI) typically arises from sudden thrombotic occlusion of a coronary artery; this serious disease poses a direct threat to human health [1]. Mechanical reperfusion by primary percutaneous coronary intervention (p-PCI) with stent implantation is currently the preferred treatment for patients with STEMI, according to the definitive guidelines [2]. Angiography imaging has indicated that multi-vessel disease (MVD) is present in approximately 40–60% of patients with STEMI and is associated with greater short- and long-term mortality [3–6]. Moreover, concurrent chronic total occlusion (CTO) in the non-infarct-associated artery (non-IRA) is present in 10–12% of patients with STEMI and is associated with higher mortality after reperfusion therapy [7–10].

Although evidence indicates that multivessel revascularization in patients with STEMI and revascularization of CTO lesions might be beneficial, whether long-term survival benefits are conferred by staged revascularization for CTO in the non-IRA, particularly in patients with STEMI undergoing p-PCI, remains unclear [11–13]. The relevant small sample retrospective studies and a recent meta-analysis have demonstrated that successful CTO revascularization in the non-IRA is associated with better clinical outcomes [14–19]. However, a randomized prospective trial has indicated that successful revascularization of CTO in the non-IRA is not associated with a decrease in long-term MACEs [20].

Because long-term follow-up data from previous prospective studies and other relevant studies have been published [21, 22], we performed a meta-analysis update to investigate the prognostic effects of staged revascularization for CTO in the non-IRA in patients with STEMI treated with p-PCI.

Methods

This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were identified through electronic searches of the PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) databases with the following search items: “chronic total occlusion,” “multivessel,” “non-culprit,” “staged,” “acute myocardial infarction,” “acute coronary syndromes” and “percutaneous coronary intervention.” Two reviewers independently performed the literature search, and any differences were resolved by discussion.

Studies were included if the following criteria were satisfied: (1) randomized controlled trials (RCTs) or cohort studies on patients who presented with acute STEMI and were found to have concurrent CTO in a non-IRA during the primary PCI for STEMI; (2) comparison between patients with successful PCI in the non-IRA with CTO (CTO-PCI) and patients with failed or non-attempted revascularization of CTO in the non-IRA (occluded CTO); (3) full-text articles or meeting abstracts reporting all-cause death, myocardial infarction, repeated revascularization or MACEs.

The exclusion criteria were as follows: (1) studies in patients with NSTEMI, unstable angina or chronic ischemic heart disease, and (2) reports or ongoing studies lacking reporting of outcomes after more than 3 months.

Data were extracted by one investigator (Yu Geng) and independently verified by another investigator (Yintang Wang). Any disagreements between investigators were resolved through discussion with a third investigator (Ping Zhang) and by referencing the original report. Data quality was assessed with the Cochrane risk of bias tools in Review Manager 5.2.

The primary endpoint was all-cause death. Secondary endpoints included cardiac death, MACEs, myocardial infarction and repeated revascularization. Outcomes of the longest follow-up period were assessed.

The analysis was performed with odds ratio (OR) random effect models and Fisher’s exact test. The available risk estimates that were extracted were primarily ORs. The quality of the included articles was assessed according to the NIH Quality Assessment Tools [23]. Heterogeneity across studies was determined with the I² statistic, and I² < 50% was considered to indicate low heterogeneity. We conducted funnel plot analysis to assess publication bias by plotting the standard error against the log risk ratio (Supplement Material Figure S1). RevMan software version 5.2 and R software version 4.1.1 were used for analysis.

Results

As shown in Figure 1, a total of 687 studies were identified through the electronic searches, 568 of which were excluded because of duplication. Another 16 studies were excluded on the basis of reading of the titles and abstracts. The remaining 103 studies were assessed by reading the full text. Among them, seven studies were included in the qualitative synthesis and meta-analysis. The characteristics of the included studies are summarized in Table 1.

Figure 1

Flow Diagram of the Study Selection Process.

Abbreviations: CTO, chronic total occlusion; non-IRA, non-infarct-associated arteries; RCT, randomized controlled trial; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Table 1

Design and Outcomes of the Studies Included in the Meta-Analysis.

Number	Author/Year	Design	Total Patients	Follow-up	Primary Outcomes	MACE Definition	Quality Assessment
1	Yang 2013 [14]	Single center, retrospective	136	2 years	Cardiac mortality and occurrence of MACEs	Cardiac death, recurrent myocardial infarction, repeat revascularization (PCI and/or CABG) and heart failure rehospitalization	Fair
2	Shi 2014 [15]	Single center retrospective	148	3 years	Survival and occurrence of MACEs	Cardiac death, recurrent myocardial infarction, repeat revascularization (PCI and/or CABG) and rehospitalization because of heart failure	Fair
3	Valenti 2014 [16]	Multicenter registry retrospective	169	1 year	1- and 3-y cardiac survival	One year outcome death/cardiac death, nonfatal reinfarction, IRA-re-PCI, CTO vessel re-PCI, coronary bypass and stroke	Fair
4	Watanabe 2017 [18]	Multicenter registry, retrospective	121	4 years	All-cause death	Not reported	Fair
5	Deng 2018 [17]	Single center, retrospective	377	4 years	MACEs	All-cause death, nonfatal myocardial infarction, ischemia-driven coronary revascularization and hospitalization for heart failure	Good
6	Elias 2018 [21]	Multicenter RCT	302	3.9 years	MACEs	composite of cardiac death, MI and CABG; other clinical endpoints: all-cause death, (repeat) PCI, stent thrombosis, stroke and major bleeding	Good
7	Cui 2020 [22]	Single-center, retrospective	287	6.06 years	MACEs	Composite of all-cause death, nonfatal myocardial infarction, stroke or unplanned revascularization	Good

Abbreviations: MACEs, major adverse cardiac events; RCT, randomized controlled trial; CABG, coronary artery bypass grafting; CTO, chronic total occlusion; PCI, percutaneous coronary intervention.

A total of 68 events among the 783 participants occurred in the PCI-CTO group, whereas 120 events were observed among 757 patients in the occluded CTO group. Compared with that in the occluded CTO group, the pooled OR value of all-cause death in the PCI-CTO group was 0.46 (95% CI: 0.23–0.95; Figure 2A), and the heterogeneity was moderate (I² = 74%, P = 0.04).

Figure 2

Forest Plot for All-Cause Mortality, Cardiac Mortality, Composite Outcomes, Myocardial Infarction, Repeat Revascularization and Heart Failure.

Forest plot reporting the ORs in patients with STEMI with PCI of CTO lesions in the non-IRA vs occluded CTO lesions during the follow-up period: A. All-cause death; B. cardiovascular death; C. MACEs; D. myocardial infarction; E. repeat revascularization; F. heart failure. Diamond indicates the overall summary estimate for the analysis (width of the diamond represents the 95% CI; width of the shaded square represents the size of the population).

Seven studies reported cardiovascular death, and the OR was 0.43 (95% CI: 0.20–0.91; Figure 2B). The heterogeneity test yielded a P value of 0.03 with an I² value of 67%, thus indicating moderate heterogeneity.

Five trials provided data for MACEs. A total of 335 MACEs occurred in 1250 participants in total. Overall, the PCI-CTO group experienced a lower risk of MACEs than the occluded CTO group (OR: 0.47; 95% CI: 0.32–0.69), with evidence of low heterogeneity (I²: 44%; P < 0.0001; Figure 2C).

A total of 76 new MI cases were reported: 3.73% (34/911) in the PCI-CTO group and 5.32% (42/789) in the occluded CTO group. No significant difference was observed between groups (OR, 0.71; 95% CI, 0.44–1.44 [P = 0.15]; Figure 2D).

Seven studies with 1540 patients were included, and moderate heterogeneity was found (I² = 0%, P = 0.09). No significant differences were observed between groups regarding myocardial infarction (RR = 0.70, 95% CI: 0.43–1.14; Figure 2E).

Four cohort studies were included for the outcome of heart failure, which involved 792 participants and 89 events. Compared with the occluded CTO group, the PCI-CTO group had a lower risk of heart failure (RR = 0.57, 95% CI: 0.37–0.89, P = 0.01), with low heterogeneity (I²: 0%; P = 0.42; Figure 2F).

In sensitivity analysis, only a slight change in risk estimates was observed after removal of a study for all outcomes. These results indicated that the present findings were robust, and no single study drove the summary effects (Figure 3).

Figure 3

Sensitivity Analyses of Pooled ORs for Outcomes.

Sensitivity analyses for the following outcomes: A. all-cause death; B. cardiovascular death; C. MACEs; D. myocardial infarction; E. repeat revascularization; F. heart failure. The OR of each study along with a pooled risk ratio with 95% CI is indicated.

Discussion

To our knowledge, this is the most recent and largest meta-analysis assessing the efficacy of successful revascularization for CTO in the non-IRA in patients with STEMI, which included 1540 participants from seven studies. An RCD and an additional cohort study with longer follow-up time have since been published. With this new published evidence, the statistical power was enhanced to provide more precise and reliable risk estimates. The most relevant heterogeneity moderators were identified through subgroup analysis. Sensitivity and publication bias analyses were performed to ensure the stability of the present results. The main findings of the present meta-analysis are as follows. First, successful revascularization for CTO in the non-IRA in patients with STEMI treated with p-PCI is associated with lower risk of all-cause death and the composite endpoint of MACEs. Second, all-cause death, cardiac death, and the incidence of repeat revascularization, heart failure and stroke decrease with CTO revascularization in non-IRA in patients with STEMI. Furthermore, successful revascularization is not strongly associated with a decreased risk of myocardial infarction.

Patients with MVD who undergo primary PCI for STEMI with CTO lesions in the non-IRA have poorer clinical outcomes compared with those without CTO lesions in the non-IRA [8–10]. Several explanations exist for the high mortality rate of patients with STEMI with concomitant CTO. First, patients with CTO in the non-IRA have a higher prevalence of cardiovascular risk factors and comorbidities than patients with MVD without CTO. Additionally, these patients, compared with patients without CTO, tend to have a lower left ventricular ejection fraction and lower baseline thrombolysis in myocardial infarction flow grades, but a higher prevalence of diabetes mellitus, previous myocardial infarction and cardiogenic shock on admission [7, 24, 25]. Furthermore, these patients are often potentially at risk of “double jeopardy” from the acute MI. The distal coronary bed of the CTO is supplied mainly by collateral blood flow from the IRA; thus, the threatened area of the IRA includes both its own supply territory and the myocardial distribution of the coronary artery in which the CTO is located, thereby resulting in a larger infarct size [15]. Considering the procedural complexity, low success rates, long procedure times, large amounts of contrast consumption and frequent complications, revascularization of CTO remains challenging. In this setting, few cardiologists are willing to perform the procedure of CTO recanalization [22].

Primary PCI is the preferred therapeutic strategy to restore blood flow in the IRA in the management of acute STEMI, according to the most recent guidelines [2]. To date, several randomized controlled trials and guidelines have supported a strategy of staged PCI of non-culprit lesions after primary PCI in patients presenting with STMEI and MVD [26, 27]. CTO is the most complex and challenging coronary lesion for PCI. According to the guidelines, revascularization of CTO lesions should be considered only after objectives of viability or ischemia in the CTO territory, or expected relief of angina symptoms [28].

Nevertheless, the effects of staged revascularization of CTO, a special subgroup of MVD, on clinical outcomes remain controversial. Previous studies have indicated that staged CTO-PCI is associated with lower risk of cardiac death and MACEs [14–19]. Additionally, successful CTO PCI is associated with a lower incidence of all-cause mortality than failed CTO PCI [29]. However, only two studies have reported the incidence of all-cause mortality in patients with failed CTO-PCI, and no conclusion regarding the association between the CTO PCI failure rate and all-cause mortality could be drawn (Supplementary Materials Table S1). The only RCT, the EXPLORE trial, has found no significant differences between strategies in term of left ventricular ejection fraction during a 1-year follow-up and clinical outcomes during a 3.9-year follow-up. However, notably, the randomized CTO recanalization was performed after 5 days (mean) of primary PCI, when inflammation plays an important role during the acute setting of STEMI and recovery, thus leading to larger infarct sizes and left ventricular remodeling after staged non-culprit PCI. In addition, a relatively lower rate of successful CTO-PCI (73%) could mask the value of CTO recanalization [21].

Possible mechanisms underlying the clinical benefits of CTO revascularization include the following. First, revascularization may improve the healing process of the infarct border zone. Some myocardium located in the infarct border zone changes from viable myocardium into stunning myocardium, as a result of the disruption of the blood supply; repetitive episodes of stunning are now widely believed to lead to the development of myocardial apoptosis. With the restoration of the myocardial blood supply, stunning myocardium becomes viable [30, 31]. Additionally, previous studies have demonstrated that successful CTO PCI is associated with improved LVEF. Some studies have found that EF improvement, particularly stress EF after revascularization, is associated with fewer cardiac events [32]. As shown in our analysis, successful CTO-PCI is associated with a lower incidence of heart failure. Moreover, because in CTO-PCI, successful CTO-PCI is a prerequisite for complete revascularization, we found that most patients in the successful CTO-PCI group experienced complete coronary revascularization, which has been found to be associated with improved survival in patients with MVD. However, most of the studies in the current meta-analysis were retrospective and therefore might have reported a large excess mortality from heart failure or causes other than MI. Thus, the exact explanations for the beneficial effects of successful CTO-PCI remain to be studied in the future. Furthermore, successful CTO-PCI was associated with a decreased incidence of ventricular arrhythmias, owing to ischemia-induced prolongation of the QT interval [33]. In the RCT, a difference in LVEF was observed in only the LAD CTO sub-group; the mean LVEF was 40% in the occluded CTO cohort – a proportion too low to significantly increase the risk of death.

The present study has several limitations. First, almost all studies included in the meta-analysis were observational, thereby making these findings susceptible to the effects of unidentified confounders. Consequently, more RCTs should be performed in the future to further support the present results. Second, because only seven studies were included, we did not conduct meta-regression. However, we observed only a slight change in risk estimates for all outcomes in the subgroup analysis after removing a study, thus indicating the robustness of the present findings. Moreover, the inclusion criteria for treating CTO with PCI, myocardial ischemia and viability tests in the included studies were unknown. Further research is warranted to evaluate viability testing in patients with STEMI with non-culprit CTO lesions and the effects of PCI on clinical outcomes.

Conclusion

In this meta-analysis, successful revascularization for CTO in the non-IRA in patients with STEMI treated with p-PCI was found to be associated with a significantly lower risk of all-cause death, MACEs, cardiac death and incidence of heart failure. Thus, successful revascularization of CTO in the non-IRA is associated with improved outcomes in patients with STEMI treated with p-PCI.

Acknowledgements

The work was supported by the Beijing Tsinghua Changgung Hospital Fund (grant No. 12019C1009). All authors contributed to the writing and editing of the manuscript. Yu Geng and YT Wang contributed equally to the manuscript. Ping Zhang, YJ Xue, YT Wang and Yu Geng conceived the project and designed the experiments; LF Liu, YJ Xue, GB Miao, O Zhang, YT Wang and Yu Geng conducted data collection and analysis.

Conflicts of Interest

There are no conflicts of interest to be declared.

Funding

The work was supported by the Beijing Tsinghua Changgung Hospital Fund (grant No. 12019C1009).

Citation Information

Download Citation.

References

1. K Thygesen, JS Alpert, AS Jaffe, BR Chaitman, JJ Bax, DA Morrow, et al. Executive Group on behalf of the Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Heart Federation Task Force for the Universal Definition of Myocardial I. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018;72:2231–64.

2. GN Levine, ER Bates, JC Blankenship, SR Bailey, JA Bittl, B Cercek, et al. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. J Am Coll Cardiol 2016;67:1235–50.

3. BE Claessen, GD Dangas, G Weisz, B Witzenbichler, G Guagliumi, M Mockel, et al. Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial. Eur Heart J 2012;33:768–75.

4. Y Bataille, JP Dery, E Larose, U Dery, O Costerousse, J Rodes-Cabau, et al. Prevalence, predictors and clinical impact of unique and multiple chronic total occlusion in non-infarct-related artery in patients presenting with ST-elevation myocardial infarction. Heart 2012;98:1732–7.

5. Y Bataille, JP Dery, E Larose, E Abdelaal, J Machaalany, J Rodes-Cabau, et al. Incidence and clinical impact of concurrent chronic total occlusion according to gender in ST-elevation myocardial infarction. Catheter Cardiovasc Interv 2013;82:19–26.

6. BE Claessen, LP Hoebers, RJ van der Schaaf, WJ Kikkert, AE Engstrom, MM Vis, et al. Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on long-term mortality in diabetic patients with ST elevation myocardial infarction. Heart 2010;96:1968–72.

7. M Tajstra, M Gasior, M Gierlotka, D Pres, M Hawranek, P Trzeciak, et al. Comparison of five-year outcomes of patients with and without chronic total occlusion of noninfarct coronary artery after primary coronary intervention for ST-segment elevation acute myocardial infarction. Am J Cardiol 2012;109:208–13.

8. Y Mizuguchi, A Takahashi, T Yamada, N Taniguchi, S Nakajima, T Hata. Chronic total occlusion in a non-infarct-related coronary artery exacerbates prognosis in acute myocardial infarction: a Japanese single-center retrospective study. Int J Cardiol 2014;176:1139–41.

9. JH Lee, HS Park, HM Ryu, H Lee, MH Bae, JH Lee, et al. Impact of multivessel coronary disease with chronic total occlusion on one-year mortality in patients with acute myocardial infarction. Korean Circ J 2012;42:95–9.

10. HY Kim. The concurrent chronic total occlusion in a non-infarct artery strongly associate with poor long-term prognosis in patients with acute myocardial infarction and multivessel coronary disease. Korean Circ J 2012;42:83–5.

11. CO Koelbl, ZS Nedeljkovic, AK Jacobs. Coronary chronic total occlusion (CTO): a review. Rev Cardiovasc Med 2018;19:33–9.

12. PA Villablanca, DF Briceno, D Massera, O Hlinomaz, M Lombardo, AE Bortnick, et al. Culprit-lesion only versus complete multivessel percutaneous intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized trials. Int J Cardiol 2016;220:251–9.

13. L Azzalini, D Karmpaliotis, R Santiago, K Mashayekhi, C Di Mario, S Rinfret, et al. Contemporary issues in chronic total occlusion percutaneous coronary intervention. JACC Cardiovasc Interv 2022;15:1–21.

14. ZK Yang, RY Zhang, J Hu, Q Zhang, FH Ding, WF Shen. Impact of successful staged revascularization of a chronic total occlusion in the non-infarct-related artery on long-term outcome in patients with acute ST-segment elevation myocardial infarction. Int J Cardiol 2013;165:76–9.

15. G Shi, P He, Y Liu, Y Lin, X Yang, J Chen, et al. Evaluation of the effect of concurrent chronic total occlusion and successful staged revascularization on long-term mortality in patients with ST-elevation myocardial infarction. ScientificWorldJ 2014;2014:756080.

16. R Valenti, M Marrani, G Cantini, A Migliorini, N Carrabba, R Vergara, et al. Impact of chronic total occlusion revascularization in patients with acute myocardial infarction treated by primary percutaneous coronary intervention. Am J Cardiol 2014;114:1794–800.

17. J Deng, X Wang, Y Shi, X Zhao, Y Han. Prognostic value of the age, creatinine, and ejection fraction score for non-infarct-related chronic total occlusion revascularization after primary percutaneous intervention in acute ST-elevation myocardial infarction patients: a retrospective study. J Interv Cardiol 2018;31:33–40.

18. H Watanabe, T Morimoto, H Shiomi, Y Furukawa, Y Nakagawa, K Ando, et al. Chronic total occlusion in a non-infarct-related artery is closely associated with increased five-year mortality in patients with ST-segment elevation acute myocardial infarction undergoing primary percutaneous coronary intervention (from the CREDO-Kyoto AMI registry). EuroIntervention 2017;12:e1874–e82.

19. PA Villablanca, W Olmedo, M Weinreich, T Gupta, D Mohananey, FN Albuquerque, et al. Staged percutaneous intervention for concurrent chronic total occlusions in patients with ST-segment-elevation myocardial infarction: a systematic review and meta-analysis. J Am Heart Assoc 2018;7:e008415.

20. JP Henriques, LP Hoebers, T Ramunddal, P Laanmets, E Eriksen, M Bax, et al. Percutaneous intervention for concurrent chronic total occlusions in patients with STEMI: the EXPLORE trial. J Am Coll Cardiol 2016;68:1622–32.

21. J Elias, IM van Dongen, T Ramunddal, P Laanmets, E Eriksen, M Meuwissen, et al. Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction. Heart 2018;104:1432–8.

22. KY Cui, F Yuan, H Liu, F Xu, M Zhang, W Wang, et al. Long-term outcomes of staged recanalization for concurrent chronic total occlusion in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention. J Geriatr Cardiol 2020;17:16–25.

23. NIH Quality Assessment Tools. Available from: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools .

24. RJ van der Schaaf, MM Vis, KD Sjauw, KT Koch, J Baan Jr., JG Tijssen, et al. Impact of multivessel coronary disease on long-term mortality in patients with ST-elevation myocardial infarction is due to the presence of a chronic total occlusion. Am J Cardiol 2006;98:1165–9.

25. BE Claessen, RJ van der Schaaf, NJ Verouden, NK Stegenga, AE Engstrom, KD Sjauw, et al. Evaluation of the effect of a concurrent chronic total occlusion on long-term mortality and left ventricular function in patients after primary percutaneous coronary intervention. JACC Cardiovasc Interv 2009;2:1128–34.

26. L Politi, F Sgura, R Rossi, D Monopoli, E Guerri, C Leuzzi, et al. A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up. Heart 2010;96:662–7.

27. T Engstrom, H Kelbaek, S Helqvist, DE Hofsten, L Klovgaard, L Holmvang, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3-PRIMULTI): an open-label, randomised controlled trial. Lancet 2015;386:665–71.

28. P Kolh, S Windecker, F Alfonso, JP Collet, J Cremer, V Falk, et al. European Association of Percutaneous Cardiovascular I. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg 2014;46:517–92.

29. M Megaly, M Khalil, MB Basir, MB McEntegart, JC Spratt, M Yamane, et al. Outcomes of successful vs. failed contemporary chronic total occlusion percutaneous coronary intervention. Cardiovasc Interv Ther 2021. DOI: [Cross Ref].

30. F Borgia, N Viceconte, O Ali, C Stuart-Buttle, A Saraswathyamma, R Parisi, et al. Improved cardiac survival, freedom from MACE and angina-related quality of life after successful percutaneous recanalization of coronary artery chronic total occlusions. Int J Cardiol 2012;161:31–8.

31. DA Jones, R Weerackody, K Rathod, J Behar, S Gallagher, CJ Knight, et al. Successful recanalization of chronic total occlusions is associated with improved long-term survival. JACC Cardiovasc Interv 2012;5:380–8.

32. BN Shah, RS Khattar, R Senior. The hibernating myocardium: current concepts, diagnostic dilemmas, and clinical challenges in the post-STICH era. Eur Heart J 2013;34:1323–36.

33. K Cui, S Lyu, X Song, F Yuan, F Xu, M Zhang, et al. Effect of coronary collaterals on prognosis in patients undergoing primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: a meta-analysis. Angiology 2018;69:803–11.

Supplementary Material

Supplementary material for this paper can be found at the following link: https://cvia-journal.org/wp-content/uploads/2022/06/Staged-Revascularization-for-Chronic-Total-Occlusion.pdf.