Procedural and In-Hospital Outcomes of Chronic Total Occlusion Percutaneous Coronary Interventions in Patients With Acute Myocardial Infarction: Insights From a Prospective Multicenter International Registry

Background. We sought to examine the procedural and clinical outcomes of patients who underwent chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in the setting of acute myocardial infarction (AMI). Methods. We assessed the clinical and procedural characteristics, technical success, procedural success, and in-hospital outcomes of 2314 patients who underwent CTO-PCI at 20 experienced centers between 2012 and 2017, classified according to whether or not they presented with AMI. Results. Mean patient age was 65 ± 10 years, 85% were men, and 154 (6.7%) presented with AMI (5.5% with non-ST segment elevation myocardial infarction, 1.1% with ST-segment elevation myocardial infarction). Compared with non-AMI patients who underwent CTO-PCI, AMI patients had higher prevalence of diabetes (56% vs 42%; P<.01) and lower median left ventricular ejection fraction (48% vs 54%; P<.001). The CTO angiographic characteristics were similar between the 2 groups. Compared with non-AMI patients undergoing CTO-PCI, AMI patients had more frequent use of antegrade wire escalation (86.0% vs 78.9%; P=.03) and more frequent use of hemodynamic support devices (16.2% vs 3.4%; P<.01), and were more likely to have a non-CTO lesion treated (34.0% vs 26.6%; P=.03). AMI and non-AMI patients had similar technical success (90% vs 87%; P=.26), procedural success (88% vs 85%; P=.38), and incidence of in-hospital MACE (2.6% vs 2.5%; P=.94). Conclusion. CTO-PCI is performed infrequently in AMI patients and is associated with similar technical and procedural success rates and in-hospital major adverse cardiovascular event rates when compared with CTO-PCI performed in non-AMI patients.

Key words: acute myocardial infarction; chronic total occlusion (CTO), percutaneous coronary intervention

Restoration of blood flow in the infarct-related artery (IRA) by percutaneous coronary intervention (PCI) is the primary treatment goal in acute myocardial infarction (AMI) in both those presenting with a ST-segment elevation myocardial infarction (STEMI) and those presenting with non-ST segment elevation myocardial infarction (NSTEMI).^1,2 Approximately 40%-60% of patients who present with AMI have multivessel coronary artery disease (MVD) and approximately 12% have chronic total occlusions (CTOs).^3,4 The presence of a CTO in STEMI patients is independently associated with higher 30-day and long-term mortality irrespective of the presence of MVD.^4-6 A similar association has been observed in patients with NSTEMI.³ The role of CTO-PCI in patients who present with recent AMI remains controversial.^4,5,6 We examined the technical and procedural success and in-hospital outcomes of CTO-PCI among patients presenting with AMI in a large, multicenter registry.

We performed a retrospective analysis of 2314 patients who underwent CTO-PCI at 20 high-volume centers participating in the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) between 2012 and 2017. We compared the clinical, angiographic, and procedural characteristics and outcomes of CTO-PCI among patients who presented with and without AMI.

Coronary CTOs were defined as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-month duration. Estimation of the duration of occlusion was clinical, based on the first onset of angina, history of myocardial infarction (MI) in the target-vessel territory, or comparison with a previous angiogram. AMI was defined using the Third Universal Definition of Myocardial Infarction.⁷Calcification was assessed by angiography as mild (spots), moderate (involving ≤50% of the reference lesion diameter), and severe (involving >50% of the reference lesion diameter). Moderate proximal vessel tortuosity was defined as the presence of at least 2 bends >70° or 1 bend >90° and severe tortuosity as 2 bends >90° or 1 bend >120° in the CTO vessel. Proximal cap ambiguity was defined as inability to determine the exact location of the proximal cap of the occlusion due to the presence of obscuring sidebranches or overlapping branches that could not be resolved despite multiple angiographic projections. Interventional collaterals were defined as collaterals considered amenable to crossing by a guidewire and a microcatheter by the operator. A procedure was defined as retrograde if an attempt was made to cross the lesion through a collateral vessel or bypass graft supplying the target vessel distal to the lesion. Antegrade dissection/re-entry was defined as antegrade PCI during which a guidewire was intentionally introduced into the subintimal space proximal to the lesion, or attempt for re-entry into the distal true lumen following intentional or inadvertent subintimal guidewire or device crossing. Technical success was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as achievement of technical success without any in-hospital major adverse cardiac event (MACE). In-hospital MACE included any of the following adverse events before hospital discharge: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft surgery, tamponade requiring either pericardiocentesis or surgery, and stroke. Donor vessel injury was defined as either iatrogenic dissection or thrombus formation in the donor vessel. The Japanese CTO (J-CTO) score was calculated as described by Morino et al,⁸ the PROGRESS-CTO score as described by Christopoulos et al,⁹ and the PROGRESS- CTO Complications score as described by Danek et al.¹⁰

Statistical analysis. Categorical variables are expressed as percentages and were compared using Pearson’s Chi-squared test or 2-tailed Fisher’s exact test. Continuous variables are presented as mean ± standard deviation or median (interquartile range [IQR]) unless otherwise specified and were compared using t-test or Wilcoxon rank-sum test, as appropriate. All statistical analyses were performed with JMP, version 14.0 (SAS Institute). A 2-sided P-value of .05 was considered statistically significant

Patient characteristics. Between 2012 and 2017, a total of 2314 patients underwent CTO-PCI at 20 experienced centers. The baseline clinical characteristics of the study patients are listed in Table 1. Mean age was 65 ± 10 years and 85% were men. A total of 154 patients (6.7%) presented with AMI (5.5% NSTEMI, 1.1% STEMI). Most non-AMI patients (1476; 64%) presented with stable angina, 432 (19%) presented with unstable angina, and 251 presented (11%) with no anginal symptoms. Compared with patients without AMI, AMI patients had higher prevalence of diabetes mellitus (56% vs 42%; P<.01), smoking (35% vs 25%; P=.01), and peripheral vascular disease (21% vs 15%; P=.04). AMI patients had significantly lower left ventricular ejection fraction (48% [IQR, 37%-58%] vs 54% [IQR, 43%-60%]; P<.001).

Procedural characteristics. The CTO angiographic characteristics were similar between the 2 groups (Table 2 and Table 3). Mean J-CTO, PROGRESS-CTO, and PROGRESS-CTO Complications scores were 2.49 ± 1.29, 1.31 ± 1.03, and 3.06 ± 1.93, respectively, and were similar in AMI and non-AMI patients.

The CTO-PCI was performed during the index PCI in AMI patients presenting with STEMI and NSTEMI. Antegrade wire escalation (AWE) was the initial strategy of choice among both groups, yet AWE was used more often as the initial crossing strategy in AMI patients (86% vs 79%; P=.03). AWE was the final crossing strategy in 52% of AMI patients vs 45% of non-AMI patients. The use of antegrade dissection re-entry and retrograde techniques was less frequent than AWE and was similar between the 2 groups, both as the initial strategy as well as the final crossing strategy. Bifemoral approach was used less often in AMI patients (38.0% vs 48.0%; P=.01), who were also more likely to undergo PCI of a non-CTO lesion (34.0 vs 26.6%; P=.03).

Compared with non-AMI patients, AMI patients were more likely to receive hemodynamic support (16.2% vs 3.4%; P<.001) (Table 4). AMI patients had higher frequency of both prophylactic (11.7% vs 2.5%; P<.001) and urgent (4.5% vs 0.9%; P<.01) left ventricular assist devices use. AMI patients had higher use of intra-aortic balloon pump, Impella 2.5, Impella CP, and TandemHeart, but venoarterial extracorporeal membrane oxygenation use was similar in both groups.

In-hospital outcomes. AMI patients had similar technical (90.0% vs 87.0%; P=.26) and procedural success (88.0% vs 85.0%, P=.38), and MACE (2.6% vs 2.5%; P=.94) compared with non-AMI patients (Table 4). AMI patients had similar in-hospital mortality compared with non-AMI patients (1.95% vs 0.51%; P=.06). There was also no significant difference in procedure time, fluoroscopy time, contrast volume, or radiation dose.

In the present study, we assessed the clinical and procedural outcomes of patients who underwent early CTO-PCI in the setting of a recent AMI as compared with non-AMI patients. The major findings of our study are that technical and procedural success rates and the incidence of complications were similar between the 2 groups.

The COMPLETE (Complete vs Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial was a multinational, randomized trial including patients with STEMI and multivessel coronary artery disease. The trial compared a strategy of staged non-IRA PCI with the goal of complete revascularization vs a strategy of culprit-lesion only PCI, and found a 26% lower risk of the composite of death from cardiovascular causes or new MI at a median follow-up of 3 years in the non-IRA PCI arm.¹¹ The benefit of complete revascularization was consistently observed regardless of whether non-IRA PCI was performed during index hospitalization or several weeks later.¹¹ However, CTO-PCI was infrequently performed in the COMPLETE trial, with only 55 patients (2.1% of the patients in the complete revascularization arm) determined to have 100% stenosis (CTO) on visual estimation.¹¹ The degree of stenosis of the non-IRA intervention did not alter the benefit of complete revascularization observed in the COMPLETE trial.¹¹

There are limited data on the effects of CTO revascularization in patients with AMI.⁷ In a study of 106 patients who underwent PCI for NSTEMI and were found to have concomitant CTO lesions of non-IRAs, successful revascularization of CTO lesions was associated with lower long-term incidence of cardiac death and MACE.³ Furthermore, an analysis of 5 observational studies involving 1083 patients demonstrated that successful PCI of non-IRA CTO lesions was associated with lowered all-cause mortality, cardiac mortality, and MACE rate.¹² The clinical benefit of CTO-PCI may be secondary to improved healing of the ischemic border post infarct, particularly when the perfusion area of the culprit vessel and the CTO are adjacent or overlapping.¹³ The territory supplied by a CTO is more susceptible to ischemia once collaterals from the IRA are cut off in the case of AMI.³ Especially when the culprit vessel is the main vessel supplying the collaterals to the non-IRA CTO territory, CTO-PCI may help salvage myocardium, prevent expansion of myocardial necrosis, and restore contractile function in the CTO territory, ie, hibernating myocardium.¹³

There is limited information on the optimal timing of CTO-PCI in AMI. Cui et al demonstrated in a retrospective observational study that staged non-IRA CTO-PCI in patients presenting with STEMI was associated with improved outcomes if done within 90 days of index STEMI-PCI.¹³ Similarly, Shi et al reported that successful staged non-IRA-CTO PCI was associated with improved survival and reduced MACE when done within 7 to 10 days from index-STEMI PCI.¹⁴ In the COMPLETE trial, the median time to non-IRA PCI was 23 days. Therefore, the optimal timing for non-IRA-CTO PCI remains unknown, but given the above data can be considered within the first month post AMI.

The EXPLORE (Evaluating Xience and Left Ventricular Function in PCI on occlusiOn afteR STEMI) trial enrolled 304 patients with STEMI who were randomized to receive early (within 1 week) CTO-PCI vs medical therapy. The study demonstrated that the final left ventricular ejection fraction at 4 months for CTO-PCI vs conservative management was 44.1% vs 44.8%, respectively, which was not significantly different from the baseline value in both groups.⁶ The study also showed that there was no difference in infarct size by magnetic resonance imaging (MRI) performed 4 months post PCI.⁶ It is important to note that in the EXPLORE trial, all patients enrolled received successful primary PCI of the IRA prior to randomization.⁶ There are a few caveats to consider regarding the EXPLORE trial. Subsequent MRI analysis has shown that revascularization of the dysfunctional myocardium supplied by the CTO resulted in a greater recovery of regional left ventricular function from baseline to 4-month follow-up, when compared with medical therapy.¹⁵ It is important to note that the procedural success in this trial was low (~72%), so it is unknown whether a higher success rate would have resulted in better outcomes.⁶ Also, there was no assessment of viability in the non-IRA CTO, which may have helped with better patient selection.⁶

Complete revascularization in acute coronary syndrome is associated with improved outcomes; however, the impact of CTO-PCI to achieve complete revascularization after AMI needs to be further studied.

Study limitations. Our study is limited by its observational nature, with all inherent limitations. The time interval between AMI and CTO-PCI was not known; however, it did occur during a single hospitalization. Particularly in the 26 patients treated with STEMI, it is unclear whether the CTO artery was felt to be the culprit artery for the AMI or was a non-culprit vessel treated in the same index procedure. Similarly, it is not known whether a coronary artery bypass graft occlusion was the culprit for the AMI with subsequent CTO-PCI. We do not have data on AMI patients with CTOs who did not undergo CTO-PCI. All procedures were performed at high-volume, experienced PCI centers, thus limiting the generalizability of our findings to centers with limited CTO PCI experience. Thus, our study cannot establish benefits of CTO-PCI in this setting compared with no CTO-PCI. Further studies are needed to define the role of CTO-PCI in the post-AMI setting.

CTO-PCI in AMI patients was associated with similar success and safety profile compared with non-AMI patients.