Prevalence and clinical significance of totally occluded infarct-related arteries in patients with non-ST-segment elevation acute coronary syndromes

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Highlights

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    In NSTE-ACS, association between totally occluded culprits and mortality was found neutral

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    Incomplete revascularization, particularly of CTO was associated with increased risk of death

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    Significant interaction emerged between the extent of revascularization and the culprit patency on mortality

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    CTO-PCI largely drived mortality risk regardless of the IRA patency in NSTE-ACS

Abstract

Background Seemingly conflicting findings exist regarding the prognostic impact of totally occluded infarct-related arteries (oIRA) in non-ST elevation acute coronary syndromes (NSTE-ACS).

Methods Retrospective analysis of prospective multicenter registry data comprising a single-center NSTE-ACS cohort, aimed at assessing the impact of occluded (TIMI flow 0/1) versus patent culprit vessels (pIRA, TIMI flow 2/3) on the composite endpoint of all-cause death and cardiogenic shock events at 30 days.

Results Of 568 patients, 183 (32.5%) had oIRA. Male sex, refractory angina, ECG suggestive of multivessel or left main disease, and larger infarct sizes with inferior/posterolateral wall involvement, were identified as highly specific markers of oIRA. Successful culprit-lesion revascularization occurred more frequently in patent than in oIRA (90% vs. 96%; P = 0.013). Conversely, patients with oIRA more frequently achieved successful revascularization of concurrent non-IRAs including chronic total occlusions than did those with pIRA (28% vs. 3%; P = 0.0005). Multivariate analysis revealed neutral effects of oIRA on outcomes and identified incomplete revascularization as a powerful predictor of mortality. Moderation analysis revealed a significant interaction between completeness of revascularization and IRA patency, whereby among the incompletely revascularized patients, those with oIRA enjoyed a significant survival advantage over their counterparts with pIRA (11.8% vs. 28%, adjusted OR 0.34; 95% CI 0.10–0.73; P interaction = 0.012).

Conclusions Approximately one third of NSTE-ACS patients in this cohort had oIRA. However, compared with pIRA, the occurrence of oIRA did not portend poor outcomes, likely resulting from the higher rate of incomplete revascularization and increased risk of subsequent mortality in patients with pIRA. These exploratory findings warrant further investigation.

Introduction

Persistent ST-segment elevation usually correlates with acute total or nearly total occlusion of the infarct-related artery (oIRA). Therefore, primary percutaneous coronary intervention (PCI) is currently the preferred strategy in ST-elevation myocardial infarction [1]. By contrast, non-ST-segment-elevation acute coronary syndromes (NSTE-ACS) represent a wide spectrum of clinical entities usually associated with rupture of an atherosclerotic plaque, resulting in an intermittent or incomplete thrombotic occlusion of the IRA [2]. Accordingly, NSTE-ACS management is guided by risk stratification, with an early invasive approach favoured in high-risk patients [2]. However, ST-segment elevation is a relatively insensitive marker for acute occlusion of the posterior coronary circulation, particularly the left circumflex coronary artery [3]. In this context, oIRA have been previously reported in about one-third of patients with NSTE-ACS [4,5]. Notwithstanding this relatively high prevalence, it remains controversial whether oIRA itself may pose increased mortality risk compared with a patent infarct-related artery (pIRA) [4,5]. Indeed, some studies have suggested worse clinical outcomes for oIRA [[6], [7], [8], [9], [10]], while other reported otherwise [[11], [12], [13], [14], [15], [16], [17]].

Given these conflicting data and the increasing incidence of NSTE-ACS worldwide, it makes sense to provide additional data and extend the currently available evidence regarding the prognostic impact of oIRA in this clinical scenario. Thus, this study aimed to assess the prevalence, determinants, and prognostic significance of oIRA in patients with NSTE-ACS.

Section snippets

Design and study population

This is a retrospective analysis of prospectively collected data from a single-center cohort of NSTE-ACS patients included in the ARIAM-Andalusia (Analysis of Delay in Acute Myocardial Infarction in Andalusia) Registry. The study protocol has been described in detail elsewhere [18,19]. Briefly, the ARIAM-Andalusia Project is an ongoing, prospective, multicenter, observational registry involving consecutive patients with ACS admitted to cardiac care units in the Autonomous Community of Andalusia

Results

Out of 2203 ACS patients screened, 568 with NSTE-ACS who fulfilled the inclusion and exclusion criteria, constituted the study population (Fig. 1). Of these, 183 (32.5%) patients were found to have an oIRA. Baseline characteristics and clinical presentation were broadly similar between groups (Table 1). Approximately 90% of patients received aspirin and P2Y12 inhibitors prior to angiography without significant differences across groups, though patients with oIRA received more frequently potent

Discussion

Main findings in the present study can be summarized as follow: (1) in current practice, almost one third of patients with NSTE-ACS had oIRA; (2) readily available markers proved helpful for predicting oIRA in a contemporary NSTE-ACS population; (3) the presence of an oIRA did not appear to portend poorer clinical outcomes as compared with pIRA; (4) however, exposure effects of oIRA on outcomes varied according to the degree of completeness of revascularization. Thereby, the extent of coronary

Study limitations

As with all retrospective studies, potential selection bias and residual confounding cannot be excluded. Therefore, the current analysis cannot address causality, and findings should still be considered hypothesis generating, rather than hypothesis testing. Likewise, information on the decision-making process for coronary revascularization was not adequately captured. Despite the monocentric nature and extrict exclusion criteria in this study may pose constraints on generalizability of results,

Conclusions

In this contemporary real-world study, the presence of oIRA in approximately one third of patients with NSTE-ACS did not seem to confer a significant increase in the 30-day risk of MACE compared with a pIRA. This neutral exposure effects of oIRA appeared to be largely driven by the joint effects of completeness of revascularization and the IRA patency on mortality risk, such that the negative impact of IR was much greater in patients with pIRA than in those with oIRA.

The current study

Authorship

All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Funding

None.

Author statement

All authors contributed and participated in the preparation of the manuscript and research steps in the present study as follows:

- Conception and design: MAD.

- Data collection: JCGR, MAD, PVC, MGR, TSG, NGG, MPRG, FJCC, BLL.

- Data Curation: MDA, JCGR.

- Endpoint/IRA validation: pair#1 (JCGR, TSG); pair#2 (RJHU, MAD).

- Statistical analysis and writing of original draft: MAD.

- Reading, critical review and final approval for submission: All.

Declaration of Competing Interest

None.

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