Francesco Prati, MD, PHD, Shiro Uemura, MD, PHD, Geraud Souteyrand, MD, PHD, Renu Virmani, MD,
Pascal Motreff, MD, PHD, Luca Di Vito, MD, PHD, Giuseppe Biondi-Zoccai, MD, PHD, Jonathan Halperin, MD, Valentin Fuster, MD, PHD, Yukio Ozaki, MD, PHD, Jagat Narula, MD, PHD

In autopsy studies, at least 25% of thrombotic coronary occlusions are caused by plaque erosion in which thrombus often overlies atherosclerotic plaque without evident disruption of the fibrous cap. We performed optical coherence tomography imaging after aspiration …thrombectomy and identified plaque erosion as the cause in 31 patients presenting with ST-segment elevation myocardial infarction. Plaque erosion was identified when the fibrous cap of the culprit lesion was intact. Based on clinical criteria, 40% of patients with subcritically occlusive plaque were treated with dual antiplatelet therapy without percutaneous revascularization (group 1), and the remaining 60% of patients underwent angioplasty and stenting (group 2). At a median follow-up of 753 days, all patients were asymptomatic, regardless of stent implantation. These observations support an alternative treatment strategy for patients with acute coronary events and optical coherence tomography–verified intact fibrous cap (or plaque erosion), where nonobstructive lesions might be managed without stenting. (J Am Coll Cardiol Img 2013;6:283–7) © 2013 by the American College of Cardiology Foundation.

Occlusive luminal thrombosis is the mechanism underlying most acute coronary syndromes (ACS). As many as 75% of autopsy studies after fatal ACS relate thrombotic occlusion to atherosclerotic plaque rupture; most of the remainder involve plaque erosion. Less common mechanisms involve thrombosis of a calcified nodule (1). Atherosclerotic lesions associated with plaque rupture may produce hemodynamically significant obstruction and typically contain a large necrotic core beneath a ruptured fibrous cap (RFC) that is attenuated and inflamed (Fig. 1). Discontinuity of the fibrous cap brings circulating platelets into contact with the highly thrombogenic plaque core, leading to acute thrombus formation that occludes the arterial lumen. In contrast, erosion of plaque rich in proteoglycans and smooth muscle cells predisposes to thrombus formation over an intact fibrous cap (IFC). Because the pathogenesis of ACS in patients with an RFC differs from that in patients with an IFC, it is possible that clinical management of these 2 groups of patients may differ.

Current treatment guidelines for patients with ACS rely heavily on catheter-based reperfusion of the infarct-related artery and intracoronary stent placement. The underlying plaque morphology is not routinely identified because of the limited resolution of conventional imaging modalities, such as intravascular ultrasound. Because stenosis of the arterial lumen might not always be significant in erosive pathology and the vessel wall not disrupted, it seems reasonable that reliable characterization of plaque morphology might justify an alternative approach that foregoes coronary stenting as the initial strategy for this subset of patients. Intracoronary optical coherence tomography (OCT) provides superior resolution, allowing more detailed analysis of plaque morphology (2), including discriminating IFC from RFC in patients with ACS. Plaque rupture and plaque erosion in the culprit lesions of patients with ACS can be distinguished as discrete syndromes on the basis of an RFC (ACS-RFC) and IFC (ACS-IFC) (2).

We describe a series of patients in whom ACS was attributed to IFC after aspiration thrombectomy. A subset of these patients was treated with dual antiplatelet therapy, without angioplasty or stent placement. Considering the risks of in-stent thrombosis and restenosis and the need for prolonged dual antiplatelet therapy that entails an increased risk of bleeding, such an approach may improve long-term outcomes. From the OCT databases of 4 institutions, we identified 31 patients with ST-segment elevation myocardial infarction who underwent coronary angiography within 12 h after the onset of symptoms with the intent to perform a primary percutaneous coronary intervention with thrombus aspiration. Patients presenting in cardiogenic shock were excluded. Procedures were performed according to current clinical practice guidelines. The management decisions, including use of glycoprotein IIb/IIIa inhibitors or antiplatelet agents, and the decision to perform bal- loon angioplasty or stent implantation were made by the operator according to the local practice. Patients received unfractionated heparin (5,000 to 10,000 IU), aspirin (300 mg before the primary percutaneous coronary intervention, followed by 100 mg/day), and clopidogrel (300 to 600 mg initially followed by 75 mg/day) or prasugrel at the discretion of the treating physician (Table 1). After discharge, patients were followed at 1 to 3 months and at 6 months, in accordance with local practice. One year after the index ACS event, patients were evaluated again, either in the clinic or by telephone by experienced research nurses.

Because thrombus hampers the assessment of un- derlying plaque anatomy, erosion of the fibrous cap was documented by OCT after the thrombus was removed or reduced by aspiration, as previously de- scribed (2). Table 2 shows procedural and angio- graphic characteristics of lesions in 12 patients in the group managed with thrombectomy only (group 1) and 19 cases in those managed with aspiration plus stent implantation (group 2). Three patients in group 1 who were initially managed with systemic throm- bolysis at community hospitals and transferred did not require aspiration (Fig. 2). Sixty-seven percent of patients in group 1 and 58% in group 2 presented with total coronary occlusions (Thrombolysis In Myocar- dial Infarction [TIMI] flow grades 0 to 1; p ? NS). The median total ischemic times were 3.5 ? 3.0 h and 3.6 ? 2.3 h in groups 1 and 2, respectively (p ? NS). There was only mild residual stenosis and no differ- ence between groups in the final TIMI flow grade achieved (3 for each). After a median follow-up of 753 days, target lesion revascularization was performed in 1 patient in group 2, but no myocardial infarction, heart failure, or deaths occurred in either group.

Plaque erosion is an entity distinct from plaque rupture (1,2). Most erosive lesions are devoid of necrotic core, and, when present, the core does not communicate with the lumen because of a thick fibrous cap. Such lesions have been reported in younger individuals, including premenopausal women, with smoking as the most prevalent risk factor. Many of these lesions display relatively minor luminal narrowing, and thrombus removal without balloon dilation or stent implantation may be suffi- cient to restore vessel patency. The luminal thrombo- sis in plaque erosion has been

FIGURE 1 – Click to enlarge

attributed to apoptosis or degradation of endothelial cells lining the plaque surface. Therefore, after thrombus removal, treatment with antiplatelet drugs may allow healing of the endothelial layer. The mechanisms involved may be similar to re-endothelialization after stent implanta- tion. Avoiding stent deployment could potentially reduce the risks of both early (dissection, embolism, occlusive thrombosis) and late (restenosis, neoathero- sclerosis, and thrombosis) complications.

These observations suggest that characterization of underlying plaque morphology by OCT may provide insight into the pathogenesis of some cases of ACS in which plaque erosion rather than rupture is an underlying cause. Reliable identification of these features may have practical implications for management, allowing selection of patients who can be treated using measures that reduce the burden of intravascular thrombus without intra-coronary stenting. Because ACS-IFC appears to involve a mechanism of luminal obstruction distinct from that in ACS-RFC, a different interventional approach to management may be warranted in these cases. Perhaps the role of antithrombin agents may warrant reconsideration in ACS-IFC. Further- more, because these lesions involve an IFC, the risk of intraplaque hemorrhage may be lower than in those with ACS-RFC, raising the possibility that specific strategies of catheter-directed lytic therapy (e.g., plasmin) may be relatively safe and efficacious. Definitive trials comparing the safety and efficacy of these alternative approaches will depend foremost on accurate imaging to exclude evidence of rupture or calcification of the offending coronary lesion.

Figure 2

Study limitations. The limitations of this observational study include its nonrandomized design, small sample size, and the lack of a comparison group of ACS-RFC patients managed either with or without stent implantation. Also, no conclusions can be drawn about various alternative methods of thrombus removal or adjunctive antithrombotic therapy, nor can we be certain about the subclinical events occurring at the plaque surface that promote thrombus formation in patients with ACS-IFC and predispose to the onset of the acute ischemic syndrome.

CONCLUSIONS

We demonstrate in a limited number of patients with ACS that characterization of plaque morphol- ogy by OCT could identify nonobstructive lesions amenable to treatment with an antiplatelet strategy alone, without angioplasty or coronary stent deployment, and result in satisfactory clinical outcomes. The PERADAM-OCT (Plaque Erosion in ACS: OCT-Based Diagnosis And Management, An In- ternational Registry) is beginning to gather additional data about the factors predisposing to plaque erosion and clinical presentation on ACS in pa- tients with lesions of this type. Randomized trials will be needed, however, to clarify the role of aspiration thrombectomy and catheter-directed lytic therapy without stent implantation in cases of OCT-verified ACS-IFC and further evaluate the long-term outcomes of an alternative management strategy for this unique cause of ACS.

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R E F E R E N C E S

1. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997;336: 1276 – 82.

2. Ozaki Y, Okumura M, Ismail TF, et al. Coronary CT angiographic characteris- tics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomog- raphy and angioscopy. Eur Heart J 2011;32:2814 –23.

OCT-Based Diagnosis and Management of STEMI Associated With Intact Fibrous Cap
Francesco Prati, MD, Shiro Uemura, MD, Geraud Souteyrand, MD, Renu Virmani, MD, Pascal Motreff, MD et 6 autres.
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