Macrophage infiltrates in coronary plaque erosion portend a worse cardiovascular outcome in patients with acute coronary syndrome

Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p<0.001], higher prevalence of thrombus [41 (80.4%) vs. 64 (62.7%), p=0.028], lipid plaque [39 (76.5%) vs. 50 (49.0%), p<0.001], TCFA [20 (39.2%) vs. 14 (13.7%), p=0.001], and a higher maximum lipid arc [median [IQR] 250.0° (177.5°-290.0°) vs. 190.0° (150.0°-260.0°), p=0.018) at the culprit lesion compared with PE without MØI. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p=0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression model, PE with MØI [HR=2.95, 95% CI (1.09–8.02), p=0.034] was an independent predictor of MACEs. Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None