Association between non-culprit healed plaque and plaque progression in acute coronary syndrome patients: an optical coherence tomography study

BACKGROUNDHealed plaques are frequently found in patients with acute coronary syndrome, but the prognostic value is debatable. This study investigated the clinical features of non-culprit healed plaques detected by optical coherence tomography (OCT) with the aim of predicting plaque progression of healed plaques.METHODSThis study retrospectively analyzed 113 non-culprit lesions from 85 patients who underwent baseline OCT imaging and follow-up angiography from January 2015 to December 2019. Plaque progression predictors were assessed by multivariate analysis.RESULTSAmong 113 non-culprit lesions, 27 healed plaques (23.9%) were identified. Patients with non-culprit healed plaques had prior antiplatelet therapy (65.0% vs. 33.8%, P = 0.019), hypertension (85.0% vs. 50.7%, P = 0.009), and dyslipidemia (70.0% vs. 41.5%, P = 0.04) which were more frequently than those without healed plaques. The thickness (r = 0.674, P < 0.001), arc ( r = 0.736, P < 0.001), and volume ( r = 0.541, P = 0.004) of healed plaque were correlated with minimum lumen diameter changes. At a mean follow-up of 11.5 months, the non-culprit healed plaques had a lower minimum lumen diameter (1.61 ± 0.46 mm vs. 1.91 ± 0.73 mm, P = 0.016), lower average lumen diameter (1.86 mm vs. 2.10 mm, P = 0.033), and a higher degree of diameter stenosis (41.4% ± 11.9% vs. 35.5% ± 13.1%, P = 0.031) when compared to baseline measurements. The plaque progression rate was higher in the healed plaque group (33.3% vs. 8.1%, P = 0.002), and multivariate analysis identified healed plaques [odds ratio (OR) = 8.49, 95% CI: 1.71−42.13] and lumen thrombus (OR = 10.69, 95% CI: 2.21−51.71) as predictors of subsequent lesion progression. CONCLUSIONSHealed plaques were a predictor for rapid plaque progression. The quantitative parameters of healed plaque showed a good agreement with plaque progression. Patients with healed plaque were associated with prior antiplatelet therapy and high level of low-density lipoprotein cholesterol. Bifurcation lesions might be the predilection sites of healed plaques.

Coronary artery diseases originate from pathological changes in the vessel endothelium, present as plaque development and lumen stenosis, that finally lead to clinical coronary symptoms.^[1] Finding the ideal time to intervene in the atherosclerosis process is difficult, especially with non-culprit lesions.^[2–4] Revascularization benefits are challenged by the quick progression of previously untreated mild to moderate lesions.^[2] Several clinical trials suggested that the rapid step-wise pattern of plaque growth may play an important role in lumen narrowing.^[5,6] This mechanism was described as a healing process that was initiated by a plaque rupture or erosion to protect the integrity of the vessel structure.^[7,8] Re-endothelialization results in a new layer of organized thrombus and collagen distinguished from the underlying ruptured or eroded site,^[9] and plaques with two or more layers of different densities are called healed plaques or layered plaques.^[8,10] Autopsy studies found that healed plaques were frequent in patients dying of sudden death or asymptomatic myocardial infarction.^[11] Optical coherence tomography (OCT) is a high-resolution intravascular imaging tool that is highly sensitive and specific for in vivo identification of layered plaque patterns by histopathology.^[12,13] A previous OCT study suggested that layered plaques at the culprit site were associated with more vulnerable features and a high degree of lumen stenosis in patients with acute coronary syndrome (ACS).^[14] However, serial observations of plaque progression at the exact site were only reported in rare cases.^[15] In this study, we investigated the OCT features, quantitative parameters, and predictive value of non-culprit healed plaques, which may help minimize plaque progression and stenosis risk.