Small vessel disease (SVD) has emerged as an intriguing issue of atherosclerotic coronary artery disease nowadays. SVD was reported to account for 30% to 67% of patients undergoing percutaneous coronary intervention (PCI) [1, 2]. Moreover, SVD also existed in patients with acute coronary syndrome (ACS), or even ST-segment elevation myocardial infarction (STEMI) [3, 4, 5]. Compared with large vessel disease (LVD), SVD had poorer prognosis [6] and more easily appeared in female patients with diabetes and chronic kidney disease [6, 7]. Although drug eluting stent (DES), drug coated balloon (DCB) or bioresorbable scaffolds (BRS) were proven to be effective for treating SVD [8, 9], the most challenge issue of SVD is equivocal definition and optimal treatment which depended on more refined classification.

Although previous observation studies illustrated the clinical features of SVD, whether the intravascular structure in lesions of small vessels differs from large vessels remained unknown. Moreover, the relationship between plaque morphology and vessel size was not investigated yet. Optical coherence tomography (OCT) is one of the powerful intracoronary image devices which not only identified plaque characteristics but also determined lumen size of culprit lesion more accurately than intravenous ultrasound (IVUS) or quantitative coronary analysis (QCA), especially in small coronary vessels [10, 11]. Herein, we measured diameters of culprit lesion determined by OCT and investigated its association with plaque characteristics.

This single centre study summarized clinical and intracoronary features of different culprit lesion size in patients with STEMI. The main results of the current study showed that patients with diameters $>$3 mm of culprit lesion tended to be female, older and thinner. Moreover, patients with larger lumen size presented with more incidence of plaque rupture and macrophage. In addition, patients with culprit diameters $\le$2.5 mm exhibited similar clinical manifestation and OCT features with patients with 2.5 mm $\le$ diameters 3 mm. The 3-year clinical outcome showed no significant difference among 3 groups.

In the past few decades, SVD has emerged as an intriguing issue of atherosclerotic coronary artery disease. Although abundant therapeutic methods were discovered, the optimal treatment option remained conflicting in various clinical trials. In patients with de novo lesion 3 mm, DCB and second-generation DES showed similar clinical outcomes at 12 months [14]. In contrast, in a recent retrospective study, patients treated with DCB in vessels $\le$2.5 mm had significantly higher incidence of restenosis than DES [15]. The prime cause of this situation is that no uniform standard of SVD was determined previously and the diameters of SVD spanned from smaller than 2.25 mm to 3.0 mm in various studies [14, 16, 17]. Moreover, the measurement approach of vessel diameters was discordant in different studies, including angiographic or intracoronary quantification and even visual estimation [18]. On the other hand, SVD also presented with distinct plaque morphology and clinical manifestation, which should be taken into consideration in decision process. For example, SVD patients with diabetes represent much more high-risk than those without diabetes [19]. Furthermore, DCBs were more beneficial for patients with diabetes than DESs [20]. However, in vivo data about association of SVD and plaque morphology are lacking.

Plaque rupture, plaque erosion and calcified nodule are three main pathological phenotypes of ACS which presented different clinical outcome [21]. Although previous study reported that direct stenting had superior clinical outcome than conventional stenting in patients of STEMI with SVD [4], a recent OCT study demonstrated that ACS patients with plaque erosion benefited from medical therapy without stenting, including SVD [22]. Also, some case reports showed that patients with AMI and plaque erosion accepted successful treatment of thrombus aspiration and balloon without stent under OCT guidance [23]. However, there is still no evidence of safety and efficacy of no stent strategy for patients with plaque rupture. The research of drug-coated balloons treating vulnerable plaques is currently ongoing [24]. For calcified lesion, smaller balloons at higher pressures without coronary injuries was needed before stent implantation [25]. In this study, we found significantly different distribution of plaque phenotypes in patients with small to large diameters of culprit lesion. SVD patients with STEMI were easier to present plaque erosion, which may provide important clues for precise management of patients with SVD. For example, SVD with plaque rupture or erosion may reacted differently to DES or DCB in clinical outcome. Although an observation study demonstrated that DCB is safe and effective for ACS complicated with vulnerable plaque [26]. There is still unknown whether DCB is useful in ACS patients with plaque rupture in SVD. The choice of DES or DCB treating SVD should be based on clinical risk factors, functional assessment and plaque characteristics. Namely, for those patients both with plaque rupture and SVD, whether DCB or DES was more effective remained still unknown.

Small coronary lumen size or area presented with regional hemodynamic change which resulted in distinct atherosclerosis progression compared with the large lumen size [27]. Coronary artery flow velocity was reported to inversely relate to the lumen size and small lumen size may suffer from higher blood flow velocity [28]. Moreover, the previous study revealed that the size of the cavity inside the ruptured plaque was positively related to vessel size [29]. The prevalence of stent restenosis was also higher in small lumen artery than large lumen size [6]. Distinct size of vessel lumen exhibited various reaction to different DES. Previous study revealed sirolimus-Eluting stent acted better than paclitaxel-Eluting Stents by reducing MACE and target lesion revascularization in SVD but not in large vessel disease [30]. Furthermore, the previous study demonstrated that small vessel size was significantly associated with poorer prognosis in patients with STEMI [3]. However, as the development of advanced therapeutic strategy and novel technique of drug-eluting stent and DCB, SVD got similar outcome compared with patients of large coronary vessels [31]. Our results also suggested that vessel size of culprit lesion had less impact on patients’ prognosis. However, the number of patients with SVD in our study is quite small. Thus, whether patients with SVD can benefit from OCT guidance for choosing DES or DCB needs future large sample cohort study.

Numerous studies demonstrated that both plaque phenotype and vessel size were essential factors for treatment strategy in the past few decades [14, 15, 22, 23]. Previous study revealed that patients with plaque rupture showed higher prevalence of no-reflow and severer systemic inflammation which needed intensive antithrombotic and anti-inflammatory treatment [32]. However, patients with plaque erosion might benefit from drug therapy without stent while distal and microcirculation embolism should be noticed [33]. Although OCT enabled to identify plaque phenotypes precisely, it was not widely used in clinics because of its high price and operational complexity. In the current study, the association of culprit vessel diameters and plaque features was revealed and size of culprit vessel might assist to evaluate plaque phenotypes which guided us to product intervention strategy. For example, small vessel with diameters $\le$3 mm tended to be plaque erosion which was suitable for drug coated balloon dilation. Culprit lesion with large diameters were prone to presenting plaque rupture and more vulnerable features which needed intensive antiplatelet, cholesterol-lowering an even anti-inflammation therapy.

The present study suggested that vessel size of culprit lesion is significantly associated with plaque phenotype in patients with STEMI. However, patients with different diameters and plaque phenotypes showed no significant difference of clinical outcomes.

First, this study was a single-centre study with small sample size, more than one fourth of the patients were excluded so that selection bias cannot be excluded. Second, due to adhesion of thrombus in culprit lesion, error may exist in diameter measurement in some cases. Third, some interventional procedures, such as guidewire entry and thrombus aspiration before OCT examination, may change the structure of the underlying plaque. Therefore, some cases of plaque phenotype were misjudged.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conceptualization—JNL; methodology—XXZ and HBY; software—YW and PZ; validation—HJZ, RZC and CL; formal analysis—JYZ, SDY and LS; investigation—HBY; resources—SDY; data curation—JNL; writing - original draft preparation—JNL, SDY, XXZ, HBY and YW; writing - review and editing—LS, PZ, HJZ and RZC; revision—JNL, CL, JYZ and YC; visualization—YC; supervision—HJZ; project administration—HBY; funding acquisition—HJZ. All authors have read and agreed to the published version of the manuscript.

This study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Fuwai Hospital, Beijing (protocol code: 2017-866, date of approval: 22 January 2017). All patients provided written informed consent.

Not applicable.

This study was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016-I2 M-1–009), National Natural Science Funds (number: 81970308), the Fund of “Sanming” Project of Medicine in Shenzhen (number: SZSM201911017) and Shenzhen Key Medical Discipline Construction Fund (number: SZXK001).

The authors declare no conflict of interest.