The study is a prospective cohort study conducted in Tianjin Chest Hospital, Tianjin city, China. Patients with SVGD referred for PCI are invited to participate in the study and VH-IVUS is performed in culprit SVG before and after PCI. Patients are recruited consecutively by surgeons at the Cardiology Department of Tianjin Chest Hospital. These subjects will be followed up at 1, 6, 12, 24 and 36 months post-PCI to assess clinical outcomes. The flow diagram of the study and the detailed study procedures are illustrated in Fig. 1.

The patients to be included in the study should meet all of the following criteria: (1) aged 18–80 years; (2) a history of previous CABG surgery more than 1 year ago; (3) diagnosed as SVGD which is defined as at least one SVG ≥50% diameter stenosis; (4) plans for receiving PCI using drug-eluting stents; (5) willing to participate in the study and sign informed consent.

Patients will be excluded from the study if any of the following criteria is met: (1) acute myocardial infarction within the previous 7 days; (2) having any contraindication to aspirin, clopidogrel, heparin or stainless steel; (3) impaired renal or hepatic function; (4) history of cerebral stroke or ischemic cerebrovascular disease within 3 months; (5) history of gastrointestinal bleeding or hemoptysis in the previous 4 weeks; (6) pregnant or breastfeeding; (7) vasculitis or other non-atherosclerotic CAD; (8) other major illnesses that would expose the participant to unexpected risk: hematologic disorder, malignancy, etc.

Participants can withdraw from the study at any time without any adverse outcome on subsequent treatment; the reasons for withdrawal will be recorded. The investigator can also exclude a participant from the study for reasons including serious adverse events or poor compliance with research protocol.

Coronary angiography is performed using angiography system with a flat-panel detector (Philips Allura Xper FD10, Philips Healthcare, Netherlands) according to the Judkins technique. Angiography of the in situ coronary artery is performed with 6F catheters through radial or femoral access, while Judkins R (JR) 4.0 is used as the first choice catheters for SVG angiography. The location of SVG is roughly determined according to previous CABG surgery procedure and it is displayed in at least two different projections. The presence of significant stenosis (≥50%) in at least one SVG is defined as SVGD.

After administration of heparin (100 U/Kg) and glyceryl trinitrate (100–200 μg), VH-IVUS is performed in SVG and other main coronary arteries before and after PCI. Data is obtained using a 20-MHz, 3.5-French EagleEye phased-array Gold catheter (Volcano Corporation, Rancho Cordova, California, USA) with motorized pullback (0.5 mm per second) from the most distal safe position to guide the catheter. The IVUS grey-scale and Virtual histology analyses are performed offline using the Volcano Image Analysis Software (version 3.0.394,Volcano Corporation, USA) and are not used for PCI guidance or subsequent management. Spectral and amplitude analyses of IVUS backscattered radiofrequency are performed by two experienced interventional cardiologists without knowledge of subsequent clinical events. Angiographic qualitative assessment and quantitative measurements are obtained for SVG. Quantitative IVUS measurements include cross-sectional areas (CAS) of the lumen, the external elastic membrane (EEM), and the plaque and media (EEM CAS minus lumen CAS), lesion length, plaque burden (plaque and media CAS divided by EEM CAS), and plaque volume. Qualitative IVUS assessments include plaque rupture (intraplaque cavity that communicated with the lumen with an overlying residual fibrous cap fragment) and characterization of lesions. On the basis of radiofrequency IVUS, plaque components and morphology are classified into the following four types: fibrous tissue (FT), fibrofatty (FF), necrotic core (NC), and dense calcium (DC). A lesion on IVUS imaging is defined as a plaque burden ≥40% in at least 3 consecutive frames. Consistent with published VH-IVUS classifications [25, 28], such lesions are classified as one of the following: 1) fibrotic plaque, mainly fibrous tissue with < 10% confluent NC, < 10% confluent DC, and < 15% FF; 2) fibrocalcific plaque (FCa), mainly fibrous tissue with > 10% confluent DC but < 10% confluent NC; 3) pathologic intimal thickening (PIT), not meeting FCa plaque definitions and predominantly fibrous tissue; 4) fibroatheroma, > 10% confluent NC, including thick-cap fibroatheroma (ThCFA) and thin-cap fibroatheroma (TCFA).

After receiving written informed consent, clinical staff will collect demographic and clinical characteristics from all participants. Medical records will be reviewed and related clinical information will be extracted. The data to be collected at baseline include demographic characteristics, medical history (diabetes mellitus, hypertension, hyperlipaemia, stroke, arrhythmia, previous myocardial infarction, PCI or CABG surgery, and medicines for cardiovascular disease), physical examination, clinical presentation (vital signs at hospital admission, onset time of chest pain, duration of chest pain, cardiac function with Killip classification), and smoking history. Cardiac color ultrasound, coronary angiogram, pre- and post-PCI VH-IVUS and 18 lead ECG will be done and used for checking inclusion/exclusion criteria. In addition, blood samples will be collected for laboratory testing, including routine blood, blood biochemistry, fasting glucose, coagulation function, homocysteine, cardiac damage markers (lactic dehydrogenase, creatine kinase, B-type natriuretic peptide, hydroxybutyrate dehydrogenase, troponin H, myoglobin), and inflammatory factors.

Eligible participants will be hospitalized for PCI treatment. In the therapy phase, patients will receive PCI for SVGD using drug-eluting stents. Operation notes (operation date, bleeding volume, medication), thrombolysis in myocardial infarction (TIMI) flow, corrected TIMI frame count (CTFC) and adverse events will be recorded in detail.

All subjects will be followed up at 1, 6, 12, 24 and 36 months after surgery, with MACEs and adverse events assessment collected at each time by clinic visits or telephone interview.

The composite primary study endpoint is the incidence of MACEs after PCI for SVGD, including death from cardiac causes, non-fatal myocardial infarction, angina pectoris, target vessel revascularization (TVR) and hospitalization for heart failure.

Secondary endpoints are defined as: (1) the occurrence of the slow/no reflow, which is defined as thrombolysis in myocardial infarction (TIMI) grade 0, 1, or 2 flow within 24 h after SVG-PCI, despite successful treatment of the vessel obstruction; (2) myocardial infarction is defined as the onset of chest pain in combination with new, typical changes in the electrocardiogram and biochemical evidence of myocardial necrosis; (3)TVR is defined as a new revascularization procedure in the target vessel; (4)successful reperfusion is defined as TIMI flow grade 3 and less than 50% residual stenosis of SVG.

We expect CAS of plaque and media 2.9 ± 1.7 mm² among patients with MACEs and 1.9 ± 1.5 mm² among patients without MACEs. It is estimated that the incidence of MACEs is 20% in 3 years after PCI for SVGD. Assuming a 20% drop-out rate, a total of 175 participants are required to provide 80% power, with a two-sided type I error of 0.05.

The first participant was enrolled in July 2017. As of August 2018, 67 participants have been enrolled and recruitment is ongoing in Tianjin Chest Hospital, China. Treatment and follow-up of all participants are planned to continue until December 2021.