Study of the Vascular Response to Percutaneous Coronary Intervention in Patients With Non-ST-elevation Acute Coronary Syndromes Using Intravascular Blood Sampling (IN HEART)

This clinical protocol will be subject to peer review according to standard local procedures, including independent scientific review by the Scientific Advisory Board of the Clinical Research Facility, Sheffield Teaching Hospitals NHS Foundation Trust; the Clinical Research Office, Sheffield Teaching Hospitals NHS Foundation Trust; and the Research Ethics Committee. The study will be a single-centre study including use of a CE-marked medical device to obtain samples, conducted at Cardiology and Cardiothoracic Surgery Directorate, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust.

Patients with a diagnosis of NSTE-ACS, receiving DAPT with a combination of aspirin and ticagrelor or prasugrel, and listed either for coronary angiography with the intention of proceeding to PCI or for PCI following coronary angiography at a referring hospital, will be approached and their informed consent sought for this study. 18 patients found to have culprit significant proximal epicardial coronary artery stenosis suitable for PCI, meeting all the inclusion and exclusion criteria, will proceed to have platelet function testing and LBS measurements. Blood will be taken from the arterial sheath or guide catheter and baseline platelet function testing will be performed (VerifyNow P2Y12 assay; light transmittance aggregometry with ADP and arachidonic acid as agonists; and serum thromboxane B2 assay). Balloon predilatation prior to stent deployment will be a mandatory requirement for the study. Following balloon predilatation, the LBS will be deployed across the treated lesion and blood sampling will be performed proximal and distal to the lesion at approximately 5 minutes after predilatation. The following assays will be performed on the sampled blood:

1. Plasma levels of soluble markers of thrombosis and inflammation including prothrombin fragments 1 and 2, fibrinopeptide A, soluble P-selectin and thromboxane B2.
2. Platelet surface P-selectin expression
3. Leukocyte surface CD11b expression Blood taken prior to PCI will also be sent to the local laboratory for measurement of the cardiac-specific marker high-sensitivity troponin T and a further venous blood sample will be collected at 6 hours after PCI to measure any rise in troponin in order to correlate this with thrombin generation. A rise of 5 times the upper limit of normal of troponin following PCI in the context of chest pain or diagnostic ECG changes will be used to define peri-procedural myocardial infarction per the Universal Definition of Myocardial Infarction (Thygesen, Alpert et al. 2012).

OCT of the culprit lesion, as well as the coronary artery proximal and distal to this, will be performed before and after the deployment of the LBS to assess any topographical changes to the vessel wall caused by the LBS and provide information on target lesion morphology.

Clinical outcomes will be reviewed and AEs (including MACE) will be recorded at 6 hours, 30 days and 6 months after the procedure. At the 6-hour visit, patients will be assessed by a medically-qualified investigator and have a blood sample collected for troponin T level and ECG performed. At the 30-day visit, patients will receive a full clinical assessment by a medically-qualified investigator, have DAPT compliance assessed, be asked about angina intensity, have any MACE or other AEs recorded and have an ECG. A telephone contact will be made at 6 months after PCI to assess any MACE or other AEs, angina intensity and DAPT compliance.