Analysis of Human Coronary Aspirate

Study Overview
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Brief Summary
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During elective percutaneous coronary intervention (PCI), both proximal and distal protection devices are used. The distal occlusion protection device temporarily occludes the vessel distal to the lesion during the intervention, thereby capturing both particular debris and soluble substances released from the lesion such that they can be aspirated and prevented from reaching the coronary microcirculation. Rather than simply discarding the material which is retrieved from use of protection devices, the investigators have recently taken advantage of this situation, sampled the particulate and soluble material and subjected it to a variety of analyses with the ultimate goal to have a better insight into the respective plaque composition and to correlate it to the individual imaging and clinical data. On the basis of such information the investigators aim to better understand the pathophysiology of plaque vulnerability and to possibly predict the clinical development of the individual patient.

Detailed Description
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Patients Symptomatic patients with a significant stenosis (diameter stenosis >75% or significant FFR) in a native coronary vessel or a saphenous vein aortocoronary bypass graft. All patients are on aspirin (100 mg/day) and received 10,000 I.U. heparin intravenously. Coronary angiography is performed via the femoral approach. Full informed consent are obtained from all patients before participating in the study. Stenosis severity/Plaque composition Quantification of stenosis severity was performed with the use of off-line caliper measurements (QCA-MEDIS, Leiden, NL). Intravascular imaging analyses before and after stent implantation to characterize plaque morphology: IVUS(Eagle-EyeTM 20 MHz catheter and R-100 pullback device, Volcano Corporation, Rancho Cordova, CA, USA) OCT (St. Jude Medical Lightlab C7 Dragonfly Imaging Catheter) NIRS (InfraReDx TVC Insight catheter) Interventional procedure Distal balloon occlusion devices: TriAktiv SVG/3.5-FX-catheter; Kensey Nash, Exton, USA or GuardWire Temporary Occlusion & Aspiration System; Medtronic Inc., Minneapolis, MN USA Implantation of balloon-expandable stents using balloon pressures between 14 and 18 atm and a balloon-to-vessel diameter ratio of 1:1. Coronary arterial blood and coronary aspirate Coronary arterial blood is taken distal to the lesion before stent implantation and coronary aspirate blood is obtained during stent implantation (each in Heparin- or EDTA- Monovettes, SARSTEDT AG & Co, Nümbrecht, Germany). Ex vivo coronary aspirate blood is filtered through a mesh filter with pores of 40 μm diameter. Immediately centrifugation of the filtered coronary arterial and aspirate blood (800g, 10 min, 4°C). Particulate debris and coronary arterial and aspirate plasma are quickly frozen in liquid nitrogen and stored at -80°C until further use. Analysis / Aim : Using different methods for determining severity of stenosis and plaque composition. Using different biochemical methods to characterize particular and soluble substances released during stenting into coronary aspirate. Using different bioassays to study vasoconstrictor potential of human coronary aspirate plasma and the impact. of coronary aspirate on the coronary microcirculation and on cardiac contraction. Correlation of ex vivo measurements with patients disease and clinical symptoms.

Official Title
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Human Coronary Aspirate: Characterization of Particular and Soluble Substances and the Impact on Microvascular Obstruction

Conditions
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Coronary Arteriosclerosis, Coronary Heart Disease, No Reflow Phenomenon

Intervention / Treatment
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* Other: Aspirated Coronary Blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic patients with a significant stenosis (diameter stenosis >75% or significant FFR) in a native coronary vessel or a saphenous vein aortocoronary bypass graft Exclusion Criteria: Patients whereby a distal balloon occlusion devices is not applicable
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aspirate Blood<br> | Other: Aspirated Coronary Blood<br>* Coronary arterial blood is taken distal to the lesion before stent implantation and serve as control and coronary aspirate blood is obtained during stent implantation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of particular and soluble substances released during stenting into coronary aspirate and its vasoconstrictor potential. | biochemical characterization: (quantification (as amount or concentration) of vasoconstrictive substances; cell fragments, proteins and lipids within the aspirate via HPLC, MS, or EIA Kits) in vitro vasoconstriction, coronary microcirculation and cardiac contraction by aspirate (vasoconstriction detected as response of isolated arteries to aspirate normalized to that by KCl in a myograph; coronary microcirculation detected as coronary flow and cardiac contraction as left ventricular pressure within in the in vitro Langendorff heart model) | up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of characteristics of soluble and particular substances within aspirate to characteristics of coronary lesion and/or patients underlying disease | e.g.: concentration of vasoconstrictors to plaque composition; concentration of vasoconstrictors to patient underlying disease; amount of particular debris to plaque composition; amount of particular debris to patient underlying disease | up to three years | 
| Comparison of stenosis severity estimation using QCA and FFR versus IVUS, OCT and NIRS | intra- individual comparison of all parameter for stenosis severity and plaque characterisation | up to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary aspirate blood, particular debris / microemboli, distal occlusion device