Blood Markers for Inflammation and Coronary Artery Vasoreactivity Testing in Patients With Chest Pain and Normal Coronary Arteries

NCT ID: NCT01162824

Last Updated: 2011-02-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2011-12-31

Brief Summary

The investigators are hoping to discover the cause of chest pain in patients with a normal coronary arteriogram. For patients with chest pain coronary angiography is the standard method by which the blood vessels of the heart can be visualized and any narrowing can be assessed. In some cases the investigators find totally normal coronary blood vessels or only minor disease. Such a finding is associated with an excellent long term prognosis. However, as a large proportion of patients with normal coronary arteries or mild coronary narrowings often continue to experience recurrent chest pains the investigators are interested in understanding the mechanisms responsible for this. The investigators hypothesise that in many cases, coronary artery spasms are responsible for the recurrent chest pains. These spasms usually respond to treatment with drugs known as vasodilators. The acetylcholine test (ACH-test) has been recommended by the European Society of Cardiology and the American College of Cardiology as a diagnostic test. This test can reveal whether the coronary blood vessels have a tendency to go into spasm. The investigators plan in this study to carry out the test in patients who have chest pains suggestive of coronary narrowings but are found to have normal or only mildly narrowed coronary arteries on angiography. A positive test -indicating a tendency for spasm- may help guiding therapy with vasodilators, which are often very effective to prevent coronary spasms. The investigators would also like to take blood samples during the test (before and after) from every patient to measure blood markers and see if there is a relation between these markers and the result of the ACH-test.

Detailed Description

This study comprises two parts:

1. Blood sample

2. ACH-test (including coronary flow measurements)

Blood will be taken, frozen and stored for up to 5 years. The following markers will be studied: C-reactive protein, E-selectin, neopterin, troponin and CD40 ligand. These are essential biochemical markers or so called pro-inflammatory substances that normally circulate in the blood but their levels can increase under certain conditions such as stress or inflammation. In addition, expansion of CD4+CD28null T-cells will be measured via flow cytometry.

Coronary angiography will be performed according to routine clinical guidelines. If the investigators find severe disease standard treatment procedures will take place and the investigators will only ask for a blood sample. If the investigators find normal coronary arteries on coronary angiography the investigators will conduct the ACH-test as part of the study. After injecting ACH into the coronary arteries narrowing can occur and provoke the same or similar symptoms as at home (i.e. chest pain). If you experience severe pain the investigators will inject a drug called nitroglycerine to relieve the pain. Then the investigators will measure the capacity of the blood vessels to dilate with a special catheter. The whole procedure including coronary angiography and ACH-test will last for about one hour. There is only very little radiation needed for the ACH-test which is unlikely to cause any health problems (~2.4mSv). In some very rare cases chest pain can be prolonged and heart rhythm disorders can occur. In worst case prolonged narrowing can lead to a heart attack (myocardial infarction, < 1%).

The result of the ACH-test can lead to 3 different results.

1. Epicardial coronary spasm. This means that the narrowing of the blood vessel occurs in a place where it can be seen on the screen during angiography.

2. Microvascular dysfunction This means that the narrowing of the blood vessel cannot be seen on the screen but on the ECG. It only affects the very small blood vessels of the heart.

3. Normal ACH-test This means that the test is normal and the patient has no chest pain during the test and also no narrowing.

Depending on the result the investigators will suggest to start with a medication according to current guidelines and inform the patient's GP about the results and further suggestions for treatment. To maintain confidentiality all participants are entered onto our secure database using only their initials and a study number.

Conditions

Endothelial Dysfunction; Atherosclerosis; Inflammation; Myocardial Ischemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

No endothelial dysfunction

Group Type: OTHER

Acetylcholine

Intervention Type: DRUG

Incremental doses of 2, 20 and 100 µg of ACH will be injected into the left coronary artery (LCA) via the diagnostic catheter for 3 minutes each. After that 80 µg of ACH will be injected into the right coronary artery. Coronary angiography will be performed after each 3 minute dose period. After the test or when intolerable chest pain due to coronary spasm occurs, 0.2 mg of glyceryltrinitrate will be injected into each vessel. During the test, heart rate, blood pressure and ECG will be monitored continuously.

Adenosine

Intervention Type: DRUG

Coronary blood flow velocity measurements will be performed in the mid segment of the left anterior descending artery with a 0.014-in intracoronary Doppler guidewire connected to the corresponding interface. Measurements will be obtained after the administration of nitroglycerin, at baseline and during maximal hyperaemia. Sustained intravenous administration of adenosine - an arteriolar vasodilator- will be used to induce maximal hyperaemia (140-180µg/kg/min).

Endothelial Dysfunction

Definition of abnormal epicardial and microvascular vasoreactivity Abnormal epicardial vasoreactivity is defined as a reduction of the baseline coronary diameter ≥75% after glyceryltrinitrate i.c. together with a reproduction of the angina symptoms reported by the patient and/or ischemic ECG-changes. Abnormal microvascular vasoreactivity is defined as the reproduction of the angina symptoms together with ischaemic ECG-changes, but without changes in epicardial vasomotion.

Group Type: OTHER

Acetylcholine

Intervention Type: DRUG

Incremental doses of 2, 20 and 100 µg of ACH will be injected into the left coronary artery (LCA) via the diagnostic catheter for 3 minutes each. After that 80 µg of ACH will be injected into the right coronary artery. Coronary angiography will be performed after each 3 minute dose period. After the test or when intolerable chest pain due to coronary spasm occurs, 0.2 mg of glyceryltrinitrate will be injected into each vessel. During the test, heart rate, blood pressure and ECG will be monitored continuously.

Adenosine

Intervention Type: DRUG

Coronary blood flow velocity measurements will be performed in the mid segment of the left anterior descending artery with a 0.014-in intracoronary Doppler guidewire connected to the corresponding interface. Measurements will be obtained after the administration of nitroglycerin, at baseline and during maximal hyperaemia. Sustained intravenous administration of adenosine - an arteriolar vasodilator- will be used to induce maximal hyperaemia (140-180µg/kg/min).

Interventions

Acetylcholine

Incremental doses of 2, 20 and 100 µg of ACH will be injected into the left coronary artery (LCA) via the diagnostic catheter for 3 minutes each. After that 80 µg of ACH will be injected into the right coronary artery. Coronary angiography will be performed after each 3 minute dose period. After the test or when intolerable chest pain due to coronary spasm occurs, 0.2 mg of glyceryltrinitrate will be injected into each vessel. During the test, heart rate, blood pressure and ECG will be monitored continuously.

Intervention Type: DRUG

Adenosine

Coronary blood flow velocity measurements will be performed in the mid segment of the left anterior descending artery with a 0.014-in intracoronary Doppler guidewire connected to the corresponding interface. Measurements will be obtained after the administration of nitroglycerin, at baseline and during maximal hyperaemia. Sustained intravenous administration of adenosine - an arteriolar vasodilator- will be used to induce maximal hyperaemia (140-180µg/kg/min).

Intervention Type: DRUG

Other Intervention Names

Acetylcholine will be used from Miochol-E (Novartis)

Eligibility Criteria

Inclusion Criteria

• Adults of either gender > 35 years of age with a stable pattern of angina pectoris suggestive of coronary artery disease, with positive responses to exercise stress testing AND/OR patients with chest pain and ischaemic ST-segment changes during pain (previous obstructive coronary artery disease with or without stent-implantation will be allowed).
• Subjects will be invited to participate only if investigations have been undertaken to rule out non-cardiac causes for chest pain (i.e. oesophageal and musculoskeletal) previously.
• Serum creatinine < 123.7µmol/L.
• Left ventricular ejection fraction > 50%.

Exclusion Criteria

• Chronic obstructive pulmonary disease.
• Cardiomyopathy.
• Severe valvular heart disease.
• Myocardial infarction within the last 3 months.
• Pregnant or lactating women.

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St George's Healthcare NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Department of Cardiology, St George's Healthcare NHS Trust

Principal Investigators

Juan C Kaski, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology, St George's Healthcare NHS Trust

Locations

Department of Cardiology, St George's Healthcare NHS Trust

London, England, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Peter E Ong, MD

Role: CONTACT

pong@sgul.ac.uk

+44208725 ext. 2628

Juan C Kaski, MD

Role: CONTACT

jkaski@sgul.ac.uk

+44208725 ext. 2628

Facility Contacts

Peter E Ong, MD

Role: primary

pong@sgul.ac.uk

+44208725 ext. 2628

Other Identifiers

ACOVA-8

Identifier Type: -

Identifier Source: org_study_id