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

NCT01162824 | Unknown

• 1 other identifier: ACOVA-8
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Endothelial Dysfunction; Atherosclerosis; Inflammation; Myocardial Ischemia

Keywords

Endothelial Dysfunction; Microvascular dysfunction; Coronary artery spasm; Inflammation; CD4+CD28null T cells; Myocardial ischemia; Early atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Endothelial Dysfunction

  As this is not a follow-up study, the intracoronary vasoreactivity tests will be conducted at the day of study entry to assess which patient suffers from endothelial dysfunction. According to this result the patients will be divided into two groups (endothelial dysfunction and NO endothelial dysfunction). Definition of endothelial dysfunction: Vasoconstriction of \>75% together with ischemic ECG changes and/or reproduction of angina OR ischemic ECG changes with reproduction of angina without vasoconstriction

  Day 1 (day of study entry)

Study Arms (2)

No endothelial dysfunction

OTHER

Drug: Acetylcholine; Drug: Adenosine

Endothelial Dysfunction

OTHER

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.

Drug: Acetylcholine; Drug: Adenosine

Interventions

Acetylcholine 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.

Also known as: Acetylcholine will be used from Miochol-E (Novartis)

Endothelial Dysfunction; No endothelial dysfunction

Adenosine 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; No endothelial dysfunction

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

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

Sponsors & Collaborators

• St George's Healthcare NHS Trust: lead

Study Sites (1)

Department of Cardiology, St George's Healthcare NHS Trust

London, England, SW17 0RE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Atherosclerosis; Inflammation; Myocardial Ischemia; Coronary Vasospasm

Interventions

Acetylcholine; lactitol; Adenosine

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Coronary Disease

Intervention Hierarchy (Ancestors)

Biogenic Amines; Amines; Organic Chemicals; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Juan C Kaski, MD

  Department of Cardiology, St George's Healthcare NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter E Ong, MD

CONTACT

+44208725; pong@sgul.ac.uk

Juan C Kaski, MD

CONTACT

+44208725; jkaski@sgul.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: July 15, 2010
• Study Start: January 1, 2011
• Primary Completion: April 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 23, 2011

Record last verified: 2011-02

Locations

GB (1)