Abnormal Coronary Vasomotion in Patients With Suspected Coronary Artery Disease (CAD) (ACOVA)

Abnormal Coronary Vasomotion in Patients With Suspected CAD But Normal Coronary Arteries

In patients with chest pain and/or shortness of breath coronary artery disease (CAD) is suspected depending on the pattern of symptoms and the electrocardiogram (ECG). Coronary angiography is the method of choice to verify this suspicion. If the patient coronary arteries on coronary angiography are totally normal or unobstructed, one can only speculate if the patients' discomfort is from the heart or not. A possibility to get further information about the healthiness of the coronary arteries is the acetylcholine test (ACH-test). When injecting this natural, body produced-substance into the coronary arteries one can test if the vessels develop coronary spasm which can be the reason for the patient's symptoms. The investigators therefore use this test in this study to look for coronary spasm in patients with suspected CAD but normal/unobstructed coronary arteries. In case of a positive test, the patient profits from having found a cause for his/her symptoms making treatment with special tablets possible. Furthermore, the investigators want to analyze blood samples of every patient to look for signs of inflammation, vasoconstriction and genetic variants that seem to be linked with coronary spasms. On the basis of these results the ACH-test could probably be avoided in the future.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Coronary Vasospasm; Microvascular Angina
• Intervention / Treatment: Other: Intracoronary acetylcholine provocation test

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Ong, MD; Phone Number: +4971181015449; Email: petereong@gmail.com
• Study Contact Backup: Name: Andreas Seitz, MD; Phone Number: +4971181015585

Study Locations

• Germany
  • Stuttgart, Germany, 70376
    • Recruiting
    • Robert Bosch Medical Center
    • Contact: Peter Ong, MD; Phone Number: +4971181016048; Email: petereong@gmail.com
    • Contact: Anastasios Athanasiadis, MD; Phone Number: +4971181015444

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults between 35 and 95 years old with angina pectoris and/or dyspnea suggestive of coronary artery disease with non-invasive proof of coronary ischemia or high pre-test probability for CAD who will be referred for coronary angiography
• Serum creatinine < 1,4 md/dl
• Left ventricular ejection fraction > 50%

Exclusion Criteria:

• Patients under 35 years and above 95 years of age
• Severe chronic obstructive pulmonary disease (contraindication for acetylcholine-testing)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CAD; Patients admitted with suspicion of CAD and proof of CAD after coronary angiography.
Experimental: No-CAD; Patients admitted with suspicion of CAD but without proof of CAD after coronary angiography will undergo intracoronary acetylcholine provocation test.	Other: Intracoronary acetylcholine provocation test; Intracoronary provocation of coronary spasm with acetylcholine in augmented dosages of 2 µg, 20 µg, 100 µg and 200 µg non-selectively in the LCA as well as 80 µg in the RCA. During the procedure, a 12 channel ECG will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
all cause mortality (cardiac vs. non-cardiac)	12-120 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Angina pectoris, repeated angiography, re-admissions for angina pectoris	12-120 months

Collaborators and Investigators

• Sponsor: Peter Ong, MD
• Collaborators: Deutsche Stiftung für Herzforschung
• Investigators: Principal Investigator: Peter Ong, MD, Robert Bosch Medical Center; Study Chair: Andreas Seitz, MD, Robert Bosch Medical Center; Study Director: Udo Sechtem, MD, Robert Bosch Medical Center

Publications and helpful links

General Publications

• Ong P, Athanasiadis A, Borgulya G, Mahrholdt H, Kaski JC, Sechtem U. High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries). J Am Coll Cardiol. 2012 Feb 14;59(7):655-62. doi: 10.1016/j.jacc.2011.11.015.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: June 8, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (Estimated): June 16, 2009

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Acetylcholine
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Angina Pectoris; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Microvascular Angina; Coronary Vasospasm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Cholinergic Agents; Cholinergic Agonists; Acetylcholine
• Other Study ID Numbers: ACOVA-1; ACOVA-2 (Other Identifier: internal)