Prevalence of Extracardiac Coronary Collateral Supply Via the Internal Mammary Arteries

In contrast to the extensively studied coronary collateral circulation within the heart, clinical attention has been paid only anecdotally to extracardiac-to-coronary anastomoses. Usually this has been in the form of case reports giving account of angiographically visible anastomoses between the coronary circulation and the internal mammary artery (IMA), typically in the presence of a chronic occlusion of a coronary artery. In the anatomical literature,the most common types of extracardiac anastomoses include bronchial-to-coronary-artery and IMA-to-coronary-artery connections. Anastomoses between the IMA and the coronary circulation have been documented to occur in 12% of post-mortem patients with CAD.

Importantly, hitherto existing observations typically have relied on visual methods insensitive for the adequate detection especially of structurally present but poorly functional anastomoses. On a diagnostic coronary angiogram, collaterals are visible only if the recipient vessel is subtotally stenotic or fully occluded, or can be rendered visible during coronary spasm or by temporary balloon occlusion of the recipient artery and simultaneous injection of contrast medium into the other arteries, respectively. Similarly, the macroscopic pathologic postmortem examination is likely to underestimate the true number of extracardiac coronary collaterals.

The purpose of this study is to determine the in vivo prevalence and functional distribution of IMA-to-coronary collateral supply via both the right and the left coronary artery.

Study Overview

• Status: Completed
• Conditions: Ischemia; Coronary Artery Disease; Collateral Circulation
• Intervention / Treatment: Procedure: Coronary Angiography with collateral flow measurements

Detailed Description

Background

Surgical bypass creates an artificial anastomosis between a diseased coronary artery and an extracardiac vessel. Often one of the internal mammary arteries (IMA) is used for this procedure. These connections have been very rarely described to occur naturally, representing extracardiac coronary collaterals.

In contrast to the extensively studied coronary collateral circulation within the heart, clinical attention has been paid only anecdotally to extracardiac-to-coronary anastomoses. Usually this has been in the form of case reports giving account of angiographically visible anastomoses between the coronary circulation and the internal mammary artery (IMA), typically in the presence of a chronic occlusion of a coronary artery. In the anatomical literature,the most common types of extracardiac anastomoses include bronchial-to-coronary-artery and IMA-to-coronary-artery connections. Anastomoses between the IMA and the coronary circulation have been documented to occur in 12% of post-mortem patients with CAD.

Importantly, hitherto existing observations typically have relied on visual methods insensitive for the adequate detection especially of structurally present but poorly functional anastomoses. On a diagnostic coronary angiogram, collaterals are visible only if the recipient vessel is subtotally stenotic or fully occluded, or can be rendered visible during coronary spasm or by temporary balloon occlusion of the recipient artery and simultaneous injection of contrast medium into the other arteries, respectively. Similarly, the macroscopic pathologic postmortem examination is likely to underestimate the true number of extracardiac coronary collaterals.

When present, pre-existing connections between the IMA and the coronary circulation could be promoted to serve as natural bypasses to diseased coronary arteries. Promotion of extracardiac blood flow to the coronary circulation has very rarely already been attempted in the past. In a minimally invasive intervention, bilateral surgical ligation of both IMA was performed in a few patients, resulting in clinical improvement and disappearance of angina. However, with the advent of coronary surgery, efforts aimed at promotion of naturally existing bypasses have been abandoned for the placing of artificially created extracardiac anastomoses to the coronary circulation.

Yet with the limitations of these established revascularization interventions becoming clear, the need to search for alternative treatment options gets evident. Therapeutic arteriogenesis with promotion of naturally existing bypasses between the coronary circulation and the internal mammary arteries presents a future possibility.

Objective

The purpose of this study is to determine the in vivo prevalence and functional distribution of IMA-to-coronary collateral supply via both the right and the left coronary artery.

Methods

Comparative observational study with CFI measurements in the IMAs (proximal IMA occlusion) and in the coronary circulation (distal IMA occlusion), and IMA angiography during distal IMA occlusion.

Study Protocol

• Diagnostic coronary angiography and LV angiography
• Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate
• Right and left IMA CFI during a 1-minute ostial vessel occlusion
• Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.
• IMA angiography (left and right) during distal IMA and coronary occlusion.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Cardiology, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients electively referred for coronary angiography

Description

Inclusion Criteria:

• age > 17 years
• electively referred for coronary angiography
• written informed consent to participate in the study

Exclusion Criteria

• Acute coronary syndrome
• Prior coronary artery bypass grafting
• Severe cardiac valve disease
• Congestive heart failure NYHA III-IV
• Severe pulmonary artery hypertension
• Severe hepatic or renal failure (creatinine clearance < 15ml/min)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; CAD	Procedure: Coronary Angiography with collateral flow measurements; Diagnostic coronary angiography and LV angiography; Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate; Right and left IMA CFI during a 1-minute ostial vessel occlusion; Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.; IMA angiography (left and right) during distal IMA and coronary occlusion.
2; no CAD	Procedure: Coronary Angiography with collateral flow measurements; Diagnostic coronary angiography and LV angiography; Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate; Right and left IMA CFI during a 1-minute ostial vessel occlusion; Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.; IMA angiography (left and right) during distal IMA and coronary occlusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Coronary Collateral Flow Index (CFI)	during coronary artery balloon occlusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Intra-coronary occlusive ECG ST segment shift (mV)	at 1 minute of coronary artery balloon occlusion
angiographic visibility of coronary collateral supply via the internal mammary artery during their distal balloon occlusion	at 1 minute of coronary artery balloon occlusion

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Christian Seiler, MD Prof, Department of Cardiology, Bern University Hospital

Publications and helpful links

General Publications

• Stoller M, de Marchi SF, Seiler C. Function of natural internal mammary-to-coronary artery bypasses and its effect on myocardial ischemia. Circulation. 2014 Jun 24;129(25):2645-52. doi: 10.1161/CIRCULATIONAHA.114.008898. Epub 2014 Apr 17.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: August 28, 2012
• First Submitted That Met QC Criteria: August 28, 2012
• First Posted (Estimate): August 30, 2012

Study Record Updates

• Last Update Posted (Estimate): January 16, 2014
• Last Update Submitted That Met QC Criteria: January 15, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: coronary artery disease; coronary collateral circulation; internal mammary artery; extracardiac coronary collaterals; coronary circulation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia
• Other Study ID Numbers: 007/12