Effect of Permanent Internal Mammary Artery Occlusion on Extracardiac Coronary Collateral Supply (IMAO)

May 10, 2016 updated by: University Hospital Inselspital, Berne

Coronary artery disease and the benefit of bypasses:

Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive.

Durable promotion of coronary collateral circulation:

Before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural IMA-to-coronary artery bypasses and their anti-ischemic effect has - for the first time - been recently demonstrated by our research group. The acute functional changes observed in response to temporary distal IMA balloon occlusion are expected to result in larger chronic structural adaptations of the IMA-to-coronary-artery connections when the distal IMA is permanently occluded. In contrast to the previously employed arteriogenic approaches in humans, the attractiveness of such an intervention lies in the potential durability of the effect.

In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Coronary artery disease and the benefit of bypasses:

Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Although widely used in stable CAD, percutaneous coronary intervention (PCI) has not been shown to reduce the incidence of myocardial infarction or death. In contrast, coronary artery bypass grafting (CABG) significantly reduced rates of death and myocardial infarction compared to PCI. Similarly, coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive.

Durable promotion of coronary collateral circulation:

While a multitude of interventions has been shown to be effective in collateral growth promotion, so far, the effect of current interventions is only temporary and therefore recurrent application is necessary to sustain the level of collaterals. However, before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural IMA-to-coronary artery bypasses and their anti-ischemic effect has - for the first time - been recently demonstrated by our research group. Levels of collateral function and myocardial ischemia were determined during two coronary balloon occlusions, the first with, the second without distal IMA balloon occlusion. Coronary collateral function, was consistently increased in the presence vs the absence of distal ipsilateral IMA balloon occlusion. These findings were corroborated by the observed reduction in ischemia. Conversely, with distal contralateral IMA occlusion, collateral function and ECG signs of ischemia remained unchanged. The acute functional changes observed in response to temporary distal IMA balloon occlusion are expected to result in larger chronic structural adaptations of the IMA-to-coronary-artery connections when the distal IMA is permanently occluded. In contrast to the previously employed arteriogenic approaches in humans, the attractiveness of such an intervention lies in the potential durability of the effect.

In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Bern University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 years
  • Referred for elective coronary angiography
  • Written informed consent to participate in the study
  • Significant stenosis of right coronary artery (FFR ≤0.80)

Exclusion Criteria:

  • Acute coronary syndrome; unstable cardiopulmonary conditions, unstable angina pectoris
  • Collateral flow index of right IMA <0.25
  • Severe cardiac valve disease
  • Congestive heart failure NYHA III-IV
  • Prior coronary artery bypass surgery / prior cardiac surgery
  • Coronary artery disease best treated by coronary artery bypass grafting
  • Coronary artery disease unsuitable for intracoronary pressure measurements
  • Prior Q-wave myocardial infarction in the vascular territory undergoing collateral function determination
  • Severe renal or hepatic failure
  • Women of childbearing age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Interventional Study Arm
In the presence of a significant right coronary artery stenosis, catheter-based occlusion of the right IMA distal to the take-off of the pericardio-phrenic branch is performed at baseline using a dedicated occlusion device (Amplatzer vascular plug).
Device: Amplatzer vascular plug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in right coronary Collateral Flow Index (CFI)
Time Frame: Follow-up (week 6)
Change from baseline in right coronary Collateral Flow Index (CFI) at follow-up (week 6) vs baseline
Follow-up (week 6)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in left coronary CFI
Time Frame: Follow-up (week 6)
Change from baseline in left coronary CFI at follow-up (week 6) vs baseline
Follow-up (week 6)
Change from baseline in intracoronary and surface ECG ST-segment shift during temporary right and left coronary balloon occlusion
Time Frame: Follow-up (week 6)
Change from baseline in intracoronary and surface ECG ST-segment shift during temporary right and left coronary balloon occlusion at follow-up (week 6) vs baseline
Follow-up (week 6)
Number of patients with angiographic visibility of right IMA-to-coronary anastomoses
Time Frame: Follow-up (week 6)
Angiographic visibility of right IMA-to-coronary anastomoses at follow-up
Follow-up (week 6)
Number of patients with catheter-based permanent right IMA occlusion
Time Frame: Baseline, Follow-up (week 6)
Baseline, Follow-up (week 6)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Investigators

  • Principal Investigator: Seiler Christian, MD, Prof, Bern University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

January 5, 2015

First Submitted That Met QC Criteria

June 15, 2015

First Posted (Estimate)

June 18, 2015

Study Record Updates

Last Update Posted (Estimate)

May 12, 2016

Last Update Submitted That Met QC Criteria

May 10, 2016

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SNCTP000000901

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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