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

Primary Purpose

Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis

Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Amplatzer vascular plug
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Circulation, Collateral focused on measuring Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Bern University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interventional Study Arm

Arm Description

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).

Outcomes

Primary Outcome Measures

Change from baseline in right coronary Collateral Flow Index (CFI)
Change from baseline in right coronary Collateral Flow Index (CFI) at follow-up (week 6) vs baseline

Secondary Outcome Measures

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

Full Information

First Posted
January 5, 2015
Last Updated
May 10, 2016
Sponsor
Insel Gruppe AG, University Hospital Bern
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1. Study Identification

Unique Protocol Identification Number
NCT02475408
Brief Title
Effect of Permanent Internal Mammary Artery Occlusion on Extracardiac Coronary Collateral Supply
Acronym
IMAO
Official Title
Effect of Permanent Internal Mammary Artery Occlusion on Extracardiac Coronary Collateral Supply
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia
Keywords
Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interventional Study Arm
Arm Type
Experimental
Arm Description
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).
Intervention Type
Device
Intervention Name(s)
Amplatzer vascular plug
Primary Outcome Measure Information:
Title
Change from baseline in right coronary Collateral Flow Index (CFI)
Description
Change from baseline in right coronary Collateral Flow Index (CFI) at follow-up (week 6) vs baseline
Time Frame
Follow-up (week 6)
Secondary Outcome Measure Information:
Title
Change from baseline in left coronary CFI
Description
Change from baseline in left coronary CFI at follow-up (week 6) vs baseline
Time Frame
Follow-up (week 6)
Title
Change from baseline in intracoronary and surface ECG ST-segment shift during temporary right and left coronary balloon occlusion
Description
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
Time Frame
Follow-up (week 6)
Title
Number of patients with angiographic visibility of right IMA-to-coronary anastomoses
Description
Angiographic visibility of right IMA-to-coronary anastomoses at follow-up
Time Frame
Follow-up (week 6)
Title
Number of patients with catheter-based permanent right IMA occlusion
Time Frame
Baseline, Follow-up (week 6)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seiler Christian, MD, Prof
Organizational Affiliation
Bern University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bern University Hospital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
24744276
Citation
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.
Results Reference
background
PubMed Identifier
6025072
Citation
Moberg A. Anastomoses between extracardiac vessels and coronary arteries. II. Via internal mammary arteries. Post-mortem angiographic study. Acta Radiol Diagn (Stockh). 1967 May;6(3):263-72. doi: 10.1177/028418516700600306. No abstract available.
Results Reference
background
PubMed Identifier
13801236
Citation
BLAIR CR, ROTH RF, ZINTEL HA. Measurement of coronary artery blood-flow following experimental ligation of the internal mammary artery. Ann Surg. 1960 Aug;152(2):325-9. doi: 10.1097/00000658-196008000-00018. No abstract available.
Results Reference
background
PubMed Identifier
28566292
Citation
Stoller M, Seiler C. Effect of Permanent Right Internal Mammary Artery Closure on Coronary Collateral Function and Myocardial Ischemia. Circ Cardiovasc Interv. 2017 Jun;10(6):e004990. doi: 10.1161/CIRCINTERVENTIONS.116.004990.
Results Reference
derived

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

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