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

Phase 1
Completed
Conditions
Circulation, Collateral
Coronary Artery Disease
Internal Mammary-Coronary Artery Anastomosis
Ischemia
Interventions
Device: Amplatzer vascular plug
Registration Number
NCT02475408
Lead Sponsor
Insel Gruppe AG, University Hospital Bern
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Interventional Study ArmAmplatzer vascular plugIn 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).
Primary Outcome Measures
NameTimeMethod
Change from baseline in right coronary Collateral Flow Index (CFI)Follow-up (week 6)

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

Secondary Outcome Measures
NameTimeMethod
Change from baseline in left coronary CFIFollow-up (week 6)

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 occlusionFollow-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

Number of patients with angiographic visibility of right IMA-to-coronary anastomosesFollow-up (week 6)

Angiographic visibility of right IMA-to-coronary anastomoses at follow-up

Number of patients with catheter-based permanent right IMA occlusionBaseline, Follow-up (week 6)

Trial Locations

Locations (1)

Bern University Hospital

🇨🇭

Bern, Switzerland

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