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Coronary Artery DiseaseCIMANCT02332564

Coronary Steal Via Natural Internal Mammary Artery-To-Coronary Artery Bypasses

An observational study of Coronary Artery Disease and Ischemia, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

CORONARY ARTERY DISEASE AND THE BENEFIT OF BYPASSES Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally. In industrialized countries, coronary artery disease (CAD) is the leading cause of death, consequence of myocardial infarction (MI). Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Coronary Artery Disease, Ischemia
What is being tested?
Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index
How many people
40 participants
Where
1 siteSwitzerland
Study dates
Dec 2014to Jul 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Patients electively referred for coronary angiography

Who may be able to join

  • Age > 18 years
  • Referred for elective coronary angiography
  • Written informed consent to participate in the study

Who cannot join

  • Acute coronary syndrome; unstable cardiopulmonary conditions
  • Severe cardiac valve disease
  • Congestive heart failure NYHA III-IV
  • Prior coronary artery bypass surgery / prior cardiac surgery
  • 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
  • Pregnancy

Trial locations and contacts

1 site in 1 country.

Switzerland1 site
  • Bern University Hospital

    Bern, 3010

Other trials in Switzerland

About this study

CORONARY ARTERY DISEASE AND THE BENEFIT OF BYPASSES

Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally. In industrialized countries, coronary artery disease (CAD) is the leading cause of death, consequence of myocardial infarction (MI). Artificial - or natural - bypasses 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. In patients with chronic CAD, sufficient coronary collaterals have been shown to confer a significant benefits in terms of overall mortality and cardiovascular events.

Read more

EXTRACARDIAC-TO-CORONARY COLLATERAL SUPPLY

Commonly, coronary collaterals are implicitly understood to exist between coronary artery branches. However, the structural existence of coronary collaterals with an extracardiac connection has been confirmed by anatomical investigations. Pathophysiologically and with regard to a potential for arteriogenic stimulation, the connections from the internal mammary arteries, are of special interest.

In a recently published work the investigators have investigated the effect of temporary balloon occlusion of the distal IMA on coronary collateral function. There were equivocal findings for the left circumflex coronary artery: CFI was increased by ipsilateral IMA occlusion, but the level of myocardial ischemia was unchanged.

MYOCARDIAL STEAL VIA INTERNAL MAMMARY ARTERIES

In the investigators' previous study, the coronary occlusion with simultaneous distal IMA occlusion was always performed first as a conservative measure against false-positive detection of internal-mammary-to-coronary artery connections. Repetitive coronary occlusions per se result in higher collateral flow by collateral recruitment and reduced ischemia by ischemic preconditioning and augmented collateral function. Conversely, the sensitivity of the employed method was reduced and might have contributed to the equivocal findings in case of the left circumflex artery. Moreover, the hypothesize d mechanism of localized pressure augmentation was not investigated.

This study aims to further characterize the prevalence and function of natural ipsilateral IMA-to-coronary connections, as well as to investigate the hemodynamic mechanisms of coronary collateral function augmentation by distal IMA occlusion. In the investigators' last study, the increased coronary collateral function in response to manipulation of a potential coronary collateral donor (in this case, the IMA) was taken as indirect evidence for the existence of IMA-to-coronary-artery connections. Thus, the employed distal IMA occlusion served as a positive stimulus. Conceptually, additional evaluation with a negative stimulus could heighten the discriminatory power of the investigation. This could be in the form of a hyperemic stimulus affecting the collateral donor, ie in analogy to myocardial or coronary steal (ie, a reduction in coronary collateral supply to a collateral recipient).

Read the 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. In industrialized countries, coronary artery disease (CAD) is the leading cause of death, consequence of myocardial infarction (MI).

In patients with acute coronary syndrome, percutaneous coronary intervention (PCI) has been shown to improve outcomes.2 However, in stable CAD, PCI has not been demonstrated to reduce the incidence of myocardial infarction or death. Coronary artery bypass grafting (CABG) was superior to PCI in patients with diabetes and multivessel coronary artery disease. CABG significantly reduced rates of death and myocardial infarction compared to PCI, but with a higher rate of stroke. Furthermore, in patients with advanced coronary artery disease, rates of myocardial infarction were more than 60% lower with CABG compared to PCI.

Conceptually, the benefit of CABG over PCI is not surprising as PCI targets significant coronary lesions thought to be responsible for causing ischemia. However, the deleterious effects of atherosclerosis are not typically preceded by significant luminal vascular narrowing. The vulnerable plaque eventually becoming the culprit plaque (causing myocardial infarction or sudden cardiac death) is typically relatively nonstenotic. Furthermore, due to being multifocal and widespread, plaque vulnerability is not a target for, nor amenable to PCI.

Conversely, artificial - or natural - bypasses 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. In patients with chronic CAD, sufficient coronary collaterals have been shown to confer a significant benefits in terms of overall mortality and cardiovascular events.

EXTRACARDIAC-TO-CORONARY COLLATERAL SUPPLY

Commonly, coronary collaterals are implicitly understood to exist between coronary artery branches. However, the structural existence of coronary collaterals with an extracardiac connection has been confirmed by anatomical investigations. Pathophysiologically and with regard to a potential for arteriogenic stimulation, the connections from the internal mammary arteries, are of special interest. Indeed, before the advent of coronary bypass surgery, several clinical studies examined the usefulness of a minimally invasive surgery to augment collateral flow to the heart via these internal-mammary-to-coronary-artery connections in patients with angina pectoris. The performed distal bilateral ligation of the internal mammary arteries was thought to improve flow over naturally pre-existing anastomoses between the internal mammary arteries and the coronary circulation.

In a recently published work the investigators have investigated the effect of temporary balloon occlusion of the distal IMA on coronary collateral function. 180 pairs of measurements were performed in 120 patients electively referred for coronary angiography. 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, determined by collateral flow index (CFI) was consistently increased by ipsilateral, but not contralateral IMA balloon occlusion in the left anterior descending (LAD) coronary artery and the right coronary artery (RCA). Furthermore, these findings were corroborated by the observed reduction in ischemia as assessed by the sensitive tool of intracoronary ECG. However, there were equivocal findings for the left circumflex coronary artery: CFI was increased by ipsilateral IMA occlusion, but the level of myocardial ischemia was unchanged.

MYOCARDIAL STEAL VIA INTERNAL MAMMARY ARTERIES

In the investigators' previous study, the coronary occlusion with simultaneous distal IMA occlusion was always performed first as a conservative measure against false-positive detection of internal-mammary-to-coronary artery connections. Repetitive coronary occlusions per se result in higher collateral flow by collateral recruitment and reduced ischemia by ischemic preconditioning and augmented collateral function. Conversely, the sensitivity of the employed method was reduced and might have contributed to the equivocal findings in case of the left circumflex artery. Moreover, the hypothesize d mechanism of localized pressure augmentation was not investigated.

This study aims to further characterize the prevalence and function of natural ipsilateral IMA-to-coronary connections, as well as to investigate the hemodynamic mechanisms of coronary collateral function augmentation by distal IMA occlusion. In the investigators' last study, the increased coronary collateral function in response to manipulation of a potential coronary collateral donor (in this case, the IMA) was taken as indirect evidence for the existence of IMA-to-coronary-artery connections. Thus, the employed distal IMA occlusion served as a positive stimulus. Conceptually, additional evaluation with a negative stimulus could heighten the discriminatory power of the investigation. This could be in the form of a hyperemic stimulus affecting the collateral donor, ie in analogy to myocardial or coronary steal (ie, a reduction in coronary collateral supply to a collateral recipient).

Being tested
Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index
Keywords
Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia
Medical subject headings
Coronary Artery Disease, Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Coronary Artery Balloon Occlusion for Determination of Collateral Flow IndexOther

    Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index

Study groups in NCT02332564
Study groupRoleWhat they receive
Coronary Artery DiseasePatient with significant coronary artery disease
Receives: Other: Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index
No Coronary Artery DiseasePatient without significant coronary artery disease
Receives: Other: Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Coronary collateral function (CFI)

    Coronary collateral function (CFI)

    Measured: Baseline

Secondary outcomes (3)
  1. Myocardial ischemia during temporary coronary balloon occlusion

    Measured: Baseline

  2. Proximal IMA pressure immediately before and during (ipsilateral) reactive arm hyperemia.

    Measured: Baseline

  3. Distal IMA CFI

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2015 (estimated)
  2. Study startDec 2014
  3. Primary completionNov 2020
  4. Study completionJul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02332564
Sponsor's protocol ID
SNCTP000001138
Other IDs
2631
Acronym
CIMA
Status last verified
Feb 2023
First submitted
5 Jan 2015
Last updated
14 Feb 2023
Results posted
No
Data monitoring committee
No

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.

    PubMed 24744276
  • 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.

    PubMed 13801236
  • Bigler MR, Buffle E, Stoller M, Grossenbacher R, Tschannen C, Seiler C. Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis. J Appl Physiol (1985). 2021 Sep 1;131(3):905-913. doi: 10.1152/japplphysiol.00082.2021. Epub 2021 Jul 8.

    PubMed 34236245

Questions about this trial

What is this clinical trial studying?

An observational study of Coronary Artery Disease and Ischemia, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Coronary collateral function (CFI) (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02332564, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023.

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