Coronary Steal Via Natural Internal Mammary Artery-To-Coronary Artery Bypasses (CIMA)

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.

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).

Study Overview

• Status: Completed
• Conditions: Ischemia; Coronary Artery Disease
• Intervention / Treatment: Other: Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index

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).

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients electively referred for coronary angiography

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Coronary Artery Disease; Patient with significant coronary artery disease	Other: Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index; Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index
No Coronary Artery Disease; Patient without significant coronary artery disease	Other: Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index; Coronary Artery Balloon Occlusion for Determination of Collateral Flow Index

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary collateral function (CFI)	Coronary collateral function (CFI)	Baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Myocardial ischemia during temporary coronary balloon occlusion	Baseline
Proximal IMA pressure immediately before and during (ipsilateral) reactive arm hyperemia.	Baseline
Distal IMA CFI	Baseline

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne

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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ACTUAL): November 1, 2020
• Study Completion (ACTUAL): July 1, 2021

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 5, 2015
• First Posted (ESTIMATE): January 7, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Ischemia; Circulation, Collateral; Internal Mammary-Coronary Artery Anastomosis
• 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: SNCTP000001138; 2631 (Bern University Hospital)