Effects of Coronary Sinus Occlusion on Myocardial Ischemia (Pilot Study)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01625832
First received: June 15, 2012
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in industrialized countries despite advances in medical, interventional, and surgical revascularization therapies. In both, acute myocardial infarction (AMI) and chronic stable disease, standard therapeutic approaches may fail to restore tissue perfusion. Indeed, a substantial number of chronic CAD patients may not be amenable to standard revascularization therapies or percutaneous coronary intervention (PCI) may fail to restore coronary artery patency following an acute vessel occlusion (no-reflow phenomenon, microvascular obstruction). As a consequence, the long pursued strategy of augmenting myocardial perfusion by diverting blood from the coronary venous system to an ischemic region (venous retroperfusion) has again gained attention during recent years. Occlusion of the coronary sinus (CSO) was introduced to provide retroperfusion by transient augmentation of coronary venous pressure. Different devices using CSO have been invented and evaluated in animal models and small clinical trials, e.g. intermittent CSO (ICSO) and pressure-controlled intermittent CSO (PICSO) which seem to be effective for myocardial salvage. However, they are not yet employed in clinical routine, and importantly, the exact underlying mechanisms by which retroperfusion due to CSO may reduce myocardial ischemia are not yet understood.

As "natural bypasses", coronary collaterals are anastomoses without an intervening capillary bed between portions of the same coronary artery or between different coronary arteries that represent an alternative source of blood supply to a myocardial area jeopardized by ischemia. Collaterals of the heart can be assessed quantitatively by coronary pressure measurements, which have become the gold standard (collateral flow index, CFI=[Poccl-CVP]/[Pao-CVP]). Theoretically, augmentation of coronary sinus pressure by CSO with an increase of venous backflow reaches the upstream collateral circulation, which in turn could lead to improved collateral flow from non-ischemic area(s) to an occluded, ischemic myocardial region by upstream flow diversion. On the other hand, when considering the formula to calculate pressure-derived CFI, it seems that augmentation of coronary back pressure would rather impair collateral flow (since central venous pressure is coronary sinus pressure). However, the regional effect of a global increase in coronary sinus pressure is unlikely to be as uniform as the above formula implies, i.e., the response is more pronounced in some than in other vascular territories. In experimental studies using dogs (with abundant collaterals), elevation of coronary sinus pressure caused an augmentation of regional myocardial blood flow in the collateralized area. In contrast, when ICSO was performed in pigs (which possess no preformed collaterals), it increased the pressure distal of an occluded LAD but did not improve blood flow or left ventricular function.

In conclusion, experimental studies and pathophysiologic considerations suggest a necessary role of the collateral circulation for the beneficial effects of coronary sinus occlusion (CSO) observed in animals and humans; however, no clinical data are available so far on the effect of CSO on myocardial ischemia in the presence of varying collateral flow.

Study hypotheses

  1. CSO decreases intra-coronary ECG ST-segment elevation during a 2-minute coronary occlusion.
  2. The decrease in occlusive intra-coronary ECG ST elevation during CSO is directly proportional to CFI.
  3. Coronary sinus oxygen saturation during coronary occlusion with CSO is directly proportional to CFI.

Condition Intervention
Coronary Artery Disease
Coronary Sinus
Circulation, Collateral
Ischemia
Collateral Flow Index
Procedure: intermittent coronary sinus occlusion

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of Coronary Sinus Occlusion on Myocardial Ischemia (Pilot Study)

Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Intra-coronary occlusive ECG ST-segment elevation (mV; 2-minute occlusion). [ Time Frame: at 2-minute coronary artery occlusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Collateral flow index (CFI as obtained during coronary sinus patency) [ Time Frame: at 2-minute coronary artery occlusion ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: September 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CSO first
Procedure: intermittent coronary sinus occlusion
Patients undergo two 2-minute coronary balloon occlusions. Patients are randomized to CSO first or CSO second.
Experimental: 2
CSO second
Procedure: intermittent coronary sinus occlusion
Patients undergo two 2-minute coronary balloon occlusions. Patients are randomized to CSO first or CSO second.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 17 years
  • Stable angina pectoris, patient electively referred for coronary angiography
  • Written informed consent to participate in the study

Exclusion Criteria

  • Acute coronary syndrome; unstable cardio-pulmonary conditions
  • Congestive heart failure NYHA III-IV
  • Previous coronary bypass surgery
  • Q-wave myocardial infarction in the area undergoing CFI measurement
  • Anatomical variants not allowing coronary sinus occlusion
  • Severe valvular heart disease
  • Severe hepatic or renal failure (creatinine clearance < 15ml/min)
  • Pregnancy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01625832

Locations
Switzerland
Department of Cardiology, Bern University Hospital
Bern, Switzerland, 3010 Bern
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
Principal Investigator: Christian Seiler Department of Cardiology, University Hospital Bern
  More Information

No publications provided by University Hospital Inselspital, Berne

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01625832     History of Changes
Other Study ID Numbers: 067/11
Study First Received: June 15, 2012
Last Updated: June 20, 2012
Health Authority: Switzerland: Ethikkommission

Keywords provided by University Hospital Inselspital, Berne:
intermittent coronary sinus occlusion
collateral flow index
collateral circulation
coronary artery occlusion

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 30, 2014