Clinical Trial: Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Role of Endothelin in Microvascular Dysfunction Following Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction

Brief Summary:

Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor and its expression is increased in atherosclerotic coronary arteries. Our hypothesis is that increased activity of the endogenous endothelin system contributes to microvascular dysfunction, and adjunctive therapy with an endothelin receptor antagonist will result in improved microvascular blood flow.

Aims: The aims of the study are to assess in patients with non ST-elevation myocardial infarction, whether: 1) PCI causes an increase in coronary blood ET-1 level; 2) an endothelin receptor antagonist acutely improves coronary microvascular blood flow following PCI.

Non-ST segment elevation myocardial infarction (NSTEMI) is one type of heart attack. It is defined as the development of heart muscle necrosis results from an acute interruption of blood supply to a part of the heart which is demonstrated by an elevation of cardiac markers Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) in the blood and the absence of ST-segment elevation in ECG (electrocardiography). ST-segment is a portion of ECG, its elevation indicates full thickness damage of heart muscle. Absence of ST-segment elevation in NSTEMI indicates partial thickness damage of heart muscle occurs. Therefore, NSTEMI is less severe type of heart attack compared to STEMI (ST-segment elevation myocardial infarction) in which full thickness damage of heart muscle occurs.


Detailed Summary:

Our hypothesis is that the endogenous endothelin system contributes to microvascular dysfunction and impaired myocardial reperfusion following successful PCI for non ST-elevation MI, and that endothelin receptor antagonism will improve microvascular flow. The study will provide new insight into the humoral regulation of the microcirculation in patients presenting with acute coronary syndromes.

General methods: This section describes our approach to investigating the specific aims. The study is a prospective, double blind, placebo-controlled trial to assess the efficacy of a selective endothelin type A receptor antagonist (BQ-123), as adjunctive therapy for PCI for non ST elevation MI. The control group will receive placebo rather than another vasodilator in order to specifically elucidate the role of the endogenous endothelin system.


Sponsor: Mayo Clinic

Current Primary Outcome: Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI) [ Time Frame: immediately following PCI procedure ]

Coronary microvascular blood flow will be assessed following successful PCI by measuring APV in the culprit vessel using Doppler echocardiography.


Original Primary Outcome: Primary endpoint: coronary flow reserve (CFR) [ Time Frame: immediately following PCI ]

Current Secondary Outcome: Percent Change in Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) From Immediately Pre-PCI to 8 and 16 Hours Post-PCI [ Time Frame: immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI ]

CK-MB is a cardiac marker that can demonstrate the development of heart muscle necrosis resulting from an acute interruption of blood supply to a part of the heart. CK-MB is measured by a blood test.


Original Secondary Outcome:

  • Secondary Endpoints: coronary sinus ET-1 levels before and after PCI [ Time Frame: Immediately pre and post PCI ]
  • Post PCI: diastolic deceleration time from the coronary Doppler signal, TIMI frame count, myocardial blush grade [ Time Frame: Immediately post PCI ]


Information By: Mayo Clinic

Dates:
Date Received: December 21, 2007
Date Started: May 2005
Date Completion:
Last Updated: July 3, 2014
Last Verified: June 2014