Myocardial Microvascular Disease in ESRD (MICROCARD)

Detection and Outcomes of Myocardial Microvascular Disease in Patients With End Stage Renal Disease

Cardiovascular diseases are the leading cause of mortality in patients with end stage renal disease (ESRD). They often have myocardial ischemia (a major predictor of mortality) on non invasive testing (Stress echocardiography and/or myocardial perfusion scintigraphy) but the incidence of significant coronary stenosis (>70%) is low. The goal of this observational study is to evaluate the incidence and clinical outcomes of proven myocardial microvascular disease in patients with end stage renal disease scheduled or not for kidney transplantation. These patients routinely undergo non invasive detection of myocardial ischemia. Patient included in the study will be followed up for 2 years for major cardiovascular events. Patients with detected myocardial ischemia during non invasive testing are being explored by coronary angiography. During coronary angiography additional detection of myocardial microvascular disease is being performed by simultaneous measurement of Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) followed by calculation of the index of microcirculatory resistance (IMR).

Comparison of cardiovascular outcomes between patients with and without myocardial ischemia and patients with and without myocardial microvascular disease will be performed.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Disease; Myocardial Microvascular Disease
• Intervention / Treatment: Procedure: Invasive FFR + CFR measurements are performed during coronary angiography using a pressure guide wire

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Service de Cardiologie D - Hôpital Louis Pradel - Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age > 18 years with end stage renal disease under dialysis and/or scheduled for kidney or kidney + pancreatic transplantation
• Having a non invasive detection of myocardial ischemia and agreeing to participate (signed informed consent document)

Exclusion Criteria:

Past medical history of

• Acute coronary syndrome
• Hypertrophic cardiomyopathy
• severe aortic and/or mitral valvular disease (grade ≥ 3)
• Known contraindications to adenosine injection: AV block grade ≥ 2 and/or sinoatrial block unless prior implantation of a pace maker, asthma, allergic reaction to adenosine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: comparator; One group of patients with no myocardial ischemia on non invasive testing will be followed up for 2 years	Procedure: Invasive FFR + CFR measurements are performed during coronary angiography using a pressure guide wire; The guide is placed in the distal segment of the coronary artery to measure instantaneously distal pressure and temperature with a tip sensor. Proximal pressure and temperature are being measured from the probe used to catheterize the coronary vessel and from the shaft of the guide. After basal measurement, intracoronary injection of 150µg of adenosine is performed to induce peripheral vasodilatation leading to hyperaemia in the vessel. Additional injection of 3mL 0.9% saline bolus at room temperature at the time of hyperaemia is performed to calculate CFR from transit mean time. FFR and CFR are being recorded at the time of hyperaemia. Subsequently IMR is being calculated from distal pressure and transit mean time. The measurements will be performed in the LAD, circumflex and right coronary arteries.
Experimental: coronary angiography group; One group of patients with myocardial ischemia on non invasive testing will undergo coronary angiography and measure of FFR + CFR to detect myocardial microvascular disease	Procedure: Invasive FFR + CFR measurements are performed during coronary angiography using a pressure guide wire; The guide is placed in the distal segment of the coronary artery to measure instantaneously distal pressure and temperature with a tip sensor. Proximal pressure and temperature are being measured from the probe used to catheterize the coronary vessel and from the shaft of the guide. After basal measurement, intracoronary injection of 150µg of adenosine is performed to induce peripheral vasodilatation leading to hyperaemia in the vessel. Additional injection of 3mL 0.9% saline bolus at room temperature at the time of hyperaemia is performed to calculate CFR from transit mean time. FFR and CFR are being recorded at the time of hyperaemia. Subsequently IMR is being calculated from distal pressure and transit mean time. The measurements will be performed in the LAD, circumflex and right coronary arteries.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major cardiovascular events	Major cardiovascular events; Death (all cause); Acute coronary syndromes (STEMI, NSTEMI, UA); New onset of stable angina; New onset of congestive heart failure or progression of previously known congestive heart failure (need for therapeutic intensification and/or hospital admission); Cardiogenic shock; Stroke; Severe cardiac arrhythmia (FV, VT); New onset of atrial fibrillation	Inclusion: 1 year - Follow up: 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of myocardial microvascular disease detected by FFR + CFR in ESRD patients with myocardial ischemia on non invasive tests.	Inclusion: 1 year

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Denis ANGOULVANT, Dr, Hospices Civils de Lyon

Publications and helpful links

General Publications

• Bejan-Angoulvant T, Bergerot C, Juillard L, Mezergues A, Morelon E, Pouteil-Noble C, Andre-Fouet X, Angoulvant D. Myocardial microvascular disease and major adverse cardiovascular events in patients with end-stage renal disease: rationale and design of the MICROCARD study. Nephrol Dial Transplant. 2012 Jul;27(7):2886-91. doi: 10.1093/ndt/gfs008. Epub 2012 Feb 17.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: February 7, 2011
• First Submitted That Met QC Criteria: February 7, 2011
• First Posted (Estimate): February 8, 2011

Study Record Updates

• Last Update Posted (Estimate): January 16, 2015
• Last Update Submitted That Met QC Criteria: January 15, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: End stage renal disease; myocardial microvascular disease; cardiorenal syndrome; coronary flow reserve; index of microvascular resistance; Patients with end stage renal disease scheduled or not for kidney or kidney + pancreatic transplantation
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 2010.611

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No