Myocardial Microvascular Disease in ESRD

Study Overview
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Brief Summary
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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.

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

Conditions
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End Stage Renal Disease, Myocardial Microvascular Disease

Intervention / Treatment
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* Procedure: Invasive FFR + CFR measurements are performed during coronary angiography using a pressure guide wire


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: comparator<br>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<br>* 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.<br>|
| Experimental: coronary angiography group<br>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<br>* 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.<br>|

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of myocardial microvascular disease detected by FFR + CFR in ESRD patients with myocardial ischemia on non invasive tests. |  | Inclusion: 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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