Diagnostic Performance of Coronary CT Angiography With CT FFR in Kidney Transplantation Candidates

Diagnostic Performance of Coronary Computed Tomography Angiography With Computed Tomography Fractional Flow Reserve in Kidney Transplantation Candidates

Patients with chronic kidney disease (CKD) before kidney transplantation require that obstructive coronary artery disease (CAD) is excluded, as cardiovascular complications are the leading cause of mortality in kidney transplant patients. However, in this patient population, the optimal method for the detection of obstructive CAD has not been identified. Noninvasive stress tests such as Dobutamine stress echocardiography or nuclear perfusion study have low diagnostic accuracy. CT fractional flow reserve measurement (CT FFR) is a novel non-invasive (FDA approved) imaging test to identify obstructive CAD. The goal of this project is to evaluate the diagnostic accuracy of CT FFR in the detection of obstructive coronary artery disease in patients with chronic kidney disease before kidney transplantation.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease; Computed Tomography
• Intervention / Treatment: Diagnostic test: CT FFR

Detailed Description

Transplantation is the therapy of choice for most patients with stage 5 chronic kidney disease (CKD) and end stage renal disease (ESRD). Kidney transplantation improves quality of life and overall survival rates. Cardiovascular disease is the most common complication and leading cause of death in the transplant population. In order to assess the risk of cardiac events perioperatively and after kidney transplantation, the majority of kidney transplantation candidates undergo cardiac evaluation, including non-invasive cardiac stress imaging or invasive coronary angiography before transplantation. Invasive coronary angiography is associated with small but definite risk of bleeding or myocardial infarction, making non-invasive cardiac stress imaging such as dobutamine stress echocardiography (DSE) or nuclear myocardial perfusion scintigraphy (MPS) the preferred method. However, non-invasive cardiac stress imaging in patients with stage 5 CKD and ESRD demonstrates only moderate accuracy. DSE and MPS showed only sensitivities ranging from 0.44 to 0.89 and from 0.29 to 0.92, respectively, for identifying one or more severe coronary artery stenosis (defined as coronary diameter stenosis of more than 70%). Due to the moderate accuracy, several transplant centers (including Stanford) still continue to rely on invasive coronary angiography for their populations instead of non-invasive cardiac testing. Thus improved non-invasive cardiac testing with higher sensitivities and specificity are highly desirable in this patient population.

A promising alternative is the use of coronary CT angiography (cCTA) in combination with CT based fractional flow reserve (CT-FFR). Non-invasive cCTA alone has recently been evaluated in kidney transplantation candidates. It demonstrated high sensitivity (0.93) but limited specificity (0.63) in the detection of obstructive coronary artery disease, most likely related to the high prevalence of coronary artery calcifications in patients with CKD and ESRD. The specificity of coronary CTA can be improved by a new image analysis techniques, which allow the calculation of the hemodynamic significance - expressed as the relative pressure drop across a lesion similar - based on computational fluid dynamics derived from the conventional coronary CTA (6). In various study populations, the combination of coronary CT angiography and CT FFR showed excellent correlation with invasive FFR derived from invasive coronary angiography, which is the current gold standard. The implementation of CT- FFR has shown an improvement of the specificity of coronary CTA , even in the presence of coronary artery calcifications. However, no study so far assessed the diagnostic accuracy of coronary angiography with CT-FFR in candidates for kidney transplantation.

Goal The objective of this project is to evaluate and establish a new non-invasive cardiac test in the detection of coronary artery disease for candidates before kidney transplantation.

Specific Aims We want to confirm the promising results of CT FFR in this specific patient population and want to establish an alternative non-invasive cardiac test.

Study Design This study is designed as a prospective observational cohort study with a study population of 50 -100 patients. All patients who are included in this study will undergo coronary CT angiography with CT-FFR (research part) and a clinically indicated invasive coronary angiography with invasive FFR (standard of care). Coronary angiography and invasive FFR will act as the reference standard.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Candidates for kidney transplantation without any residual kidney function and referred to cardiac evaulation.

Description

Inclusion Criteria:

• Candidates for kidney transplantation on dialysis without any residual kidney function AND referred to invasive coronary angiography for cardiac evaluation
• Referral to invasive coronary angiography is based on algorithm used at the Transplant Readiness Assessment Clinic (TRAC) at Stanford:
• A. Diabetic Candidates older than 45 years.
• B. Diabetic Candidates under 45 years old and any one of the following criteria is present:
• a) 25 year History of Diabetes
• b) 5 year Smoking History
• c) Abnormal EKG (ST-T wave changes)

Exclusion Criteria:

• Hemodynamically and clinically unstable condition (angina at rest, malignant arrhythmias)
• Known ischemic heart disease (prior, documented myocardial infarction, prior stenting or coronary artery bypass graft surgery)
• BMI>30 kg/m2, or weight >120 kg.
• Atrial fibrillation or other arrhythmia, >6 ectopic beats per minute
• Known or suspected allergy to iodinated contrast medium
• Pregnancy cannot be excluded

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of CT FFR.	Diagnostic accuracy of CT FFR (per vessel) in the detection of hemodynamically significant CAD as compared to invasive FFR derived from invasive coronary angiography (reference standard). Presence or absence of hemodynamically significant coronary artery disease in concordance between CT FFR and invasive FFR. Hemodynamically significant stenosis is defined as CT FFR value below 0.8.	CT FFR and Invasive FFR are calculated immediately after coronary CT angiography and invasive coronary angiography

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Siemens Medical Solutions
• Investigators: Principal Investigator: Dominik Fleischmann, M.D., Stanford Radiology

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2017
• Primary Completion (Actual): January 24, 2020
• Study Completion (Actual): January 24, 2020

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 14, 2017

Study Record Updates

• Last Update Posted (Actual): January 6, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: IRB-41455

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes