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

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.

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