Prognostic value of fractional flow reserve using computed tomography for predicting major adverse cardiac events and mortality in kidney transplant candidates
Authors: Dahl J N D , Nielsen M B N , Bottcher M B , Birn H B , Ivarsen P I , Svensson M S , Rasmussen L D R , Bangalore S B , Winther S W 
Published: October 2021

Abstract

Background
Coronary artery disease (CAD) is highly prevalent in patients with severe chronic kidney disease (CKD), it is the leading cause of mortality and morbidity in the short and long term among kidney transplant candidates, and the prevalence of CAD is high even after kidney transplantation. Most institutions recommend non-invasive cardiac tests prior to transplantation. Previous studies have indicated that cardiac screening by coronary computed tomography angiography (CTA) in kidney transplant candidates before transplantation yields both diagnostic and prognostic information. Additional analysis by CT-derived fractional flow reserve (FFRct) may improve diagnostic performance and have prognostic information.

Purpose
To establish the occurrence of major adverse cardiac events (MACE) and all-cause mortality in kidney transplantation candidates undergoing cardiac screening with coronary CTA with additional FFRct.

Methods
Coronary CTA scans from 340 consecutive kidney transplant candidates (CKD stage 4–5) undergoing cardiac evaluation with coronary CTA as part of the diagnostic work-up, between February 2011 and September 2019, were evaluated with subsequent FFRct analysis, the FFRct results were not clinically available.
Patients were categorized into three groups based on distal FFRct; normal FFRct &gt;0.80, moderate FFRct 0.80 to &gt;0.75, low FFRct ≤0.75. Secondary analysis was performed using lesion specific (≥50% stenosis on coronary CTA) FFRct values, with normal FFRct &gt;0.80 and abnormal ≤0.80.
The primary end-point was MACE (cardiac death, cardiac arrest, myocardial infarction or revascularization unrelated to baseline work-up). The secondary end-point was all-cause mortality. End-point and baseline data were identified through patient files and registry data.

Results
Patients had a median age of 53 [45–63], 63% were men, 31% were on dialysis, the median follow-up time was 3.3 years [2.0–5.1]. During follow-up, MACE occurred in 28 patients (8.2%) and 28 patients (8.2%) died.
When adjusting for risk factors and kidney transplantation during follow-up, the primary analysis identified increased risk of MACE in patients with lower distal FFRct compared to patients with FFRct &gt;0.80; FFRct 0.80 to &gt;0.75; Hazard ratio (HR): 1.63 (95% CI: 0.48–5.58; p=0.44), and FFRct with FFRct ≤0.75; HR: 3.27 (95% CI: 1.34–7.96; p&lt;0.01). In the secondary analysis based on lesion-specific FFRct values, a FFRct ≤0.80 was associated with a higher risk of MACE compared to FFRct &gt;0.80; HR 3.21 (95% CI 1.01–10.20, p&lt;0.05).
There were no significant differences in mortality between groups.

Conclusions
In kidney transplant candidates, a low FFRct ≤0.75 was predictive of MACE but not mortality. A lesion-specific approach found similar results with increased risk of MACE in patients with lesion-specific FFRct ≤0.80. Thus, FFRct adds prognostic information to the cardiac evaluation of these patients with severe CKD.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The Private Company, HeartFlow Inc, Redwood City, Califonia US- sponsored the fractional flow reserve using computed tomography scans, with no exchange of financial meansThe Public, Health Research Fund of the Central Denmark Region.- provided parts of the salary for two authors. FFRct distal values – MACE and MortalityFFRct lesion values – MACE and Mortality