Background The recently updated pre-test probability (PTP) model for diagnosing chronic coronary syndrome suggested by the European Society of Cardiology (ESC) was designed to predict the presence of obstructive coronary artery disease (CAD). In addition to this model, identification of non-obstructive CAD and utilization of preventive interventions may also lower rates of death and non-fatal myocardial infarction. Opposite to the ESC PTP, the minimal risk tool (MRT) is a new model developed to identify individuals without CAD but symptoms suggestive of CAD. We explored a combined use of the 2 models to predict the absence or presence of obstructive CAD. Methods This was a sub-study of the Danish study of Non-Invasive testing in Coronary Artery Disease (Dan-NICAD) which included patients with low-intermediate PTP of CAD. Minimal risk was defined as having a coronary calcium score of 0, no evidence of coronary atherosclerosis at coronary computed tomography angiography, and no cardiovascular (CV) events defined as myocardial infarction, death or revascularization in the mean observation period of 3.1 [2.7–3.4] years. Obstructive CAD was defined as a fractional flow reserve <0.80 in a major vessel during invasive coronary angiography (ICA) or a high-grade stenosis by visual assessment (>90% lumen reduction). The risk factors included in the MRT were age, sex, smoking history, diabetes mellitus, dyslipidaemia, family history of premature CAD, hypertension, symptoms related to stress, and high-density lipoprotein concentration. Based on a point-system ranging from 0–5, the MRT and the ESC PTP were combined (dual-PTP) (figure 1). A dual-PTP ≤1 indicated very low risk. Using both minimal risk and obstructive CAD as references, the dual PTP was compared to the MRT and the ESC PTP through tests of model discrimination. Results Of the 1544 eligible patients, 710 (46%) had normal coronary arteries and no CV events. Obstructive CAD was diagnosed in 152 (10%). Equivalent to a dual-PTP <1 point, 209 patients with ESC PTP<5% and MRT>50% or ESC PTP 5–15% and MRT >75% were classified as very low risk. Of these patients, 84% were at true minimal risk (red area figure 1). Furthermore, only 6 patients would have been diagnosed with obstructive CAD at ICA, and 0 events would be missed. The dual-PTP was non-inferior to the MRT and the ESC PTP in identifying patients having minimal risk and obstructive CAD, respectively (minimal risk: c-statistics 0.74 (0.72–0.77) vs. 0.76 (0.73–0.78); obstructive CAD: c-statistics 0.66 (0.62–0.70) vs. (0.67 (0.63–0.72)). The dual-PTP was superior to the ESC PTP in discriminating patients at minimal risk (c-statistics 0.74 (0.72–0.77) vs. 0.69 (0.67–0.71). Conclusions Combining the ESC PTP and the MRT, the dual-PTP seems to enable accurate prediction of both patients with minimal risk and patients with obstructive CAD. Based on the dual-PTP, patients can safely be deferred from or referred for diagnostic testing Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Aarhus University, Health Research Fund of Central Denmark Region

Introduction Guidelines recommend secondary ischemia assessment following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Coronary CTA-derived quantitative flow ratio (CT-QFR) is an on-site technique performed on acquired CTA images that estimates the functional severity of a coronary stenosis. However, CT-QFR measurements are available throughout the coronary vessel with no clear recommendations as to which specific values should be used for identifying obstructive CAD, e.g. most distal or lesion-specific values. Purpose First, to investigate the feasibility of CT-QFR and the correlation and agreement with invasive fractional flow reserve (FFR). Secondly, to compare the diagnostic performance of distal versus lesion-specific CT-QFR for identifying obstructive CAD defined by invasive coronary angiography (ICA) with FFR. Methods A total of 1732 prospectively included patients with symptoms suggestive of CAD referred for CTA were included. All patients with ≥50% diameter stenosis (DS) on CTA were subsequently referred for ICA with conditional FFR in lesions with 30–89%DS. Obstructive CAD was defined by ICA as FFR ≤0.80 or high-grade stenosis by visual assessment (≥90%DS). A blinded analysis of CT-QFR was performed in patients referred to ICA with measurements at the distal end of a vessel (distal CT-QFR) and 1 cm distal to stenotic lesions on CTA (lesion-specific). CT-QFR ≤0.80 was defined as abnormal. For correlation analyses to invasive FFR, CT-QFR was assessed corresponding to the position of the invasive pressure sensor. Results In total, 445/1732 (25%) patients had suspected obstructive CAD at CTA and underwent subsequent ICA. CT-QFR analysis was feasible in 423/445 (95%) patients. CT-QFR correlated (Pearson's rho 0.54, p<0.001) and agreed (mean difference –0.02±0.09) to FFR with CT-QFR overestimating FFR (Fig. 1). Obstructive CAD was identified in 190/423 (44%) patients by ICA. Distal and lesion-specific CT-QFR classified 196 (46%) and 171 (40%) patients as abnormal, respectively. Areas under the receiver-operating characteristic curves for distal versus lesion-specific CT-QFR were similar (0.86 (95% CI: 0.82–0.89) vs. 0.86 (0.82–0.90), p=0.80). Sensitivities for distal and lesion-specific CT-QFR were 78% (95% CI: 71–84) vs. 74% (67–80), p=0.01, respectively, and specificities 79% (95% CI: 74–84) vs. 87% (82–91), p<0.01, respectively. Distal and lesion-specific CT-QFR had similar diagnostic accuracy (79 (95% CI: 75–83), vs. 81 (77–85), p=0.07) (Fig. 2). Conclusion In patients with suspected obstructive CAD on CTA, non-invasive estimation of FFR using CT-QFR is feasible with moderate correlation and good agreement with invasive FFR. Overall diagnostic performance of distal and lesion-specific values for discriminating obstructive CAD by invasive FFR are similar. The use of CT-QFR could therefore potentially reduce the need for referral to invasive angiography after CTA. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Aarhus UniversityRegion Mid Jutland

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 >0.80, moderate FFRct 0.80 to >0.75, low FFRct ≤0.75. Secondary analysis was performed using lesion specific (≥50% stenosis on coronary CTA) FFRct values, with normal FFRct >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 >0.80; FFRct 0.80 to >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<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 >0.80; HR 3.21 (95% CI 1.01–10.20, p<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. FUNDunding 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 Mortality FFRct lesion values – MACE and Mortality

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