Optimal diagnostic approach for using CT-derived quantitative flow ratio in patients with stenosis on coronary computed tomography angiography.

BACKGROUND: Coronary computed tomography angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is an on-site non-invasive technique estimating invasive fractional flow reserve (FFR). This study assesses the diagnostic performance of using most distal CT-QFR versus lesion-specific CT-QFR approach for identifying hemodynamically obstructive coronary artery disease (CAD). METHODS: Prospectively enrolled de novo chest pain patients (n â€‹= â€‹445) with ≥50 â€‹% visual diameter stenosis on CCTA were referred for invasive evaluation. On-site CT-QFR was analyzed post-hoc blinded to angiographic data and obtained as both most distal (MD-QFR) and lesion-specific CT-QFR (LS-QFR). Abnormal CT-QFR was defined as ≤0.80. Hemodynamically obstructive CAD was defined as invasive FFR ≤0.80 or ≥70 â€‹% diameter stenosis by 3D-quantitative coronary angiography. RESULTS: In total 404/445 patients had paired CT-QFR and invasive analyses of whom 149/404 (37 â€‹%) had hemodynamically obstructive CAD. MD-QFR and LS-QFR classified 188 (47 â€‹%) and 165 (41 â€‹%) patients as abnormal, respectively. Areas under the receiver-operating characteristic curve for MD-QFR was 0.83 vs. 0.85 for LS-QFR, p â€‹= â€‹0.01. Sensitivities for MD-QFR and LS-QFR were 80 â€‹% (95%CI: 73-86) vs. 77 â€‹% (95%CI: 69-83), p â€‹= â€‹0.03, respectively, and specificities were 73 â€‹% (95%CI: 67-78) vs. 80 â€‹% (95%CI: 75-85), p â€‹< â€‹0.01, respectively. Positive predictive values for MD-QFR and LS-QFR were 63 â€‹% vs. 69 â€‹%, p â€‹< â€‹0.01, respectively, and negative predictive values for MD-QFR and LS-QFR were 86 â€‹% vs. 85 â€‹%, p â€‹= â€‹0.39, respectively). CONCLUSION: Using a lesion-specific CT-QFR approach has superior discrimination of hemodynamically obstructive CAD compared to a most distal CT-QFR approach. CT-QFR identified most cases of hemodynamically obstructive CAD while a normal CT-QFR excluded hemodynamically obstructive CAD in the majority of patients.

Calcium Scoring Improves Clinical Management in Patients With Low Clinical Likelihood of Coronary Artery Disease.

BACKGROUND: Coronary artery calcium scoring (CACS) improves management of chest pain patients. However, it is unknown whether the benefit of CACS is dependent on the clinical likelihood (CL). OBJECTIVES: This study aims to investigate for which patients CACS has the greatest benefit when added to a CL model. METHODS: Based on data from a clinical database, the CL of obstructive coronary artery disease (CAD) was calculated for 39,837 patients referred for cardiac imaging due to symptoms suggestive of obstructive CAD. Patients were categorized according to the risk factor-weighted (RF-CL) model (very low, ≤5%; low, >5 to ≤15%; moderate >15 to ≤50%; high, >50%). CL was then recalculated incorporating the CACS result (CACS-CL). Reclassification rates and the number needed to test with CACS to reclassify patients were calculated and validated in 3 independent cohorts (n = 9,635). RESULTS: In total, 15,358 (39%) patients were down- or upclassified after including CACS. Reclassification rates were 8%, 75%, 53%, and 30% in the very low, low, moderate, and high RF-CL categories, respectively. Reclassification to very low CACS-CL occurred in 48% of reclassified patients. The number needed to test to reclassify 1 patient from low RF-CL to very low CACS-CL was 2.1 with consistency across age, sex, and cohorts. CACS-CL correlated better to obstructive CAD prevalence than RF-CL. CONCLUSIONS: Added to an RF-CL model for obstructive CAD, CACS identifies more patients unlikely to benefit from further testing. The number needed to test with CACS to reclassify patients depends on the pretest RF-CL and is lowest in patients with low (>5% to ≤15%) likelihood of CAD.

Prognostic value of computed tomography derived fractional flow reserve for predicting cardiac events and mortality in kidney transplant candidates.

BACKGROUND: Cardiac screening using coronary computed tomography angiography (CCTA) in kidney transplant candidates before transplantation yields both diagnostic and prognostic information. Whether CT-derived fractional flow reserve (FFRCT) analysis provides prognostic information is unknown. This study aimed to assess the prognostic value of FFRCT for predicting major adverse cardiac events (MACE) and all-cause mortality in kidney transplant candidates. METHODS: Among 553 consecutive kidney transplant candidates, 340 CCTA scans (61%) were evaluated with FFRCT analysis. Patients were categorized into groups based on lowest distal FFRCT; normal >0.80, intermediate 0.80-0.76, and low ≤0.75. In patients with ≥50% stenosis, a lesion-specific FFRCT was defined as; normal >0.80 and abnormal ≤0.80. The primary endpoint was MACE (cardiac death, resuscitated cardiac arrest, myocardial infarction or revascularization). The secondary endpoint was all-cause mortality. RESULTS: Median follow-up was 3.3 years [2.0-5.1]. MACE occurred in 28 patients (8.2%), 29 patients (8.5%) died. When adjusting for risk factors and transplantation during follow-up, MACE occurred more frequently in patients with distal FFRCT ≤0.75 compared to patients with distal FFRCT >0.80: Hazard Ratio (HR): 3.8 (95%CI: 1.5-9.7), p â€‹< â€‹0.01. In the lesion-specific analysis with <50% stenosis as reference, patients with lesion-specific FFRCT >0.80 had a HR for MACE of 1.5 (95%CI: 0.4-4.8), p â€‹= â€‹0.55 while patients with lesion-specific FFRCT ≤0.80 had a HR of 6.0 (95%CI: 2.5-14.4), p â€‹< â€‹0.01. Abnormal FFRCT values were not associated with increased mortality. CONCLUSION: In kidney transplant candidates, abnormal FFRCT values were associated with increased MACE but not mortality. Use of FFRCT may improve cardiac evaluation prior to transplantation.

Coronary Calcium Scoring Improves Risk Prediction in Patients With Suspected Obstructive Coronary Artery Disease.

BACKGROUND: In patients with suspected obstructive coronary artery disease (CAD), the risk factor-weighted clinical likelihood (RF-CL) model and the coronary artery calcium score-weighted clinical likelihood (CACS-CL) model improves the identification of obstructive CAD compared with basic pretest probability (PTP) models. OBJECTIVES: The aim of this study was to assess the prognostic value of the new models. METHODS: The incidences of myocardial infarction and death were stratified according to categories by the RF-CL and CACS-CL and compared with categories by the PTP model. We used cohorts from a Danish register (n = 41,177) and a North American randomized study (n = 3,952). All patients were symptomatic and were referred for diagnostic testing because of clinical indications. RESULTS: Despite substantial down-reclassification of patients to a likelihood ≤5% of CAD with either the RF-CL (45%) or CACS-CL (60%) models compared with the PTP (18%), the annualized event rates of myocardial infarction and death were low using all 3 models; RF-CL 0.51% (95% CI: 0.46-0.56), CACS-CL 0.48% (95% CI: 0.44-0.56), and PTP 0.37% (95% CI: 0.31-0.44), respectively. Overall, comparison of the predictive power of the 3 models using Harrell's C-statistics demonstrated superiority of the RF-CL (0.64 [95% CI: 0.63-0.65]) and CACS-CL (0.69 [95% CI: 0.67-0.70]) compared with the PTP model (0.61 [95% CI: 0.60-0.62]). CONCLUSIONS: The simple clinical likelihood models that include classical risk factors or risk factors combined with CACS provide improved risk stratification for myocardial infarction and death compared with the standard PTP model. Hence, the optimized RF-CL and CACS-CL models identify 2.5 and 3.3 times more patients, respectively, who may not benefit from further diagnostic testing.

The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD.

BACKGROUND: Guidelines for evaluating patients with suspected coronary artery disease (CAD) recommend pretest probability (PTP) estimation but provide no clear recommendations regarding diagnostic testing in patients with >5% to 15% risk of obstructive CAD. The diagnostic and prognostic value of PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS) calculation in this patient group is unknown. OBJECTIVES: This work aims to improve the evaluation of stable patients with suspected CAD by using the PMRS, which identifies patients at minimal risk of CAD and events in patients with >5% to 15% PTP of obstructive CAD. METHODS: Greater than 5% to 15% PTP patients from 2 large clinical trials were used for subcohort derivation: PROMISE (N = 10,003) and Dan-NICAD (Danish study of Non-Invasive Testing in Coronary Artery Disease) (N = 3,252). First, the PMRS cutoff associated with a prevalence of obstructive CAD ≤5% was determined in the >5% to 15% PTP PROMISE core lab computed tomographic angiography patients (discovery cohort: n = 2,191). This cutoff was validated for obstructive CAD in >5% to 15% PTP Dan-NICAD patients (CAD validation cohort: n = 1,386) and for prognostic impact on death and myocardial infarction in >5% to 15% PTP PROMISE non-core lab computed tomographic angiography patients (prognosis validation cohort: n = 2,753). RESULTS: In the discovery cohort, a CAD prevalence of ≤5% was found at a PMRS of ≥34%. In the CAD validation cohort, this cutoff down-classified 442 (31.9%) of >5% to 15% PTP patients into the low PTP group (CAD ≤5%); the prevalence of obstructive CAD in down-classified patients was 3.2% compared to 7.1% in non-down-classified patients. A PMRS ≥34% was nonsignificantly associated with a lower risk of myocardial infarction and death in the prognosis validation cohort (HR: 0.58 [95% CI: 0.29-1.18]; P = 0.13). CONCLUSIONS: For evaluating patients with suspected CAD, a combined use of traditional PTP and the PMRS correctly down-classified one-third of >5% to 15% PTP patients into a group with very low prevalence of obstructive CAD and adverse events. The proposed strategy may improve risk stratification and help reduce unneeded diagnostic testing.