Completeness of revascularization by FFRCT in stable angina: Association to adverse cardiovascular outcomes.

BACKGROUND: The prognostic impact of complete coronary revascularization relative to non-invasive testing methods is unknown. OBJECTIVES: To assess the association between completeness of revascularization defined by CTA-derived fractional flow reserve (FFRCT) and cardiovascular outcomes in patients with stable angina. METHODS: Multicenter 3-year follow-up study of patients with new onset stable angina and ≥ 30% stenosis by CTA. The lesion-specific FFRCT value (two cm-distal-to-stenosis) was registered in all vessels with stenosis and considered abnormal when ≤ 0.80. Patients with FFRCT ≤ 0.80 were categorized as: Completely revascularized (CR-FFRCT), all vessels with FFRCT ≤ 0.80 revascularized; incompletely revascularized (IR-FFRCT), ≥ 1 vessels with FFRCT ≤ 0.80 non-revascularized. Early revascularization (< 90 days from index CTA) categorized vessels as revascularized. The primary endpoint comprised cardiovascular death and non-fatal myocardial infarction; the secondary endpoint vessel-specific late revascularization and non-fatal myocardial infarction. RESULTS: Amongst 900 patients and 1759 vessels, FFRCT was ≤ 0.80 in 377 (42%) patients, 536 (30%) vessels; revascularization was performed in 244 (27%) patients, 340 (19%) vessels. Risk of the primary endpoint was higher for IR-FFRCT (15/210 [7.1%]) compared to CR-FFRCT (4/167 [2.4%]), RR: 2.98; 95% CI: 1.01-8.8, p â€‹= â€‹0.036, and to normal FFRCT (3/523 [0.6%]), RR: 12.45; 95% CI: 3.6-42.6, p â€‹< â€‹0.001. Incidence of the secondary endpoint was higher in non-revascularized vessels with FFRCT ≤ 0.80 (29/250 [12%]) compared to revascularized vessels with FFRCT ≤ 0.80 (5/286 [1.7%]), p â€‹= â€‹0.001, and to vessels with FFRCT > 0.80 (10/1223 [0.8%]), p â€‹< â€‹0.001. CONCLUSION: Incomplete revascularization of patients with lesion-specific FFRCT ≤ 0.80 is associated to unfavorable cardiovascular outcomes compared to those with complete revascularization or FFRCT > 0.80.

Impact of Smoking on Coronary Volume-to-Myocardial Mass Ratio: An ADVANCE Registry Substudy.

Purpose To examine the relationship between smoking status and coronary volume-to-myocardial mass ratio (V/M) among individuals with coronary artery disease (CAD) undergoing CT fractional flow reserve (CT-FFR) analysis. Materials and Methods In this secondary analysis, participants from the ADVANCE registry evaluated for suspected CAD from July 15, 2015, to October 20, 2017, who were found to have coronary stenosis of 30% or greater at coronary CT angiography (CCTA) were included if they had known smoking status and underwent CT-FFR and V/M analysis. CCTA images were segmented to calculate coronary volume and myocardial mass. V/M was compared between smoking groups, and predictors of low V/M were determined. Results The sample for analysis included 503 current smokers, 1060 former smokers, and 1311 never-smokers (2874 participants; 1906 male participants). After adjustment for demographic and clinical factors, former smokers had greater coronary volume than never-smokers (former smokers, 3021.7 mm3 ± 934.0 [SD]; never-smokers, 2967.6 mm3 ± 978.0; P = .002), while current smokers had increased myocardial mass compared with never-smokers (current smokers, 127.8 g ± 32.9; never-smokers, 118.0 g ± 32.5; P = .02). However, both current and former smokers had lower V/M than never-smokers (current smokers, 24.1 mm3/g ± 7.9; former smokers, 24.9 mm3/g ± 7.1; never-smokers, 25.8 mm3/g ± 7.4; P < .001 [unadjusted] and P = .002 [unadjusted], respectively). Current smoking status (odds ratio [OR], 0.74 [95% CI: 0.59, 0.93]; P = .009), former smoking status (OR, 0.81 [95% CI: 0.68, 0.97]; P = .02), stenosis of 50% or greater (OR, 0.62 [95% CI: 0.52, 0.74]; P < .001), and diabetes (OR, 0.67 [95% CI: 0.56, 0.82]; P < .001) were independent predictors of low V/M. Conclusion Both current and former smoking status were independently associated with low V/M. Keywords: CT Angiography, Cardiac, Heart, Ischemia/Infarction Clinical trial registration no. NCT02499679 Supplemental material is available for this article. © RSNA, 2024.

Coronary computed tomography angiography derived fractional flow reserve and risk of recurrent angina: A 3-year follow-up study.

BACKGROUND: The association between coronary computed tomography angiography (CTA) derived fractional flow reserve (FFRCT) and risk of recurrent angina in patients with new onset stable angina pectoris (SAP) and stenosis by CTA is uncertain. METHODS: Multicenter 3-year follow-up study of patients presenting with symptoms suggestive of new onset SAP who underwent first-line CTA evaluation and subsequent standard-of-care treatment. All patients had at least one ≥30 â€‹% coronary stenosis. A per-patient lowest FFRCT-value ≤0.80 represented an abnormal test result. Patients with FFRCT ≤0.80 who underwent revascularization were categorized according to completeness of revascularization: 1) Completely revascularized (CR-FFRCT), all vessels with FFRCT ≤0.80 revascularized; or 2) incompletely revascularized (IR-FFRCT) ≥1 vessels with FFRCT ≤0.80 non-revascularized. Recurrent angina was evaluated using the Seattle Angina Questionnaire. RESULTS: Amongst 769 patients (619 [80 â€‹%] stenosis ≥50 â€‹%, 510 [66 â€‹%] FFRCT ≤0.80), 174 (23 â€‹%) reported recurrent angina at follow-up. An FFRCT ≤0.80 vs â€‹> â€‹0.80 associated to increased risk of recurrent angina, relative risk (RR): 1.82; 95 â€‹% CI: 1.31-2.52, p â€‹< â€‹0.001. Risk of recurrent angina in CR-FFRCT (n â€‹= â€‹135) was similar to patients with FFRCT >0.80, 13 â€‹% vs 15 â€‹%, RR: 0.93; 95 â€‹% CI: 0.62-1.40, p â€‹= â€‹0.72, while IR-FFRCT (n â€‹= â€‹90) and non-revascularized patients with FFRCT ≤0.80 (n â€‹= â€‹285) had increased risk, 37 â€‹% vs 15 â€‹% RR: 2.50; 95 â€‹% CI: 1.68-3.73, p â€‹< â€‹0.001 and 30 â€‹% vs 15 â€‹%, RR: 2.03; 95 â€‹% CI: 1.44-2.87, p â€‹< â€‹0.001, respectively. Use of antianginal medication was similar across study groups. CONCLUSION: In patients with SAP and coronary stenosis by CTA undergoing standard-of-care guided treatment, FFRCT provides information regarding risk of recurrent angina.

Derivation and validation of a novel functional FFRCT score incorporating the burden of coronary stenosis severity and flow impairment to predict clinical events.

BACKGROUND: A score combining the burden of stenosis severity on coronary computed tomography angiography (CCTA) and flow impairment by fractional flow reserve derived from computed tomography (FFRCT) may be a better predictor of clinical events than either parameter alone. METHODS: The Functional FFRCT Score (FFS) combines CCTA and FFRCT parameters in an allocated point-based system. The feasibility of the FFS was assessed in cohort of 72 stable chest pain patients with matched CCTA and FFRCT datasets. Validation was performed using 2 cohorts: (a) 4468 patients from the ADVANCE Registry to define its association with revascularization and major adverse cardiovascular events (MACE); (b) 212 patients from the FORECAST trial to determine predictors of MACE. RESULTS: The median calculation time for the FFS was 10 (interquartile range 6-17) seconds, with strong intra-operator and inter-operator agreement (Cohen's Kappa 0.89 (±0.37, p â€‹< â€‹0.001) and 0.83 (±0.04, p â€‹< â€‹0.001, respectively). The FFS correlated strongly with both the CT-SYNTAX and the Functional CT-SYNTAX scores (rS â€‹= â€‹0.808 for both, p â€‹< â€‹0.001). In the ADVANCE cohort the FFS had good discriminatory abilities for revascularization with an area under the curve of 0.82, 95 â€‹% confidence interval (CI) 0.81-0.84, p â€‹< â€‹0.001. Patients in the highest FFS tertile had significantly higher rates of revascularization (61 â€‹% vs 5 â€‹%, p â€‹< â€‹0.001) and MACE (1.9 â€‹% vs 0.5 â€‹%, p â€‹= â€‹0.001) compared with the lowest FFS tertile. In the FORECAST cohort the FFS was an independent predictor of MACE at 9-month follow-up (hazard ratio 1.04, 95 â€‹% CI 1.01-1.08, p â€‹< â€‹0.01). CONCLUSION: The FFS is a quick-to-calculate and reproducible score, associated with revascularization and MACE in two distinct populations of stable symptomatic patients.

Impact of Coronary CT Angiography-derived Fractional Flow Reserve on Downstream Management and Clinical Outcomes in Individuals with and without Diabetes.

Purpose: To compare the clinical use of coronary CT angiography (CCTA)-derived fractional flow reserve (FFR) in individuals with and without diabetes mellitus (DM). Materials and Methods: This secondary analysis included participants (enrolled July 2015 to October 2017) from the prospective, multicenter, international The Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care (ADVANCE) registry (ClinicalTrials.gov identifier, NCT02499679) who were evaluated for suspected coronary artery disease (CAD), with one or more coronary stenosis ≥30% on CCTA images, using CT-FFR. CCTA and CT-FFR findings, treatment strategies at 90 days, and clinical outcomes at 1-year follow-up were compared in participants with and without DM. Results: The study included 4290 participants (mean age, 66 years ± 10 [SD]; 66% male participants; 22% participants with DM). Participants with DM had more obstructive CAD (one or more coronary stenosis ≥50%; 78.8% vs 70.6%, P < .001), multivessel CAD (three-vessel obstructive CAD; 18.9% vs 11.2%, P < .001), and proportionally more vessels with CT-FFR ≤ 0.8 (74.3% vs 64.6%, P < .001). Treatment reclassification by CT-FFR occurred in two-thirds of participants which was consistent regardless of the presence of DM. There was a similar graded increase in coronary revascularization with declining CT-FFR in both groups. At 1 year, presence of DM was associated with higher rates of major adverse cardiovascular events (hazard ratio, 2.2; 95% CI: 1.2, 4.1; P = .01). However, no between group differences were observed when stratified by stenosis severity (<50% or ≥50%) or CT-FFR positivity. Conclusion: Both anatomic CCTA findings and CT-FFR demonstrated a more complex pattern of CAD in participants with versus without DM. Rates of treatment reclassification were similar regardless of the presence of DM, and DM was not an adverse prognostic indicator when adjusted for diameter stenosis and CT-FFR.Clinical trial registration no. NCT 02499679Keywords: Fractional Flow Reserve, CT Angiography, Diabetes Mellitus, Coronary Artery Disease Supplemental material is available for this article. See also the commentary by Ghoshhajra in this issue.© RSNA, 2023.

Prognostic Value of Coronary CT Angiography-derived Fractional Flow Reserve on 3-year Outcomes in Patients with Stable Angina.

Background The prognostic value of coronary CT angiography (CTA)-derived fractional flow reserve (FFR) beyond 1-year outcomes and in patients with high levels of coronary artery calcium (CAC) is uncertain. Purpose To assess the prognostic value of coronary CTA-derived FFR test results on 3-year clinical outcomes in patients with coronary stenosis and among a subgroup of patients with high levels of CAC. Materials and Methods This study represents a 3-year follow-up of patients with new-onset stable angina pectoris who were consecutively enrolled in the Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care, known as ADVANCE (ClinicalTrials.gov: NCT02499679) registry, between December 2015 and October 2017 at three Danish sites. A high CAC was defined as an Agatston score of at least 400. A lesion-specific coronary CTA-derived FFR value of 2 cm with distal-to-stenosis value at or below 0.80 represented an abnormal test result. The primary end point was a composite of all-cause death and nonfatal spontaneous myocardial infarction. Event rates were estimated using the one-sample binomial model, and relative risk was compared between participants stratified by results of coronary CTA-derived FFR. Results This study included 900 participants: 523 participants with normal results (mean age, 64 years ± 9.6 [SD]; 318 male participants) and 377 with abnormal results from coronary CTA-derived FFR (mean age, 65 years ± 9.6; 264 male participants). The primary end point occurred in 11 of 523 (2.1%) and 25 of 377 (6.6%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 3.1; 95% CI: 1.6, 6.3; P < .001). In participants with high CAC, the primary end point occurred in four of 182 (2.2%) and 19 of 212 (9.0%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 4.1; 95% CI: 1.4, 11.8; P = .001). Conclusion In individuals with stable angina, a normal coronary CTA-derived FFR test result identified participants with a low 3-year risk of all-cause death or nonfatal spontaneous myocardial infarction, both in the overall cohort and in participants with high CAC scores. Clinical trial registration no. NCT02499679 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Cardiovascular imaging research priorities.

OBJECTIVES: Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research. METHODS: First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner. RESULTS: The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey. CONCLUSIONS: We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.

Coronary Volume to Left Ventricular Mass Ratio in Patients With Hypertension.

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myocardial hypertrophy, which could explain the detected abnormal myocardial perfusion reserve reported in patients with hypertension. Individuals enrolled in the multicenter ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry who underwent clinically indicated CCTA for analysis of suspected coronary artery disease with known hypertension status were included in current analysis. The V/M ratio was calculated from CCTA by segmenting the coronary artery luminal volume and left ventricular myocardial mass. In total, 2,378 subjects were included in this study, of whom 1,346 (56%) had hypertension. Left ventricular myocardial mass and coronary volume were higher in subjects with hypertension than normotensive patients (122.7 ± 32.8 g vs 120.0 ± 30.5 g, p = 0.039, and 3,105.0 ± 992.0 mm3 vs 2,965.6 ± 943.7 mm3, p <0.001, respectively). Subsequently, the V/M ratio was higher in patients with hypertension than those without (26.0 ± 7.6 mm3/g vs 25.3 ± 7.3 mm3/g, p = 0.024). After correcting for potential confounding factors, the coronary volume and ventricular mass remained higher in patients with hypertension (least square) mean difference estimate: 196.3 (95% confidence intervals [CI] 119.9 to 272.7) mm3, p <0.001, and 5.60 (95% CI 3.42 to 7.78) g, p <0.001, respectively), but the V/M ratio was not significantly different (least square mean difference estimate: 0.48 (95% CI -0.12 to 1.08) mm3/g, p = 0.116). In conclusion, our findings do not support the hypothesis that the abnormal perfusion reserve would be caused by reduced V/M ratio in patients with hypertension.

The journal of cardiovascular computed tomography: A year in review: 2022.

This review aims to summarize key articles published in the Journal of Cardiovascular Computed Tomography (JCCT) in 2022, focusing on those that had the most scientific and educational impact. The JCCT continues to expand; the number of submissions, published manuscripts, cited articles, article downloads, social media presence, and impact factor continues to grow. The articles selected by the Editorial Board of the JCCT in this review highlight the role of cardiovascular computed tomography (CCT) to detect subclinical atherosclerosis, assess the functional relevance of stenoses, and plan invasive coronary and valve procedures. A section is dedicated to CCT in infants and other patients with congenital heart disease, in women, and to the importance of training in CT. In addition, we highlight key consensus documents and guidelines published in JCCT last year. The Journal values the tremendous work by authors, reviewers, and editors to accomplish these contributions.

Coronary volume to left ventricular mass ratio in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes. METHODS: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes. RESULTS: Of the 3053 patients (age 66 â€‹± â€‹10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 â€‹± â€‹940 â€‹mm3 vs. 3040 â€‹± â€‹970 â€‹mm3, p â€‹< â€‹0.0001), whereas the myocardial mass was comparable between the 2 groups (122 â€‹± â€‹33 â€‹g vs. 122 â€‹± â€‹32 â€‹g, p â€‹= â€‹0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 â€‹± â€‹6.8 â€‹mm3/g vs. 25.7 â€‹± â€‹7.5 â€‹mm3/g, p â€‹< â€‹0.0001). Among subjects with obstructive CAD (n â€‹= â€‹2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 â€‹± â€‹6.7 â€‹mm3/g vs. 25.0 â€‹± â€‹7.3 â€‹mm3/g, p â€‹< â€‹0.0001 and 25.6 â€‹± â€‹6.9 â€‹mm3/g vs. 27.3 â€‹± â€‹7.6 â€‹mm3/g, respectively, p â€‹= â€‹0.006). CONCLUSION: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation.

Quality of Life Assessment in Patients Undergoing Trans-Catheter Aortic Valve Implantation Using MacNew Questionnaire.

The MacNew questionnaire is a disease-specific quality of life measure that has been used in patients with myocardial infarction and heart failure. We aimed to investigate the impact of transcatheter aortic valve implantation (TAVI) on health-related quality of life (HRQoL) using MacNew Questionnaire and identify predictors associated with a change in its score. This was a prospective multi-center study performed across 5 National Health Service hospitals in the United Kingdom performing TAVI between 2016 and 2018. HRQoL was assessed using MacNew Questionnaire, Euro Quality of Life-5D-5L, and Short Form 36 questionnaires collected at baseline, 3-, 6- and 12 months after the procedure. Out of 225 recruited patients, 19 did not have TAVI and 4 withdrew their consent, and hence 202 patients were included. HRQoL was assessed in 181, 161, and 147 patients at 3, 6, and 12 months, respectively. Using MacNew, there was a significant improvement in all domains of HRQoL as early as 3 months after TAVI which was sustained up to 12 months with improved discrimination of change in HRQoL compared with other scales. Poor mobility at baseline and history of myocardial infarction were independent predictors of reduced improvement in HRQoL at 3 months. HRQoL increased in all subgroups of patients including frail ones. In conclusion, the MacNew assessment tool performed well in a representative TAVI cohort and could be used as an alternative disease-specific method for assessing HRQoL change after TAVI.

Cardiac computed tomography-derived coronary artery volume to myocardial mass.

In the absence of disease impacting the coronary arteries or myocardium, there exists a linear relationship between vessel volume and myocardial mass to ensure balanced distribution of blood supply. This balance may be disturbed in diseases of either the coronary artery tree, the myocardium, or both. However, in contemporary evaluation the coronary artery anatomy and myocardium are assessed separately. Recently the coronary lumen volume to myocardial mass ratio (V/M), measured noninvasively using coronary computed tomography angiography (CTCA), has emerged as an integrated measure of myocardial blood supply and demand in vivo. This has the potential to yield new insights into diseases where this balance is altered, thus impacting clinical diagnoses and management. In this review, we outline the scientific methodology underpinning CTCA-derived measurement of V/M. We describe recent studies describing alterations in V/M across a range of cardiovascular conditions, including coronary artery disease, cardiomyopathies and coronary microvascular dysfunction. Lastly, we highlight areas of unmet research need and future directions, where V/M may further enhance our understanding of the pathophysiology of cardiovascular disease.

Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis.

OBJECTIVES: To obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD). METHODS: We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as 'all-cause mortality (ACM) or myocardial infarction (MI)' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint. RESULTS: Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001). CONCLUSIONS: The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry.

BACKGROUND: The role of change in fractional flow reserve derived from CT (FFRCT) across coronary stenoses (ΔFFRCT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown. OBJECTIVES: To investigate the incremental value of ΔFFRCT in predicting early revascularization and improving efficiency of catheter laboratory utilization. MATERIALS: Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFRCT was measured 2 â€‹cm distal to stenosis. ΔFFRCT was manually measured as the difference of FFRCT across visible stenosis. RESULTS: Of 4730 patients (66 â€‹± â€‹10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFRCT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26-1.35]; p â€‹< â€‹0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFRCT. Among the 3 models (model 1: risk factors â€‹+ â€‹stenosis type and location â€‹+ â€‹CAD-RADS; model 2: model 1 â€‹+ â€‹FFRCT; model 3: model 2 â€‹+ â€‹ΔFFRCT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86-0.88] vs 0.85 [0.84-0.86]; p â€‹< â€‹0.001), with the greatest incremental value for FFRCT 0.71-0.80. ΔFFRCT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, a diagnostic strategy incorporating ΔFFRCT >0.13, would potentially reduce ICA by 32.2% (1638-1110, p â€‹< â€‹0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%. CONCLUSIONS: ΔFFRCT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFRCT, particularly for those with FFRCT 0.71-0.80. ΔFFRCT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.

The clinical utility of FFRCT stratified by age.

BACKGROUND: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFRCT) is a safe alternative to invasive coronary angiography. A negative FFRCT has been shown to have low cardiac event rates compared to those with a positive FFRCT. However, the clinical utility of FFRCT according to age is not known. METHODS: Patients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or <65 years of age. The impact of FFRCT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFRCT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFRCT was deemed to be â€‹≤ â€‹0.8. RESULTS: FFRCT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) â€‹≥ â€‹65 years of age. Subjects ≥65 years were more likely to have anatomic obstructive disease on CTA (≥50% stenosis), compared to those aged <65 (69.7% and 73.2% respectively, p â€‹= â€‹0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFRCT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those â€‹≥ â€‹or <65, regardless of FFRCT positivity or stenosis severity <50% or ≥50%. With a negative FFRCT result, and anatomical stenosis ≥50%, those â€‹≥ â€‹and <65 years of age, had similar rates of MACE (0.2% for both, p â€‹= â€‹0.1) and revascularisation (8.7% and 10.4% respectively p â€‹= â€‹0.4). Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFRCT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006-1.08, p â€‹= â€‹0.02). Amongst patients with a FFRCT > 0.80, there was no effect of age on the odds of revascularisation. CONCLUSION: The findings of this study point to a low risk of MACE events or need for revascularisation in those aged â€‹≥ â€‹or <65 with a FFRCT>0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFRCT are largely constant regardless of age.

Temporal changes in FFRCT-Guided Management of Coronary Artery Disease - Lessons from the ADVANCE Registry.

BACKGROUND: The ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFRCT). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFRCT within the ADVANCE registry. METHODS: 5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFRCT findings, and clinical outcomes through 1-year follow-up, were recorded and compared between tertiles. RESULTS: The number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1-3). The rate of positive FFRCT ≤0.80 was higher for cohorts 2 (67.3%) and 3 (74.6%) than for cohort 1 (57.1%, p < 0.001). Invasive FFR rates decreased from 25.8% to 22.4% between cohort 1 and 3 (p = 0.023). Moreover, patients with a FFRCT ≤0.80 were less frequently referred for invasive coronary angiography (ICA) (from 62.9% to 52.9%, p < 0.001), and underwent fewer revascularizations between cohort 1 and 3 (from 41.9% to 32.0%, p < 0.001). The prevalence of major events was low (1.2%) and similar between cohorts. CONCLUSIONS: Growing experience with FFRCT improved the likelihood of identifying hemodynamically significant CAD and safely reduced the need for ICA and revascularization in patients with anatomically significant disease even in the instance of an abnormal FFRCT.

Sex Differences in Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve: Lessons From ADVANCE.

OBJECTIVES: This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) according to sex. BACKGROUND: Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFRCT improves sex-based patient management decisions compared to CCTA alone is unknown. METHODS: Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFRCT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFRCT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates. RESULTS: A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFRCT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFRCT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFRCT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFRCT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFRCT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm3/g vs. 24.76 ± 7.22 mm3/g; p < 0.0001) that is associated with higher FFRCT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFRCT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284). CONCLUSIONS: FFRCT differs between the sexes, as women have a higher FFRCT for the same degree of stenosis. In FFRCT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFRCT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679).

1-Year Impact on Medical Practice and Clinical Outcomes of FFRCT: The ADVANCE Registry.

OBJECTIVES: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. BACKGROUND: Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. METHODS: Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. RESULTS: At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFRCT ≤0.80 and 12 occurred in those with an FFRCT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). CONCLUSIONS: The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679).

Effect of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve on Physicians' Clinical Behavior　- Differences Between Sites With and Without Appropriate Use Criteria as Designated by the Japanese Reimbursement System.

Background: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is an established tool for identifying lesion-specific ischemia that is now approved for use by the Japanese insurance system. However, current clinical reimbursement is strictly limited to institutions with designated appropriate use criteria (AUC). This study assessed differences in physicians' behavior (e.g., use and interpretation of FFRCT, final management) according to Japanese AUC and non-AUC site designation. Methods and Results: Of 5,083 patients in the ADVANCE Registry, 1,829 from Japan were enrolled in this study. Physicians' behavior after interrogating CCTA and FFRCT was analyzed separately according to AUC and non-AUC site designation. Compared with AUC sites, patients referred for FFRCT from non-AUC sites had a higher rate of negative FFRCT, less severe anatomic stenosis, and a slightly lower rate of management plan reclassification (51.2% vs. 61.3%), with near-identical utility in both groups. Actual care corresponded equally well to post-FFRCT plans in both groups. The likelihood of revascularization for positive or negative FFRCT was similar between the 2 groups. Importantly, AUC and non-AUC sites were equally unlikely to revascularize patients with negative FFRCT and stenosis >50% or patients with positive FFRCT and stenosis <50%. Conclusions: Compared with AUC sites, non-AUC sites had lower disease burden and reclassification of management plans, but nearly identical clinical integration. Actual care corresponded equally well to post-FFRCT recommendations at both sites.