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Background: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization., Objectives: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA)., Methods: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort., Results: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA., Conclusions: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328)., Competing Interests: Funding Support and Author Disclosures This study received funding from HeartFlow Inc. The company performed the computational fluid dynamics, and artificial intelligence quantitative coronary plaque analysis but was not involved in the study design, collection, analysis, and interpretation of data; the writing of this paper; or the decision to submit it for publication. Dr Koo has received institutional research grants from Abbott, Philips, and HeartFlow Inc. Dr Nam has received institutional research grants from Abbott and Genoss. Dr Merkely has received direct personal payments for speaker fees or studies from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Medtronic, and Novartis and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr de Bruyne has received institutional unrestricted research grants from Abbott, Boston Scientific, and Biotronik; has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE, Bayer, Philips, HeartFlow Inc, Edwards Life Sciences, Sanofi, and Omega Pharma. Dr Ko has equity in Artrya and has received honoraria from Medtronic, Abbott Vascular, and Canon Medical. Dr Leipsic is a consultant for and holds stock options in HeartFlow Inc and modest personal core lab fees from Arineta. Dr Shah has received honoraria as a speaker for HeartFlow Inc. Dr Bax has received unrestricted research grants from Abbott and Edwards Lifesciences to the Department of Cardiology, Leiden University Medical Center, the Netherlands. Dr Shaw has received honoraria from HeartFlow Inc and Elucid Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary disease complexity is commonly used to guide revascularization strategy in patients with multivessel disease (MVD)., Objectives: The aim of this study was to assess the interactive effects of coronary complexity on percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) outcomes and identify the optimal threshold at which PCI can be considered a reasonable option., Methods: A total of 1,444 of 1,500 patients with MVD from the FAME (Fractional Flow Reserve versus Angiography for Multi-vessel Evaluation) 3 randomized trial were included in the analysis (710 CABG vs 734 PCI). SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were transformed into restricted cubic splines, and logistic regression models were fitted, with multiplicative interaction terms for revascularization strategy. Optimal thresholds at which PCI is a reasonable alternative to CABG were determined on the basis of Cox regression model performance., Results: The mean SYNTAX score (SS) was 25.9 ± 7.1. SS was associated with 1-year major adverse cardiac and cerebrovascular events among PCI patients and 3-year death, myocardial infarction, and stroke among CABG patients. Significant interactions were present between revascularization strategy and SS for 1- and 3-year composite endpoints (P for interaction <0.05 for all). In Cox regression models, outcomes were comparable between CABG and PCI for the 3-year primary endpoint for SS ≤24 (P = 0.332), with 44% of patients below this threshold and 32% below the conventional SS threshold of ≤22., Conclusions: In patients with MVD without left main disease, PCI and CABG outcomes remain comparable up to SS values in the mid- rather than low 20s, which allows the identification of a greater proportion of patients in whom PCI may be a reasonable alternative to CABG., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from Medtronic and Abbott Vascular. Dr Dawson is supported by the Australian National Health and Medical Research Council and the Australian National Heart Foundation postgraduate scholarships. Dr Kobayashi serves as a consultant for Abbott Vascular. Dr Fearon has received institutional research support from Abbott Vascular, and Medtronic; and has stock options with HeartFlow. Dr De Bruyne has consulting relationships with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; has received research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds minor equities in Philips-Volcano, Siemens, GE Healthcare, Edwards Lifesciences, HeartFlow, Sanofi, and Celyad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This study focuses on identifying anatomical markers with predictive capacity for long-term myocardial infarction (MI) in focal coronary artery disease (CAD). Eighty future culprit lesions (FCL) and 108 non-culprit lesions (NCL) from 80 patients underwent 3D quantitative coronary angiography. The minimum lumen area (MLA), minimum lumen ratio (MLR), and vessel fractional flow reserve (vFFR) were evaluated. MLR was defined as the ratio between MLA and the cross-sectional area at the proximal lesion edge, with lower values indicating more abrupt luminal narrowing. Significant differences were observed between FCL and NCL in MLR (0.41 vs. 0.53, p < 0.001). MLR correlated inversely with translesional vFFR (r =  - 0.26, p = 0.0004) and was the strongest predictor of MI at 5 years (AUC = 0.75). Lesions with MLR < 0.40 had a fourfold increased MI incidence at 5 years. MLR is a robust predictor of future adverse coronary events., (© 2024. The Author(s).)

Background: Coronary CT angiography (CCTA) is well-established for diagnosis and stratification of coronary artery disease (CAD). Its usefulness in guiding percutaneous coronary interventions (PCI) and stent sizing is unknown., Methods: This is a sub-analysis of the Precise Percutaneous Coronary Intervention Plan (P3) study (NCT03782688). We analyzed 65 vessels with matched CCTA and pre-PCI optical coherence tomography (OCT) assessment. The CCTA-guided stent size was defined by the mean distal reference lumen diameter rounded up to the nearest stent diameter. The OCT lumen-guided stent size was the mean distal reference lumen diameter rounded to the closest stent diameter. The agreement on stent diameters was determined with Kappa statistics, Passing-Bablok regression analysis, and the Bland-Altman method., Results: The distal reference lumen diameter by CCTA and OCT were 2.75 ​± ​0.53 ​mm and 2.72 ​± ​0.55 ​mm (mean difference 0.06, limits of agreement -0.7 to 0.82). There were no proportional or systematic differences (coefficient A 1.06, 95% CI 0.84 to 1.3 and coefficient B -0.22, 95% CI -0.83 to 0.36) between methods. The agreement between the CCTA and OCT stent size was substantial (Cohen's weighted Kappa 0.74, 95% CI 0.64 to 0.85). Compared to OCT stent diameter, CCTA stent size was concordant in 52.3% of the cases; CCTA overestimated stent size in 20.0% and underestimated in 27.7%., Conclusion: CCTA accurately assessed the reference vessel diameter used for stent sizing. CCTA-based stent sizing showed a substantial agreement with OCT. CCTA allows for PCI planning and may aid in selecting stent diameter., Competing Interests: Declaration of competing interest TM reports receiving consulting fees from Zeon Medical and HeartFlow Inc, and speaker fees from Abbott Vascular. BLN has received an unrestricted institutional research grant from HeartFlow Inc. MM is supported by a grant from the Novo Nordisk Foundation (grant NNF22OC0074083). BKK received an Institutional Research Grant from Abbott Vascular, Boston Scientific Corporation, and Philips. BDB reports receiving consultancy fees from Boston Scientific and Abbott Vascular, research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular, and owning equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, Celyad. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, Abbott Vascular, and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. The other authors have no further disclosures., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques., Aims: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements., Methods: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment., Results: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001)., Conclusions: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment., (© 2024 Wiley Periodicals LLC.)

Background: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear., Methods: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year., Results: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively., Conclusions: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFR CT ) is a safe alternative to invasive coronary angiography. A negative FFR CT has been shown to have low cardiac event rates compared to those with a positive FFR CT . However, the clinical utility of FFR CT 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 FFR CT 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 FFR CT 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 FFR CT was deemed to be ​≤ ​0.8., Results: FFR CT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) ​≥ ​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 ​= ​0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFR CT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those ​≥ ​or <65, regardless of FFR CT positivity or stenosis severity <50% or ≥50%. With a negative FFR CT result, and anatomical stenosis ≥50%, those ​≥ ​and <65 years of age, had similar rates of MACE (0.2% for both, p ​= ​0.1) and revascularisation (8.7% and 10.4% respectively p ​= ​0.4). Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFR CT 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 ​= ​0.02). Amongst patients with a FFR CT > 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 ​≥ ​or <65 with a FFR CT >0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFR CT are largely constant regardless of age., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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 (FFR CT ). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFR CT 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 FFR CT 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 FFR CT ≤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 FFR CT ≤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 FFR CT 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 FFR CT., Competing Interests: Declaration of competing interest Dr. Nous has received travel sponsorship from HeartFlow. Dr. Fairbairn has served on the Speakers Bureau for HeartFlow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Hurwitz-Koweek has received research support and fee as speaker from HeartFlow and Siemens. Dr. Pontone has received research grant and/or fee as speaker from GE Healthcare, Bracco, and HeartFlow. Dr. Budde has institutional research support from HeartFlow and Siemens Healthineers. Dr. Sonck has received research grant support from the Cardiopath PhD program. Dr. Rabbat has served as a consultant for HeartFlow. Dr. Mullen is an employee of and owns equity in HeartFlow. Dr. De Bruyne has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE Healthcare, Bayer, Philips, HeartFlow, Edwards Lifesciences, and Sanofi. Dr. Rogers is employee of and owns equity in HeartFlow. Dr. Leipsic has served as a consultant for and owns stock options in Circle CVI and HeartFlow. Dr. Patel has received research grants from HeartFlow, Bayer, Janssen, and the National Heart, Lung, and Blood Institute; and has served on the advisory board for HeartFlow, Bayer, and Janssen. Dr. Nieman has received institutional research support from Siemens Healthineers, HeartFlow, GE Healthcare, and Bayer Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Coronary artery calcifications (CAC) are frequently observed in patients referred for coronary CT angiography (CTA). Calcification volume (in mm 3 ) can accurately be assessed during catheterization by optical coherence tomography (OCT). The aim of the present study was to investigate the accuracy of CTA-derived assessment of calcification volume as compared with OCT. 66 calcified plaques (32 vessels) from 31 patients undergoing OCT-guided PCI with coronary CT acquired as a standard of care were included. Coronary CT and OCT images were matched using fiduciary points. Calcified plaques were reconstructed in three dimensions to calculate calcium volume. A Passing-Bablok regression analysis and the Bland-Altman method were used to assess the agreement between imaging modalities. Twenty-seven left anterior descending arteries and 5 right coronary arteries were analyzed. Median calcium volume by CTA and OCT were 18.23 mm 3 [IQR 8.09, 36.48] and 10.03 mm 3 [IQR 3.6, 22.88] respectively; the Passing-Bablok analysis showed a proportional without a systematic difference (Coefficient A 0.08, 95% CI - 1.37 to 1.21, Coefficient B 1.61, 95% CI 1.45 to 1.84) and the mean difference was 9.69 mm3 (LOA - 10.2 to 29.6 mm 3 ). No differences were observed for minimal lumen area (Coefficient A 0.07, 95% CI - 0.46 to 0.15, Coefficient B 0.85, 95% CI 0.64 to 1.2). CTA volumetric calcium evaluation overestimates calcium volume by 60% compared to OCT. This may allow for an appropriate interpretation of calcific burden in the non-invasive setting. Even in presence of calcific plaques, a good agreement in the MLA assessment was found. Coronary CT may emerge as a tool to quantify calcium burden for invasive procedural planning.

Objective: The prognostic importance of a coronary stenosis depends on its functional severity and its depending myocardial mass. Functional severity can be assessed by fractional flow reserve (FFR), estimated non-invasively by a specific validated CT algorithm (FFR CT ). Calculation of myocardial mass at risk by that same set of CT data (CTmass), however, has not been prospectively validated so far. The aim of the present study was to compare relative territorial-based CTmass assessment with relative flow distribution, which is closely linked to true myocardial mass., Methods: In this exploratory study, 35 patients with (near) normal coronary arteries underwent CT scanning for computed flow-based CTmass assessment and underwent invasive myocardial perfusion measurement in all 3 major coronary arteries by continuous thermodilution. Next, the mass and flows were calculated as relative percentages of total mass and perfusion., Results: The mean difference between CTmass per territory and invasively measured myocardial perfusion, both expressed as percentage of total mass and perfusion, was 5.3±6.2% for the left anterior descending territory, -2.0±7.4% for the left circumflex territory and -3.2±3.4% for the right coronary artery territory. The intraclass correlation between the two techniques was 0.90., Conclusions: Our study shows a close relationship between the relative mass of the perfusion territory calculated by the specific CT algorithm and invasively measured myocardial perfusion. As such, these data support the use of CTmass to estimate territorial myocardium-at-risk in proximal coronary arteries., Competing Interests: Competing interests: SF: institutional consultance/speaker fees from Bayer and Cathworks. CC: grants from HeartFlow, Abbott Vascular, Biosensors, Pie Medical and consultancy fees from HeartFlow and Philips. Member of the advisory board of Abbott Vascular, Pie Medical and Opsens. BDB: institutional grant; Abbott, Boston Scientific, Biotronik AG. Institutional consultance fees; Abbott, Opsens and Boston Scientific outside of the submitted work. Minor equities: Siemens, GE, Bayer, Philips, HeartFlow, Edwards Life Sciences and Ceyliad. NHJP: institutional grant; Abbott, Hexacath. Consultant; Abbott, Opsens. Minor equities Philips, GE, ASML, HeartFlow. Consultant GE and personal fees GE., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease (MVD), recent studies have demonstrated the superiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions compared to culprit lesion treatment-only therapy. FFR- and angio-guided PCI have however never been compared in STEMI patients., Trial Design: FLOWER-MI is an open-label multicenter national randomized clinical trial. The aim is to investigate FFR-guided complete revascularization in comparison to angio-guided complete revascularization in STEMI patients with successful PCI of the culprit lesion and ≥50% stenosis in at least one additional non-culprit lesion requiring PCI. Eligible patients will be randomized after successful primary PCI in a 1:1 fashion to either FFR-guided or angio-guided complete revascularization during the index procedure or a staged procedure before discharge (≤5 days). Patients assigned to FFR guidance first have FFR measured in each non-culprit vessel and only undergo PCI if FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac events, including all-cause death, non-fatal MI, and unplanned hospitalization leading to urgent revascularization at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, and 3-year outcomes. Based on estimated event rates, a sample size of 1170 patients is needed to show superiority of the FFR-guided revascularization with 80% power., Conclusion: The aim of FLOWER-MI trial is to assess whether FFR-guided complete revascularization in the acute setting is superior angio-guided complete revascularization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Fractional flow reserve (FFR) pullback allows to assess the distribution of pressure loss along the coronary vessels. FFR derived from CT (FFR CT ) provides a virtual pullback curve that may also aid in the assessment of the distribution of epicardial coronary resistance in the non-invasive setting. The present study aims to determine the accuracy of the virtual FFR CT pullback curve using a motorized invasive FFR pullback as reference in patients with stable coronary artery disease., Methods and Results: FFR values were extracted from coronary vessels at approximately 1 mm to generate pullback curves. Invasive motorized FFR pullbacks were acquired using a dedicated device at a speed of 1 mm/s. A total of 3172 matched FFR CT and FFR values were obtained in 24 vessels. The correlation coefficient between FFR CT and FFR was 0.76 (95%CI 0.75 to 0.78; p < 0.001). The area under the pullback curve was similar between FFR CT and invasive FFR (79.0 ± 16.1 vs. 85.3 ± 16.4, p = 0.097). The mean difference in lesion gradient between FFR CT and FFR was -0.07 (LOA -0.26 to 0.13) whereas in non-obstructive segments was -0.01 (LOA -0.06 to 0.05)., Conclusion: The evaluation of epicardial coronary resistance using coronary CT angiography with FFR CT was feasible. FFR CT virtual pullback appears to be accurate for the evaluation of pressure gradients. FFR CT has the potential to identify the pathophysiological pattern of coronary artery disease in the non-invasive setting., Competing Interests: Declaration of competing interest TM has been supported by a research grant provided by HeartFlow Inc. JS reports receiving research grant from the Cardiopath PhD. program. CC has been supported by a research grant provided by HeartFlow Inc and Biosensors. BDB declares that the Cardiovascular Center Aalst receives on his behalf grant support from Abbott, Boston Scientific, Biotronik, and St. Jude Medical and consulting fees from St. Jude Medical, Opsens, and Boston Scientific. He is a shareholder for Siemens, GE, Bayer, Philips, Heartflow Inc, Edwards LifeSciences, Sanofi, and Omega Pharma. DA received research grant from GE Healthcare and Bracco. The other authors have nothing to disclose., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the diagnostic performance of FFRangio (CathWorks, Kfar Saba, Israel), an angiogram-derived fractional flow reserve (FFR) technology., Background: Despite practice guidelines recommendations, the use of coronary physiologic assessment in daily practice remains low for patients undergoing coronary angiography. Angiogram-derived FFR technologies have the potential to promote the integration of physiologic assessment in daily practice., Methods: The study performed an analysis of pooled patient- and lesion-level data from 5 prospective cohort studies that examined the diagnostic performance of FFRangio compared with the reference standard wire-based FFR., Results: A total of 700 lesions from 588 patients were analyzed. Mean age was 65 years, 71% were men, and 40% presented with acute coronary syndromes. Mean FFR and FFRangio were 0.81 ± 0.12 and 0.81 ± 0.11, with 31.6% and 31.4% of lesions were in the 0.75 to 0.85 range, respectively. When using a binary cutoff FFR value of 0.80, FFRangio showed a sensitivity of 91%, a specificity of 94%, and a diagnostic accuracy of 93%. The mean difference between FFR and FFRangio was 0.00 ± 0.12. The correlation coefficient between FFR and FFRangio was 0.83 (p < 0.001). The C-statistic for FFRangio was 0.95 (p < 0.001). The accuracy of FFRangio was consistent across all subgroups examined., Conclusions: In the largest reported cohort examining the performance of angiogram-derived FFR technology, FFRangio showed excellent diagnostic performance, which was robust and consistent across all patient and lesion subgroups. Additional studies are needed allow FFRangio and fulfill its potential expand the implementation of functional assessment of coronary lesions in routine clinical practice., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary computed tomography angiography (CCTA) is at the frontline of the diagnostic strategies to detect coronary artery disease (CAD). Anatomical information have proven to be insufficient to detect hemodynamic significant epicardial stenosis. In the present invited review we discuss on FFR CT and stress CTP, emerging technologies for an accurate and comprehensive evaluation of patients with suspected CAD, offering both anatomical (i.e. luminal and plaque) and functional assessment in one single technique., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFR CT 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 (FFR CT ) 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 FFR CT 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 FFR CT  ≤0.80 and in 89 (5.60%) with an FFR CT >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 FFR CT  ≤0.80 and 12 occurred in those with an FFR CT >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 FFR CT  ≤0.80 compared with 10 (0.60%) patients with an FFR CT >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 FFR CT  ≤0.80 compared with patients with an FFR CT >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 FFR CT 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 FFR CT compared with patients with abnormal FFR CT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: We explored the anatomical, plaque, and hemodynamic characteristics of high-risk non-obstructive coronary lesions that caused acute coronary syndrome (ACS)., Methods: From the EMERALD study which included ACS patients with available coronary CT angiography (CCTA) before the ACS, non-obstructive lesions (percent diameter stenosis < 50%) were selected. CCTA images were analyzed for lesion characteristics by independent CCTA and computational fluid dynamics core laboratories. The relative importance of each characteristic was assessed by information gain., Results: Of the 132 lesions, 24 were the culprit for ACS. The culprit lesions showed a larger change in FFR CT across the lesion (ΔFFR CT ) than non-culprit lesions (0.08 ± 0.07 vs 0.05 ± 0.05, p = 0.012). ΔFFR CT showed the highest information gain (0.051, 95% confidence interval [CI] 0.050-0.052), followed by low-attenuation plaque (0.028, 95% CI 0.027-0.029) and plaque volume (0.023, 95% CI 0.022-0.024). Lesions with higher ΔFFR CT or low-attenuation plaque showed an increased risk of ACS (hazard ratio [HR] 3.25, 95% CI 1.31-8.04, p = 0.010 for ΔFFR CT ; HR 2.60, 95% CI 1.36-4.95, p = 0.004 for low-attenuation plaque). The prediction model including ΔFFR CT , low-attenuation plaque and plaque volume showed the highest ability in ACS prediction (AUC 0.725, 95% CI 0.724-0.727)., Conclusion: Non-obstructive lesions with higher ΔFFR CT or low-attenuation plaque showed a higher risk of ACS. The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk in non-obstructive lesions., Key Points: • Change in FFR CT across the lesion (ΔFFR CT ) was the most important predictor of ACS risk in non-obstructive lesions. • Non-obstructive lesions with higher ΔFFR CT or low-attenuation plaque were associated with a higher risk of ACS. • The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk.

Background: Diffuse atherosclerosis is commonly observed in angiographically normal segments in patients with stable coronary artery disease (CAD). The distribution of epicardial resistance along the vessel can be evaluated using coronary physiology., Objectives: The purpose of this study was to characterize the pathophysiological patterns of CAD using invasive pressure pullbacks during continuous hyperemia., Methods: In this prospective, multicenter study of patients undergoing clinically-indicated coronary angiography due to stable angina, a pressure-wire pullback device was set at a speed of 1 mm/s. Based on coronary angiography and on the fractional flow reserve (FFR) pullback curve, the patterns of CAD were adjudicated as focal, diffuse, or a combination of both. The distribution of epicardial resistance was characterized using the hyperemic pullback pressure gradients (PPGs). The PPG index, a continuous metric based on the magnitude of pressure drop over 20 mm and on the extent of functional disease was computed to determine the pattern of CAD. Low PPG index indicates diffuse CAD., Results: A total of 158 vessels (n = 117) were included. Overall, 984,813 FFR values were used to generate 100 FFR pullback curves. Using coronary physiology, 36% of the vessel disease patterns were reclassified compared to angiography. The median of maximal PPG over 20 mm was 0.083 (interquartile range: 0.063 to 0.118) FFR units, and the mean extent of functional disease was 39.3 ± 21.3 mm. The mean PPG index was 0.58 ± 0.18 and differentiated pathophysiological focal and diffuse disease (p < 0.001)., Conclusions: Pathophysiological patterns of CAD can be characterized by motorized hyperemic PPGs. The evaluation of the FFR pullback curve reclassified one-third of the vessels' disease patterns compared with conventional angiography. The PPG index is a novel metric that quantifies the distribution of epicardial resistance and discriminates focal from diffuse CAD. (Physiological Patterns of Coronary Artery Disease; NCT03824600)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR)., Background: The iFR was found to be non-inferior to the gold-standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices., Methods: Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively)., Results: Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR-) in 69 (11.8%) patients and positive discordant (FFR-/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta-blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR., Conclusions: During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR., (© 2019 Wiley Periodicals, Inc.)

Objectives: The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS)., Background: ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known., Methods: Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR CT ], change in FFR CT across the lesion [△FFR CT ], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR CT , △FFR CT , WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC)., Results: The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR CT and higher △FFR CT , WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001)., Conclusions: Noninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the impact of pre-diabetes (pre-DM) on coronary plaque characteristics and ischemic outcomes in patients with acute coronary syndromes (ACS)., Background: Pre-DM (i.e., the early stages of glucometabolic disturbance) is common among patients with ACS, but the extent to which pre-DM influences coronary plaque characteristics and the risk for adverse ischemic events is unclear., Methods: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in Coronary Tree) study, patients with ACS underwent quantitative coronary angiography, grayscale intravascular ultrasound, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention. Patients were divided into 3 groups according to their glucometabolic status, as defined by the American Diabetes Association: normal glucose metabolism (NGM), pre-DM, and diabetes mellitus (DM). These groups were compared with regard to coronary plaque characteristics and the risk for major adverse cardiac events (MACEs) (defined as cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina)., Results: Among 547 patients, 162 (29.6%) had NGM, 202 (36.9%) had pre-DM, and 183 (33.4%) had DM. There were no significant differences between the groups with regard to intravascular ultrasound findings indicative of vulnerable plaques. Patients with DM had a higher crude rate of MACEs than those with pre-DM or NGM (25.9% vs. 16.3% and 16.1%; p = 0.03 and p = 0.02, respectively). In an adjusted Cox regression model using NGM as the reference group, DM (hazard ratio: 2.20; 95% confidence interval: 1.25 to 3.86; p = 0.006) but not pre-DM (hazard ratio: 1.29; 95% confidence interval: 0.71 to 2.33; p = 0.41) was associated with increased risk for MACEs., Conclusions: Impaired glucose metabolism is common among patients presenting with ACS. DM but not pre-DM is associated with an increased risk for MACEs. Thus, preventing patients from progressing from pre-DM to DM is important. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Measuring fractional flow reserve (FFR) with a pressure wire remains underutilized because of the invasiveness of guide wire placement or the need for a hyperemic stimulus. FFR derived from routine coronary angiography (FFR angio ) eliminates both of these requirements and displays FFR values of the entire coronary tree. The FFR angio Accuracy versus Standard FFR (FAST-FFR) study is a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFR angio ., Methods: Coronary angiography was performed in a routine fashion in patients with suspected coronary artery disease. FFR was measured in vessels with coronary lesions of varying severity using a coronary pressure wire and hyperemic stimulus. Based on angiograms of the respective arteries acquired in ≥2 different projections, on-site operators blinded to FFR then calculated FFR angio using proprietary software. Coprimary end points were the sensitivity and specificity of the dichotomously scored FFR angio for predicting pressure wire-derived FFR using a cutoff value of 0.80. The study was powered to meet prespecified performance goals for sensitivity and specificity., Results: Ten centers in the United States, Europe, and Israel enrolled a total of 301 subjects and 319 vessels meeting inclusion/exclusion criteria which were included in the final analysis. The mean FFR was 0.81 and 43% of vessels had an FFR≤0.80. The per-vessel sensitivity and specificity were 94% (95% CI, 88% to 97%) and 91% (86% to 95%), respectively, both of which exceeded the prespecified performance goals. The diagnostic accuracy of FFR angio was 92% overall and remained high when only considering FFR values between 0.75 to 0.85 (87%). FFR angio values correlated well with FFR measurements ( r=0.80, P<0.001) and the Bland-Altman 95% confidence limits were between -0.14 and 0.12. The device success rate for FFR angio was 99%., Conclusions: FFR angio measured from the coronary angiogram alone has a high sensitivity, specificity, and accuracy compared with pressure wire-derived FFR. FFR angio has the promise to substantially increase physiological coronary lesion assessment in the catheterization laboratory, thereby potentially leading to improved patient outcomes., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT03226262.

Aims: Non-invasive assessment of stable chest pain patients is a critical determinant of resource utilization and clinical outcomes. Increasingly coronary computed tomography angiography (CCTA) with selective CCTA-derived fractional flow reserve (FFRCT) is being used. The ADVANCE Registry, is a large prospective examination of using a CCTA and FFRCT diagnostic pathway in real-world settings, with the aim of determining the impact of this pathway on decision-making, downstream invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular events (MACE)., Methods and Results: A total of 5083 patients with symptoms concerning for coronary artery disease (CAD) and atherosclerosis on CCTA were enrolled at 38 international sites from 15 July 2015 to 20 October 2017. Demographics, symptom status, CCTA and FFRCT findings, treatment plans, and 90 days outcomes were recorded. The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management plans occurred in 66.9% [confidence interval (CI): 64.8-67.6] of patients. Non-obstructive coronary disease was significantly lower in ICA patients with FFRCT ≤0.80 (14.4%) compared to patients with FFRCT >0.80 (43.8%, odds ratio 0.19, CI: 0.15-0.25, P < 0.001). In total, 72.3% of subjects undergoing ICA with FFRCT ≤0.80 were revascularized. No death/myocardial infarction (MI) occurred within 90 days in patients with FFRCT >0.80 (n = 1529), whereas 19 (0.6%) MACE [hazard ratio (HR) 19.75, CI: 1.19-326, P = 0.0008] and 14 (0.3%) death/MI (HR 14.68, CI 0.88-246, P = 0.039) occurred in subjects with an FFRCT ≤0.80., Conclusions: In a large international multicentre population, FFRCT modified treatment recommendation in two-thirds of subjects as compared to CCTA alone, was associated with less negative ICA, predicted revascularization, and identified subjects at low risk of adverse events through 90 days.

Background: The residual SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (RSS) quantitatively assesses angiographic completeness of revascularization after percutaneous coronary intervention (PCI) and has been shown to be a predictor of events after angiography-guided PCI. In stable patients undergoing functionally complete revascularization with fractional flow reserve (FFR) guidance, RSS did not predict outcome. Whether this is also true in patients with acute coronary syndromes (ACS) is unknown., Objectives: The purpose of this study was to determine whether the RSS could predict outcomes in patients with ACS., Methods: From the DANAMI-3-PRIMULTI (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), and FAMOUS-NSTEMI (Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes) trials, 547 patients presented with ACS and underwent functionally complete revascularization. Major adverse cardiac events (MACE) were defined as the composite endpoint of all-cause death, nonfatal myocardial infarction, and any repeat revascularization. The RSS was based on the recalculation of the SYNTAX score after PCI. We compared differences in 2-year outcome by the RSS subgroups: 0, 1 to <5, 5 to <10, ≥10 (RSS = 0 represents angiographically complete revascularization)., Results: The study population consisted of 271 patients with unstable angina/non-ST-segment elevation myocardial infarction and 276 with ST-segment elevation myocardial infarction. The mean RSS was 6.7 ± 5.8. MACE at 2 years occurred in 69 patients (12.6%). Patients with and without MACE had similar RSS after PCI (RSS: 7.2 ± 5.5 vs. 6.6 ± 5.9; p = 0.23). Kaplan-Meier curve analysis showed a similar incidence of MACE regardless of the RSS subgroups (p = 0.54). With and without adjustment of clinical variables, RSS was not a significant predictor of MACE or of each component of MACE., Conclusions: After complete revascularization of functionally significant stenosis by FFR, the extent of residual angiographic disease is not associated with subsequent ischemic events in patients presenting with ACS. These results suggest that the concept of functionally complete revascularization is applicable even in ACS patients. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [F.A.M.E.] NCT00267774; Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes [FAMOUS NSTEMI] NCT01764334; Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization [DANAMI-3-PRIMULTI]; NCT01960933)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Pressure-wire assessment of coronary stenosis is considered the invasive reference standard for detection of ischaemia-generating lesions. Recently, methods to estimate the fractional flow reserve (FFR) from conventional angiography without the use of a pressure wire have been developed, and were shown to have an excellent diagnostic accuracy. The present systematic review and meta-analysis aimed at determining the diagnostic performance of angiography-derived FFR for the diagnosis of haemodynamically significant coronary artery disease., Methods and Results: A systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR systems were performed. The primary outcome of interest was pooled sensitivity and specificity. Thirteen studies comprising 1842 vessels were included in the final analysis. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89% (95% credible interval 83-94%), specificity of 90% (95% credible interval 88-92%), positive likelihood ratio (+LR) of 9.3 (95% credible interval 7.3-11.7) and negative likelihood ratio (-LR) of 0.13 (95% credible interval 0.07-0.2). The summary area under the receiver-operating curve was 0.84 (95% credible interval 0.66-0.94). Meta-regression analysis did not find differences between the methods for pressure-drop calculation (computational fluid dynamics vs. mathematical formula), type of analysis (on-line vs. off-line) or software packages., Conclusion: The accuracy of angiography-derived FFR was good to detect haemodynamically significant lesions with pressure-wire measured FFR as a reference. Computational approaches and software packages did not influence the diagnostic accuracy of angiography-derived FFR. A diagnostic strategy trial with angiography-derived FFR evaluating clinical endpoints is warranted.

Clinical benefit of invasive functionally guided revascularization has been mostly investigated and proven for percutaneous coronary intervention. It has never been prospectively evaluated whether a systematic fractional flow reserve (FFR) assessment is also beneficial in guiding coronary artery bypass graft surgery (CABG). The objective of the GRAft patency after FFR-guided versus angiography-guIded CABG (GRAFFITI) trial was to compare an FFR-guided revascularization strategy to the traditional angiography-guided revascularization strategy for patients undergoing CABG. Patients were enrolled with significantly diseased left anterior descending or left main stem and at least one major coronary artery with angiographically intermediate stenosis (30-90% diameter stenosis) that was assessed by FFR. Thereafter, while the FFR values were kept concealed, cardiac surgeons decided their intended procedural strategy based on the coronary angiography alone. At this point, patients underwent 1:1 randomization to either an FFR-guided or an angiography-guided CABG strategy. In case the patient was randomized to angiography-guided arm, cardiac surgeons kept their intended procedural strategy, i.e., CABG was guided solely on the basis of the coronary angiography. In case the patient was randomized to the FFR-guided arm, FFR values were disclosed to the surgeons who revised the surgical protocol according to the functional significance of each coronary stenosis. The primary endpoint of the trial was the rate of graft occlusion at 12 months, assessed by coronary computed tomography or coronary angiography. The secondary endpoints were (1) length of postoperative hospital stay; (2) changes in surgical strategy depending upon FFR results (in FFR-guided group only); and (3) rate of major adverse cardiac and cerebrovascular events, i.e., composite of death, myocardial infarction, stroke, and any revascularization during the follow-up period. This study is the first prospective randomized trial investigating potential clinical benefits, associated with FFR-guided surgical revascularization., Trial Registration: NCT01810224.

Background: Fractional flow reserve (FFR)-guided coronary artery bypass graft (CABG) surgery has been associated with lower number of graft anastomoses, lower rate of on-pump surgery, and higher graft patency rate as compared with angiography-guided CABG surgery. However, no clinical benefit has been reported to date., Methods and Results: Consecutive patients (n=627) treated by CABG between 2006 and 2010 were retrospectively included. In 198 patients, at least 1 stenosis was grafted according to FFR (FFR-guided group), whereas in 429 patients all stenoses were grafted based on angiography (angiography-guided group). The 2 coprimary end points were overall death or myocardial infarction and major adverse cardiovascular events (composite of overall death, myocardial infarction, and target vessel revascularization) up to 6-year follow-up. In the FFR-guided group, patients were significantly younger (66 [57-73] versus 70 [63-76]; P <0.001), more often male (82% versus 72%; P =0.008), and less often diabetic (21% versus 30%; P =0.023). Clinical follow-up (median, 85 [66-104] months) was analyzed in 396 patients after 1:1 propensity-score matching for these 3 variables. The rate of overall death or myocardial infarction was significantly lower in the FFR-guided (n=31 [16%] versus n=49 [25%]; hazard ratio, 0.59 [95% confidence interval, 0.38-0.93]; P =0.020) as compared with the angiography-guided group. Major adverse cardiovascular events rate was also numerically lower in the FFR-guided than in the angiography-guided group (n=42 [21%] versus n=52 [26%]; hazard ratio, 0.77 [95% confidence interval, 0.51-1.16]; P =0.21)., Conclusions: FFR-guided CABG is associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG., (© 2018 American Heart Association, Inc.)

Background: Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history., Methods: The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR≤0.80; DS≥50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR≤0.80; DS<50%), and negative mismatch (FFR>0.80; DS≥50%)., Results: The rate of VOCE was highest in the positive concordance group (log rank: X 2 =80.96; P =0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21-0.67; P =0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR≤0.80; hazard ratio, 0.77; 95% confidence interval, 0.57-1.09; P =0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96-3.74; P =0.067)., Conclusions: In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS)., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01132495., (© 2017 American Heart Association, Inc.)

Objectives: The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR., Background: In patients with stable ischemic heart disease, FFR-guided revascularization, as compared with medical therapy alone, is reported to improve outcomes. Because morphological characteristics are the basis of plaque rupture and acute coronary events, a relationship between FFR and lesion characteristics may exist., Methods: This is a subanalysis of NXT (HeartFlowNXT: HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography), a prospective, multicenter study of 254 patients (age 64 ± 10 years, 64% male) with suspected stable ischemic heart disease; coronary computed tomography angiography including plaque morphology assessment, invasive angiography, and FFR were obtained for 383 lesions. Ischemia was defined by invasive FFR ≤0.80. Computed tomography angiography-defined morphological characteristics of plaques and their vascular location were used in univariate and multivariate analyses to examine their predictive value for invasive FFR. The distribution of various combinations of plaque morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR were examined., Results: The percentage of luminal stenosis, low-attenuation plaque (LAP) or necrotic core volume, left anterior descending coronary artery territory, and the presence of multiple lesions per vessel were the predictors of FFR. When grouped on the basis of degree of luminal stenosis, FFR-negative lesions had consistently smaller LAP volumes compared with FFR-positive lesions. The distribution of plaque characteristics in lesions with normal and abnormal FFR demonstrated that whereas FFR-negative lesions excluded likelihood of stenotic plaques with moderate to high LAP volumes, only one-third of FFR-positive lesions demonstrated obstructive plaques with moderate to high LAP volumes., Conclusions: In addition to the severity of luminal stenosis, necrotic core volume is an independent predictor of FFR. The distribution of plaque characteristics among lesions with varying luminal stenosis and normal and abnormal FFR may explain the outcomes associated with FFR-guided therapy., (Copyright © 2018. Published by Elsevier Inc.)

Background: To date, the clinical utility of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT) has been limited to trials and single center experiences. We herein report the incidence of abnormal FFRCT (≤0.80) and the relationship of lesion-specific ischemia to subject demographics, symptoms, and degree of stenosis in the multicenter, prospective ADVANCE registry., Methods: One thousand patients with suspected angina having documented coronary artery disease on coronary CTA and clinically referred for FFR CT were prospectively enrolled in the registry. Patient demographics, symptom status, coronary CTA and FFR CT findings were recorded. Univariate and multivariate analyses were performed to investigate the predictors related to abnormal FFR CT ., Results: FFR CT data were analyzed in 952 patients (95.2%). Overall, 51.1% patients had a positive FFR CT value (≤0.80). Patients with ≥3 risk factors had a significantly higher rate of abnormal FFR CT than those with <3 risk factors (60.2% vs. 43.9%, p = 0.0001). On multivariate analysis, baseline diabetes (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.04-2.21, p = 0.030) and hypertension (OR 1.56, 95%CI 1.14-2.14, p = 0.005) were both predictive of abnormal FFR CT . In addition, >70% stenosis was significantly associated with low FFR CT (OR 31.16, 95%CI 12.25-79.22, p < 0.0001) vs. <30% stenosis. Notably, stenosis 30-49% vs. <30% had an increased likelihood of ischemia (OR 3.74, 95%CI 1.52-9.17, p < 0.0001)., Conclusions: In this real-world registry, CT angiographic stenosis severity in addition to baseline cardiovascular risk factors conferred an increased likelihood of an abnormal FFR CT . Importantly, however, mild CT angiographic stenoses were noted to have an increased hazard for ischemia and the converse holding true for more severe stenoses as well., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Pressure measurement for the duration of the wave-free period (WFP) is considered essential for resting-state physiological assessment of coronary stenosis severity using the instantaneous wave-free ratio (iFR)., Objectives: The aim of this study was to compare other diastolic resting indexes to iFR., Methods: In the population of the VERIFY2 (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography) study, iFR calculated by proprietary software (Volcano Harvest, Volcano Corporation, Rancho Cordova, California) was compared with the ratio of resting distal coronary pressure and aortic pressure during the complete duration of diastole (dPR), 25% to 75% of diastole (dPR 25-75 ), and midpoint of diastole (dPR mid ), along with Matlab calculated iFR (iFR matlab ) and iFR-like indexes shortening the length of the WFP by 50 and 100 ms (iFR -50ms and iFR -100ms ), respectively. Mutual differences, Spearman correlations, area under the curve values from receiver-operating characteristic analyses, and diagnostic performance with respect to iFR and fractional flow reserve (FFR) were calculated for all indexes., Results: Median iFR in 197 patients with 257 vessels was 0.91 with an interquartile range of 0.87 to 0.95. The mutual differences (± SD) with iFR were 0.006 ± 0.011 (dPR), 0.001 ± 0.007 (dPR 25-75 ), 0.001 ± 0.008 (dPR mid ), 0.005 ± 0.009 (iFR matlab ), 0.003 ± 0.008 (iFR -50ms ), and 0.001 ± 0.009 (iFR -100ms ). Correlations for all indexes with iFR were >0.99 (p < 0.001 for all). Area under the curve values for predicting iFR were >0.99 for all indexes as well. Diagnostic accuracy compared with FFR was 76% to 77% for all indexes including iFR., Conclusions: All diastolic resting indexes tested were identical to iFR, both numerically and with respect to their agreement with FFR. A numerically equal value to iFR can be determined without restriction to the WFP. Cutoff values, guidelines, and clinical recommendations for iFR can therefore be extended to these other indexes. (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography [VERIFY2]; NCT02377310)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We hypothesize that in patients with suspected coronary artery disease (CAD), lower values of the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) result in lower fractional flow reserve (FFR)., Methods: V/M was computed in 238 patients from the NXT trial who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography (QCA) and FFR measurement in 438 vessels. Nitroglycerin was administered prior to CT, QCA and FFR acquisition. The V/M ratio was quantified on a patient-level from CT image data by segmenting the epicardial coronary arterial lumen volume (V) and the left ventricular myocardial mass (M). Calcified and noncalcified plaque volumes were quantified using semi-automated software., Results: The median value of V/M (18.57 mm 3 /g) was used to define equal groups of low and high V/M patients. Patients with low V/M had greater diameter stenosis by QCA, more plaque and lower FFR (0.80 ± 0.12 vs. 0.87 ± 0.08; P < 0.0001) than those with high V/M. A total of 365 vessels in 202 patients had QCA stenosis ≤50% and measured FFR. In these patients, those with low V/M had higher percent diameter stenosis by QCA, greater total plaque volume and lower FFR (0.81 ± 0.12 vs. 0.88 ± 0.07; P < 0.0001) than those with high V/M. In multivariate logistic regression analysis, V/M was an independent predictor of FFR ≤0.80 (all p-values < 0.001)., Conclusions: Patients with a low V/M ratio have lower FFR overall and in non-obstructive CAD, independent of plaque measures., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fractional flow reserve (FFR), an index of the hemodynamic severity of coronary stenoses, is derived from invasive measurements and requires a pressure-monitoring guidewire and hyperemic stimulus. Angiography-derived FFR measurements (FFR angio ) may have several advantages. The aim of this study is to assess the diagnostic performance and interobserver reproducibility of FFR angio in patients with stable coronary artery disease., Methods and Results: FFR angio is a computational method based on rapid flow analysis for the assessment of FFR. FFR angio uses the patient's hemodynamic data and routine angiograms to generate a complete 3-dimensional coronary tree with color-coded FFR values at any epicardial location. Hyperemic flow ratio is derived from an automatic resistance-based lumped model of the entire coronary tree. A total of 203 lesions were analyzed in 184 patients from 4 centers. Values derived using FFR angio ranged from 0.5 to 0.97 (median 0.85) and correlated closely (Spearman ρ=0.90; P <0.001) with the invasive FFR measurements, which ranged from 0.5 to 1 (median 0.84). In Bland-Altman analyses, the 95% limits of agreement between these methods ranged from -0.096 to 0.112. Using an FFR cutoff value of 0.80, the sensitivity, specificity, and diagnostic accuracy of FFR angio were 88%, 95%, and 93%, respectively. The intraclass coefficient between 2 blinded operators was 0.962 with a 95% confidence interval from 0.950 to 0.971, P <0.001., Conclusions: There is a high concordance between FFR angio and invasive FFR. The color-coded display of FFR values during coronary angiography facilitates the integration of physiology and anatomy for decision making on revascularization in patients with stable coronary artery disease., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03005028., (© 2017 American Heart Association, Inc.)

The application of computational fluid dynamics to coronary computed tomography angiography allows Fractional Flow Reserve (FFR) to be calculated non-invasively (FFR CT ), enabling computation of FFR from coronary computed tomography angiography acquired at rest both for individual lesions as well as along the entire course of a coronary artery. FFR CT , validated in a number of accuracy studies and a large clinical utility trial, is beginning to penetrate clinical practice. Importantly, while accuracy trials compared FFR CT to invasively measured FFR at a single point in the coronary tree, clinical reports of FFR CT provide information regarding a patient's entire coronary vasculature. Specifically, in distal coronary segments, calculated FFR CT values may be low and below 0.80 even in the absence of localized stenoses within the course of the artery. As a result, the reporting physician needs to understand how to interpret the findings in a clinically useful and thoughtful fashion. This review provides a brief overview of the background of both invasively measured and computationally derived FFR, explains changes in FFR along the course of normal coronary arteries and those affected by coronary atherosclerosis, and outlines the relevance of measurement location when interpreting and reporting FFR and FFR CT results., (Published by Elsevier Inc.)

Background: The correlation between angiographic assessment of coronary stenoses and fractional flow reserve (FFR) is weak. Whether and how risk factors impact the diagnostic accuracy of angiography is unknown. We sought to evaluate the diagnostic accuracy of angiography by visual estimate and by quantitative coronary angiography when compared with FFR and evaluate the influence of risk factors (RF) on this accuracy., Methods and Results: In 1382 coronary stenoses (1104 patients), percent diameter stenosis by visual estimation (DS VE ) and by quantitative coronary angiography (DS QCA ) was compared with FFR. Patients were divided into 4 subgroups, according to the presence of RFs, and the relationship between DS VE , DS QCA , and FFR was analyzed. Overall, DS VE was significantly higher than DS QCA ( P <0.0001); nonetheless, when examined by strata of DS, DS VE was significantly smaller than DS QCA in mild stenoses, although the reverse held true for severe stenoses. Compared with FFR, a large scatter was observed for both DS VE and DS QCA . When using a dichotomous FFR value of 0.80, C statistic was significantly higher for DS VE than for DS QCA (0.712 versus 0.640, respectively; P <0.001). C statistics for DS VE decreased progressively as RFs accumulated (0.776 for ≤1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for ≥4 RFs; P =0.0053). In addition, in diabetics, the relationship between FFR and angiographic indices was particularly weak (C statistics: 0.524 for DS VE and 0.511 for DS QCA )., Conclusions: Overall, DS VE has a better diagnostic accuracy than DS QCA to predict the functional significance of coronary stenosis. The predictive accuracy of angiography is moderate in patients with ≤1 RFs, but weakens as RFs accumulate, especially in diabetics., (© 2017 American Heart Association, Inc.)

Background: Coronary CT angiography (CTA) is a reliable tool for the detection of coronary artery disease (CAD) that conveys significant prognostic information. It does not provide data on the hemodynamic significance of a given lesion, particularly in intermediate-grade stenosis. Fractional flow reserve by CT (FFR CT ) can accurately predict the hemodynamic significance of coronary lesions. The primary objective of this registry is to determine whether the integration of FFR CT as an adjunct to coronary CTA will lead to a significant change in the management of CAD in patients with stable angina., Methods: The ADVANCE Registry is a multi-center, prospective registry designed to evaluate utility, clinical outcomes and resource utilization following FFR CT -guided treatment in clinically stable, symptomatic patients diagnosed with CAD by coronary CTA. Approximately 5000 patients will be enrolled from up to 50 sites in Europe, USA, Canada and Asia. Requirement for enrollment is the presence of atherosclerosis on coronary CTA. For each enrolled patient, a clinical management review committee will use data from coronary CTA and FFR CT to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The primary endpoint of the registry is the reclassification rate between the management plan based on coronary CTA alone versus CTA plus FFR CT . The secondary endpoints of the registry include the evaluation of the rate of invasive coronary angiography (ICA), revascularization, major adverse coronary events, resource utilization, cumulative radiation dose exposure and the rate of ICA without obstructive CAD at 3-year follow-up., Conclusions: The ADVANCE registry is designed to assess the real-world impact of FFR CT on the clinical management of stable CAD when used along with coronary CTA., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the distribution of pressure and shear-related forces acting on atherosclerotic plaques and their association with lesion characteristics using coronary CT angiography (cCTA)-based computational fluid dynamics (CFD) model of epicardial coronary arteries., Methods: Patient-specific models of epicardial coronary arteries were reconstructed from cCTA in 80 patients (12 women, 63.8±9.0 years). The pressure and wall shear stress (WSS) in left anterior descending coronary arteries were assessed using CFD. High-risk plaques were defined as the presence of at least one of the following adverse plaque characteristics: low-density plaque, positive remodelling, napkin-ring sign and spotty calcification., Results: At resting condition, 39.5% of stenotic segments (% diameter stenosis 52.3±14.4%) were exposed to high WSS (>40 dyne/cm(2)). When the stenotic lesion was subdivided into three segments, the distribution of WSS was different from that of pressure change and its magnitude was highest at minimal lumen area (p<0.001). High pressure gradient, proximal location, small lumen and short length were independent determinants of WSS (all p<0.05). The plaques exposed to the highest WSS tertile had a significantly greater proportion of high-risk plaques. The addition of WSS to % diameter stenosis significantly improved the measures of discrimination and reclassification of high-risk plaques (area under the curves from 0.540 to 0.718, p=0.031; net reclassification index 0.827, p<0.001)., Conclusions: The cCTA-based CFD method can improve the identification of high-risk plaques and the risk stratification for coronary artery disease patients by providing non-invasive measurements of WSS affecting coronary plaques., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) might occur more frequently during challenging procedures such as PCI of chronic coronary total occlusion (CTO). The prognostic implication of PMI in CTO-PCI remains unclear., Methods: From January 2006 to September 2012, a total of 715 consecutive patients undergoing CTO-PCI were screened at three centers. Only patients with available pre-PCI and post-PCI troponin (cTn) were included (n = 442). PMI was defined as an elevation of cTn >5x the upper reference limit (URL), or a rise of cTn >20% if baseline values were elevated., Results: Patients were grouped into: (1) successful CTO-PCI and no-PMI (Group A; n = 195); (2) successful CTO-PCI with PMI (Group B; n = 133); failed CTO-PCI (Group C; n = 114). Occurrence of major adverse cardiovascular event (MACE) was assessed in 431 patients (97%), at a median follow-up of 25 months, and were significantly lower in patients successfully treated without PMI occurrence, while increased in cases of PMI or failed CTO-PCI (Group A, 9%; Group B, 15%; Group C, 28%; hazard ratio, 1.57 (95% confidence interval, 1.12-2.18); P<.01). At Kaplan-Meier analysis, MACE-free survival was significantly higher in Group A (log-rank, 21.46; P<.001)., Conclusion: Successful CTO revascularization is still associated with a better long-term clinical outcome vs patients in whom it failed, regardless of the occurrence of PMI.

Background: Coronary computed tomographic angiography (CTA) plus estimation of fractional flow reserve using CTA (FFRCT) safely and effectively guides initial care over 90 days in patients with stable chest pain. Longer-term outcomes are unknown., Objectives: The study sought to determine the 1-year clinical, economic, and quality-of-life (QOL) outcomes of using FFRCT instead of usual care., Methods: Consecutive patients with stable, new onset chest pain were managed by either usual testing (n = 287) or CTA (n = 297) with selective FFRCT (submitted in 201, analyzed in 177); 581 of 584 (99.5%) completed 1-year follow-up. Endpoints were adjudicated major adverse cardiac events (MACE) (death, myocardial infarction, unplanned revascularization), total medical costs, and QOL., Results: Patients averaged 61 years of age with a mean 49% pre-test probability of coronary artery disease. At 1 year, MACE events were infrequent, with 2 in each arm of the planned invasive group and 1 in the planned noninvasive cohort (usual care strategy). In the planned invasive stratum, mean costs were 33% lower with CTA and selective FFRCT ($8,127 vs. $12,145 usual care; p < 0.0001); in the planned noninvasive stratum, mean costs did not differ when using an FFRCT cost weight of zero ($3,049 FFRCT vs. $2,579; p = 0.82), but were higher when using an FFRCT cost weight equal to CTA. QOL scores improved overall at 1 year (p < 0.001), with similar improvements in both groups, apart from the 5-item EuroQOL scale scores in the noninvasive stratum (mean change of 0.12 for FFRCT vs. 0.07 for usual care; p = 0.02)., Conclusions: In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial., Methods: From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both ≤ 40%, n = 90 and ≤ 50%, n = 252) and preserved EF (> 40%, n = 825 and > 50%, n = 663) according to the angiographic stenosis severity. We also compared differences in 1 year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF., Results: Both groups had similar FFR values in lesions with 50-70% stenosis (p = 0.49) and with 71-90% stenosis (p = 0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91-99% stenosis (0.55 vs. 0.50, p = 0.02), although the vast majority of FFR values remained ≤ 0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk = 0.76, p = 0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk = 0.81, p = 0.25). The results were similar with an EF cutoff of 40%., Conclusion: Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Fractional flow reserve estimated using computed tomography (FFRCT) might improve evaluation of patients with chest pain., Objectives: The authors sought to determine the effect on cost and quality of life (QOL) of using FFRCT instead of usual care to evaluate stable patients with symptoms suspicious for coronary disease., Methods: Symptomatic patients without known coronary disease were enrolled into 2 strata based on whether invasive or noninvasive diagnostic testing was planned. In each stratum, consecutive observational cohorts were evaluated with either usual care or FFRCT. The number of diagnostic tests, invasive procedures, hospitalizations, and medications during 90-day follow-up were multiplied by U.S. cost weights and summed to derive total medical costs. Changes in QOL from baseline to 90 days were assessed using the Seattle Angina Questionnaire, the EuroQOL, and a visual analog scale., Results: In the 584 patients, 74% had atypical angina, and the pre-test probability of coronary disease was 49%. In the planned invasive stratum, mean costs were 32% lower among the FFRCT patients than among the usual care patients ($7,343 vs. $10,734 p < 0.0001). In the noninvasive stratum, mean costs were not significantly different between the FFRCT patients and the usual care patients ($2,679 vs. $2,137; p = 0.26). In a sensitivity analysis, when the cost weight of FFRCT was set to 7 times that of computed tomography angiography, the FFRCT group still had lower costs than the usual care group in the invasive testing stratum ($8,619 vs. $ 10,734; p < 0.0001), whereas in the noninvasive testing stratum, when the cost weight of FFRCT was set to one-half that of computed tomography angiography, the FFRCT group had higher costs than the usual care group ($2,766 vs. $2,137; p = 0.02). Each QOL score improved in the overall study population (p < 0.0001). In the noninvasive stratum, QOL scores improved more in FFRCT patients than in usual care patients: Seattle Angina Questionnaire 19.5 versus 11.4, p = 0.003; EuroQOL 0.08 versus 0.03, p = 0.002; and visual analog scale 4.1 versus 2.3, p = 0.82. In the invasive cohort, the improvements in QOL were similar in the FFRCT and usual care patients., Conclusions: An evaluation strategy based on FFRCT was associated with less resource use and lower costs within 90 days than evaluation with invasive coronary angiography. Evaluation with FFRCT was associated with greater improvement in quality of life than evaluation with usual noninvasive testing. (Prospective Longitudinal Trial of FFRCT: Outcomes and Resource Impacts [PLATFORM]; NCT01943903)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up., Methods: The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774., Findings: After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001)., Interpretation: The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients., Funding: St Jude Medical, Friends of the Heart Foundation, and Medtronic., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Fractional flow reserve derived from coronary computed tomography angiography enables noninvasive assessment of the hemodynamic significance of coronary artery lesions and coupling of the anatomic severity of a coronary stenosis with its physiological effects. Since its initial demonstration of feasibility of use in humans in 2011, a significant body of clinical evidence has developed to evaluate the diagnostic performance of coronary computed tomography angiography-derived fractional flow reserve compared with an invasive fractional flow reserve reference standard. The purpose of this paper was to describe the scientific principles and to review the clinical data of this technology recently approved by the U.S. Food and Drug Administration., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI., Trial Design: The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ≥50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ≥50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up., Conclusion: The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Fractional flow reserve (FFR) measured by coronary computed tomography angiography (FFRCT) has been validated against invasive FFR. However, there are no data on how the use of FFRCT affects patient care and outcomes. The aim of this study is to compare standard practice guided by usual care testing to FFRCT-guided management in symptomatic subjects with suspected coronary artery disease (CAD)., Methods: In this prospective nonrandomized trial, symptomatic patients with suspected CAD will be enrolled in 2 consecutive cohorts: a usual care-guided pathway (cohort 1) and an FFRCT-guided pathway (cohort 2). Each cohort is divided into 2 groups according to whether noninvasive or invasive diagnostic testing was planned before enrollment. In all subjects, the patient's clinical team will review all diagnostic test results and determine a treatment strategy. A total sample size of 580 subjects will be enrolled and followed up for 12 months., Results: The primary end point is the comparison of the percentage of patients with planned invasive testing who have a catheterization (invasive coronary angiography) within 90 days from initial assessment, which does not show a significant stenosis (defined as coronary artery stenosis >50% or invasive FFR ≤0.80). Secondary end points include the rate of invasive coronary angiography without obstructive CAD in those with planned noninvasive testing and, in all groups, noninferiority of resource use, quality of life, medical radiation exposure, and major adverse cardiac events up to 365 days of follow-up., Conclusions: The study compares clinical and economic outcomes based on diagnostic evaluation using FFRCT with that based on standard diagnostic strategies., (Copyright © 2015 Elsevier Inc. All rights reserved.)