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Introduction and Objectives: Several studies have investigated the effectiveness of fractional flow reserve (FFR) guidance in improving clinical outcomes after myocardial revascularization, yielding conflicting results. The aim of this study was to compare clinical outcomes in patients with coronary artery disease following FFR-guided or angiography-guided revascularization., Methods: Both randomized controlled trials (RCTs) and nonrandomized intervention studies were included. Coprimary endpoints were all-cause death, myocardial infarction, and major adverse cardiovascular events (MACE). The study is registered with PROSPERO (CRD42022344765)., Results: A total of 30 studies enrolling 393 588 patients were included. FFR-guided revascularization was associated with significantly lower rates of all-cause death (OR, 0.63; 95%CI, 0.53-0.73), myocardial infarction (OR, 0.70; 95%CI, 0.59-0.84), and MACE (OR, 0.77; 95%CI, 0.70-0.85). When only RCTs were considered, no significant difference between the 2 strategies was observed for any endpoints. However, the use of FFR was associated with reduced rates of revascularizations and treated lesions. Metaregression suggested that the higher the rate of revascularized patients the lower the benefit of FFR guidance on MACE reduction compared with angiography guidance (P=.012). Similarly, higher rates of patients with acute coronary syndromes were associated with a lower benefit of FFR-guided revascularization (P=.039)., Conclusions: FFR-guided revascularization was associated with lower rates of all-cause death, myocardial infarction and MACE compared with angiographic guidance, with RCTs and nonrandomized intervention studies yielding conflicting data. The benefits of FFR-guidance seem to be less evident in studies with high revascularization rates and with a high prevalence of patients with acute coronary syndrome., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. 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.)

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes., Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI., Results: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P <0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P <0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97])., Conclusions: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317., Competing Interests: Dr Collet reports receiving research grants from Biosensors, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; consultancy fees from HeartFlow, OpSens Medical, Abbott Vascular, and Philips Volcano; and has patents pending on diagnostic methods for coronary artery disease. Dr Munhoz reports a research grant provided by the CardioPath PhD programme and speaker fees from Abbott Vascular. Dr Mizukami reports receiving research grants from Boston Scientific and speaker fees from Abbott Vascular, CathWorks, and Boston Scientific. Dr Matsuo has received consulting fees from Kaneka and Zeon and speaker’s fees from Abbott Medical Japan, Boston Scientific, Philips, and Amgen. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Biscaglia received research grants provided by Sahajanand Medical Technologies, Medis Medical Imaging, Eukon Srl, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr Engstrøm reports speaker and advisory board fees from Abbott, Boston Scientific, and Novo Nordisk. Dr Leone reports receiving consultancy fees from Abbott and honoraria for sponsored symposia from Abbott, Medtronic, and Abiomed. Dr Fearon receives institutional research support from Abbott, Boston Scientific, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options from HeartFlow. Dr Christiansen has received consulting fees from Abbott Medical Denmark A/S. Dr Yong has received minor honoraria from Abbott Vascular and research grants from Abbott Vascular and Philips. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from the Spanish Instituto de Salud Carlos III and received speaker and advisory board member fees from Abbott and Philips. Dr Storozhenko reports a grant provided by the EAPCI Fellowship Programme. Dr West is an employee of Abbott Vascular. Dr De Potter is a paid consultant for Biosense Webster and receives grant support (institutional) and consultancy fees (institutional) from Abbott. Dr Berry receives research funding from the British Heart Foundation (grants RE/18/6134217, BHF/FS/17/26/32744, and PG/19/28/34310) and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis Research, GlaxoSmithKline, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. Dr Collison has received consulting fees from Abbott. Dr Johnson has received consultancy or speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, and Terumo, and research grants from Abbott Vascular. Dr Amano reports receiving lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi Sankyo, and Bristol Myers Squibb. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Jeremias has received consulting fees from Canon Medical, Artrya Medical, and Boston Scientific. Dr Ali reports institutional grant support from Abbott, Abiomed, Acist, Amgen, Boston Scientific, CathWorks, Canon Medical, Conavi, HeartFlow, Inari, Medtronic, the US National Institutes of Health, Nipro, OpSens Medical, Medis, Philips, Shockwave, Siemens, SpectraWAVE, and Teleflex; consulting fees from Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens Medical, Philips, and Shockwave; and equity in Elucid, Lifelink, SpectraWAVE, Shockwave, and VitalConnect. Dr Pijls has received research grants from Abbott and Hexacath; consultancy fees from Abbott, GE, Philips, and HeartFlow; and has equity in General Electric, Philips, and HeartFlow. Dr De Bruyne reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular. Dr Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02184117]) and Philips Volcano (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820]) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510[k] K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology and on methods to correct pressure tracings from fluid-filled catheters.

Background: The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance., Objectives: The authors tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function., Methods: In a cohort of 16 patients who had undergone proximal left anterior descending artery stenting, we created 4 grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) to assess their response to changing epicardial resistance., Results: Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ± 0.05; mild: 0.72 ± 0.04; moderate: 0.61 ± 0.05; severe: 0.48 ± 0.09; P < 0.001). This translated into a linear decrease in mean hyperemic coronary flow (no stenosis: 170.5 ± 66.8 mL/min; mild: 149.8 ± 58.8 mL/min; moderate: 124.4 ± 53.0 mL/min; severe: 94.0 ± 45.2 mL/min; P < 0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ± 0.9; mild: 2.2 ± 0.8; moderate: 1.8 ± 0.7; severe: 1.4 ± 0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (P < 0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ± 1.0; mild: 3.0 ± 1.0; moderate: 2.9 ± 1.0; severe: 2.8 ± 1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (P < 0.001)., Conclusions: MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease., Competing Interests: Funding Support and Author Disclosures Dr Mahendiran is supported by a grant from the Swiss National Science Foundation. Drs Bertolone, Viscusi, and Wilgenhof have received research grants provided by the Cardiopath PhD program. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and has received consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. Dr Pijls has received institutional research grants from Abbott; has consulting relationships with and receives fees from Abbott and Coroventis; has equity in ASML, General Electric, HeartFlow, and Philips; is a member of the Scientific Advisory Board of Heartflow; and has patents pending in the field of the coronary microcirculation and aortic valve stenosis. Dr De Bruyne has a consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; has received research grants from Abbott Vascular, Coroventis Research, Cathworks, 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).)

Objective: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFR CT Planner) across different levels of image quality., Materials and Methods: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFR CT Planner. Patient- and technical-related factors that could affect the FFR CT Planner accuracy were evaluated. The FFR CT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR., Results: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFR CT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFR CT Planner was accurate across different levels of image quality with a mean difference between FFR CT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFR CT Planner (95%CI - 0.06 to - 0.001, p = 0.040)., Conclusion: The FFR CT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality., Clinical Relevance Statement: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFR CT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFR CT Planner., Key Points: • The fractional flow reserve derived from coronary CT angiography (FFR CT ) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFR CT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFR CT Planner could potentially enhance and guide the invasive treatment., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Aims: Coronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition., Methods: Prospective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained., Results: One hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56-0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30-0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6-24.3] vs. 7.03 [4.8-11.7] Pa, p < 0.001) and TSVI (163.9 [117.6-249.2] vs. 76.8 [23.1-140.9] m -1 , p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00-1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19-9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11-7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002)., Conclusions: Focal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features., Clinical Trial Registration: https://clinicaltrials,gov/ct2/show/NCT03782688., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Following percutaneous coronary intervention (PCI), optical coherence tomography provides prognosis information. The pullback pressure gradient is a novel index that discriminates focal from diffuse coronary artery disease based on fractional flow reserve pullbacks. We sought to investigate the association between coronary artery disease patterns, defined by coronary physiology, and optical coherence tomography after stent implantation in stable patients undergoing PCI., Methods and Results: This multicenter, prospective, single-arm study was conducted in 5 countries (NCT03782688). Subjects underwent motorized fractional flow reserve pullbacks evaluation followed by optical coherence tomography-guided PCI. Post-PCI optical coherence tomography minimum stent area, stent expansion, and the presence of suboptimal findings such as incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were compared between patients with focal versus diffuse disease. Overall, 102 patients (105 vessels) were included. Fractional flow reserve before PCI was 0.65±0.14, pullback pressure gradient was 0.66±0.14, and post-PCI fractional flow reserve was 0.88±0.06. The mean minimum stent area was 5.69±1.99 mm 2 and was significantly larger in vessels with focal disease (6.18±2.12 mm 2 versus 5.19±1.72 mm 2 , P =0.01). After PCI, incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were observed in 27.6%, 10.5%, and 51.4% of the cases, respectively. Vessels with focal disease at baseline had a lower prevalence of incomplete stent apposition (11.3% versus 44.2%, P =0.002) and more irregular tissue protrusion (69.8% versus 32.7%, P <0.001)., Conclusions: Baseline coronary pathophysiological patterns are associated with suboptimal imaging findings after PCI. Patients with focal disease had larger minimum stent area and a higher incidence of tissue protrusion, whereas stent malapposition was more frequent in patients with diffuse disease.

Background: To identify anatomical and morphological plaque features predictors of PCI and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFR CT (Fractional Flow Reserve derived from CCTA) trans-lesion gradient (ΔFFR CT ) when integrated into the score., Methods: Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFR CT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70 ​% of the study population) and tested in a validation cohort (30 ​% of patients)., Results: The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS ​≥ ​50 ​%, volume of NCP>113 ​mm 3 and PAV>17 ​%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74-0.86). The integration of ΔFFR CT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77-0.87, p ​= ​0.328)., Conclusions: Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI., Competing Interests: Declaration of competing interest MB, PP, DTB, AL and MMV report research grants provided by Cardiopath Ph.D. program. NM has received speaker fees from Abbott. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc., and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular, and Philips Volcano. BDB reports receiving consultancy fees from Boston Scientific, and Abbott and receiving research grants from Coroventis Research, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc., and Abbott Vascular. DA reports research grants from GE Healthcare and Bracco. The other authors have nothing to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Luminal stenosis, computed tomography-derived fractional-flow reserve (FFR CT ), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described., Methods: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFR CT in Coronary Care) registry underwent artificial intelligence-enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFR CT , and translesional delta-FFR CT . Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction., Results: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFR CT , total plaque volume above the receiver-operator characteristic curve-derived optimal cutoff (total plaque volume >564 mm 3 ) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093-2.099]; P =0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474-2.839]; P <0.0001) and cardiovascular death/myocardial infarction (total percent atheroma volume >37.17%, hazard ratio, 4.53 [95% CI, 1.943-10.576]; P =0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes., Conclusions: Analysis of the ADVANCE registry using artificial intelligence-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFR CT ., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02499679., Competing Interests: 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 Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr Fairbairn has served on the Speakers Bureau for HeartFlow. Dr Nieman has received institutional research support from Siemens Healthineers, HeartFlow, GE Healthcare, and Bayer Healthcare. Dr Hurwitz Koweek has received research support and speaking fees from HeartFlow and Siemens. Dr Pontone has received institutional research grant and honorarium as consultant/speaker from GE Healthcare, Bracco, Medtronic, Bayer, and HeartFlow. Dr Rabbat has served as a consultant for HeartFlow. Ms Mullen is an employee of and owns equity in HeartFlow. Dr De Bruyne has an institutional consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; has received institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds equities in Philips, Siemens, GE Healthcare, Edwards Lifesciences, HeartFlow, Opsens, and Celiad. Dr Rogers is employee of and owns equity in HeartFlow. Dr Leipsic has received an unrestricted research grant from GE Healthcare, has stock options and received consulting fees from HeartFlow and Circle CVI, and speaking fees from GE and Philips. Dr Ng is an employee of HeartFlow. The other authors report no conflicts.

The present study establishes a link between blood flow energy transformations in coronary atherosclerotic lesions and clinical outcomes. The predictive capacity for future myocardial infarction (MI) was compared with that of established quantitative coronary angiography (QCA)-derived predictors. Angiography-based computational fluid dynamics (CFD) simulations were performed on 80 human coronary lesions culprit of MI within 5 years and 108 non-culprit lesions for future MI. Blood flow energy transformations were assessed in the converging flow segment of the lesion as ratios of kinetic and rotational energy values (KER and RER, respectively) at the QCA-identified minimum lumen area and proximal lesion sections. The anatomical and functional lesion severity were evaluated with QCA to derive percentage area stenosis (%AS), vessel fractional flow reserve (vFFR), and translesional vFFR (ΔvFFR). Wall shear stress profiles were investigated in terms of topological shear variation index (TSVI). KER and RER predicted MI at 5 years (AUC = 0.73, 95% CI 0.65-0.80, and AUC = 0.76, 95% CI 0.70-0.83, respectively; p < 0.0001 for both). The predictive capacity for future MI of KER and RER was significantly stronger than vFFR (p = 0.0391 and p = 0.0045, respectively). RER predictive capacity was significantly stronger than %AS and ΔvFFR (p = 0.0041 and p = 0.0059, respectively). The predictive capacity for future MI of KER and RER did not differ significantly from TSVI. Blood flow kinetic and rotational energy transformations were significant predictors for MI at 5 years (p < 0.0001). The findings of this study support the hypothesis of a biomechanical contribution to the process of plaque destabilization/rupture leading to MI., (© 2023. The Author(s).)

Objective: To compare the effects of ticagrelor and prasugrel on absolute coronary blood flow (Q) and microvascular resistance (R) in patients with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI) (NCT05643586). Besides being at least as effective as prasugrel in inhibiting platelet aggregation, ticagrelor has been shown to have additional properties potentially affecting coronary microcirculation., Methods: We randomly assigned 50 patients to ticagrelor (180 mg) or prasugrel (60 mg) at least 12 hours before intervention. Continuous thermodilution was used to measure Q and R before and after PCI. Platelet reactivity was measured before PCI. Troponin I was measured before, 8 and 24 hours after PCI., Results: At baseline, fractional flow reserve, Q and R were similar in two study groups. Patients in the ticagrelor group showed higher post-PCI Q (242±49 vs 205±53 mL/min, p=0.015) and lower R values (311 (263, 366) vs 362 (319, 382) mm Hg/L/min, p=0.032). Platelet reactivity showed a negative correlation with periprocedural variation of Q values (r=-0.582, p<0.001) and a positive correlation with periprocedural variation of R values (r=0.645, p<0.001). The periprocedural increase in high-sensitivity troponin I was significantly lower in the ticagrelor compared with the prasugrel group (5 (4, 9) ng/mL vs 14 (10, 24) ng/mL, p<0.001)., Conclusions: In patients with stable CAD undergoing PCI, pretreatment with a loading dose of ticagrelor compared with prasugrel improves post-procedural coronary flow and microvascular function and seems to reduce the related myocardial injury., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) can, in principle, be derived by any method assessing coronary flow., Objectives: The aim of this study was to compare CFR and MRR as derived by continuous (CFR cont and MRR cont ) and bolus thermodilution (CFR bolus and MRR bolus )., Methods: A total of 175 patients with chest pain and nonobstructive coronary artery disease were studied. Bolus and continuous thermodilution measurements were performed in the left anterior descending coronary artery. MRR was calculated as the ratio of CFR to fractional flow reserve and corrected for changes in systemic pressure. In 102 patients, bolus and continuous thermodilution measurements were performed in duplicate to assess test-retest reliability., Results: Mean CFR bolus was higher than CFR cont (3.47 ± 1.42 and 2.67 ± 0.81 [P < 0.001], mean difference 0.80, upper limit of agreement 3.92, lower limit of agreement -2.32). Mean MRR bolus was also higher than MRR cont (4.40 ± 1.99 and 3.22 ± 1.02 [P < 0.001], mean difference 1.2, upper limit of agreement 5.08, lower limit of agreement -2.71). The correlation between CFR and MRR values obtained using both methods was significant but weak (CFR, r = 0.28 [95% CI: 0.14-0.41]; MRR, r = 0.26 [95% CI: 0.16-0.39]; P < 0.001 for both). The precision of both CFR and MRR was higher when assessed using continuous thermodilution compared with bolus thermodilution (repeatability coefficients of 0.89 and 2.79 for CFR cont and CFR bolus , respectively, and 1.01 and 3.05 for MRR cont and MRR bolus , respectively)., Conclusions: Compared with bolus thermodilution, continuous thermodilution yields lower values of CFR and MRR accompanied by an almost 3-fold reduction of the variability in the measured results., Competing Interests: Funding Support and Author Disclosures Drs Paolisso and Esposito are supported by a research grant from the CardioPaTh PhD Program. Dr Barbato has received speaker fees from Abbott Vascular, Boston Scientific, and GE Healthcare. Dr Collet has received research grants from Biosensors, GE Healthcare, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and has received consultancy fees from HeartFlow, Opsens, Pie Medical Imaging, Abbott Vascular, and Philips. Dr De Bruyne has institutional consulting relationships with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; has received institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and has minor equity holdings in Philips, Siemens, GE Healthcare, Edwards Lifesciences, HeartFlow, Opsens, Celiad, Bayer, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The interplay between coronary hemodynamics and plaque characteristics remains poorly understood., Objectives: The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics., Methods: This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value., Results: A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87)., Conclusions: Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688)., Competing Interests: Funding and Author Disclosures The study was sponsored by the Cardiac Research Institute Aalst with unrestricted grants from HeartFlow Inc. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow Inc; and speaker fees from Abbott Vascular. Dr Leipsic is a consultant and has holding stock options in Circle CVI and HeartFlow Inc; has received a research grant from GE; and modest speaker fees from GE and Philips. Drs Sonck and Munhoz have received research grants provided by the Cardiopath Ph.D. program. Dr Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow Inc. Dr Otake has received research grants from Abbott Vascular; and speaker fees from HeartFlow Inc and Abbott Vascular. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Koo has received institutional research grants from HeartFlow Inc. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordisk; and research grants from Bayer and Philips Healthcare. Dr Jensen has received unrestricted institutional research grants from Siemens and HeartFlow Inc. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Shinke has received research grants from Boston Scientific and Abbott Vascular. CT is an employee of HeartFlow Inc. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; significant institutional research support from St. Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?]; NCT02184117) and Philips/Volcano Corporation (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses]; NCT02328820) for studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm commercialized under 510(k) K191008; and has pending patents on diagnostic methods for quantifying aortic stenosis and transcatheter aortic valve replacement physiology, as well as algorithms to correct pressure tracings from fluid-filled catheters. Dr De Bruyne has received 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 owns equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum., Aim: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR., Methods: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events., Results: Recruitment is ongoing and is expected to be completed in the second half of 2023., Conclusion: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes., Competing Interests: Disclosures AML reports receiving consultancy fees from Abbott and honoraria for sponsored symposiums from Abbott, Medtronic and Abiomed. DM report a research grant provided by the Cardiopath PhD program and speaker fees from Abbott Vascular. BDB reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular and Philips Volcano. BK has received consulting fees from Canon Medical, Abbott and Medtronic. AI has received consulting fees from Canon, Artrya Medical and Boston Scientific. TWJ has received consultancy/speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, Terumo and research grants from Abbott Vascular. NPJ received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St. Jude Medical (CONTRAST, NCT02184117) and Philips Volcano Corporation (DEFINE-FLOW, NCT02328820) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510(k) K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology, and on methods to correct pressure tracings from fluid-filled catheters. SB received research grants provided by Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech. EHC has received consulting fees from Abbott Medical Denmark A/S. CB receives research funding from the British Heart Foundation (RE/18/6134217, BHF/FS/17/26/32744, PG/19/28/34310). Colin Berry is employed by the University of Glasgow which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis, GSK, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. WFF receives institutional research support from Abbot, Boston, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options with HeartFlow. TE reports speakers and advisory board fees from Abbott, Boston and Novo Nordisk. AY has received minor honoraria from Abbott Vascular, and research grants from Abbott Vascular and Philips. DC has received consulting fees from Abbott. TS reports a grant provided by the EAPCI Fellowship Programme., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated., Objectives: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery., Methods: We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization., Results: Overall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005)., Conclusions: The LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels., Competing Interests: Funding Support and Author Disclosures Dr Collet received research grants from Biosensors, HeartFlow Inc, Abbott Vascular, Insight Lifetech, GE Healthcare, Siemens and Shockwave Medical. Dr Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St. Jude Medical (CONTRAST, NCT02184117) and Philips Volcano (DEFINE-FLOW, NCT02328820) for studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm commercialized under 510(k) K191008; and has pending patents on diagnostic methods for quantifying aortic stenosis and TAVI physiology and also algorithms to correct pressure tracings from fluid-filled catheters. Dr Mizukami has received consultancy fees from Zeon Medical. Dr Fearon receives institutional research support from Abbott Vascular, Boston Scientific, Medtronic, and Edwards Lifesciences; he has a consulting relationship with CathWorks and Siemens; and he owns minor stock options in HeartFlow. Dr Berry receives research funding from the British Heart Foundation grant (RE/18/6134217); and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health. Dr Sonck is supported by a grant provided by the CardioPath PhD program. Dr Collison has received honoraria/speaker fees from Abbott. Dr Koo has received an institutional research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr Meneveau has received consultancy and speaker fees from Abbott Vascular, Edwards Lifesciences, Terumo, Boston Scientific, Bayer Healthcare, BMS-Pfizer, Boehringer, and AstraZeneca. Dr Oldroyd is an employee of Biosensors International. Dr Leipsic is a consultant for and holds stock options in Circle CVI and HeartFlow; and has a research grant from GE Healthcare. Dr Taylor is an employee of HeartFlow Inc. Dr Ko has received consultancy fees from Abbott Vascular and Medtronic; and has received research support from Canon Medical. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Leone received consultant fees and honoraria for lectures in sponsored symposia with Abbott Vascular and Bracco Imaging/ACIST Medical. Dr Matsuo has received consultancy fees from Zeon Medical; and has received speaker fees from Abbott Vascular Japan, Philips, and Boston Scientific. Dr Amabile reports consulting/proctoring fees from Abbott Vascular, Boston Scientific, and Shockwave Medical; and has received an institutional research grant from Abbott Vascular and Boston Scientific. Dr Piróth has received consultancy and speaker fees from Abbott Vascular, Opsens, and Boston Scientific. Dr Toth has received consultancy fees and research support from Abbott, Biotronik, Medtronic, and Terumo. Dr Ihdayhid reports receiving consulting honorarium from Abbott Medical, Edwards Lifesciences, Boston Scientific, Artrya Pty Ltd (including equity interest). Dr West is an employee of Abbott Vascular. Dr Munhoz is supported with a PhD grant from CardioPath. Dr Barbato has received speaker fees from Abbott and Boston Scientific. Dr Engstrøm has received consultancy and speaker fees from Abbott Vascular, Novo Nordisk, and Bayer AS. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from Spanish Instituto de Salud Carlos III, and served as speaker and advisory board member for Abbott and Philips. Dr Ali has received institutional grant support Abbott, Abiomed, ACIST Medical, Amgen, Boston Scientific, Cathworks, Canon, Conavi, Heartflow, Inari, Medtronic Inc, National Institute of Health, Nipro, Opsens Medical, Medis, Philips, Shockwave, Siemens, Spectrawave, Teleflex; and consulting fees from Abiomed, AstraZeneca, Boston Scientific, Cathworks, Opsens, Philips, Shockwave and equity in Elucid, Lifelink, Spectrawave, Shockwave, VitalConnect. Dr Kern has received speaker fees from Abbott, ACIST Medical, Boston Scientific, Opsens, and Philips. Dr Pijls has received research grants from Abbott and Hexacath and consultancy fees from Abbott, GE, Philips, and HeartFlow and have equity in GE, Philips, and Heartflow. Dr De Bruyne has received institutional consulting fees from Abbott Vascular, Boston Scientific, Siemens, and GE; has received institutional grant support from Abbott Vascular, Boston Scientific, Biotronic, CathWorks, Pie Medical, and HeartFlow; and holds minor equities in Philips, Siemens, GE, Bayer, HeartFlow, Edwards Lifesciences, and Ceyliad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Trials showing equivalent or better outcomes with initial evaluation using coronary computed tomography angiography (cCTA) compared with stress testing in patients with stable chest pain have informed guidelines but raise questions about overtesting and excess catheterization., Objective: To test a modified initial cCTA strategy designed to improve clinical efficiency vs usual testing (UT)., Design, Setting, and Participants: This was a pragmatic randomized clinical trial enrolling participants from December 3, 2018, to May 18, 2021, with a median of 11.8 months of follow-up. Patients from 65 North American and European sites with stable symptoms of suspected coronary artery disease (CAD) and no prior testing were randomly assigned 1:1 to precision strategy (PS) or UT., Interventions: PS incorporated the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) minimal risk score to quantitatively select minimal-risk participants for deferred testing, assigning all others to cCTA with selective CT-derived fractional flow reserve (FFR-CT). UT included site-selected stress testing or catheterization. Site clinicians determined subsequent care., Main Outcomes and Measures: Outcomes were clinical efficiency (invasive catheterization without obstructive CAD) and safety (death or nonfatal myocardial infarction [MI]) combined into a composite primary end point. Secondary end points included safety components of the primary outcome and medication use., Results: A total of 2103 participants (mean [SD] age, 58.4 [11.5] years; 1056 male [50.2%]) were included in the study, and 422 [20.1%] were classified as minimal risk. The primary end point occurred in 44 of 1057 participants (4.2%) in the PS group and in 118 of 1046 participants (11.3%) in the UT group (hazard ratio [HR], 0.35; 95% CI, 0.25-0.50). Clinical efficiency was higher with PS, with lower rates of catheterization without obstructive disease (27 [2.6%]) vs UT participants (107 [10.2%]; HR, 0.24; 95% CI, 0.16-0.36). The safety composite of death/MI was similar (HR, 1.52; 95% CI, 0.73-3.15). Death occurred in 5 individuals (0.5%) in the PS group vs 7 (0.7%) in the UT group (HR, 0.71; 95% CI, 0.23-2.23), and nonfatal MI occurred in 13 individuals (1.2%) in the PS group vs 5 (0.5%) in the UT group (HR, 2.65; 95% CI, 0.96-7.36). Use of lipid-lowering (450 of 900 [50.0%] vs 365 of 873 [41.8%]) and antiplatelet (321 of 900 [35.7%] vs 237 of 873 [27.1%]) medications at 1 year was higher in the PS group compared with the UT group (both P < .001)., Conclusions and Relevance: An initial diagnostic approach to stable chest pain starting with quantitative risk stratification and deferred testing for minimal-risk patients and cCTA with selective FFR-CT in all others increased clinical efficiency relative to UT at 1 year. Additional randomized clinical trials are needed to verify these findings, including safety., Trial Registration: ClinicalTrials.gov Identifier: NCT03702244.

Background and Aims: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated., Methods: We compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated., Results: Median (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0., Conclusions: An ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Koo reported receiving grants from Abbott Vascular and Philips Volcano during the conduct of the study. Dr. Tanaka reported receiving personal fees from Abbott Vascular Japan and personal fees from Daiichi-Sankyo Co Ltd during the conduct of the study. Dr. Azzalini received honoraria from Teleflex, Abiomed, Asahi Intecc, Philips, GE Healthcare, Abbott Vascular, and Cardiovascular System, Inc. No other disclosures were reported. Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Guidelines recommend deferral of testing for symptomatic people with suspected coronary artery disease (CAD) and low pretest probability. To our knowledge, no randomized trial has prospectively evaluated such a strategy., Objective: To assess process of care and health outcomes in people identified as minimal risk for CAD when testing is deferred., Design, Setting, and Participants: This randomized, pragmatic effectiveness trial included prespecified subgroup analysis of the PRECISE trial at 65 North American and European sites. Participants identified as minimal risk by the validated PROMISE minimal risk score (PMRS) were included., Intervention: Randomization to a precision strategy using the PMRS to assign those with minimal risk to deferred testing and others to coronary computed tomography angiography with selective computed tomography-derived fractional flow reserve, or to usual testing (stress testing or catheterization with PMRS masked). Randomization was stratified by PMRS risk., Main Outcome: Composite of all-cause death, nonfatal myocardial infarction (MI), or catheterization without obstructive CAD through 12 months., Results: Among 2103 participants, 422 were identified as minimal risk (20%) and randomized to deferred testing (n = 214) or usual testing (n = 208). Mean age (SD) was 46 (8.6) years; 304 were women (72%). During follow-up, 138 of those randomized to deferred testing never had testing (64%), whereas 76 had a downstream test (36%) (at median [IQR] 48 [15-78] days) for worsening (30%), uncontrolled (10%), or new symptoms (6%), or changing clinician preference (19%) or participant preference (10%). Results were normal for 96% of these tests. The primary end point occurred in 2 deferred testing (0.9%) and 13 usual testing participants (6.3%) (hazard ratio, 0.15; 95% CI, 0.03-0.66; P = .01). No death or MI was observed in the deferred testing participants, while 1 noncardiovascular death and 1 MI occurred in the usual testing group. Two participants (0.9%) had catheterizations without obstructive CAD in the deferred testing group and 12 (5.8%) with usual testing (P = .02). At baseline, 70% of participants had frequent angina and there was similar reduction of frequent angina to less than 20% at 12 months in both groups., Conclusion and Relevance: In symptomatic participants with suspected CAD, identification of minimal risk by the PMRS guided a strategy of initially deferred testing. The strategy was safe with no observed adverse outcome events, fewer catheterizations without obstructive CAD, and similar symptom relief compared with usual testing., Trial Registration: ClinicalTrials.gov Identifier: NCT03702244.

Background: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI., Methods: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke., Results: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P =0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P =0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P =0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P =0.02)., Conclusions: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02100722., Competing Interests: Disclosures Dr Pijls receives research funding from Abbott, has consulting relationships with Abbott and Opsens, and has stock or stock options with ASML, General Electric, HeartFlow, Hexacath, and Philips. Dr Mansour has consulting relationships with Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Servier Affaires, and received a research grant from Opsens Inc and Abbott Vascular. Dr Kala has a consulting relationship with Boston Scientific, Medtronic, and Servier Affaires, and receives honoraria from AstraZeneca and Bayer. Dr Angeras receives research funding from Abbott Vascular and AstraZeneca and has a consulting relationship with Abbott Vascular and Boston Scientific. Dr Miner has a consulting relationship with Abbott, Amgen, Astra Zeneca, Bayer, Boehringer, Novartis, Opsens, Pfizer, and Servier Affaires Medicales. Dr Engstrøm has a consulting relationship with Abbott Vascular, Bayer, and Novo Nordisk. Dr Christiansen has a consulting relationship with Abbott Vascular and has received research grants from Abbott Vascular. Dr Tonino has received research grants from Biosensors and Opsens. Dr Reardon has a consulting relationship with Boston Scientific and W.L. Gore & Associates. Dr Otsuki has received research grants from the Uehara Memorial Foundation, Abbott, Medtronic, Boston Scientific, and Terumo. Dr Kobayashi has a consulting relationship with Abbott Vascular. Dr Hlatky has a consulting relationship with Blue Cross and Blue Shield and research support from HeartFlow. Dr Mahaffey has received research grants or contracts from the American Heart Association, Apple, Inc, Bayer, California Institute Regenerative Medicine, Eidos, Ferring, Gilead, Google (Verily), Idorsia, Johnson & Johnson, Luitpold, PAC-12, Precordior, and Sanifit; has provided consulting or other services for Amgen, Applied Therapeutics, AstraZeneca, Bayer, CSL Behring, Elsevier, FibroGen, Inova, Johnson & Johnson, Lexicon, MyoKardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, Sanofi, and Theravance; and has equity in Precordior. Dr Yeung has a consulting relationship with Medtronic. Dr De Bruyne has an institutional consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; receives institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds minor equities in Philips, Siemens, GE Healthcare, CathWorks, Edwards Life Sciences, HeartFlow, Opsens, Celyad, Xenter, Medyria, Bayer, and Sanofi. Dr Fearon receives research funding from Abbott, Medtronic, and Boston Scientific and has a consulting relationship with Siemens and CathWorks and stock options with HeartFlow. The other authors report no conflicts of interest.

Background: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD)., Objectives: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG)., Methods: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG., Results: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively., Conclusions: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate., Competing Interests: Funding Support and Author Disclosures Dr Kobayashi serves as a consultant for Abbott Vascular. Dr Oldroyd serves as a chief medical officer for Biosensors International. Dr Reardon serves as a consultant for Medtronic, Boston Scientific, Abbott, and Gore Medical. De Bruyne has stock or stock options with Edwards LifeSciences, General Electric, HeartFlow, Philips, and Siemens. Dr Pijls has received research funding from Abbott; has consulting relationships with Abbott and Opsens; and has stock or stock options with ASML, General Electric, HeartFlow, Hexacath, and Philips. Dr Fearon has received institutional research support from Abbott Vascular, Boston Scientific, and Medtronic; has a consulting relationship with CathWorks and Siemens; and has stock options with HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P <0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P =0.03) and vice versa (area under the curve 0.68 versus 0.78; P =0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.

Background: Graft occlusion after coronary artery bypass grafting (CABG) has been associated with competitive flow of native coronary arteries., Objectives: To assess with coronary computed tomography angiography (CCTA) graft occlusion and coronary artery disease (CAD) progression of native vessels after CABG and their relationship with angiography-derived vessel fractional flow reserve (vFFR) performed before surgery., Methods: Between 2006 and 2018, serial vFFR analyses were obtained before CABG in each major native coronary vessel from two institutions. All patients underwent follow-up CCTA., Results: In 171 consecutive patients, serial preoperative angiograms were suitable for vFFR analysis of 298 grafted and 59 nongrafted vessels. Median time between CABG and CCTA was 2.1 years. Preoperative vFFR was assessed in 131 left anterior descending artery (LAD), 132 left circumflex artery (LCX) and 94 right coronary aretry (RCA) and was less than 0.80 in 255 of 298 bypassed vessels. Graft occlusion was observed at CCTA in 28 of 298 grafts. The median preoperative vFFR value of native coronaries was higher in occluded compared with patent grafts (0.75 vs. 0.60, P < 0.001) and was associated with graft. The best vFFR cut-off to predict graft occlusion was 0.67. Progression of CAD was higher in grafted than in nongrafted vessels (89.6 vs. 47.5%, P < 0.001). Pre-CABG vFFR predicted disease progression of grafted native vessels (AUC = 0.83)., Conclusion: Preoperative vFFR derived from invasive coronary angiography was able to predict graft occlusion and CAD progression of grafted coronary arteries., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

The clinical value of fractional flow reserve and non-hyperaemic pressure ratios are well established in determining an indication for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). In addition, over the last 5 years we have witnessed a shift towards the use of physiology to enhance procedural planning, assess post-PCI functional results, and guide PCI optimisation. In this regard, clinical studies have reported compelling data supporting the use of longitudinal vessel analysis, obtained with pressure guidewire pullbacks, to better understand how obstructive CAD contributes to myocardial ischaemia, to establish the likelihood of functionally successful PCI, to identify the presence and location of residual flow-limiting stenoses and to predict long-term outcomes. The introduction of new functional coronary angiography tools, which merge angiographic information with fluid dynamic equations to deliver information equivalent to intracoronary pressure measurements, are now available and potentially also applicable to these endeavours. Furthermore, the ability of longitudinal vessel analysis to predict the functional results of stenting has played an integral role in the evolving field of simulated PCI. Nevertheless, it is important to have an awareness of the value and challenges of physiology-guided PCI in specific clinical and anatomical contexts. The main aim of this European Association of Percutaneous Cardiovascular Interventions clinical consensus statement is to offer up-to-date evidence and expert opinion on the use of applied coronary physiology for procedural PCI planning, disease pattern recognition and post-PCI optimisation.

Background: A bolus thermodilution-derived index of microcirculatory resistance (IMR) has emerged as the standard for assessing coronary microvascular dysfunction (CMD). Continuous thermodilution has recently been introduced as a tool to quantify absolute coronary flow and microvascular resistance directly. Microvascular resistance reserve (MRR) derived from continuous thermodilution has been proposed as a novel metric of microvascular function, which is independent of epicardial stenoses and myocardial mass., Aims: We aimed to assess the reproducibility of bolus and continuous thermodilution in assessing coronary microvascular function., Methods: Patients with angina and non-obstructive coronary artery disease (ANOCA) at angiography were prospectively enrolled. Bolus and continuous intracoronary thermodilution measurements were obtained in duplicate in the left anterior descending artery (LAD). Patients were randomly assigned in a 1:1 ratio to undergo either bolus thermodilution first or continuous thermodilution first., Results: A total of 102 patients were enrolled. The mean fractional flow reserve (FFR) was 0.86±0.06. Coronary flow reserve (CFR) calculated with continuous thermodilution (CFR cont ) was significantly lower than bolus thermodilution-derived CFR (CFR bolus ; 2.63±0.65 vs 3.29±1.17; p<0.001). CFR cont showed a higher reproducibility than CFR bolus (variability: 12.7±10.4% continuous vs 31.26±24.85% bolus; p<0.001). MRR showed a higher reproducibility than IMR (variability 12.4±10.1% continuous vs 24.2±19.3% bolus; p<0.001). No correlation was found between MRR and IMR (r=0.1, 95% confidence interval: -0.09 to 0.29; p=0.305)., Conclusions: In the assessment of coronary microvascular function, continuous thermodilution demonstrated significantly less variability on repeated measurements than bolus thermodilution.

Background: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) carries prognostic information. Yet, myocardial mass subtended by a stenosis influences FFR. We hypothesized that a smaller coronary lumen volume and a large myocardial mass might be associated with lower post-PCI FFR., Aim: We sought to assess the relationship between vessel volume, myocardial mass, and post-PCI FFR., Methods: This was a subanalysis with an international prospective study of patients with significant lesions (FFR ≤ 0.80) undergoing PCI. Territory-specific myocardial mass was calculated from coronary computed tomography angiography (CCTA) using the Voronoi's algorithm. Vessel volume was extracted from quantitative CCTA analysis. Resting full-cycle ratio (RFR) and FFR were measured before and after PCI. We assessed the association between coronary lumen volume (V) and its related myocardial mass (M), and the percent of total myocardial mass (%M) with post-PCI FFR., Results: We studied 120 patients (123 vessels: 94 left anterior descending arteries, 13 left Circumflex arteries, 16 right coronary arteries). Mean vessel-specific mass was 61 ± 23.1 g (%M 39.6 ± 11.7%). The mean post-PCI FFR was 0.88 ± 0.06 FFR units. Post-PCI FFR values were lower in vessels subtending higher mass (0.87 ± 0.05 vs. 0.89 ± 0.07, p = 0.047), and with lower V/M ratio (0.87 ± 0.06 vs. 0.89 ± 0.07, p = 0.02). V/M ratio correlated significantly with post-PCI RFR and FFR (RFR r = 0.37, 95% CI: 0.21-0.52, p < 0.001 and FFR r = 0.41, 95% CI: 0.26-0.55, p < 0.001)., Conclusion: Post-PCI RFR and FFR are associated with the subtended myocardial mass and the coronary volume to mass ratio. Vessels with higher mass and lower V/M ratio have lower post-PCI RFR and FFR., (© 2023 Wiley Periodicals LLC.)

Background: The relationship between body size and cardiovascular events is complex. This study utilized the ADVANCE (Assessing Diagnostic Value of Noninvasive FFR CT in Coronary Care) Registry to investigate the association between body mass index (BMI), coronary artery disease (CAD), and clinical outcomes., Methods: The ADVANCE registry enrolled patients undergoing evaluation for clinically suspected CAD who had >30% stenosis on cardiac computed tomography angiography. Patients were stratified by BMI: normal <25 kg/m 2 , overweight 25-29.9 kg/m 2 , and obese ≥30 kg/m 2 . Baseline characteristics, cardiac computed tomography angiography and computed tomography fractional flow reserve (FFR CT ), were compared across BMI groups. Adjusted Cox proportional hazards models assessed the association between BMI and outcomes., Results: Among 5014 patients, 2166 (43.2%) had a normal BMI, 1883 (37.6%) were overweight, and 965 (19.2%) were obese. Patients with obesity were younger and more likely to have comorbidities, including diabetes and hypertension (all P <0.001), but were less likely to have obstructive coronary stenosis (65.2% obese, 72.2% overweight, and 73.2% normal BMI; P <0.001). However, the rate of hemodynamic significance, as indicated by a positive FFR CT , was similar across BMI categories (63.4% obese, 66.1% overweight, and 67.8% normal BMI; P =0.07). Additionally, patients with obesity had a lower coronary volume-to-myocardial mass ratio compared with patients who were overweight or had normal BMI (obese BMI, 23.7; overweight BMI, 24.8; and normal BMI, 26.3; P <0.001). After adjustment, the risk of major adverse cardiovascular events was similar regardless of BMI (all P >0.05)., Conclusions: Patients with obesity in the ADVANCE registry were less likely to have anatomically obstructive CAD by cardiac computed tomography angiography but had a similar degree of physiologically significant CAD by FFR CT and similar rates of adverse events. An exclusively anatomic assessment of CAD in patients with obesity may underestimate the burden of physiologically significant disease that is potentially due to a significantly lower volume-to-myocardial mass ratio., Competing Interests: Disclosures Dr Lowenstern reports consulting for Edwards Lifesciences. Dr Takagi reports speaking fees from HeartFlow Japan GK and consulting fee from HeartFlow Inc. Dr Koweek reports a research grant from HeartFlow. Dr Douglas reports a research grant from HeartFlow. Dr Pontone reports grants from GE Healthcare and HeartFlow and personal fees from GE, Bracco, and Medtronic. Dr Berman reports research support from HeartFlow. Dr de Bruyne reports grants from Abbott, St Jude Medical, and Medtronic, and other support from St Jude Medical, Boston Scientific, Opsens, Omega Pharma, Siemens, Edwards, GE, Sanofi, HeartFlow, and Bayer. Dr Bax reports grants from Boston Scientific, Medtronic, Biotronik, and Edwards Lifesciences. T. Akasaka reports grants from Daiichi-Sankyo, St. Jude Medical Japan, Boehringer Ingelheim Japan, Bayer, Pfizer Inc, Foundation for Biomedical Research and Innovation, Otsuka Pharmaceutical Co, Astellas Pharma, Terumo, Abbott Vascular Japan, Goodman Co, and Boston Scientific Japan and has served as a consultant for Daiichi-Sankyo, St. Jude Medical Japan, Boehringer Ingelheim Japan, Bayer, Pfizer Inc, Otsuka Pharmaceutical Co, Astellas Pharma Inc, Terumo, Abbott Vascular Japan, Goodman Co, Boston Scientific Japan, and HeartFlow Japan. Dr Nieman reports support from the National Institutes of Health (NIH R01–HL141712; NIH R01–HL146754) and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc, Novartis unrelated to this work, consulting for Siemens Medical Solutions USA, and equity in Lumen Therapeutics. Dr Rogers reports receiving salary and equity in HeartFlow and is a full-time employee of HeartFlow; Dr Fairbairn is on the speaker’s bureau for HeartFlow. S. Mullen reports being an employee of and owning equity in HeartFlow. Dr Norgaard reports an unrestricted institutional research grant from HeartFlow Inc. Dr Patel reports research grants from Bayer, Janssen, HeartFlow, Novartis, the National Heart, Lung, and Blood Institute, and the Advisory Board/Consulting for Bayer, Janssen, HeartFlow, and Novartis. Dr Leipsic reports being a consultant and having stock options for Circle CVI and HeartFlow. The other authors report no conflicts.

Background: Cardiac stress tests remain the cornerstone for evaluating patients suspected of having obstructive coronary artery disease (CAD). Coronary microvascular dysfunction (CMD) can lead to abnormal non-invasive tests., Aims: We sought to assess the diagnostic performance of exercise stress tests with indexes of epicardial and microvascular resistance as reference., Methods: This was a prospective, single-arm, multicentre study of patients with an intermediate pretest probability of CAD and positive exercise stress tests who were referred for invasive angiography. Patients underwent an invasive diagnostic procedure (IDP) with measurement of fractional flow reserve (FFR) and index of microvascular resistance (IMR) in at least one coronary vessel. Obstructive CAD was defined as diameter stenosis (DS) >50% by quantitative coronary angiography (QCA). The objective was to determine the false discovery rate (FDR) of cardiac exercise stress tests with both FFR and IMR as references., Results: One hundred and seven patients (137 vessels) were studied. The mean age was 62.1±8.7, and 27.1% were female. The mean diameter stenosis was 37.2±27.5%, FFR was 0.84±0.10, coronary flow reserve was 2.74±2.07, and IMR 20.3±11.9. Obstructive CAD was present in 39.3%, whereas CMD was detected in 20.6%. The FDR was 60.7% and 62.6% with QCA and FFR as references (p-value=0.803). The combination of FFR and IMR as clinical reference reduced the FDR by 25% compared to QCA (45.8% vs 60.7%; p-value=0.006)., Conclusions: In patients with evidence of ischaemia, an invasive functional assessment accounting for the epicardial and microvascular compartments led to an improvement in the diagnostic performance of exercise tests, driven by a significant FDR reduction.

Background/purpose: Matching phasic pressure tracings between a fluid-filled catheter and high-fidelity pressure wire has received limited attention, although each part contributes half of the information to clinical decisions. We aimed to study the impact of a novel and automated method for improving the phasic calibration of a fluid-filled catheter by accounting for its oscillatory behavior., Methods/materials: Retrospective analysis of drift check tracings was performed using our algorithm that corrects for mean difference (offset), temporal delays (timing), differential sensitivity of the manifold transducer and pressure wire sensor (gain), and the oscillatory behavior of the fluid-filled catheter described by its resonant frequency and damping factor (how quickly oscillations disappear after a change in pressure)., Results: Among 2886 cases, correcting for oscillations showed a large improvement in 28 % and a medium improvement in 41 % (decrease in root mean square error >0.5 mmHg to <1 or 1-2 mmHg, respectively). 96 % of oscillators were underdamped with median damping factor 0.27 and frequency 10.6 Hz. Fractional flow reserve or baseline Pd/Pa demonstrated no clinically important bias when ignoring oscillations. However, uncorrected subcycle non-hyperemic pressure ratios (NHPR) displayed both bias and scatter., Conclusions: By automatically accounting for the oscillatory behavior of a fluid-filled catheter system, phasic matching against a high-fidelity pressure wire can be improved compared to standard equalization methods. The majority of tracings contain artifacts, mainly due to underdamped oscillations, and neglecting them leads to biased estimates of equalization parameters. No clinically important bias exists for whole-cycle metrics, in contrast to significant effects on subcycle NHPR., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Angiographic parameters can facilitate the risk stratification of coronary lesions but remain insufficient in the prediction of future myocardial infarction (MI)., Aims: We compared the ability of humans, angiographic parameters and deep learning (DL) to predict the lesion that would be responsible for a future MI in a population of patients with non-significant CAD at baseline., Methods: We retrospectively included patients who underwent invasive coronary angiography (ICA) for MI, in whom a previous angiogram had been performed within 5 years. The ability of human visual assessment, diameter stenosis, area stenosis, quantitative flow ratio (QFR) and DL to predict the future culprit lesion (FCL) was compared., Results: In total, 746 cropped ICA images of FCL and non-culprit lesions (NCL) were analysed. Predictive models for each modality were developed in a training set before validation in a test set. DL exhibited the best predictive performance with an area under the curve of 0.81, compared with diameter stenosis (0.62, p=0.04), area stenosis (0.58, p=0.05) and QFR (0.67, p=0.13). DL exhibited a significant net reclassification improvement (NRI) compared with area stenosis (0.75, p=0.03) and QFR (0.95, p=0.01), and a positive nonsignificant NRI when compared with diameter stenosis. Among all models, DL demonstrated the highest accuracy (0.78) followed by QFR (0.70) and area stenosis (0.68). Predictions based on human visual assessment and diameter stenosis had the lowest accuracy (0.58)., Conclusion: In this feasibility study, DL outperformed human visual assessment and established angiographic parameters in the prediction of FCLs. Larger studies are now required to confirm this finding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief., Objectives: The aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG)., Methods: This is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques-Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score <100., Results: A total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020)., Conclusions: Residual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques-Fractional Flow Reserve [TARGET-FFR]; NCT03259815)., Competing Interests: Funding Support and Author Disclosures Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and has received consultancy fees from HeartFlow, OpSens, Abbott Vascular, and Philips Volcano. Dr Collison has received consultancy and speaker fees from Abbott. Dr Munhoz has received research grants provided by the Cardiopath PhD program. Dr Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health; and has received research funding from the British Heart Foundation grant (RE/18/6134217) and EPSRC (EP/R511705/1, EP/S030875/1). Dr De Bruyne has received consultancy fees from Boston Scientific and Abbott Vascular; has received research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow, Edwards Life Sciences, Bayer, Sanofi, and Celyad. Dr Oldroyd is an employee of Biosensors International. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Coronary artery disease (CAD) patterns play an essential role in the decision-making process about revascularization. The pullback pressure gradient (PPG) quantifies CAD patterns as either focal or diffuse based on fractional flow reserve (FFR) pullbacks. The objective of this study was to evaluate the impact of CAD patterns on acute percutaneous coronary intervention (PCI) results considered surrogates of clinical outcomes. Methods and Results This was a prospective, multicenter study of patients with hemodynamically significant CAD undergoing PCI. Motorized FFR pullbacks and optical coherence tomography (OCT) were performed before and after PCI. Post-PCI FFR >0.90 was considered an optimal result. Focal disease was defined as PPG >0.73 (highest PPG tertile). Overall, 113 patients (116 vessels) were included. Patients with focal disease were younger than those with diffuse CAD (61.4±9.9 versus 65.1±8.7 years, P =0.042). PCI in vessels with high PPG (focal CAD) resulted in higher post-PCI FFR (0.91±0.07 in the focal group versus 0.86±0.05 in the diffuse group, P <0.001) and larger minimal stent area (6.3±2.3 mm 2 in focal versus 5.3±1.8 mm 2 in diffuse CAD, P =0.015) compared withvessels with low PPG (diffuse CAD). The PPG was associated with the change in FFR after PCI ( R 2 =0.51, P <0.001). The PPG significantly improved the capacity to predict optimal PCI results compared with an angiographic assessment of CAD patterns (area under the curve PPG 0.81 [95% CI, 0.73-0.88] versus area under the curve angio 0.51 [95% CI, 0.42-0.60]; P <0.001). Conclusions PCI in vessels with focal disease defined by the PPG resulted in greater improvement in epicardial conductance and larger minimal stent area compared with diffuse disease. PPG, but not angiographically defined CAD patterns, distinguished patients attaining superior procedural outcomes. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03782688.

Background: We evaluate the prognostic value of measuring fractional flow reserve (FFR) after percutaneous coronary intervention (post-PCI FFR) and intravascular imaging in patients undergoing PCI for 3-vessel coronary artery disease in the FAME 3 trial (Fractional Flow Reserve versus Angiography for Multivessel Evaluation)., Methods: The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with coronary artery bypass grafting in patients with multivessel coronary artery disease. PCI was not noninferior with respect to the primary end point of death, myocardial infarction, stroke, or repeat revascularization at 1 year. Post-PCI FFR data were acquired on a patient and vessel-related basis. Intravascular imaging guidance was tracked. The primary end point is a comparison of target vessel failure (TVF) defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 1 year based on post-PCI FFR values. Cox regression with robust SEs was used for analysis., Results: Of the 757 patients randomized to PCI, 461 (61%) had post-PCI FFR measurement and 11.1% had intravascular imaging performed. The median post-PCI FFR was 0.89 [IQR' 0.85-0.94]. On a vessel-level, post-PCI FFR was found to be a significant predictor of TVF univariately (hazard ratio=0.67 [95% CI' 0.48-0.93] for 0.1 unit increase, P =0.0165). On a patient-level, the single lowest post-PCI FFR value was also found to be a significant predictor of TVF univariately (hazard ratio=0.65 [95% CI' 0.48-0.89] for 0.1 unit increase, P =0.0074). Post-PCI FFR was an independent predictor of TVF in multivariable analysis adjusted for key clinical parameters. Outcomes were similar between patients who had intravascular imaging guidance and those who did not., Conclusions: Post-PCI FFR measurement was a significant predictor of TVF on a vessel and patient level and an independent predictor of outcomes in a population with complex 3-vessel coronary artery disease eligible for coronary artery bypass grafting. The limited use of intravascular imaging did not affect outcomes., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02100722.

Background: Hemodynamic assessment of untreated nonculprit lesions was not studied in the PROSPECT study (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). We developed a virtual intravascular ultrasound-derived lesion-specific fractional flow reserve (lesion-specific IVUS-FFR) algorithm to assess individual lesion-level FFR. We sought to investigate the relation between lesion-specific IVUS-FFR and major adverse cardiovascular events (MACE) arising from untreated nonculprit lesions in the PROSPECT study., Methods: In PROSPECT, 697 patients with acute coronary syndromes underwent 3-vessel grayscale and virtual histology-IVUS to correlate untreated nonculprit plaque morphology with 3-year nonculprit related MACE (composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina). Lesion-specific IVUS-FFR was calculated from volumetric IVUS lumen area measurements at 0.4 mm intervals by applying a mathematical circulation model using basic fluid dynamics equations., Results: Lesion-specific IVUS-FFR was analyzable in 3227 nonculprit lesions in 660 patients among whom 54 nonculprit MACE events (3 myocardial infarctions) occurred at median 3.4-year follow-up. By receiver-operating characteristic analysis, the best cutoff value of lesion-specific IVUS-FFR to predict nonculprit MACE was ≤0.95. After adjusting for patient and lesion characteristics, lesion-specific IVUS-FFR (hazard ratio, 4.83 [95% CI, 2.20-10.61]; P <0.001) was an independent predictor of 3-year nonculprit MACE, in addition to minimum lumen area≤4.0 mm 2 , plaque burden ≥70%, and virtual histology thin-cap fibroatheroma., Conclusions: Minor reductions in lesion-specific IVUS-FFR were independently associated with future nonculprit MACE arising from untreated angiographically mild stenoses along with previously established high-risk lesion morphological characteristics., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00180466.

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P <0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P =0.02). Conclusions In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years.

Importance: Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is generally considered to reflect residual disease. Yet the clinical relevance of post-PCI FFR after drug-eluting stent (DES) implantation remains unclear., Objective: To evaluate the clinical relevance of post-PCI FFR measurement after DES implantation., Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant published articles from inception to June 18, 2022., Study Selection: Published articles that reported post-PCI FFR after DES implantation and its association with clinical outcomes were included., Data Extraction and Synthesis: Patient-level data were collected from the corresponding authors of 17 cohorts using a standardized spreadsheet. Meta-estimates for primary and secondary outcomes were analyzed per patient and using mixed-effects Cox proportional hazard regression with registry identifiers included as a random effect. All processes followed the Preferred Reporting Items for Systematic Review and Meta-analysis of Individual Participant Data., Main Outcomes and Measures: The primary outcome was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel myocardial infarction (TVMI), and target vessel revascularization (TVR). The secondary outcome was a composite of cardiac death or TVMI at 2 years., Results: Of 2268 articles identified, 29 studies met selection criteria. Of these, 28 articles from 17 cohorts provided data, including a total of 5277 patients with 5869 vessels who underwent FFR measurement after DES implantation. Mean (SD) age was 64.4 (10.1) years and 4141 patients (78.5%) were men. Median (IQR) post-PCI FFR was 0.89 (0.84-0.94) and 690 vessels (11.8%) had a post-PCI FFR of 0.80 or below. The cumulative incidence of TVF was 340 patients (7.2%), with cardiac death or TVMI occurring in 111 patients (2.4%) at 2 years. Lower post-PCI FFR significantly increased the risk of TVF (adjusted hazard ratio [HR] per 0.01 FFR decrease, 1.04; 95% CI, 1.02-1.05; P < .001). The risk of cardiac death or MI also increased inversely with post-PCI FFR (adjusted HR, 1.03; 95% CI, 1.00-1.07, P = .049). These associations were consistent regardless of age, sex, the presence of hypertension or diabetes, and clinical diagnosis., Conclusions and Relevance: Reduced FFR after DES implantation was common and associated with the risks of TVF and of cardiac death or TVMI. These results indicate the prognostic value of post-PCI physiologic assessment after DES implantation.

Background: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone., Methods: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non-ST-segment-elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events., Results: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3-5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613-£7015); and angiography+FFR, £4510 (£2721-£7415; P =0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60-87); and angiography+FFR, 75 (interquartile range, 60-90; P =0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR ( P =0.64)., Conclusions: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01070771.

Background: The treatment of a coronary bifurcation with a single stent (the provisional stenting technique) is associated with a good outcome in most cases. In the majority of cases, after provisional stenting technique, a residual significant angiographic stenosis is associated with the absence of ischemia when fractional flow reserve (FFR) is measured. Jailing an optical pressure guidewire in the side branch (SB) could potentially reduce unnecessary SB interventions after provisional stenting technique. The aim of this study was to compare distal pressure to aortic pressure ratio (Pd/Pa) measurements between 2 second-generation optical pressure guidewires in bifurcation treatment-a jailed wire (JW) and a second free-floating wire (FW) advanced into the SB after stenting., Methods: In an in vitro bifurcation hydrodynamic model with pressure sensors, a JW was advanced into the SB and the FW into the main branch. Bifurcation stenting is performed with the proximal optimization technique (POT)-side-POT technique using a 3.0 x 22-mm stent, a 4.0 x 12-mm noncompliant balloon for the POT, and a 2.5 x 12-mm semicompliant balloon for the SB opening. The same steps were performed in a second model where a surgical clamp was placed in the main vessel to lower overall absolute values pressures., Results: A strong correlation was found between JW and FW values (Pearson's coefficient, r=0.91). All wires could be safely retrieved., Conclusion: In bifurcation stenting, the Pd/Pa value of a second-generation optical pressure guidewire jailed in the SB is reliable compared with a FW inserted after stent implantation.

Background: Low fractional flow reserve (FFR) values after percutaneous coronary intervention (PCI) carry a worse prognosis than high post-PCI FFR values. Therefore, the ability to predict post-PCI FFR might play an important role in procedural planning. Post-PCI FFR values can now be computed from pre-PCI coronary computed tomography angiography (CTA) using the fractional flow reserve derived from coronary computed tomography angiography revascularization planner (FFR CT Planner)., Objectives: The aim of this study was to validate the accuracy of the FFR CT Planner., Methods: In this multicenter, investigator-initiated, prospective study, patients with chronic coronary syndromes and significant lesions based on invasive FFR ≤0.80 were recruited. The FFR CT Planner was applied to the fractional flow reserve derived from coronary computed tomography angiography (FFR CT ) model, simulating PCI. The primary objective was the agreement between the predicted post-PCI FFR by the FFR CT Planner and measured post-PCI FFR. Accuracy of the FFR CT Planner's luminal dimensions was assessed by using post-PCI optical coherence tomography as the reference., Results: Overall, 259 patients were screened, with 120 patients (123 vessels) included in the final analysis. The mean patient age was 64 ± 9 years, and 24% had diabetes. Measured FFR post-PCI was 0.88 ± 0.06, and the FFR CT Planner FFR was 0.86 ± 0.06 (mean difference: 0.02 ± 0.07 FFR unit; limits of agreement: -0.12 to 0.15). Optical coherence tomography minimal stent area was 5.60 ± 2.01 mm 2 , and FFR CT Planner minimal stent area was 5.0 ± 2.2 mm 2 (mean difference: 0.66 ± 1.21 mm 2 ; limits of agreement: -1.7 to 3.0). The accuracy and precision of the FFR CT Planner remained high in cases with focal and diffuse disease and with low and high calcium burden., Conclusions: The FFR CT -based technology was accurate and precise for predicting FFR after PCI. (Precise Percutaneous Coronary Intervention Plan Study [P3]; NCT03782688)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by the Cardiac Research Institute Aalst with unrestricted grants from HeartFlow and Cardiopath. Drs Sonck and Munhoz have received research grants provided by the Cardiopath PhD program. Dr De Bruyne has received consultancy fees from Boston Scientific and Abbott Vascular; research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow, Edwards LifeSciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and consultancy fees from HeartFlow, OpSens, Abbott Vascular, and Philips Volcano. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow; and speaker fees from Abbott Vascular. Dr Heggermont reports that Cardiac Research Institute Aalst receives consultancy fees on his behalf from Boston Scientific, Abbott Vascular, MicroPort, Medtronic, Biotronik, and AstraZeneca. Dr Updegrove and Ms Collinsworth are employees of HeartFlow. Dr Leipsic is a consultant and reports holding stock options in Circle CVI and HeartFlow; and has received a research grant from GE and modest speaker fees from GE and Philips. Drs Norgaard and Møller Jensen have received unrestricted institutional research grants from Siemens and HeartFlow. Dr Otake has received research grants from Abbott Vascular; and speaker fees from HeartFlow and Abbott Vascular. Dr Ihdayhid has received consulting fees from Canon, Artrya Medical, and Boston Scientific. Dr Koo has received institutional research grants from HeartFlow. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordics; and research grants from Bayer and Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG., Methods: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve-guided PCI. Quality of life was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status., Results: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, -0.016 to 0.017]; P =0.946). The trajectory of EQ-5D during the 12 months differed ( P <0.001) between PCI and CABG: at 1 month, EQ-5D was 0.063 (95% CI, 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ (EuroQol) visual analogue scale. The proportion of patients with Canadian Cardiovascular Class 2 or greater angina at 12 months was 6.2% versus 3.1% (odds ratio, 2.5 [95% CI, 0.96-6.8]), respectively, in the PCI group compared with the CABG group. A greater percentage of younger patients (<65 years old) were working at 12 months in the PCI group compared with the CABG group (68% versus 57%; odds ratio, 3.9 [95% CI, 1.7-8.8])., Conclusions: In the FAME 3 trial, quality of life after fractional flow reserve-guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those <65 years old., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02100722.

Competing Interests: Funding Support and Author Disclosures Drs Paolisso, Bertolone, and Esposito are supported by a research grant from the CardioPaTh PhD Program. Dr De Bruyne has an institutional consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; has received institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds minor equities in Philips, Siemens, GE Healthcare, Edwards Life Sciences, HeartFlow, Opsens, and Celiad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Coronary artery disease (CAD) continues to be the leading cause of mortality and morbidity in developed countries. Assessment of pre-test probability (PTP) based on patient's characteristics, gender and symptoms, help to identify more accurate patient's clinical likelihood of coronary artery disease. Consequently, non-invasive imaging tests are performed more appropriately to rule in or rule out CAD rather than invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) is the first-line non-invasive imaging technique in patients with suspected CAD and could be used to plan and guide coronary intervention. Invasive coronary angiography remains the gold-standard method for the identification and characterization of coronary artery stenosis. However, it is recommended in patients where the imaging tests are non-conclusive, and the clinical likelihood is very high, remembering that in clinical practice, approximately 30 to 70% of patients with symptoms and/or signs of ischemia, referred to coronary angiography, have non obstructive coronary artery disease (INOCA). In this contest, physiology and imaging-guided revascularization represent the cornerstone of contemporary management of chronic coronary syndromes (CCS) patients allowing us to focus specifically on ischemia-inducing stenoses. Finally, we also discuss contemporary medical therapeutic approach for secondary prevention. The aim of this review is to provide an updated diagnostic and therapeutic approach for the management of patients with stable coronary artery disease., (© 2022. The Author(s).)

Background: Percutaneous coronary interventions (PCI) in calcified coronary artery lesions are associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using calcium modifying techniques such as Rotational Atherectomy (RA) or Intravascular Lithotripsy (IVL) has been advocated. Studies comparing these technologies are lacking. We aimed to compare in-stent pressure gradients, evaluated by vessel fractional flow reserve (vFFR), in calcific lesions treated using either RA or IVL., Methods: Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post-PCI in-stent pressure gradients calculated by vFFR (vFFRgrad). Secondary outcomes included the proportion of patients with complete functional revascularization defined as distal vFFR post-PCI (vFFRpost) ≥ 0.90., Results: From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0.65 ± 0.13 RA and 0.67 ± 0.11 IVL). After PCI, in-stent pressure gradients were significantly lower in the IVL group (0.032 ± 0.026 vs 0.043 ± 0.026 in the RA group, p = 0.024). The proportions of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p = 0.669)., Conclusions: Calcific lesions preparation with IVL is effective and resulted in lower in-stent pressure gradients compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL., (Copyright © 2022. Published by Elsevier B.V.)

Fractional flow reserve (FFR) pullbacks assess the location and magnitude of pressure drops along the coronary artery. The pullback pressure gradient (PPG) quantifies the FFR pullback curve and provides a numeric expression of focal versus diffuse coronary artery disease. This study aims (1) to validate the PPG using manual FFR pullbacks compared with motorized FFR pullbacks as a reference; and (2) to determine the intra- and interoperator reproducibility of the PPG derived from manual FFR pullbacks. Patients with stable coronary artery disease and an FFR ≤ 0.80 were included. All patients underwent FFR pullback evaluation either with a motorized device or manually, depending on the study cohort. The agreement of the PPG between repeated pullbacks was assessed using the Bland-Altman method. Overall, 116 FFR pullback maneuvers (96 manual and 20 motorized) were analyzed. There was excellent agreement between the PPG derived from manual and motorized pullbacks (mean difference -0.01 ± 0.07, 95% limits of agreement [LOA] -0.14 to 0.12). The intra- and interoperator reproducibility of PPG derived from manual pullbacks were excellent (mean difference <0.01, 95% LOA -0.11 to 0.12, and mean difference <0.01, 95% LOA -0.12 to 0.11, respectively). The duration of the pullback maneuver did not impact the reproducibility of the PPG (r = 0.12, 95% CI: -0.29 to 0.49, p = 0.567). Manual pullbacks allow for an accurate PPG calculation. The inter- and intraoperator reproducibility of PPG derived from manual pullbacks were excellent., (© 2022 Wiley Periodicals LLC.)

Objective: To investigate the impact of invasive functional guidance for coronary artery bypass graft surgery (CABG) on graft failure., Background: Data on the impact of fractional flow reserve (FFR) in guiding CABG are still limited., Methods: Systematic review and individual patient data meta-analysis were performed. Primary objective was the risk of graft failure, stratified by FFR. Risk estimates are reported as odds ratios (ORs) derived from the aggregated data using random-effects models. Individual patient data were analyzed using mixed effect model to assess relationship between FFR and graft failure. This meta-analysis is registered in PROSPERO (CRD42020180444)., Results: Four prospective studies comprising 503 patients referred for CABG, with 1471 coronaries, assessed by FFR were included. Graft status was available for 1039 conduits at median of 12.0 [IQR 6.6; 12.0] months. Risk of graft failure was higher in vessels with preserved FFR (OR 5.74, 95% CI 1.71-19.29). Every 0.10 FFR units decrease in the coronaries was associated with 56% risk reduction of graft failure (OR 0.44, 95% CI 0.34 to 0.59). FFR cut-off to predict graft failure was 0.79., Conclusion: Surgical grafting of coronaries with functionally nonsignificant stenoses was associated with higher risk of graft failure., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking., Methods: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed., Results: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group., Conclusions: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: The role of change in fractional flow reserve derived from CT (FFR CT ) across coronary stenoses (ΔFFR CT ) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown., Objectives: To investigate the incremental value of ΔFFR CT in predicting early revascularization and improving efficiency of catheter laboratory utilization., Materials: Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR CT was measured 2 ​cm distal to stenosis. ΔFFR CT was manually measured as the difference of FFR CT across visible stenosis., Results: Of 4730 patients (66 ​± ​10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26-1.35]; p ​< ​0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR CT . Among the 3 models (model 1: risk factors ​+ ​stenosis type and location ​+ ​CAD-RADS; model 2: model 1 ​+ ​FFR CT ; model 3: model 2 ​+ ​ΔFFR CT ), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86-0.88] vs 0.85 [0.84-0.86]; p ​< ​0.001), with the greatest incremental value for FFR CT 0.71-0.80. ΔFFR CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR CT ≤0.8, a diagnostic strategy incorporating ΔFFR CT >0.13, would potentially reduce ICA by 32.2% (1638-1110, p ​< ​0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%., Conclusions: ΔFFR CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR CT , particularly for those with FFR CT 0.71-0.80. ΔFFR CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization., Competing Interests: Declaration of competing interest This study was supported by HeartFlow, Inc., Redwood City, California, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events. Dr. Leipsic receives institutional grants to provide core lab services to Edwards Life Sciences, Medtronic and is a consultant to Circle CVI and HeartFlow. Dr. Fairbairn is 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. Chinnaiyan has received institutional grants from HeartFlow. Dr. Hurwitz-Koweek is on the Speakers Bureau for HeartFlow; and has unrestricted grant funding from Siemens and HeartFlow. Dr. Pontone is a consultant for GE Healthcare; and has research grants from GE Healthcare and HeartFlow. Dr. Rabbat has received institutional grants from HeartFlow. Dr. Mullen is an employee of HeartFlow. Dr. Rogers is an employee of and has equity in HeartFlow. Dr. Bax has received unrestricted research grants from Edwards Lifescience, Medtronic, Boston Scientific, Biotronik, and GE Healthcare; and is on the Speakers Bureau with Abbott. Dr. Douglas receives an institutional research grant from HeartFlow. Dr. Patel has received grants from HeartFlow, Jansen, Bayer, AstraZeneca, and NHLBI; and has served as a consultant for Jansen, Bayer, AstraZeneca, Genzyme, and Merck. Dr. Nieman reports institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc. and is a consultant to Siemens Medical Solutions USA. Dr. Ihdayhid is supported by the National Health and Medical Research Council of Australia and National Heart Foundation Scholarships; and has received honoraria from Canon Medical and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To characterize hemodynamics of serial coronary stenoses using fractional flow reserve (FFR) pullbacks and the pullback pressure gradients (PPG) index., Background: The cross-talk between stenoses within the same coronary artery makes the prediction of the functional contribution of each lesion challenging., Methods and Results: One-hundred seventeen patients undergoing coronary angiography for stable angina were prospectively recruited. Serial lesions were defined as two or more narrowings with visual diameter stenosis >50% on conventional angiography. Motorized FFR pullback tracings were obtained at 1 mm/s. Pullbacks were visually adjudicated as presenting two, one, and no focal pressure drops. The pattern of disease (i.e., focal or diffuse) was quantified using the PPG index. Twenty-five vessels presented serial lesions (mean PPG 0.48 ± 0.17). Two, one or no focal pressure drops were observed in 40% (n = 10; PPG 0.59 ± 0.17), 52% (n = 13; PPG 0.44 ± 0.12) and 8% of cases (n = 2; PPG 0.27 ± 0.01; p-value = 0.01). Distal FFR was similar between vessels with two, one and no focal pressure drops in the pullback curve (p-value = 0.27). The PPG index independently predicted the presence of two focal pressure drops in the pullback curve (p = 0.04)., Conclusions: FFR pullbacks in serial coronary lesions exhibit three distinct functional patterns. High PPG was associated with pullback curves presenting two pressure drops. The PPG provides a quantitative assessment of the pattern of coronary artery disease in cases with serial lesions and might be useful to assess the appropriateness of percutaneous revascularization., (© 2021 Wiley Periodicals LLC.)

Objectives: We sought to characterize the hemodynamic impact of mild coronary artery disease (CAD) using quantitative flow ratio (QFR, an angiography-derived fractional flow reserve [FFR]) in a population of patients with only non-significant CAD at baseline that subsequently experienced a myocardial infarction (MI)., Background: The discriminatory value of FFR in patients with mild CAD remains imperfect., Methods: We retrospectively included patients who underwent invasive coronary angiography for an MI, in whom another angiogram had been performed within the previous 5 years. Three-dimensional quantitative coronary angiography, QFR, and lesion length analysis were conducted on lesions responsible for the MI (future culprit lesions, [FCL]) as well as on control lesions (non-culprit lesions, [NCL])., Results: Eighty-three FCL and 117 NCL were analyzed in 83 patients: FCL were more severe (median % diameter of stenosis [DS] 39.1% [29.8; 45.7] vs. 29.8% [25.0; 37.2], p < .001), had lower QFR values (0.94 [0.86; 0.98] vs. 0.98 [0.96; 1.00], p < .001) and tended to be longer (15.2 mm [10.0; 27.3] vs. 12.7 mm [9.3; 22.4], p = .070) than NCL. In lesions with an interval < 2 years between baseline angiography and MI, the difference in QFR was more pronounced compared to the lesions with a longer interval (FCL: 0.92 [0.85; 0.97] vs. NCL: 0.98 [0.94; 1.00], p < .001 and FCL: 0.96 [0.88; 1.00] vs. NCL: 0.98 [0.96;1.00], p = .006 respectively) CONCLUSION: Mild coronary stenoses that are subsequently responsible for an MI (FCL) exhibit a higher DS and lower QFR years before the event. Furthermore, FCL with a lower QFR at baseline appear to lead earlier to MI., (© 2021 Wiley Periodicals LLC.)