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α-tricalcium phosphate (α-TCP) is the most widespread raw material for hydraulic calcium phosphate cements (CPCs). CPCs are widely used in bone repair due to their injectability, setting ability, and osteoconductivity. This study investigated the reactivity of α-TCP powders, focusing on the impact of minor phase impurities, β-calcium pyrophosphate and hydroxyapatite, and the synthesis temperature. The α-TCP powders were synthesized via a solid-state reaction of calcium carbonate and anhydrous dicalcium phosphate, with varying Ca/P molar ratios (1.4850–1.5075) and synthesis temperatures (1175°C–1350 °C). Powders produced with a Ca/P molar ratio below 1.50 and synthesized at a temperature above the melting point of β-CPP (1296 °C) had a broader size distribution and a two to fourfold lower hydraulic reactivity. Conversely, a higher Ca/P molar ratio improved reactivity. The study underscores the importance of precise control over synthesis parameters to enhance the performance of α-TCP-based CPCs, offering insights for optimizing material design in biomedical applications.

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy., Methods: FAVOR III Europe was a multicentre, randomised, open-label, non-inferiority trial comparing a QFR-based with an FFR-based diagnostic strategy for patients with intermediate coronary stenosis. Enrolment was performed in 34 centres across 11 European countries. Patients aged 18 years or older with either chronic coronary syndrome or stabilised acute coronary syndrome, and with at least one intermediate non-culprit stenosis (40-90% diameter stenosis by visual estimate; referred to here as a study lesion), were randomly assigned (1:1) to the QFR-guided or the FFR-guided group. Randomisation was done using a concealed web-based system and was stratified by diabetes and presence of a left anterior descending coronary artery study lesion. The primary endpoint was a composite of death, myocardial infarction, and unplanned revascularisation at 12 months. The predefined non-inferiority margin was 3·4% and the primary analysis was performed in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03729739) and long-term follow-up is ongoing., Findings: Between Nov 6, 2018, and July 21, 2023, 2000 patients were enrolled and randomly assigned to the QFR-guided strategy (1008 patients) or the FFR-guided strategy (992 patients). The median age was 67·3 years (IQR 59·9-74·7); 1538 (76·9%) patients were male and 462 (23·1%) were female. Median follow-up time was 365 days (IQR 365-365). At 12 months, a primary endpoint event had occurred in 67 (6·7%) patients in the QFR group, and in 41 (4·2%) patients in the FFR group (hazard ratio 1·63 [95% CI 1·11-2·41]). The event proportion difference was 2·5% (90% two-sided CI 0·9-4·2). The upper limit of the 90% CI exceeded the prespecified non-inferiority margin of 3·4%. Therefore, QFR did not meet non-inferiority to FFR. A total of 18 (1·8%) patients in each group experienced an adverse procedural event, the most frequent being procedure-related myocardial infarction, which occurred in ten (1·0%) patients in the QFR group and seven (0·7%) in the FFR group. One patient in the QFR group died in relation to the index procedure., Interpretation: The results of the FAVOR III Europe trial do not support the use of QFR if FFR is available to guide revascularisation decisions in patients with intermediate coronary stenosis. This finding could have implications for current clinical guidelines recommending QFR for this purpose., Funding: Medis Medical Imaging Systems and Aarhus University., Competing Interests: Declaration of interests BKA reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. GCam reports institutional research grants from SMT, Medis Medical Imaging, Abbott Vascular, GADA, Siemens, and GE Healthcare outside the present work. TR reports consultant and proctoring honoraria from Boston Scientific, EPS Vascular, and Cardirad. BES is supported by the H H Sheikh Khalifa bin Hamad Al-Thani Research Programme; has received research grants to the institution from Boston Scientific, the B Braun Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, Edwards Lifesciences, the Iten-Kohaut Foundation, and the OPO Foundation; has received consulting and speaker fees from Abbott Vascular, Abiomed, and Boston Scientific; and received free licences for the QFR application from Medis Medical Imaging during the trial. LDS reports consulting fees from Abbott Vascular, Boston Scientific, and Philips outside the submitted work. JE reports serving as a speaker or advisory board member for Abbott, Boston Scientific, Medis Medical Imaging, and Philips. RL-P received a free licence for the QFR software from Medis Medical Imaging during the trial. UL reports research grants to the institution from Abbott, Amgen, Bayer, and Novartis. RSD reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. HM-R reports consultancy fees from Medis Medical Imaging and speaker fees from Philips and Abbott. LK received free licences for the QFR application from Medis Medical Imaging during the trial. JA reports teaching grants from Biotronik and Medis Medical Imaging. YSA reports consulting fees from Boston Scientific and Shockwave. TL served as a Medis technical and research support consultant in Haga Hospital (The Hague, Netherlands) and performed beta testing of software from Medis Medical Imaging, neither of which was study related, and received a free licence for the QFR application from Medis Medical Imaging during the trial. KL received free licences for the QFR application from Medis Medical Imaging during the trial; speaker fees and travel support from BMS and Boston Scientific; speaker fees from DGK; and served as an advisory board member for BMS. GCas received a free licence for the QFR application from Medis Medical Imaging during the trial. SB reports institutional research grants from Medis Medical Imaging, SMT, Abbott, Siemens, Insight Lifetech, and Amgen; free licences for the QFR application from Medis Medical Imaging during the trial; speaker's fee from SMT, Medis Medical Imaging, Abbott, and Siemens; and advisory board activities for Siemens. NTO reports institutional research grants from Abbott and from Shockwave. RS reports an institutional research grant from Abbott; institutional research contract with Medis Medical Imaging; and speaker and consultation fees from Abbott and Fondazione Menarini. EHC reports institutional research grants from Abbott, Biosensors, Meril, and Medis Medical Imaging; and speaker fees from Abbott and EPS. NRH reports Institutional research grants from Abbott, B Braun, Biosensors, Boston Scientific, and Medis Medical Imaging; and speaker fees from Abbott and EPS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Aims: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features., Methods: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis., Results: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03)., Conclusion: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making., Competing Interests: Declaration of competing interest A. C. has consultancy agreements with Medyria and Nanoflex. B. S. received research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), Boston Scientific, and Edwards Lifesciences and has received consulting and speaker fees from Boston Scientific and Abbott Vascular. B.S. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme. The remaining authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Vascular complications remain high in transfemoral transcatheter aortic valve implantation (TAVI). Careful evaluation of the femoral arteries is important to select the optimal access site., Objectives: This study sought to describe a novel risk score (the passage-puncture score) for transfemoral access using a single suture-based closure system., Methods: The passage-puncture score consists of the evaluation of 1) passage feasibility of the ilio-femoral arteries (passage score) and 2) puncture site feasibility (puncture score) based on pre-TAVI computed tomography. All patients underwent fluoroscopy-guided arterial puncture and closure with a suture-based closure system. The primary endpoint was the rate of vascular complications in discharge, including minor and major vascular complications according to the definitions of the Third Valve Academic Research Consortium., Results: From September 2020 to June 2021, transfemoral TAVI was performed in 98 of 99 patients. Passage score (right) was significantly higher in patients treated by left compared to those treated by right femoral access (3 vs. 1; p <0.001). Puncture score was significantly different between patients undergoing mid-femoral as compared to nonmid-femoral puncture (0 vs. 3, p <0.001). Minor vascular complications occurred in six (6%) patients., Conclusions: The passage-puncture score is effective in defining the optimal access site for transfemoral TAVI. The systematic evaluation has the potential to further reduce access-site complications., Competing Interests: M. Chen received grant from Boston Scientific and she is a consultant for Jenscare Scientific. J. Michel is a proctor for Boston Scientific. B. E. Stähli received grants to the institution from Edwards Lifesciences and Boston Scientific. A. M. Kasel is a consultant and proctor for Edwards Lifesciences and received grants to the institution from Edwards Lifesciences. The other authors had no conflicts to declare., (© 2024 The Author(s).)

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: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown., Methods: The culprit lesion (CL) of 346 ACS-patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end-point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to unstable or progressive angina at two years., Results: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC-ACS) (79.8% vs. 56.8%; p < 0.001) and other high-risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0° vs. 259.3°; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC-patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040)., Conclusions: CCs were associated with conventional high-risk plaque features and associated with increased MACE+-rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future., Competing Interests: Declaration of Competing Interest GN, YA, CS, HR, LS, DM, LSi, JM, TG, MR, URK, AH, DS, HD, FK,TT, MK, JK have no conflicts of interest to declare. CSk reports a grant from DFG Sk 276/3–1. BS has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme, and research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, the B. Braun Foundation, Boston Scientific, and Edwards Lifesciences. DL received lecture honoraria from Amgen, Abott Vascular, AstraZeneca, and Novo Nordisk. MJ received consulting fees from Biotronik, TriCares, Veryan and Shockwave; he is in the steering committee of Biotronik and Edwards lifesciences. UL reports lecture and advisory honorary from Abott., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Spontaneous coronary artery dissection (SCAD) has been described as an infrequent cause of acute coronary syndrome (ACS). Knowledge about the disease is still limited and SCAD might still be underdiagnosed., Objectives: Trends in incidence, presentation, angiographic appearance, management, and outcomes of SCAD over 25 years were analyzed., Methods: Patients with SCAD between 1997 and 2021 at the University Hospital Zurich, Switzerland, were included. Incidences were assessed as total numbers and proportions of ACS cases. Clinical data were collected from medical records and angiographic findings were reviewed. Major adverse cardiac events (MACE) were defined as the composite of all-cause death, cardiac arrest, SCAD recurrence or progression, other myocardial infarction, and stroke., Results: One hundred fifty-six SCAD cases were included in this study. The incidence increased significantly in total (p < 0.001) and relative to ACS cases (p < 0.001). This was based on an increase of shorter lesions (p = 0.004), SCAD type 2 (p < 0.001), and lesions in side branches (p = 0.014), whereas lesions in the left main coronary artery and proximal segments were decreasing (p-values 0.029 and < 0.001, respectively). There was an increase in conservative therapy (p < 0.001). The rate of MACE (24%) was stable, however, there was a reduced proportion of patients with a need for intensive care treatment (p = 0.017)., Conclusions: SCAD represents an important entity of ACS that still might be underappreciated. The increasing incidence of SCAD is likely based on better awareness and familiarity with the disease. A lower need for intensive care treatment suggests positive effects of the increasing implementation of conservative management., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Spotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients., Methods: CL of the first 155 consecutive ACS-patients from the translational OPTICO-ACS-study program were investigated by OCT-characterization of the calcium phenotype at ACS-causing culprit lesions. Simultaneous immunophenotyping by flow-cytometric analysis and cytokine bead array technique across the CL gradient (ratio local/systemic levels) was performed and incidental major adverse cardiovascular events plus (MACE+) at 12 months after ACS were assessed., Results: SCD were observed within 45.2% of all analyzed ACS-causing culprit lesions (CL). Culprits containing spotty calcium were characterized by an increased culprit ratio of innate effector cytokines interleukin (IL)-8 [2.04 (1.24) vs. 1.37 (1.10) p < 0.05], as well as TNF (tumor necrosis factor)-α [1.17 (0.93) vs. 1.06 (0.89); p < 0.05)] and an increased ratio of circulating neutrophils [0.96 (0.85) vs. 0.91 (0.77); p < 0.05] as compared to culprit plaques without SCD. Total monocyte levels did not differ between the two groups (p = n.s.). However, SCD-containing CLs were characterized by an increased culprit ratio of intermediate monocytes [(1.15 (0.81) vs. 0.96 (0.84); p < 0.05)] with an enhanced surface expression of the integrin receptor CD49d as compared to intermediate monocytes derived from SCD-free CLs [(1.06 (0.94) vs. 0.97 (0.91)] p < 0.05. Finally, 12 months rates of MACE+ were higher in patients with, as compared to patients without SCD at CL (16.4% vs. 5.3%; p < 0.05)., Conclusions: This study for the first time identified a specific inflammatory profile of CL with SCD, with a predominance of neutrophils, intermediate monocytes and their corresponding effector molecules. Hence, this study advances our understanding of ACS-causing CL and provides the basis for future personalized anti-inflammatory, therapeutic approaches to ACS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GN, YA, AA, CS, DM, NK, AH, CSk, HD, FK, TT, MK, LS, TG, LZ, JK have no conflicts of interest to declare. BS has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme, and research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, the B. Braun Foundation, Boston Scientific, and Edwards Lifesciences. DL received lecture honoraria from Amgen, Abott Vascular, AstraZeneca, and Novo Nordisk. MJ received consulting fees from Biotronik, TriCares, Veryan and Shockwave; he is in the steering committee of Biotronik and Edwards lifesciences. UL reports lecture and advisory honorary from Abott., (Copyright © 2023. Published by Elsevier B.V.)

Aims: Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of myocardial infarction with unclear pathophysiology. The aim of the study was to test if vascular segments site of SCAD present distinctive local anatomy and hemodynamic profiles., Methods: Coronary arteries with spontaneously healed SCAD (confirmed by follow-up angiography) underwent three-dimensional reconstruction, morphometric analysis with definition of vessel local curvature and torsion, and computational fluid dynamics (CFD) simulations with derivation of time-averaged wall shear stress (TAWSS) and topological shear variation index (TSVI). The (reconstructed) healed proximal SCAD segment was visually inspected for co-localization with curvature, torsion, and CFD-derived quantities hot spots., Results: Thirteen vessels with healed SCAD underwent the morpho-functional analysis. Median time between baseline and follow-up coronary angiograms was 57 (interquartile range [IQR] 45-95) days. In seven cases (53.8%), SCAD was classified as type 2b and occurred in the left anterior descending artery or near a bifurcation. In all cases (100%), at least one hot spot co-localized within the healed proximal SCAD segment, in 9 cases (69.2%) ≥ 3 hot spots were identified. Healed SCAD in proximity of a coronary bifurcation presented lower TAWSS peak values (6.65 [IQR 6.20-13.20] vs. 3.81 [2.53-5.17] Pa, p = 0.008) and hosted less frequently TSVI hot spots (100% vs. 57.1%, p = 0.034)., Conclusion: Vascular segments of healed SCAD were characterized by high curvature/torsion and WSS profiles reflecting increased local flow disturbances. Hence, a pathophysiological role of the interaction between vessel anatomy and shear forces in SCAD is hypothesized., Competing Interests: Conflict of interest AC has consultancy agreements with Medyria, HiD-Imaging and Nanoflex. JS is supported by a Monash University scholarship and received speaker's fees from Abbott and Edwards Lifesciences and a travel grant from Abbott. BS received research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), Boston Scientific, and Edwards Lifesciences and has received consulting and speaker fees from Boston Scientific and Abbott Vascular. CT received institutional grants from Abbott Vascular, Medtronic, SMT, the Iten-Kohaut Foundation and the Swiss Heart Foundation as well as consulting grants from Biotronik, Microport, Schnell Medical. CT and BS have been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme. The remaining authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Chen has received grant from Boston Scientific; and is a consultant for Jenscare Scientific. Dr Michel has been a proctor for Boston Scientific. Dr Stähli has received institutional grants from Edwards Lifesciences and Boston Scientific. Dr Kasel has been a consultant and proctor for Edwards Lifesciences; and has received institutional grants from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.