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Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000-40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms., (© 2024. The Author(s).)

Background: The 12-month outcomes of BIOMAG-I - the first-in-human study investigating the third-generation drug-eluting resorbable magnesium scaffold (DREAMS 3G) - showed promising results regarding clinical outcomes and late lumen loss., Aims: The current study aimed to investigate vascular healing parameters assessed by optical coherence tomography (OCT) and intravascular ultrasound (IVUS), focusing on strut visibility, vessel and scaffold areas, and neointimal growth patterns., Methods: This is a BIOMAG-I substudy including patients with available serial OCT and IVUS data. We conducted a frame-based analysis of OCT findings in conjunction with IVUS-derived vessel and scaffold areas, evaluating the qualitative and quantitative aspects of vascular healing., Results: Among the 116 patients enrolled in this trial, 56 patients treated with DREAMS 3G were included in the analysis. At 12 months, OCT imaging revealed that 99.0% of the struts were invisible, and no malapposed struts were depicted. While the vessel area showed no significant difference between the timepoints, the minimum lumen area significantly decreased from post-percutaneous coronary intervention to 6 months (6.88 mm 2 to 4.75 mm 2 ; p<0.0001), but no significant changes were observed between 6 and 12 months. Protruding neointimal tissue (PNT) - a unique neointimal presentation observed following resorbable magnesium scaffold implantation - was observed in 89.3% of the study patients at 12 months, and its area exhibited a 47.4% decrease from 6 to 12 months., Conclusions: This imaging substudy revealed that, at 12-month follow-up, virtually all struts of the DREAMS 3G scaffold became invisible, without evident malapposition. The vascular healing response to DREAMS 3G implantation also appeared favourable up to 12 months, which is indicated by advanced strut degradation and spontaneous regressing PNT between 6 and 12 months.

Objectives: INCORPORATE trial was designed to evaluate whether default coronary-angiography (CA) and ischemia-targeted revascularization is superior compared to a conservative approach for patients with treated critical limb ischemia (CLI). Registered at clinicaltrials.gov (NCT03712644) on October 19, 2018., Background: Severe peripheral artery disease is associated with increased cardiovascular risk and poor outcomes., Methods: INCORPORATE was an open-label, prospective 1:1 randomized multicentric trial that recruited patients who had undergone successful CLI treatment. Patients were randomized to either a conservative or invasive approach regarding potential coronary artery disease (CAD). The conservative group received optimal medical therapy alone, while the invasive group had routine CA and fractional flow reserve-guided revascularization. The primary endpoint was myocardial infarction (MI) and 12-month mortality., Results: Due to COVID-19 pandemic burdens, recruitment was halted prematurely. One hundred eighty-five patients were enrolled. Baseline cardiac symptoms were scarce with 92% being asymptomatic. Eighty-nine patients were randomized to the invasive approach of whom 73 underwent CA. Thirty-four percent had functional single-vessel disease, 26% had functional multi-vessel disease, and 90% achieved complete revascularization. Conservative and invasive groups had similar incidences of death and MI at 1 year (11% vs 10%; hazard ratio 1.21 [0.49-2.98]). Major adverse cardiac and cerebrovascular events (MACCE) trended for hazard in the Conservative group (20 vs 10%; hazard ratio 1.94 [0.90-4.19]). In the per-protocol analysis, the primary endpoint remained insignificantly different (11% vs 7%; hazard ratio 2.01 [0.72-5.57]), but the conservative approach had a higher MACCE risk (20% vs 7%; hazard ratio 2.88 [1.24-6.68])., Conclusion: This trial found no significant difference in the primary endpoint but observed a trend of higher MACCE in the conservative arm., (© 2024. The Author(s).)

Background: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI)., Methods: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed., Results: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001)., Conclusions: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of the study is to assess the impact of the baseline plaque composition on the DREAMS 3G luminal late loss and to compare the serial plaque changes between baseline and 6 and 12 months (M) follow-up., Methods and Results: A total of 116 patients were enrolled in the BIOMAG-I trial. Patients were imaged with optical coherence tomography (OCT) pre- and post-DREAMS 3G implantation and at 6 and 12 M. OCTPlus software uses artificial intelligence to assess composition (i.e. lipid, calcium, and fibrous tissue) of the plaque. The differences between the OCT-derived minimum lumen area (MLA) post-percutaneous coronary intervention and 12 M were grouped into three terciles. Patients with larger MLA differences at 12 M (P = 0.0003) had significantly larger content of fibrous tissue at baseline. There was a reduction of 24.8% and 20.9% in lipid area, both P < 0.001, between the pre-DREAMS 3G OCT and the 6 and 12 M follow-up. Conversely, the fibrous tissue increased by 48.4% and 36.0% at 6 and 12 M follow-up, both P < 0.001., Conclusion: The larger the fibrous tissue in the lesion at baseline, the larger the luminal loss seen at 6 and 12 M. Following the implantation of DREAMS 3G, favourable healing of the vessel coronary wall occurs as shown by a decrease in the lipid area and an increase in fibrous tissue., Competing Interests: Conflict of interest: H.M.G.-G., R.W., G.D.M., M.G., S.B., A.K., and M.B.L. were core laboratory members, and the remaining authors were investigators of the trial. H.M.G.-G. has grants or contracts from Medtronic, Biotronik, Abbott, Neovasc, Corflow, Alucentbio, Philips, and Chiesi (paid to institution), received consulting fees from Boston Scientific and ACIST, and participates in DSMB/advisory board of the VIVID study. R.W. has grants or contracts from Amgen, Biotronik, Boston Scientific, Medtronic, and Philips IGT; received consulting fees from Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd, Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc, and Venous MedTech; received honoraria from AstraZeneca; participates in DSMB/advisory boards of Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd; and is an investor in MedAlliance and Transmural Systems Inc. J.T. reports grants and contracts from Abbott paid to his institution, speaker honoraria and support for attending meetings from Biotronik, and is an associate editor of Cardiovascular Biologics and Regenerative Medicine and Frontiers in Cardiovascular Medicine. J.E. reports personal fees/speaker honoraria from Abbott, Boston Scientific, Philips, and Shockwave, patents from Shared, and participation in advisory boards of Abbott and Phillips. The institution of J.F.I. receives grants or contracts from Terumo Corp, Biosensors, Concept Medical, Biotronik, Abbott Vascular, and Philips Volcano. J.F.I. reports consulting fees from Biotronik, Medtronic, Cordis, Terumo Corp., and ReCor Medical; speaker fees/honoraria from Terumo Corp, Biosensors, Medalliance, OrbusNeich, Concept Medical, Bristol Myers Squibb/Pfizer, Novartis, Cordis, AstraZeneca, and Philips Volcano; and support to attend meetings from Biotronik and Amgen. The institution of J.B. receives grants or contracts from Shockwave IVLS. J.B. receives consulting fees from Biotronik AG and Boston Scientific and speaker fees/honoraria from Biotronik AG, Boston Scientific, and Abbott Vascular, participates in the DSMB of Boston Scientific, and has a leadership or fiduciary role for Biotronik. G.G.T. reports consulting fees from Biotronik, Medtronic, Abbott, and Terumo and honoraria from Biotronik, Medtronic, Abbott, and Terumo. M.J. reports grant support from Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, and Infraredx; consulting fees from AlchiMedics SAS, Biotronik, TriCares, Veryan, and Shockwave; speaker fees/honoraria from Abbott Vascular, Biotronik, Boston Scientific, Edwards Lifesciences, Cardiac Dimensions, AstraZeneca, Recor Medical, and Shockwave; travel support from SIS Medical, Edwards Lifesciences, Boston Scientific, and Cardiac Dimensions; and participation in Steering Committees of Biotronik and Edwards Lifesciences. R.T. reports lecture fees from Biotronik. M.W. reports speaker honoraria and conference attendance support from Biotronik. G.O. reports lecturer honoraria from Abbott Vascular, Biotronik, and Cordis and is a DSMB member of the SCIENCE trial and a CEC-member of the BIOFREEDOM STEMI trial. M.H. reports grants/contracts from Biotronik, Cardiac Dimensions, OrbusNeich, and Philips; consulting fees from Biotronik, Cardiac Dimensions, Shockwave Medical, and OrbusNeich; honoraria/speaker fees from Biotronik, Cardiac Dimensions, Shockwave Medical, OrbusNeich, and Philips; and support to attend meetings/travel support from Biotronik, is a steering committee member of the BIOSOLVE and BIOMAG trials, and is a past president of EAPCI. All other authors have no conflict of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

(1) Background : Mechanical circulatory support (MCS) in myocardial infarction-associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS's timing on patient outcomes, based on data from the PREPARE CS registry. (2) Methods : The PREPARE CS prospective registry includes patients who experienced cardiogenic shock (SCAI classes C-E) and were subsequently referred for cardiac catheterization. Our present analysis included a subset of this registry, in whom MCS was used and who underwent coronary intervention due to myocardial infarction. Patients were categorized into an Upfront group and a Procedural group, depending on the timing of MCS's introduction in relation to their PCI. The endpoint was in-hospital mortality. (3) Results : In total, 71 patients were included. MCS was begun prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after the initiation of PCI (Procedural). The groups' baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of the Impella ® device compared to extracorporeal membrane oxygenation (67% vs. 33%), while the Procedural group exhibited a balanced use of both (50% vs. 50%). Most patients suffered from multi-vessel disease in both groups (82% vs. 84%, respectively; p = 0.99), and most patients required a complex PCI procedure; the latter was more prevalent in the Upfront group (94% vs. 71%, respectively; p = 0.02). Their rates of complete revascularization were comparable (52% vs. 34%, respectively; p = 0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs. 79%, p < 0.05); however, in-hospital mortality was similar (61% vs. 79%, respectively; p = 0.12). (4) Conclusions : The upfront implantation of MCS in myocardial infarction-associated CS did not provide an in-hospital survival benefit.

Background: Discordance between coronary angiographic findings and invasive functional significance is well-established. Yet, the prevalence of this mismatch in an era increasingly utilizing invasive functional assessments, such as fractional flow reserve (FFR), remains unclear. This study examines the extent of such discrepancies in current clinical practice., Methods: This single-center prospective registry included consecutive patients with chronic coronary syndrome (CCS) who underwent elective coronary angiography, with or without revascularization. Coronary angiograms deemed not requiring FFR due to clear anatomical distinctions, either anatomically severe indicating a need for revascularization or mild suggesting no need for intervention, were selected for evaluation. These were then subjected to post-hoc analysis by three independent operators who were blinded to the definitive treatment strategies. Importantly, the post-hoc analysis was conducted in two distinct phases: firstly, a re-evaluation of coronary stenosis, and secondly, a separate functional assessment, each carried out independently. Coronary stenosis severity was assessed visually, while functional relevance was determined by quantitative flow ratio (QFR), calculated using a computational fluid dynamics algorithm applied to angiographic images. Analysis focused on discrepancies between QFR-based functional indications and revascularization strategies actually performed., Results: In 191 patients, 488 vessels were analyzed. Average diameter stenosis (DS) was 37 ± 34%, and QFR was 0.87 ± 0.15, demonstrating a moderate correlation ( r  = -0.84; 95% CI: -0.86 to -0.81, p  < 0.01). Agreement with QFR at conventional anatomical cutoffs was 88% for 50% DS and 91% for 70% DS. Mismatches between revascularization decisions and QFR indications occurred in 10% of cases. Discrepancies were more frequent in the left anterior descending artery (14%) compared to the left circumflex (6%) and the right coronary artery (9%; p  = 0.07)., Conclusion: In a cardiac-center where FFR utilization is high, discordance between coronary angiography and functional significance persists, even when operators are confident in their decisions not to use functional interrogation. This gap, most evident in the left anterior descending artery, highlights the potential need for integrated angiography-based functional assessments to refine revascularization decisions in CCS., Competing Interests: GT receives personal fees from Abbott, Medtronic, Biotronik and Boston Scientific, outside the present work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kanoun Schnur, Pranevičius, Stark, Prunea, Andreka, Schmidt, Harb, Ruzsa, Zweiker, Kane and Toth.)

Background: Patients with high bleeding risk (HBR) are often treated with abbreviated dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) to reduce bleeding risk, however this strategy is associated with an increase in ischemic events, especially if the acute PCI result is suboptimal. We compared clinical outcomes among patients with HBR treated with 1-month DAPT who underwent intravascular ultrasound (IVUS)- or optical coherence tomography (OCT)-guided PCI versus those who underwent angiography-guided PCI without intravascular imaging., Methods: The Onyx ONE Clear study includes patients with HBR from the Onyx ONE US/Japan and Onyx ONE randomized studies who were treated with the Resolute Onyx zotarolimus-eluting stent. The primary endpoint was the composite of cardiac death (CD) or myocardial infarction (MI) between 1 month and 2 years after PCI. Propensity-score adjustments and matching were performed for differences in baseline and procedural characteristics between groups., Results: Among the 1507 patients in Onyx ONE Clear, 271 (18.0 %) had IVUS or OCT used during PCI (Imaging-guided group) and 1236 (82.0 %) underwent Angiography-guided PCI (Angio-guided group). Imaging-guided patients were less likely to present with atrial fibrillation, acute coronary syndrome, and left ventricle ejection fraction ≤35 %. Conversely, Imaging-guided patients were more likely to have complex (ACC/AHA type B2/C), longer, and heavily calcified lesions. Between 1 month and 2 years, the composite rate of CD or MI was similar between Imaging-guided and Angio-guided patients (9.9 % vs. 12.4 %, P = 0.33). There was also no difference between groups after adjustment; (P = 0.56). However, CD was significantly lower among Imaging-guided patients (2.7 % vs. 6.1 %, P = 0.048). There were no between-group differences in MI or stent thrombosis. Propensity score matching results were similar., Conclusion: Despite higher lesion complexity, using intravascular imaging guidance for PCI between 1-month and 2-years follow-up had comparable outcomes with angiographic guidance alone in patients with HBR treated with 1-month DAPT. (ClinicalTrials.gov: Identifier: NCT03647475 and NCT03344653)., Non-Standard Abbreviations and Acronyms: BARC: Bleeding Academic Research Consortium; DAPT: dual antiplatelet therapy; DES: drug-eluting stent; HBR: high bleeding risk; IVUS: intravascular ultrasound; OCT: optical coherence tomography; SAPT: single antiplatelet therapy., Competing Interests: Declaration of competing interest G.G.T. reports consultancy fees and unrestricted research supports from Medtronic, Biotronik, Terumo and Abbott, outside of this project. D.E.K. reports institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, Inc., Orbus Neich, Teleflex, Medtronic and Ablative Solutions; and personal consulting honoraria from Ablative Solutions, Cardiovascular Systems, Inc., Magenta Medical, Medtronic, and Terumo. A.J.K. reports institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Neurotronic. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr. Kirtane controlled the content. Personal: Consulting from IMDS; Travel Expenses/Meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. S.W. reports research and educational grants to the institution from Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, V-Wave. He serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. A. Latib reports consulting fees from Medtronic, Abbott Vascular, and Boston Scientific. E.K. has speaker honoraria from Medtronic, Abbott, Aortic Lab, and has received institutional grants from Abbott and Medtronic. R.M. reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Applied Therapeutics, Arena, AstraZeneca, BAIM, Bayer, Beth Israel Deaconess, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CellAegis, CeloNova, CERC, Chiesi, Concept Medical, CSL Behring, Cytosorbents, DSI, Duke University, Element Science, Faraday, Humacyte, Idorsia, Insel Gruppe AG, Magenta, Medtronic, Novartis, OrbusNeich, Philips, RenalPro, Vivasure, Zoll; personal fees from Cine-Med Research, WebMD; consulting fees paid to the institution from Abbott, Janssen, Medtronic, Novartis; Equity <1 % in Applied Therapeutics, Elixir Medical, STEL, CONTROLRAD (spouse); Scientific Advisory Board for AMA, ACC (BOT Member), SCAI (Women in Innovations Committee Member), JAMA Associate Editor; Faculty CRF (no fee). M.J.P. reports consulting and speaker's honoraria from Abbott Vascular, Baylis Medical, Boston Scientific, Medtronic, Shockwave Medical, and W.L. Gore and consulting honoraria from Biotronik, InnovHeart, and Philips. J.W.C. is an advisory board member for Medtronic and is on the speaker bureau for Shockwave Medical. R.C. has nothing to disclose. R.T. reports institutional grant/support from Medtronic, Biotronik, Micell Technologies, B/Braun, Sahajanand Medical Technologies, Abbot Vascular, Pfizer, Amgen, Regeneron, Novartis, Bayer, Medicins Company, Esperion, Daiichi Sankyo, CLS Behring, Boehringer Ingelheim, and Celecor Therapeutics. E.D. has nothing to disclose. S.S. has nothing to disclose. S.S.B. reports institutional research/grant support from Medtronic, Boston Scientific, and Edwards Lifesciences. A. Loussararian has nothing to disclose. S.C. is a consultant for CoreValve and Medtronic. M.T. has nothing to disclose. G.W.S. has received speaker honoraria from Medtronic, Pulnovo, Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, Amgen; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, Xenter. Dr. Stone's daughter is an employee at Medtronic. Institutional disclosure: Dr. Stone's employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems Inc., Phillips, Biosense-Webster, Shockwave, Vascular Dynamics and V-wave. T.L. is an employee and shareholder of Medtronic. D.M. reports proctor and consultation fees from Medtronic, Boston Scientific, and Microport., (Copyright © 2023. Published by Elsevier Inc.)

Background: Both left ventricular systolic function and fractional flow reserve (FFR) are prognostic factors after percutaneous coronary intervention (PCI). However, how these prognostic factors are inter-related in risk stratification of patients after PCI remains unclarified., Objectives: This study evaluated differential prognostic implication of post-PCI FFR according to left ventricular ejection fraction (LVEF)., Methods: A total of 2,965 patients with available LVEF were selected from the POST-PCI FLOW (Prognostic Implications of Physiologic Investigation After Revascularization with Stent) international registry of patients with post-PCI FFR measurement. The primary outcome was a composite of cardiac death or target-vessel myocardial infarction (TVMI) at 2 years. The secondary outcome was target-vessel revascularization (TVR) and target vessel failure, which was a composite of cardiac death, TVMI, or TVR., Results: Post-PCI FFR was independently associated with the risk of target vessel failure (per 0.01 decrease: HR adj : 1.029; 95% CI: 1.009-1.049; P = 0.005). Post-PCI FFR was associated with increased risk of cardiac death or TVMI (HR adj : 1.145; 95% CI: 1.025-1.280; P = 0.017) among patients with LVEF ≤40%, and with that of TVR in patients with LVEF >40% (HR adj : 1.028; 95% CI: 1.005-1.052; P = 0.020). Post-PCI FFR ≤0.80 was associated with increased risk of cardiac death or TVMI in the LVEF ≤40% group and with that of TVR in LVEF >40% group. Prognostic impact of post-PCI FFR for the primary outcome was significantly different according to LVEF ( P interaction  = 0.019)., Conclusions: Post-PCI FFR had differential prognostic impact according to LVEF. Residual ischemia by post-PCI FFR ≤0.80 was a prognostic indicator for cardiac death or TVMI among patients with patients with LVEF ≤40%, and it was associated with TVR among patients with patients with LVEF>40%. (Prognostic Implications of Physiologic Investigation After Revascularization with Stent [POST-PCI FLOW]; NCT04684043)., Competing Interests: Dr Joo Myung Lee has received an institutional research grant from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Donga-ST, and Zoll Medical. Dr Bon-Kwon Koo has received an institutional research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr Joon Hyung Doh has received a research grant from Philips Volcano. Dr Shao-Liang Chen is a consultant for Microport and Boston Scientific International; and has received a grant from the National Natural Scientific Foundation of China. Dr Toth receives consultancy fees and unrestricted research grants from Abbott, Medtronic, and Terumo. Dr Johnson has received institutional research support from Volcano/Philips (DEFINE-FLOW, NCT02328820), Abiomed (for study of Impella-related coronary physiology) and St. Jude Medical (CONTRAST, NCT02184117); 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 TAVR physiology, and also algorithms to correct pressure tracings from fluid-filled catheters. Dr Leesar has received an institutional research grant from ACIST. Dr Azzalini has received honoraria from Teleflex, Abiomed, GE Healthcare, Asahi Intecc, Philips, Abbott Vascular, and Cardiovascular System, Inc. Dr Diletti has received an institutional research grant to Erasmus University Medical Center; and has served as a consultant to ACIST Medical Systems. Dr Collison has received consultancy/speaker fees from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months., Aims: We aimed to report the final study outcomes at 5 years., Methods: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components)., Results: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups., Conclusions: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

Background: Cardiogenic shock (CS) exhibits high (~50%) in-hospital mortality. The recently published Extracorporeal life Support in Cardiogenic Shock (ECLS-SHOCK) trial demonstrated the neutral effects of the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on all-cause death, as well as on all secondary outcomes in subjects presenting with myocardial-infarction (MI)-related CS. Here, we compared ECLS-SHOCK eligibility criteria with a real-world cohort of CS patients., Methods and Results: ECLS-SHOCK eligibility criteria were applied to a prospective single-center CS registry (the PREPARE CS registry) consisting of 557 patients who were consecutively admitted to the catheterization laboratory (cath lab) of the Medical University of Graz, Austria, due to CS (SCAI C-E). Overall use of mechanical circulatory support (MCS) in this cohort was 19%. Sixty-nine percent of the entire cohort had MI-related CS, 38% of whom would have met ECLS-SHOCK eligibility criteria, thus representing only 27% of the PREPARE CS registry. Exclusion from the ECLS-SHOCK trial was based on patients with initial lactate values below 3 mmol/L (n = 168; 43.6%), aged over 80 years (n = 65; 16.9%), and with a duration of cardiopulmonary resuscitation (CPR) exceeding 45 min (n = 22; 5.7%). The 30-day mortality of patients of the PREPARE CS registry who met the ECLS-SHOCK eligibility criteria was 57.0%, compared to 48.4% of patients in the ECLS-SHOCK trial. The patients' baseline characteristics, however, differed considerably with respect to type of infarction, age, and gender., Conclusions: In a real-world cohort of patients with MI-related CS, only 38% of patients met the eligibility criteria of the ECLS-SHOCK trial. Thus, the impact of the use of VA-ECMO on outcome parameters in MI-related CS, as observed in the ECLS-SHOCK trial, may differ in a more heterogeneous real-world CS population of the PREPARE CS registry.

Since the publication of the 2015 EAPCI consensus on rotational atherectomy, the number of percutaneous coronary interventions (PCI) performed in patients with severely calcified coronary artery disease has grown substantially. This has been prompted on one side by the clinical demand for the continuous increase in life expectancy, the sustained expansion of the primary PCI networks worldwide, and the routine performance of revascularization procedures in elderly patients; on the other side, the availability of new and dedicated technologies such as orbital atherectomy and intravascular lithotripsy, as well as the optimization of the rotational atherectomy system, has increased operators' confidence in attempting more challenging PCI. This current EAPCI clinical consensus statement prepared in collaboration with the EURO4C-PCR group describes the comprehensive management of patients with heavily calcified coronary stenoses, starting with how to use non-invasive and invasive imaging to assess calcium burden and inform procedural planning. Objective and practical guidance is provided on the selection of the optimal interventional tool and technique based on the specific calcium morphology and anatomic location. Finally, the specific clinical implications of treating these patients are considered, including the prevention and management of complications and the importance of adequate training and education., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

The optimal duration of dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) with implantation of the Orsiro Mission stent remains unclear. The BIOFLOW-DAPT (clinicaltrials.gov, NCT04137510) trial is a prospective, multi-center, randomized controlled study designed to assess the safety of the Orsiro Mission versus the Resolute Onyx stent in HBR patients. Patients are treated with DAPT (aspirin and a P2Y 12 inhibitor) for 1 month, followed by a single antiplatelet therapy (SAPT). The primary endpoint is the composite of cardiac death, myocardial infarction, and definite or probable stent thrombosis at 1 year. With a final sample size of 1948 HBR patients, this study is powered to assess the noninferiority of the Orsiro Mission stent with respect to the primary study endpoint. The BIOFLOW-DAPT is the first randomized clinical trial investigating 1-month DAPT duration in HBR patients after implantation of the Orsiro Mission stent.Trial Registration: ClinicalTrials.gov number, NCT04137510 Study design and key features. Patient selection starts before the index PCI, when consented patients will be randomized to the Orsiro Mission or the Resolute Onyx stent with mandated 1-month DAPT. At 1 month, eligibility is reassessed and if met, patients will discontinue DAPT and continue with P2Y 12 inhibitor or aspirin monotherapy. PCI, percutaneous coronary intervention; DAPT, dual antiplatelet therapy; DES, drug-eluting stent; HBR, high bleeding risk; P2Y12i, P2Y12 inhibitor; ST, stent thrombosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Background: Limited information is available on the comparative efficacy and safety of different stent platforms in patients at high bleeding risk undergoing an abbreviated dual antiplatelet therapy duration after percutaneous coronary intervention (PCI). The aim of this study was to compare the safety and effectiveness of the biodegradable-polymer sirolimus-eluting stent with the durable-polymer zotarolimus-eluting stent in patients at high bleeding risk receiving 1 month of dual antiplatelet therapy after PCI., Methods: The Bioflow-DAPT Study is an international, randomized, open-label trial conducted at 52 interventional cardiology hospitals in 18 countries from February 24, 2020, through September 20, 2021. Patients with a clinical indication to PCI because of acute or chronic coronary syndrome who fulfilled 1 or more criteria for high bleeding risk were eligible for enrollment. Patients were randomized to receive either biodegradable-polymer sirolimus-eluting stents or durable-polymer, slow-release zotarolimus-eluting stents after successful lesion preparation, followed by 1 month of dual antiplatelet therapy and thereafter single antiplatelet therapy. The primary outcome was the composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year, and was powered for noninferiority, with an absolute margin of 4.1% at 1-sided 5% alpha., Results: A total of 1948 patients at high bleeding risk were randomly assigned (1:1) to receive biodegradable-polymer sirolimus-eluting stents (969 patients) or durable-polymer zotarolimus-eluting stents (979 patients). At 1 year, the primary outcome was observed in 33 of 969 patients (3.6%) in the biodegradable-polymer sirolimus-eluting stent group and in 32 of 979 patients (3.4%) in the durable-polymer zotarolimus-eluting stent group (risk difference, 0.2 percentage points; upper boundary of the 1-sided 95% CI, 1.8; upper boundary of the 1-sided 97.5% CI, 2.1; P <0.0001 for noninferiority for both tests)., Conclusions: Among patients at high risk for bleeding who received 1 month of dual antiplatelet therapy after PCI, the use of biodegradable-polymer sirolimus-eluting stents was noninferior to the use of durable-polymer zotarolimus-eluting stents with regard to the composite of death from cardiac causes, myocardial infarction, or stent thrombosis., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04137510., Competing Interests: Disclosures Dr Valgimigli reports grants and personal fees from Terumo and personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, IDORSIA Pharmaceuticals Ltd, Universität Basel, Department Klinische Forschung, Vifor, Bristol Myers Squibb SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio. Dr Wlodarczak has no conflicts of interest to report. Dr Tölg reports personal fees for lectures from Biotronik. Dr Merkely reports personal fees from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, Duke Clinical Research Institute, Medtronic, and Novartis, and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, Duke Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr Kelbæk has no conflicts of interest to report. Dr Legutko reports lecture fees from Abiomed, AstraZeneca, Berlin Chemie-Menarini, Abbott, Bayer AG, Ely Lilly, Medtronic, MSD, Philips-Volcano, Procardia, Sanofi, and Novartis; meeting or travel fees from Abbott, Boston, Medtronic, and Abiomed; and data safety monitoring board or advisory board fees from AstraZeneca, Berlin Chemie-Menarini, Abbott, Sanofi, Gedeon Richte, Hemolens Diagnostics, Novartis, and Ferrer. Dr Galli reports consulting fees from BIOACADEMY and lecture fees from PCR. Dr Godin reports lecture fees from B. Braun, Medtronic, and Edwards, and data safety monitoring board or advisory board fees from Terumo and Microport. Dr Toth reports grants and personal fees from Terumo, Abbott Vascular, Biotronik, and Medtronic. Dr Lhermusier reports consulting fees from Abbott and meeting or travel fees from Medtronic. Dr Honton reports consulting fees from Medtronic, Shockwave, Terumo, and Microport; lecture fees from Shockwave, Medtronic, and Boston; and data safety monitoring board or advisory board fees from Microport, Terumo, and Medtronic. Dr Dietrich reports educational event fees to his institution from Cordis. Drs. Stammen and Ferdinande have no conflicts of interest to report. Dr Silvain reports consulting fees from AstraZeneca, Bayer Health Care SAS, CSL Behring SA, Sanofi-Aventis France, and Zoll, and stock options without payment at 4P-Pharma. Dr Capodanno reports honoraria fees from Biotronik and honoraria fees to his institution from Medtronic. Dr Cayla reports personal consulting fees from Edwards, Medtronic, and Microport CRM, and personal honoraria fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Edwards, Microport, Medtronic, Pfizer, and Sanofi-Aventis.

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.

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: The third-generation coronary sirolimus-eluting magnesium scaffold, DREAMS 3G, is a further development of the DREAMS 2G (commercial name Magmaris), aiming to provide performance outcomes similar to drug-eluting stents (DES)., Aims: The BIOMAG-I study aims to assess the safety and performance of this new-generation scaffold., Methods: This is a prospective, multicentre, first-in-human study with clinical and imaging follow-up scheduled at 6 and 12 months. The clinical follow-up will continue for 5 years., Results: A total of 116 patients with 117 lesions were enrolled. At 12 months, after completion of resorption, in-scaffold late lumen loss was 0.24±0.36 mm (median 0.19, interquartile range 0.06-0.36). The minimum lumen area was 4.95±2.24 mm² by intravascular ultrasound and 4.68±2.32 mm² by optical coherence tomography. Three target lesion failures were reported (2.6%, 95% confidence interval: 0.9-7.9), all clinically driven target lesion revascularisations. Cardiac death, target vessel myocardial infarction and definite or probable scaffold thrombosis were absent., Conclusions: Data at the end of the resorption period of DREAMS 3G showed that the third-generation bioresorbable magnesium scaffold is clinically safe and effective, making it a possible alternative to DES., Clinicaltrials: gov: NCT04157153.

Competing Interests: Funding Support and Author Disclosures Dr Toth has received personal fees from Abbott, Medtronic, Biotronik, and Boston Scientific, outside the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Percutaneous closure of patent foramen ovale (PFO) is conventionally performed under continuous transesophageal echocardiographic (TEE) guidance. We aimed to evaluate whether a simplified procedural approach, including pure fluoroscopy-guidance and final TEE control, as well as an aimed 'next-day-discharge' is comparable with the conventional TEE-guided procedure in terms of periprocedural and intermediate-term outcomes., Methods: All patients who underwent a PFO closure at our center between 2010 and 2022 were retrospectively included. Prior to June 2019 cases were performed with continuous TEE guidance (TEE-guided group). Since June 2019, only pure fluoroscopy-guided PFO closures have been performed with TEE insertion and control just prior to device release (fluoroscopy-guided group). We analyzed procedural aspects, as well as long term clinical and echocardiographic outcomes., Results: In total 291 patients were included in the analysis: 197 in the TEE-guided group and 94 in the fluoroscopy-guided group. Fluoroscopy-guided procedures were markedly shorter (48 ± 20 min vs. 25 ± 9 min; p < .01). There was no difference in procedural complications, including death, major bleeding, device dislodgement, stroke or clinically relevant peripheral embolization between the two groups (.5% vs. 0%; p = .99). Hospital stay was also shorter with the simplified approach (2.5 ± 1.6 vs. 3.5 ± 1.2 days; p < .01), allowing 85% same-day discharges during the last 12 months of observation period. At 6 ± 3 months echocardiographic follow-up a residual leakage was described in 8% of the TEE-guided cases and 2% of the fluoroscopy-guided cases (p = .08)., Conclusion: While a complete TEE-free PFO closure might have potential procedural risks, our approach of pure fluoroscopy-guided with a brisk final TEE check seems to be advantageous in terms of procedural aspects with no sign of any acute or intermediate-term hazard and it could offer an equitable compromise between the two worlds: a complete TEE procedure and a procedure without any TEE., (© 2023 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Background: Isolate features of the coronary anatomy have been associated with the pathophysiology of atherosclerotic disease. Computational methods have been described to allow precise quantification of the complex three-dimensional (3D) coronary geometry. The present study tested whether quantitative parameters that describe the spatial 3D coronary geometry is associated with the extension and composition of the underlying coronary artery disease (CAD)., Methods: Patients with CAD scheduled for percutaneous intervention were investigated with coronary computed tomography angiography (CCTA), and invasive coronary angiography, and virtual histology intravascular ultrasound (IVUS-VH). For all target vessels, 3D centerlines were extracted from CCTA images and processed to quantify 23 geometric indexes, grouped into 3 main categories as follows: (i) length-based; (ii) curvature-based, torsion-based, and curvature/torsion-combined; (iii) vessel path-based. The geometric variables were compared with IVUS-VH parameters assessing the extent and composition of coronary atherosclerosis., Results: A total of 36 coronary patients (99 vessels) comprised the study population. From the 23 geometric indexes, 18 parameters were significantly (p < 0.05) associated with at least 1 IVUS-VH parameter at a univariate analysis. All three main geometric categories provided parameters significantly related with atherosclerosis variables. The 3D geometric indexes were associated with the degree of atherosclerotic extension, as well as with plaque composition. Geometric features remained significantly associated with all IVUS-VH parameters even after multivariate adjustment for clinical characteristics., Conclusions: Quantitative 3D vessel morphology emerges as a relevant factor associated with atherosclerosis in patients with established CAD., (© 2023 Wiley Periodicals LLC.)

More than a decade after the Clinical Outcomes Utilising Revascularization and Aggressive Drug Evaluation (COURAGE) trial, International Study of Comparative Health Effectiveness With Medical And Invasive Approaches (ISCHEMIA) is the second large clinical trial to challenge the concept of revascularization in chronic coronary syndromes whilst addressing some of the shortfalls of its predecessor., (Copyright © 2021. Published by Elsevier Inc.)

Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3−5) and the median HAS-BLED score was 3 (2−4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65−0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5−68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.

Competing Interests: Funding Support and Author Disclosures Dr G Toth has received personal fees from Abbott, Medtronic, Biotronik and Boston Scientific, outside the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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.

Aim: Cardiogenic shock (CS) is a hemodynamically complex multisystem syndrome associated with persistently high morbidity and mortality. As CS is characterized by progressive failure to provide adequate systemic perfusion, supporting end-organ perfusion using mechanical circulatory support (MCS) seems intriguing. Since most patients with CS present in the catheterization laboratory, percutaneously implantable systems have the widest adoption in the field. We evaluated feasibility, outcomes, and complications after the introduction of a full-percutaneous program for both the Impella CP device and venoarterial extracorporeal membrane oxygenator (VA-ECMO)., Methods: PREPARE CardShock (PRospective REgistry of PAtients in REfractory cardiogenic shock) is a prospective single-center registry, including 248 consecutive patients between May 2019 and April 2021, who underwent cardiac catheterization and displayed advanced cardiogenic shock. The median age was 70 (58-77) years and 28% were female. Sixty-five percent of the cases had cardiac arrest, of which 66% were out-of-hospital cardiac arrest. A local standard operating procedure (SOP) indicating indications as well as relative and absolute contraindications for different means of MCS (Impella CP or VA-ECMO) was used to guide MCS use. The primary endpoint was in-hospital death and secondary endpoints were spontaneous myocardial infarction and major bleedings during the hospital stay., Results: Overall mortality was 50.4% with a median survival of 2 (0-6) days. Significant independent predictors of mortality were cardiac arrest during the index event (odds ratio [OR] with 95% confidence interval [CI]: 2.53 [1.43-4.51]; p = 0.001), age > 65 years (OR: 2.05 [1.03-4.09]; p = 0.036]), pH < 7.30 (OR: 2.69 [1.56-4.66]; p < 0.001), and lactate levels > 2 mmol/L (OR: 4.51 [2.37-8.65]; p < 0.001)., Conclusions: Conclusive SOPs assist target-orientated MCS use in CS. This study provides guidance on the implementation, validation, and modification of newly established MCS programs to aid centers that are establishing such programs., (© 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Atherosclerosis is a systemic arterial disease with heterogeneous involvement in all vascular beds; however, studies examining the relationship between coronary and radial artery calcification are lacking. The purpose of this study was to assess the relationship between the two sites and the prognostic value of radial artery calcification (RC) for coronary artery disease., Methods: This is a single-center, retrospective cross-sectional study based on Doppler ultrasound of radial artery (RUS) and coronary artery angiography (CAG). We included a total of 202 patients undergoing RUS during distal radial access and CAG at the same procedure, between December 2020 and May 2021, from which 103 were found having RC during RUS (RC group) and 99 without (NRC group). Coronary calcifications were evaluated either by angiography examination (moderate and severe), positive CT (>100 Agatson units), or intracoronary imaging (IVUS, OCT)., Results: A significant correlation was observed between radial calcification and coronary calcification variables (67.3% vs. 32.7%, p =0.001). The correlation between risk factors such as age, smoking, chronic kidney disease, and diabetes mellitus was higher while sex did not play a role. The need of PCI and/or CABG was higher in the RC group (60% vs. 44%, p =0.02). RC, therefore, predicts the extent and severity of coronary artery disease., Conclusion: RC may be frequently associated with calcific coronary plaques. These findings highlight the potential beneficial examination of radial arteries whenever CAD is suspected., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Alexandru Achim et al.)

Background: While radial stent deformation has been thoroughly investigated, data on longitudinal deformation are scarce., Aims: The aim of the study was to describe longitudinal stent deformation associated with the proximal optimisation technique (POT)., Methods: Longitudinal stent deformation was assessed by bench testing and by clinical evaluation. Bench testing was performed in silicone models using 3.00 (n=15) and 3.50 mm (n=14) stent platforms. After deployment, stents were sequentially post-dilated in the proximal main branch up to 5.50 mm, in increments of 0.50 mm, in order to simulate a spectrum of overexpansion. Stent length was redefined by optical coherence tomography (OCT) after each step. Clinical data were collected retrospectively from OCT-guided bifurcation percutaneous coronary intervention cases., Results: In bench tests, POT has led to significant stent elongation in all cases. The magnitude of elongation was comparable between the 3.00 and the 3.50 mm stent platforms, with 0.86±0.74 mm vs 0.86±0.73 mm, respectively (p=0.71), per 0.5 mm overexpansion. For 3.00 mm stent platforms, maximal elongation was 4.31±1.47 mm after up to 5.5 mm overexpansion. For 3.50 mm platforms, maximal elongation was 2.87±0.94 mm after up to 5.5 mm overexpansion. Thirty-six clinical cases were analysed, of which 22 (61%) were performed in the distal left main. Post-dilation was performed with 0.98±0.36 mm absolute overexpansion, resulting in 2.22±1.35 mm elongation, as compared to nominal stent length., Conclusions: Overexpansion by POT results in proximal stent elongation. This has to be considered once the stent length is selected and the stent is positioned, especially in the left main stem, where proximal overexpansion is marked and accurate ostial landing is critical.

Clinical guidelines recommend the development of ST-elevation myocardial infarction (STEMI) networks at community, regional and/or national level to ideally offer primary coronary angioplasty, or at least the best available STEMI care to all patients. However, there is a discrepancy between this clinical recommendation and daily practice, with no coordinated care for STEMI patients in many regions of the world. While this can be a consequence of lack of resources, in reality it is more frequently a lack of organisational power. In this paper, the Stent - Save a Life! Initiative (www.stentsavealife.com) proposes a practical methodology to set up a STEMI network effectively in any region of the world with existing resources, and to develop the STEMI network continuously once it has been established.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aims: In the randomized GRAFFITI trial, surgeons drew their strategy based on coronary angiography. When patients were randomized to fractional flow reserve (FFR)-guidance, surgeons were informed of the FFR values and asked to redraw their strategy. The aim of this study was to investigate the changes induced by FFR knowledge., Methods and Results: The intended and performed strategy (before and after FFR) were compared. Among 172 patients, 84 with 300 lesions were randomized to the FFR-guided group. The intended strategy was to bypass 236 stenoses:108 with a venous and 128 with an arterial graft. After disclosing FFR, a change in strategy occurred in 64 lesions (21.3%) of 48 (55%) patients. Among 64 lesions for which the intended strategy was medical therapy, 16 (25%) were bypassed after disclosing FFR. The number of procedures with >1 venous graft planned was significantly reduced from 37 to 27 patients (p = .031). The proportion of on-pump surgery was significantly reduced from 71 to 61 patients (p = .006). The rates of clinical events at 1 year were similar between patients with or without at least one change in strategy., Discussion: FFR-guided CABG is associated with a simplified surgical procedure in 55% of the patients, with similar clinical outcomes., (© 2021 Wiley Periodicals LLC.)

A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant 'major' periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The proposed 2020 Core Curriculum for Percutaneous Cardiovascular Interventions aims to provide an updated European consensus that defines the level of experience and knowledge in the field of percutaneous cardiovascular intervention (PCI). It promotes homogenous education and training programmes among countries, and is the cornerstone of the new EAPCI certification, designed to support the recognition of competencies at the European level and the free movement of certified specialists in the European Community. It is based on a thorough review of the ESC guidelines and of the EAPCI textbook on percutaneous interventional cardiovascular medicine. The structure of the current core curriculum evolved from previous EAPCI core curricula and from the "2013 core curriculum of the general cardiologist" to follow the current ESC recommendations for core curricula. In most subject areas, there was a wide - if not unanimous - consensus among the task force members on the training required for the interventional cardiologist of the future. The document recommends that acquisition of competence in interventional cardiology requires at least two years of postgraduate training, in addition to four years devoted to cardiology. The first part of the curriculum covers general aspects of training and is followed by a comprehensive description of the specific components in 54 chapters. Each of the chapters includes statements of the objectives, and is further subdivided into the required knowledge, skills, behaviours, and attitudes.

Background: Right ventricular (RV) function predicts survival in numerous cardiac conditions, including left heart disease. The reference standard for non-invasive assessment of RV function is cardiac magnetic resonance imaging (CMR). The aim of this study was to investigate the association between pre-procedural CMR-derived RV functional parameters and mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: Patients scheduled for TAVI were recruited to undergo pre-procedural CMR. Volumetric function and global longitudinal and circumferential strain (GLS and GCS) of the RV and left ventricle (LV) were measured. The association with the primary endpoint (1-year all-cause mortality) was analyzed with Cox regression. Results: Of 133 patients undergoing CMR, 113 patients were included in the analysis. Mean age was 81.8 ± 5.8 years, and 65% were female. Median follow-up was 3.9 [IQR 2.3-4.7] years. All-cause and cardiovascular mortality was 14 and 12% at 1 year, and 28 and 20% at 3 years, respectively. One-year all-cause mortality was significantly predicted by RV GLS [HR = 1.109 (95% CI: 1.023-1.203); p = 0.012], RV ejection fraction [HR = 0.956 (95% CI: 0.929-0.985); p = 0.003], RV end-diastolic volume index [HR = 1.009 (95% CI: 1.001-1.018); p = 0.025], and RV end-systolic volume index [HR = 1.010 (95% CI: 1.003-1.017); p = 0.005]. In receiver operating characteristic (ROC) analysis for 1-year all-cause mortality, the area under the curve was 0.705 (RV GLS) and 0.673 (RV EF). Associations decreased in strength at longer follow-up. None of the LV parameters was associated with mortality. Conclusions: RV function predicts intermediate-term mortality in TAVI patients while LV parameters were not associated with outcomes. Inclusion of easily obtainable RV GLS may improve future risk scores., Competing Interests: GT received consultancy fees and unrestricted research support from Abbott, Medtronic, Biotronic and Boston Scientific, not related to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schmid, Kamml, Zweiker, Hatz, Schmidt, Reiter, Toth, Fuchsjäger, Zirlik, Binder and Rainer.)

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long-term clinical outcome of patients with stable coronary artery disease but no ischemia-inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all-cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post-percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80-2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5-year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log-rank P =0.040). The higher 5-year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log-rank P =0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977-0.998; P =0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966-0.998; P =0.032), and revascularization (HR, 0.985; 95% CI, 0.972-0.999; P =0.040). Conclusions Even in the absence of ischemia-producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5-year follow-up.

Background:  For patients treated with dual antiplatelet therapy, standardized drug-specific 3-to-7 day cessation is recommended prior to major surgery to reach sufficient platelet function recovery. Here we investigated the hypothesis that supplemental fibrinogen might mitigate the inhibitory effects of antiplatelet therapy., Methods and Results:  To this end blood from healthy donors was treated in vitro with platelet inhibitors, and in vitro thrombus formation and platelet activation were assessed. Ticagrelor, acetylsalicylic acid, the combination of both, and tirofiban all markedly attenuated the formation of adherent thrombi, when whole blood was perfused through collagen-coated microchannels at physiological shear rates. Addition of fibrinogen restored in vitro thrombus formation in the presence of antiplatelet drugs and heparin. However, platelet activation, as investigated in assays of P-selectin expression and calcium flux, was not altered by fibrinogen supplementation. Most importantly, fibrinogen was able to restore in vitro thrombogenesis in patients on maintenance dual antiplatelet therapy after percutaneous coronary intervention., Conclusion:  Thus, our in vitro data support the notion that supplementation of fibrinogen influences the perioperative hemostasis in patients undergoing surgery during antiplatelet therapy by promoting thrombogenesis without significantly interfering with platelet activation., Competing Interests: None declared., (Thieme. All rights reserved.)