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Background: Quantitative coronary angiography (QCA) typically employs traditional edge detection algorithms that often require manual correction. This has important implications for the accuracy of downstream 3D coronary reconstructions and computed haemodynamic indices (e.g. angiography-derived fractional flow reserve). We developed AngioPy, a deep-learning model for coronary segmentation that employs user-defined ground-truth points to boost performance and minimise manual correction. We compared its performance without correction with an established QCA system., Methods: Deep learning models integrating user-defined ground-truth points were developed using 2455 images from the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) study. External validation was performed on a dataset of 580 images. Vessel dimensions from 203 images with mild/moderate stenoses segmented by AngioPy (without correction) and an established QCA system (Medis QFR®) were compared (609 diameters)., Results: The top-performing model had an average F1 score of 0.927 (pixel accuracy 0.998, precision 0.925, sensitivity 0.930, specificity 0.999) with 99.2 % of masks exhibiting an F1 score > 0.8. Similar results were seen with external validation (F1 score 0.924, pixel accuracy 0.997, precision 0.921, sensitivity 0.929, specificity 0.999). Vessel dimensions from AngioPy exhibited excellent agreement with QCA (r = 0.96 [95 % CI 0.95-0.96], p < 0.001; mean difference - 0.18 mm [limits of agreement (LOA): -0.84 to 0.49]), including the minimal luminal diameter (r = 0.93 [95 % CI 0.91-0.95], p < 0.001; mean difference - 0.06 mm [LOA: -0.70 to 0.59])., Conclusion: AngioPy, an open-source tool, performs rapid and accurate coronary segmentation without the need for manual correction. It has the potential to increase the accuracy and efficiency of QCA., Competing Interests: Declaration of competing interest BDB reports receiving consultancy fees from Boston Scientific and Abbott Vascular, research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc., and Abbott Vascular, and owning equity in Siemens, GE, Philips, HeartFlow Inc., Edwards Life Sciences, Bayer, Sanofi, Celyad. All the other authors have nothing to disclose. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijcard.2024.132598., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Meier has received an institutional grant from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: The transcaval (TCv) vascular approach is increasingly used in transcatheter aortic valve replacement (TAVR) in patients unsuitable for the gold-standard transfemoral approach. We aimed to evaluate the efficacy, safety, and clinical outcomes associated with TCv-TAVR., Methods: A systematic review and meta-analysis was conducted by searching PubMed/Medline, Embase, and the Cochrane Library for all articles assessing the TCv approach published through December 2023. Outcomes included 30-day and 1-year all-cause mortality (ACM), 30-day rehospitalisation, perioperative complications and postoperative complications at 30 days. The meta-analysis was registered on the PROSPERO database with the identifier CRD42024501921., Results: A total of 8 studies with 467 patients were included. TCv-TAVR procedures achieved a success rate of 98.5%. TCv-TAVR was associated with a 30-day ACM rate of 6.1% (95% confidence interval [CI]: 3.9%-8.2%), a 1-year ACM rate of 14.9% (95% CI 2.3%-27.6%) and a 30-day rehospitalisation rate of 4.2% (95% CI -2.2% to 10.6%). Postoperative stroke or transient ischemic attack, major vascular complications, and major or life-threatening bleeding occurred in 3.3%, 8.7%, and 7.5% of cases, respectively. Cumulative meta-analyses showed a temporal trend of decreasing rates of vascular complications., Conclusions: The TCv approach in TAVR demonstrated a reassuring efficacy and safety profile, with mortality and postoperative complication rates similar to those reported for supra-aortic alternative TAVR access routes. The temporal decrease in vascular complications suggests potential improvements in procedural techniques and device technology. These findings further support the TCv approach as a viable option in patients ineligible for the transfemoral access., Prospero: CRD42024501921., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain., Methods: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310., Findings: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988)., Interpretation: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation., Funding: Biotronik., Competing Interests: Declaration of interests JFI reports a research grant to their institution, speaker fees, and support for attending meetings from Biotronik; research grants to their institution from Abbott Vascular, Astra Zeneca, Biosensors, Concept Medical, Philips, and Terumo Corporation, outside the submitted work; and speaker fees from AstraZeneca, Biosensors, Biotronik, Bristol Myers Squibb, Cordis, Concept Medical, Medalliance, Medtronic, Novartis, Terumo Corporation, Pfizer, and Philips, outside the submitted work. MR reports research grants to the institution from Biotronik, Boston Scientific, Cordis, Medtronic, and Terumo Corporation, outside the submitted work. SL and DH are employed by the CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organisations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. An up-to-date list of CTU Bern's conflicts of interest can be found online. OM reports a research grant to their institution, and speaker and personal fees from Edwards Lifesciences, outside the submitted work; and speaker fees from Abbott Vascular, outside the submitted work. SD reports research grants to their institution from Abbott Vascular and Biotronik, outside the submitted work; and speaker fees from Biotronik, Medalliance, and Medtronic, outside the submitted work. LH reports research grants to their institution from Abbott Vascular, Abiomed, Amarin, Amgen, AstraZeneca, Bayer, Biosense Webster, Biotronik, Boston Scientific, Bracco, Bristol Myers Squibb, B-Braun, Daiichi-Sankyo, Edwards Lifesciences, GE HealthCare, Medtronic, Microport, Novartis, Pfizer, Vascular Medical, and Zoll, outside the submitted work; speaker fees from Medtronic, outside the submitted work; and support for attending meetings from Daiichi-Sankyo and Biotronik. CK reports consulting fees to the institution from Unimedtec Switzerland; and support for attending meetings from Medtronic, outside the submitted work. SW reports research, travel, or educational grants to their institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Bbraun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Farapulse, Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo Corporation, Vifor, and V-Wave; and served as an advisory board member or member of the steering or executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo Corporation, and V-Wave, with payments to the institution but no personal payments. He is also a member of the steering or executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. TP reports a research grant to their institution from Biotronik; research, travel, or educational grants to their institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens, outside the submitted work; and speaker fees and consultancy fees to their institution from Abbott Vascular, Biotronik, Biosensors, Boston Scientific, Edwards Lifesciences, Highlife, and Medtronic, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Carnitine metabolism produces numerous molecular species of short-, medium-, and long-chain acylcarnitines, which play important roles in energy homeostasis and fatty acid transport in the myocardium. Given that disturbances in the carnitine metabolism are linked to cardiometabolic disease, we studied the relationship of circulating acylcarnitines with outcomes in patients with acute coronary syndromes (ACS) and evaluated differences in circulating levels of these metabolites between diabetic and non-diabetic patients., Methods: Harnessing a prospective multicentre cohort study (SPUM-ACS; NCT01000701), we measured plasma levels of acylcarnitines, carnitine, and carnitine metabolites to assess their relationship with adjudicated major adverse cardiac events (MACE), defined as composite of myocardial infarction, stroke, clinically indicated revascularization, or death of any cause. The SPUM-ACS study enrolled patients presenting with ACS to Swiss University Hospitals between 2009 and 2012. Acetylcarnitine, octanoylcarnitine, proprionylcarnitine, butyrylcarnitine, pentanoylcarnitine, hexanoylcarnitine, carnitine, γ-butyrobetaine, and trimethylamine N-oxide were measured in plasma using stable isotope dilution high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry., Results: A total of 1683 patients with ACS were included in the study. All measured metabolites except γ-butyrobetaine and carnitine were higher in diabetic subject (n = 294) than in non-diabetic subjects (n = 1389). On univariate analysis, all metabolites, apart from octenoylcarnitine, were significantly associated with MACE at 1 year. After multivariable adjustment for established risk factors, acetylcarnitine remained an independent predictor of MACE at 1-year (quartile 4 vs. quartile 1, adjusted hazard ratio 2.06; 95% confidence interval 1.12-3.80, P = 0.020)., Conclusion: Circulating levels of acetylcarnitine independently predict residual cardiovascular risk in patients with ACS., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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

Background: Pre-partecipation ECG screening of large populations has a significant socioeconomic impact. Technological progress now allows for high-tech-low-cost ECG screening using validated smartphone-based devices capable of guiding to the correct performance of a 12‑lead ECG by layman with no medical background., Methods: We enrolled 728 (364, 52% males) individuals, aged 12-13 years who underwent ECG screening with a smartphone 12‑lead ECG during school hours by layman volunteers. Correct electrodes placement was provided by a validated image-processing algorithm by the smartphone camera in the App. ECG interpretation was via a telecardiology platform and alterations classified following current standards., Results: A total of 741 ECGs were recorded, of which 13(2%) were technically not interpretable. Mean PR, QRS and QTc were: 145 ± 22, 85 ± 19 and 387 ± 57 msec. No QTc prolongation was observed. Mean QRS axis was 15°; 26 (4%) patients presented an iRBB. T-wave inversion from V1-V3 was present in 145 (21%) subjects. Twenty-one(3%) patients were referred to second level examination: deep Q-waves in inferior leads in 12(1.6%), ventricular ectopics in 5(0.7%), anterior T-waves inversions V1-V4 in 3(0.4%); extreme right axis deviation in 1(0.3%). Second line investigations did not provide any definitive diagnosis. Total project costs (material equipment and human cost) was 14.460€, 19.51€ per individual. The potential net saving with respect to current pre-participation screening cost was 19%., Conclusions: Layman 12‑lead Smartphone-ECG population screening proved feasible and effective, with a rate of non-interpretable ECG of <5%. Potential cost-saving in ECG screening and recording was 19%, providing an appealing opportunity when large campaigns should be addressed also in developing countries., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Arrhythmogenic right ventricular cardiomyopathy is a hereditary myocardial condition in most cases that affects the right ventricle, but also the left ventricle with variable degree. It predisposes patients to ventricular arrhythmia, heart failure and sudden death. Its diagnosis remains challenging and is mostly based on reference task-force criteria. The latter, divided between major and minor criteria, include structural abnormalities (visualized on echocardiography or cardiac magnetic resonance), electrocardiographic anomalies, ventricular arrythmia documentation, histological proof of fibro-fatty infiltrates within myocardial tissue and family history. Following a correct diagnosis, patient-tailored care is essential. First, implantation of an implantable cardioverter-defibrillator is recommended in case of history of sudden death, sustained ventricular tachycardia or advanced right/left ventricular dysfunction. It should be considered in case of cardiac syncope or non-sustained ventricular tachycardia. Secondly, eviction of high intensity physical activity is mandatory. Finally, beta-blockers are recommended for all patients with clinically manifest arrhythmogenic right ventricular cardiomyopathy., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

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.

Background: The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics., Methods: We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland., Findings: Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group., Interpretation: The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification., Funding: Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation., Competing Interests: Declaration of interests SK received travel support from the European Atherosclerosis Society and equipment and materials from Roche Diagnostics, outside the submitted work. MR declares institutional research grants from Terumo, Biotronik, Medtronic, Cordis/Cardinal Health, and Boston Scientific, outside the submitted work. LR received funding from Abbott, Biotronik, Boston Scientific, Sanofi, Regeneron, and Heartflow, consulting fees from Abbott, Amgen, AstraZeneca, Canon, NovoNordisk, Medtronic, Sanofi, Occlutech, and Vifor, payment or honoraria from Abbott and Occlutech, and travel support from AstraZeneca. MdB is Chair of the Data Monitoring and Ethics Committee of the UK GRIS Trial and part of the Steering Committee of the DAPA MI Trial. CW is the clinical lead of the MINAP registry. JD received consulting fees from GENinCode UK Ltd, honoraria or consulting fees from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer, and travel support from the Einstein Professorship Foundation (Berlin, Germany), outside the submitted work. JD holds unpaid leadership positions at Our Future Health and Public Health England. TFL declares institutional educational and research grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daichi Sankyo, Novartis, and Vifor, and consulting fees from Daichi Sankyo, Philipps, Pfizer, and Ineeo Inc, outside the submitted work. TFL holds leadership positions at the European Society of Cardiology, Swiss Heart Foundation, and the Foundation for Cardiovascular Research—Zurich Heart House. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: CCN family member 1 (CCN1) has recently been proposed as a novel biomarker of myocardial injury, improving prediction of 30-day and one-year mortality following acute coronary syndromes. Among ST-elevation myocardial infarction (STEMI) patients, we evaluated the utility of CCN1 measured immediately before primary percutaneous coronary intervention (PPCI) as a predictor of two earlier endpoints: final myocardial infarct size and post-infarction left ventricular ejection fraction (LVEF). Furthermore, we evaluated the impact of CCN1 on the discriminatory power of the CADILLAC score., Methods: STEMI patients were obtained from the SPUM-ACS cohort. Serum CCN1 was measured prior to PPCI. Linear regression assessed the association between CCN1, peak creatinine kinase (CK), and post-infarction LVEF. Cox models assessed an association between CCN1 and 30-day all-cause mortality., Results: CCN1 was measured in 989 patients with a median value of 706.2 ng/l (IQR 434.3-1319.6). A significant correlation between CCN1, myocardial infarct size (peak CK) and LVEF was observed in univariate and multivariate analysis (both p < 0.001). Even among patients with normal classical cardiac biomarker levels at the time of PPCI, CCN1 correlated significantly with final infarct size. CCN1 significantly improved prediction of 30-day all-cause mortality by the CADILLAC score (C-index 0.864, likelihood-ratio chi-square test statistic 6.331, p = 0.012; IDI 0.026, p= 0.050)., Conclusions: Compared with classical cardiac biomarkers, CCN1 is potentially the earliest predictor of final myocardial infarct size and post-infarction LVEF. CCN1 improved the discriminatory capacity of the CADILLAC score suggesting a potential role in the very-early risk stratification of STEMI patients., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Randomized evidence comparing newer-generation drug-eluting stents for multivessel percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is limited. We sought to investigate clinical outcomes in STEMI patients undergoing multivessel PCI with thin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES)., Methods: We performed a subgroup analysis of the BIOSTEMI (NCT02579031) randomized trial, which included individual patient data from STEMI patients enrolled into the BIOSCIENCE (NCT02579031) study. STEMI patients randomly allocated to BP-SES or DP-EES were divided into those undergoing multivessel versus culprit lesion-only PCI. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial re-infarction or clinically indicated target lesion revascularization (TLR), within 24 months., Results: Among 1707 STEMI patients, 145 patients underwent multivessel PCI. At 2 years, TLF occurred in 2 patients (2.8%) treated with BP-SES and 13 patients (18.7%) treated with DP-EES (hazard ratio [HR], 0.14; 95% confidence interval (CI), 0.03-0.61; p = 0.009) in the multivessel PCI group, and in 40 (5.3%) and 61 (8.2%) patients treated with BP-SES and DP-EES respectively (HR, 0.64; 95%CI, 0.43-0.96; p = 0.03; p for interaction = 0.050) in the culprit lesion-only PCI group. In the multivessel PCI group, the rates of clinically indicated TLR (0% vs. 12.4%) and target vessel myocardial re-infarction (0% vs. 4.6%) at 2 years were lower in patients treated with BP-SES compared with DP-EES., Conclusion: In a subgroup analysis of the BIOSTEMI trial, BP-SES were associated with lower 2-year TLF rates compared to DP-EES in STEMI patients undergoing multivessel PCI., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the safety and efficacy of biodegradable-polymer sirolimus-eluting stents (BP-SES) compared with durable-polymer everolimus-eluting stents (DP-EES) in patients with ST-segment elevation myocardial infarction (STEMI)., Background: Primary percutaneous coronary intervention (PCI) is an effective treatment for patients with STEMI, and long-term outcomes are determined by the safety and efficacy profile of the newest generation drug-eluting stents., Methods: BIOSTEMI (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention) was an investigator-initiated, multicenter, assessor-blind, randomized superiority trial using Bayesian methods. Patients with STEMI undergoing primary PCI within 24 h of symptom onset were randomized in a 1:1 ratio to receive BP-SES (n = 649) or DP-EES (n = 651). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial reinfarction, and clinically indicated target lesion revascularization (TLR) at 2 years., Results: Between April 2016 and March 2018, 1,300 patients were included. Baseline characteristics were comparable between the 2 treatment groups. Follow-up through 2 years was complete in 1,221 patients (94%). At 2 years, TLF occurred in 33 patients (5.1%) treated with BP-SES and in 53 patients (8.1%) treated with DP-EES (rate ratio: 0.58; 95% Bayesian credible interval: 0.40 to 0.84; posterior probability of superiority = 0.998). The difference was driven by a lower incidence of clinically indicated TLR in patients treated with BP-SES compared with DP-EES (2.5% vs. 5.1%; rate ratio: 0.52; 95% Bayesian credible interval: 0.30 to 0.87; posterior probability of superiority = 0.993). There were no significant differences in rates of cardiac death, target vessel myocardial reinfarction, and definite stent thrombosis between the 2 treatment arms., Conclusions: In patients with STEMI undergoing primary PCI, BP-SES were superior to DP-EES with respect to TLF at 2 years. The difference was driven by lower rates of ischemia-driven TLR. (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention [BIOSTEMI]; NCT02579031)., Competing Interests: Funding Support And Author Disclosures The BIOSTEMI trial was an investigator-initiated study supported by a dedicated research grant from Biotronik. Dr. Pilgrim has received research grants to the institution from Biotronik and Boston Scientific; has received speaker fees from Biotronik and Boston Scientific; and is a consultant for HighlifeSAS. Dr. Roffi has received institutional research grants from Terumo, Boston Scientific, Medtronic, Abbott Vascular, and Biotronik, outside the submitted work. Dr. Valgimigli has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, IDORSIA PHARMACEUTICALS LTD, Universität Basel/Dept. Klinische Forschung, Vifor, Bristol Myers Squibb SA, iVascular, Medscape, and Biotronik; and has received grants and personal fees from Terumo, outside the submitted work. Dr. Jüni is a Tier 1 Canada Research Chair in Clinical Epidemiology of Chronic Diseases, and this research was completed, in part, with funding from the Canada Research Chairs Programme; and serves as an unpaid member of the steering groups of trials funded by AstraZeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company. Dr. Windecker has received research and educational grants to the institution from Abbott, Amgen, Bristol Myers Squibb, Bayer, Boston Scientific, Biotronik, Cardinal Health, Cardiovalve, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Johnson & Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, and Sinomed; serves as an unpaid member of the steering and/or executive groups of trials funded by Abbott, Abiomed, Amgen, Bristol Myers Squibb, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Polares, Sinomed, V-Wave, and Xeltis (but has not received personal payments from any pharmaceutical company or device manufacturer); and is a member of the steering and/or executive committee groups of several investigated-initiated trials that receive funding from industry, without impact on his personal remuneration. Dr. Iglesias has received a research grant to the institution and personal fees from Biotronik during the conduct of the study; has received research grants to the institution and personal fees from Biotronik, Philips Volcano, Abbott Vascular, and AstraZeneca; and has received personal fees from Terumo, Medtronic, and Cardinal Health, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The transfemoral (TF) approach is the gold-standard access route for transcatheter aortic valve replacement (TAVR). Alternative approaches, among which the transcervical (TC) approach, are needed in some patients. We aimed to compare TC-TAVR with TF-TAVR., Methods: All patients who underwent TAVR in our institution between 2016 and 2020, using Edwards SAPIEN family balloon-expandable transcatheter heart valves, were retrospectively included. Endpoints included 30-day all-cause mortality, procedural complications (according to the VARC-2 criteria), procedure duration, hospital length of stay (LOS) and echocardiographic outcomes. For 30-day all-cause mortality, we furthermore used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics as well as anesthesia modality., Results: TAVR was performed in 306 patients, using a TF approach (n = 255) or a TC approach (n = 51). TC-TAVR was associated with significantly higher STS scores (4.06 [IQR (interquartile range), 2.05, 5.56] vs. 2.97 [IQR, 2.08, 4.88], p < 0.001) and higher prevalence of peripheral artery disease, history of stroke, previous cardiovascular surgery. 30-day mortality (hazard ratio, 0.87 [0.77, 9.77], p = 0.909) and stroke rates (2.0% vs. 1.6%, p = 0.840) were similar, as well as procedural duration (74.0 [53.0, 99.5] vs. 77.0 [58.0, 98.0] minutes, p = 0.370), LOS (6.0 [IQR, 3.0, 8.0] vs. 6.0 [IQR, 4.0, 9.0] days, p = 0.175) and postprocedural mean transvalvular gradient (10.00 [IQR, 8.00, 13.00] vs. 10.00 [IQR, 8.00, 12.00] mmHg, p = 0.724)., Conclusion: Despite a higher cardiovascular disease burden in TC patients, TC-TAVR and TF-TAVR yielded similar outcomes. TC-TAVR may be a safe alternative when TF-TAVR is contraindicated., Competing Interests: Declaration of Competing Interest Stephane Fournier reports consulting fees from Bayer and Cathworks, Eric Eeckhout reports grants from Edwards, Olivier Muller reports grants from Abbott and Edwards. The other authors do not have any conflict of interest in relation with this article., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: We aimed to examine cardiovascular risk factors and health behaviors in patients with acute coronary syndromes (ACS) according to potential extension of eligibility criteria for protein convertase subtilisin/kexin-9 inhibitors (PCSK9i) to all patients with low-density lipoprotein cholesterol (LDL-c) equal or above 1.8 mmol/l., Methods: In this prospective cross-sectional study, patients with ACS between 2009 and 2016 and with available LDL-c at one year were considered. We defined three mutually exclusive groups of patients according to eligibility for PCSK9i: "not eligible", "currently eligible", and "newly eligible". We explored the control of cardiovascular risk factors and health behaviors., Results: Out of 3025 patients who had an ACS one year ago, 1071 (35.4%) were not eligible for PCSK9i, 415 (13.7%) were currently eligible, and 1539 (50.9%) were newly eligible. The proportion of patients with uncontrolled hypertension in the not eligible group was lower than in the group currently eligible (27.6% vs 33.6%, p = 0.02), but similar to the group newly eligible (27.6% vs 28.2%, p = 0.73). The proportion of smokers in the not eligible group was lower than in the group currently eligible (21.2% vs 28.0%, p = 0.02), but similar to the group newly eligible (21.2% vs 22.5%, p = 0.51)., Conclusions: More than half of patients with ACS would be additionally eligible for PCSK9i if prescription is extended from current guidelines to all patients with LDL-c equal or above 1.8 mmol/l. Patients currently eligible for PCSK9i one year after an ACS had a worst control of cardiovascular risk factors than patients potentially newly eligible., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI., Methods: The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031., Findings: Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up., Interpretation: In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents., Funding: Biotronik., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Many parameters can affect the level of inflammation during acute coronary syndromes (ACS). We aimed to assess the one-year risk of major adverse cardiovascular events (MACE) and bleeding associated with elevated hsCRP levels during ACS, taking into account the severity of myocardial infarction, the timing of blood sampling and established long-term prognostic factors., Methods: We studied 1864 consecutive patients with ACS enrolled in a contemporary multicenter prospective cohort study in Switzerland. HsCRP levels were determined at hospital admission. One year after discharge MACE and bleeding events were assessed. Multivariable adjusted Cox proportional hazards were computed with age, sex, time from symptom onset to blood draw, body mass index, current smoking, hypertension, diabetes mellitus, pre-existing cardiovascular disease, history of inflammatory disease, LDL-cholesterol levels, type of ACS, left ventricular ejection fraction and GRACE 1.0 risk score., Results: At one-year follow-up, 151 (8.1%) patients suffered MACE. Compared to patients with hsCRP below 2 mg/l, the risk of MACE was higher in patients with hsCRP levels between 2 and 5 mg/l, with a multivariate adjusted hazard ratio (HR) of 1.63 (95% confidence interval (CI) 0.93-2.84), in those with levels between 5 and 10 mg/l, with a HR of 2.80 (95% CI 1.58-4.96), and in those with levels above 10 mg/l, with a HR of 2.23 (95% CI 1.28-3.88). There was no difference in bleeding risk between the four groups., Conclusions: Systemic inflammation in the acute phase of myocardial infarction is an independent predictor for cardiovascular events, but not for bleeding., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Influence of pre-existing treatment with aspirin and/or statins prior to a first acute coronary syndrome (ACS) on clinical presentation, infarct size and inflammation markers. We analyzed patients from the Swiss Program University Medicine ACS-cohort (SPUM-ACS; ClinicalTrials.govnumber:NCT01075867)., Methods: 1639 patients were categorized into 4 groups: (1) patients without either drug (n = 1181); (2) patients only on aspirin (n = 157); (3) patients only on statins (n = 133) and (4) patients on both drugs (n = 168). Clinical features, electrocardiogram (ECG), creatinine kinase (CK, U/l), high-sensitivity troponin T (hsTNT, μg/l), N-terminal brain natriuretic peptide (NT-proBNP, ng/l), leucocytes (Lc, G/l), neutrophils (Nc, G/l), C-reactive protein (CRP, mg/l) and angiographic features were documented at baseline., Results: Incidences of ST-elevation myocardial infarction (STEMI) were 64% in group 1, 45% in group 2, 52% in group 3 and 40% in group 4 (p < 0.0001). Those with both drugs had significantly lower CK (median 145 U/l, interquartile range (IQR) 89-297), hsTNT (median 0.13 μg/l, IQR 0.03-0.52) and higher left ventricular ejection fraction values (LVEF) (mean 55 ± 12%) compared to untreated patients (median CK 273 U/l, IQR 128-638; median hsTNT 0.26 μg/l, IQR 0.08-0.85; mean LVEF 51 ± 11%) (p < 0.0001, p = 0.001, p = 0.028, respectively). Co-medicated groups matched for high risk factors presented less frequently as STEMIs (p < 0.0001), had significantly smaller infarcts determined by CK and hsTNT (both p < 0.0001) and lower CRP levels (p = 0.01) compared to patients without pre-existing treatment with either drug., Conclusion: Pre-existing treatment with aspirin and/or statins and particularly with their combination changes the clinical presentation, infarct size, inflammation markers and LVEF in patients suffering their first ACS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Pulse pressure (PP) is a surrogate of aortic stiffness (AS) easily obtainable. The link between AS and cardio-vascular disease is documented, however, data regarding acute coronary syndrome (ACS) patients are scarce and contradictory. We aimed to assess the prognostic value of PP measured at admission, with regard to major adverse outcomes (all-cause mortality, recurrence of MI, and stroke), during the first year following an acute coronary syndrome (ACS)., Methods: The SPUM-ACS project is a prospective cohort study of patients with ACS conducted in 4 Swiss University hospitals. Patients with no PP at admission or with severe clinical heart failure or cardiogenic shock were excluded. Cox regression analyses were performed to determine associations between PP and outcomes (all-cause mortality, recurrence of myocardial infarction (MI), and stroke). Three multivariate Cox regression models were adjusted for hemodynamic, cardiovascular, and non-cardiovascular confounders, added successively., Results: Of 5635 eligible patients, 5070 met the inclusion criteria. Mean patient age was 63 years (range: 54-72), 79.6% were male, and mean blood pressure and PP were 93.9 ± 15.6 and 54 ± 17 mmHg, respectively. Multivariate analyses confirmed the prognostic significance of PP for each 10-mmHg increase for the composite endpoint, hazard ratio (HR) 1.126 [1.051-1.206], p = 0.001; all-cause mortality, HR1.129 [1.013-1.260], p = 0.029; and recurrence of MI, HR1.206 [1.102-1.320], p < 0.001; but not for stroke, HR1.014[0.853-1.205]., Conclusions: PP measured at admission is a strong, independent prognostic marker predicting mortality and recurrence of MI after ACS. PP should be considered for the management of secondary prevention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Drug-eluting stents combining an ultrathin cobalt-chromium stent platform with a biodegradable polymer eluting sirolimus have been shown to be non-inferior or superior to thin-strut, durable-polymer, everolimus-eluting stents in terms of 1 year safety and efficacy outcomes., Methods: In the randomised, single-blind, multicentre, non-inferiority BIOSCIENCE trial, we compared biodegradable-polymer sirolimus-eluting stents with durable-polymer everolimus-eluting stents in patients with chronic stable coronary artery disease or acute coronary syndromes. Here, we assess the final 5-year clinical outcomes of BIOSCIENCE with regards to the primary clinical outcome of target lesion failure, which was a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation. The primary analysis was done by intention to treat. The BIOSCIENCE trial is registered with ClinicalTrials.gov, number NCT01443104., Findings: 2008 (95%) of 2119 patients recruited between March 1, 2012, and May 31, 2013, completed 5 years of follow-up. Target lesion failure occurred in 198 patients (cumulative incidence 20·2%) treated with biodegradable-polymer sirolimus-eluting stents and in 189 patients (18·8%) treated with durable-polymer everolimus-eluting stents (rate ratio [RR] 1·07, 95% CI 0·88-1·31; p=0·487). All-cause mortality was significantly higher in patients treated with biodegradable-polymer sirolimus-eluting stents than in those treated with durable-polymer everolimus-eluting stents (14·1% vs 10·3%; RR 1·36, 95% CI 1·06-1·75; p=0·017), driven by a difference in non-cardiovascular deaths. We observed no difference between groups in cumulative incidence of definite stent thrombosis at 5 years (1·6% in both groups; 1·02, 0·51-2·05; p=0·950)., Interpretation: 5-year risk of target lesion failure among all-comer patients undergoing percutaneous coronary intervention is similar after implantation of ultrathin-strut, biodegradable-polymer, sirolimus-eluting stents or thin-strut, durable-polymer, everolimus-eluting stents. Higher incidences of all-cause and non-cardiovascular mortality in patients treated with biodegradable-polymer stents eluting sirolimus than in those treated with durable-polymer stents eluting everolimus warrant careful observation in ongoing clinical trials., Funding: Clinical Trials Unit of the University of Bern and Biotronik., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to investigate whether early post-infarction cardiac magnetic resonance (CMR) parameters provide additional long-term prognostic value beyond traditional outcome predictors in ST-segment elevation myocardial infarction (STEMI) patients., Background: Long-term prognostic significance of CMR in STEMI patients has not been assessed yet., Methods: This was a longitudinal study from a multicenter registry that prospectively included STEMI patients undergoing CMR after infarction. Between May 2003 and August 2015, 810 revascularized STEMI patients were included. CMR was performed at a median of 4 days after STEMI. Infarct size, microvascular obstruction (MVO), and left ventricular (LV) volumes and function were measured. Primary endpoint was a composite of all death and decompensated heart failure (HF)., Results: During median follow-up of 5.5 years (range 1.0 to 13.1 years), primary endpoint occurred in 99 patients (39 deaths and 60 HF hospitalization). MVO was a strong predictor of the composite endpoint after correction for important clinical, CMR, and angiographic parameters, including age, LV systolic function, and infarct size. The independent prognostic value of MVO was confirmed in all multivariate models irrespective of whether it was included as a dichotomous (presence of MVO, hazard ratio [HR]: 1.985 to 1.995), continuous (MVO extent as % LV, HR: 1.095 to 1.097), or optimal cutoff value (MVO extent ≥2.6% of LV; HR: 3.185 to 3.199; p < 0.05 for all). MVO extent ≥2.6% of LV was a strong independent predictor of all death (HR: 2.055; 95% confidence interval: 1.076 to 3.925; p = 0.029) and HF hospitalization (HR: 5.999; 95% confidence interval: 3.251 to 11.069; p < 0.001). Finally, MVO extent ≥2.6% of LV provided incremental prognostic value over traditional outcome predictors (net reclassification improvement index: 0.16 to 0.30; p < 0.05 for all models)., Conclusions: Early post-infarction CMR-based MVO is a strong independent prognosticator in revascularized STEMI patients. Remarkably, MVO extent ≥2.6% of LV improved long-term risk stratification over traditional outcome predictors., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the ischemia threshold and additional prognostic factors that identify patients for safe deferral from revascularizations in a large cohort of all-comer patients with known or suspected coronary artery disease (CAD)., Background: Stress-perfusion cardiac magnetic resonance (CMR) is increasingly used in daily practice for ischemia detection. However, there is insufficient evidence about the ischemia burden that identifies patients who benefit from revascularization versus those with a good prognosis who receive drugs only., Methods: All patients with known or suspected CAD referred to stress-perfusion CMR for myocardial ischemia assessment were prospectively enrolled. The CMR examination included standard functional adenosine stress first-pass perfusion (gadobutrol 0.1 mmol/kg Gadovist, Bayer AG, Zurich, Switzerland) and late gadolinium enhancement (LGE) acquisitions. Presence of ischemia and ischemia burden (number of ischemic segments on a 16-segment model), and of scar and scar burden (number and transmurality of scar segments in a 17-segment model) were assessed. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction (MI), and late coronary revascularization (>90 days post-CMR); the secondary endpoint was a composite of cardiac death and nonfatal MI., Results: During a follow-up of 2.5 ± 1.0 years, 86 and 32 of 1,024 patients (1,103 screened patients) experienced the primary and secondary endpoints, respectively. On Kaplan-Meier curves for the primary and secondary endpoints, patients without ischemia had excellent outcomes that did not differ from patients with <1.5 ischemic segments. In multivariate Cox regression analyses of the entire population and of the subgroups, ischemia burden (threshold: ≥1.5 ischemic segments) was consistently the strongest predictor of the primary and secondary endpoints with hazard ratios (HRs) of 7.42 to 8.72 (p < 0.001), whereas age (≥67 years), left ventricular ejection fraction (≤40%), and scar burden (LGE score ≥0.03) contributed significantly, but to a lesser extent, in all models with HRs of 2.01 to 3.48, 1.75 to 1.96, and 1.66 to 1.76, respectively., Conclusions: In a large all-comer patient cohort with known and suspected CAD, an ischemia burden of ≥1.5 ischemic segments on stress-perfusion CMR was the strongest predictor of the primary and secondary endpoints. Patients with zero or 1 ischemic segment can be safely deferred from revascularizations., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Elevated serum levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and atherogenesis. In patients with suspected coronary artery disease (CAD), we assessed the correlation of serum ADMA levels with extent and functional significance of coronary atherosclerosis., Methods: We enrolled 281 patients with suspected CAD undergoing coronary angiogram. Angiographic CAD severity was evaluated by Bogaty score. In patients with angiographic evidence of at least one intermediate coronary stenosis (≥50% diameter stenosis), functional significance was assessed by fractional flow reserve (FFR). Blood samples were collected in all patients prior to coronary angiography for measurement of serum ADMA levels., Results: We observed across tertiles of ADMA levels increasingly higher values of both Stenosis Score (2.25±1.70 vs. 2.89±1.99 vs. 2.95±1.82, p=0.016) and Extent Index (0.52±0.32 vs. 0.61±0.39 vs. 0.72±0.47, p=0.003). The association between ADMA levels and Extent Index remained significant after multivariate adjustment (p=0.005). Patients with FFR ≤0.80 in at least one vessel (n=113) had significantly higher ADMA levels compared with patients without functionally significant CAD (0.51 [0.43-0.64] vs. 0.46 [0.39-0.58]μmol/L, p=0.005). Serum ADMA levels were independent predictors of abnormal FFR after adjustment for extent score (odds ratio 7.35, 95% confidence interval 1.05-56.76, p=0.046)., Conclusions: Serum ADMA levels are independent predictors of coronary atherosclerosis extent and functional significance of CAD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected., Background: Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose., Methods: In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %)., Results: Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine., Conclusions: This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent., Methods: We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104., Findings: Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014)., Interpretation: In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study., Funding: Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR)., Background: When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized., Methods: In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was ≥ 0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population., Results: The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 ± 14% vs. 54 ± 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001)., Conclusions: Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR ≥ 0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)