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Acute coronary syndromes (ACS) are one of the leading causes of mortality worldwide, with atherosclerotic plaque rupture and subsequent thrombus formation as the main underlying substrate. Thrombus burden evaluation is important for tailoring treatment therapy and predicting prognosis. Coronary optical coherence tomography (OCT) enables in-vivo visualization of thrombus that cannot otherwise be achieved by other image modalities. However, automatic quantification of thrombus on OCT has not been implemented. The main challenges are due to the variation in location, size and irregularities of thrombus in addition to the small data set. In this paper, we propose a novel dual-coordinate cross-attention transformer network, termed DCCAT, to overcome the above challenges and achieve the first automatic segmentation of thrombus on OCT. Imaging features from both Cartesian and polar coordinates are encoded and fused based on long-range correspondence via multi-head cross-attention mechanism. The dual-coordinate cross-attention block is hierarchically stacked amid convolutional layers at multiple levels, allowing comprehensive feature enhancement. The model was developed based on 5,649 OCT frames from 339 patients and tested using independent external OCT data from 548 frames of 52 patients. DCCAT achieved Dice similarity score (DSC) of 0.706 in segmenting thrombus, which is significantly higher than the CNN-based (0.656) and Transformer-based (0.584) models. We prove that the additional input of polar image not only leverages discriminative features from another coordinate but also improves model robustness for geometrical transformation.Experiment results show that DCCAT achieves competitive performance with only 10% of the total data, highlighting its data efficiency. The proposed dual-coordinate cross-attention design can be easily integrated into other developed Transformer models to boost performance., Competing Interests: Declaration of competing interest S Tu reported research grants and consultancy from Pulse Medical. A Banning reports institutional research grant from Boston Scientific. G De Maria reports research grant from Miracor, Medtronic, Terumo, Abbott, Philips and consultant fee from Miracor. R Kotronias, K Channon, A Banning, and G De Maria acknowledge support/funding from the Oxford NIHR Biomedical Research center. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In suspected non-ST-segment elevation myocardial infarction (NSTEMI), this presumed diagnosis may not hold true in all cases, particularly in patients with nonobstructive coronary arteries (NOCA). Additionally, in multivessel coronary artery disease, the presumed infarct-related artery may be incorrect., Objectives: This study sought to assess the diagnostic utility of cardiac magnetic resonance (CMR) before invasive coronary angiogram (ICA) in suspected NSTEMI., Methods: A total of 100 consecutive stable patients with suspected acute NSTEMI (70% male, age 62 ± 11 years) prospectively underwent CMR pre-ICA to assess cardiac function (cine), edema (T 2 -weighted imaging, T 1 mapping), and necrosis/scar (late gadolinium enhancement). CMR images were interpreted blinded to ICA findings. The clinical care and ICA teams were blinded to CMR findings until post-ICA., Results: Early CMR (median 33 hours postadmission and 4 hours pre-ICA) confirmed only 52% (52 of 100) of patients had subendocardial infarction, 15% transmural infarction, 18% nonischemic pathologies (myocarditis, takotsubo, and other forms of cardiomyopathies), and 11% normal CMR; 4% were nondiagnostic. Subanalyses according to ICA findings showed that, in patients with obstructive coronary artery disease (73 of 100), CMR confirmed only 84% (61 of 73) had MI, 10% (7 of 73) nonischemic pathologies, and 5% (4 of 73) normal. In patients with NOCA (27 of 100), CMR found MI in only 22% (6 of 27 true MI with NOCA), and reclassified the presumed diagnosis of NSTEMI in 67% (18 of 27: 11 nonischemic pathologies, 7 normal). In patients with CMR-MI and obstructive coronary artery disease (61 of 100), CMR identified a different infarct-related artery in 11% (7 of 61)., Conclusions: In patients presenting with suspected NSTEMI, a CMR-first strategy identified MI in 67%, nonischemic pathologies in 18%, and normal findings in 11%. Accordingly, CMR has the potential to affect at least 50% of all patients by reclassifying their diagnosis or altering their potential management., Competing Interests: Funding Support and Author Disclosures The OxAMI study is supported by a British Heart Foundation (BHF) Centre of Research Excellence (CRE) Oxford (RE/13/1/30181), and the National Institute for Health Research Oxford Biomedical Research Centre. Dr Shanmuganathan has received funding from the Alison Brading Memorial Graduate Scholarship in Medical Science, Lady Margaret Hall, University of Oxford. Dr Burrage has received support from a British Heart Foundation Clinical Research Training Fellowship (FS/19/65/34692). Dr Gara has received a European Society of Cardiology, EACVI Research grant. Dr Piechnik has received support from the BHF CRE Oxford (RE/18/3/34214); and has patent authorship rights for U.S. patent 9285446 B2 (systems and methods for Shortened Look Locker Inversion Recovery [Sh-MOLLI] cardiac gated mapping of T1), granted March 15, 2016; intellectual properties are owned and managed by Oxford University Innovations. Dr Channon has received funding from a BHF Chair award (CH/16/1/32013). Dr Ferreira has received funding from the BHF, BHF CRE Oxford, and National Institute for Health Research Oxford Biomedical Research Center. The funders were not involved in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Publication of the BRIGHT-4 trial results has restimulated discussion about the optimal periprocedural antithrombotic strategy for patients undergoing percutaneous coronary intervention (PCI) with acute coronary syndromes (ACS). It is possible that variation in the infusion duration, may contribute to observed differences in safety-efficacy profiles of bivalirudin in this clinical setting., Methods: Up to December 2022, randomized controlled trials (RCTs) comparing bivalirudin (either administered peri-procedurally or accompanied by postprocedural infusion) and heparin, both with or without GPI, were searched and entered in a frequentist network meta-analysis. Co-primary endpoints were trial-defined major adverse composite events (MACE) and major bleeding. Incident rate ratios (IRR) and 95 % confidence intervals (CI) were estimated., Results: 10 RCTs (N = 57,137 patients/month) were included. As compared to heparin, prolonged bivalirudin infusion resulted in lower rates of major bleeding (IRR 0.58, 95 % CI 0.36-0.91), but there was no differences in MACE rates between these strategies. With regard to NACE, prolonged bivalirudin infusion yielded lower risk (IRR 0.86, 95 % CI 0.77-0.96), whereas both bivalirudin and heparin increased risk when coupled with GPI (IRR 1.24, 95 % CI 1.01-1.51 and IRR 1.24, 95 % CI 1.06-1.44, respectively). Both these combination strategies also increased minor bleeding rates (IRR 1.49, 95 % CI 1.16-1.93 and IRR 1.58, 95 % CI 1.29-1.95, respectively, for bivalirudin and heparin). Results were consistent across several sensitivity analyses., Conclusion: In patients with ACS undergoing PCI, procedural bivalirudin administration followed by prolonged infusion results in lower major bleeding rates, but there does not appear to be a difference in observed MACE., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) is widely adopted to treat chronic coronary artery disease. Numerous randomised trials have been conducted to test whether PCI may provide any prognostic advantage over oral medical therapy (OMT) alone, without definitive results. This has maintained the paradigm of OMT as the first-line standard of care for patients, reserving PCI for symptom control. In this review, we discuss the current evidence in favour and against PCI in stable coronary syndromes and highlight the pitfalls of the available studies. We offer a critical appraisal of the possible reasons why the existing data does not provide evidence supporting the role of PCI in improving clinical outcomes in patients with stable coronary syndromes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment of coronary artery disease (CAD) has advanced significantly in recent years due to improvements in medical therapy and percutaneous or surgical revascularization. However, a persistent obstacle in the percutaneous management of CAD is coronary artery calcification (CAC), which portends to higher rates of procedural challenges, post-intervention complications, and overall poor prognosis. With the advent of novel multimodality imaging technologies spanning from intravascular ultrasound to optical coherence tomography to coronary computed tomography angiography combined with advances in calcium debulking and modification techniques, CACs are now targets for intervention with growing success. This review will summarize the most recent developments in the diagnosis and characterization of CAC, offer a comparison of the aforementioned imaging technologies including which ones are most suitable for specific clinical presentations, and review the CAC modifying therapies currently available., Competing Interests: The 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. The handling editor [CB] declared a past co-authorship with author [GLDM]., (© 2023 Wopperer, Kotronias, Marin, Benenati, Della Mora, Portolan, Banning and De Maria.)

Background: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19., Methods: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes., Findings: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [<6·99] C19-RS; hazard ratio [HR] 3·31 [95% CI 1·49-7·33], p=0·0033; and 2·58 [1·10-6·05], p=0·028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8·24 (95% CI 2·16-31·36, p=0·0019) in patients who received no dexamethasone treatment, but 2·27 (0·69-7·55, p=0·18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0·61, p=0·00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways., Interpretation: Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy., Funding: Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation., Competing Interests: Declaration of Interests CA, KC, CS, and SN are founders, shareholders, and directors of Caristo Diagnostics, a CT image analysis company. CS is a full-time employee and MS is a part-time employee of Caristo diagnostics. JD is shareholder and chair of the advisory board of Caristo Diagnostics. EKO is a consultant and minor shareholder of Caristo Diagnostics. The technology described in this work is subject to patent US10,695,023B2 and patent applications PCT/GB2017/053262, GB2018/1818049.7, GR20180100490, and GR20180100510, licensed through exclusive license to Caristo Diagnostics. Caristo Diagnostics and the authors linked to it have no further conflicts of interest, beyond the above. JD is CMO of Our Future Health; Senior Advisor for Cardiovascular Disease Prevention, NHS Healthcheck Expert Scientific and Clinical Advisory Panel; and Chair of the Review of the National Health Check Programme for Public Health England. JCLR received a Research for Patient Benefit Grant from NIHR, and consulting fees from HeartFlow for physician services. DAd received support from Leicester NIHR Biomedical Research Unit and Innovate UK; grants and contracts from the Medical Research Council; and has two patents issued (Cardiac assist device: EP3277337A1; and angioplasty of calcified arteries: PCT/GB2017/050877) outside the scope of the current study. 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 Purpose: Whether incomplete functional revascularization has an impact on the clinical outcome of patients treated with transcatheter aortic valve implantation (TAVI) is still unknown. We aim to assess the prognostic value of residual functional SYNTAX score (rFSS) in a cohort of patients undergoing TAVI., Methods and Results: One-hundred-twenty-four patients (229 lesions) with severe aortic stenosis and coronary artery disease (CAD) underwent fractional flow reserve (FFR)-guided revascularization. The primary endpoint of the study was the composite of cardiac death, myocardial infarction, and revascularization at the last available follow-up after TAVI. Median SYNTAX score (SS) and Functional SYNTAX score (FSS) at baseline were 7 (range 5-12) and 0 (range 0-7) respectively. After revascularization or deferral according to FFR, residual SS (rSS) and rFSS were 5 (range 0-8) and 0 (range 0-0) respectively. Angiographic incomplete revascularization (rSS > 0) was not associated with the primary endpoint (HR 1.2; 95% CI 0.4-3.9; p = 0.69), whereas functional incomplete revascularization (rFSS>0) was associated with worse event-free survival at follow up after adjusting for clinical confounders (HR 3.7; 95% CI 1.0-13.7; p = 0.04)., Conclusion: Incomplete functional revascularization is associated with adverse clinical outcomes after TAVI. Residual functional SYNTAX score may be regarded as a treatment goal for patients with CAD undergoing TAVI. Further studies are warranted to confirm our hypothesis., Competing Interests: Declaration of competing interest None. All authors participated in the research and preparation of the manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The index of microvascular resistance (IMR) is an established tool to assess the status of coronary microcirculation. However, the need for a pressure wire and hyperemic agents have limited its routine use and have led to the development of angiography-derived pressure-wire-free methods (angiography-derived IMR [IMRAngio]). In this review and meta-analysis, we aim to assess the global diagnosis accuracy of IMRAngio versus IMR., Methods: A systematic review of the literature was performed. Studies directly evaluating IMRAngio versus IMR were considered eligible. Pooled values of diagnostic test and summary receiver operator curve were calculated., Results: Seven studies directly comparing IMRAngio versus IMR were included (687 patients; 807 vessels). Pooled sensitivity, specificity, +likelihood ratio (LR), and -LR were 82%, 83%, 4.5, and 0.26 respectively. Pooled accuracy was 83% while pooled positive predictive value and negative predictive value were 76% and 85%, respectively. Comparable results were obtained when analyzing by clinical scenario (acute and nonacute coronary syndromes)., Conclusion: IMRAngio shows a good diagnostic performance for the prediction of abnormal IMR., (© 2022 Wiley Periodicals LLC.)

Objectives: Vascular complications (VC) are the most frequent drawback of transcatheter aortic valve implantation (TAVI), affecting up to 20% of overall procedures. Data on the treatment and their long-term impact are scarce. The goal of this study was to report on the incidence, management and impact on the long-term outcomes of VC following TAVI., Methods: This was a multicentric retrospective analysis of consecutive patients undergoing TAVI. The primary endpoint was freedom from major adverse cardiac and cerebrovascular events at long-term follow-up. Adverse events were evaluated according to Valve Academic Research Consortium-2 criteria., Results: A total of 2145 patients were included: VC occurred in 188 (8.8%); of which 180 were limited to the access site. Two-thirds of the VC were minor; 8% required surgical treatment; the remaining were repaired percutaneously. The major adverse cardiac and cerebrovascular events-free survival at 2 years was 83.0% for patients with VC and 86.7% for those without (P = 0.143), but 71.9% for patients with major compared to 89.0% in those with minor VC (P = 0.022). Major VC and diabetes mellitus independently predicted worse outcomes at 2 years. The major adverse cardiac and cerebrovascular events-free survival rate and the occurrence of vascular adverse events in the long term among patients with VC at the access site treated by endovascular techniques (covered stent implantation or angioplasty) were similar to those without VC (84.2% vs 86.7%; P = 0.635)., Conclusions: Major but not minor VC impact long-term survival after TAVI. Covered stents implanted to manage VC at the access site have no impact on the long-term clinical outcome of TAVI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

For many decades, the severity of coronary artery disease (CAD) and the indication to proceed with either percutaneous coronary intervention (PCI) or surgical revascularization has been based on anatomically derived parameters of vessel stenosis, and typically on the percentage of lumen diameter stenosis (DS%) as determined by invasive coronary angiography (CA). However, it is currently a well-accepted concept that pre-specified thresholds of DS% have a weak correlation with the ischemic and functional potential of an epicardial coronary stenosis. In this regard, the introduction of fractional-flow reserve (FFR) has represented a paradigm-shift in the understanding, diagnosis, and treatment of CAD, but the adoption of FFR into the clinical practice remains surprisingly limited and sub-standard, probably because of the inherent drawbacks of pressure-wire-based technology such as additional costs, prolonged procedural time, invasive instrumentation of the target vessel, and use of vaso-dilatory agents causing side effects for patients. For this reason, new modalities are under development or validation to derive FFR from computational fluid dynamics (CFD) applied to a three-dimensional model (3D) of the target vessel obtained from CA, intravascular imaging, or coronary computed tomography angiography. The purpose of this review was to describe the technical details of these anatomy-derived indices of coronary physiology with a special focus on summarizing their workflow, available evidence, and future perspectives about their application in the clinical practice.

Objective: The visual appearance of coronary thrombi may be clinically informative in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). However, subjective assessment is poorly reproducible and cannot provide an objective basis for treatment decisions or patient stratification. We have assessed the feasibility of a novel reflectance spectroscopy technique to systematically characterize coronary artery thrombi retrieved by aspiration during pPCI in patients with STEMI, and the clinical utility for predicting distal microvascular obstruction., Approach: Patients with STEMI treated with pPCI and thrombus aspiration (n = 288) were recruited from the Oxford Acute Myocardial Infarction (OxAMI) Study. Of these, 158 patients underwent cardiac magnetic resonance imaging within 48 h for assessment of microvascular obstruction (MVO). Coronary thrombi were imaged by reflectance spectroscopy across wavelengths 500-800 nm., Main Results: Spectral data were analysed using function fitting and multivariate models. The coefficient 'c red ' determined from the fitting procedure correlated with the visually-assessed colour of thrombi ('red' or 'white') and with MVO. When applied to a reduced data set, consisting of spectra from 20 patients with the largest MVO and from 20 propensity-score-matched patients with no MVO, three multivariate analysis methods were able to discriminate spectra of thrombi from patients without MVO and with the largest MVO., Significance: Reflectance spectral analysis of coronary thrombus provides new insights into the pathology of STEMI, with potential clinical implications for emergency patient care. Further studies are warranted for validation as a point-of-care stratification tool in predicting the degree of microvascular injury and clinical outcomes in STEMI.

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 μg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20 ± 0.12 vs 1.17 ± 0.78,p = 0.29), while AV calcification progressed in the placebo group (1.22 ± 0.15 vs 1.53 ± 0.23,p = 0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.

Background: Stroke is a rare but potentially catastrophic complication of cardiac catheterization. Although some procedural aspects are known to influence stroke risk, the impact of radial versus femoral access site use is unclear. Early observational studies and limited randomized trial data suggested more frequent embolic events with radial access. Subsequently, larger pooled analyses have shown no clear differences in stroke risk but were limited by low event rates. Recent publication of relevant new data prompted our reevaluation of this concern. Therefore, we conducted a systematic review and meta-analysis to evaluate stroke complicating cardiac catheterization with use of transradial versus transfemoral access., Methods and Results: A search of MEDLINE and EMBASE was undertaken using OVID SP with appropriate search terms. RevMan 5.3.5 was used to conduct a random-effects meta-analysis using the inverse variance method for pooling risk ratios (RRs) or the Mantel-Haenszel method for pooling dichotomous data. Pooled data from >24,000 patients in randomized controlled trials and >475,000 patients from observational studies were used. The risk ratio (RR) for (any) stroke, using randomized controlled trial data, was not significant (RR 0.87, 95% CI 0.58-1.29). Using observational data, a significant difference favoring radial access was seen (RR 0.71, 95% CI 0.52-0.98)., Conclusions: Radial access site utilization for cardiac catheterization is not associated with an increased risk of stroke events. These data provide reassurance and should remove another potential barrier to conversion to a "default" radial practice among those who are currently predominantly femoral operators., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Vascular calcification is an active process, sharing common molecular mechanisms with bone formation. Bisphosphonates are components, which inhibit calcification. The aim of the present study was to evaluate the safety and effectiveness of local delivery of the bisphosphonate zoledronate on inhibition of calcium formation in the arterial wall in an experimental animal model., Methods: Sixteen New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. Subsequently, all animals underwent angiography of abdominal aorta and common iliac arteries. A mixture containing 500 μg/l zoledronate was delivered on the vascular wall of the target iliac artery, using a dedicated balloon catheter. A placebo mixture was administered on the contralateral iliac artery of each animal, which was used as control. At 28 days all animals were sacrificed. Histologic sections of each common iliac artery were stained with hematoxylin-eosin and von Kossa. Computer-assisted histomorphometry was performed for the calcium content quantification of each section from the target and the control iliac artery., Results: In all animals the local delivery of zoledronate and placebo mixtures was successful and uncomplicated. The mean percentage of the calcium content of the media was higher in the control artery segments compared to the target (2.66 ± 0.73 versus 1.08 ± 0.62 % of the area of the media, p<0.01)., Conclusions: Inhibition of vascular calcification by local catheter-based delivery of bisphosphonate zolendronic acid is effective without evident short-term complications. These finding and its potential clinical implication remain to be confirmed in human studies., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)