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Intracoronary continuous thermodilution has been recently proposed as an invasive method to quantify absolute coronary flow (Q abs ) and resistance (R abs ) in vivo. The aim of the present study is to develop and validate of a novel pressure-wire- and microcatheter-free surrogate of coronary flow and resistance derived from a standard coronary angiogram. Angiography derived coronary flow (Q angio ) and resistance (R angio) was prospectively validated in a two-center cohort of patients from Oxford Heart Centre and the Essex Cardiothoracic Centre. Q abs and R abs were measured during resting and hyperemic conditions with continuous thermodilution using the Rayflow microcatheter. Q angio and R angio were computed from the diagnostic coronary angiogram in a blinded fashion in resting and hyperemic conditions. A total of 62 patients and 115 vessels were included in the present analysis. The median Q abs at rest was 75 ml/min (53-95) and 151 ml/min (105-203) during hyperemia; Q angio at rest was 84 ml/min (66-108) and 154 ml/min (115-195) during hyperemia. There was a strong correlation between Q abs and Q angio (R = 0,72; p < 0.001, R = 0,86; p < 0.001 respectively) with satisfactory interclass correlation (0.841, 95% CI 0.509-0.957; p = 0.0003). The median R abs was 1111 mmHg/(L/min) (830-1581.4) at rest and 454 mmHg/(L/min) (348-610) during hyperemia; angiographic resistance (R angio ) was 937.4 mmHg/(L/min) (695.4-1261.9) at rest and 492.4 mmHg/(L/min) (406-697) during hyperemia. There was a strong correlation between R abs and R angio in both conditions (R = 0,81; p < 0.001 and R = 0,78; p < 0.001 respectively). The was a good correlation between absolute coronary flow reserve (CFR) and angiography-derived CFR (R = 0,61; p < 0.001) and between absolute microvascular resistance reserve (MRR) and angiography-derived MRR (R = 0,49; p < 0.001)., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population., Methods: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population., Findings: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events., Interpretation: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators., Funding: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre., Competing Interests: Declaration of interests AT has received research funding from National Institute of Health and Care Research (NIHR) Oxford Health Biomedical Research Center and NIHR Applied Research Collaboration Oxford. AKa has received grants from Lantheus Medical USA and honoraria from Bracco UK/Philips Medical. BM has received honoraria from Chiesi, Sanofi, Novartis, and Boston Scientific. CA has a leadership role in British Atherosclerosis Society, and participates in several European Commission Marie Curie panels, has received honoraria from Amarin and Covance, and has received consulting fees from Slience Therapeutics. DA has a leadership role in the Spontaneous Coronary Artery Dissection Study group, is inventor of patents related to a cardiac assist device (EP3277337A1, PCT/GB2017/050877), and has received grant support from AstraZeneca and Abbott Vascular, and consulting fees from General Electric. EM has received research support from the NHS AI award. EN has a leadership role in the Society of Cardiovascular Computed Tomography and has received consulting fees from Caristo Diagnostics. EKO is a stock option holder of Caristo Diagnostics, is co-founder of Evidence2Health, and is inventor of patents (WO2018078395A1, WO2020058713A1, US17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, and 63/562,335). JD has a leadership role and has received consulting fees from Novo Nordisk, has received honoraria from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. JR has a leadership role in Heart & Lung Imaging, has received consulting fees from NHSX and HeartFlow, and honoraria from Sanofi, Aidence, and 4-C. KMC has received consulting fees from Caristo Diagnostics. MD has received consulting fees from Bristol Myers Squibb, Tenaya Therapeutics, and VizAL, and has participated on an advisory board for Caristo Diagnostics. NSa receives royalties from a patent (PCT/GB2015/052359). PL has received research support from National Heart, Lung and Blood Institute, Simard Fund, and RRM Charitable Fund, grants from Novartis, Novo Nordisk, and Genentech, honoraria from Pri-Med and Medtelligence, has a leadership role in XBiotech, is the inventor of patents (US20240043525A1, US20220041710A1 and US20220389090A1), and has advisory roles for Novartis, DalCor, XBiotech, TenSixteen Bio, and Soley Therapeutics. RB has a leadership role in the Society of Cardiovascular Computed Tomography, has received grants from Amgen, Novartis, and Nanox AI, and consulting fees from Caristo Diagnostics and Heartflow. SEP has a leadership role for the European Association of Cardiovascular Imaging, has received consulting fees from Circle Cardiovascular Imaging, and holds an advisory role for PROTEUS Trial. PT, YS, and MS are employees of Caristo Diagnostics. SN, KMC, and CA are founders, shareholders, and directors of Caristo Diagnostics, a CT-image analysis company. CA is the inventor of patents US10695023B2, US11393137B2, GB2018/1818049.7, GR20180100490, and GR20180100510. ASA, SN, and KMC are co-inventors of patent US10695023B2. These are licensed to Caristo Diagnostics. All other authors declare no competing interests., (Copyright © 2024 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.)

Competing Interests: Conflict of interest: C.A. and S.N. are founders, shareholders, and directors of Caristo Diagnostics. C.A. declares several patents in the space of CT (US10,695,023B2, PCT/GB2017/053262, GB2018/1818049.7, GR20180100490, and GR20180100510) licenced to Caristo Diagnostics. C.A. is the Chair of the British Atherosclerosis Society. R.A.K, B.R., and V.F. have no relevant conflicts of interest to declare.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges., Competing Interests: G.L.D.M. has received research grants from Medtronic, Terumo, and Opsesns and consultancy fees from Corflow. A.P.B. reports receiving an unrestricted research grant from Boston Scientific and speaker and consultancy fees from Abbott, Boston Scientific, Philips, and Miracor Medical SA.

Objective: Takotsubo syndrome (TTS) is an acute heart failure syndrome which resembles acute coronary syndrome (ACS) at presentation. Differentiation requires coronary angiography, but where this does not occur immediately, cardiac biomarkers may provide additional utility. We performed a meta-analysis to compare troponin and natriuretic peptides (NPs) in TTS and ACS to determine if differences in biomarker profile can aid diagnosis., Methods: We searched five literature databases for studies reporting NPs (Brain NP (BNP)/NT-pro-BNP) or troponin I/T in TTS and ACS, identifying 28 studies for troponin/NPs (5618 and 1145 patients, respectively)., Results: Troponin was significantly lower in TTS than ACS (standardised mean difference (SMD) -0.86; 95% CI, -1.08 to -0.64; p<0.00001), with an absolute difference of 75 times the upper limit of normal (×ULN) higher in ACS than TTS. Conversely, NPs were significantly higher in TTS (SMD 0.62; 95% CI, 0.44 to 0.80; p<0.00001) and 5.8×ULN greater absolutely. Area under the curve (AUC) for troponin in ACS versus TTS was 0.82 (95% CI, 0.70 to 0.93), and 0.92 (95% CI, 0.80 to 1.00) for ST-segment elevation myocardial infarction versus TTS. For NPs, AUC was 0.69 (95% CI, 0.48 to 0.89). Combination of troponin and NPs with logistic regression did not improve AUC. Recursive Partitioning and Regression Tree analysis calculated a troponin threshold ≥26×ULN that identified 95% cases as ACS where and specificity for ACS were 85.71% and 53.57%, respectively, with 94.32% positive predictive value and 29.40% negative predictive value., Conclusions: Troponin is lower and NPs higher in TTS versus ACS. Troponin had greater power than NPs at discriminating TTS and ACS, and with troponin ≥26×ULN patients are far more likely to have ACS., Competing Interests: Competing interests: ARL has received speaker, advisory board or consultancy fees and/or research grants from Janssens-Cilag Ltd, Astellas Pharma, Pfizer, Novartis, Servier, AstraZeneca, Bristol Myers Squibb, GSK, Amgen, Takeda, Roche, Clinigen Group, Eli Lilly, Eisai Ltd, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health and Heartfelt Technologies Ltd., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The assessment of coronary microvascular dysfunction (CMD) using invasive methods is a field of growing interest, however the preferred method remains debated. Bolus and continuous thermodilution are commonly used methods, but weak agreement has been observed in patients with angina with non-obstructive coronary arteries (ANOCA). This study examined their agreement in revascularized acute coronary syndromes (ACS) and chronic coronary syndromes (CCS) patients., Objective: To compare bolus thermodilution and continuous thermodilution indices of CMD in revascularized ACS and CCS patients and assess their diagnostic agreement at pre-defined cut-off points., Methods: Patients from two centers underwent paired bolus and continuous thermodilution assessments after revascularization. CMD indices were compared between the two methods and their agreements at binary cut-off points were assessed., Results: Ninety-six patients and 116 vessels were included. The mean age was 64 ± 11 years, and 20 (21 %) were female. Overall, weak correlations were observed between the Index of Microcirculatory Resistance (IMR) and continuous thermodilution microvascular resistance (R µ ) (rho = 0.30p = 0.001). The median coronary flow reserve (CFR) from continuous thermodilution (CFR cont ) and bolus thermodilution (CFR bolus ) were 2.19 (1.76-2.67) and 2.55 (1.50-3.58), respectively (p < 0.001). Weak correlation and agreement were observed between CFR cont and CFR bolus (rho = 0.37, p < 0.001, ICC 0.228 [0.055-0.389]). When assessed at CFR cut-off values of 2.0 and 2.5, the methods disagreed in 41 (35 %) and 45 (39 %) of cases, respectively., Conclusions: There is a significant difference and weak agreement between bolus and continuous thermodilution-derived indices, which must be considered when diagnosing CMD in ACS and CCS patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Patients with ST-segment-elevation myocardial infarction but no coronary microvascular injury are at low risk of early cardiovascular complications (ECC). We aim to assess whether nonhyperemic angiography-derived index of microcirculatory resistance (NH-IMR angio ) could be a user-friendly tool to identify patients at low risk of ECC, potentially candidates for expedited care pathway and early hospital discharge., Methods: Retrospective analysis of 2 independent, international, prospective, observational cohorts included 568 patients with ST-segment-elevation myocardial infarction. NH-IMR angio was calculated based on standard coronary angiographic views with 3-dimensional-modeling and computational analysis of the coronary flow., Results: Overall, ECC (a composite of cardiovascular death, cardiogenic shock, acute heart failure, life-threatening arrhythmias, resuscitated cardiac arrest, left ventricular thrombus, post-ST-segment-elevation myocardial infarction mechanical complications, and rehospitalization for acute heart failure or acute myocardial infarction at 30 days follow-up), occurred in 54 (9.3%) patients. NH-IMR angio was significantly correlated with pressure/thermodilution-based index of microcirculatory resistance (r=0.607; P <0.0001) and demonstrated good accuracy in predicting ECC (area under the curve, 0.766 [95% CI, 0.706-0.827]; P <0.0001). Importantly, ECC occurred more frequently in patients with NH-IMR angio ≥40 units (18.1% versus 1.4%; P <0.0001). At multivariable analysis, NH-IMR angio provided incremental prognostic value to conventional clinical, angiographic, and echocardiographic features (adjusted-odds ratio, 14.861 [95% CI, 5.177-42.661]; P <0.0001). NH-IMR angio <40 units showed an excellent negative predictive value (98.6%) in ruling out ECC. Discharging patients with NH-IMR angio <40 units at 48 hours after admission would reduce the total in-hospital stay by 943 days (median 2 [1-4] days per patient)., Conclusions: NH-IMR angio is a valuable risk-stratification tool in patients with ST-segment-elevation myocardial infarction. NH-IMR angio guided strategies to early discharge may contribute to safely shorten hospital stay, optimizing resources utilization., Competing Interests: Dr Scarsini reports research grant from Abbott Vascular and Philips and speakers fee from Abbott. Dr Banning reports institutional research grant from Boston Scientific. Dr De Maria reports research grant from Miracor, Medtronic, Terumo, Abbott, Philips and consultant fee from Miracor. Dr Ribichini reports research grant from Abbott Vascular and Philips. Drs Kotronias, Marin, Channon, Banning, and De Maria acknowledge support/funding from the Oxford NIHR Biomedical Research center. The other authors report no conflicts.

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: ST-elevation myocardial infarction (STEMI) is typically caused by thrombotic occlusion of a coronary artery with subsequent hypoperfusion and myocardial necrosis. In approximately half of patients with STEMI, despite successful restoration of epicardial coronary patency, downstream myocardium perfusion remains impeded. Coronary microvascular injury is one of the key mechanisms behind suboptimal myocardial perfusion and it is primarily, yet not exclusively, related to distal embolization of atherothrombotic material following recanalization of the culprit artery. Routine manual thrombus-aspiration has failed to show clinical efficacy in this scenario. This could be related with limitations in technology adopted as well as patients' selection. To this end, we set out to explore the efficacy and safety of stent retriever-assisted thrombectomy based on clot-removal device routinely used in stroke intervention., Study Design and Objectives: The stent RETRIEVEr thrombectomy for thrombus burden reduction in patients with Acute Myocardial Infarction (RETRIEVE-AMI) study has been designed to establish whether stent retriever-based thrombectomy is safe and more efficacious in thrombus modification than the current standard of care: manual thrombus aspiration or stenting. The RETRIEVE-AMI trial will enrol 81 participants admitted for primary PCI for inferior STEMI. Participants will be 1:1:1 randomised to receive either standalone PCI, thrombus aspiration and PCI, or retriever-based thrombectomy and PCI. Change in thrombus burden will be assessed via optical coherence tomography imaging. A telephone follow-up at 6 months will be arranged., Conclusions: It is anticipated by the investigators that stent retriever thrombectomy will more effectively reduce the thrombotic burden compared to current standard of care whilst being clinically safe., Competing Interests: Declaration of competing interest Rafail A Kotronias reports grants from Medtronic and Terumo Inc. in relation to the submitted work during the conduct of the study. Prof. Banning reports grants from Boston Scientific, personal fees from Boston Scientific, personal fees from Abbott, personal fees from Medtronic, personal fees from Phillips, outside the submitted work. Dr. De Maria reports grants from Medtronic, grants from Terumo, during the conduct of the study in relation to the submitted work. Dr. De Maria reports grants, personal fees and speaker fees from Miracor Medical SA, speaker fees from Abbott, grants from Opsens, grants from Hexacath, grants from Medis, outside the submitted work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the clinical care provided to cancer patients hospitalized for acute pulmonary embolism (PE), as well as the association between type of cancer, in-hospital care, and clinical outcomes., Methods: This study examined the in-hospital care (systemic thrombolysis, catheter-directed thrombolysis, and surgical thrombectomy/embolectomy) and clinical outcomes (mortality, major bleeding, and hemorrhagic stroke) among adults hospitalized due to acute PE between October 2015 to December 2018 using the National Inpatient Sample (NIS). Multivariable logistic regression analysis was used to determine adjusted odds ratios (aOR) with 95% confidence interval (95% CI)., Results: Of 1,090,130 hospital records included in the analysis, 216,825 (19.9%) had current cancer diagnoses, including lung (4.7%), hematological (2.5%), colorectal (1.6%), breast (1.3%), prostate (0.8%), and 'other' cancer (9.0%). Cancer patients had lower adjusted odds of receiving systemic thrombolysis, catheter-directed therapy, and surgical thrombectomy/embolectomy compared with their non-cancer counterparts (P < 0.001), except for systemic thrombolysis (aOR 0.96, 95% CI 0.85-1.09, P = 0.553) and catheter-directed therapy (aOR 0.82, 95% CI 0.67-1.00, P = 0.053) for prostate cancer. Cancer patients had greater odds of mortality (P < 0.05). Lung cancer patients had the highest odds of mortality (aOR 2.68, 95% CI 2.61-2.76, P < 0.001) and hemorrhagic stroke (aOR 1.75, 95% CI 1.61-1.90, P < 0.001), while colorectal cancer patients had the greatest odds of bleeding (aOR 2.04, 95% CI 1.94-2.15, P < 0.001)., Conclusion: Among those hospitalized for PE, cancer diagnoses were associated with lower odds of invasive management and poorer in-hospital outcomes, with metastatic status being an especially important determinant. Appropriateness of care could not be assessed in this study., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Acute ST-segment elevation myocardial infarction (STEMI) has effects on the myocardium beyond the immediate infarcted territory. However, pathophysiologic changes in the noninfarcted myocardium and their prognostic implications remain unclear., Objectives: The purpose of this study was to evaluate the long-term prognostic value of acute changes in both infarcted and noninfarcted myocardium post-STEMI., Methods: Patients with acute STEMI undergoing primary percutaneous coronary intervention underwent evaluation with blood biomarkers and cardiac magnetic resonance (CMR) at 2 days and 6 months, with long-term follow-up for major adverse cardiac events (MACE). A comprehensive CMR protocol included cine, T2-weighted, T2∗, T1-mapping, and late gadolinium enhancement (LGE) imaging. Areas without LGE were defined as noninfarcted myocardium. MACE was a composite of cardiac death, sustained ventricular arrhythmia, and new-onset heart failure., Results: Twenty-two of 219 patients (10%) experienced an MACE at a median of 4 years (IQR: 2.5-6.0 years); 152 patients returned for the 6-month visit. High T1 (>1250 ms) in the noninfarcted myocardium was associated with lower left ventricular ejection fraction (LVEF) (51% ± 8% vs 55% ± 9%; P = 0.002) and higher NT-pro-BNP levels (290 pg/L [IQR: 103-523 pg/L] vs 170 pg/L [IQR: 61-312 pg/L]; P = 0.008) at 6 months and a 2.5-fold (IQR: 1.03-6.20) increased risk of MACE (2.53 [IQR: 1.03-6.22]), compared with patients with normal T1 in the noninfarcted myocardium (P = 0.042). A lower T1 (<1,300 ms) in the infarcted myocardium was associated with increased MACE (3.11 [IQR: 1.19-8.13]; P = 0.020). Both noninfarct and infarct T1 were independent predictors of MACE (both P = 0.001) and significantly improved risk prediction beyond LVEF, infarct size, and microvascular obstruction (C-statistic: 0.67 ± 0.07 vs 0.76 ± 0.06, net-reclassification index: 40% [IQR: 12%-64%]; P = 0.007)., Conclusions: The acute responses post-STEMI in both infarcted and noninfarcted myocardium are independent incremental predictors of long-term MACE. These insights may provide new opportunities for treatment and risk stratification in STEMI., Competing Interests: Funding Support and Author Disclosures The OxAMI study is supported by the British Heart Foundation (BHF) Centre of Research Excellence (CRE) Oxford (RE/13/1/30181), and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. Dr Shanmuganathan is supported by the Alison Brading Memorial Graduate Scholarship in Medical Science, Lady Margaret Hall, University of Oxford. Dr Burrage was supported by a BHF Clinical Research Training Fellowship (FS/19/65/34692). Prof Channon is funded by a BHF Chair award (CH/16/1/32013). Prof Ferreira has received support from the BHF, BHF CRE Oxford, and NIHR Oxford BRC. Prof Piechnik and Dr Zhang have received support from the BHF CRE Oxford (RE/18/3/34214). Prof Piechnik 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; all rights transferred to Siemens Medical. 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 paper. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Aims: We set out to further develop reflectance spectroscopy for the characterisation and quantification of coronary thrombi. Additionally, we explore the potential of our approach for use as a risk stratification tool by exploring the relation of reflectance spectra to indices of coronary microvascular injury., Methods and Results: We performed hyperspectral imaging of coronary thrombi aspirated from 306 patients presenting with ST-segment elevation acute coronary syndrome (STEACS). Spatially resolved reflected light spectra were analysed using unsupervised machine learning approaches. Invasive [index of coronary microvascular resistance (IMR)] and non-invasive [microvascular obstruction (MVO) at cardiac magnetic resonance imaging] indices of coronary microvascular injury were measured in a sub-cohort of 36 patients. The derived spectral signatures of coronary thrombi were correlated with both invasive and non-invasive indices of coronary microvascular injury. Successful machine-learning-based classification of the various thrombus image components, including differentiation between blood and thrombus, was achieved when classifying the pixel spectra into 11 groups. Fitting of the spectra to basis spectra recorded for separated blood components confirmed excellent correlation with visually inspected thrombi. In the 36 patients who underwent successful thrombectomy, spectral signatures were found to correlate well with the index of microcirculatory resistance and microvascular obstruction; R 2 : 0.80, p < 0.0001, n = 21 and R 2 : 0.64, p = 0.02, n = 17, respectively., Conclusion: Machine learning assisted reflectance spectral analysis can provide a measure of thrombus composition and evaluate coronary microvascular injury in patients with STEACS. Future work will further validate its deployment as a point-of-care diagnostic and risk stratification tool for STEACS care., Competing Interests: Author RK reports grants from Medtronic and Terumo Inc. outside the submitting work. Author AB reports grants from Boston Scientific and personal fees from Boston Scientific, Abbott, Medtronic, and Phillips outside the submitted work. Author GD reports consultancy fee from Miracor Medical SA, speaker fees from Miracor Medical SA and Abbott, and grants from Miracor Medical SA, Abbott, Philips, Medtronic, and Terumo outside the submitted work. In addition, Authors GD, KC, CV, RL, and MA have a patent PCT/US20/55240 pending relevant to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotronias, Fielding, Greenhalgh, Lee, Alkhalil, Marin, Emfietzoglou, Banning, Vallance, Channon and De Maria.)

Aims: Little is known about the association between the type of admission ward and quality of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI)., Methods and Results: We analysed data from 337 155 NSTEMI admissions between 2010 and 2017 in the UK Myocardial Ischaemia National Audit Project (MINAP) database. The cohort was dichotomised according to receipt of care either on a medical (n = 142,876) or cardiac ward, inclusive of acute cardiac wards and cardiac care unit (n = 194,279) on admission to hospital. Patients admitted to a cardiac ward were younger (median age 70 y vs. 75 y, P &lt; 0.001), and less likely to be female (33% vs. 40%, P &lt; 0.001). Independent factors associated with admission to a cardiac ward included ischaemic ECG changes (OR: 1.20, 95% CI: 1.18-1.23) and prior percutaneous coronary intervention (PCI) (OR: 1.19, 95% CI: 1.16-1.22). Patients admitted to a cardiac ward were more likely to receive optimal pharmacotherapy with statin (85% vs. 81%, P &lt; 0.001) and dual antiplatelet therapy (DAPT) (91% vs. 88%, P &lt; 0.001) on discharge, undergo invasive coronary angiography (78% vs. 59%, P &lt; 0.001), and receive revascularisation in the form of PCI (52% vs. 36%, P &lt; 0.001). Following multivariable logistic regression, the odds of inhospital all-cause mortality (OR: 0.75, 95% CI: 0.70-0.81) and major adverse cardiovascular events (MACE) (OR: 0.84, 95% CI: 0.78-0.91) were lower in patients admitted to a cardiac ward., Conclusion: Patients with NSTEMI admitted to a cardiac ward on admission were more likely to receive guideline directed management and had better clinical outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. A large retrospective multicenter cohort of 1381 patients treated with TAVI was analyzed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and 1 year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl ≥ 2.2 was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.09-1.22, p < 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (odds ratio: 1.18, 95% CI: 1.08-1.28, p < 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01-3.60, p = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21-3.11, p = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI., (© 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Microvascular dysfunction (MVD) contributes to several conditions that increase morbidity and mortality, including ischemic heart disease, heart failure, dementia, chronic kidney disease and hypertension. Consequently, MVD imposes a substantial burden on healthcare systems worldwide. In comparison to macrovascular dysfunction, MVD has been incompletely investigated, and it remains uncertain whether MVD in an organ constitutes a distinct pathology or a manifestation of a systemic disorder. Here, we summarize and appraise the techniques that are used to diagnose MVD. We review the disorders of the heart, brain and kidneys in which the role of MVD has been highlighted and summarize evidence hinting at a systemic or multi-organ nature of MVD. Finally, we discuss the benefits and limitations of implementing MVD testing in clinical practice with a focus on new interventions that are beginning to emerge., (© 2022. Crown.)

Background: Preliminary data suggest that pressure-controlled intermittent coronary sinus occlusion (PICSO) might reduce the infarct size (IS) in patients with anterior ST-elevation myocardial infarction (STEMI). However, the applicability of this therapy to patients with inferior STEMI and its exact mechanism of action is uncertain., Methods and Results: Thirty-six patients (27 anterior and 9 inferior) with STEMI underwent PICSO-assisted-primary percutaneous intervention (PPCI) and were compared with matched controls who underwent standard PCI (n = 72). Median age was 63 (55-70) years and 82% were male. Coronary microvascular status was assessed using thermodilution-derived index of microcirculatory resistance (IMR) and the vasodilatory capacity was assessed using the resistive reserve ratio (RRR). IS and microvascular obstruction (MVO) were assessed using cardiovascular magnetic resonance imaging (CMR) within 48 h and 6 months of follow-up. At completion of PPCI, IMR improved significantly in PICSO-treated patients compared with controls in patients with either anterior (63.7 [49.8-74.6] vs. 35.9 [27.9-47.6], p < 0.001) or inferior STEMI (60.0 [47.6-67.1] vs. 22.7 [18.4-35.0], p < 0.001). RRR significantly improved after PICSO treatment for anterior (1.21 [1.01-1.42] vs. 1.73 [1.51-2.16], p = 0.002) or inferior STEMI (1.39 [1.05-1.90] vs. 2.87 [2.17-3.78], p = 0.001), whereas it did not change in controls compared with baseline. Patients treated with PICSO presented significantly less frequently with MVO (66.6% vs. 86.1%, p = 0.024) and smaller 6-month IS compared with controls (26% [17%-30%] vs. 30% [21%-37%], p = 0.045)., Conclusion: PICSO therapy may improve microvascular function and vasodilatory capacity, which contributes to reducing IS in patients with STEMI undergoing PPCI., (© 2021 Wiley Periodicals LLC.)

Background: Venous Thromboembolism (VTE) is common among patients with severe Coronavirus Disease 2019 (COVID-19). Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal thromboprophylaxis strategy has not yet been defined., Objective: To identify published guidance reports by national and international societies regarding thromboprophylaxis strategies in COVID-19 patients in different settings (outpatients, hospitalized, post-discharge)., Methods: A systematic review of the literature (Pubmed/EMBASE) was conducted independently by two investigators., Results: Among 1942 initially identified articles, 33 guidance documents were included: 20 published by national and 13 by international societies. These documents provide recommendations mainly for hospitalized (97% of reports) and post-discharge (75%) COVID-19 patients, and less so for outpatients (34%). Thrombotic and bleeding risk stratification prior to any treatment decision is the cornerstone of all suggested thromboprophylaxis strategies; 81% of the documents recommend thromboprophylaxis for all hospitalized patients with a prophylactic dosage of low molecular weight heparin irrespective of VTE risk. Intermediate or therapeutic dose intensity is recommended in high VTE risk patients by 56% and 28% of documents, respectively. Mechanical thromboprophylaxis is suggested in case of high bleeding risk or contraindication to pharmacological thromboprophylaxis (59% of documents). Extended pharmacological thromboprophylaxis is recommended for patients with high VTE risk after hospital discharge (63% of documents). For non-hospitalized outpatients, 28% of documents recommend pharmacological thromboprophylaxis for high VTE risk., Conclusion: The current guidance identifies thromboprophylaxis in COVID-19 patients, especially during hospitalization, as of major importance for the prevention of VTE. Recommendations are derived from limited evidence from observational studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Invasive assessment of coronary physiology has radically changed the paradigm of myocardial revascularization in patients with coronary artery disease. Despite the prognostic improvement associated with ischemia-driven revascularization strategy, functional assessment of angiographic intermediate epicardial stenosis remains largely underused in clinical practice. Multiple tools have been developed or are under development in order to reduce the invasiveness, cost, and extra procedural time associated with the invasive assessment of coronary physiology. Besides epicardial stenosis, a growing body of evidence highlights the role of coronary microcirculation in regulating coronary flow with consequent pathophysiological and clinical and prognostic implications. Adequate assessment of coronary microcirculation function and integrity has then become another component of the decision-making algorithm for optimal diagnosis and treatment of coronary syndromes. This review aims at providing a comprehensive description of tools and techniques currently available in the catheterization laboratory to obtain a thorough and complete functional assessment of the entire coronary tree (both for the epicardial and microvascular compartments)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Optical flow ratio (OFR) is a novel method for fast computation of fractional flow reserve (FFR) from optical coherence tomography (OCT) images., Aims: We aimed to evaluate the accuracy of OFR in predicting post-percutaneous coronary intervention (PCI) FFR and the impact of stent expansion on within-stent OFR pressure drop (in-stent OFR)., Methods: Post-PCI OFR was computed in patients with both OCT and FFR interrogation immediately after PCI. Calculation of post-PCI OFR (called simulated residual OFR) from pre-PCI OCT pullbacks after elimination of the stenotic segment by virtual stenting was performed in a subgroup of patients who had pre-PCI OCT images. Stent underexpansion was quantified by the minimum expansion index (MEI) of the stented segment., Results: A total of 125 paired comparisons between post-PCI OFR and FFR were obtained in 119 patients, among which simulated residual OFR was obtained in 64 vessels. Mean post-PCI FFR was 0.92±0.05. Post-PCI OFR showed good correlation (r=0.74, p<0.001) and agreement (mean difference=-0.01±0.03, p=0.051) with FFR. The accuracy in predicting post-PCI FFR ≤0.90 was 84% for post-PCI OFR. Simulated residual OFR significantly correlated with post-PCI FFR (r=0.42, p<0.001). MEI showed a moderate correlation (r=-0.49, p<0.001) with in-stent OFR., Conclusions: Post-PCI OFR showed good diagnostic concordance with post-PCI FFR. Simulated residual OFR significantly correlated with post-PCI FFR. Stent underexpansion significantly correlated with in-stent pressure drop.

[Figure: see text].

Background: The risk of nosocomial COVID-19 infection for vulnerable aortic stenosis patients and intensive care resource utilization has led to cardiac surgery deferral. Untreated severe symptomatic aortic stenosis has a dismal prognosis. TAVR offers an attractive alternative to surgery as it is not reliant on intensive care resources. We set out to explore the safety and operational efficiency of restructuring a TAVR service and redeploying it to a new non-surgical site during the COVID-19 pandemic., Methods: The institutional prospective service database was retrospectively interrogated for the first 50 consecutive elective TAVR cases prior to and after our institution's operational adaptations for the COVID-19 pandemic. Our endpoints were VARC-2 defined procedural complications, 30-day mortality or re-admission and service efficiency metrics., Results: The profile of patients undergoing TAVR during the pandemic was similar to patients undergoing TAVR prior to the pandemic with the exception of a lower mean age (79 vs 82 years, p < 0.01) and median EuroScore II (3.1% vs 4.6%, p = 0.01). The service restructuring and redeployment contributed to the pandemic-mandated operational efficiency with a reduction in the distribution of pre-admission hospital visits (3 vs 3 visits, p < 0.001) and the time taken from TAVR clinic to procedure (26 vs 77 days, p < 0.0001) when compared to the pre-COVID-19 service. No statistically significant difference was noted in peri-procedural complications and 30-day outcomes, while post-operative length of stay was significantly reduced (2 vs 3 days, p < 0.0001) when compared to pre-COVID-19 practice., Conclusions: TAVR service restructuring and redeployment to align with pandemic-mandated healthcare resource rationalization is safe and feasible., Competing Interests: Declaration of competing interest Adrian P. Banning reports grants from Boston Scientific, personal fees from Boston Scientific, personal fees from Abbott, personal fees from Medtronic, personal fees from Phillips, outside the submitted work; Rajesh K. Kharbanda reports personal fees from Boston Scientific, during the conduct of the work; Adrian P. Banning & Rajesh K. Kharbanda are partially funded by the NHS NIHR Biomedical Research Center, Oxford; Rafail A Kotronias's post is funded by the National Institute for Health Research. The rest of the authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the long-term prognostic implications of coronary microvascular dysfunction (CMD) when assessed with both cardiovascular magnetic resonance (CMR) and index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI)., Background: Post-ischemic CMD can be assessed using the pressure-wire based IMR and/or by the presence of microvascular obstruction (MVO) on CMR., Methods: A total of 198 patients with STEMI underwent IMR and MVO assessment. Patients were classified as follows: Group 1, no significant CMD (low IMR [≤40 U] and no MVO); Group 2, CMD with either high IMR (>40 U) or MVO; Group 3, CMD with both IMR >40 U and MVO. The primary endpoint was the composite of all-cause mortality, diagnosis of new heart failure, cardiac arrest, sustained ventricular tachycardia/fibrillation, and cardioverter defibrillator implantation., Results: CMD with both high IMR and MVO was present in 23.7% of the cases (Group 3) and CMD with either high IMR or MVO was observed in 40.9% of cases (Group 2). At a median follow-up of 40.1 months, the primary endpoint occurred in 34 (17%) cases. At 1 year of follow-up, Group 3 (hazard ratio [HR]: 12.6; 95% confidence interval [CI]: 1.6 to 100.6; p = 0.017) but not Group 2 (HR: 7.2; 95% CI: 0.9 to 57.9; p = 0.062) had worse clinical outcomes compared with those with no significant CMD in Group 1. However, in the long-term, patients in Group 2 (HR: 4.2; 95% CI: 1.4 to 12.5; p = 0.009) and those in Group 3 (HR: 5.2; 95% CI: 1.7 to 16.2; p = 0.004) showed similar adverse outcomes, mainly driven by the occurrence of heart failure., Conclusions: Post-ischemic CMD predicts a more than 4-fold increase in long-term risk of adverse outcomes, mainly driven by the occurrence of heart failure. Defining CMD by either invasive IMR >40 U or by CMR-assessed MVO showed similar risk of adverse outcomes., Competing Interests: Funding Support and Author Disclosures Supported by British Heart Foundation (grant CH/16/1/32013) BHF Centre of Research Excellence, Oxford (RG/13/1/30181), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. Dr. Shanmuganathan was funded by the Alison Brading Memorial Scholarship in Medical Science, Lady Margaret Hall, University of Oxford. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The ATI (Age-Thrombus burden-Index of Microvascular Resistance [IMR]) score was developed to predict suboptimal myocardial reperfusion in patients with ST-Elevation Myocardial Infarction (STEMI). When applied in the early phases of revascularization (e.g. before stent insertion), it predicts which patients are most likely to have a larger infarct size. In this study, we assessed the score's utility in determining which STEMI patients are at highest risk of clinical events during follow-up., Methods: The ATI-score was calculated prospectively in 254 STEMI patients using age (>50 years = 1 point), pre-stenting IMR (>40 U and < 100 U = 1 point; ≥100 U = 2 points) and angiographic thrombus score (4 = 1 point, 5 = 3 points); the cohort was stratified in high vs. low-intermediate ATI-score strata (≥4 vs. < 4, respectively)., Results: After 3 years of follow-up, patients with high ATI-score presented a higher rate of Major Adverse Cardiac Events (MACE) defined as the composite of all-cause mortality, resuscitated cardiac arrest and new heart failure diagnosis (Hazard Ratio [HR]: 3.07; 95% Confidence Interval [CI]: 1.19-7.93; p = 0.02). The ATI-score showed a moderate discriminative power (c-stat: 0.69), not significantly different from that of other risk scores used in the STEMI setting. A high ATI-score was an independent predictor of MACE (HR: 3.24; 95% CI: 1.22-8.58; p = 0.018)., Conclusions: The ATI-score can discriminate patients at higher risk of long-term adverse events. The score allows predication of subsequent events even before coronary stenting, and consequently it may allow the option of individualized therapy in the early stages of the clinical care-pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: Despite the prognostic value of coronary microvascular dysfunction (CMD) in patients with ST-segment-elevation myocardial infarction (STEMI), its assessment with pressure-wire-based methods remains limited due to cost, technical and procedural complexities. The non-hyperaemic angiography-derived index of microcirculatory resistance (NH IMR angio ) has been shown to reliably predict microvascular injury in patients with STEMI. We investigated the prognostic potential of NH IMR angio as a pressure-wire and adenosine-free tool. Methods and Results: NH IMR angio was retrospectively derived on the infarct-related artery at completion of primary percutaneous coronary intervention (pPCI) in 262 prospectively recruited STEMI patients. Invasive pressure-wire-based assessment of the index of microcirculatory resistance (IMR) was performed. The combination of all-cause mortality, resuscitated cardiac arrest and new heart failure was the primary endpoint. NH IMR angio showed good diagnostic performance in identifying CMD (IMR > 40U); AUC 0.78 (95%CI: 0.72-0.84, p < 0.0001) with an optimal cut-off at 43U. The primary endpoint occurred in 38 (16%) patients at a median follow-up of 4.2 (2.0-6.5) years. On survival analysis, NH IMR angio > 43U (log-rank test, p < 0.001) was equivalent to an IMR > 40U(log-rank test, p = 0.02) in predicting the primary endpoint (hazard ratio comparison p = 0.91). NH IMRangio > 43U was an independent predictor of the primary endpoint (adjusted HR 2.13, 95% CI: 1.01-4.48, p = 0.047). Conclusion: NH IMR angio is prognostically equivalent to invasively measured IMR and can be a feasible alternative to IMR for risk stratification in patients presenting with STEMI., Competing Interests: GD reports grants from Miracor Medical SA, outside the submitted work. In addition, GD has a patent PCT/US20/55240 pending. AB reports grants from Boston Scientific, personal fees from Boston Scientific, personal fees from Abbott, personal fees from Medtronic, personal fees from Phillips, outside the submitted work. HG-G reports institutional research grants from Medtronic, Boston Scientific, Abbott, Biotronik, Neovasc, Corflow, Shockwave, Chiesi, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kotronias, Terentes-Printzios, Shanmuganathan, Marin, Scarsini, Bradley-Watson, Langrish, Lucking, Choudhury, Kharbanda, Garcia-Garcia, Channon, Banning and De Maria.)

To investigate the diagnostic accuracy of (1) hyperaemic angiography-derived index of microcirculatory resistance (IMR angio ) in defining coronary microvascular dysfunction (CMD) across patients with acute coronary syndromes (ST-elevation myocardial infarction [STEMI]; non-ST elevation acute coronary syndrome [NSTE-ACS]) and stable chronic coronary syndrome [CCS]) and (2) the accuracy of non-hyperaemic IMR angio (NH-IMR angio ) to detect CMD in STEMI. 145 patients (STEMI = 66; NSTEMI = 43; CCS = 36) were enrolled. 246 pressure-wire IMR measurements were made in 189 coronary vessels. IMR angio and NH-IMR angio was derived using quantitative flow ratio. In patients with STEMI, cardiac magnetic resonance was performed to quantify microvascular obstruction (MVO). IMR angio was correlated with IMR (overall rho = 0.78, p < 0.0001; STEMI, rho = 0.85 p < 0.0001; NSTE-ACS and rho = 0.72, p < 0.0001; CCS, rho = 0.70, p < 0.0001) and demonstrated good diagnostic performance in predicting high IMR (STEMI AUC ROC  = 0.93 [0.88-0.98]; NSTE-ACS AUC ROC  = 0.77 [0.63-0.92]; CCS AUC ROC  = 0.88 [0.79-0.97]). Agreement between the two indices was evident on Bland Altman analysis. In STEMI, NH-IMR angio was also well correlated with IMR (rho = 0.64, p < 0.0001), with good diagnostic accuracy in predicting high invasive IMR (AUC ROC  = 0.82 [0.74-0.90]). Both IMR angio (AUC ROC  = 0.74 [0.59-0.89]) and NH-IMR angio (AUC ROC  = 0.76 [0.54-0.87]) were significantly associated with MVO in STEMI. In conclusions, IMR angio is a valid alternative to invasive IMR to detect CMD in patients with acute and stable coronary syndromes, whilst NH-IMR angio has a good diagnostic accuracy in STEMI where it could become a user-friendly diagnostic tool as it is adenosine-free.

Aims: Assessment of microvascular function in patients with ST-elevation acute myocardial infarction (STEMI) may be useful to determine treatment strategy. The possible role of pressure-bounded coronary flow reserve (pb-CFR) in this setting has not been determined. In this study we aimed to compare pb-CFR with thermodilution-derived physiology including the index of microcirculatory resistance (IMR) and CFRthermo in a consecutive series of patients enrolled in the OxAMI study. Moreover, we aimed to assess the presence of microvascular obstruction (MVO) and myocardial injury on cardiovascular magnetic resonance (CMR) imaging performed at 48 hours and six months in STEMI patients stratified according to pb-CFR., Methods and Results: Thermodilution-pressure-wire assessment of the infarct-related artery was performed in 148 STEMI patients before stenting and/or at completion of primary percutaneous coronary intervention (PPCI). The extent of the myocardial injury was assessed with CMR imaging at 48 hours and six months after STEMI. Post-PPCI pb-CFR was impaired (<2) and normal (>2) in 69.9% and 9.0% of the cases, respectively. In the remaining 21.1% of the patients, pb-CFR was "indeterminate". In this cohort, pb-CFR correlated poorly with thermodilution-derived coronary flow reserve (k=0.03, p=0.39). The IMR was significantly different across the pb-CFR subgroups. Similarly, significant differences were observed in MVO, myocardium area at risk and 48-hour infarct size (IS). A trend towards lower six-month IS was observed in patients with high (>2) post-PPCI pb-CFR. Nevertheless, pb-CFR was inferior to IMR in predicting MVO and the extent of IS., Conclusions: Pb-CFR can identify microvascular dysfunction in patients after STEMI. It provided superior diagnostic performance compared to thermodilution-derived CFR in predicting MVO. However, IMR was superior to both pb-CFR and thermodilution-derived CFR and, consequently, IMR was the most accurate in predicting all of the studied CMR endpoints of myocardial injury after PPCI.

Coronary artery disease (CAD) is highly prevalent in patients with severe aortic stenosis (AS). The management of CAD is a central aspect of the work-up of patients undergoing transcatheter aortic valve implantation (TAVI), but few data are available on this field and the best percutaneous coronary intervention (PCI) practice is yet to be determined. A major challenge is the ability to elucidate the severity of bystander coronary stenosis independently of the severity of aortic valve stenosis and subsequent impact on blood flow. The prognostic role of CAD in patients undergoing TAVI is being still debated and the benefits and the best timing of PCI in this context are currently under evaluation. Additionally, PCI in the setting of advanced AS poses some technical challenges, due to the complex anatomy, risk of hemodynamic instability, and the increased risk of bleeding complications. This review aims to provide a comprehensive synthesis of the available literature on myocardial revascularization in patients with severe AS undergoing TAVI. This work can assist the Heart Team in individualizing decisions about myocardial revascularization, taking into account available diagnostic tools as well as the risks and benefits.

Objectives: We performed a systematic review and meta-analysis to evaluate the early and midterm outcomes of patients who underwent surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) against patients who had transcatheter aortic valve replacement (TAVR) and percutaneous coronary intervention (PCI)., Background: Contemporary guidelines suggest that surgical or percutaneous revascularization of significant coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is a reasonable strategy., Methods: We conducted a comprehensive search of Medline and Embase to identify studies comparing a percutaneous transcatheter versus a surgical approach. Random effects meta-analyses using the Mantel-Haenszel method were performed to estimate the effect of percutaneous compared surgical strategies using aggregate data., Results: Six studies reporting on 1770 participants were included in the meta-analysis. There were no significant differences in effect estimates for early and midterm mortality (OR: 0.78; 95% CI, 0.50-1.20 and OR: 1.09; 95% CI, 0.80-1.49, respectively) or myocardial infarction (OR: 0.52; 95% CI, 0.20-1.33 and OR: 1.34; 95% CI, 0.67-2.65, respectively). No significant difference was shown for peri-procedural stroke (OR: 0.80; 95% CI, 0.35-1.87). A transcatheter approach had a higher rate of major vascular complications (OR: 14.44; 95% CI, 4.42-47.16), but a lower rate of acute kidney injury (OR: 0.41; 95% CI, 0.19-0.91)., Conclusion: Our analysis suggests that a percutaneous transcatheter approach confers similar outcomes compared to a surgical approach in patients with severe AS and CAD. However, our findings are based on low quality studies and should serve as hypothesis generating. In the absence of adequately powered studies yielding high level evidence, individualized decision making should be based on surgical risk assessment., (© 2020 Wiley Periodicals LLC.)

Objectives: To identify clinical and procedural practice predictors of avoidable complications during transcatheter aortic valve replacement (TAVR)., Background: TAVR is evolving as a viable strategy for treatment of aortic stenosis (AS). Vascular complications, major bleeding, or pericardial tamponade may be influenced by procedural practice., Methods: The Oxford TAVR (OxTAVI) prospective registry was retrospectively analyzed to identify predictors of avoidable procedural complications in a contemporary cohort of transfemoral TAVR between January 2015 and September 2018. The primary endpoint was defined as a hierarchic composite of in-hospital mortality, pericardial effusion/cardiac tamponade, major bleeding, and vascular access complications. Individual components of the primary endpoint have been analyzed separately., Results: Five-hundred-twenty-nine patients underwent transfemoral TAVR using contemporary techniques during the study period and were enrolled in the OxTAVI registry. Female sex and high frailty were associated with a higher risk of death, major bleeding, vascular complication or pericardial tamponade. The use of ultrasound (US) guidance for vascular access management was independently associated with a reduced composite primary endpoint (OR = 0.35, CI:0.14-0.86, p = .02) after adjustment for clinical confounders, largely driven by a threefold reduction in vascular access complication (OR = 0.29, CI:0.15-0.55, p < .001). Performing rapid pacing via the left ventricle guidewire (LV-GW) was associated with a significant decrease in the risk of cardiac tamponade/pericardial effusion (OR = 0.19, CI:0.05-0.66, p = .009)., Conclusion: US-guided vascular access management and rapid pacing via the LV-GW are important determinants of reduced procedural complications during TAVR., (© 2019 Wiley Periodicals, Inc.)

Background: As transcatheter aortic valve replacement (TAVR) expands to younger and lower-risk severe aortic stenosis patients, appropriate coronary artery disease treatment is key to reducing long-term adverse cardiovascular outcomes. Recently, studies have been exploring the role of coronary-physiology guided revascularization strategies. Our aim was to investigate whether TAVR influences coronary physiology measurements using quantitative meta-analytic methods., Methods: We performed a Medline and Embase search for studies evaluating coronary physiology indices before and after TAVR. Double independent screening and extractions of baseline, procedural, angiographic, and echocardiographic data were performed. Risk of bias was assessed using the ACROBAT-NRSI tool. Pooled mean difference estimates of coronary hemodynamic indices before and after TAVR were derived using random-effects models with the inverse variance method (RevMan, Review Manager, version 5.3.5; Nordic Cochrane Centre)., Results: Five studies evaluating 250 coronary vessels in 169 severe aortic stenosis patients were quantitatively synthesized. Coronary flow reserve did not change immediately after TAVR in non-diseased vessels (n = 3; mean difference, 0.11; 95% confidence interval [CI], -0.10-0.32; P=.29; I²=0%; P=.68). Importantly, fractional flow reserve also did not vary significantly following TAVR in both non-diseased (n = 3; mean difference, -0.01; 95% CI, -0.04-0.03; P=.75; I²=41; P=.19) and diseased coronaries (n = 3; mean difference, -0.01; 95% CI, -0.03-0.01; P=.49; I²=0%; P=.46). Similarly, instantaneous wave-free ratio remained stable following TAVR (n = 2; mean difference, 0.00; 95% CI, -0.02-0.02; P>.99; I²=0; P>.99., Conclusions: Pooled coronary physiology measurements before and after TAVR are similar, but data on variation within individual lesions are limited.

The reliability of fractional flow reserve (FFR) in aortic stenosis (AS) has been questioned because of the uncertain response to vasodilators. A retrospective multicenter cohort of 114 AS patients who underwent coronary physiology assessment was compared with 154 controls before and after propensity matching adjustment. The difference between resting distal coronary vs aortic pressure ratio (Pd/Pa) and FFR (ΔPd/Pa-FFR) was tested against the severity of AS. ΔPd/Pa-FFR was not influenced by the severity of AS in terms of aortic valve area (r = - 0.02, p = 0.83) and gradient (r = - 0.05, p = 0.64) or by the left ventricle hypertrophy (r = - 0.03, p = 0.88). Conversely, ΔPd/Pa-FFR was influenced by the presence of diabetes (r = - 0.24, p = 0.005), peripheral vascular disease (r = - 0.16, p = 0.047), and chronic kidney disease (r = - 0.19, p = 0.03). No significant difference was observed in the ΔPd/Pa-FFR between patients with AS and matched controls. Further studies are warranted to validate the FFR-guided revascularization in patients with AS.

Background: Resistive reserve ratio (RRR) is a novel index that expresses the ratio between basal and hyperemic microcirculatory resistance. We sought to compare the performance of RRR, coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in predicting the extent of infarct size (IS) after ST-elevation myocardial infarction., Methods: Thermodilution parameters were measured after primary percutaneous coronary intervention (PPCI) in 45 patients. In 30 (67%) cases pre-stenting measurements were also performed to assess the effect of PPCI on myocardial reperfusion, defined by CFR. Cardiovascular magnetic resonance (CMR) was performed at 48-h to assess area-at-risk (AAR), microvascular obstruction (MVO) and IS. CMR was repeated at 6 months in 39/45 patients., Results: RRR (AUC RRR  = 0.85, CI: 0.71-0.99) performed better compared to CFR (AUC CFR  = 0.67, CI: 0.48-0.86) and IMR (AUC IMR  = 0.70, CI: 0.52-0.88) in predicting IS% at 6-months. Patients with impaired RRR showed larger acute-IS% (27.4 [14.5-42.5] vs 15.4 [8.3-26], p = 0.018), MVO% (3.44 [0-5.97] vs 0 [0-0.89], p = 0.026), AAR% (43 [35-52] vs 34 [25-46], p = 0.03) and 6-months-IS% (22.7 [10.2-35] vs 8.8 [6.9-12.3], p = 0.006), higher rate of adverse remodeling (22.2% vs 0%, p = 0.04) and lower myocardial salvage index (34% [22.8-59.2] vs 53.2% [37.7-71], p = 0.032) compared with other patients. Furthermore, RRR but not IMR or CFR resulted independently associated with 6-months-IS%. CFR (1.48 ± 0.87 vs 1.47 ± 0.61, p = 0.94) did not improve after PPCI in patients with impaired RRR, whereas it improved significantly in other patients (CFR: 1.37 ± 0.43 vs 1.93 ± 0.49, p = 0.018)., Conclusions: Patients with post-PPCI impaired RRR were more likely to have suboptimal myocardial reperfusion and larger IS at follow-up. RRR may offer incremental prognostic value compared with other thermodilution-derived indices., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite frequent percutaneous coronary intervention (PCI) in calcified vessels of older patients, rotational atherectomy (RA) has not been endorsed in patients with severe aortic stenosis (AS) due to safety concerns and lack of data. We explored periprocedural safety and mortality in severe AS patients undergoing RA. Prospective anonymized clinical, echocardiographic, procedural and outcome data of patients undergoing RA PCI between January 2012 and July 2018 were retrospectively extracted from the institutional coronary database. Patients with severe AS undergoing RA PCI were 1:1 propensity matched with patients undergoing RA PCI in the absence of AS. Outcomes of interest were RA related periprocedural complications, 30-day and 1-year mortality. A prespecified subgroup analysis examined the influence of transcatheter aortic valve replacement on mortality following RA PCI. A total of 544 patients underwent RA PCI; 478 without AS and 66 with AS. Propensity matching yielded 35 matched pairs with improved balance in covariates of interest and no significant differences in baseline characteristics postmatching. In the matched cohort (n = 70) slow flow/no-reflow, coronary dissection, perforation, and hemodynamic instability were rare and not significantly different. Survival analyses revealed significantly higher 30-day (Log-Rank p = 0.02) and 1-year mortality (Log rank p = 0.02, HR 5.24 [95% CI 1.13 to 24.28]) in the severe AS group; driven by a fivefold increase in the hazard of death among patients who did not undergo transcatheter aortic valve replacement HR 4.98 [95% CI 1.03 to 24.1]. In conclusion, our study of 70 patients undergoing radial RA PCI suggests that it can be safely performed in patients with severe AS. Long-term outcomes after RA in patients with severe AS are determined by the presence of the valve disease and other co-morbidities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies., Areas Covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of-the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects., Expert Opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.

Cerebrovascular accidents including stroke or transient ischaemic attack are one of the most feared complications after transcatheter aortic valve implantation. Transcatheter aortic valve implantation procedures have been consistently associated with silent ischaemic cerebral embolism as assessed by diffusion-weighted MRI. To reduce the risk of cerebrovascular accidents and silent emboli, cerebral embolic protection devices were developed with the aim of preventing procedural debris reaching the cerebral vasculature. The authors summarise the available data regarding cerebral embolic protection devices and its clinical significance., Competing Interests: Disclosure: The authors have no conflict of interest to declare.

[This corrects the article DOI: 10.21037/jtd.2018.05.187.].

Balloon aortic valvuloplasty (BAV) has historically been recommended prior to transcatheter aortic valve implantation (TAVI). Pre-implantation BAV (pBAV) creates fractures at the level of calcified leaflets, thereby facilitating delivery of the transcatheter valve system across the diseased aortic valve and, enhances prosthesis implantation and expansion within the calcified aortic valve annulus. New device designs, lower profile delivery systems and increasing operator experience have enabled direct-TAVI (without pBAV), and its appeal amongst TAVI operators enhanced the dissemination of a direct TAVI approach across many centres. In this review, we discuss contemporary evidence that inform the debate on the need for routine pBAV for TAVI candidates and present a framework that may assist operators in selecting patients for pBAV., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objectives: This study sought to assess the clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) with early discharge (ED) versus standard discharge (SD) pathways., Background: Minimalist approaches for TAVR have been developed targeting different aspects of the procedure such as local anesthesia or sedation, intraprocedural imaging, vascular access, post-operative monitoring and care, and discharge planning. Their incorporation into routine clinical practice aims to reduce length of hospital stay and health care cost utilization without adversely affecting outcomes when compared with standard approaches., Methods: The authors conducted a search of MEDLINE and EMBASE to identify studies that investigated ED (≤3 days) versus SD in TAVR patients. Random-effects meta-analyses were used to estimate the effect of ED compared with SD with regard to 30-day mortality after discharge, 30-day readmission rate, and need for permanent pacemaker implantation (PPI) following discharge., Results: Eight studies including 1,775 participants (ED, n = 642) fulfilled the inclusion criteria. The mean age was 82.4 years and STS score was 6.7. Meta-analyses evaluating discharge to 30-day mortality (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.23 to 1.82; I 2  = 0%) and discharge to 30-day new PPI (OR: 1.61; 95% CI: 0.19 to 13.71; I 2  = 40%) showed no significant difference in an ED compared with a SD strategy. Notably, ED patients were less likely to be readmitted after ED when compared with SD patients (OR: 0.63; 95% CI: 0.41 to 0.98; p = 0.04, I 2  = 0%)., Conclusions: ED following uncomplicated TAVR is safe in terms of discharge to 30-day mortality or need for PPI following discharge. Moreover, ED patients experienced a lower rate of readmissions. These data support the safety of programs aiming an ED pathway in selected TAVR patients. Institutional protocols with the input from different members of the multidisciplinary heart team should be devised to optimize discharge processes to improve health care resource utilization., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Aspirin therapy improves saphenous vein graft (SVG) patency in patients undergoing coronary artery bypass graft (CABG), however, its use in the pre-operative period remains controversial. Therefore, we conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) to update the evidence about risk and benefits of pre-operative aspirin therapy in patients undergoing CABG., Methods: Electronic databases (Medline, Embase, PubMed, Cochrane Library, and Scopus) were searched to identify RCTs evaluating the effect of aspirin versus placebo/control before CABG. Two investigators independently and in duplicate screened citations and extracted data and rated the risk of bias. The strength of evidence was appraised using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Meta-analysis was performed using a random-effects model. The main outcomes of interest were 30-day mortality, peri-operative myocardial infarction (MI), chest tube drainage and SVG occlusion., Results: A total of 13 RCTs involving 4,377 participants (2,266/2,111 pre-operative aspirin/control) met the inclusion criteria. Pre-operative aspirin reduced the risk of SVG occlusion [risk ratio (RR): 0.69, 95% confidence interval (CI): 0.49-0.97, P=0.03, I 2 =16%], but no differences in mortality (RR: 1.41, 95% Cl: 0.73-2.74, I 2 =0%) and MI (RR: 0.84, 95% CI: 0.69-1.03, I 2 =0%) were found. However, pre-operative aspirin increased chest tube drainage (MD: 100.40 mL, 95% CI: 24.32-176.47 mL, P=0.01, I 2 =84%) and surgical re-exploration (RR: 1.52, 95% CI: 1.02-2.27, P=0.04, I 2 =8%), with no significant difference in RBC transfusion (RR: 1.06, 95% CI: 0.90-1.25, I 2 =35%)., Conclusions: Based on trials where the rated body of evidence was of low to very-low quality, pre-operative aspirin improves SVG patency but increases chest tube drainage and need for surgical re-exploration., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.