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Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows sophisticated quantification of left atrial (LA) blood flow, and could yield novel biomarkers of propensity for intra-cardiac thrombus formation and embolic stroke. As reproducibility is critically important to diagnostic performance, we systematically investigated technical and temporal variation of LA 4D flow in atrial fibrillation (AF) and sinus rhythm (SR). Methods: Eighty-six subjects (SR, n = 64; AF, n = 22) with wide-ranging stroke risk (CHA2DS2VASc 0–6) underwent LA 4D flow assessment of peak and mean velocity, vorticity, vortex volume, and stasis. Eighty-five (99%) underwent a second acquisition within the same session, and 74 (86%) also returned at 30 (27–35) days for an interval scan. We assessed variability attributable to manual contouring (intra- and inter-observer), and subject repositioning and reacquisition of data, both within the same session (same-day scan–rescan), and over time (interval scan). Within-subject coefficients of variation (CV) and bootstrapped 95% CIs were calculated and compared. Results: Same-day scan–rescan CVs were 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis, and were similar between SR and AF subjects (all p > 0.05). Interval-scan variability was similar to same-day scan–rescan variability for peak velocity, vorticity, and vortex volume (all p > 0.05), and higher for stasis and mean velocity (interval scan CVs of 14% and 8%, respectively, both p < 0.05). Longitudinal changes in heart rate and blood pressure at the interval scan in the same subjects were associated with significantly higher variability for LA stasis (p = 0.024), but not for the remaining flow parameters (all p > 0.05). SR subjects showed significantly greater interval-scan variability than AF patients for mean velocity, vortex volume, and stasis (all p < 0.05), but not peak velocity or vorticity (both p > 0.05). Conclusions: LA peak velocity and vorticity are the most reproducible and temporally stable novel LA 4D flow biomarkers, and are robust to changes in heart rate, blood pressure, and differences in heart rhythm. [ABSTRACT FROM AUTHOR]

Cardiovascular magnetic resonance T1-mapping is increasingly used for tissue characterization, commonly based on Modified Look-Locker Inversion recovery (MOLLI). However, there are numerous MOLLI variants with differing normal ranges. This lack of standardization presents confusion and difficulty in inter-center comparisons, hindering widespread adoption of T1-mapping. To address this, we performed a structured literature search for native left ventricular myocardial T1-mapping in healthy humans measured using MOLLI variants at 1.5 and 3 Tesla, across scanner vendors. We then used k-means clustering to structure normal MOLLI-T1 values according to magnetic field strength, and investigated correlations between common imaging parameters: repetition time (TR), echo time (TE), flip angle (FA). We analyzed data from 2207 healthy controls in 76 independent reports. Normal MOLLI-T1 standard deviations varied by 11-fold, and dependencies on TE, TR, and FA differed between 1.5 T and 3 T, thwarting meaningful T1 standardization even within a single field strength, including the use of Z-score. However, divergent MOLLI-T1 norms may be structured using data clustering. For 1.5 T, two clusters emerged: Cluster1 1.5T : T1 = 958 ± 16 ms (n = 1280); Cluster2 1.5T : T1 = 1027 ± 19 ms (n = 386). For 3 T, three clusters emerged: Cluster1 3T : T1 = 1160 ± 21 ms (n = 330); Cluster2 3T : T1 = 1067 ± 18 ms (n = 178); Cluster3 3T : T1 = 1227 ± 19 ms (n = 41). We then propose the concept of an online calculator for assigning local norms to a known MOLLI-T1 cluster, allowing benchmarking against published norms. Clustered structuring allows T1 standardization of widely-divergent MOLLI variants, benchmarking local norms (usually based on smaller samples) against published norms (larger samples). This may increase confidence and quality control in method implementation, facilitating wider clinical adoption of T1-mapping. • Normal myocardial T1 values vary widely across different MOLLI T1-mapping methods. • Clustered structuring via an online calculator is practical for T1 standardization. • Clustered structuring allows benchmarking of local norms against published norms. • Clustered structuring increases confidence and quality in T1-mapping implementation. [ABSTRACT FROM AUTHOR]

The presentation and identification of cardiovascular disease in women pose unique diagnostic challenges compared to men, and underrecognized conditions in this patient population may lead to clinical mismanagement. This article reviews the sex differences in cardiovascular disease, explores the diagnostic and prognostic role of cardiovascular magnetic resonance (CMR) in the spectrum of cardiovascular disorders in women, and proposes the added value of CMR compared to other imaging modalities. In addition, this article specifically reviews the role of CMR in cardiovascular diseases occurring more frequently or exclusively in female patients, including Takotsubo cardiomyopathy, connective tissue disorders, primary pulmonary arterial hypertension and peripartum cardiomyopathy. Gaps in knowledge and opportunities for further investigation of sex-specific cardiovascular differences by CMR are also highlighted. [ABSTRACT FROM AUTHOR]

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 (AUCRRR = 0.85, CI: 0.71-0.99) performed better compared to CFR (AUCCFR = 0.67, CI: 0.48-0.86) and IMR (AUCIMR = 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. [ABSTRACT FROM AUTHOR]

Abstract Background Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are common disorders associated with increased rates of cardiovascular disease (CVD), but the contribution of cytokine-induced inflammation to impaired cardiovascular function in these conditions remains poorly understood. Objectives We assessed the effect of anti-TNF therapy on myocardial and vascular function, myocardial tissue characteristics and perfusion in inflammatory arthropathy and systemic rheumatic disease (IASRD) patients, using cardiovascular magnetic resonance (CMR). Methods 20 RA patients, 7 AS patients, 5 PsA patients without previously known CVD scheduled to commence anti-TNF therapy and 8 RA patients on standard disease modifying antirheumatic drugs underwent CMR at 1.5 T, including cine, tagging, pulse wave velocity (PWV), T2-weighted, native and postcontrast T1 mapping, ECV quantification, rest and stress perfusion and late gadolinium enhancement (LGE) imaging. Results Following anti-TNF therapy, there was significant reversal of baseline subclinical cardiovascular dysfunction, as evidenced by improvement in peak systolic circumferential strain (p < 0.001), peak diastolic circumferential strain rate (p < 0.001), and total aortic PWV, (p < 0.001). This was accompanied by a reduction in myocardial inflammation, as assessed by T2-weighted imaging (p = 0.005), native T1 mapping (p = 0.009) and ECV quantification (p = 0.001), as well as in serum inflammatory markers like CRP (p < 0.001) and ESR (p < 0.001), and clinical measures of disease activity (DAS28-CRP, p = 0.001; BASDAI, p < 0.001). A trend towards improvement in myocardial perfusion was observed (p = 0.07). Focal myocardial fibrosis, as detected by LGE CMR was not altered by anti-TNF therapy (p = 0.92). Conclusions Anti-TNF therapy reduces subclinical myocardial inflammation and improves cardiovascular function in RA, AS and PsA. CMR may be used to track disease progression and response to therapy. Future CMR-based studies to demonstrate effect of anti-TNF therapy modulation of vascular structure and function on hard clinical events and outcomes would be useful. Highlights • We hypothesized that anti-TNF therapy would result in an improvement in myocardial and vascular characteristics in patients with IASRDs. • We show that CMR can detect subclinical cardiovascular involvement and track response to anti-TNF therapy in asymptomatic RA, AS and PsA patients. • Anti-TNF therapy improves strain, diastolic strain rate, aortic stiffness, and myocardial edema (T2-weighted, T1 and ECV quantification). • While a trend towards improvement in myocardial perfusion was observed, this did not reach statistical significance. • These novel observations were supported by parallel improvements in inflammatory parameters (CRP and ESR) and in disease activity indices. [ABSTRACT FROM AUTHOR]

Background: In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD).Objectives: The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography.Methods: Fifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements.Results: In patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 ± 0.4 vs. controls 2.0 ± 0.3; p = 0.49); myocardium with IMR ≥25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 ± 0.3 vs. 1.2 ± 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR ≥25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (<25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value.Conclusions: In angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation. [ABSTRACT FROM AUTHOR]

Background: Novel cardiac magnetic resonance (CMR) stress T1 mapping can detect ischemia and myocardial blood volume changes without contrast agents and may be a more comprehensive ischemia biomarker than myocardial blood flow.Objectives: This study describes the performance of the first prospective validation of stress T1 mapping against invasive coronary measurements for detecting obstructive epicardial coronary artery disease (CAD), defined by fractional flow reserve (FFR <0.8), and coronary microvascular dysfunction, defined by FFR ≥0.8 and the index of microcirculatory resistance (IMR ≥25 U), compared with first-pass perfusion imaging.Methods: Ninety subjects (60 patients with angina; 30 healthy control subjects) underwent CMR (1.5- and 3-T) to assess left ventricular function (cine), ischemia (adenosine stress/rest T1 mapping and perfusion), and infarction (late gadolinium enhancement). FFR and IMR were assessed ≤7 days post-CMR. Stress and rest images were analyzed blinded to other information.Results: Normal myocardial T1 reactivity (ΔT1) was 6.2 ± 0.4% (1.5-T) and 6.2 ± 1.3% (3-T). Ischemic viable myocardium downstream of obstructive CAD showed near-abolished T1 reactivity (ΔT1 = 0.7 ± 0.7%). Myocardium downstream of nonobstructive coronary arteries with microvascular dysfunction showed less-blunted T1 reactivity (ΔT1 = 3.0 ± 0.9%). Stress T1 mapping significantly outperformed gadolinium-based first-pass perfusion, including absolute quantification of myocardial blood flow, for detecting obstructive CAD (area under the receiver-operating characteristic curve: 0.97 ± 0.02 vs. 0.91 ± 0.03, respectively; p < 0.001). A ΔT1 of 1.5% accurately detected obstructive CAD (sensitivity: 93%; specificity: 95%; p < 0.001), whereas a less-blunted ΔT1 of 4.0% accurately detected microvascular dysfunction (area under the receiver-operating characteristic curve: 0.95 ± 0.03; sensitivity: 94%; specificity: 94%: p < 0.001).Conclusions: CMR stress T1 mapping accurately detected and differentiated between obstructive epicardial CAD and microvascular dysfunction, without contrast agents or radiation. [ABSTRACT FROM AUTHOR]

The article presents the concerns raised regarding the data in the article "Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance."

Background: Perfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the "splenic switch-off" sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium. Methods: Two-hundred and twelve subjects underwent adenosine stress CMR: 1.5 T (n = 104; 75 patients, 29 healthy controls); 3 T (n = 108; 86 patients, 22 healthy controls). Native T1spleen was assessed using heart-rate-independent ShMOLLI prototype sequence at rest and during adenosine stress (140 µg/kg/min, 4 min, IV) in 3 short-axis slices (basal, mid-ventricular, apical). This was compared with changes in peak splenic perfusion signal intensity (ΔSIspleen) and the "splenic switch-off" sign on conventional stress/rest gadolinium perfusion imaging. T1spleen values were obtained blinded to perfusion ΔSIspleen, both were derived using regions of interest carefully placed to avoid artefacts and partial-volume effects. Results: Normal resting splenic T1 values were 1102 ± 66 ms (1.5 T) and 1352 ± 114 ms (3 T), slightly higher than in patients (1083 ± 59 ms, p = 0.04; 1295 ± 105 ms, p =0.01, respectively). T1spleen decreased significantly during adenosine stress (mean ΔSIspleen ~ -40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔSIspleen correlated strongly with ΔSIspleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔSIspleen threshold of = -30 ms during stress predicted the "splenic switch-off" sign (AUC 0.90, p < 0.0001) with sensitivity (90%), specificity (88%), accuracy (90%), PPV (98%), NPV (42%). Conclusions: Adenosine stress and rest splenic T1-mapping is a novel method for assessing stress responses, independent of conventional hemodynamic parameters. It enables prediction of the visual "splenic switch-off" sign without the need for gadolinium, and correlates well to changes in splenic signal intensity during stress/rest perfusion imaging. ΔSIspleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR. [ABSTRACT FROM AUTHOR]

• Quality control-driven framework for cardiac segmentation and quality control. • Exploiting variability within deep neural network ensemble to estimate uncertainty. • Novel on-the-fly selection mechanism for the final optimal segmentation. • Accurate, reliable, and fully automated analysis of T1 map with visualization. • Highlighting a potential flaw of the Pearson correlation to evaluate quality score. [Display omitted] Recent developments in artificial intelligence have generated increasing interest to deploy automated image analysis for diagnostic imaging and large-scale clinical applications. However, inaccuracy from automated methods could lead to incorrect conclusions, diagnoses or even harm to patients. Manual inspection for potential inaccuracies is labor-intensive and time-consuming, hampering progress towards fast and accurate clinical reporting in high volumes. To promote reliable fully-automated image analysis, we propose a quality control-driven (QCD) segmentation framework. It is an ensemble of neural networks that integrate image analysis and quality control. The novelty of this framework is the selection of the most optimal segmentation based on predicted segmentation accuracy, on-the-fly. Additionally, this framework visualizes segmentation agreement to provide traceability of the quality control process. In this work, we demonstrated the utility of the framework in cardiovascular magnetic resonance T1-mapping - a quantitative technique for myocardial tissue characterization. The framework achieved near-perfect agreement with expert image analysts in estimating myocardial T1 value (r = 0.987 , p <. 0005 ; mean absolute error (MAE)=11.3ms), with accurate segmentation quality prediction (Dice coefficient prediction MAE=0.0339) and classification (accuracy=0.99), and a fast average processing time of 0.39 second/image. In summary, the QCD framework can generate high-throughput automated image analysis with speed and accuracy that is highly desirable for large-scale clinical applications. [ABSTRACT FROM AUTHOR]

Cardiac magnetic resonance quantitative T1-mapping is increasingly used for advanced myocardial tissue characterisation. However, cardiac or respiratory motion can significantly affect the diagnostic utility of T1-maps, and thus motion artefact detection is critical for quality control and clinically-robust T1 measurements. Manual quality control of T1-maps may provide reassurance, but is laborious and prone to error. We present a deep learning approach with attention supervision for automated motion artefact detection in quality control of cardiac T1-mapping. Firstly, we customised a multi-stream Convolutional Neural Network (CNN) image classifier to streamline the process of automatic motion artefact detection. Secondly, we imposed attention supervision to guide the CNN to focus on targeted myocardial segments. Thirdly, when there was disagreement between the human operator and machine, a second human validator reviewed and rescored the cases for adjudication and to identify the source of disagreement. The multi-stream neural networks demonstrated 89.8% agreement, 87.4% ROC-AUC on motion artefact detection with the human operator in the 2568 T1 maps. Trained with additional supervision on attention, agreements and AUC significantly improved to 91.5% and 89.1%, respectively (p < 0.001). Rescoring of disagreed cases by the second human validator revealed that human operator error was the primary cause of disagreement. Deep learning with attention supervision provides a quick and high-quality assurance of clinical images, and outperforms human operators. [ABSTRACT FROM AUTHOR]

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: Hospitalized COVID-19 patients with troponin elevation have a higher prevalence of cardiac abnormalities than control individuals. However, the progression and impact of myocardial injury on COVID-19 survivors remain unclear., Objectives: This study sought to evaluate myocardial injury in COVID-19 survivors with troponin elevation with baseline and follow-up imaging and to assess medium-term outcomes., Methods: This was a prospective, longitudinal cohort study in 25 United Kingdom centers (June 2020 to March 2021). Hospitalized COVID-19 patients with myocardial injury underwent cardiac magnetic resonance (CMR) scans within 28 days and 6 months postdischarge. Outcomes were tracked for 12 months, with quality of life surveys (EuroQol-5 Dimension and 36-Item Short Form surveys) taken at discharge and 6 months., Results: Of 342 participants (median age: 61.3 years; 71.1% male) with baseline CMR, 338 had a 12-month follow-up, 235 had a 6-month CMR, and 215 has baseline and follow-up quality of life surveys. Of 338 participants, within 12 months, 1.2% died; 1.8% had new myocardial infarction, acute coronary syndrome, or coronary revascularization; 0.8% had new myopericarditis; and 3.3% had other cardiovascular events requiring hospitalization. At 6 months, there was a minor improvement in left ventricular ejection fraction (1.8% ± 1.0%; P < 0.001), stable right ventricular ejection fraction (0.4% ± 0.8%; P = 0.50), no change in myocardial scar pattern or volume (P = 0.26), and no imaging evidence of continued myocardial inflammation. All pericardial effusions (26 of 26) resolved, and most pneumonitis resolved (95 of 101). EuroQol-5 Dimension scores indicated an overall improvement in quality of life (P < 0.001)., Conclusions: Myocardial injury in severe hospitalized COVID-19 survivors is nonprogressive. Medium-term outcomes show a low incidence of major adverse cardiovascular events and improved quality of life. (COVID-19 Effects on the Heart; ISRCTN58667920)., Competing Interests: Funding Support and Author Disclosures This work was supported by NIHR (National Institute for Health and Care Research) and UK Research and Innovation (COV0254). West Yorkshire and Humber Clinical Research Network (CV070) funded the patient information leaflet translation. Dr Berry has received British Heart Foundation support (RE/18/6134217). Dr Artico received funding from the European Association of Cardiovascular Imaging (EACVI Research Grant App000073878). Dr McCann is funded by a NIHR Research Professorship (RP-2017-08-ST2-007). Dr Manisty is funded by a NIHR Clinician Scientist Award (CS-2015-15-003). Drs Ferreira, Piechnik, and Neubauer acknowledge the NIHR Oxford BRC for support of this study. Dr Bucciarelli-Ducci is in part supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS (National Health Service) Foundation Trust and the University of Bristol. Additional support was provided by the NIHR Leicester Biomedical Research Centre and the NIHR Leeds Clinical Research Facility. Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. Dr Moon has served on Advisory Boards for Sanofi and Genzyme. Dr Miller has served on Advisory Boards for Novartis, Boehringer Ingelheim and Lilly Alliance, and AstraZeneca; serves as an advisor for HAYA Therapeutics and PureTech Health; and has received research support from Amicus Therapeutics, Guerbet Laboratories Limited, Roche, and Univar Solutions B.V. Dr Bucciarelli-Ducci is the chief executive officer (part-time) of the Society for Magnetic Resonance. Dr Berry is employed by the University of Glasgow, which holds research and/or consultancy agreements with AstraZeneca, Abbott Vascular, Boehringer Ingelheim, GlaxoSmithKline, HeartFlow, Opsens, and Novartis. 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: Cardiovascular magnetic resonance (CMR) is increasingly utilized to evaluate expanding cardiovascular conditions. The Society for Cardiovascular Magnetic Resonance (SCMR) Registry is a central repository for real-world clinical data to support cardiovascular research, including those relating to outcomes, quality improvement, and machine learning. The SCMR Registry is built on a regulatory-compliant, cloud-based infrastructure that houses searchable content and Digital Imaging and Communications in Medicine images. The goal of this study is to summarize the status of the SCMR Registry at 150,000 exams., Methods: The processes for data security, data submission, and research access are outlined. We interrogated the Registry and presented a summary of its contents., Results: Data were compiled from 154,458 CMR scans across 20 United States sites, containing 299,622,066 total images (∼100 terabytes of storage). Across reported values, the human subjects had an average age of 58 years (range 1 month to >90 years old), were 44% (63,070/145,275) female, 72% (69,766/98,008) Caucasian, and had a mortality rate of 8% (9,962/132,979). The most common indication was cardiomyopathy (35,369/131,581, 27%), and most frequently used current procedural terminology code was 75561 (57,195/162,901, 35%). Macrocyclic gadolinium-based contrast agents represented 89% (83,089/93,884) of contrast utilization after 2015. Short-axis cines were performed in 99% (76,859/77,871) of tagged scans, short-axis late gadolinium enhancement (LGE) in 66% (51,591/77,871), and stress perfusion sequences in 30% (23,241/77,871). Mortality data demonstrated increased mortality in patients with left ventricular ejection fraction <35%, the presence of wall motion abnormalities, stress perfusion defects, and infarct LGE, compared to those without these markers. There were 456,678 patient-years of all-cause mortality follow-up, with a median follow-up time of 3.6 years., Conclusion: The vision of the SCMR Registry is to promote evidence-based utilization of CMR through a collaborative effort by providing a web mechanism for centers to securely upload de-identified data and images for research, education, and quality control. The Registry quantifies changing practice over time and supports large-scale real-world multicenter observational studies of prognostic utility., Competing Interests: Declaration of 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10 1 50% tissue culture infectious dose (TCID 50 ) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals., Methods: Healthy, UK volunteers aged 18-30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×10 1 , 1×10 2 , 1×10³, 1×10 4 , or 1×10 5 TCID 50 SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal-nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (NCT04864548); enrolment and follow-up to 12 months post-enrolment are complete., Findings: Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×10 1 to 1×10 5 TCID 50 SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×10 5 TCID 50 , we were unable to induce sustained infection in any volunteers. Five (14%) of 36 volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8 + T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events., Interpretation: Our study demonstrates potent protective immunity induced by homologous vaccination and homologous or heterologous previous SARS-CoV-2 infection. The community breakthrough infections seen with the omicron variant supports the use of newer variants to establish a model with sufficient rate of infection for use in vaccine and therapeutic development., Funding: Wellcome Trust and Department for Health and Social Care., Competing Interests: Declaration of interests MC and SLa are supported by the Oak Foundation. TT, SLo, and SLa are supported by the US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085. VMF acknowledges support from the British Heart Foundation (CH/16/1/32013). AC is a full time paid employee of hVIVO. AJP is chair of the UK Department of Health and Social Care’s (DHSC) Joint Committee on Vaccination and Immunisation, was a member of WHO’s Strategic Advisory Group of Experts until 2022, receives consulting fees from Shionogi, and is in receipt of grants from the UK Medical Research Council, AstraZeneca, Gates Foundation, Wellcome Trust, National Institute for Health and Care Research (NIHR), Serum Institute of India, CEPI, and European Commission through the University of Oxford. AJP, SJ, HMo, SAH, RT, RL-R, and ICP contributed to intellectual property licensed by Oxford University Innovation to AstraZeneca. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa)., Methods and Results: One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as 'normal' when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate., Conclusion: Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice., Competing Interests: Conflict of interest: S.K.P. has patent authorship rights for US patent US20120078084A1: ‘System and methods for shortened Look-Locker inversion recovery (Sh-MOLLI) cardiac gated mapping of T1’, granted on 15 March 2016. S.K.P., I.A.P., and V.M.F. have authorship rights for patent pending PCT/GB2020/051189: ‘A method for identity validation and quality assurance of quantitative magnetic resonance imaging protocols’, filed on 15 May 2020. IPs are owned and managed by Oxford University Innovations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Arrhythmogenic-cardiomyopathy (ACM) is an inherited heart disease with right, left, or biventricular (BVACM) involvement based on EKG, imaging, family history, and genetic testing. We present a 64-year-old woman with prior myocarditis and diagnosis of BVACM 29 years later. We propose myocarditis as a promoter of gene expression of plakophilin-2 mutation., (© 2023 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for non-invasive myocardial tissue characterisation. However, accurate segmentation of the left ventricular (LV) myocardium remains a challenge due to limited training data and lack of quality control. This study addresses these issues by leveraging generative adversarial networks (GAN)-generated virtual native enhancement (VNE) images to expand the training set and incorporating an automated quality control-driven (QCD) framework to improve segmentation reliability., Methods: A dataset comprising 4,716 LGE images (from 1,363 patients with hypertrophic cardiomyopathy and myocardial infarction) was used for development. To generate additional clinically validated data, LGE data were augmented with a GAN-based generator to produce VNE images. LV was contoured on these images manually by clinical observers. To create diverse candidate segmentations, the QCD framework involved multiple U-Nets, which were combined using statistical rank filters. The framework predicted the Dice Similarity Coefficient (DSC) for each candidate segmentation, with the highest predicted DSC indicating the most accurate and reliable result. The performance of the QCD ensemble framework was evaluated on both LGE and VNE test datasets (309 LGE/VNE images from 103 patients), assessing segmentation accuracy (DSC) and quality prediction (mean absolute error (MAE) and binary classification accuracy)., Results: The QCD framework effectively and rapidly segmented the LV myocardium (<1 s per image) on both LGE and VNE images, demonstrating robust performance on both test datasets with similar mean DSC (LGE: 0.845 ± 0.075 ; VNE: 0.845 ± 0.071 ; p = n s ). Incorporating GAN-generated VNE data into the training process consistently led to enhanced performance for both individual models and the overall framework. The quality control mechanism yielded a high performance ( MAE = 0.043 , accuracy = 0.951 ) emphasising the accuracy of the quality control-driven strategy in predicting segmentation quality in clinical settings. Overall, no statistical difference ( p = n s ) was found when comparing the LGE and VNE test sets across all experiments., Conclusions: The QCD ensemble framework, leveraging GAN-generated VNE data and an automated quality control mechanism, significantly improved the accuracy and reliability of LGE segmentation, paving the way for enhanced and accountable diagnostic imaging in routine clinical use., Competing Interests: VF, QZ, and SP have authorship rights for patent WO2021/044153 (“Enhancement of Medical Images”; granted March 11, 2021). EH, IP, VF, QZ and SP have authorship rights for patent WO/2020/161481 (“Method and Apparatus for Quality Prediction”; granted August 13, 2020). SP has patent authorship rights for US patent US20120078084A1 (“Systems and Methods for Shortened Look Locker Inversion Recovery [Sh-MOLLI] Cardiac Gated Mapping of T1”; granted March 15, 2016). DI was employed by Artificio Inc. 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., (© 2023 Gonzales, Ibáñez, Hann, Popescu, Burrage, Lee, Altun, Weintraub, Kwong, Kramer, Neubauer, Ferreira, Zhang and Piechnik.)

Background: Up to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms., Objectives: This study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF., Methods: The authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA 2 DS 2 VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts., Results: Patients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA 2 DS 2 VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA 2 DS 2 VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05)., Conclusions: Reduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm., Competing Interests: Funding Support and Author Disclosures The study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and by the British Heart Foundation (BHF). Drs Spartera, Pessoa-Amorim, and Wijesurendra are funded by the NIHR Oxford BRC. Drs Ferreira and Casadei are funded by the BHF. Drs Spartera, Hess, and Wijesurendra have received support from the BHF Centre of Research Excellence, Oxford. Dr Spartera has received support from a competitive scholarship for young cardiologists awarded by the Italian Society of Cardiology and funded via MSD Italia–Merck Sharp and Dohme Corp. Dr Casadei has received support in kind from Roche Diagnostics (blood assays) and iRhythm (ECG monitors) for clinical studies on atrial fibrillation. Dr Wijesurendra has received travel assistance from Abbott. Dr Harston has received funding from Brainomix Limited. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures of conflicts of interest: M.K.B. No relevant relationships. V.M.F. Grants from British Heart Foundation (BHF), National Institute of Heath Research (NIHR), NIHR Oxford Biomedical Research Centre; payment or honoraria from Massive Open Online Course (MOOC) Cardiac Imaging 2020; support for attending meetings and/or travel from European Society of Cardiology (ESC); patents planned, issued, or pending: Hann E, Piechnik SK, Popescu IA, Zhang Q, Werys K, Ferreira VM: “Method and Apparatus for quality prediction,” PCT/GB2020/050249, publication date August 13, 2020 (Publication number WO/2020/161481); Zhang Q, Piechnik SK, Ferreira VM, Hann E, Popescu IA: “Method and apparatus for enhancing medical images,” PCT/GB2020/052117, published March 11, 2021 (Publication number WO/2021/044153); Zhang Q, Piechnik SK, Ferreira VM, Werys K, Popescu IA: “A method for identity validation and quality assurance of quantitative magnetic resonance imaging protocols,” PCT/GB2020/051189, publication date November 26, 2020 (Publication number WO/2020/234570); Society for Cardiovascular Magnetic Resonance (SCMR), Vice Secretary Treasurer, SCMR Executive Committee, SCMR Board of Trustees.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection., (© 2023. The Author(s).)

Background: Patients with a history of COVID-19 infection are reported to have cardiac abnormalities on cardiovascular magnetic resonance (CMR) during convalescence. However, it is unclear whether these abnormalities were present during the acute COVID-19 illness and how they may evolve over time., Methods: We prospectively recruited unvaccinated patients hospitalized with acute COVID-19 ( n  = 23), and compared them with matched outpatient controls without COVID-19 ( n  = 19) between May 2020 and May 2021. Only those without a past history of cardiac disease were recruited. We performed in-hospital CMR at a median of 3 days (IQR 1-7 days) after admission, and assessed cardiac function, edema and necrosis/fibrosis, using left and right ventricular ejection fraction (LVEF, RVEF), T1-mapping, T2 signal intensity ratio (T2SI), late gadolinium enhancement (LGE) and extracellular volume (ECV). Acute COVID-19 patients were invited for follow-up CMR and blood tests at 6 months., Results: The two cohorts were well matched in baseline clinical characteristics. Both had normal LVEF (62 ± 7 vs. 65 ± 6%), RVEF (60 ± 6 vs. 58 ± 6%), ECV (31 ± 3 vs. 31 ± 4%), and similar frequency of LGE abnormalities (16 vs. 14%; all p  > 0.05). However, measures of acute myocardial edema (T1 and T2SI) were significantly higher in patients with acute COVID-19 when compared to controls (T1 = 1,217 ± 41 ms vs. 1,183 ± 22 ms; p  = 0.002; T2SI = 1.48 ± 0.36 vs. 1.13 ± 0.09; p  < 0.001). All COVID-19 patients who returned for follow up ( n  = 12) at 6 months had normal biventricular function, T1 and T2SI., Conclusion: Unvaccinated patients hospitalized for acute COVID-19 demonstrated CMR imaging evidence of acute myocardial edema, which normalized at 6 months, while biventricular function and scar burden were similar when compared to controls. Acute COVID-19 appears to induce acute myocardial edema in some patients, which resolves in convalescence, without significant impact on biventricular structure and function in the acute and short-term. Further studies with larger numbers are needed to confirm these findings., Competing Interests: SP 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; IPs are owned and managed by Oxford University Innovations. 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 © 2023 Shanmuganathan, Kotronias, Burrage, Ng, Banerjee, Xie, Fletcher, Manley, Borlotti, Emfietzoglou, Mentzer, Marin, Raman, Oxford Acute Myocardial Infarction (OxAMI) investigators, Tunnicliffe, Neubauer, Piechnik, Channon and Ferreira.)

Background: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation., Methods: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months., Results: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P <0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P <0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P <0.01) or microinfarction (9% versus 0% and 1%; P <0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P =0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 ( P =0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P =0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P =0.02)., Conclusions: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction., Registration: URL: https://www.isrctn.com; Unique identifier: 58667920.

Women's engagement in medicine, and more specifically cardiovascular imaging and cardiovascular MRI (CMR), has undergone a slow evolution over the past several decades. As a result, an increasing number of women have joined the cardiovascular imaging community to contribute their expertise. This collaborative work summarizes the barriers that women in cardiovascular imaging have overcome over the past several years, the positive interventions that have been implemented to better support women in the field of CMR, and the challenges that still remain, with a special emphasis on women physicians., 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., (Copyright © 2023 Sierra-Galan, Aggarwal, Stojanovska, Raman, Han, Ferreira, Thomas, Seiberlich, Parwani, Bucciarelli-Ducci, Baldassarre, Mavrogeni, Ordovas, Schulz-Menger and Bandettini.)

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.)

Myocardial inflammation occurs following activation of the cardiac immune system, producing characteristic changes in the myocardial tissue. Cardiovascular magnetic resonance is the non-invasive imaging gold standard for myocardial tissue characterization, and is able to detect image signal changes that may occur resulting from inflammation, including edema, hyperemia, capillary leak, necrosis, and fibrosis. Conventional cardiovascular magnetic resonance for the detection of myocardial inflammation and its sequela include T2-weighted imaging, parametric T1- and T2-mapping, and gadolinium-based contrast-enhanced imaging. Emerging techniques seek to image several parameters simultaneously for myocardial tissue characterization, and to depict subtle immune-mediated changes, such as immune cell activity in the myocardium and cardiac cell metabolism. This review article outlines the underlying principles of current and emerging cardiovascular magnetic resonance methods for imaging myocardial inflammation.

Background The sympathetic cotransmitter, neuropeptide Y (NPY), is released into the coronary sinus during ST-segment-elevation myocardial infarction and can constrict the coronary microvasculature. We sought to establish whether peripheral venous (PV) NPY levels, which are easy to obtain and measure, are associated with microvascular obstruction, myocardial recovery, and prognosis. Methods and Results NPY levels were measured immediately after primary percutaneous coronary intervention and compared with angiographic and cardiovascular magnetic resonance indexes of microvascular function. Patients were prospectively followed up for 6.4 (interquartile range, 4.1-8.0) years. PV (n=163) and coronary sinus (n=68) NPY levels were significantly correlated ( r =0.92; P <0.001) and associated with multiple coronary and imaging parameters of microvascular function and infarct size (such as coronary flow reserve, acute myocardial edema, left ventricular ejection fraction, and late gadolinium enhancement 6 months later). We therefore assessed the prognostic value of PV NPY during follow-up, where 34 patients (20.7%) developed heart failure or died. Kaplan-Meier survival analysis demonstrated that high PV NPY levels (>21.4 pg/mL by binary recursive partitioning) were associated with increased incidence of heart failure and mortality (hazard ratio, 3.49 [95% CI, 1.65-7.4]; P <0.001). This relationship was maintained after adjustment for age, cardiovascular risk factors, and previous myocardial infarction. Conclusions Both PV and coronary sinus NPY levels correlate with microvascular function and infarct size after ST-segment-elevation myocardial infarction. PV NPY levels are associated with the subsequent development of heart failure or mortality and may therefore be a useful prognostic marker. Further research is required to validate these findings.

Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction. Neutrophils increased ventricular tachycardia via lipocalin-2 in mice, whereas neutrophilia associated with ventricular tachycardia in patients. In contrast, macrophages protected against arrhythmia. Depleting recruited macrophages in Ccr2 -/- mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36 -/- and Mertk -/- mice, viewed together with reduced mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. Thus, modulation of leukocyte function provides a potential therapeutic pathway for reducing the risk of sudden cardiac death., Competing Interests: Competing interests J.G. and M.N. filed an invention disclosure on the STORM model. M.N. has received funds or material research support from Alnylam, Biotronik, CSL Behring, GlycoMimetics, GlaxoSmithKline, Medtronic, Novartis and Pfizer as well as consulting fees from Eli Lilly, Biogen, Gimv, IFM Therapeutics, Molecular Imaging, Sigilon and Verseau Therapeutics. P.T.E. has received sponsored research support from Bayer AG and IBM Health and has consulted for Bayer AG, Novartis and MyoKardia. A.D.A. has received sponsored research support from Amgen and Philip Research. The other authors declare no competing interests.

COVID-19 is associated with myocardial injury caused by ischemia, inflammation, or myocarditis. Cardiovascular magnetic resonance (CMR) is the noninvasive reference standard for cardiac function, structure, and tissue composition. CMR is a potentially valuable diagnostic tool in patients with COVID-19 presenting with myocardial injury and evidence of cardiac dysfunction. Although COVID-19-related myocarditis is likely infrequent, COVID-19-related cardiovascular histopathology findings have been reported in up to 48% of patients, raising the concern for long-term myocardial injury. Studies to date report CMR abnormalities in 26% to 60% of hospitalized patients who have recovered from COVID-19, including functional impairment, myocardial tissue abnormalities, late gadolinium enhancement, or pericardial abnormalities. In athletes post-COVID-19, CMR has detected myocarditis-like abnormalities. In children, multisystem inflammatory syndrome may occur 2 to 6 weeks after infection; associated myocarditis and coronary artery aneurysms are evaluable by CMR. At this time, our understanding of COVID-19-related cardiovascular involvement is incomplete, and multiple studies are planned to evaluate patients with COVID-19 using CMR. In this review, we summarize existing studies of CMR for patients with COVID-19 and present ongoing research. We also provide recommendations for clinical use of CMR for patients with acute symptoms or who are recovering from COVID-19., Competing Interests: Funding Support and Author Disclosures Dr Petersen provides consultancy to and is a shareholder of Circle Cardiovascular Imaging, Inc, Calgary, Alberta, Canada. Dr Friedrich is board member, shareholder, and consultant of Circle Cardiovascular Imaging Inc. Dr Kramer is a consultant to Bristol Myers Squibb. Dr Nagel has received research support from Bayer AG, Neosoft, and Medis. Dr Pennell has received research support from Siemens. Dr Bluemke is a consultant to Bayer AG. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr Petersen has received support from the National Institute for Health Research Biomedical Research Centre at Barts. Dr Ferreira receives support from the British Heart Foundation, British Heart Foundation Centre of Research Excellence, Oxford, and the National Institute for Health Research Oxford Biomedical Research Centre at Oxford University Hospitals NHS Foundation Trust. Dr Raisi-Estabragh was supported by British Heart Foundation Clinical Research Training Fellowship number FS/17/81/33318., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Aims: Altered left atrial (LA) blood flow characteristics account for an increase in cardioembolic stroke risk in atrial fibrillation (AF). Here, we aimed to assess whether exposure to stroke risk factors is sufficient to alter LA blood flow even in the presence of sinus rhythm (SR)., Methods and Results: We investigated 95 individuals: 37 patients with persistent AF, who were studied before and after cardioversion [Group 1; median CHA2DS2-VASc = 2.0 (1.5-3.5)]; 35 individuals with no history of AF but similar stroke risk to Group 1 [Group 2; median CHA2DS2-VASc = 3.0 (2.0-4.0)]; and 23 low-risk individuals in SR [Group 3; median CHA2DS2-VASc = 0.0 (0.0-0.0)]. Cardiac function and LA flow characteristics were evaluated using cardiac magnetic resonance. Before cardioversion, Group 1 displayed impaired left ventricular (LV) and LA function, reduced LA flow velocities and vorticity, and a higher normalized vortex volume (all P < 0.001 vs. Groups 2 and 3). After restoration of SR at ≥4-week post-cardioversion, LV systolic function and LA flow parameters improved significantly (all P < 0.001 vs. pre-cardioversion) and were no longer different from those in Group 2. However, in the presence of SR, LA flow peak and mean velocity, and vorticity were lower in Groups 1 and 2 vs. Group 3 (all P < 0.01), and were associated with impaired LA emptying fraction (LAEF) and LV diastolic dysfunction., Conclusion: Patients at moderate-to-high stroke risk display altered LA flow characteristics in SR in association with an LA myopathic phenotype and LV diastolic dysfunction, regardless of a history of AF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Quantitative cardiovascular magnetic resonance (CMR) T1 mapping has shown promise for advanced tissue characterisation in routine clinical practise. However, T1 mapping is prone to motion artefacts, which affects its robustness and clinical interpretation. Current methods for motion correction on T1 mapping are model-driven with no guarantee on generalisability, limiting its widespread use. In contrast, emerging data-driven deep learning approaches have shown good performance in general image registration tasks. We propose MOCOnet, a convolutional neural network solution, for generalisable motion artefact correction in T1 maps. Methods: The network architecture employs U-Net for producing distance vector fields and utilises warping layers to apply deformation to the feature maps in a coarse-to-fine manner. Using the UK Biobank imaging dataset scanned at 1.5T, MOCOnet was trained on 1,536 mid-ventricular T1 maps (acquired using the ShMOLLI method) with motion artefacts, generated by a customised deformation procedure, and tested on a different set of 200 samples with a diverse range of motion. MOCOnet was compared to a well-validated baseline multi-modal image registration method. Motion reduction was visually assessed by 3 human experts, with motion scores ranging from 0% (strictly no motion) to 100% (very severe motion). Results: MOCOnet achieved fast image registration (<1 second per T1 map) and successfully suppressed a wide range of motion artefacts. MOCOnet significantly reduced motion scores from 37.1±21.5 to 13.3±10.5 ( p < 0.001), whereas the baseline method reduced it to 15.8±15.6 ( p < 0.001). MOCOnet was significantly better than the baseline method in suppressing motion artefacts and more consistently ( p = 0.007). Conclusion: MOCOnet demonstrated significantly better motion correction performance compared to a traditional image registration approach. Salvaging data affected by motion with robustness and in a time-efficient manner may enable better image quality and reliable images for immediate clinical interpretation., Competing Interests: SP has patent authorship rights for U.S. patent 9285446 B2 systems and methods for Shortened Look-Locker Inversion Recovery ShMOLLI cardiac gated mapping of T1, granted March 15, 2016; licensed to Siemens Medical. KW is an employee of Circle Cardiovascular Imaging since 2019. 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 Gonzales, Zhang, Papież, Werys, Lukaschuk, Popescu, Burrage, Shanmuganathan, Ferreira and Piechnik.)

Background: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process., Methods: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer., Results: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P <0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P <0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P <0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P <0.001), lower left ventricular diastolic reserve (r=0.55; P <0.001), left atrial dilatation (r=-0.52; P <0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P <0.001), and right atrial dilation (r=-0.71; P <0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P =0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P =0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P =0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P =0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P =0.004)., Conclusions: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.

Background: The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19., Methods: Fifty-eight patients and thirty matched controls (single visit), recruited between 14 th March - 25 th May 2020, underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months., Findings: At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T 1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O 2 ) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m 2 , P =0·005) decreased and RV ejection fraction (+3·2%, P =0·0003) increased. Native T 1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O 2 , although better, were abnormal in patients versus controls. 31% had reduced pV̇O 2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures., Interpretation: In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health., Funding: The authors' work was supported by the NIHR Oxford Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE/18/3/34214), United Kingdom Research Innovation and Wellcome Trust. This project is part of a tier 3 study (C-MORE) within the collaborative research programme entitled PHOSP-COVID Post-hospitalization COVID-19 study: a national consortium to understand and improve long-term health outcomes, funded by the Medical Research Council and Department of Health and Social Care/National Institute for Health Research Grant (MR/V027859/1) ISRCTN number 10980107., Competing Interests: MC reports a grant from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. EMT reports a grant from the NIHR Oxford Biomedical Research Centre and is a shareholder in Perspectum. AL is a shareholder in Perspectum. SKP acknowledges support from the British Heart Foundation (BHF) Centre of Research Excellence and the NIHR Oxford Biomedical Research Centre at the Oxford University Hospitals, University of Oxford, UK. SKP has a US patent 61/387,591 licensed to Siemens and US patents 61/630,508 and 61-630,510 licensed to Perspectum. RAE reports a grant from the NIHR/Medical Research Council (MRC) for the PHOSP-COVID study. VMF reports grants from the BHF and the NIHR Oxford Biomedical Research Centre. SN reports grants from the NIHR Oxford Biomedical Research Centre, UK Research and Innovation, BHF and is a shareholder in Perspectum. SN was a board member and consultant to Perspectum until 2019. SN has patents ‘Multi-parametric magnetic resonance diagnosis & staging of liver disease’ and ‘System and methods for gated mapping of T1 values in abdominal visceral organs’ licensed to Perspectum. BR reports grants from the Oxford BHF Centre for Research Excellence (RE/18/3/34214), the NIHR Oxford Biomedical Research Centre and the United Kingdom Research Innovation Award. All other authors do not have relationships with industry or funding sources to declare., (© 2021 The Authors.)

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: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined., Objectives: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality., Methods: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome., Results: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m 2 ) and small (LVEDVi ≤55 mL/m 2 ) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort., Conclusions: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR., Competing Interests: Funding Support and Author Disclosures The work was supported by a National Research Foundation of Korea grant funded by the Korea government (Ministry of Science and ICT; No. 2019R1A2C2084099) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI18C2383). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Stress and rest T1-mapping may assess for myocardial ischemia and extracellular volume (ECV). However, the stress T1 response is method-dependent, and underestimation may lead to misdiagnosis. Further, ECV quantification may be affected by time, as well as the number and dosage of gadolinium (Gd) contrast administered. We compared two commonly available T1-mapping approaches in their stress T1 response and ECV measurement stability. Healthy subjects (n = 10, 50% female, 35 ± 8 years) underwent regadenoson stress CMR (1.5 T) on two separate days. Prototype ShMOLLI 5(1)1(1)1 sequence was used to acquire consecutive mid-ventricular T1-maps at rest, stress and post-Gd contrast to track the T1 time evolution. For comparison, standard MOLLI sequences were used: MOLLI 5(3)3 Low (256 matrix) & High (192 matrix) Heart Rate (HR) to acquire rest and stress T1-maps, and MOLLI 4(1)3(1)2 Low & High HR for post-contrast T1-maps. Stress and rest myocardial blood flow (MBF) maps were acquired after IV Gd contrast (0.05 mmol/kg each). Stress T1 reactivity (delta T1) was defined as the relative percentage increase in native T1 between rest and stress. Myocardial T1 values for delta T1 (dT1) and ECV were calculated. Residuals from the identified time dependencies were used to assess intra-method variability. ShMOLLI achieved a greater stress T1 response compared to MOLLI Low and High HR (peak dT1 = 6.4 ± 1.7% vs. 4.8 ± 1.3% vs. 3.8 ± 1.0%, respectively; both p < 0.0001). ShMOLLI dT1 correlated strongly with stress MBF (r = 0.77, p < 0.001), compared to MOLLI Low HR (r = 0.65, p < 0.01) and MOLLI High HR (r = 0.43, p = 0.07). ShMOLLI ECV was more stable to gadolinium dose with less time drift (0.006-0.04% per minute) than MOLLI variants. Overall, ShMOLLI demonstrated less intra-individual variability than MOLLI variants for stress T1 and ECV quantification. Power calculations indicate up to a fourfold (stress T1) and 7.5-fold (ECV) advantage in sample-size reduction using ShMOLLI. Our results indicate that ShMOLLI correlates strongly with increased MBF during regadenoson stress and achieves a significantly higher stress T1 response, greater effect size, and greater ECV measurement stability compared with the MOLLI variants tested.

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.

Background: Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials., Purpose: To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use., Methods: MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites., Results: T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R 2  > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions., Conclusions: The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials., Competing Interests: Declaration of Competing Interest SKP has patent authorship rights for U.S. patent US20120078084A1. Systems and methods for shortened Look Locker inversion recovery (Sh-MOLLI) cardiac gated mapping of T1. Granted March 15, 2016. IP is managed by Oxford University Innovations; the license exclusively transferred to Siemens Healthcare. QZ, SKP, KW, IAP, VMF have authorship rights for pending patent PCT/GB2020/051189. A method for identity validation and quality assurance of quantitative magnetic resonance imaging protocols. Filed May 15, 2020. IP is owned and managed by Oxford University Innovations., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood., Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments., Findings: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls ( p <0.0001 to 0.044)., Interpretation: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness., Funding: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation., Competing Interests: Dr. Raman reports grants from NIHR Oxford Biomedical Research Centre, grants from United Kingdom Research Innovation Award, during the conduct of the study. Dr. Cassar reports grants from NIHR Oxford Biomedical Research Centre, during the conduct of the study. Dr. Tunnicliffe reports grants from NIHR Oxford Biomedical Research Centre, during the conduct of the study; shareholding in Perspectum, outside the submitted work; In addition, Dr. Tunnicliffe has a patent Systems and methods for gated mapping of T1 values in abdominal visceral organs GB2497668B licensed to Perspectum, a patent Multi-parametric magnetic resonance diagnosis and staging of liver disease GB2498254B licensed to Perspectum, and a patent Processing MR relaxometry data of visceral tissue to obtain a corrected value of relaxometry data based on a normal iron content for the visceral tissue GB2513474B licensed to Perspectum. Dr. Okell reports grants from Wellcome Trust/Royal Society, during the conduct of the study; personal fees from SBGNeuro, personal fees from Oxford University Press, personal fees from Siemens Healthineers, outside the submitted work; In addition, Dr. Okell has a patent Combined angiography and perfusion using radial imaging and arterial spin labeling pending, a patent Off-resonance Correction for Pseudo-continuous Arterial Spin Labeling pending, a patent Estimation of blood flow rates issued, a patent Fast analysis method for non-invasive imaging of blood flow using vessel-encoded arterial spin labelling with royalties paid to Siemens Healthineers, and a patent Quantification of blood volume flow rates from dynamic angiography data with royalties paid to Siemens Healthineers. Dr. Lewandowski reports non-financial support from Perspectum as a minority share-holder. Dr. Jenkinson reports personal fees from Oxford University Innovations, outside the submitted work. Dr. Channon reports grants funding from the British Heart Foundation and the National Institute for Health Research. Dr. Ferreira reports grants from British Heart Foundation, grants from National Institute Health Research Oxford Biomedical Research Centre, during the conduct of the study. Dr. Piechnik has a patent US patent 61/387,591 licensed to Siemens, a patent US patent 61/630,508 licensed to Perspectum, and a patent US patent 61-630,510 licensed to Perspectum. Dr. Pavlides reports other from Perspectum, outside the submitted work. Dr. Neubauer reports grants from Oxford NIHR Biomedical Research Centre, grants from UKRI, during the conduct of the study; personal fees and other from Perspectum Diagnostics, outside the submitted work; In addition, Dr. Neubauer has a patent Multi-parametric magnetic resonance diagnosis & staging of liver disease licensed to Perspectum., (Crown Copyright © 2020 Published by Elsevier Ltd.)

Microvascular angina is caused by cardiac small vessel disease, and dysregulation of the endothelin system is implicated. The minor G allele of the non-coding single nucleotide polymorphism (SNP) rs9349379 enhances expression of the endothelin 1 gene in human vascular cells, increasing circulating concentrations of ET-1. The prevalence of this allele is higher in patients with ischemic heart disease. Zibotentan is a potent, selective inhibitor of the ET A receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina. METHODS: We will assess the efficacy and safety of adjunctive treatment with oral zibotentan (10 mg daily) in patients with microvascular angina and assess whether rs9349379 (minor G allele; population prevalence ~36%) acts as a theragnostic biomarker of the response to treatment with zibotentan. The PRIZE trial is a prospective, randomized, double-blind, placebo-controlled, sequential cross-over trial. The study population will be enriched to ensure a G-allele frequency of 50% for the rs9349379 SNP. The participants will receive a single-blind placebo run-in followed by treatment with either 10 mg of zibotentan daily for 12 weeks then placebo for 12 weeks, or vice versa, in random order. The primary outcome is treadmill exercise duration using the Bruce protocol. The primary analysis will assess the within-subject difference in exercise duration following treatment with zibotentan versus placebo. CONCLUSION: PRIZE invokes precision medicine in microvascular angina. Should our hypotheses be confirmed, this developmental trial will inform the rationale and design for undertaking a larger multicenter trial., Competing Interests: Disclosures CB is employed by the University of Glasgow which holds consultancy and research agreements with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis, GSK, HeartFlow, Menarini, Neovasc, Novartis, and Siemens Healthcare. APD is a member of the scientific advisory board of ENB Therapeutics. AW is a full-time employee of AstraZeneca. The remaining authors have no disclosures., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Left ventricular hypertrophy (LVH) is a common presentation encountered in clinical practice with a diverse range of potential aetiologies. Differentiation of pathological from physiological hypertrophy can be challenging but is crucial for further management and prognostication. Cardiovascular magnetic resonance (CMR) with advanced myocardial tissue characterisation is a powerful tool that may help to differentiate these aetiologies in the assessment of LVH., Recent Findings: The use of CMR for detailed morphological assessment of LVH is well described. More recently, advanced CMR techniques (late gadolinium enhancement, parametric mapping, diffusion tensor imaging, and myocardial strain) have been used. These techniques are highly promising in helping to differentiate key aetiologies of LVH and provide valuable prognostic information. Recent advancements in CMR tissue characterisation, such as parametric mapping, in combination with detailed morphological assessment and late gadolinium enhancement, provide a powerful resource that may help assess and differentiate important causes of LVH.

Early risk stratification after ST-segment-elevation myocardial infarction (STEMI) is of major clinical importance. Strain quantifies myocardial deformation and can demonstrate abnormal global and segmental myocardial function in acute ischaemia. Native T1-mapping allows assessment of the severity of acute ischemic injury, however its clinical applicability early post MI is limited by the complex dynamic changes happening in the myocardium post MI. We aimed to explore relationship between T1-mapping and feature tracking imaging, to establish whether combined analysis of these parameters could predict recovery after STEMI. 96 STEMI patients (aged 60 ± 11) prospectively recruited in the Oxford Acute Myocardial Infarction (OxAMI) study underwent 3T-CMR scans acutely (within 53 ± 32 h from primary percutaneous coronary intervention) and at 6 months (6M). The imaging protocol included: cine, ShMOLLI T1-mapping and late gadolinium enhancement (LGE). Segments were divided in the infarct, adjacent and remote zones based on the presence of LGE. Peak circumferential (Ecc) and radial (Err) strain was assessed using cvi42 software. Acute segmental strain correlated with segmental T1-mapping values (T1 vs. Err - 0.75 ± 0.25, p < 0.01; T1 vs. Ecc 0.72 ± 0.32, p < 0.01) and with LGE segmental injury (LGE vs. Err - 0.56 ± 0.29, p < 0.01; LGE vs. Ecc 0.54 ± 0.35, p < 0.01). Moreover, acute segmental T1 and strain predicted segmental LGE transmurality on 6M scans (p < 0.001, r = 0.5). Multiple regression analysis confirmed combined analysis of global Ecc and T1-mapping was significantly better than either method alone in predicting final infarct size at 6M (r = 0.556 vs r = 0.473 for global T1 only and r = 0.476 for global Ecc only, p < 0.001). This novel CMR method combining T1-mapping and feature tracking analysis of acute CMR scans predicts LGE transmurality and infarct size at 6M following STEMI.

This JACC Scientific Expert Panel provides consensus recommendations for an update of the cardiovascular magnetic resonance (CMR) diagnostic criteria for myocardial inflammation in patients with suspected acute or active myocardial inflammation (Lake Louise Criteria) that include options to use parametric mapping techniques. While each parameter may indicate myocardial inflammation, the authors propose that CMR provides strong evidence for myocardial inflammation, with increasing specificity, if the CMR scan demonstrates the combination of myocardial edema with other CMR markers of inflammatory myocardial injury. This is based on at least one T2-based criterion (global or regional increase of myocardial T2 relaxation time or an increased signal intensity in T2-weighted CMR images), with at least one T1-based criterion (increased myocardial T1, extracellular volume, or late gadolinium enhancement). While having both a positive T2-based marker and a T1-based marker will increase specificity for diagnosing acute myocardial inflammation, having only one (i.e., T2-based OR T1-based) marker may still support a diagnosis of acute myocardial inflammation in an appropriate clinical scenario, albeit with less specificity. The update is expected to improve the diagnostic accuracy of CMR further in detecting myocardial inflammation., (Copyright © 2018. Published by Elsevier Inc.)

In vivo mapping of the myocardial T1 relaxation time has recently attained wide clinical validation of its potential utility. In this review, we address the basic principles of the T1 mapping techniques, with particular attention to the emerging application of vasodilatory stress agents to interrogate the myocardial microvascular compartment, and differences between commonly used T1 mapping methods when applied in clinical practice.