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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.)

Objectives: Despite rising rates of multimorbidity, existing risk assessment tools are mostly limited to a single outcome of interest. This study tests the feasibility of producing multiple disease risk estimates with at least 70% discrimination (area under the receiver operating curve, AUROC) within the time and information constraints of the existing primary care health check framework., Design: Observational prospective cohort study SETTING: UK Biobank., Participants: 228 240 adults from the UK population., Interventions: None., Main Outcome Measures: Myocardial infarction, atrial fibrillation, heart failure, stroke, all-cause dementia, chronic kidney disease, fatty liver disease, alcoholic liver disease, liver cirrhosis and liver failure., Results: Using a set of predictors easily gathered at the standard primary care health check (such as the National Health Service Health Check), we demonstrate that it is feasible to simultaneously produce risk estimates for multiple disease outcomes with AUROC of 70% or greater. These predictors can be entered once into a single form and produce risk scores for stroke (AUROC 0.727, 95% CI 0.713 to 0.740), all-cause dementia (0.823, 95% CI 0.810 to 0.836), myocardial infarction (0.785, 95% CI 0.775 to 0.795), atrial fibrillation (0.777, 95% CI 0.768 to 0.785), heart failure (0.828, 95% CI 0.818 to 0.838), chronic kidney disease (0.774, 95% CI 0.765 to 0.783), fatty liver disease (0.766, 95% CI 0.753 to 0.779), alcoholic liver disease (0.864, 95% CI 0.835 to 0.894), liver cirrhosis (0.763, 95% CI 0.734 to 0.793) and liver failure (0.746, 95% CI 0.695 to 0.796)., Conclusions: Easily collected diagnostics can be used to assess 10-year risk across multiple disease outcomes, without the need for specialist computing or invasive biomarkers. Such an approach could increase the utility of existing data and place multiorgan risk information at the fingertips of primary care providers, thus creating opportunities for longer-term multimorbidity prevention. Additional work is needed to validate whether these findings would hold in a larger, more representative cohort outside the UK Biobank., Competing Interests: Competing interests: SEP provides consultancy to Cardiovascular Imaging, Calgary, Alberta, Canada. BR consulted for Axcella Therapeutics. AR-F is an employee and shareholder in Perspectum, Oxford, UK. SN is a founder, shareholder and former board member of Perspectum. TEN provides consultancy to Perspectum, Oxford, UK. All other authors declare no conflicts of interest. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population., Methods: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population., Findings: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events., Interpretation: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators., Funding: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre., Competing Interests: Declaration of interests AT has received research funding from National Institute of Health and Care Research (NIHR) Oxford Health Biomedical Research Center and NIHR Applied Research Collaboration Oxford. AKa has received grants from Lantheus Medical USA and honoraria from Bracco UK/Philips Medical. BM has received honoraria from Chiesi, Sanofi, Novartis, and Boston Scientific. CA has a leadership role in British Atherosclerosis Society, and participates in several European Commission Marie Curie panels, has received honoraria from Amarin and Covance, and has received consulting fees from Slience Therapeutics. DA has a leadership role in the Spontaneous Coronary Artery Dissection Study group, is inventor of patents related to a cardiac assist device (EP3277337A1, PCT/GB2017/050877), and has received grant support from AstraZeneca and Abbott Vascular, and consulting fees from General Electric. EM has received research support from the NHS AI award. EN has a leadership role in the Society of Cardiovascular Computed Tomography and has received consulting fees from Caristo Diagnostics. EKO is a stock option holder of Caristo Diagnostics, is co-founder of Evidence2Health, and is inventor of patents (WO2018078395A1, WO2020058713A1, US17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, and 63/562,335). JD has a leadership role and has received consulting fees from Novo Nordisk, has received honoraria from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. JR has a leadership role in Heart & Lung Imaging, has received consulting fees from NHSX and HeartFlow, and honoraria from Sanofi, Aidence, and 4-C. KMC has received consulting fees from Caristo Diagnostics. MD has received consulting fees from Bristol Myers Squibb, Tenaya Therapeutics, and VizAL, and has participated on an advisory board for Caristo Diagnostics. NSa receives royalties from a patent (PCT/GB2015/052359). PL has received research support from National Heart, Lung and Blood Institute, Simard Fund, and RRM Charitable Fund, grants from Novartis, Novo Nordisk, and Genentech, honoraria from Pri-Med and Medtelligence, has a leadership role in XBiotech, is the inventor of patents (US20240043525A1, US20220041710A1 and US20220389090A1), and has advisory roles for Novartis, DalCor, XBiotech, TenSixteen Bio, and Soley Therapeutics. RB has a leadership role in the Society of Cardiovascular Computed Tomography, has received grants from Amgen, Novartis, and Nanox AI, and consulting fees from Caristo Diagnostics and Heartflow. SEP has a leadership role for the European Association of Cardiovascular Imaging, has received consulting fees from Circle Cardiovascular Imaging, and holds an advisory role for PROTEUS Trial. PT, YS, and MS are employees of Caristo Diagnostics. SN, KMC, and CA are founders, shareholders, and directors of Caristo Diagnostics, a CT-image analysis company. CA is the inventor of patents US10695023B2, US11393137B2, GB2018/1818049.7, GR20180100490, and GR20180100510. ASA, SN, and KMC are co-inventors of patent US10695023B2. These are licensed to Caristo Diagnostics. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank., Methods: PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods., Results: We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models., Conclusions: The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF., Clinical Relevance Statement: This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF., Key Points: •PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure., (© 2023. The Author(s).)

Aims: To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women., Methods and Results: The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust., Conclusion: Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women., Competing Interests: Conflict of interest: S.E.P. provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. The remaining authors have no disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations., Methods and Results: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control., Conclusion: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control., Competing Interests: Conflict of interest: S.E.P. provides consultancy to Cardiovascular Imaging Inc., Calgary, Alberta, Canada. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Sleep duration and chronotype have been associated with increased morbidity and mortality. We assessed for associations between sleep duration and chronotype on cardiac structure and function. UK Biobank participants with CMR data and without known cardiovascular disease were included. Self-reported sleep duration was categorized as short (<7 h/d), normal (7-9 h/d) and long (>9 h/d). Self-reported chronotype was categories as "definitely morning" or "definitely evening." Analysis included 3903 middle-aged adults: 929 short, 2924 normal and 50 long sleepers; with 966 definitely-morning and 355 definitely-evening chronotypes. Long sleep was independently associated with lower left ventricular (LV) mass (-4.8%, P = 0.035), left atrial maximum volume (-8.1%, P = 0.041) and right ventricular (RV) end-diastolic volume (-4.8%, P = 0.038) compared to those with normal sleep duration. Evening chronotype was independently associated with lower LV end-diastolic volume (-2.4%, P = 0.021), RV end-diastolic volume (-3.6%, P = 0.0006), RV end systolic volume (-5.1%, P = 0.0009), RV stroke volume (RVSV -2.7%, P = 0.033), right atrial maximal volume (-4.3%, P = 0.011) and emptying fraction (+1.3%, P = 0.047) compared to morning chronotype. Sex interactions existed for sleep duration and chronotype and age interaction for chronotype even after considering potential confounders. In conclusion, longer sleep duration was independently associated with smaller LV mass, left atrial volume and RV volume. Evening chronotype was independently associated with smaller LV and RV and reduced RV function compared to morning chronotype. Sex interactions exist with cardiac remodeling most evident in males with long sleep duration and evening chronotype. Recommendations for sleep chronotype and duration may need to be individualized based on sex., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer., Methods: Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics., Results: We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk., Conclusions: Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors., Competing Interests: Competing interests: SEP provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Left ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT., Methods: We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study., Results: Twenty-one genetic loci were discovered at P <5×10 -8 . Several novel candidate genes were identified including PROX1 , PXN , and PTK2 , with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (r g =0.53) and substantial loci overlap (19/21)., Conclusions: Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.

Objective: To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021., Methods: COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up., Results: Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period., Conclusions: Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes., Competing Interests: Competing interests: SEP provides consultancy to Cardiovascular Imaging, Calgary, Alberta, Canada. BR has consulted for Axcella Therapeutics. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention., (© 2022. The Author(s).)

Background: Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known., Objectives: The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort., Methods: The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall., Results: From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01)., Conclusions: This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding., Competing Interests: Funding Support and Author Disclosures This work was partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement number 825903 (euCanSHare project, Dr Petersen). Dr Petersen acknowledges support from the National Institute for Health Research (NIHR) Biomedical Research Centre at Barts, London, United Kingdom. Drs Petersen, Neubauer, and Piechnik acknowledge the British Heart Foundation, London, United Kingdom, for funding the manual analysis to create a cardiovascular magnetic resonance imaging reference standard for the UK Biobank imaging resource in 5000 CMR scans (PG/14/89/31194). This project was enabled through access to the Medical Research Council eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council (MR/L016311/1). Dr Zugwitz acknowledges funding received from the European Society of Cardiology, Sophia Antipolis Cedex, France, in the form of an European Society of Cardiology Training Grant. Dr Neubauer acknowledges support from the Oxford NIHR Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence. Dr Aung recognizes the NIHR Integrated Academic Training program, which supports his Academic Clinical Lectureship post. Drs McCracken and Neubauer are supported by the Oxford NIHR Biomedical Research Centre. Drs Petersen and Rauseo acknowledge support by the London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare (AI4VBH), which is funded from the Data to Early Diagnosis and Precision Medicine strand of the government’s Industrial Strategy Challenge Fund, managed and delivered by Innovate UK on behalf of United Kingdom Research and Innovation (UKRI). Dr Nijveldt has received research grants from Philips Volcano and Biotronik. Dr Petersen provides consultancy to Circle Cardiovascular Imaging, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying mechanism in 42 598 UK Biobank participants., Methods and Results: We extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships., Conclusion: We demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk., Competing Interests: Conflict of interest: S.E.P. provides consultancy to and owns stock of Circle Cardiovascular Imaging Inc, Calgary, Alberta, Canada. CA and SN are Founders, Share holders and Directors of Caristo Diagnostics, a CT Image analysis spinout company from the University of Oxford. C.A. is also inventor of relevant patents US10,695,023B2, PCT/GB2017/053262, GB2018/1818049.7, GR20180100490, and GR20180100510, licensed through exclusive license to Caristo Diagnostics. The remaining authors have no disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants., Methods and Results: We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations., Conclusion: LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction., Competing Interests: Conflict of interest: S.E.P. provides consultancy to and owns stock of Cardiovascular Imaging Inc., Calgary, AB, Canada., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Accurate 3D modelling of cardiac chambers is essential for clinical assessment of cardiac volume and function, including structural, and motion analysis. Furthermore, to study the correlation between cardiac morphology and other patient information within a large population, it is necessary to automatically generate cardiac mesh models of each subject within the population. In this study, we introduce MCSI-Net (Multi-Cue Shape Inference Network), where we embed a statistical shape model inside a convolutional neural network and leverage both phenotypic and demographic information from the cohort to infer subject-specific reconstructions of all four cardiac chambers in 3D. In this way, we leverage the ability of the network to learn the appearance of cardiac chambers in cine cardiac magnetic resonance (CMR) images, and generate plausible 3D cardiac shapes, by constraining the prediction using a shape prior, in the form of the statistical modes of shape variation learned a priori from a subset of the population. This, in turn, enables the network to generalise to samples across the entire population. To the best of our knowledge, this is the first work that uses such an approach for patient-specific cardiac shape generation. MCSI-Net is capable of producing accurate 3D shapes using just a fraction (about 23% to 46%) of the available image data, which is of significant importance to the community as it supports the acceleration of CMR scan acquisitions. Cardiac MR images from the UK Biobank were used to train and validate the proposed method. We also present the results from analysing 40,000 subjects of the UK Biobank at 50 time-frames, totalling two million image volumes. Our model can generate more globally consistent heart shape than that of manual annotations in the presence of inter-slice motion and shows strong agreement with the reference ranges for cardiac structure and function across cardiac ventricles and atria., Competing Interests: Declaration of Competing Interest 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function., Methods and Results: UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468 629 individuals (56.2 ± 8.1 years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.83-0.92; P < 0.001] and CV mortality (multivariate HR = 0.83, 95% CI: 0.74-0.94; P = 0.006), and incident stroke (multivariate HR = 0.79, 95% CI: 0.63-0.99 P = 0.037) after a median follow-up of 11 years. CMR data were available in 30 650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass., Conclusion: Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Existing evidence suggests links between brain and cardiovascular health. We investigated associations between cognitive performance and cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank, considering a range of potential confounders., Methods and Results: We studied 29 763 participants with CMR and cognitive testing, specifically, fluid intelligence (FI, 13 verbal-numeric reasoning questions), and reaction time (RT, a timed pairs matching exercise); both were considered continuous variables for modelling. We included the following CMR metrics: left and right ventricular (LV and RV) volumes in end-diastole and end-systole, LV/RV ejection fractions, LV/RV stroke volumes, LV mass, and aortic distensibility. Multivariable linear regression models were used to estimate the association of each CMR measure with FI and RT, adjusting for age, sex, smoking, education, deprivation, diabetes, hypertension, high cholesterol, prior myocardial infarction, alcohol intake, and exercise level. We report standardized beta-coefficients, 95% confidence intervals, and P-values adjusted for multiple testing. In this predominantly healthy cohort (average age 63.0 ± 7.5 years), better cognitive performance (higher FI, lower RT) was associated with larger LV/RV volumes, higher LV/RV stroke volumes, greater LV mass, and greater aortic distensibility in fully adjusted models. There was some evidence of non-linearity in the relationship between FI and LV end-systolic volume, with reversal of the direction of association at very high volumes. Associations were consistent for men and women and in different ages., Conclusion: Better cognitive performance is associated with CMR measures likely representing a healthier cardiovascular phenotype. These relationships remained significant after adjustment for a range of cardiometabolic, lifestyle, and demographic factors, suggesting possible involvement of alternative disease mechanisms., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes., Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107)., Findings: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity., Interpretation: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care., Funding: UK Research and Innovation and National Institute for Health Research., Competing Interests: Declaration of interests JDC reports grants and personal fees from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Insmed, personal fees from Chiesi, Zambon, Janssen, and Grifols, and grants from Gilead Sciences, outside the submitted work. TC reports grants from Guy's and St Thomas' Charity, fees from workshops, and fees from writing self-help books on fatigue, outside the submitted work. NE received a donation of SARS-CoV-2 lateral flow antigen test kits from Mologic, in relation to an unrelated COVID-19 project. Neither NE nor his institution have received any financial compensation and he has no financial relationship of any kind with Mologic. RAE reports grants from GlaxoSmithKline during the conduct of the study; and grants from the National Institute for Health Research (NIHR) and personal fees from GlaxoSmithKline, AstraZeneca, and Chiesi, outside the submitted work. AH reports personal fees from Vertex Pharmaceuticals, Mylan Healthcare, and the Cystic Fibrosis Foundation, and grants from JP Moulton Trust and NIHR, outside the submitted work. LGH reports receiving sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceuticals, personal fees from Novartis, Hoffman la Roche/Genentech, Sanofi, Evelo Biosciences, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia, and grants from Medimmune, Novartis UK, Roche/Genentech, GlaxoSmithKline, Amgen, Genentech/Hoffman la Roche, AstraZeneca, Medimmune, Aerocrine, and Vitalograph, outside the submitted work. NH reports that his research group has received unrestricted grants (managed by Guy's & St Thomas' Foundation Trust) from Philips and Resmed. Philips are contributing to the development of the MYOTRACE technology. SH reports personal fees and fees to institution for advisory boards and consultancy from Novo Nordisk, Eli Lilly, Zealand Pharma, and Sanofi Aventis, outside the submitted work. JJ reports personal fees from Boehringer Ingelheim, Roche, GlaxoSmithKline, and NHSX, outside the submitted work. RGJ reports personal fees and research funding from Biogen, personal fees from Galapagos, Heptares, Boehringer Ingelheim, Pliant, Roche/InterMune, MedImmune, PharmAkea, Bristol Myers Squibb, Chiesi, Roche/Promedior, Veracyte, and GlaxoSmithKline research funding from Galecto, collaborative award from RedX and Nordic Biosciences, and was an advisory board member for NuMedii, outside the submitted work. RGJ is supported by an NIHR Professorship (RP-2017-08-ST2-014) and is a trustee for Action for Pulmonary Fibrosis. GM reports grants from AstraZeneca, outside the submitted work. PJMO reports grants from the Medical Research Council (MRC), the EU, and NIHR, and personal fees from Pfizer, Nestle, and Janssen, outside the submitted work. PP reports a grant from NIHR, outside the submitted work. MRo reports a senior clinical fellowship as part of research training and a 1-year post working in Pharma Development Neurosciences with Roche Pharmaceuticals, outside the submitted work. ADS reports grants and personal fees from AstraZeneca, Bayer, Boehringer, Chiesi, Forest Laboratories, GlaxoSmithKline, Grifols, Insmed, MedImmune, Novartis, Pfizer, and 30T, outside the submitted work. MGS reports grants from NIHR, MRC, and the Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, during the conduct of the study; and reports being a minority owner and chair of the infectious disease scientific advisory board for Integrum Scientific, outside the submitted work. AShe reports being a Member of the Scottish Government's Chief Medical Officer's COVID-19 Advisory Group. MT reports personal fees from Merck Sharp & Dohme and GlaxoSmithKline, and grants and personal fees from Bayer and Actelion, during the conduct of the study. LVW reports grants from GlaxoSmithKline and Orion, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: Data regarding the effects of regular alcohol consumption on cardiac anatomy and function are scarce. Therefore, we sought to determine the relationship between regular alcohol intake and cardiac structure and function as evaluated with cardiac magnetic resonance imaging., Methods and Results: Participants of the UK Biobank who underwent cardiac magnetic resonance were enrolled in our analysis. Data regarding regular alcohol consumption were obtained from questionnaires filled in by the study participants. Exclusion criteria were poor image quality, missing, or incongruent data regarding alcohol drinking habits, prior drinking, presence of heart failure or angina, and prior myocardial infarction or stroke. Overall, 4335 participants (61.5 ± 7.5 years, 47.6% male) were analysed. We used multivariate linear regression models adjusted for age, ethnicity, body mass index, smoking, hypertension, diabetes mellitus, physical activity, cholesterol level, and Townsend deprivation index to examine the relationship between regular alcohol intake and cardiac structure and function. In men, alcohol intake was independently associated with marginally increased left ventricular end-diastolic volume [β = 0.14; 95% confidence interval (CI) = 0.05-0.24; P = 0.004], left ventricular stroke volume (β = 0.08; 95% CI = 0.03-0.14; P = 0.005), and right ventricular stroke volume (β = 0.08; 95% CI = 0.02-0.13; P = 0.006). In women, alcohol consumption was associated with increased left atrium volume (β = 0.14; 95% CI = 0.04-0.23; P = 0.006)., Conclusion: Alcohol consumption is independently associated with a marginal increase in left and right ventricular volumes in men, but not in women, whereas alcohol intake showed an association with increased left atrium volume in women. Our results suggest that there is only minimal relationship between regular alcohol consumption and cardiac morphology and function in an asymptomatic middle-aged population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear., Methods: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity., Discussion: COVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity., Clinical Trial Registration: ISRCTN 58667920. Registered 04 August 2020.

Background and Objectives: Obstructive sleep apnea (OSA) is a common disorder with an increased risk for left ventricular and right ventricular dysfunction. Most studies to date have examined populations with manifest cardiovascular disease using echocardiography to analyze ventricular dysfunction with little or no reference to ventricular volumes or myocardial mass. Our aim was to explore these parameters with cardiac MRI. We hypothesized that there would be stepwise increase in left ventricular mass and right ventricular volumes from the unaffected, to the snoring and the OSA group. Materials and Methods: We analyzed cardiac MRI data from 4978 UK Biobank participants free from cardiovascular disease. Participants were allocated into three cohorts: with OSA, with self-reported snoring and without OSA or snoring ( n = 118, 1886 and 2477). We analyzed cardiac parameters from balanced cine-SSFP sequences and indexed them to body surface area. Results: Patients with OSA were mostly males (47.3% vs. 79.7%; p < 0.001) with higher body mass index (25.7 ± 4.0 vs. 31.3 ± 5.3 kg/m²; p < 0.001) and higher blood pressure (135 ± 18 vs. 140 ± 17 mmHg; p = 0.012) compared to individuals without OSA or snoring. Regression analysis showed a significant effect for OSA in left ventricular end-diastolic index (LVEDVI) (β = -4.9 ± 2.4 mL/m²; p = 0.040) and right ventricular end-diastolic index (RVEDVI) (β = -6.2 ± 2.6 mL/m²; p = 0.016) in females and for right ventricular ejection fraction (RVEF) (β = 1.7 ± 0.8%; p = 0.031) in males. A significant effect was discovered in snoring females for left ventricular mass index (LVMI) (β = 3.5 ± 0.9 g/m²; p < 0.001) and in males for left ventricular ejection fraction (LVEF) (β = 1.0 ± 0.3%; p = 0.001) and RVEF (β = 1.2 ± 0.3%; p < 0.001). Conclusion: Our study suggests that OSA is highly underdiagnosed and that it is an evolving process with gender specific progression. Females with OSA show significantly lower ventricular volumes while males with snoring show increased ejection fractions which may be an early sign of hypertrophy. Separate prospective studies are needed to further explore the direction of causality.

Background: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes., Aims: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19., Methods: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction., Results: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity., Discussion: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors., Conclusions: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.

The UK Biobank (UKB) is a health research resource of major international importance, incorporating comprehensive characterization of >500 000 men and women recruited between 2006 and 2010 from across the UK. There is prospective tracking of health outcomes for all participants through linkages with national cohorts (death registers, cancer registers, electronic hospital records, and primary care records). The dataset has been enhanced with the UKB imaging study, which aims to scan a subset of 100 000 participants. The imaging protocol includes magnetic resonance imaging of the brain, heart, and abdomen, carotid ultrasound, and whole-body dual X-ray absorptiometry. Since its launch in 2015, over 48 000 participants have completed the imaging study with scheduled completion in 2023. Repeat imaging of 10 000 participants has been approved and commenced in 2019. The cardiovascular magnetic resonance (CMR) scan provides detailed assessment of cardiac structure and function comprising bright blood anatomic assessment (sagittal, coronal, and axial), left and right ventricular cine images (long and short axes), myocardial tagging, native T1 mapping, aortic flow, and imaging of the thoracic aorta. The UKB is an open access resource available to health researchers across all scientific disciplines from both academia and industry with no preferential access or exclusivity. In this paper, we consider how we may best utilize the UKB CMR data to advance cardiovascular research and review notable achievements to date., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults., Methods: 5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45-54, 55-64, 65-74 years)., Results: Overall, 721 (14.2%) truly healthy participants aged 45-74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m 2 ) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m 2 ) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m 2 ) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m 2 ) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m 2 ) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m 2 ) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m 2 ) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m 2 ) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97., Conclusions: We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions.

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart-brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m 2 ; P =0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; P =0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; P =0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m 2 ; P =0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; P =0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; P =0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm 2 ; P =0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure ( P <0.01, P =0.01, and P =0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.

UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.

Background: Current guidance from International Society for Heart and Lung Transplantation recommends using body weight for donor-recipient size matching for heart transplantation. However, recent studies have shown that predicted heart mass, using body weight, height, age, and sex, may represent a better method of size matching. We aim to validate a cardiovascular magnetic resonance (CMR)-derived equation for predicted left ventricular mass (LVM) in a cohort of normal individuals in the United Kingdom., Methods: This observational study was conducted in 5065 middle-aged (44-77 years old) UK Biobank participants who underwent CMR imaging in 2014 to 2015. Individuals with cancer diagnosis in the previous 12 months or history of cardiovascular disease were excluded. Predicted LVM was calculated based on participants' sex, height, and weight recorded at the time of imaging. Correlation analyses were performed between the predicted LVM and the LVM obtained from manual contouring of CMR cine images. The analysis included 3398 participants (age 61.5±7.5 years, 47.8% males)., Results: Predicted LVM was considerably higher than CMR-derived LVM (mean±SD of 138.8±28.9 g versus 86.3±20.9 g). However, there was a strong correlation between the 2 measurements (Spearman correlation coefficient 0.802, P <0.0001)., Conclusions: Predicted LVM calculated using a CMR-derived equation that incorporates height, weight, and sex has a strong correlation with CMR LVM in large cohort of normal individuals in the United Kingdom. Our findings suggest that predicted heart mass equations may be a valid tool for donor-recipient size matching for heart transplantation in the United Kingdom.

Introduction: Cardiovascular disease (CVD) is more common in women who have had pregnancy complications such as spontaneous pregnancy loss. We used cross-sectional data from the UK Biobank Imaging Enhancement Study to determine whether pregnancy loss is associated with cardiac or vascular remodelling in later life, which might contribute to this increased risk., Methods: Pregnancy history was reported by women participating in UK Biobank between 2006 and 2010 at age 40-69 years using a self-completed touch-screen questionnaire. Associations between self-reported spontaneous pregnancy loss and cardiovascular measures, collected in women who participated in the Imaging Enhancement Study up to the end of 2015, were examined. Cardiac structure and function were assessed by magnetic resonance (CMR) steady-state free precession imaging at 1.5 Tesla. Carotid intima-media thickness (CIMT) measurements were taken for both common carotid arteries using a CardioHealth Station. Statistical associations with CMR and carotid measures were adjusted for age, BMI and other cardiovascular risk factors., Results: Data were available on 2660 women of whom 111 were excluded because of pre-existing cardiovascular disease and 30 had no pregnancy information available. Of the remaining 2519, 446 were nulligravid and 2073 had a history of pregnancies, of whom 622 reported at least one pregnancy loss (92% miscarriages and 8% stillbirths) and 1451 reported no pregnancy loss. No significant differences in any cardiac or carotid parameters were evident in women who reported pregnancy loss compared to other groups (Table 1)., Conclusion: Women who self-report pregnancy loss do not have significant differences in cardiac structure, cardiac function, or carotid structure in later life to explain their increased cardiovascular risk. This suggests any cardiovascular risks associated with pregnancy loss operate through other disease mechanisms. Alternatively, other characteristics of pregnancy loss, which we were not able to take account of, such as timing and number of pregnancy losses may be required to identify those at greatest cardiovascular risk., Competing Interests: The authors have declared that no competing interests exist.

Left ventricular (LV) hypertrophy is a strong risk factor for heart failure and cardiovascular death. ECG measures of LV mass are estimated as heritable in twin and family-based analyses and heritability estimates of LV mass measured by echocardiography are lower. We hypothesised that CMR-derived measurements, being more precise than echocardiographic measurements, would advance our understanding of heritable LV traits. We phenotyped 116 British families (427 individuals) by CMR and ECG, and undertook heritability analyses using variance-components (QTDT) and GWAS SNP-based (GCTA-GREML) methods. ECG-based traits such as LV mass and Sokolow-Lyon duration showed substantial estimates of heritability (60%), whereas CMR-derived LV mass was only modestly heritable (20%). However, the ECG LV mass was positively correlated with the lateral diameter of the chest (rho = 0.67), and adjustment for this attenuated the heritability estimate (42%). Finally, CMR-derived right ventricular mass showed considerable heritability (44%). Heritability estimates of LV phenotypes show substantial variation depending on the modality of measurement, being greater when measured by ECG than CMR. This may reflect the differences between electrophysiological as opposed to anatomical hypertrophy. However, ECG LV hypertrophy traits are likely to be influenced by genetic association with anthropometric measures, inflating their overall measured heritability.

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases., Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes., Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10 -8 ). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease., Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases., Lay Summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content., (Copyright © 2019 European Association for the Study of the Liver. All rights reserved.)

Background: Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease. Detection of early cardiac changes before manifest disease develops is important. We investigated early alterations in cardiac structure and function associated with DM using cardiovascular magnetic resonance imaging., Methods: Participants from the UK Biobank Cardiovascular Magnetic Resonance Substudy, a community cohort study, without known cardiovascular disease and left ventricular ejection fraction ≥50% were included. Multivariable linear regression models were performed. The investigators were blinded to DM status., Results: A total of 3984 individuals, 45% men, (mean [SD]) age 61.3 (7.5) years, hereof 143 individuals (3.6%) with DM. There was no difference in left ventricular (LV) ejection fraction (DM versus no DM; coefficient [95% CI]: -0.86% [-1.8 to 0.5]; P =0.065), LV mass (-0.13 g/m 2 [-1.6 to 1.3], P =0.86), or right ventricular ejection fraction (-0.23% [-1.2 to 0.8], P =0.65). However, both LV and right ventricular volumes were significantly smaller in DM, (LV end-diastolic volume/m 2 : -3.46 mL/m 2 [-5.8 to -1.2], P =0.003, right ventricular end-diastolic volume/m 2 : -4.2 mL/m 2 [-6.8 to -1.7], P =0.001, LV stroke volume/m 2 : -3.0 mL/m 2 [-4.5 to -1.5], P <0.001; right ventricular stroke volume/m 2 : -3.8 mL/m 2 [-6.5 to -1.1], P =0.005), LV mass/volume: 0.026 (0.01 to 0.04) g/mL, P =0.006. Both left atrial and right atrial emptying fraction were lower in DM (right atrial emptying fraction: -6.2% [-10.2 to -2.1], P =0.003; left atrial emptying fraction:-3.5% [-6.9 to -0.1], P =0.043). LV global circumferential strain was impaired in DM (coefficient [95% CI]: 0.38% [0.01 to 0.7], P =0.045)., Conclusions: In a low-risk general population without known cardiovascular disease and with preserved LV ejection fraction, DM is associated with early changes in all 4 cardiac chambers. These findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally.

Population imaging studies generate data for developing and implementing personalised health strategies to prevent, or more effectively treat disease. Large prospective epidemiological studies acquire imaging for pre-symptomatic populations. These studies enable the early discovery of alterations due to impending disease, and enable early identification of individuals at risk. Such studies pose new challenges requiring automatic image analysis. To date, few large-scale population-level cardiac imaging studies have been conducted. One such study stands out for its sheer size, careful implementation, and availability of top quality expert annotation; the UK Biobank (UKB). The resulting massive imaging datasets (targeting ca. 100,000 subjects) has put published approaches for cardiac image quantification to the test. In this paper, we present and evaluate a cardiac magnetic resonance (CMR) image analysis pipeline that properly scales up and can provide a fully automatic analysis of the UKB CMR study. Without manual user interactions, our pipeline performs end-to-end image analytics from multi-view cine CMR images all the way to anatomical and functional bi-ventricular quantification. All this, while maintaining relevant quality controls of the CMR input images, and resulting image segmentations. To the best of our knowledge, this is the first published attempt to fully automate the extraction of global and regional reference ranges of all key functional cardiovascular indexes, from both left and right cardiac ventricles, for a population of 20,000 subjects imaged at 50 time frames per subject, for a total of one million CMR volumes. In addition, our pipeline provides 3D anatomical bi-ventricular models of the heart. These models enable the extraction of detailed information of the morphodynamics of the two ventricles for subsequent association to genetic, omics, lifestyle habits, exposure information, and other information provided in population imaging studies. We validated our proposed CMR analytics pipeline against manual expert readings on a reference cohort of 4620 subjects with contour delineations and corresponding clinical indexes. Our results show broad significant agreement between the manually obtained reference indexes, and those automatically computed via our framework. 80.67% of subjects were processed with mean contour distance of less than 1 pixel, and 17.50% with mean contour distance between 1 and 2 pixels. Finally, we compare our pipeline with a recently published approach reporting on UKB data, and based on deep learning. Our comparison shows similar performance in terms of segmentation accuracy with respect to human experts., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: The associations between cardiovascular disease (CVD) risk factors and the biventricular geometry of the right ventricle (RV) and left ventricle (LV) have been difficult to assess, due to subtle and complex shape changes. We sought to quantify reference RV morphology as well as biventricular variations associated with common cardiovascular risk factors., Methods: A biventricular shape atlas was automatically constructed using contours and landmarks from 4329 UK Biobank cardiovascular magnetic resonance (CMR) studies. A subdivision surface geometric mesh was customized to the contours using a diffeomorphic registration algorithm, with automatic correction of slice shifts due to differences in breath-hold position. A reference sub-cohort was identified consisting of 630 participants with no CVD risk factors. Morphometric scores were computed using linear regression to quantify shape variations associated with four risk factors (high cholesterol, high blood pressure, obesity and smoking) and three disease factors (diabetes, previous myocardial infarction and angina)., Results: The atlas construction led to an accurate representation of 3D shapes at end-diastole and end-systole, with acceptable fitting errors between surfaces and contours (average error less than 1.5 mm). Atlas shape features had stronger associations than traditional mass and volume measures for all factors (p < 0.005 for each). High blood pressure was associated with outward displacement of the LV free walls, but inward displacement of the RV free wall and thickening of the septum. Smoking was associated with a rounder RV with inward displacement of the RV free wall and increased relative wall thickness., Conclusion: Morphometric relationships between biventricular shape and cardiovascular risk factors in a large cohort show complex interactions between RV and LV morphology. These can be quantified by z-scores, which can be used to study the morphological correlates of disease.

Background: The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools such as image segmentation methods are employed to derive quantitative measures or biomarkers for further analyses. Manual inspection and visual QC of each segmentation result is not feasible at large scale. However, it is important to be able to automatically detect when a segmentation method fails in order to avoid inclusion of wrong measurements into subsequent analyses which could otherwise lead to incorrect conclusions., Methods: To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4800 cardiovascular magnetic resonance (CMR) scans. We then apply our method to a large cohort of 7250 CMR on which we have performed manual QC., Results: We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using the predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4800 scans for which manual segmentations were available. We mimic real-world application of the method on 7250 CMR where we show good agreement between predicted quality metrics and manual visual QC scores., Conclusions: We show that Reverse classification accuracy has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study.

Left ventricular (LV) mass and volume are important indicators of clinical and pre-clinical disease processes. However, much of the shape information present in modern imaging examinations is currently ignored. Morphometric atlases enable precise quantification of shape and function, but there has been no objective comparison of different atlases in the same cohort. We compared two independent LV atlases using MRI scans of 4547 UK Biobank participants: (i) a volume atlas derived by automatic non-rigid registration of image volumes to a common template, and (ii) a surface atlas derived from manually drawn epicardial and endocardial surface contours. The strength of associations between atlas principal components and cardiovascular risk factors (smoking, diabetes, high blood pressure, high cholesterol and angina) were quantified with logistic regression models and five-fold cross validation, using area under the ROC curve (AUC) and Akaike Information Criterion (AIC) metrics. Both atlases exhibited similar principal components, showed similar relationships with risk factors, and had stronger associations (higher AUC and lower AIC) than a reference model based on LV mass and volume, for all risk factors (DeLong p < 0.05). Morphometric variations associated with each risk factor could be quantified and visualized and were similar between atlases. UK Biobank LV shape atlases are robust to construction method and show stronger relationships with cardiovascular risk factors than mass and volume.

Purpose: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender., Methods: MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m 2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk., Results: The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values., Conclusion: The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver. All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g). Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy. Further analysis using univariate models showed elevated liver iron to be related to male sex (p<10(-16), r2 = 0.008), increasing age (p<10(-16), r2 = 0.013), and red meat intake (p<10(-16), r2 = 0.008). Elevated liver fat (>5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p = 0.0007). This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment., Competing Interests: The authors of this manuscript have the following competing interests: Andy McKay, Andrea Dennis, Matt Kelly, Michael Gyngell and Rajarshi Banerjee are employees of a commercial funder: Perspectum Diagnostics. Andy McKay, Andrea Dennis, Matt Kelly, Michael Gyngell, Stefan Neubauer, Rajarshi Banerjee, Henry Wilman are also stockholders of Perspectum Diagnostics. Stefan Neubauer has a paid consultancy with Perspectum Diagnostics, and also holds the position of non-executive director for the company. Jimmy Bell and E. Louise Thomas hold a Knowledge Transfer Partnership award from Innovate UK in collaboration with Perspectum Diagnostics, which funds Henry Wilman’s employment at the University of Westminster. Jimmy Bell and E. Louise Thomas have also received funds for a contract research project from Perspectum Diagnostics to deliver image analysis for a project undertaken by Perspectum Diagnostics. Employment and consultancy of these authors does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders., Methods: Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders., Results: The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter <2.5 μm concentration was significantly associated with larger left ventricular end-diastolic volume and end-systolic volume (effect size = 0.82%, 95% CI, 0.09-1.55%, P =0.027; and effect size = 1.28%, 95% CI, 0.15-2.43%, P =0.027, respectively, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 μm) and right ventricular end-diastolic volume (effect size = 0.85%, 95% CI, 0.12-1.58%, P =0.023, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 μm). Likewise, higher nitrogen dioxide concentration was associated with larger biventricular volume. Distance from the major roads was the only metric associated with lower left ventricular mass (effect size = -0.74%, 95% CI, -1.3% to -0.18%, P =0.01, per interquartile range increment). Neither left and right atrial phenotypes nor left ventricular geometric remodeling patterns were influenced by the ambient pollutants., Conclusions: In a large asymptomatic population with no prevalent cardiovascular disease, higher past exposure to particulate matter with an aerodynamic diameter <2.5 μm and nitrogen dioxide was associated with cardiac ventricular dilatation, a marker of adverse remodeling that often precedes heart failure development., Competing Interests: Disclosures Dr Petersen provides consultancy to Circle Cardiovascular Imaging Inc, Calgary, Canada. The other authors report no conflicts.

UK Biobank, a large cohort study, plans to acquire 100,000 cardiac MRI studies by 2020. Although fully-automated left ventricular (LV) analysis was performed in the original acquisition, this was not designed for unsupervised incorporation into epidemiological studies. We sought to evaluate automated LV mass and volume (Siemens syngo InlineVF versions D13A and E11C), against manual analysis in a substantial sub-cohort of UK Biobank participants. Eight readers from two centers, trained to give consistent results, manually analyzed 4874 UK Biobank cases for LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass (LVM). Agreement between manual and InlineVF automated analyses were evaluated using Bland-Altman analysis and the intra-class correlation coefficient (ICC). Tenfold cross-validation was used to establish a linear regression calibration between manual and InlineVF results. InlineVF D13A returned results in 4423 cases, whereas InlineVF E11C returned results in 4775 cases and also reported LVM. Rapid visual assessment of the E11C results found 178 cases (3.7%) with grossly misplaced contours or landmarks. In the remaining 4597 cases, LV function showed good agreement: ESV -6.4 ± 9.0 ml, 0.853 (mean ± SD of the differences, ICC) EDV -3.0 ± 11.6 ml, 0.937; SV 3.4 ± 9.8 ml, 0.855; and EF 3.5 ± 5.1%, 0.586. Although LV mass was consistently overestimated (29.9 ± 17.0 g, 0.534) due to larger epicardial contours on all slices, linear regression could be used to correct the bias and improve accuracy. Automated InlineVF results can be used for case-control studies in UK Biobank, provided visual quality control and linear bias correction are performed. Improvements between InlineVF D13A and InlineVF E11C show the field is rapidly advancing, with further improvements expected in the near future.

Background: Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45-74., Methods: Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45-54, 55-64, 65-74)., Results: After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m 2 vs 42 ± 7 g/m 2 ). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females., Conclusions: We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population.

Objectives: This paper reviews the international literature that employed time-series analysis to evaluate the effects of advertising bans on aggregate consumption of cigarettes or tobacco., Methods: A systematic search of the literature was conducted. Three groups of studies representing analyses of advertising bans in the U.S.A., in other countries and in 22 OECD countries were defined. The estimated effects of advertising bans and their significance were analysed., Results: 24 studies were identified. They used a wide array of explanatory variables, models, estimating methods and data sources. 18 studies found a negative effect of an advertising ban on aggregate consumption, but only ten of these studies found a significant effect. Two studies using data from 22 OECD countries suggested that partial bans would have little or no influence on aggregate consumption, whereas complete bans would significantly reduce consumption., Conclusions: The results imply that advertising bans have a negative but sometimes only narrow impact on consumption. Complete bans let expect a higher effectiveness. Because of methodological restrictions of analysing advertising bans' effects by time series approaches, also different approaches should be used in the future.