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Aims Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering. Methods and results Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03–1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36–2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance. Conclusions Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that epicardial adipose tissue (EAT) is an independent atrial fibrillation (AF) prognostic marker and has influence on the myocardial function. In computed tomography (CT), EAT volume (EATv) and density (EATd) are parameters that are often used to quantify EAT. While increased EATv has been found to correlate with the prevalence and the recurrence of AF after ablation therapy, higher EATd correlates with inflammation due to arrest of lipid maturation and with high risk of plaque presence and plaque progression. Automation of the quantification task diminishes the variability in readings introduced by different observers in manual quantification and results in high reproducibility of studies and less time-consuming analysis. Our objective is to develop a fully automated quantification of EATv and EATd using a deep learning (DL) framework. Methods: We proposed a framework that consists of image classification and segmentation DL models and performs the task of selecting images with EAT from all the CT images acquired for a patient, and the task of segmenting the EAT from the output images of the preceding task. EATv and EATd are estimated using the segmentation masks to define the region of interest. For our experiments, a 300-patient dataset was divided into two subsets, each consisting of 150 patients: Dataset 1 (41,979 CT slices) for training the DL models, and Dataset 2 (36,428 CT slices) for evaluating the quantification of EATv and EATd. Results: The classification model achieved accuracies of 98% for precision, recall and F1 scores, and the segmentation model achieved accuracies in terms of mean (± std.) and median dice similarity coefficient scores of 0.844 (± 0.19) and 0.84, respectively. Using the evaluation set (Dataset 2), our approach resulted in a Pearson correlation coefficient of 0.971 (R² = 0.943) between the label and predicted EATv, and the correlation coefficient of 0.972 (R² = 0.945) between the label and predicted EATd. Conclusions: We proposed a framework that provides a fast and robust strategy for accurate EAT segmentation, and volume (EATv) and attenuation (EATd) quantification tasks. The framework will be useful to clinicians and other practitioners for carrying out reproducible EAT quantification at patient level or for large cohorts and high-throughput projects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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/m2) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m2) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m2) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m2) 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/m2) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m2) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m2) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m2) 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. [ABSTRACT FROM AUTHOR]

The theory for the calculation of nuclear shielding constants with London atomic orbitals using density functional theory is presented. The theory includes the use of a local exchange–correlation functional which depends on both the electron density ρ(r) and the paramagnetic current density jp(r). The resulting coupled-perturbed Kohn–Sham equations are presented, together with the working expression for the nuclear shielding tensor. The entire theory has been programmed and exhaustively checked, using standard Gaussian basis sets. A variety of ρ(r) dependent exchange–correlation functionals have been used, together with a current dependence suggested by Vignale, Rasolt, and Geldart. Certain numerical difficulties arose with this form which necessitated a cutoff in its evaluation for low densities. Calculations have been performed on HF, N2, CO, F2, H2O, and CH4. Including the current dependence is seen here to have a slightly deshielding effect. The major deficiency in the reported calculations appears to arise from the use of local functionals which give poor values for the Kohn–Sham eigenvalues. © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The theory for the coupled perturbed Kohn–Sham calculation of hyperpolarizabilities using nonlocal density functionals is presented. Results for calculations on formaldehyde, acetonitrile, and methyl fluoride using moderate size basis sets are reported. These results are compared with previous density functional calculations using the local density approximation, Hartree–Fock, and correlated methods, and with the experimental values. © 1994 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Background: Reduced lung function is common and associated with increased cardiovascular morbidity and mortality, even in asymptomatic individuals without diagnosed respiratory disease. Previous studies have identified relationships between lung function and cardiovascular structure in individuals with pulmonary disease, but the relationships in those free from diagnosed cardiorespiratory disease have not been fully explored. Methods: UK Biobank is a prospective cohort study of community participants in the United Kingdom. Individuals self-reported demographics and co-morbidities, and a subset underwent cardiovascular magnetic resonance (CMR) imaging and spirometry. CMR images were analysed to derive ventricular volumes and mass. The relationships between CMR-derived measures and spirometry and age were modelled with multivariable linear regression, taking account of the effects of possible confounders. Results: Data were available for 4,975 individuals, and after exclusion of those with pre-existing cardiorespiratory disease and unacceptable spirometry, 1,406 were included in the analyses. In fully-adjusted multivariable linear models lower FEV1 and FVC were associated with smaller left ventricular end-diastolic (−5.21ml per standard deviation (SD) change in FEV1, −5.69ml per SD change in FVC), end-systolic (−2.34ml, −2.56ml) and stroke volumes (−2.85ml, −3.11ml); right ventricular end-diastolic (−5.62ml, −5.84ml), end-systolic (−2.47ml, −2.46ml) and stroke volumes (−3.13ml, −3.36ml); and with lower left ventricular mass (−2.29g, −2.46g). Changes of comparable magnitude and direction were observed per decade increase in age. Conclusions: This study shows that reduced FEV1 and FVC are associated with smaller ventricular volumes and reduced ventricular mass. The changes seen per standard deviation change in FEV1 and FVC are comparable to one decade of ageing. [ABSTRACT FROM AUTHOR]

Background: Handgrip strength, a measure of muscular fitness, is associated with cardiovascular (CV) events and CV mortality but its association with cardiac structure and function is unknown. The goal of this study was to determine if handgrip strength is associated with changes in cardiac structure and function in UK adults. Methods and results: Left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), mass (M), and mass-to-volume ratio (MVR) were measured in a sample of 4,654 participants of the UK Biobank Study 6.3 ± 1 years after baseline using cardiovascular magnetic resonance (CMR). Handgrip strength was measured at baseline and at the imaging follow-up examination. We determined the association between handgrip strength at baseline as well as its change over time and each of the cardiac outcome parameters. After adjustment, higher level of handgrip strength at baseline was associated with higher LVEDV (difference per SD increase in handgrip strength: 1.3ml, 95% CI 0.1–2.4; p = 0.034), higher LVSV (1.0ml, 0.3–1.8; p = 0.006), lower LVM (-1.0g, -1.8 –-0.3; p = 0.007), and lower LVMVR (-0.013g/ml, -0.018 –-0.007; p<0.001). The association between handgrip strength and LVEDV and LVSV was strongest among younger individuals, while the association with LVM and LVMVR was strongest among older individuals. Conclusions: Better handgrip strength was associated with cardiac structure and function in a pattern indicative of less cardiac hypertrophy and remodeling. These characteristics are known to be associated with a lower risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: The effect of menopausal hormone therapy (MHT)–previously known as hormone replacement therapy–on cardiovascular health remains unclear and controversial. This cross-sectional study examined the impact of MHT on left ventricular (LV) and left atrial (LA) structure and function, alterations in which are markers of subclinical cardiovascular disease, in a population-based cohort. Methods: Post-menopausal women who had never used MHT and those who had used MHT ≥3 years participating in the UK Biobank who had undergone cardiovascular magnetic resonance (CMR) imaging and free of known cardiovascular disease were included. Multivariable linear regression was performed to examine the relationship between cardiac parameters and MHT use ≥3 years. To explore whether MHT use on each of the cardiac outcomes differed by age, multivariable regression models were constructed with a cross-product of age and MHT fitted as an interaction term. Results: Of 1604 post-menopausal women, 513 (32%) had used MHT ≥3 years. In the MHT cohort, median age at menopause was 50 (IQR: 45–52) and median duration of MHT was 8 years. In the non-MHT cohort, median age at menopause was 51 (IQR: 48–53). MHT use was associated with significantly lower LV end-diastolic volume (122.8 ml vs 119.8 ml, effect size = -2.4%, 95% CI: -4.2% to -0.5%; p = 0.013) and LA maximal volume (60.2 ml vs 57.5 ml, effect size = -4.5%, 95% CI: -7.8% to -1.0%; p = 0.012). There was no significant difference in LV mass. MHT use significantly modified the effect between age and CMR parameters; MHT users had greater decrements in LV end-diastolic volume, LV end-systolic volume and LA maximal volume with advancing age. Conclusions: MHT use was not associated with adverse, subclinical changes in cardiac structure and function. Indeed, significantly smaller LV and LA chamber volumes were observed which have been linked to favourable cardiovascular outcomes. These findings represent a novel approach to examining MHT’s effect on the cardiovascular system. [ABSTRACT FROM AUTHOR]

Objectives The electronic health record (EHR) is underused in the hospital setting. The aim of this service evaluation study was to respond to National Health Service (NHS) Digital's ambition for a paperless NHS by capturing routinely collected cardiac outpatient data in the EHR to populate summary patient reports and provide a resource for audit and research. Design A PowerForm template was developed within the Cerner EHR, for real-time entry of routine clinical data by clinicians attending a cardiac outpatient clinic. Data captured within the PowerForm automatically populated a SmartTemplate to generate a view-only report that was immediately available for the patient and for electronic transmission to the referring general practitioner (GP). Results During the first 8 months, the PowerForm template was used in 61% (360/594) of consecutive outpatient referrals increasing from 42% to 77% during the course of the study. Structured patient reports were available for immediate sharing with the referring GP using Cerner Health Information Exchange technology while electronic transmission was successfully developed in a substudy of 64 cases, with direct delivery by the NHS Data Transfer Service in 29 cases and NHS mail in the remainder. In feedback, the report's immediate availability was considered very or extremely important by >80% of the patients and GPs who were surveyed. Both groups reported preference of the patient report to the conventional typed letter. Deidentified template data for all 360 patients were successfully captured within the Trust system, confirming availability of these routinely collected outpatient data for audit and research. Conclusion Electronic template development tailored to the requirements of a specialist outpatient clinic facilitates capture of routinely collected data within the Cerner EHR. These data can be made available for audit and research. They can also be used to enhance communication by populating structured reports for immediate delivery to patients and GPs. [ABSTRACT FROM AUTHOR]

Aims: The UK Biobank is a large-scale population-based study utilising cardiovascular magnetic resonance (CMR) to generate measurements of atrial and ventricular structure and function. This study aimed to quantify the association between modifiable cardiovascular risk factors and cardiac morphology and function in individuals without known cardiovascular disease. Methods: Age, sex, ethnicity (non-modifiable) and systolic blood pressure, diastolic blood pressure, smoking status, exercise, body mass index (BMI), high cholesterol, diabetes, alcohol intake (modifiable) were considered important cardiovascular risk factors. Multivariable regression models were built to ascertain the association of risk factors on left ventricular (LV), right ventricular (RV), left atrial (LA) and right atrial (RA) CMR parameters. Results: 4,651 participants were included in the analysis. All modifiable risk factors had significant effects on differing atrial and ventricular parameters. BMI was the modifiable risk factor most consistently associated with subclinical changes to CMR parameters, particularly in relation to higher LV mass (+8.3% per SD [4.3 kg/m2], 95% CI: 7.6 to 8.9%), LV (EDV: +4.8% per SD, 95% CI: 4.2 to 5.4%); ESV: +4.4% per SD, 95% CI: 3.5 to 5.3%), RV (EDV: +5.3% per SD, 95% CI: 4.7 to 5.9%; ESV: +5.4% per SD, 95% CI: 4.5 to 6.4%) and LA maximal (+8.6% per SD, 95% CI: 7.4 to 9.7%) volumes. Increases in SBP were associated with higher LV mass (+6.8% per SD, 95% CI: 5.9 to 7.7%), LV (EDV: +4.5% per SD, 95% CI: 3.6 to 5.4%; ESV: +2.0% per SD, 95% CI: 0.8 to 3.3%) volumes. The presence of diabetes or high cholesterol resulted in smaller volumes and lower ejection fractions. Conclusions: Modifiable risk factors are associated with subclinical alterations in structure and function in all four cardiac chambers. BMI and systolic blood pressure are the most important modifiable risk factors affecting CMR parameters known to be linked to adverse outcomes. [ABSTRACT FROM AUTHOR]

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/m² vs 4² ± 7 g/m²). 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. [ABSTRACT FROM AUTHOR]

An efficient general algorithm for the computation of molecular momentum intracule densities from Hartree–Fock wavefunctions using Gaussian basis functions is described. The momentum intracules for a number of systems are examined, and comparison with their position space counterparts discussed. [ABSTRACT FROM AUTHOR]

Myocardial strain using cardiac magnetic resonance (CMR) is a sensitive marker for predicting adverse outcomes in many cardiac disease states, but the prognostic value in the general population has not been studied conclusively. The goal of this study was to assess the independent prognostic value of CMR feature tracking (FT)—derived LV global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) metrics in predicting adverse outcomes (heart failure, myocardial infarction, stroke, and death). Participants from the UK Biobank population imaging study were included. Univariable and multivariable Cox models were used for each outcome and each strain marker (GLS, GCS, GRS) separately. The multivariable models were tested with adjustment for prognostically important clinical features and conventional global LV imaging markers relevant for each outcome. Overall, 45,700 participants were included in the study (average age 65 ± 8 years), with a median follow-up period of 3 years. All univariable and multivariable models demonstrated that lower absolute GLS, GCS, and GRS were associated with increased incidence of heart failure, myocardial infarction, stroke, and death. All strain markers were independent predictors (incrementally above some respective conventional LV imaging markers) for the morbidity outcomes, but only GLS predicted death independently: (HR: 1.18; 95% CI: 1.07-1.30). In the general population, LV strain metrics derived using CMR-FT in radial, circumferential, and longitudinal directions are strongly and independently predictive of heart failure, myocardial infarction, and stroke, but only GLS is independently predictive of death in an adult population cohort. [ABSTRACT FROM AUTHOR]

Aims: Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering., Methods and Results: Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance., Conclusions: Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes., Competing Interests: Conflict of interest. G.G.S. provides consultancy to MindRank AI, Intellicloud, and Derq. S.E.P. provides consultancy to Circle 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.)

A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their "trustworthiness" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a "trustworthy AI system." We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development., Competing Interests: Author SEP provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. Author MK was employed by Siemens Healthcare Hungary. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Szabo, Raisi-Estabragh, Salih, McCracken, Ruiz Pujadas, Gkontra, Kiss, Maurovich-Horvath, Vago, Merkely, Lee, Lekadir and Petersen.)

Objectives: Currently, administering contrast agents is necessary for accurately visualizing and quantifying presence, location, and extent of myocardial infarction (MI) with cardiac magnetic resonance (CMR). In this study, our objective is to investigate and analyze pre- and post-contrast CMR images with the goal of predicting post-contrast information using pre-contrast information only. We propose methods and identify challenges., Methods: The study population consists of 272 retrospectively selected CMR studies with diagnoses of MI ( n = 108) and healthy controls ( n = 164). We describe a pipeline for pre-processing this dataset for analysis. After data feature engineering, 722 cine short-axis (SAX) images and segmentation mask pairs were used for experimentation. This constitutes 506, 108, and 108 pairs for the training, validation, and testing sets, respectively. We use deep learning (DL) segmentation (UNet) and classification (ResNet50) models to discover the extent and location of the scar and classify between the ischemic cases and healthy cases (i.e., cases with no regional myocardial scar) from the pre-contrast cine SAX image frames, respectively. We then capture complex data patterns that represent subtle signal and functional changes in the cine SAX images due to MI using optical flow, rate of change of myocardial area, and radiomics data. We apply this dataset to explore two supervised learning methods, namely, the support vector machines (SVM) and the decision tree (DT) methods, to develop predictive models for classifying pre-contrast cine SAX images as being a case of MI or healthy., Results: Overall, for the UNet segmentation model, the performance based on the mean Dice score for the test set ( n = 108) is 0.75 (±0.20) for the endocardium, 0.51 (±0.21) for the epicardium and 0.20 (±0.17) for the scar. For the classification task, the accuracy, F1 and precision scores of 0.68, 0.69, and 0.64, respectively, were achieved with the SVM model, and of 0.62, 0.63, and 0.72, respectively, with the DT model., Conclusion: We have presented some promising approaches involving DL, SVM, and DT methods in an attempt to accurately predict contrast information from non-contrast images. While our initial results are modest for this challenging task, this area of research still poses several open problems., Competing Interests: AS, AA-K, and PB were employed by Circle Cardiovascular Imaging Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdulkareem, Kenawy, Rauseo, Lee, Sojoudi, Amir-Khalili, Lekadir, Young, Barnes, Barckow, Khanji, Aung and Petersen.)

Objectives: Cardiac computed tomography (CCT) is a common pre-operative imaging modality to evaluate pulmonary vein anatomy and left atrial appendage thrombus in patients undergoing catheter ablation (CA) for atrial fibrillation (AF). These images also allow for full volumetric left atrium (LA) measurement for recurrence risk stratification, as larger LA volume (LAV) is associated with higher recurrence rates. Our objective is to apply deep learning (DL) techniques to fully automate the computation of LAV and assess the quality of the computed LAV values., Methods: Using a dataset of 85,477 CCT images from 337 patients, we proposed a framework that consists of several processes that perform a combination of tasks including the selection of images with LA from all other images using a ResNet50 classification model, the segmentation of images with LA using a UNet image segmentation model, the assessment of the quality of the image segmentation task, the estimation of LAV, and quality control (QC) assessment., Results: Overall, the proposed LAV estimation framework achieved accuracies of 98% (precision, recall, and F1 score metrics) in the image classification task, 88.5% (mean dice score) in the image segmentation task, 82% (mean dice score) in the segmentation quality prediction task, and R 2 (the coefficient of determination) value of 0.968 in the volume estimation task. It correctly identified 9 out of 10 poor LAV estimations from a total of 337 patients as poor-quality estimates., Conclusions: We proposed a generalizable framework that consists of DL models and computational methods for LAV estimation. The framework provides an efficient and robust strategy for QC assessment of the accuracy for DL-based image segmentation and volume estimation tasks, allowing high-throughput extraction of reproducible LAV measurements to be possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdulkareem, Brahier, Zou, Taylor, Thomaides, Bergquist, Srichai, Lee, Vargas and Petersen.)

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: Convolutional neural network (CNN) based segmentation methods provide an efficient and automated way for clinicians to assess the structure and function of the heart in cardiac MR images. While CNNs can generally perform the segmentation tasks with high accuracy when training and test images come from the same domain (e.g., same scanner or site), their performance often degrades dramatically on images from different scanners or clinical sites. Methods: We propose a simple yet effective way for improving the network generalization ability by carefully designing data normalization and augmentation strategies to accommodate common scenarios in multi-site, multi-scanner clinical imaging data sets. We demonstrate that a neural network trained on a single-site single-scanner dataset from the UK Biobank can be successfully applied to segmenting cardiac MR images across different sites and different scanners without substantial loss of accuracy. Specifically, the method was trained on a large set of 3,975 subjects from the UK Biobank. It was then directly tested on 600 different subjects from the UK Biobank for intra-domain testing and two other sets for cross-domain testing: the ACDC dataset (100 subjects, 1 site, 2 scanners) and the BSCMR-AS dataset (599 subjects, 6 sites, 9 scanners). Results: The proposed method produces promising segmentation results on the UK Biobank test set which are comparable to previously reported values in the literature, while also performing well on cross-domain test sets, achieving a mean Dice metric of 0.90 for the left ventricle, 0.81 for the myocardium, and 0.82 for the right ventricle on the ACDC dataset; and 0.89 for the left ventricle, 0.83 for the myocardium on the BSCMR-AS dataset. Conclusions: The proposed method offers a potential solution to improve CNN-based model generalizability for the cross-scanner and cross-site cardiac MR image segmentation task., (Copyright © 2020 Chen, Bai, Davies, Bhuva, Manisty, Augusto, Moon, Aung, Lee, Sanghvi, Fung, Paiva, Petersen, Lukaschuk, Piechnik, Neubauer and Rueckert.)

No published data are available regarding infliximab use in Kawasaki disease patients with recent live virus vaccination. We investigated 38 acute Kawasaki disease patients who received infliximab within 90 days of receiving measles-mumps-rubella, varicella-zoster virus, or Rotavirus vaccines. There were no adverse events or serious infections, which suggests that infliximab use in acute Kawasaki disease patients with recent live viral vaccinations is safe.

Advances in theory and algorithms for electronic structure calculations must be incorporated into program packages to enable them to become routinely used by the broader chemical community. This work reviews advances made over the past five years or so that constitute the major improvements contained in a new release of the Q-Chem quantum chemistry package, together with illustrative timings and applications. Specific developments discussed include fast methods for density functional theory calculations, linear scaling evaluation of energies, NMR chemical shifts and electric properties, fast auxiliary basis function methods for correlated energies and gradients, equation-of-motion coupled cluster methods for ground and excited states, geminal wavefunctions, embedding methods and techniques for exploring potential energy surfaces.