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Abstract Background Use of electronic methods to support informed consent (‘eConsent’) is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK. Main text We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system’s generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system. We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake. Conclusions We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach.

Background and Objectives: Cardiovascular magnetic resonance (CMR) is emerging as an important imaging tool for sub-phenotyping and estimating left ventricular (LV) filling pressure (LVFP). The N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) is released from cardiac myocytes in response to mechanical load and wall stress. This study sought to investigate if CMR-derived LVFP is associated with the serum levels of NT-proBNP and, in addition, if it provides any incremental prognostic value in heart failure (HF). Materials and Methods: This study recruited 380 patients diagnosed with HF who underwent same-day CMR and clinical assessment between February 2018 and January 2020. CMR-derived LVFP was calculated, as previously, from long- and short-axis cines. During CMR assessment, serum NT-proBNP was measured. The pathological cut-offs were defined as follows: NT-proBNP ≥ 125 pg/mL and CMR LVFP > 15 mmHg. The incidence of HF hospitalisation was treated as a clinical outcome. Results: In total, 305 patients had NT-proBNP ≥ 125 pg/mL. Patients with raised NT-proBNP were older (54 ± 14 vs. 64 ± 11 years, p < 0.0001). Patients with raised NT-proBNP had higher LV volumes and mass. In addition, CMR LVFP was higher in patients with raised NT-proBNP (13.2 ± 2.6 vs. 15.4 ± 3.2 mmHg, p < 0.0001). The serum levels of NT-proBNP were associated with CMR-derived LVFP (R = 0.42, p < 0.0001). In logistic regression analysis, this association between NT-proBNP and CMR LVFP was independent of all other CMR variables, including LV ejection fraction, LV mass, and left atrial volume (coefficient = 2.02, p = 0.002). CMR LVFP demonstrated an independent association with the incidence of HF hospitalisation above NT-proBNP (hazard ratio 2.7, 95% confidence interval 1.2 to 6, p = 0.01). Conclusions: A CMR-modelled LVFP is independently associated with serum NT-proBNP levels. Importantly, it provides an incremental prognostic value over and above serum NT-proBNP levels.

Abstract Objectives Mitral regurgitation (MR) and microvascular obstruction (MVO) are common complications of myocardial infarction (MI). This study aimed to investigate the association between MR in ST-elevation MI (STEMI) subjects with MVO post-reperfusion. STEMI subjects undergoing primary percutaneous intervention were enrolled. Cardiovascular magnetic resonance (CMR) imaging was performed within 48-hours of initial presentation. 4D flow images of CMR were analysed using a retrospective valve tracking technique to quantify MR volume, and late gadolinium enhancement images of CMR to assess MVO. Results Among 69 patients in the study cohort, 41 had MVO (59%). Patients with MVO had lower left ventricular (LV) ejection fraction (EF) (42 ± 10% vs. 52 ± 8%, P 2.5 ml. We conclude that in patients with reperfused STEMI, the degree of acute MR is associated with the degree of MVO.

Abstract Metformin is an antihyperglycemic used to treat type 2 diabetes mellitus (T2DM). Patients with T2DM are at increased risk of cardiovascular disease. We explored the association between metformin use and cardiovascular magnetic resonance (CMR) derived stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR) and major adverse cardiovascular events (MACE; all cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation) in patients with T2DM. Multi-centre study of patients with T2DM, and healthy controls, underwent quantitative myocardial perfusion CMR using an artificial intelligence supported process. Multivariable regression analysis, and cox proportional hazard models of propensity score weighted patients quantified associations between metformin use, MBF, MPR, all cause death and MACE. Analysis included 572 patients with T2DM (68% prescribed metformin) with median follow-up 851 days (IQR 935 − 765). Metformin use was associated with an increase of MPR of 0.12 [0.08–0.40], p = 0.004. There were 82 MACE events (14.3%) including 25 (4.4%) deaths of which 16 were in those not prescribed metformin (8.7%), compared to 9 in patients prescribed metformin (2.3%): adjusted hazard ratio 0.24 (95% CI 0.08–0.70, p = 0.009). MACE events were similar between groups. This multicentre, inverse probability weighting propensity score analysis study showed that in patients with T2DM, metformin use is associated with higher MPR and improved all cause survival.

Abstract Background Cardiac magnetic resonance (CMR) in the four-chamber plane offers comprehensive insight into the volumetrics of the heart. We aimed to develop an artificial intelligence (AI) model of time-resolved segmentation using the four-chamber cine. Methods A fully automated deep learning algorithm was trained using retrospective multicentre and multivendor data of 814 subjects. Validation, reproducibility, and mortality prediction were evaluated on an independent cohort of 101 subjects. Results The mean age of the validation cohort was 54 years, and 66 (65%) were males. Left and right heart parameters demonstrated strong correlations between automated and manual analysis, with a ρ of 0.91−0.98 and 0.89−0.98, respectively, with minimal bias. All AI four-chamber volumetrics in repeatability analysis demonstrated high correlation (ρ = 0.99−1.00) and no bias. Automated four-chamber analysis underestimated both left ventricular (LV) and right ventricular (RV) volumes compared to ground-truth short-axis cine analysis. Two correction factors for LV and RV four-chamber analysis were proposed based on systematic bias. After applying the correction factors, a strong correlation and minimal bias for LV volumetrics were observed. During a mean follow-up period of 6.75 years, 16 patients died. On stepwise multivariable analysis, left atrial ejection fraction demonstrated an independent association with death in both manual (hazard ratio (HR) = 0.96, p = 0.003) and AI analyses (HR = 0.96, p

Abstract Background Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. Methods We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF)

Background: Left atrial (LA) assessment is an important marker of adverse cardiovascular outcomes. Cardiovascular magnetic resonance (CMR) accurately quantifies LA volume and function based on biplane long-axis imaging. We aimed to validate single-plane-derived LA indices against the biplane method to simplify the post-processing of cine CMR. Methods: In this study, 100 patients from Leeds Teaching Hospitals were used as the derivation cohort. Bias correction for the single plane method was applied and subsequently validated in 79 subjects. Results: There were significant differences between the biplane and single plane mean LA maximum and minimum volumes and LA ejection fraction (EF) (all p < 0.01). After correcting for biases in the validation cohort, significant correlations in all LA indices were observed (0.89 to 0.98). The area under the curve (AUC) for the single plane to predict biplane cutoffs of LA maximum volume ≥ 112 mL was 0.97, LA minimum volume ≥ 44 mL was 0.99, LA stroke volume (SV) ≤ 21 mL was 1, and LA EF ≤ 46% was 1, (all p < 0.001). Conclusions: LA volumetric and functional assessment by the single plane method has a systematic bias compared to the biplane method. After bias correction, single plane LA volume and function are comparable to the biplane method.

(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability.

Abstract Aims Left ventricular filling pressure (LVFP) can be estimated from cardiovascular magnetic resonance (CMR). We aimed to investigate whether CMR‐derived LVFP is associated with signs, symptoms, and prognosis in patients with recently diagnosed heart failure (HF). Methods and results This study recruited 454 patients diagnosed with HF who underwent same‐day CMR and clinical assessment between February 2018 and January 2020. CMR‐derived LVFP was calculated, as previously, from long‐ and short‐axis cines. CMR‐derived LVFP association with symptoms and signs of HF was investigated. Patients were followed for median 2.9 years (interquartile range 1.5–3.6 years) for major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, HF hospitalization, non‐fatal stroke, and non‐fatal myocardial infarction. The mean age was 62 ± 13 years, 36% were female (n = 163), and 30% (n = 135) had raised LVFP. Forty‐seven per cent of patients had an ejection fraction

Abstract Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p

Abstract Background When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. Methods 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). Results 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; − 29 ± 21 ml/m2 vs − 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (− 23 ± 30 ml/m2 and − 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p

Background: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR., Objectives: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial., Methods: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m 2 ) [95% CI: 26.1-29.5 kg/m 2 )]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31 phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments., Results: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009)., Conclusions: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939)., Competing Interests: Funding Support and Author Disclosures The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the Department of Health and Social Care. This independent research has been jointly funded by the Wellcome Trust (grant number: 221690/Z/20/Z) and Diabetes UK (grant number:18/0005870) and has been performed at the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC) (NIHR203331). Funding for open access charge is from Wellcome Trust (grant number: 221690/Z/20/Z). Dr Chowdhary has received grants from the British Heart Foundation (grant number: FS/CRTF/20/24003). Dr Valkovič has received grants from the Sir Henry Dale Fellowship supported jointly by the Wellcome Trust and the Royal Society (#221805/Z/20/Z), and Slovak Grant Agencies VEGA (#2/0004/23) and APVV (#21-0299). Dr Levelt acknowledges support from the Wellcome Trust Clinical Career Development Fellowship (grant number: 221690/Z/20/Z), Diabetes UK (grant number: UK 18/0005908) and the NIHR Leeds Biomedical Research Centre. 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.)

Aims: Heart failure (HF) with preserved ejection fraction disproportionately affects women. There are no validated sex-specific tools for HF diagnosis despite widely reported differences in cardiac structure. This study investigates whether sex, as assigned at birth, influences cardiac magnetic resonance (CMR) assessment of left ventricular filling pressure (LVFP), a hallmark of HF agnostic to ejection fraction., Methods and Results: A derivation cohort of patients with suspected pulmonary hypertension and HF from the Sheffield centre underwent invasive right heart catheterization and CMR within 24 h of each other. A sex-specific CMR model to estimate LVFP, measured as pulmonary capillary wedge pressure (PCWP), was developed using multivariable regression. A validation cohort of patients with confirmed HF from the Leeds centre was used to evaluate for the primary endpoints of HF hospitalization and major adverse cardiovascular events (MACEs). Comparison between generic and sex-specific CMR-derived PCWP was undertaken. A total of 835 (60% female) and 454 (36% female) patients were recruited into the derivation and validation cohorts respectively. A sex-specific model incorporating left atrial volume and left ventricular mass was created. The generic CMR PCWP showed significant differences between males and females (14.7 ± 4 vs. 13 ± 3.0 mmHg, P > 0.001), not present with the sex-specific CMR PCWP (14.1 ± 3 vs. 13.8 mmHg, P = 0.3). The sex-specific, but not the generic, CMR PCWP was associated with HF hospitalization (hazard ratio 3.9, P = 0.0002) and MACE (hazard ratio 2.5, P = 0.001) over a mean follow-up period of 2.4 ± 1.2 years., Conclusion: Accounting for sex improves precision and prognostic performance of CMR biomarkers for HF., Competing Interests: Conflict of interest: P.G. is a clinical advisor for Pie Medical Imaging and Medis Medical Imaging. All other authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Turbulent aortic flow makes the cardiovascular system less effective. It remains unknown if patients with heart failure with preserved ejection fraction (HFpEF) have disturbed aortic flow. This study sought to investigate advanced markers of aortic flow disturbances in HFpEF., Methods: This case-controlled observational study used four-dimensional flow cardiovascular magnetic resonance derived, two-dimensional phase-contrast reformatted plane data at an orthogonal plane just above the sino-tubular junction. We recruited 10 young healthy controls (HCs), 10 old HCs and 23 patients with HFpEF. We analysed average systolic aortic flow displacement (FDsavg), systolic flow reversal ratio (sFRR) and pulse wave velocity (PWV). In a sub-group analysis, we compared old HCs versus age-gender-matched HFpEF (N=10)., Results: Differences were significant in mean age (P<0.001) among young HCs (22.9±3.5 years), old HCs (60.5±10.2 years) and HFpEF patients (73.7±9.7 years). FDsavg, sFRR and PWV varied significantly (P<0.001) in young HCs (8±4%, 2±2%, 4±2m/s), old HCs (16±5%, 7±6%, 11±8m/s), and HFpEF patients (23±10%, 11±10%, 8±3). No significant PWV differences existed between old HCs and HFpEF.HFpEF had significantly higher FDsavg versus old HCs (23±10% vs 16±5%, P<0.001). A FDsavg > 17.7% achieved 74% sensitivity, 70% specificity for differentiating them. sFRR was notably higher in HFpEF (11±10% vs 7±6%, P<0.001). A sFRR > 7.3% yielded 78% sensitivity, 70% specificity in differentiating these groups. In sub-group analysis, FDsavg remained distinctly elevated in HFpEF (22.4±9.7% vs 16±4.9%, P=0.029). FDsavg of >16% showed 100% sensitivity and 70% specificity (P=0.01). Similarly, sFRR remained significantly higher in HFpEF (11.3±9.5% vs 6.6±6.4%, P=0.007). A sFRR of >7.2% showed 100% sensitivity and 60% specificity (P<0.001)., Conclusion: Aortic flow haemodynamics namely FDsavg and sFRR are significantly affected in ageing and HFpEF patients., Competing Interests: Competing interests: PG is a clinical advisor for Pie Medical Imaging, Neosoft and Medis Medical Imaging; he provides consultancy to Edwards Lifesciences and Anteris. SEP provides Consultancy to Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada. All other authors have no competing interests to declare., (Copyright: © 2024 Mehmood Z et al.)

Background: Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell's immediate environment: signal reception and transduction to/from the ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies and certain neurodevelopmental disorders. In the developing brain cilia play well-documented roles for the expansion of the neural progenitor cell pool, while information about the roles of cilia during post-mitotic neuron differentiation and maturation is scarce., Results: We employed ciliated Lund Human Mesencephalic (LUHMES) cells in time course experiments to assess the impact of ciliary signaling on neuron differentiation. By comparing ciliated and non-ciliated neuronal precursor cells and neurons in wild type and in RFX2 -/- mutant neurons with altered cilia, we discovered an early-differentiation "ciliary time window" during which transient cilia promote axon outgrowth, branching and arborization. Experiments in neurons with IFT88 and IFT172 ciliary gene knockdowns, leading to shorter cilia, confirm these results. Cilia promote neuron differentiation by tipping WNT signaling toward the non-canonical pathway, in turn activating WNT pathway output genes implicated in cyto-architectural changes., Conclusions: We provide a mechanistic entry point into when and how ciliary signaling coordinates, promotes and translates into anatomical changes. We hypothesize that ciliary alterations causing neuron differentiation defects may result in "mild" impairments of brain development, possibly underpinning certain aspects of neurodevelopmental disorders., (© 2024. The Author(s).)

The benefits of exercise are irrefutable with a well-established dose-dependent relationship between exercise intensity and reduction in cardiovascular disease. Differentiating the physiological adaptation to exercise, termed the "athlete's heart" from cardiomyopathies, has been advanced by the advent of more sophisticated imaging modalities such as cardiac magnetic resonance imaging (CMR). Myocardial fibrosis on CMR is a mutual finding amongst seemingly healthy endurance athletes and individuals with cardiomyopathy. As a substrate for arrhythmias, fibrosis is traditionally associated with increased cardiovascular risk. In this article, we discuss the aetiologies, distribution and potential implications of myocardial fibrosis in athletes., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 The Author. Published by Elsevier B.V. All rights reserved.)

Aims: Blood pressure (BP) is a crucial factor in cardiovascular health and can affect cardiac imaging assessments. However, standard outpatient cardiovascular MR (CMR) imaging procedures do not typically include BP measurements prior to image acquisition. This study proposes that brachial systolic BP (SBP) and diastolic BP (DBP) can be modelled using patient characteristics and CMR data., Methods: In this multicentre study, 57 patients from the PREFER-CMR registry and 163 patients from other registries were used as the derivation cohort. All subjects had their brachial SBP and DBP measured using a sphygmomanometer. Multivariate linear regression analysis was applied to predict brachial BP. The model was subsequently validated in a cohort of 169 healthy individuals., Results: Age and left ventricular ejection fraction were associated with SBP. Aortic forward flow, body surface area and left ventricular mass index were associated with DBP. When applied to the validation cohort, the correlation coefficient between CMR-derived SBP and brachial SBP was (r=0.16, 95% CI 0.011 to 0.305, p=0.03), and CMR-derived DBP and brachial DBP was (r=0.27, 95% CI 0.122 to 0.403, p=0.0004). The area under the curve (AUC) for CMR-derived SBP to predict SBP>120 mmHg was 0.59, p=0.038. Moreover, CMR-derived DBP to predict DBP>80 mmHg had an AUC of 0.64, p=0.002., Conclusion: CMR-derived SBP and DBP models can estimate brachial SBP and DBP. Such models may allow efficient prospective collection, as well as retrospective estimation of BP, which should be incorporated into assessments due to its critical effect on load-dependent parameters., Competing Interests: Competing interests: PG is a clinical advisor for Pie Medical Imaging and Medis Medical Imaging. PG is consultant for Anteris and Edwards Lifesciences. All other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Research utilising artificial intelligence (AI) and cardiovascular magnetic resonance (CMR) is rapidly evolving with various objectives, however AI model development, generalisation and performance may be hindered by availability of robust training datasets including contrast enhanced images., Methods: NotIs CMR is a large UK, prospective, multicentre, observational cohort study to guide the development of a biventricular AI scar model. Patients with ischaemic heart disease undergoing clinically indicated contrast-enhanced cardiac magnetic resonance imaging will be recruited at Nottingham University Hospitals NHS Trust and Mid-Yorkshire Hospital NHS Trust. Baseline assessment will include cardiac magnetic resonance imaging, demographic data, medical history, electrocardiographic and serum biomarkers. Participants will undergo monitoring for a minimum of 5 years to document any major cardiovascular adverse events. The main objectives include (1) AI training, validation and testing to improve the performance, applicability and adaptability of an AI biventricular scar segmentation model being developed by the authors and (2) develop a curated, disease-specific imaging database to support future research and collaborations and, (3) to explore associations in clinical outcome for future risk prediction modelling studies., Conclusion: NotIs CMR will collect and curate disease-specific, paired imaging and clinical datasets to develop an AI biventricular scar model whilst providing a database to support future research and collaboration in Artificial Intelligence and ischaemic heart disease., (© 2023. The Author(s).)

Background and objectives : Evaluating left ventricular filling pressure (LVFP) plays a crucial role in diagnosing and managing heart failure (HF). While traditional assessment methods involve multi-parametric transthoracic echocardiography (TTE) or right heart catheterisation (RHC), cardiovascular magnetic resonance (CMR) has emerged as a valuable diagnostic tool in HF. This study aimed to assess a simple CMR-derived model to estimate pulmonary capillary wedge pressure (PCWP) in a cohort of patients with suspected or proven heart failure and to investigate its performance in risk-stratifying patients. Materials and methods : A total of 835 patients with breathlessness were evaluated using RHC and CMR and split into derivation (85%) and validation cohorts (15%). Uni-variate and multi-variate linear regression analyses were used to derive a model for PCWP estimation using CMR. The model's performance was evaluated by comparing CMR-derived PCWP with PCWP obtained from RHC. Results : A CMR-derived PCWP incorporating left ventricular mass and the left atrial area (LAA) demonstrated good diagnostic accuracy. The model correctly reclassified 66% of participants whose TTE was 'indeterminate' or 'incorrect' in identifying raised filling pressures. On survival analysis, the CMR-derived PCWP model was predictive for mortality (HR 1.15, 95% CI 1.04-1.28, p = 0.005), which was not the case for PCWP obtained using RHC or TTE. Conclusions : The simplified CMR-derived PCWP model provides an accurate and practical tool for estimating PCWP in patients with suspected or proven heart failure. Its predictive value for mortality suggests the ability to play a valuable adjunctive role in echocardiography, especially in cases with unclear echocardiographic assessment.

Background: Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR., Methods: Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing., Results: Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P <0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P <0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P =0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P =0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P =0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P =0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P =0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P =0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P =0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P =0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D., Conclusions: Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D., Competing Interests: Disclosures None.

Objectives: To determine baseline characteristics predictive of left ventricular ejection fraction (LVEF) recovery in patients diagnosed with heart failure with reduced ejection fraction (HFrEF) and presumed non-ischaemic aetiology., Methods: We prospectively recruited patients who were diagnosed with HFrEF (LVEF ≤40%) on echocardiography and subsequently underwent cardiac MRI. Patients were excluded if they had a known history of coronary artery disease (>70% on invasive coronary angiography), myocardial infarction, coronary revascularisation or anginal symptoms. At cardiac MRI assessment, patients were categorised as either ongoing HFrEF or heart failure with improved ejection fraction (HFimpEF, LVEF >40% with ≥10% of absolute improvement). Clinical characteristics were compared between the groups. Logistic regression was performed to identify variables that were associated with LVEF recovery. Optimal cut-offs in QRISK3 score and baseline LVEF for prediction of LVEF recovery were identified through receiver operating characteristic curve analysis., Results: A total of 407 patients were diagnosed with HFrEF, and 139 (34%) attained HFimpEF at cardiac MRI assessment (median 63 days, IQR 41-119 days). Mean age of the patients was 63±12 years, and 260 (63.9%) were male. At multivariate logistic regression, both QRISK3 score (HR 0.978; 95% CI 0.963 to 0.993, p=0.004) and baseline LVEF (HR 1.044; 95% CI 1.015 to 1.073, p=0.002) were independent predictors of HFimpEF. Among patients with baseline LVEF ≤25%, only 22 (21.8%) recovered. In patients with baseline LVEF 25-40%, QRISK3 score >18% was associated with lack of recovery (HR 2.75; 95% CI 1.70 to 4.48, p<0.001). Additionally, QRISK3 score was associated with the presence of ischaemic late gadolinium enhancement (HR 1.035; 95% CI 1.018 to 1.053, p<0.001)., Conclusions: The QRISK3 score helps identify patients with HFrEF with undiagnosed vascular disease. Patients with either a very low baseline LVEF or a high QRISK3 score have less chance of left ventricular recovery and should be prioritised for early cardiac MRI and close monitoring., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Cilia, either motile or non-motile (a.k.a primary or sensory), are complex evolutionarily conserved eukaryotic structures composed of hundreds of proteins required for their assembly, structure and function that are collectively known as the ciliome. Ciliome gene mutations underlie a group of pleiotropic genetic diseases known as ciliopathies. Proper cilium function requires the tight coregulation of ciliome gene transcription, which is only fragmentarily understood. RFX transcription factors (TF) have an evolutionarily conserved role in the direct activation of ciliome genes both in motile and non-motile cilia cell-types. In vertebrates, FoxJ1 and FoxN4 Forkhead (FKH) TFs work with RFX in the direct activation of ciliome genes, exclusively in motile cilia cell-types. No additional TFs have been described to act together with RFX in primary cilia cell-types in any organism. Here we describe FKH-8, a FKH TF, as a direct regulator of the sensory ciliome genes in Caenorhabditis elegans . FKH-8 is expressed in all ciliated neurons in C. elegans , binds the regulatory regions of ciliome genes, regulates ciliome gene expression, cilium morphology and a wide range of behaviors mediated by sensory ciliated neurons. FKH-8 and DAF-19 ( C. elegans RFX) physically interact and synergistically regulate ciliome gene expression. C. elegans FKH-8 function can be replaced by mouse FOXJ1 and FOXN4 but not by other members of other mouse FKH subfamilies. In conclusion, RFX and FKH TF families act jointly as direct regulators of ciliome genes also in sensory ciliated cell types suggesting that this regulatory logic could be an ancient trait predating functional cilia sub-specialization., Competing Interests: RB, AE, CM, MF, PS, JT, MV, NF No competing interests declared, (© 2023, Brocal-Ruiz et al.)

Objective: To investigate whether left atrial (LA) volume and left ventricular filling pressure (LVFP) assessed by cardiovascular magnetic resonance (CMR) change during adenosine delivered myocardial hyperaemia as part of a first-pass stress perfusion study., Methods and Results: We enrolled 33 patients who had stress CMR. These patients had a baseline four-chamber cine and stress four-chamber cine, which was done at peak myocardial hyperaemic state after administering adenosine. The left and right atria were segmented in the end ventricular diastolic and systolic phases. Short-axis cine stack was segmented for ventricular functional assessment. At peak hyperaemic state, left atrial end ventricular systolic volume just before mitral valve opening increased significantly from baseline in all (91 ± 35ml vs. 81 ± 33ml, P = 0.0002), in males only (99 ± 35ml vs. 88 ± 33ml, P = 0.002) and females only (70 ± 26ml vs. 62 ± 22ml, P = 0.02). The right atrial end ventricular systolic volume increased less significantly from baseline (68 ± 21ml vs. 63 ± 20ml, P = 0.0448). CMR-derived LVFP (equivalent to pulmonary capillary wedge pressure) increased significantly at the peak hyperaemic state in all (15.1 ± 2.9mmHg vs. 14.4 ± 2.8mmHg, P = 0.0002), females only (12.9 ± 2.1mmHg vs. 12.3 ± 1.9mmHg, P = 0.029) and males only (15.9 ± 2.8mmHg vs. 15.2 ± 2.7mmHg, P = 0.002) cohorts., Conclusion: Left atrial volume assessment by CMR can measure acute and dynamic changes in preloading conditions on the left ventricle. During adenosine administered first-pass perfusion CMR, left atrial volume and LVFP rise significantly., (© 2023. The Author(s).)

Primary cilia are antenna-like organelles emanating from the cell surface. They are involved in cell-to-cell communication and bidirectional signal transduction to/from the extracellular environment. During brain formation, cilia critically aid in neurogenesis and maturation of neuronal structures such as axons, dendrites and synapses. Aberrations in cilia function can induce neuron differentiation defects and pathological consequences of varying severity, resulting in ciliopathies and likely a number of neurodevelopmental disorders. Despite the documented relevance of cilia for proper brain development, human neuronal models to recognize and study cilia biology are still scarce. We have established two types of cell models, Lund Human Mesencephalic (LUHMES) cells and neuroepithelial stem (NES) cells derived from induced pluripotent stem cells (iPSC), to investigate cilia biology in both proliferating neuronal progenitors/precursors and during the entire neuron differentiation and maturation process. We employ improved immunocytochemistry assays able to specifically detect cilia by confocal and super-resolution microscopy. We provide straightforward and robust methods to easily maintain cells in culture, for immunostaining and characterization of cilia orientation, anatomy and shape in human neurons across all stages of differentiation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics., Research Design and Methods: Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio., Results: Participants were matched for age, gestational age, and ethnicity. The following data are reported as mean ± SD. The women with GDM had higher BMI (27 ± 4 vs. 33 ± 5 kg/m2; P = 0.0001) and systolic (115 ± 11 vs. 121 ± 13 mmHg; P = 0.04) and diastolic (72 ± 7 vs. 76 ± 9 mmHg; P = 0.04) blood pressures. There was no difference in N-terminal pro-brain natriuretic peptide concentrations between the groups. The women with GDM had lower myocardial PCr to ATP ratio (2.2 ± 0.3 vs. 1.9 ± 0.4; P < 0.0001), accompanied by lower LV end-diastolic volumes (76 ± 12 vs. 67 ± 11 mL/m2; P = 0.002) and higher LV mass (90 ± 13 vs. 103 ± 18 g; P = 0.001). Although ventricular ejection fractions were similar, the GLS was reduced in women with GDM (-20% ± 3% vs. -18% ± 3%; P = 0.008)., Conclusions: Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared with lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM., (© 2022 by the American Diabetes Association.)

Objective: Type 2 diabetes mellitus (T2DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. We sought to investigate whether HCM patients with T2DM comorbidity exhibit adverse cardiac alterations in myocardial energetics, function, perfusion, or tissue characteristics., Research Design and Methods: A total of 55 participants with concomitant HCM and T2DM (HCM-DM) (n = 20) or isolated HCM (n = 20) and healthy volunteers (HV) (n = 15) underwent 31P-MRS and cardiovascular MRI. The HCM groups were matched for HCM phenotype., Results: Mean ± SD European Society of Cardiology sudden cardiac death risk scores were comparable between the HCM groups (HCM 2.2 ± 1.5%, HCM-DM 1.9 ± 1.2%; P = not significant), and sarcomeric mutations were equally common. HCM-DM patients had the highest median NT-proBNP levels (HV 42 ng/L [interquartile range 35-66], HCM 298 ng/L [157-837], HCM-DM 726 ng/L [213-8,695]; P < 0.0001). Left ventricular (LV) ejection fraction, mass, and wall thickness were similar between the HCM groups. HCM-DM patients displayed a greater degree of fibrosis burden with higher scar percentage and lower global longitudinal strain compared with HCM patients. PCr/ATP (the relative concentrations of phosphocreatine and ATP) was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.17 ± 0.49, HCM 1.93 ± 0.38, HCM-DM 1.54 ± 0.27; P = 0.002). In a similar pattern, stress myocardial blood flow was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.06 ± 0.42 mL/min/g, HCM 1.74 ± 0.44 mL/min/g, HCM-DM 1.39 ± 0.42 mL/min/g; P = 0.002)., Conclusions: We show for the first time that HCM-DM patients display greater reductions in myocardial energetics, perfusion, and contractile function and higher myocardial scar burden and serum NT-proBNP levels compared with patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and T2DM., (© 2022 by the American Diabetes Association.)

Aims: Non-invasive imaging is routinely used to estimate left ventricular (LV) filling pressure (LVFP) in heart failure (HF). Cardiovascular magnetic resonance (CMR) is emerging as an important imaging tool for sub-phenotyping HF. However, currently, LVFP cannot be estimated from CMR. This study sought to investigate (i) if CMR can estimate LVFP in patients with suspected HF and (ii) if CMR-modelled LVFP has prognostic power., Methods and Results: Suspected HF patients underwent right heart catheterization (RHC), CMR and transthoracic echocardiography (TTE) (validation cohort only) within 24 h of each other. Right heart catheterization measured pulmonary capillary wedge pressure (PCWP) was used as a reference for LVFP. At follow-up, death was considered as the primary endpoint. We enrolled 835 patients (mean age: 65 ± 13 years, 40% male). In the derivation cohort (n = 708, 85%), two CMR metrics were associated with RHC PCWP:LV mass and left atrial volume. When applied to the validation cohort (n = 127, 15%), the correlation coefficient between RHC PCWP and CMR-modelled PCWP was 0.55 (95% confidence interval: 0.41-0.66, P < 0.0001). Cardiovascular magnetic resonance-modelled PCWP was superior to TTE in classifying patients as normal or raised filling pressures (76 vs. 25%). Cardiovascular magnetic resonance-modelled PCWP was associated with an increased risk of death (hazard ratio: 1.77, P < 0.001). At Kaplan-Meier analysis, CMR-modelled PCWP was comparable to RHC PCWP (≥15 mmHg) to predict survival at 7-year follow-up (35 vs. 37%, χ2 = 0.41, P  = 0.52)., Conclusion: A physiological CMR model can estimate LVFP in patients with suspected HF. In addition, CMR-modelled LVFP has a prognostic role., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: This study sought to assess whether diabetes affects coronary microvascular function in individuals with normal body weight., Methods: Seventy-five participants (30 patients with type 2 diabetes [T2D] who were overweight [O-T2D], 15 patients with T2D who were lean [LnT2D], 15 healthy volunteers who were lean [LnHV], and 15 healthy volunteers who were overweight [O-HV]) without established cardiovascular disease were recruited. Participants underwent magnetic resonance imaging for assessment of subcutaneous, epicardial, and visceral adipose tissue areas, adenosine stress myocardial blood flow (MBF), and cardiac structure and function., Results: Stress MBF was reduced only in the O-T2D group (mean [SD], LnHV = 2.07 [0.47] mL/g/min, O-HV = 2.08 [0.42] mL/g/min, LnT2D = 2.16 [0.36] mL/g/min, O-T2D = 1.60 [0.28] mL/g/min; p ≤ 0.0001). Accumulation of visceral fat was evident in the LnT2D group at similar levels to the O-HV group (LnHV = 127 [53] cm 2 , O-HV = 181 [60] cm 2 , LnT2D = 182 [99] cm 2 , O-T2D = 288 [72] cm 2 ; p < 0.0001). Only the O-T2D group showed reductions in left ventricular ejection fraction (LnHV = 63% [4%], O-HV = 63% [4%], LnT2D = 60% [5%], O-T2D = 58% [6%]; p = 0.0008) and global longitudinal strain (LnHV = -15.1% [3.1%], O-HV= -15.2% [3.7%], LnT2D = -13.4% [2.7%], O-T2D = -11.1% [2.8%]; p = 0.002) compared with both control groups., Conclusions: Patients with T2D and normal body weight do not show alterations in global stress MBF, but they do show significant increases in visceral adiposity. Patients with T2D who were overweight and had no prior cardiovascular disease showed an increase in visceral adiposity and significant reductions in stress MBF., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

Cilia are important for the interaction with environments and the proper function of tissues. While the basic structure of cilia is well conserved, ciliated cells have various functions. To understand the distinctive identities of ciliated cells, the identification of cell-specific proteins and its regulation is essential. Here, we report the mechanism that confers a specific identity on IL2 neurons in Caenorhabditis elegans, neurons important for the dauer larva-specific nictation behavior. We show that DAF-19M, an isoform of the sole C. elegans RFX transcription factor DAF-19, heads a regulatory subroutine, regulating target genes through an X-box motif variant under the control of terminal selector proteins UNC-86 and CFI-1 in IL2 neurons. Considering the conservation of DAF-19M module in IL2 neurons for nictation and in male-specific neurons for mating behavior, we propose the existence of an evolutionarily adaptable, hard-wired genetic module for distinct behaviors that share the feature "recognizing the environment.", Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: In a cohort of type 2 diabetic (T2D) patients who underwent baseline cardiac magnetic resonance (CMR) and biomarker testing, during a median follow-up of 6 years, we aimed to determine longitudinal changes in the phenotypic expression of heart disease in diabetes, report clinical outcomes, and compare baseline clinical characteristics and CMR findings of patients who experienced major adverse cardiovascular events (MACE) to those remaining MACE free., Background: T2D increases the risk of heart failure (HF) and cardiovascular mortality. The long-term impact of T2D on cardiac phenotype in the absence of cardiovascular disease and other clinical events is unknown., Methods: Patients with T2D ( n  = 100) with no history of cardiovascular disease or hypertension were recruited at baseline. Biventricular volumes, function, and myocardial extracellular volume fraction (ECV) were assessed by CMR, and blood biomarkers were taken. Follow-up CMR was repeated in those without interim clinical events after 6 years., Results: Follow-up was successful in 83 participants. Of those, 29 experienced cardiovascular/clinical events (36%). Of the remaining 59, 32 patients who experienced no events received follow-up CMR. In this cohort, despite no significant changes in blood pressure, weight, or glycated hemoglobin, significant reductions in biventricular end-diastolic volumes and ejection fractions occurred over time. The mean ECV was unchanged. Baseline plasma high-sensitivity cardiac troponin T (hs-cTnT) was significantly associated with a change in left ventricular (LV) ejection fraction. Patients who experienced MACE had higher LV mass and greater LV concentricity than those who remained event free., Conclusions: T2D results in reductions in biventricular size and systolic function over time even in the absence of cardiovascular/clinical events., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Amrit Chowdhary et al.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and 31 P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and 31 P-MRS scans before and after 12 weeks' empagliflozin treatment. Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycemic control underwent an identical scan protocol at a single visit. Empagliflozin treatment was associated with significant improvements in phosphocreatine-to-ATP ratio (1.52 to 1.76, P = 0.009). This was accompanied by a 7% absolute increase in the mean left ventricular ejection fraction ( P = 0.001), 3% absolute increase in the mean global longitudinal strain ( P = 0.01), 8 mL/m 2 absolute reduction in the mean myocardial cell volume ( P = 0.04), and 61% relative reduction in the mean NT-proBNP ( P = 0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected. Empagliflozin thus ameliorates the "cardiac energy-deficient" state, regresses adverse myocardial cellular remodeling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate HF in T2D., (© 2021 by the American Diabetes Association.)

The role of inflammation in cardiovascular pathophysiology has gained a lot of research interest in recent years. Cardiovascular Magnetic Resonance has been a powerful tool in the non-invasive assessment of inflammation in several conditions. More recently, Ultrasmall superparamagnetic particles of iron oxide have been successfully used to evaluate macrophage activity and subsequently inflammation on a cellular level. Current evidence from research studies provides encouraging data and confirms that this evolving method can potentially have a huge impact on clinical practice as it can be used in the diagnosis and management of very common conditions such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathy, myocarditis and atherosclerosis. Another important emerging concept is that of myocardial energetics. With the use of phosphorus magnetic resonance spectroscopy, myocardial energetic compromise has been proved to be an important feature in the pathophysiological process of several conditions including diabetic cardiomyopathy, inherited cardiomyopathies, valvular heart disease and cardiac transplant rejection. This unique tool is therefore being utilized to assess metabolic alterations in a wide range of cardiovascular diseases. This review systematically examines these state-of-the-art methods in detail and provides an insight into the mechanisms of action and the clinical implications of their use., (© 2021. The Author(s).)

Objective: Handheld ultrasound devices (HUD) has diagnostic value in the assessment of patients with suspected left ventricular (LV) dysfunction. This meta-analysis evaluates the diagnostic ability of HUD compared with transthoracic echocardiography (TTE) and assesses the importance of operator experience., Methods: MEDLINE and EMBASE databases were searched in October 2020. Diagnostic studies using HUD and TTE imaging to determine LV dysfunction were included. Pooled sensitivities and specificities, and summary receiver operating characteristic curves were used to determine the diagnostic ability of HUD and evaluate the impact of operator experience on test accuracy., Results: Thirty-three studies with 6062 participants were included in the meta-analysis. Experienced operators could predict reduced LV ejection fraction (LVEF), wall motion abnormality (WMA), LV dilatation and LV hypertrophy with pooled sensitivities of 88%, 85%, 89% and 85%, respectively, and pooled specificities of 96%, 95%, 98% and 91%, respectively. Non-experienced operators are able to detect cardiac abnormalities with reasonable sensitivity and specificity. There was a significant difference in the diagnostic accuracy between experienced and inexperienced users in LV dilatation, LVEF (moderate/severe) and WMA. The diagnostic OR for LVEF (moderate/severe), LV dilatation and WMA in an experienced hand was 276 (95% CI 58 to 1320), 225 (95% CI 87 to 578) and 90 (95% CI 31 to 265), respectively, compared with 41 (95% CI 18 to 94), 45 (95% CI 16 to 123) and 28 (95% CI 20 to 41), respectively, for inexperienced users., Conclusion: This meta-analysis is the first to establish HUD as a powerful modality for predicting LV size and function. Experienced operators are able to accurately diagnose cardiac disease using HUD. A cautious, supervised approach should be implemented when imaging is performed by inexperienced users. This study provides a strong rationale for considering HUD as an auxiliary tool to physical examination in secondary care, to aid clinical decision making when considering referral for TTE., Trial Registration Number: CRD42020182429., Competing Interests: Competing interests: PG is an advisor for Pie Medical Imaging and Medis Medical Imaging. JW lists commercial relationships with AstraZeneca, Bayer and Novartis., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)