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AIMS: We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. METHODS AND RESULTS: Sixteen normal weight participants with dilated cardiomyopathy (DCMNW), and 27 with DCM and obesity (DCMOB), were compared to 26 normal weight controls (CTLNW). All underwent cardiac magnetic resonance imaging and 31P spectroscopy to assess function and energetics. Nineteen DCMOB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCMNW than in CTLNW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCMOB 41 ± 7%, DCMNW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCMOB (P < 0.001), due to higher rate through CK [median kf 0.21 (0.14) vs. 0.11 (0.12) s-1, P = 0.002]. During increased workload, the CTLNW heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCMNW and fell in DCMOB (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049). CONCLUSIONS: In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss.

Additional file2 .

Introduction: Abnormal cardiac mitochondrial function and energetics may be a unifying feature in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), while transient pulmonary congestion during exercise is an important determinant of reduced exercise capacity and symptoms. Hypothesis: We hypothesized that a gradient of myocardial energetic impairment exists across the spectrum of HFpEF and limits cardiac reserve during exercise, leading to transient pulmonary congestion. Methods: 43 patients across the spectrum of diastolic dysfunction and HFpEF (age-matched controls n=11; type 2 diabetes (T2DM) n=9; HFpEF n=14; severe diastolic dysfunction due to cardiac amyloid n=9) underwent assessment of cardiac energetics (myocardial phosphocreatine to ATP ratio, PCr/ATP) and function using CMR, and lung water using a novel MR proton density mapping sequence. Studies were performed at rest and during exercise (20 W for 6 minutes). Results: Paralleling the stepwise decline in diastolic function across the groups (E/e’ ratio p Conclusion: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF, leading to impaired cardiac functional reserve and transient exercise-induced pulmonary congestion.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously demonstrated decreased energy reserves in the form of phosphocreatine to adenosine-tri-phosphate ratio (PCr/ATP) in the hearts of patients with type 2 diabetes (T2DM). Recent 31P-MRS techniques using 7T systems, e.g. long mixing time stimulated echo acquisition mode (STEAM), allow deeper insight into cardiac metabolism through assessment of inorganic phosphate (Pi) content and myocardial pH, which play pivotal roles in energy production in the heart. Therefore, we aimed to further explore the cardiac metabolic phenotype in T2DM using STEAM at 7T. Seventeen patients with T2DM and twenty-three healthy controls were recruited and their cardiac PCr/ATP, Pi/PCr and pH were assessed at 7T. Diastolic function of all patients with T2DM was assessed using echocardiography to investigate the relationship between diastolic dysfunction and cardiac metabolism. Mirroring the decreased PCr/ATP (1.70±0.31 vs. 2.07±0.39; p2 = 0.33; p = 0.02) in T2DM. No correlation was observed between diastolic function and Pi/PCr and (R2 = 0.16; p = 0.21). In addition, we did not observe any correlation between cardiac PCr/ATP and Pi/PCr (p = 0.19). Using STEAM 31P-MRS at 7T we have for the first time explored Pi/PCr in the diabetic human heart and found it increased when compared to healthy controls. The lack of correlation between measured PCr/ATP and Pi/PCr suggests that independent mechanisms might contribute to these perturbations.

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

The subject of "fairness" in artificial intelligence (AI) refers to assessing AI algorithms for potential bias based on demographic characteristics such as race and gender, and the development of algorithms to address this bias. Most applications to date have been in computer vision, although some work in healthcare has started to emerge. The use of deep learning (DL) in cardiac MR segmentation has led to impressive results in recent years, and such techniques are starting to be translated into clinical practice. However, no work has yet investigated the fairness of such models. In this work, we perform such an analysis for racial/gender groups, focusing on the problem of training data imbalance, using a nnU-Net model trained and evaluated on cine short axis cardiac MR data from the UK Biobank dataset, consisting of 5,903 subjects from 6 different racial groups. We find statistically significant differences in Dice performance between different racial groups. To reduce the racial bias, we investigated three strategies: (1) stratified batch sampling, in which batch sampling is stratified to ensure balance between racial groups; (2) fair meta-learning for segmentation, in which a DL classifier is trained to classify race and jointly optimized with the segmentation model; and (3) protected group models, in which a different segmentation model is trained for each racial group. We also compared the results to the scenario where we have a perfectly balanced database. To assess fairness we used the standard deviation (SD) and skewed error ratio (SER) of the average Dice values. Our results demonstrate that the racial bias results from the use of imbalanced training data, and that all proposed bias mitigation strategies improved fairness, with the best SD and SER resulting from the use of protected group models., Comment: MICCAI 2021 conference

Additional file 1. Additional reference ranges. Tables reporting additional normal reference ranges of mitral and tricuspid annular dimensions and tethering indices.

Additional file 1: Table S1. Reproducibility of strain parameters. Table S2. Diagnostic accuracy of predicting new onset AF. Table S3. Differences in age and rate of hypertension between those with and without sarcomeric variants. Figure S1. Flow chart showing inclusion of subjects. Figure S2. Survival curve for HCM patients.

Additional file 1: Supplementary material.

Purpose: To demonstrate the feasibility and performance of a fully automated deep learning framework to estimate myocardial strain from short-axis cardiac magnetic resonance tagged images. Methods and Materials: In this retrospective cross-sectional study, 4508 cases from the UK Biobank were split randomly into 3244 training and 812 validation cases, and 452 test cases. Ground truth myocardial landmarks were defined and tracked by manual initialization and correction of deformable image registration using previously validated software with five readers. The fully automatic framework consisted of 1) a convolutional neural network (CNN) for localization, and 2) a combination of a recurrent neural network (RNN) and a CNN to detect and track the myocardial landmarks through the image sequence for each slice. Radial and circumferential strain were then calculated from the motion of the landmarks and averaged on a slice basis. Results: Within the test set, myocardial end-systolic circumferential Green strain errors were -0.001 +/- 0.025, -0.001 +/- 0.021, and 0.004 +/- 0.035 in basal, mid, and apical slices respectively (mean +/- std. dev. of differences between predicted and manual strain). The framework reproduced significant reductions in circumferential strain in diabetics, hypertensives, and participants with previous heart attack. Typical processing time was ~260 frames (~13 slices) per second on an NVIDIA Tesla K40 with 12GB RAM, compared with 6-8 minutes per slice for the manual analysis. Conclusions: The fully automated RNNCNN framework for analysis of myocardial strain enabled unbiased strain evaluation in a high-throughput workflow, with similar ability to distinguish impairment due to diabetes, hypertension, and previous heart attack., Comment: accepted in Radiology Cardiothoracic Imaging

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kfCK ) for healthy volunteers and obese patients. TRiST measures kfCK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kfCK measurement during

Supplemental Digital Content is available in the text., Background: Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders. Methods: Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders. Results: The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter

Background: Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. Methods: 27 HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-magnetic resonance spectroscopy (1H-MRS) to measure MTG (lipid/water, %), 31P-MRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking magnetic resonance imaging for diastolic strain rate. Results: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45±0.25% vs. 0.64±0.16%, p=0.009) and reduced PCr/ATP (1.60±0.09 vs. 2.00±0.10, p=0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. Conclusions: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF., This work was supported by Chest Heart and Stroke Association, Scotland. MM acknowledges support from the National University of Malaysia and Ministry of Higher Education Malaysia. SN and OR acknowledge support from the Oxford NIHR Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence. JES is a Senior BHF Basic Science Research Fellow (FS/11/50/29038). CTR is funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society [098436/Z/12/Z/B]. OR is a BHF Clinical Intermediate Research Fellow FS/16/70/32157.

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kfCK ) for healthy volunteers and obese patients. TRiST measures kfCK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kfCK measurement during

Background: The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools, e.g. image segmentation methods, are employed to derive quantitative measures or biomarkers for later analyses. Manual inspection and visual QC of each segmentation isn't feasible at large scale. However, it's important to be able to automatically detect when a segmentation method fails so as to avoid inclusion of wrong measurements into subsequent analyses which could lead to incorrect conclusions. Methods: To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4,800 cardiac magnetic resonance scans. We then apply our method to a large cohort of 7,250 cardiac MRI on which we have performed manual QC. Results: We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4,800 scans for which manual segmentations were available. We mimic real-world application of the method on 7,250 cardiac MRI where we show good agreement between predicted quality metrics and manual visual QC scores. Conclusions: We show that RCA has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study., Comment: 14 pages, 7 figures, Journal of Cardiovascular Magnetic Resonance

Accelerating the acquisition of magnetic resonance imaging (MRI) is a challenging problem, and many works have been proposed to reconstruct images from undersampled k-space data. However, if the main purpose is to extract certain quantitative measures from the images, perfect reconstructions may not always be necessary as long as the images enable the means of extracting the clinically relevant measures. In this paper, we work on jointly predicting cardiac motion estimation and segmentation directly from undersampled data, which are two important steps in quantitatively assessing cardiac function and diagnosing cardiovascular diseases. In particular, a unified model consisting of both motion estimation branch and segmentation branch is learned by optimising the two tasks simultaneously. Additional corresponding fully-sampled images are incorporated into the network as a parallel sub-network to enhance and guide the learning during the training process. Experimental results using cardiac MR images from 220 subjects show that the proposed model is robust to undersampled data and is capable of predicting results that are close to that from fully-sampled ones, while bypassing the usual image reconstruction stage., Comment: This work is published at MLMIR 2018: Machine Learning for Medical Image Reconstruction

Figure S2. Animations of the first four PCA components. (PPTX 2780 kb)

Large prospective epidemiological studies acquire cardiovascular magnetic resonance (CMR) images for pre-symptomatic populations and follow these over time. To support this approach, fully automatic large-scale 3D analysis is essential. In this work, we propose a novel deep neural network using both CMR images and patient metadata to directly predict cardiac shape parameters. The proposed method uses the promising ability of statistical shape models to simplify shape complexity and variability together with the advantages of convolutional neural networks for the extraction of solid visual features. To the best of our knowledge, this is the first work that uses such an approach for 3D cardiac shape prediction. We validated our proposed CMR analytics method against a reference cohort containing 500 3D shapes of the cardiac ventricles. Our results show broadly significant agreement with the reference shapes in terms of the estimated volume of the cardiac ventricles, myocardial mass, 3D Dice, and mean and Hausdorff distance., Comment: Accepted for publication in MICCAI 2019

Figure S1 â Detailed effect of CMR scan on occupational disposal. (PPTX 68 kb)

Aims Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97–13.48 g] to 6.30 g (IQR 1.38–17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (≺MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate ≺1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85–13.79; P = 0.002). Conclusion Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.

Synopsis: Determination of human cardiac Pi using 31P-MRS is challenging as the resonance frequency of Pi is concealed by a close resonating 2,3-DPG signal originating from blood. Long TR acquisition using adiabatic excitation at 7T can compensate for the rapid blood signal replacement in partially-saturated short TR scans. In order to quantify Pi concentration in vivo, knowledge about longitudinal relaxation of Pi is still required. We have measured the T1 of Pi in 4 healthy volunteers at 7T using dual-TR method and used this value to quantify cardiac Pi concentration in 8 healthy volunteers., We acknowledge financial support from a Sir Henry Dale Fellowship awarded by the Wellcome Trust and the Royal Society (098436/Z/12/Z), and from Slovak Grant Agencies VEGA (2/0001/17) and APVV (15-0029).

Image demonstrating visual assessment and comparison between automated segmentation and manual segmentation. (PDF 210 kb)

Background In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD). Objectives The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography. Methods Fifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements. Results In patients with NOCAD, myocardium with IMR 0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (, Central Illustration

CMR Cooperative web database: Clinical Outcomes. Common cardiovascular outcomes and their recurrent statuses can be collected. All dates are encrypted by a siteâ s own created encryption key. (PDF 99Â kb)

List of current GCMR Steering Committee Members. (PDF 306Â kb)

CMR Cooperative web database: User Access Management. Each participating site will assign its own site account administrator(s), who will administer the siteâ s usersâ levels and durations of account access. (PDF 75 kb)

CMR Cooperative web database: Segmental Myocardial Viability. Collection of segmental myocardial viability according to the AHA 17-segmental model. (PDF 110Â kb)

CMR Cooperative web database: A Sample Cardiac Computed Tomography (CCT) Page. (PDF 195Â kb)

CMR Cooperative web database: Quantitative CMR Data. Data entry for left and right ventricular measurements. “White” fields are data that need to be entered whereas “grey” fields are automatically calculated. (PDF 135 kb)

CMR Cooperative web database: Patient Medical History. (PDF 175Â kb)

Supplementary materials. (PDF 475 kb)

CMR Cooperative web database: Medications. A medication dictionary allows searching using either brand or generic drug names and automated entry of drug names into the database. In addition, medications are automatically categorized into specific drug classes for the ease of pooling multicenter data. (PDF 153Â kb)

CMR Cooperative web database: Segmental Myocardial Perfusion by CMR. Collection of segmental perfusion defects according to the AHA 17-segmental model, during stress and rest hemodynamic states. (PDF 173Â kb)

Enrichment of the peroxisomal marker protein Pex3p in the peroxisomal fraction. (PDF 271 kb)

Rationale: The recent development of hyperpolarized 13C Magnetic Resonance Spectroscopy (MRS) has made it possible to measure cellular metabolism in vivo, in real time. Objective: By comparing participants with and without type 2 diabetes (T2DM), we report the first case-control study to use this technique to record changes in cardiac metabolism in the healthy and diseased human heart. Methods and Results: Thirteen people with type 2 diabetes (HbA1c 6.9{plus minus}1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics (31P-MRS) and lipid content (1H-MRS) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1-13C]pyruvate MR spectra were also acquired and in five of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75g oral glucose challenge. Downstream metabolism of [1-13C]pyruvate via pyruvate dehydrogenase (PDH, [13C]bicarbonate), lactate dehydrogenase ([1-13C]lactate) and alanine transaminase ([1-13C]alanine) was assessed. Metabolic flux through cardiac PDH was significantly reduced in the people with type 2 diabetes (Fasted:0.0084{plus minus}0.0067[Control] vs. 0.0016{plus minus}0.0014[T2DM], Fed:0.0184{plus minus}0.0109 vs. 0.0053{plus minus}0.0041, p=.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge (p

AIMS: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. METHODS AND RESULTS: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (

BACKGROUND: Cardiovascular phosphorus MR spectroscopy (31P-CMRS) is a powerful tool for probing energetics in the human heart, through quantification of phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. In principle, 31P-CMRS can also measure cardiac intracellular pH (pHi) and the free energy of ATP hydrolysis (ΔGATP). However, these require determination of the inorganic phosphate (Pi) signal frequency and amplitude that are currently not robustly accessible because blood signals often obscure the Pi resonance. Typical cardiac 31P-CMRS protocols use low (e.g. 30°) flip-angles and short repetition time (TR) to maximise signal-to-noise ratio (SNR) within hardware limits. Unfortunately, this causes saturation of Pi with negligible saturation of the flowing blood pool. We aimed to show that an adiabatic 90° excitation, long-TR, 7T 31P-CMRS protocol will reverse this balance, allowing robust cardiac pHi measurements in healthy subjects and patients with hypertrophic cardiomyopathy (HCM). METHODS: The cardiac Pi T1 was first measured by the dual TR technique in seven healthy subjects. Next, ten healthy subjects and three HCM patients were scanned with 7T 31P-MRS using long (6 s) TR protocol and adiabatic excitation. Spectra were fitted for cardiac metabolites including Pi. RESULTS: The measured Pi T1 was 5.0 ± 0.3 s in myocardium and 6.4 ± 0.6 s in skeletal muscle. Myocardial pH was 7.12 ± 0.04 and Pi/PCr ratio was 0.11 ± 0.02. The coefficients of repeatability were 0.052 for pH and 0.027 for Pi/PCr quantification. The pH in HCM patients did not differ (p = 0.508) from volunteers. However, Pi/PCr was higher (0.24 ± 0.09 vs. 0.11 ± 0.02; p = 0.001); Pi/ATP was higher (0.44 ± 0.14 vs. 0.24 ± 0.05; p = 0.002); and PCr/ATP was lower (1.78 ± 0.07 vs. 2.10 ± 0.20; p = 0.020), in HCM patients, which is in agreement with previous reports. CONCLUSION: A 7T 31P-CMRS protocol with adiabatic 90° excitation and long (6 s) TR gives sufficient SNR for Pi and low enough blood signal to permit robust quantification of cardiac Pi and hence pHi. Pi was detectable in every subject scanned for this study, both in healthy subjects and HCM patients. Cardiac pHi was unchanged in HCM patients, but both Pi/PCr and Pi/ATP increased that indicate an energetic impairment in HCM. This work provides a robust technique to quantify cardiac Pi and pHi.

Figure S1. Shape changes due to (a) previous MI, (b) angina, (c) obesity, (d) diabetes, (e) high cholesterol, (f) sex and (h) age, adjusted for other factors. Colors denote difference from the mean shape in mm (red outward, blue inward) for factor positive (Positive) and factor negative (Negative) groups. Outward directions are shown on the top right picture. Top row: anterior view of the RV (left) and LV (right). Bottom row: posterior view (left: LV, right: RV). Histograms show morphometric scores for reference healthy group and factor positive group. (PPTX 8496 kb)

OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

CMR data for scan-rescan results compared to interval scan results. (DOCX 11Â kb)

CMR data for scan-rescan results compared to interval scan results. (DOCX 11Â kb)