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BackgroundMetformin is an antihyperglycemic agent frequently used in the treatment of Type 2 Diabetes Mellitus (T2DM). Patients with T2DM are at increased risk of cardiovascular diseases, including coronary artery disease (CAD), silent myocardial infarction (MI) and coronary microvascular dysfunction (CMD), all of which can be detected and quantified using Cardiovascular Magnetic Resonance (CMR). We explored the association between metformin use, stress Myocardial Blood Flow (MBF), Myocardial Perfusion Reserve (MPR), survival and major adverse cardiovascular and cerbrovasular events (MACCE; a composite of all-cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation) in patients with T2DM.MethodsA multi-centre study of patients with T2DM, and a cohort of healthy controls underwent quantitative myocardial perfusion CMR. Global MBF and MPR were derived using an automatic artificial intelligence-supported process. Multivariable regression analysis and cox proportional hazard models quantified associations between metformin use, MBF, MPR, all-cause death and MACCE.ResultsAnalysis included 572 patients with T2DM (68% prescribed metformin) with median follow-up 851 days (interquartile range 935-765). Metformin use was associated with an increase in MPR of 0.12 [0.08-0.40], P=0.004. There was a total of 82 (14.3%) first MACCE in all T2DM patients including a total of 25 (4.4%) deaths. Although the number of first MACCE events was similar for patients prescribed metformin (53 (14%)) compared to those who were not (29 (15.8%) (P=0.73)), there was a total of 9 deaths (2.3%) in patients prescribed metformin compred to 16 (8.7%) in patients who were not, adjusted hazard ratio 0.29 [95% CI 0.12-0.73] P=0.009).ConclusionIn patients with T2DM, metformin use is associated with higher MPR and improved survival.Clinical PerspectivePatients with Type 2 Diabetes Mellitus (T2DM) are at increased risk of cardiovascular disease. Cardiovascular Magnetic Resonane (CMR) can be used to detect and quantify absolute stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), both of which are objective measures of coronary microvascular function. Metformin is frequently used in the treatment of T2DM. We investigated the association between metformin use, CMR-derived stress MBF, MPR and clinical outcomes in patients with T2DM.In a longitudinal cohort study of patients with T2DM, metformin use was associated with higher MPR as a marker of microvascular function, and improved survival after adjusting for certain confounding parameters.Further prospective studies are needed to confirm the association between metformin use and improved MPR and reduced mortality, as well as to clarify the mechanisms responsible and quantify the dose these associated outcomes are observed.Central illustration

Background Measurement of peak velocities is important in the evaluation of heart failure. This study compared the performance of automated 4D flow cardiac MRI (CMR) with traditional transthoracic Doppler echocardiography (TTE) for the measurement of mitral inflow peak diastolic velocities. Methods Patients with Doppler echocardiography and 4D flow cardiac magnetic resonance data were included retrospectively. An established automated technique was used to segment the left ventricular transvalvular flow using short-axis cine stack of images. Peak mitral E-wave and peak mitral A-wave velocities were automatically derived using in-plane velocity maps of transvalvular flow. Additionally, we checked the agreement between peak mitral E-wave velocity derived by 4D flow CMR and Doppler echocardiography in patients with sinus rhythm and atrial fibrillation (AF) separately. Results Forty-eight patients were included (median age 69 years, IQR 63 to 76; 46% female). Data were split into three groups according to heart rhythm. The median peak E-wave mitral inflow velocity by automated 4D flow CMR was comparable with Doppler echocardiography in all patients (0.90 ± 0.43 m/s vs 0.94 ± 0.48 m/s, P = 0.132), sinus rhythm-only group (0.88 ± 0.35 m/s vs 0.86 ± 0.38 m/s, P = 0.54) and in AF-only group (1.33 ± 0.56 m/s vs 1.18 ± 0.47 m/s, P = 0.06). Peak A-wave mitral inflow velocity results had no significant difference between Doppler TTE and automated 4D flow CMR (0.81 ± 0.44 m/s vs 0.81 ± 0.53 m/s, P = 0.09) in all patients and sinus rhythm-only groups. Automated 4D flow CMR showed a significant correlation with TTE for measurement of peak E-wave in all patients group (r = 0.73, P P P P = 0.014). Excellent intra-and inter-observer variability was demonstrated for both parameters. Conclusion Automated dynamic peak mitral inflow diastolic velocity tracing using 4D flow CMR is comparable to Doppler echocardiography and has excellent repeatability for clinical use. However, 4D flow CMR can potentially underestimate peak velocity in patients with AF.

Purpose 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 its association with cardiac arrhythmia. Methods Fifty asymptomatic male endurance athletes (inclusion criteria: age ≥50, >10 hours/week training for >15 years) and 26 matched controls 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-hour ECG. Results Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral wall of the left ventricle. Blood pressure was reduced in athletes without fibrosis compared to controls, a trend not seen in athletes with fibrosis. Fibrotic areas compared to healthy myocardium had longer T2 time (44±4 vs 40±2ms, pConclusion In veteran endurance athletes, myocardial fibrosis is a common finding. Possible mechanisms for fibrosis include inflammation and blood pressure. Presence of myocardial fibrosis is associated with an increased burden of ventricular ectopy. Further studies are needed to establish whether fibrosis increases risk of malignant arrhythmic events.

Background The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. Methods Prospective case–control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. Results Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. Conclusions In this prospective case–control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Objective\ud \ud We aim to validate four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) peak velocity tracking methods for measuring the peak velocity of mitral inflow against Doppler echocardiography.\ud \ud \ud \ud Method\ud \ud Fifty patients were recruited who had 4D flow CMR and Doppler Echocardiography. After transvalvular flow segmentation using established valve tracking methods, peak velocity was automatically derived using three-dimensional streamlines of transvalvular flow. In addition, a static-planar method was used at the tip of mitral valve to mimic Doppler technique.\ud \ud \ud \ud Results\ud \ud Peak E-wave mitral inflow velocity was comparable between TTE and the novel 4D flow automated dynamic method (0.9 ± 0.5 vs 0.94 ± 0.6 m/s; p = 0.29) however there was a statistically significant difference when compared with the static planar method (0.85 ± 0.5 m/s; p = 0.01). Median A-wave peak velocity was also comparable across TTE and the automated dynamic streamline (0.77 ± 0.4 vs 0.76 ± 0.4 m/s; p = 0.77). A significant difference was seen with the static planar method (0.68 ± 0.5 m/s; p = 0.04). E/A ratio was comparable between TTE and both the automated dynamic and static planar method (1.1 ± 0.7 vs 1.15 ± 0.5 m/s; p = 0.74 and 1.15 ± 0.5 m/s; p = 0.5 respectively). Both novel 4D flow methods showed good correlation with TTE for E-wave (dynamic method; r = 0.70; P < 0.001 and static-planar method; r = 0.67; P < 0.001) and A-wave velocity measurements (dynamic method; r = 0.83; P < 0.001 and static method; r = 0.71; P < 0.001). The automated dynamic method demonstrated excellent intra/inter-observer reproducibility for all parameters.\ud \ud \ud \ud Conclusion\ud \ud Automated dynamic peak velocity tracing method using 4D flow CMR is comparable to Doppler echocardiography for mitral inflow assessment and has excellent reproducibility for clinical use.

Background: Left atrial (LA) dilatation is linked to cardiovascular disease and atrial fibrillation but its associations in athletes are unknown. The authors investigated whether aerobic fitness and clinical parameters are associated with LA dilatation and emptying fraction (EF) in endurance athletes. Materials & methods: 65 endurance athletes underwent cardiovascular magnetic resonance to assess LA size and function along with fitness assessment. 25 sedentary controls underwent an identical cardiovascular magnetic resonance protocol. Results: In athletes, LA volume index was elevated, while total and passive LAEFs were decreased versus sedentary controls. Increasing age and maximal oxygen uptake were associated with LA volume index. Only older age was associated with decreased total LAEF. Conclusion: LA dilatation in athletes is associated with increasing age and aerobic fitness rather than conventional cardiovascular risk factors.

Background Cardiac diffusion tensor imaging (cDTI) allows for in vivo characterization of myocardial microstructure. In cDTI, mean diffusivity and fractional anisotropy (FA)-markers of magnitude and anisotropy of diffusion of water molecules-are known to change after myocardial infarction. However, little is known about regional changes in helix angle (HA) and secondary eigenvector angle (E2A), which reflects orientations of laminar sheetlets, and their association with long-term recovery of left ventricular ejection fraction (LVEF). Purpose To assess serial changes in cDTI biomarkers in participants following ST-segment elevation myocardial infarction (STEMI) and to determine their associations with long-term left ventricular remodeling. Materials and Methods In this prospective study, 30 participants underwent cardiac MRI (3 T) after STEMI at 5 days and 3 months after reperfusion (National Institute of Health Research study no. 33963 and Research Ethics no. REC17/YH/0062). Spin-echo cDTI with second-order motion-compensation (approximate duration, 13 minutes; three sections; 18 noncollinear diffusion-weighted scans with b values of 100 sec/mm2 [three acquisitions], 200 sec/mm2 [three acquisitions], and 500 sec/mm2 [12 acquisitions]), functional images, and late gadolinium enhancement images were obtained. Multiple regression analysis was used to assess associations between acute cDTI parameters and 3-month LVEF. Results Acutely infarcted myocardium had reduced FA, E2A, and myocytes with right-handed orientation (RHM) on HA maps compared with remote myocardium (mean remote FA = 0.36 ± 0.02 [standard deviation], mean infarcted FA = 0.25 ± 0.03, P < .001; mean remote E2A = 55° ± 9, mean infarcted E2A = 49° ± 10, P < .001; mean remote RHM = 16% ± 6, mean infarcted RHM = 9% ± 5, P < .001). All three parameters (FA, E2A, and RHM) correlated with 3-month LVEF (r = 0.68, r = 0.59, and r = 0.53, respectively), with acute FA being independently predictive of 3-month LVEF (standardized β = 0.56, P = .008) after multivariable analysis adjusting for factors, including acute LVEF and infarct size. Conclusion After ST-segment elevation myocardial infarction, diffusion becomes more isotropic in acutely infarcted myocardium as reflected by decreased fractional anisotropy. Reductions in secondary eigenvector angle suggest that the myocardial sheetlets are unable to adopt their usual steep orientations in systole, whereas reductions in myocytes with right-handed orientation on helix angle maps are likely reflective of a loss of organization among subendocardial myocytes. Correlations between these parameters and 3-month left ventricular ejection fraction highlight the potential clinical use of cardiac diffusion tensor imaging after myocardial infarction in predicting long-term remodeling. © RSNA, 2021 Online supplemental material is available for this article.

Aims Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers. Methods and results A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = −0.43, P < 0.001 and r = −0.34, P < 0.001, respectively). Conclusion Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use.

Aims\ud \ud The clinical reliability of echocardiographic surrogate markers of left ventricular filling pressures (LVFPs) across different cardiovascular pathologies remains unanswered. The main objective was to evaluate the evidence of how effectively different echocardiographic indices estimate true LVFP.\ud \ud \ud Methods and results\ud \ud Design: this is a systematic review and meta‐analysis. Data source: Scopus, PubMed and Embase. Eligibility criteria for selecting studies were those that used echocardiography to predict or estimate pulmonary capillary wedge pressure or left ventricular end‐diastolic pressures. Twenty‐seven studies met criteria. Only eight studies (30%) reported both correlation coefficient and bias between non‐invasive and invasively measured LVFPs. The majority of studies (74%) recorded invasive pulmonary capillary wedge pressure as a surrogate for left ventricular end‐diastolic pressures. The pooled correlation coefficient overall was r = 0.69 [95% confidence interval (CI) 0.63–0.75, P < 0.01]. Evaluation by cohort demonstrated varying association: heart failure with preserved ejection fraction (11 studies, n = 575, r = 0.59, 95% CI 0.53–0.64) and heart failure with reduced ejection fraction (8 studies, n = 381, r = 0.67, 95% CI 0.61–0.72).\ud \ud \ud Conclusions\ud \ud Echocardiographic indices show moderate pooled association to invasively measured LVFP; however, this varies widely with disease state. In heart failure with preserved ejection fraction, no single echocardiography‐based metric offers a reliable estimate. In heart failure with reduced ejection fraction, mitral inflow‐derived indices (E/e′, E/A, E/Vp, and EDcT) have reasonable clinical applicability. While an integrated approach of several echocardiographic metrics provides the most promise for estimating LVFP reliably, such strategies need further validation in larger, patient‐specific studies.

Background Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D‐HF). Methods In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age‐matched controls (n = 25), DM (n = 10), CHF (n = 52), and D‐HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole‐body exercise capacity. Results Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D‐HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D‐HF patients only (P < 0.05), which strongly correlated to exercise capacity (R 2 = 0.64; P < 0.001). Mitochondrial impairments in D‐HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti‐oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D‐HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). Conclusions Patients with D‐HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D‐HF.

The accelerated risk of cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) requires further study of the underlying pathophysiology and determination of the at-risk RA phenotype. Our objectives were to describe the cardiac structure and function and arterial stiffness, and association with disease phenotype in patients with established) RA, in comparison to healthy controls, as measured by cardiovascular magnetic resonance imaging (CMR). 76 patients with established RA and no history of CVD/diabetes mellitus were assessed for RA and cardiovascular profile and underwent a non-contrast 3T-CMR, and compared to 26 healthy controls. A univariable analysis and multivariable linear regression model determined associations between baseline variables and CMR-measures. Ten-year cardiovascular risk scores were increased in RA compared with controls. Adjusting for age, sex and traditional cardiovascular risk factors, patients with RA had reduced left ventricular ejection fraction (mean difference − 2.86% (− 5.17, − 0.55) p = 0.016), reduced absolute values of mid systolic strain rate (p 2 (− 8.92, − 0.20), p = 0.041). CMR-measures predominantly associated with traditional cardiovascular risk factors; male sex and systolic blood pressure independently with increasing LVMI. Patients with established RA and no history of CVD have evidence of reduced LV systolic function and LVMI after adjustment for traditional cardiovascular risk factors; the latter suggesting cardiac pathology other than atherosclerosis in RA. Traditional cardiovascular risk factors, rather than RA disease phenotype, appear to be key determinants of subclinical CVD in RA potentially warranting more effective cardiovascular risk reduction programs.

Background: Previous studies in heart failure with reduced ejection fraction (HFrEF) suggest that skeletal muscle mitochondrial impairments are associated with exercise intolerance in men. However, the nature of this relationship in female patients remains to be elucidated. This study aimed to determine the relationship between skeletal muscle mitochondrial impairments and exercise intolerance in male and female patients with HFrEF. Methods: Mitochondrial respiration, enzyme activity, and gene expression were examined in pectoralis major biopsies from age‐matched male (n = 45) and female (n = 11) patients with HFrEF and healthy‐matched male (n = 24) and female (n = 11) controls. Mitochondrial variables were compared between sex and related to peak exercise capacity. Results: Compared with sex‐matched controls, complex I mitochondrial oxygen flux was 17% (P = 0.030) and 29% (P = 0.013) lower in male and female patients with HFrEF, respectively, which correlated to exercise capacity (r = 0.71; P > 0.0001). Female HFrEF patients had a 32% (P = 0.023) lower mitochondrial content compared with controls. However, after adjusting for mitochondrial content, male patients demonstrated lower complex I function by 15% (P = 0.030). Expression of key mitochondrial genes regulating organelle dynamics and maintenance (i.e. optic atrophy 1, peroxisome proliferator‐activated receptor γ coactivator‐1α, NADH:ubiquinone oxidoreductase core subunit S1/S3, and superoxide dismutase 2) were selectively lower in female HFrEF patients. Conclusions: These data provide novel evidence that HFrEF induces divergent sex‐specific mitochondrial phenotypes in skeletal muscle that predispose towards exercise intolerance, impacting mitochondrial ‘quantity’ in female patients and mitochondrial ‘quality’ in male patients. Therapeutic strategies to improve exercise tolerance in HFrEF should consider targeting sex‐specific mitochondrial abnormalities in skeletal muscle.

Aims The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40–49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF. Methods and results Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF. Conclusion Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy.

ObjectiveHandheld 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.MethodsMEDLINE 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.ResultsThirty-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.ConclusionThis 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 numberCRD42020182429.

Sodium–glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization for heart failure in type 2 diabetes (T2D) patients. Utilising cardiovascular magnetic resonance imaging (CMR) and 31phosphorus magnetic resonance spectroscopy(31P-MRS) in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2i empagliflozin on myocardial energetics, cellular volume, function and perfusion. Eighteen T2D patients underwent CMR and 31P-MRS scans before and after twelve-week empagliflozin treatment. Plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycaemic control underwent an identical scan protocol on a single visit. Empagliflozin treatment was associated with significant improvements in PCr/ATP ratio (1.52 to 1.76, p=0.009). This was accompanied by a 7% absolute increase in the mean LVEF (p=0.001), 3% absolute increase in the mean global longitudinal strain (p=0.01), 8 ml/m2 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 remodelling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate heart failure in T2D.

This study evaluated the potential associations between DT-CMR performed soon after STEMI and long-term adverse left ventricular (LV) remodeling following STEMI.Adverse LV remodeling post-ST-segment elevation myocardial infarction (STEMI) is associated with a poor prognosis, but the underlying mechanisms are not fully understood. Diffusion tensor (DT)-cardiac magnetic resonance (CMR) allows in vivo characterization of myocardial architecture and provides unique mechanistic insight into pathophysiologic changes following myocardial infarction.A total of 100 patients with STEMI underwent CMR at 5 days and 12 months post-reperfusion. The protocol included DT-CMR for assessing fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA), cine imaging for assessing LV volumes, and late gadolinium enhancement for calculating infarct and microvascular obstruction size. Adverse remodeling was defined as a 20% increase in LV end-diastolic volume at 12 months.A total of 32 patients experienced adverse remodeling at 12 months. Compared with patients without adverse remodeling, they had lower FA (0.23 ± 0.03 vs 0.27 ± 0.04; P 0.001), lower E2A (37 ± 6° vs 51 ± 7°; P 0.001), and, on HA maps, a lower proportion of myocytes with right-handed orientation (RHM) (8% ± 5% vs 17% ± 9%; P 0.001) in their acutely infarcted myocardium. On multivariable logistic regression analysis, infarct FA (odds ratio [OR]: 0.01; P = 0.014) and E2A (OR: 0.77; P = 0.001) were independent predictors of adverse LV remodeling after adjusting for LV ejection fraction and infarct size. There were no significant changes in infarct FA, E2A, or RHM between the 2 scans.Extensive cardiomyocyte disorganization (evidenced by low FA), acute loss of sheetlet angularity (evidenced by low E2A), and a greater loss of organization among cardiomyocytes with RHM, corresponding to the subendocardium, can be detected within 5 days post-STEMI. These changes persist post-injury, and low FA and E2A are independently associated with long-term adverse remodeling.

Objectives Four-dimensional flow CMR allows for a comprehensive assessment of the blood flow kinetic energy of the ventricles of the heart. In comparison to standard two-dimensional image acquisition, 4D flow CMR is felt to offer superior reproducibility, which is important when repeated examinations may be required. The objective was to evaluate the inter-observer and intra-observer reproducibility of blood flow kinetic energy assessment using 4D flow of the left ventricle in 20 healthy volunteers across two centres in the United Kingdom and the Netherlands. Data description This dataset contains 4D flow CMR blood flow kinetic energy data for 20 healthy volunteers with no known cardiovascular disease. Presented is kinetic energy data for the entire cardiac cycle (global), the systolic and diastolic components, in addition to blood flow kinetic energy for both early and late diastolic filling. This data is available for reuse and would be valuable in supporting other research, such as allowing for larger sample sizes with more statistical power for further analysis of these variables.

Cardiovascular magnetic resonance (CMR) imaging is a versatile tool that has established itself as the reference method for functional assessment and tissue characterisation. CMR helps to diagnose, monitor disease course and sub-phenotype disease states. Several emerging CMR methods have the potential to offer a personalised medicine approach to treatment. CMR tissue characterisation is used to assess myocardial oedema, inflammation or thrombus in various disease conditions. CMR derived scar maps have the potential to inform ablation therapy—both in atrial and ventricular arrhythmias. Quantitative CMR is pushing boundaries with motion corrections in tissue characterisation and first-pass perfusion. Advanced tissue characterisation by imaging the myocardial fibre orientation using diffusion tensor imaging (DTI), has also demonstrated novel insights in patients with cardiomyopathies. Enhanced flow assessment using four-dimensional flow (4D flow) CMR, where time is the fourth dimension, allows quantification of transvalvular flow to a high degree of accuracy for all four-valves within the same cardiac cycle. This review discusses these emerging methods and others in detail and gives the reader a foresight of how CMR will evolve into a powerful clinical tool in offering a precision medicine approach to treatment, diagnosis, and detection of disease.

Aims Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigenvector angle (E2A). In this cardiac magnetic resonance (CMR) study, we examine associations between perfusion and cDTI parameters to understand the sequence of pathophysiology and the interrelation between vascular function and underlying microstructure. Methods and results Twenty HCM patients underwent 3.0T CMR which included: spin-echo cDTI, adenosine stress and rest perfusion mapping, cine-imaging, and late gadolinium enhancement (LGE). Ten controls underwent cDTI. Myocardial perfusion reserve (MPR), MD, FA, E2A, and wall thickness were calculated per segment and further divided into subendocardial (inner 50%) and subepicardial (outer 50%) regions. Segments with wall thickness ≤11 mm, MPR ≥2.2, and no visual LGE were classified as ‘normal’. Compared to controls, ‘normal’ HCM segments had increased MD (1.61 ± 0.09 vs. 1.46 ± 0.07 × 10−3 mm2/s, P = 0.02), increased E2A (60 ± 9° vs. 38 ± 12°, P Conclusion In HCM patients, even in segments with normal wall thickness, normal perfusion, and no scar, diffusion is more isotropic than in controls, suggesting the presence of underlying cardiomyocyte disarray. Increased E2A suggests the myocardial sheetlets adopt hypercontracted angulation in systole. Increased MD, most notably in the subendocardium, is suggestive of regional remodelling which may explain the reduced subendocardial blood flow.

Background Biventricular volume and great vessel flow assessment during continuous supine free-breathing exercise cardiovascular magnetic resonance (Ex-CMR) has recently been validated in healthy volunteers using Compressed SENSEx3 (CS3) sequences. Exercise transthoracic echocardiography (TTE) provides prognostic information in primary mitral regurgitation (MR). Resting CMR offers reference standard biventricular assessment and MR quantification with superior reproducibility to TTE. Ex-CMR assessment of biventricular volumes and quantitated MR may offer additional prognostic information in primary MR. Therefore we aimed to determine the feasibility of biventricular assessment and MR quantification in primary MR patients during continuous supine Ex-CMR using CS3 sequences. Methods 10 asymptomatic patients with at least moderate primary MR on TTE (8 male, median age 62, 55-67years interquartile range) underwent continuous in-scanner (1.5T Philips Ingenia) supine cycle ergometer (Lode BV) Ex-CMR. Target heart rates (THR) were individually prescribed using heart rate reserve (HRR) and age predicted maximal heart rate model. Participants exercised for 2-minutes at no resistance, then an increase of 25-Watts every 2-minutes until THR achieved at low (30-39% HRR), then moderate (40-59% HRR) exercise. CMR imaging: free-breathing CS3 respiratory navigated short axis cine imaging and free-breathing CS3 aortic phase-contrast magnetic-resonance at rest, low and moderate exercise stages. MR was quantified indirectly from LV and aortic stroke volumes. Intra/inter-observer reproducibility was assessed by coefficient of variance (CV). Results All patients completed the Ex-CMR protocol without complication. During exercise, there were no statistically significant changes in biventricular volumes or global left ventricular ejection fraction (LVEF) (table 1). From rest to low and moderate exercise: right ventricular ejection fraction increased (55±5.4% to 60±6.0% and 63±6.6% respectively, p=0.001) and MR fraction decreased (40±14% to 36±11% and 30±15% respectively, p=0.006). Intra-observer reproducibility (table 2) was excellent (CV Conclusion Biventricular assessment and MR quantification during continuous supine Ex-CMR is feasible and reproducible in asymptomatic primary MR patients. Research assessing the techniques prognostic ability in primary MR patients is now warranted. Conflict of Interest Nil

Funding Acknowledgements Type of funding sources: None. Background Biventricular volume and great vessel flow assessment during continuous supine free-breathing exercise cardiovascular magnetic resonance (Ex-CMR) is feasible in healthy volunteers using Compressed SENSEx3 (CS3) sequences1. Exercise transthoracic echocardiography (TTE) provides prognostic information in primary mitral regurgitation (MR). Resting CMR offers reference standard biventricular assessment and MR quantification with superior reproducibility to TTE. Ex-CMR assessment of biventricular volumes and quantitated MR may offer additional prognostic information. Purpose Determine the feasibility of biventricular assessment and MR quantification in primary MR patients during continuous supine Ex-CMR using the recently validated protocol1. Methods 10 asymptomatic patients with at least moderate primary MR on TTE (8 male, median age 62, 55-67years interquartile range) underwent continuous in-scanner (1.5T Philips Ingenia) supine cycle ergometer (Lode BV) Ex-CMR. Target heart rates (THR) were individually prescribed using heart rate reserve (HRR) and age predicted maximal heart rate model. Participants exercised for 2-minutes at no resistance, then an increase of 25-Watts every 2-minutes until THR achieved at low (30-39% HRR), then moderate (40-59% HRR) stages. CMR imaging: free-breathing CS3 respiratory navigated short axis cine imaging and free-breathing CS3 aortic phase-contrast magnetic-resonance at rest, low and moderate exercise stages. MR was quantified indirectly from left ventricular (LV) and aortic stroke volumes. Intra/inter-observer reproducibility was assessed by coefficient of variance (CV). Results All patients completed the Ex-CMR protocol without complication. During exercise, no statistically significant changes occurred in LV volumes, global left ventricular ejection fraction (LVEF), right ventricular end-diastolic or systolic volumes (Table 1). From rest to low and moderate exercise: right ventricular ejection fraction increased (55 ± 5.4% to 60 ± 6.0% and 63 ± 6.6% respectively, p = 0.001) and MR fraction decreased (40 ± 14% to 36 ± 11% and 30 ± 15% respectively, p = 0.006) allowing effective forward LVEF (aortic stroke volume/ left ventricular end-diastolic volume) to increase (38 ± 9.3% to 43 ± 9.3% and 46 ± 11% respectively, p = 0.004). Intra-observer reproducibility (Table 2) was excellent (CV Conclusion Biventricular assessment and MR quantification during continuous supine Ex-CMR is feasible in asymptomatic primary MR patients, further research assessing the techniques prognostic ability is now warranted.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship and Wellcome Trust Background Cardiovascular disease represents the primary cause of death in patients with type 2 diabetes (T2D). Heart failure (HF) is the commonest initial presentation of cardiovascular disease in T2D. Development of HF in patients with T2D is associated with a 4 to 6-fold increase in mortality, making the prevention of cardiac dysfunction an important goal. The long-term impact of T2D on cardiac function in the absence of cardiovascular disease is unknown. This is the first prospective longitudinal study utilising cardiovascular magnetic resonance (CMR) to evaluate the impact of T2D on cardiac remodeling. Objectives To determine longitudinal changes in the phenotypic expression of heart disease in diabetes over 6 years, and examine the association of baseline blood and imaging biomarkers with remodeling over time in patients who remained free of cardiovascular/clinical events, and to report clinical outcomes in the entire cohort. Methods 100 asymptomatic T2D patients with no history of cardiovascular disease or hypertension were previously studied. Biventricular volumes, function, and myocardial strain were assessed by CMR and blood biomarkers taken. 6-year follow-up CMR was repeated in those without interim cardiovascular events. Results Of the 100 patients, 78 could be contacted for follow-up. 29 participants experienced cardiovascular/clinical events over 6 years. 32 patients who were asymptomatic and without events received follow-up CMR. The major adverse cardiovascular event rate (MI, angina, revascularisation, stroke, death) during the 6-year follow-up period, including the patients with a silent MI, amounted to 25% in this study with an overall clinical event rate of 35%. There were no significant changes in BP, BMI or HBA1c between baseline and follow-up (Table 1). Left ventricular end-diastolic-volume(p = 0.005), mass (p = 0.01), ejection fraction (p = 0.0001), and right ventricular end-diastolic-volume(p = 0.03) and ejection fraction(p = 0.003) reduced over time (Figure 2 and Table 1). Baseline plasma high-sensitivity cardiac-troponin-T (hs-cTnT) (R=-0.44; p = 0.01) was significantly associated with change in left ventricular ejection fraction over time. Conclusions Even in the absence of overt clinical CAD, significant valvular disease, uncontrolled hypertension or change in BMI, T2D results in significant reductions in cardiac size and biventricular systolic function over time. The major adverse cardiovascular event rate (MI, angina, revascularisation, stroke, death) during the 6-year follow-up period was high in diabetes patients (25%). Plasma biomarker hs-cTnT measured at baseline was associated with change in LV systolic function over the 6-year follow-up period. hs-cTnT could potentially have a significant utility as a risk-predicting tool for cardiac dysfunction in T2D patients.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Cardiac diffusion tensor imaging (cDTI) is a novel technique for the non-invasive assessment of myocardial microstructure. It allows in-vivo characterisation of microstructural changes post myocardial infarction (MI). Previously published evidence shows significant loss of sheetlet orientation as derived by cDTI secondary eigenvector (E2A), and loss of subendocardial cardiomyocytes derived by reductions in the proportions of myocytes with right-handed orientation (RHM) on helix angle (HA) maps. The assessment of myocardial strain by feature tracking (FT) allows the measurement of radial strain (RS), thought to be driven by the dynamic reorientation of laminar sheetlets, and longitudinal strain (LS), which is thought to relate to subendocardial function. We sought to explore the relationship between the strain and cDTI parameters in patients at 3 months following ST-elevation MI (STEMI). Methods Twenty five STEMI patients (M:F = 18:7, mean age 58 ± 9) underwent 3T CMR scan (mean interval 106 ± 17 days) with the following protocol: second order motion compensated (M2), free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2, 200s/mm2 and 500s/mm2, acquired resolution was 2.20*2.27*8mm3; cine gradient echo and Late Gadolinium Enhancement (LGE) imaging. HA maps were described by dividing values into left-handed HA (LHM, -90< HA < -30), circumferential HA (CM, -30° < HA < 30°), and right-handed HA (RHM, 30° < HA < 90°) and reported as relative proportions. Segmental analysis were undertaken to derive: HA proportions, E2A, longitudinal strain and LGE%. Segments positive for LGE were classed as infarct segments. Results cDTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Mean ejection fraction was 47 ± 8% with mean LGE in the infarcted segment of 57 ± 27%. Mean radial strain was 21 (95% confidence interval, 15-26). The mean E2A was 44 (95% confidence interval 41-47). There was a significant correlation between segmental radial strain and segmental E2A in infarcted segments (p Conclusion Through the combined use of cDTI and FT in patients with chronic infarcts, our results show that the loss of sheetlet orientation assessed using E2A, correlates with worsening radial strain. Segments with less subendocardial cardiomyocytes, evidenced by a lower proportion of myocytes with right-handed orientation on HA maps, correlated with worse longitudinal strain. While this could potentially elucidate the complex association between myocardial microstructure and regional function, further studies are needed to define the incremental clinical value of cDTI.

Objectives In a cohort of type 2 diabetes (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 (figure 1). 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 T2D patients (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 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%) (figure 2). 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 (tables 1 & 2). The mean ECV was unchanged. Baseline plasma high-sensitivity cardiac-troponin-T (hs-cTnT) was significantly associated with 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. Conflict of Interest Nil

Background Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular (CV) mortality. Sodium–glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization for HF in T2D patients with high cardiovascular risk, despite only a modest improvement in glycaemic control. Restoring cellular energy homeostasis and reversing adverse cardiac remodelling in diabetes have been speculated as a potential metabolic modulatory effect of SGLT2 inhibitors leading to their beneficial CV outcomes. Myocardial energy deficient states can be detected non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS). Objectives Utilising cardiovascular magnetic resonance imaging (CMR) and 31P-MRS in a single centre longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics, function, perfusion, and myocardial cellular volume in patients with T2D. Methods Eighteen consecutive T2D patients who were commenced on empagliflozin in cardiometabolic optimisation clinics underwent CMR and 31P-MRS scans before and after twelve-week empagliflozin treatment, and plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. (Table 1) Ten controls with no diabetes underwent an identical 31P-MRS and CMR protocol on a single visit. Results When compared to controls, patients with T2D showed: lower myocardial energetics (1.52±0.40 vs 2.20±0.5, p=0.0005), lower stress myocardial blood flow (1.60±0.50 vs 2.10±0.50, p=0.02) and lower left ventricular ejection fraction (52±13% vs 63±4%, p=0.01). Treatment with empagliflozin led to significant improvements in myocardial energetics (PCr/ATP: 1.52 to 1.76, p=0.009). This was accompanied by a relative 13% improvement in left ventricular ejection fraction (p=0.001), 3% improvement in global longitudinal strain (p=0.01), 61% reduction in NTproBNP (p=0.05), and 9% reduction in myocardial cell volume (p=0.04). No significant change in myocardial blood flow or diastolic strain was detected (table 1). Conclusions Empagliflizon improves myocardial energetics and function, reduces myocardial cellular volume, and reduces NT-proBNP levels in patients with T2D (figure 1). This study, by using the myocardial phosphocreatine to ATP ratio to monitor the early energetic response of the heart to treatment, and CMR to monitor structural and functional changes, provides significant novel insights into potential mechanisms by which empagliflozin exerts its beneficial cardiovascular effects. Conflict of Interest NONE

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance imaging (MRI) is an emerging technique used for intra-cardiac blood flow assessment. The role of 4D flow cardiovascular MRI in the assessment of trans-valvular flow in patients with atrial fibrillation (AF) has not previously been assessed. The purpose of this study was to assess the feasibility, image quality, and internal validity of 4D flow cardiovascular MRI in the quantification of trans-valvular flow in patients with AF. Methods: Patients with AF and healthy controls in sinus rhythm underwent cardiovascular MRI, including 4D flow studies. Quality assurance checks were done on the raw data and streamlines. Consistency was investigated by trans-valvular flow assessment between the mitral valve (MV) and the aortic valve (AV). Results: Eight patients with AF (88% male, mean age 62±13 years, mean heart rate (HR) 83±16 beats per minute (bpm)) were included and compared with ten healthy controls (70% male, mean age 41±20 years, mean HR 68.5±9 bpm). All scans were of either good quality with minimal blurring artefacts, or excellent quality with no artefacts. No significant bias was observed between the AV and MV stroke volumes in either healthy controls (–4.8, 95% CI –15.64 to 6.04; P=0.34) or in patients with AF (1.64, 95% CI –4.7 to 7.94; P=0.56). A significant correlation was demonstrated between MV and AV stroke volumes in both healthy controls (r=0.87, 95% CI 0.52 to 0.97; P=0.001) and in AF patients (r=0.82, 95% CI 0.26 to 0.97; P=0.01). Conclusions: In patients with AF, 4D flow cardiovascular MRI is feasible with good image quality, allowing for quantification of trans-valvular flow.

Background: Late gadolinium enhancement (LGE) imaging is well validated for the diagnosis and quantification of myocardial infarction (MI). 2D LGE imaging involves multiple breath‐holds for acquisition of short‐axis slices to cover the left ventricle (LV). 3D LGE methods cover the LV in a single breath‐hold; however, breath‐hold duration is typically long with images susceptible to motion artifacts. Purpose/Hypothesis: To assess a single breath‐hold 3D mDIXON LGE pulse sequence for image quality and quantitation of MI. Study Type: Prospective. Population: Ninety‐ two patients with prior MI. Field Strength/Sequence: 1.5T cardiac MRI protocol using both conventional 2D phase sensitive inversion recovery and 3D mDIXON LGE imaging 10 minutes following contrast administration in random order to avoid bias. Assessment: Data were analyzed qualitatively for image quality (three observers). Quantitative assessment of myocardial scar mass (full‐width half‐maximum), scar transmurality, and contrast‐to‐noise ratio measurements were performed. Time for 2D and 3D LGE imaging was recorded. Statistical Tests: Paired Student's t‐test, Wilcoxon rank test, Cohen κ statistic, Pearson correlation, linear regression, and Bland–Altman analysis. Results: Image quality scores were comparable between 3D and 2D LGE (1.4 ± 0.6 vs. 1.3 ± 0.5; P = 0.162). 3D LGE was associated with greater scar tissue mass (3D: 18.9 ± 17.5 g vs. 2D: 17.8 ± 16.2 g P = 0.03), although this difference was less pronounced when scar tissue was expressed as %LV mass (3D: 13.4 ± 9.9% vs. 2D: 12.7 ± 9.5% P = 0.07). For 3D vs. 2D scar mass there was a strong and significant positive correlation; Bland–Altman analysis showed mean mass bias of 1.1 g (95% confidence interval [CI]: –5.7 to 7.9). Segmental level agreement of scar transmurality between 3D and 2D LGE at the clinical viability threshold of 50% transmurality was excellent (κ = 0.870). 3D image acquisition (15.6 ± 1.4 sec) was just 5% of time required for 2D images (311.6 ± 43.2 sec) P < 0.0001. Data Conclusion: Single breath‐hold 3D mDIXON LGE imaging allows quantitative assessment of MI mass and transmurality, with comparable image quality, in vastly shorter overall acquisition time compared with standard 2D LGE imaging. Level of Evidence: 1 Technical Efficacy: Stage 2

Background Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) disease. In patients with T2D and established CV disease, selective inhibitors of sodium–glucose cotransporter 2 (SGLT2) have been shown to decrease CV and all-cause mortality, and heart failure (HF) admissions. Utilising CV magnetic resonance imaging (CMR) and continuous glucose monitoring (CGM) by FreeStyle Libre Pro Sensor, we aim to explore the mechanisms of action which give Empagliflozin, an SGLT2 inhibitor, its beneficial CV effects and compare these to the effects of dipeptidyl peptidase-4 inhibitor Sitagliptin. Methods This is a single centre, open-label, cross-over trial conducted at the Leeds Teaching Hospitals NHS Trust. Participants are randomised for the order of treatment and receive three months therapy with Empagliflozin, and three months therapy with Sitagliptin sequentially. Twenty eight eligible T2D patients with established ischemic heart disease will be recruited. Patients undergo serial CMR scans on 3 visits, at week 0, week 12 and week 24 of the study.Discussion The primary outcome measure is the myocardial perfusion reserve in remote myocardium. The secondary outcome measures are myocardial fibrosis, ECV, aortic distensibility, LV/RV volume and function, and the relationship between glycemic markers and CV parameters.We hypothesize that Empaglifozin treatment is associated with improvements in myocardial blood flow and reductions in myocardial interstitial fibrosis, independent of CGM measured glycemic control in patients with T2D and established CV disease. Trial registration This study has full research ethics committee approval (REC: 18/YH/0190) and data collection is anticipated to finish in December 2021. This study was retrospectively registered at https://doi.org/10.1186/ISRCTN82391603 and monitored by the University of Leeds. The study results will be submitted for publication within 6 months of completion.

Background: Left ventricular maximum wall thickness (MWT) is central to diagnosis and risk stratification of hypertrophic cardiomyopathy, but human measurement is prone to variability. We developed an automated machine learning algorithm for MWT measurement and compared precision (reproducibility) with that of 11 international experts, using a dataset of patients with hypertrophic cardiomyopathy. Methods: 60 adult patients with hypertrophic cardiomyopathy, including those carrying hypertrophic cardiomyopathy gene mutations, were recruited at three institutes in the UK from August, 2018, to September, 2019: Barts Heart Centre, University College London Hospital (The Heart Hospital), and Leeds Teaching Hospitals NHS Trust. Participants had two cardiovascular magnetic resonance scans (test and retest) on the same day, ensuring no biological variability, using four cardiac MRI scanner models represented across two manufacturers and two field strengths. End-diastolic short-axis MWT was measured in test and retest by 11 international experts (from nine centres in six countries) and an automated machine learning method, which was trained to segment endocardial and epicardial contours on an independent, multicentre, multidisease dataset of 1923 patients. Machine learning MWT measurement was done with a method based on solving Laplace's equation. To assess test–retest reproducibility, we estimated the absolute test–retest MWT difference (precision), the coefficient of variation (CoV) for duplicate measurements, and the number of patients reclassified between test and retest according to different thresholds (MWT >15 mm and >30 mm). We calculated the sample size required to detect a prespecified MWT change between pairs of scans for machine learning and each expert. Findings: 1440 MWT measurements were analysed, corresponding to two scans from 60 participants by 12 observers (11 experts and machine learning). Experts differed in the MWT they measured, ranging from 14·9 mm (SD 4·2) to 19·0 mm (4·7; p

Contains fulltext : 245701.pdf (Publisher’s version ) (Open Access) 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.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation HRUK Background. Four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) imaging provides quantification of intra-cavity left ventricular (LV) flow kinetic energy (KE) parameters in three dimensions. Myocardial infarction (MI) is known to cause acute alterations in intra-cardiac blood flow but assessments of longitudinal changes are lacking. Purpose. Assess longitudinal changes in LV flow post ST-elevation myocardial infarction (STEMI). Method. Twenty acutely reperfused STEMI patients (13 men, 7 women, mean age 54 ± 9 years) underwent 3T CMR acutely (within 5-7 days) and 3 months post-MI. CMR protocol included functional imaging, late gadolinium enhancement and 4D flow. Using Q-MASS, LV KE parameters were derived and indexed to LV end-diastolic volume (LVKEiEDV). Based on acute ejection fraction (EF), patients were grouped as follows: preserved (pEF) EF >50%, reduced (rEF) EF Results. Out of 20 patients, 13 had rEF acutely (7 mild rEF, 6 moderate to severe rEF). Acute LVKEiEDV parameters varied significantly between pEF and rEF (Table). At 3 months, pEF and mild rEF patients showed a significant (P Conclusion. Following MI, 4D flow LVKE derived biomarkers significantly decreased over time in pEF and mild rEF groups but not in moderate to severe rEF group. 4D flow assessment might provide incremental prognostic value beyond EF assessment alone. Table pEF (n = 7) rEF (n = 13) V1 V2 P-value V1 V2 P-value EF(%) 56 ± 5 55 ± 4 0.40 41 ± 7 47 ± 9 0.01 Infarct Size(%) 31 ± 20 15 ± 9 0.04 18 ± 13† 16 ± 11 0.41 LV KEiEDV parameters Average(µJ/ml) 9 ± 2 7 ± 2 0.02 10 ± 3† 8 ± 3 0.01 Minimal(µJ/ml) 1 ± 0.6 1 ± 0.5 0.46 1.3 ± 0.5 1 ± 0.6 0.03 Systolic(µJ/ml) 10 ± 4 7 ± 2

Funding Acknowledgements Type of funding sources: None. Background Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. Objectives We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. Methods We recruited 110 patients (84 in final analysis) into two observational CMR studies. Patients (n = 34) with a dual chamber device and preserved atrioventricular (AV) conduction underwent CMR in two asynchronous pacing modes (AOO & DOO) to compare intrinsic conduction with RV pacing. Patients (n = 50) with high-grade AV block underwent CMR before and 6 months after pacemaker implantation to investigate the long-term effects of RV pacing. Results: The three key findings were 1) Initiation of RV pacing in patients with fibrosis, compared to those without, was associated with greater immediate changes in both LV end-systolic volume index (LVESVi) (5.3 ± 3.5 vs 2.1 ± 2.4 mL/m2; p Conclusions Fibrosis detected on CMR is associated with immediate and long-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure prior to pacemaker implantation. Characteristics before and after pacing Study 1 No fibrosis (n = 16) Fibrosis (n = 18) AOO DOO p-value AOO DOO p-value LVEDVi - mL/m² 66 ± 13 66 ± 12 0.67 78 ± 14 79 ± 13 0.34 LVESVi - mL/m² 30 ± 10 32 ± 9 0.003 38 ± 11 43 ± 12

Objectives SSc primary heart involvement (SSc-pHI) is a significant cause of mortality. We aimed to characterize and identify predictors of subclinical SSc-pHI using cardiovascular MRI. Methods A total of 83 SSc patients with no history of cardiovascular disease or pulmonary arterial hypertension and 44 healthy controls (HCs) underwent 3 Tesla contrast-enhanced cardiovascular MRI, including T1 mapping and quantitative stress perfusion. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide were also measured. Results Cardiovascular MRI revealed a lower myocardial perfusion reserve in the SSc patients compared with HCs {median (interquartile range (IQR)] 1.9 (1.6–2.4) vs 3 (2–3.6), P < 0.001}. Late gadolinium enhancement, indicating focal fibrosis, was observed in 17/83 patients but in none of the HCs, with significantly higher extracellular volume (ECV), suggestive of diffuse fibrosis, in SSc vs HC [mean (s.d.) 31 (4) vs 25 (2), P Conclusion Subclinical SSc-pHI is characterized by myocardial microvasculopathy, diffuse and focal myocardial fibrosis but preserved myocardial contractile function. This subclinical phenotype of SSc-pHI was associated with high-sensitivity troponin I, N-terminal pro-brain natriuretic peptide, SSc disease severity and complicated peripheral vasculopathy. These data provide information regarding the underlying pathophysiological processes and provide a basis for identifying individuals at risk of SSc-pHI.