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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- Gestational diabetes mellitus (GDM) is the most prevalent metabolic disorder during pregnancy and is associated with increased risks of cardiovascular morbidity and mortality in later life. Compromised cardiac energy production is an important contributor to most forms of heart disease. The changes in myocardial energetics in GDM have not been characterized previously. Objective- We investigated if women with GDM in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function or tissue characteristics. Methods- Thirty-eight healthy pregnant (HP) women and thirty women with GDM were recruited. Participants underwent phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine to ATP ratio (PCr/ATP)), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS) and mitral in-flow E/A ratio. Results- Participants were matched for age, gestational age and ethnicity. The women with GDM had higher body-mass index (27±4 versus 33±5kg/m2; p=0.0001), systolic (115±11 versus 121±13mmHg; p=0.04) and diastolic (72±7 versus 76±9mmHg; p=0.04) blood pressure. There was no difference in NTproBNP concentrations between the groups. The women with GDM had lower myocardial PCr/ATP ratio (2.2±0.3 versus 1.9±0.4; p Conclusions- Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared to lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM.

A previously fit and well 30-year-old man presented with palpitations, fever, and pleuritic chest pain. Multimodality imaging and histopathology confirmed the diagnosis of primary cardiac angiosarcoma. We present the details of the presentation, diagnostic process using multimodality imaging, and clinical management. (Level of Difficulty: Beginner.), Central Illustration

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.

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 Using serial imaging over time, this case reviews the natural history of co-morbid Type two diabetes (T2D) and apical hypertrophic cardiomyopathy (HCM) and assesses the potential combined impact on myocardial structure and perfusion. Case summary A 59-year-old patient with concomitant T2D and an apical phenotype of HCM was seen over a 11-year period with a significant burden of anginal chest pain. Chest pain was refractory to anti-anginal medical therapy and persisted at on-going follow-up. Multi-modality imaging demonstrated significant deterioration in coronary microvascular function and increased myocardial scar burden despite unobstructed epicardial coronary arteries. Discussion Comorbidity with T2D and apical HCM resulted in a significant increase in myocardial fibrosis and deterioration in coronary microvascular function.

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 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.

Introduction: Despite the initial recovery from the acute COVID-19 infection, an increasing number of patients are experiencing a wide spectrum of symptoms more than 12 weeks after the index diagnosis. The underlying pathophysiology of post-acute sequelae of SARS-CoV-2 (PASC) syndrome remains unknown. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease. The relative concentration of phosphocreatine to ATP (PCr/ATP) measured non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) is a sensitive index of the myocardial energetic state. It is currently unknown whether PASC is associated with abnormalities of myocardial structure, function, perfusion and tissue characteristics or energetic derangement. Methods: A total of 13 patients with a clinical diagnosis of PASC syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and ten matching controls underwent 31P-MRS and CMR at 3T at a single time point. Results: Clinical characteristics and imaging results are provided in Table-1. Between the PASC syndrome patients and controls there were no differences in myocardial energetics (PCr/ATP), in cardiac structure (left ventricular volumes, mass), function (ejection fraction, global longitudinal strain), tissue characterization (T1 and extracellular volume fraction mapping, late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). Conclusion: Patients with a clinical PASC syndrome with no prior CVD exhibit no significant abnormalities in cardiac energetics, structure, function, myocardial blood flow or tissue characteristics.

Background: Pregnancy requires significant cardiometabolic adaptation and is therefore considered a “stress test” for future cardiovascular disease. Cardiovascular magnetic resonance (CMR) allows evaluation of cardiac structure, function and tissue characteristics with excellent reproducibility. There is scarcity of CMR data on pregnancy-associated cardiovascular adaptive changes. Moreover, no studies to date assessed the physiological impact of pregnancy on cardiac high energy phosphate metabolism, measured as the phosphocreatine (PCr)/ATP ratio, using 31 Phosphorus magnetic resonance spectroscopy ( 31 P-MRS). Objectives: We aimed to investigate the physiological effects of pregnancy in women in the third trimester of a healthy singleton pregnancy on cardiac energetics, function and tissue characteristics using 31 P-MRS and CMR at 3T. Methods: Thirty pregnant women and fifteen age-matching nulliparous healthy female controls were recruited. Results: Clinical characteristics and CMR/ 31 P-MRS results are provided in Table1.Resting heart rates and cardiac output were higher in pregnancy, with no significant differences in left-ventricular volumes, mass or ejection fraction, diastolic function (mitral in-flow E/A), global longitudinal strain or MAPSE. There were subtle reductions in cardiac PCr/ATP in pregnancy. Compared to non-pregnant controls, myocardial T1 was 2% higher in pregnant women, whilst T2 was 5% lower. Conclusions: Healthy pregnancy was associated with no significant changes in cardiac size, mass or function. Consistent with the haemodynamic changes in pregnancy, subtle reductions in cardiac energetics were detected, though these remained within normal range.CMR is well tolerated in pregnancy and may play a role in assessing cardiac involvement in women at risk of perinatal complications, offering the opportunity of early initiation of risk modifying treatment and prevention of adverse maternal cardiovascular outcomes.

Background: Due to varying cardiac workloads, efficient demand-supply matching is crucial for maintaining normal cardiac function. Cardiac metabolism is profoundly affected by changes in cardiac workload. There is scarcity of non-invasive studies evaluating how the heart adapts to hemodynamic stress in type 2 diabetes (T2D) patients. Objectives: Using cardiovascular magnetic resonance (CMR) and 31 Phosphorus MR spectroscopy ( 31 P-MRS) we assessed changes in cardiac energetics, perfusion, strain, systolic and diastolic function in response to increases in cardiac workload with dobutamine stress in T2D patients and healthy volunteers (HV). Methods: 24 T2D patients and 18 matched HV were recruited. Participants with ischemic heart disease were excluded. Results: Table-1 shows clinical and CMR/ 31 P-MRS data. Compared to HV, T2D patients showed reductions in left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at rest, and a blunted increase in LVEF and GLS during stress. Diastolic function was impaired in T2D with lower mitral in-flow E/A ratio compared to HV at rest, which was further reduced during stress in both groups. Stress myocardial blood flow was lower in T2D patients.Compared to HV, rest phosphocreatinine (PCr)/ATP ratio was 17% lower in T2D patients, with a further 8% reduction during stress. However, there was a more pronounced reduction in the PCr/ATP with stress in HV (33% relative reduction), although stress PCr/ATP remained numerically higher in HV compared to T2D patients. Conclusions: T2D is associated with blunted ability of the myocardium to significantly increase contractile function from rest to stress. Moreover, T2D patients show exacerbated reductions in myocardial energetics and diastolic function during stress. Although reductions in myocardial energetics and diastolic function in response to acute stress were also detected in HV, these assessments remained higher in HV at stress compared to T2D patients.

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.

Background Heart failure (HF) is a leading cardiovascular complication of type 2 diabetes (T2D). Coronary microvascular dysfunction (CMD) precedes HF in diabetes and carries important prognostic information. CMD is also evident in metabolically healthy obese individuals without diabetes or hypertension. Whether diabetes causes CMD in the absence of obesity is uncertain. The interrelation among visceral adiposity and CMD has not been assessed previously. Objectives We sought to better understand the links between visceral and epicardial adipose tissue (VAT and EAT respectively) distribution, insulin resistance with myocardial perfusion, energetics and function in asymptomatic lean (LnT2D) and overweight/obese T2D patients (ObT2D) without cardiovascular disease. Methods 62 participants [27 Ob-T2D, 15 Ln-T2D, and 20 overweight controls] were recruited. Subjects underwent cardiac and abdominal magnetic resonance imaging and 31P-magnetic resonance spectroscopy, for measurements of EAT and VAT areas, rest and adenosine stress myocardial blood flow (MBF), cardiac function and phosphocreatine to ATP ratio (PCr/ATP). Fasting blood samples were taken for plasma homeostasis model assessment of insulin resistance (HOMA-IR) index calculations. Results The biochemical characteristics and multiparametric MR results are given in Table 1 and results of Pearson's regression analysis in the entire study population are given in Table 2. Stress MBF was lowest in ObT2D, while rest MBF was highest in LnT2D. Left ventricular ejection fraction (LVEF) and myocardial PCr/ATP were similarly reduced in diabetes groups. In the absence of obesity, there was no significant increase in VAT, EAT or HOMA-IR in T2D patients compared to controls. BMI and VAT, negatively correlated with LVEF, and strain parameters. PCr/ATP correlated with LVEF, but not HOMA-IR. BMI, EAT and VAT all correlated significantly with HOMA-IR, and HOMA-IR correlated with cardiac functional parameters. There was no association between HOMA-IR and myocardial perfusion. Conclusions In this study CMD was only evident in ObT2D patients, with normal rest and stress MBF in LnT2D patients. Despite normal perfusion and no significant increase in insulin resistance, LVEF and myocardial PCr/ATP were similarly reduced in LnT2D and ObT2D, and PCr/ATP correlated with LVEF. This suggests that alterations in cardiac energy metabolism are mechanistically more relevant for the pathophysiology of diabetic cardiomyopathy in LnT2D patients. In the absence of correlation between insulin resistance and myocardial perfusion, factors like inflammation and altered adipokine profile may play important roles for the pathophysiology of CMD in ObT2D patients. A better understanding of the underlying pathophysiological mechanisms of diabetic cardiomyopathy in LnT2D and ObT2D may help to develop contemporary tailored treatment and prevention strategies to tackle excess heart failure risk. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): BHFWellcome trust Table 1Table 2

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.

Background Percutaneous mitral valve leaflet repair can be an effective treatment for primary mitral regurgitation (MR) patients deemed high-risk for surgery. Accurate assessment of cardiac reverse remodelling is essential to optimise future patient selection. Cardiovascular magnetic resonance (CMR) is the reference standard for cardiac volumetric assessment and compared to transthoracic echocardiography (TTE) provides superior reproducibility in MR quantification. Prior CMR studies have analysed cardiac reverse remodelling following percutaneous intervention in combined cohorts of primary and secondary MR patients. However, as aetiology of MR can significantly impact outcomes, focused studies are warranted. Therefore, we aimed to assess cardiac reverse remodelling and quantify changes in MR following percutaneous mitral valve leaflet repair for primary MR using the reference standard (CMR). Methods 12 patients with at least moderate-severe MR on TTE were prospectively recruited to undergo CMR imaging and 6-minute walk tests (6MWT) at baseline and 6 months following percutaneous mitral valve leaflet repair (MitraClip). CMR protocol involved: left-ventricular (LV) short axis cines (bSSFP, SENSE-2, 10mm, no gap), transaxial right-ventricular (RV) cines (bSSFP, SENSE-2, 8mm, no gap), two and four chamber cines and aortic through-plane phase contrast imaging, planned at the sino-tubular junction. MR was quantified indirectly using LV and aortic stroke volumes. Results 12 patients underwent percutaneous mitral valve leaflet repair (MitraClip) for posterior mitral valve leaflet prolapse, however 1 patient declined follow up after single-leaflet clip detachment resulting in 11 patients (age 83±5years, 9 male) completing follow up imaging. At 6-months: significant improvements occurred in New York Heart Association functional class and 6MWT distances (223±71m to 281±65m, p=0.005) (table 1) and significant reductions occurred in indexed left ventricular end-diastolic volumes (LVEDVi) (118±21ml/m2 to 94±27ml/m2, p=0.001), indexed left ventricular end-systolic volumes (58±19ml/m2 to 48±21ml/m2, p=0.007) and quantitated MR volume (55±22ml to 24±12ml, p=0.003) and MR fraction (49±9.4% to 29±14%, p≤0.001) (table 2). There were no statistically significant changes in left ventricular ejection fraction (LVEF), right ventricular dimensions/ejection fraction or bi-atrial dimensions (table 2). All patients demonstrated decreased LVEDVi and quantified MR (figure 1). Conclusion Successful percutaneous mitral valve leaflet repair for primary MR results in reduction in MR, positive LV reverse remodelling, preservation of LVEF, and functional improvements. Larger CMR studies are now required to further guide optimal patient selection. Conflict of Interest Nil

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.

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

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background The microstructural changes following myocardial infarction (MI) can be characterised in-vivo with cardiac diffusion tensor imaging (cDTI) imaging, using mean diffusivity (MD), fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA) maps. In this study, we use cDTI to explore the microstructural differences between subendocardial and transmural chronic infarct segments. Method Twenty STEMI patients (15 men, 5 women, mean age 59) underwent 3T CMR scan at 3 months following presentation (mean interval 107 ± 18 days). Scan protocol included: second order motion compensated (M012) free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2[3], 200s/mm2[3] and 500s/mm2[12], acquired resolution was 2.20x2.27x8mm3; cine gradient echo and LGE imaging. Average MD, FA, E2A and HA parameters were calculated on a 16-AHA-segmental level. 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. Infarct segments were identified using LGE; patients were categorised according to the maximal transmurality of their infarct segments, into subendocardial (50% LGE) MI. Results DTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Ten patients had transmural MI. The results are shown in table 1. Transmurally infarcted segments had significantly lower FA (FA subendocardial MI = 0.27 ± 0.04, FA transmural MI = 0.23 ± 0.02, p Conclusion Compared to subendocardial MI segments, the diffusion of water molecules is more isotropic in transmurally infarcted myocardium as evidenced by lower FA values, signifying increased structural disarray. The significantly lower E2A values suggest that laminar sheetlets of transmural infarct segments remain fixed at shallower angles during systole and are unable to reach their usual contractile configuration. The lower proportions of RHM on HA maps highlight the significantly greater loss of subendocardial cardiomyocytes in transmural infarct segments. Further studies are required to assess if these segmental changes can be predictive of long-term LV remodelling.

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

Funding Acknowledgements Type of funding sources: None. Background Percutaneous mitral valve leaflet repair can be an effective treatment for primary mitral regurgitation (MR) patients deemed high-risk for surgery. Accurate assessment of cardiac reverse remodelling is essential to optimise future patient selection. Cardiovascular magnetic resonance (CMR) is the reference standard for cardiac volumetric assessment and compared to transthoracic echocardiography (TTE) provides superior reproducibility in MR quantification. Prior CMR studies have analysed cardiac reverse remodelling following percutaneous intervention in combined cohorts of primary and secondary MR patients. However, as aetiology of MR can significantly impact outcomes, focused studies are warranted. Purpose Assess cardiac reverse remodelling and quantify changes in MR following percutaneous mitral valve leaflet repair for primary MR using the reference standard (CMR). Methods 12 patients with at least moderate-severe MR on TTE were prospectively recruited to undergo CMR imaging and 6-minute walk tests (6MWT) at baseline and 6 months following percutaneous mitral valve leaflet repair (MitraClip). CMR protocol involved: left-ventricular (LV) short axis cines (bSSFP, SENSE-2, 10mm, no gap), transaxial right-ventricular (RV) cines (bSSFP, SENSE-2, 8mm, no gap), two and four chamber cines and aortic through-plane phase contrast imaging, planned at the sino-tubular junction. MR was quantified indirectly using LV and aortic stroke volumes. Results 12 patients underwent percutaneous mitral valve leaflet repair (MitraClip) for posterior mitral valve leaflet prolapse, however 1 patient declined follow up after single-leaflet clip detachment resulting in 11 patients (age 83 ± 5years, 9 male) completing follow up imaging. At 6-months: significant improvements occurred in New York Heart Association functional class (Table 1) and 6MWT distances (223 ± 71m to 281 ± 65m, p = 0.005) and significant reductions occurred in indexed left ventricular end-diastolic volumes (LVEDVi) (118 ± 21ml/m2 to 94 ± 27ml/m2, p = 0.001), indexed left ventricular end-systolic volumes (58 ± 19ml/m2 to 48 ± 21ml/m2, p = 0.007) and quantitated MR volume (55 ± 22ml to 24 ± 12ml, p = 0.003) and MR fraction (49 ± 9.4% to 29 ± 14%, p= Conclusion Successful percutaneous mitral valve leaflet repair for primary MR results in reduction in MR, positive LV reverse remodelling, preservation of LVEF, and functional improvements. Larger CMR studies are now required to further guide optimal patient selection.

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.