BACKGROUND:Mixed venous oxygen saturation (SvO2), measured with right heart catheterization, is a crucial prognostic tool in patients with heart failure. The prognostic significance of SvO2 estimated noninvasively using cardiovascular magnetic resonance (CMR) from the T2 of intracardiac blood pools remains unknown. OBJECTIVES:The objective of the study was to develop a CMR model of mixed venous saturation (imaging-derived SvO2 [iSvO2]), and establish if it is associated with future adverse events in heart failure. METHODS:The iSvO2 was modeled in the discovery cohort (N = 30), who underwent CMR T2 mapping and invasive right heart catheterization, by linear regression. The validation cohort of 628 patients with recently diagnosed heart failure underwent clinical assessment, CMR, and follow-up (median 3 years [IQR: 1.5-4.8]) for a primary endpoint of all-cause mortality or heart failure hospitalization. RESULTS:Significant positive correlation was found between the ratio of right ventricular blood pool T2/left ventricular blood pool T2 and invasive mixed venous oxygen saturation (R = 0.82; 95% CI: 0.66-0.91; P < 0.001), giving the equation: iSvO2 = 95·(RV-T2BP/LV-T2BP). In the validation cohort, there was a strong association between iSvO2 and the primary endpoint (HR: 0.66 for 10% change in iSvO2; 95% CI: 0.54-0.81; P < 0.001), which remained significant after adjusting for age, sex, left ventricular ejection fraction, right ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, NYHA functional class, and diabetes. CONCLUSIONS:The CMR iSvO2, measured from simple T2 maps of left and right ventricular blood pool, allows accurate estimation of the invasive SvO2. In a real-world heart failure registry, iSvO2 is an independent predictor of mortality and heart failure hospitalization.

Background and purpose: The use of magnetic resonance imaging (MRI) for radiotherapy (RT) simulation has grown, prompting quality assurance (QA) guidelines by the Institute of Physics and Engineering in Medicine (IPEM) and the American Association of Physicists in Medicine (AAPM). This study compares a novel multimodality anthropomorphic phantom to an American College of Radiology (ACR) phantom for a subset of these MRI-specific QA tests in RT. Materials and methods: A novel 3D-printed multimodality head-and-neck anthropomorphic phantom was compared to an ACR large MRI phantom. IPEM and AAPM-recommended QA tests were conducted, including informatics/connectivity/data transfer, MRI-CT registration, end-to-end QA, and signal-to-noise ratio (SNR)/ percentage integral uniformity (PIU) assessments using RT accessories. Results: Both phantoms were suitable for informatics/connectivity/data transfer. In MRI-CT registration, no errors were found; the ACR phantom offered more quantitative landmarks, while the anthropomorphic phantom provided limited structures. Both phantoms achieved target registration errors (TREs) below 0.97 mm and dice similarity coefficient (DSC) values above 0.9, meeting guidelines. For end-to-end QA, the anthropomorphic phantom facilitated dose measurements of 1.994 Gy versus a calculated 2.01 Gy (-0.8 %). SNR and PIU assessments showed higher values in radiology setups compared to RT setups for both phantoms. Conclusions: Multimodality anthropomorphic phantoms compatible with dosimetric equipment allow realistic end-to-end QA, unlike the ACR phantom. While the ACR phantom is suitable for informatics and MRI-CT registration, anthropomorphic phantoms better represent clinical scenarios. For comprehensive QA, both ACR and anthropomorphic phantoms are required. Additionally, large field-of-view (FOV) phantoms are crucial for evaluating large FOV MRI distortions.

Objective: This study aims to identify and evaluate suitable and stable materials for developing a head and neck anthropomorphic multimodality phantom for radiotherapy purposes. These materials must mimic human head and neck tissues in both computed tomography (CT) and magnetic resonance imaging (MRI) and maintain stable imaging properties over time and after radiation exposure, including the high levels associated with linear accelerator (linac) use. Approach: Various materials were assessed by measuring their CT numbers and T1 and T2 relaxation times. These measurements were compared to literature values to determine how closely the properties of the candidate materials resemble those of human tissues in the head and neck region. The stability of these properties was evaluated monthly over a year and after radiation exposure to doses up to 1000 Gy. Statistical analyzes were conducted to identify any significant changes over time and after radiation exposure. Main results: 10% and 12.6% Polyvinyl alcohol cryogel (PVA-c) both exhibited T1 and T2 relaxation times and CT numbers within the range appropriate for brain grey matter. 14.3% PVA-c and some plastic-based materials matched the MRI properties of brain white matter, with CT numbers close to the clinical range. Additionally, some plastic-based materials showed T1 and T2 relaxation times consistent with MRI properties of fat, although their CT numbers were not suitable. Over time and after irradiation, 10% PVA-c maintained consistent properties for brain grey matter. 12.6% PVA-c's T1 relaxation time decreased beyond the range after the first month. Significance: This study identified 10% PVA-c as a substitute for brain grey matter, demonstrating stable imaging properties over a year and after radiation exposure up to 1000 Gy. However, the results highlight a need for further research to find additional materials to accurately simulate a wider range of human tissues.

Background Patients with diabetes demonstrate early left ventricular systolic dysfunction. Notably reduced global longitudinal strain (GLS) is related to poor outcomes, the underlying pathophysiology is however still not clearly understood. We hypothesized that pathophysiologic changes with microvascular dysfunction and interstitial fibrosis contribute to reduced strain. Methods 211 patients with type 2 diabetes and 25 control subjects underwent comprehensive cardiovascular phenotyping by magnetic resonance imaging. Myocardial blood flow (MBF), perfusion reserve (MPR), extracellular volume (ECV), and 3D feature tracking GLS and global circumferential (GCS) and radial strain (GRS) were quantified. Results Patients (median age 57 [IQR 50, 67] years, 70% males) had a median diabetes duration of 12 [IQR 6, 18] years. Compared to control subjects GLS, GCS, and GRS were reduced in the total diabetes cohort, and GLS was also reduced in the sub-group of patients without diabetic complications compared to control subjects (controls − 13.9 ± 2.0%, total cohort − 11.6 ± 3.0%; subgroup − 12.3 ± 2.6%, all p < 0.05). Reduced GLS, but not GCS or GRS, was associated with classic diabetes complications of albuminuria (UACR ≥ 30 mg/g) [β (95% CI) 1.09 (0.22–1.96)] and autonomic neuropathy [β (95% CI) 1.43 (0.54–2.31)] but GLS was not associated with retinopathy or peripheral neuropathy. Independently of ECV, a 10% increase in MBF at stress and MPR was associated with higher GLS [multivariable regression adjusted for age, sex, hypertension, smoking, and ECV: MBF stress (β (95% CI) − 0.2 (− 0.3 to − 0.08), MPR (β (95% CI) − 0.5 (− 0.8 to − 0.3), p < 0.001 for both]. A 10% increase in ECV was associated with a decrease in GLS in univariable [β (95% CI) 0.6 (0.2 to 1.1)] and multivariable regression, but this was abolished when adjusted for MPR [multivariable regression adjusted for age, sex, hypertension, smoking, and MPR (β (95% CI) 0.1 (− 0.3 to 0.6)]. On the receiver operating characteristics curve, GLS showed a moderate ability to discriminate a significantly lowered stress MBF (AUC 0.72) and MPR (AUC 0.73). Conclusions Myocardial microvascular dysfunction was independent of ECV, a biomarker of myocardial fibrosis, associated with GLS. Further, 3D GLS could be a potential screening tool for myocardial microvascular dysfunction. Future directions should focus on confirming these results in longitudinal and/or interventional studies.

Objective. This study aimed to optimise Cone Beam Computed Tomography (CBCT) protocols for head and neck (H&N) radiotherapy treatments using a 3D printed anthropomorphic phantom. It focused on precise patient positioning in conventional treatment and adaptive radiotherapy (ART). Approach. Ten CBCT protocols were evaluated with the 3D-printed H&N anthropomorphic phantom, including one baseline protocol currently used at our centre and nine new protocols. Adjustments were made to milliamperage and exposure time to explore their impact on radiation dose and image quality. Additionally, the effect on image quality of varying the scatter correction parameter for each of the protocols was assessed. Each protocol was compared against a reference CT scan. Usability was assessed by three Clinical Scientists using a Likert scale, and statistical validation was performed on the findings. Main results. The work revealed variability in the effectiveness of protocols. Protocols optimised for lower radiation exposure maintained sufficient image quality for patient setup in a conventional radiotherapy pathway, suggesting the potential for reducing patient radiation dose by over 50% without compromising efficacy. Optimising ART protocols involves balancing accuracy across brain, bone, and soft tissue, as no single protocol or scatter correction parameter achieves optimal results for all simultaneously. Significance. This study underscores the importance of optimising CBCT protocols in H&N radiotherapy. Our findings highlight the potential to maintain the usability of CBCT for bony registration in patient setup while significantly reducing the radiation dose, emphasizing the significance of optimising imaging protocols for the task in hand (registering to soft tissue or bone) and aligning with the as low as reasonably achievable principle. More studies are needed to assess these protocols for ART, including CBCT dose measurements and CT comparisons. Furthermore, the novel 3D printed anthropomorphic phantom demonstrated to be a useful tool when optimising CBCT protocols.

Abstract Background Patients with diabetes often develop heart failure with preserved ejection and often demonstrate early indications of myocardial dysfunction by decreased strain, notably the global longitudinal (GLS). The underlying myocardial phenotypical changes in patients with diabetes are coronary microvascular dysfunction and myocardial interstitial fibrosis. The relation of these to strain-indicators of early systolic dysfunction is not established. Purpose We hypothesized that coronary microvascular function and interstitial fibrosis contribute to the subclinical myocardial dysfunction seen in patients with diabetes. Method With gadolinium contrast and adenosine-stress magnetic resonance imaging, we determined myocardial blood flow (MBF) and perfusion ratio (MPR) and extracellular volume (ECV; an imaging biomarker of diffuse fibrosis) in 211 patients with type 2 diabetes without macrovascular coronary artery disease and 25 control subjects. Left ventricular (LV) function was determined from its ejection fraction and 3D feature tracking of GLS, circumferential (GCS), and radial strains (GRS). Results Without a significant age- or sex-differences to control subjects, patients (median age 57 years [IQR 50, 67], 70% males) had a median diabetes duration of 12 [IQR 6, 18] years. LV ejection fraction was normal and similar to controls. Compared to control subjects (GLS -13.9±2.0%), GLS, GCS and GRS were reduced in the total diabetes cohort, and GLS was reduced also in the subgroup of patients without any diabetes complications (total -11.6±3.0%; without-complications -12.3±2.6%). GLS, but not GCS or GRS or LVEF, was associated with albuminuria (b (95%CI) 1.09 (0.22-1.96)) and autonomic neuropathy (b (95%CI) 1.43 (0.54-2.31)). Independently of ECV, a 10% increase in MBF at adenosine-stress and MPR was associated with improved GLS in uni- and multivariable regression analyses. A 10% increase in ECV was associated with a decrease in GLS in univariable and multivariable regression analysis, but this was abolished when adjusted for MPR. GLS showed a moderate ability to discriminate a significantly lowered myocardial blood flow at stress defined as <1.49 mL/min/g (AUC 0.72, GLS threshold -11.5%; sensitivity 75% and specificity 53%) and myocardial perfusion ratio defined as as <2.1 (AUC 0.73, GLS threshold -10.8% resulted in a sensitivity of 71% and a specificity of 70%). GLS had a poor ability to predict increased extracellular volume defined as > 31% (AUC 0.60, GLS threshold -13.5 resulted in a sensitivity of 72% and a specificity of 34%). Conclusion Of the two important phenotypical changes seen with type 2 diabetes, microvascular dysfunction and fibrosis, coronary microvacular dysfunction demonstrates the more important relation to early systolic compromise as determined from the left ventricle global longitudinal strain.Associations of Systolic parametersROC curve

Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p < 0.0001) and lower rest myocardial blood flow (MBF, 0.5 ± 0.1 vs. 0.6 ± 0.1 ml/g/min, p < 0.0001). On 24-h ECG, athletes with fibrosis had greater burden of premature ventricular beats (0.3 ± 0.6 vs. 0.05 ± 0.2%, p = 0.03), with higher prevalence of ventricular couplets and triplets (33 vs. 8%, p = 0.02). In veteran endurance athletes, myocardial fibrosis is common and associated with an increased burden of ventricular ectopy. Possible mechanisms include inflammation and blood pressure. Further studies are needed to establish whether fibrosis increases risk of malignant arrhythmic events.

PURPOSE:Guidelines recommend measuring myocardial extracellular volume (ECV) using T1 -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS). METHODS:Twenty-five patients with severe AS and 5 healthy controls were recruited. T1 measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T1 measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T1 measurements and a two-site exchange model (2SXM) accounting for WX. RESULTS:Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%). CONCLUSION:Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

Introduction Histological studies show that myocardial fibrosis accompanies cellular hypertrophy in severe aortic stenosis (AS). Following aortic valve replacement (AVR), left ventricular hypertrophy regresses by 20%-30% by one year (1) and both cellular hypertrophy and fibrosis may regress as early as 6 months post AVR (2, 3). With T1 mapping, CMR can measure diffuse fibrosis by quantifying extracellular volume fraction (ECV) which reflects the fraction of the myocardium occupied by the extracellular matrix and is an independent predictor of mortality and outcome in patients with severe AS (4). Previous methods of measuring T1 and quantifying ECV in patients with severe AS have used Modified Look-Locker Inversion recovery (MOLLI) sequences and have shown a significant reduction in both cell volume and extracellular matrix volume 12 months post AVR(5). We aimed to investigate the changes in ECV seen pre and post AVR, using multiparametric SAturation-recovery single-SHot Acquisition (mSASHA) which has higher accuracy and precision due to its reduced sensitivity to T2 (6). This is particularly important as the T2 of blood changes markedly after contrast administration (7). Methods 16 patients with severe AS referred for AVR were recruited after consent. Mean age was 66 ± 6 years with 56% male. Patients were scanned before (visit 1) and after AVR (visit 2). T1 measurements were made on a 3 T Siemens system using mSASHA before contrast and at 10 minutes post gadobutrol injection (0.15 mmol/kg) as per recommendations by SCMR for calculation of ECV (8) . Derived indexed cell volume and derived indexed matrix volume were calculated from the product of left ventricular mass index ´ [1-ECV] and ECV, respectively as previously described.(5) Results Visit 2 data were acquired 167 ± 44 days post AVR. There was significant reduction in left ventricular hypertrophy, left ventricular end-diastolic volume and left ventricular mass (table 1, figure 1). Post AVR there was a significant reduction in derived indexed cell volume and, while there was a significant increase in ECV, there was no significant change in derived indexed matrix volume (table 2, figure 2). Conclusion For the first time using mSASHA, we have shown that in patients with severe AS, less than 6 months post AVR, there is a significant reduction in cell volume (derived indexed cell volume decreases) with no significant change in matrix volume (derived indexed matrix volume remains stable). Further studies will need to be undertaken to determine if matrix volume decreases at 12 months using mSASHA. Conflict of Interest No

Abstract Background Diffuse myocardial fibrosis and microvascular dysfunction are suggested to underlie cardiac dysfunction in patients with type 2 diabetes, but studies investigating their relative impact are lacking. We aimed to study imaging biomarkers of these and hypothesized that fibrosis and microvascular dysfunction would affect different phases of left ventricular (LV) diastole. Methods In this cross-sectional study myocardial blood flow (MBF) at rest and adenosine-stress and perfusion reserve (MPR), as well as extracellular volume fraction (ECV), were determined with cardiovascular magnetic resonance (CMR) imaging in 205 patients with type 2 diabetes and 25 controls. Diastolic parameters included echocardiography-determined lateral e’ and average E/e’, and CMR-determined (rest and chronotropic-stress) LV early peak filling rate (ePFR), LV peak diastolic strain rate (PDSR), and left atrial (LA) volume changes. Results In multivariable analysis adjusted for possible confounders including each other (ECV for blood flow and vice versa), a 10% increase of ECV was independently associated with ePFR/EDV (rest: β = − 4.0%, stress: β = − 7.9%), LAmax /BSA (rest: β = 4.8%, stress: β = 5.8%), and circumferential (β = − 4.1%) and radial PDSR (β = 0.07%/sec). A 10% stress MBF increase was associated with lateral e′ (β = 1.4%) and average E/e’ (β = − 1.4%) and a 10% MPR increase to lateral e′ (β = 2.7%), and average E/e’ (β = − 2.8%). For all the above, p < 0.05. No associations were found with longitudinal PDSR or left atrial total emptying fraction. Conclusion In patients with type 2 diabetes, imaging biomarkers of microvascular dysfunction and diffuse fibrosis impacts diastolic dysfunction independently of each other. Microvascular dysfunction primarily affects early left ventricular relaxation. Diffuse fibrosis primarily affects diastasis. Trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331. Date of registration: February 18, 2016.

Background Cardiac MRI is an important imaging tool in congenital cardiac disease, but its use has been limited in the neonatal population as general anesthesia has been needed for breath‐holding. Technological advances in four‐dimensional (4D) flow MRI have now made nonsedated free‐breathing acquisition protocols a viable clinical option, but the method requires prospective validation in neonates. Purpose To test the feasibility of compressed sensing (CS) 4D flow MRI in the neonatal population and to compare with standard previously validated two‐dimensional (2D) phase‐contrast (PC) flow MRI. Study type Prospective, cohort, image quality. Population A total of 14 healthy neonates (median [range] age: 2.5 [0–80] days; 8 male). Field Strength and Sequence Noncontrast 2D cine gradient echo sequence with through‐plane velocity encoding (PC) sequence and compressed sensing (CS) three‐dimensional (3D), time‐resolved, cine phase‐contrast MRI with 3D velocity‐encoding (4D flow MRI) at 3 T. Assessment Aortic 2D PC, and aortic, pulmonary trunk and superior vena cava CS 4D flow MRI were acquired using the feed and wrap technique (nonsedated) and quantified using commercially available software. Aortic flow and peak velocity were compared between methods. Internal consistency of 4D flow MRI was determined by comparing mean forward flow of the main pulmonary artery (MPA) vs. the sum of left and right pulmonary artery flows (LPA and RPA) and by comparing mean ascending aorta forward flow (AAo) vs. the sum of superior vena cava (SVC) and descending aorta flows (DAo). Statistical Tests Flow and peak‐velocity comparisons were assessed using paired t ‐tests, with P < 0.05 considered significant, and Bland–Altman analysis. Interobserver and intraobserver agreement and internal consistency were analyzed by intraclass correlation co‐efficient (ICC). Results There was no statistically significant difference between ascending aortic forward flow between 2D PC and CS 4D Flow MRI ( P = 0.26) with a bias of 0.11 mL (−0.59 to 0.82 mL) nor peak velocity ( P = 0.11), with a bias of −5 cm/sec and (−26 to 16 cm/sec). There was excellent interobserver and intraobserver agreement for each vessel (interobserver ICC: AAo 1.00; DAo 0.94, SVC 0.90, MPA 0.99, RPA 0.98, LPA 0.96; intraobserver ICC: AAo 1.00; DAo 0.99, SVC 0.98, MPA 1.00, RPA 1.00, LPA 0.99). Internal consistency measures showed excellent agreement for both mean forward flow of main pulmonary artery vs. the sum of left and right pulmonary arteries (ICC: 0.95) and mean ascending aorta forward flow vs. the sum of superior vena cava and descending aorta flows (ICC: 1.00). Conclusion Sedation‐free neonatal feed and wrap MRI is well tolerated and feasible. CS 4D flow MRI quantification is similar to validated 2D PC free‐breathing imaging with excellent interobserver and intraobserver agreement. Evidence Level 1 Technical Efficacy Stage 2

Background and purpose:Improving the accuracy of brain tumour radiotherapy (RT) treatment planning is important to optimise patient outcomes. This systematic review investigates primary studies providing clinical evidence for the integration of quantitative magnetic resonance imaging (qMRI) biomarkers and MRI radiomics to optimise brain tumour RT planning. Materials and methods:PubMed, Scopus, Embase and Web of Science databases were searched for all years until June 21, 2022. The search identified original articles demonstrating clinical evidence for the use of qMRI biomarkers and MRI radiomics for the optimization of brain cancer RT planning. Relevant information was extracted and tabulated, including qMRI metrics and techniques, impact on RT plan optimization and changes in target and normal tissue contouring and dose distribution. Results:Nineteen articles met the inclusion criteria. Studies were grouped according to the qMRI biomarkers into: 1) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI; five studies); 2) diffusion tensor imaging (DTI; seven studies); and 3) MR spectroscopic imaging (MRSI; seven studies). No relevant MRI-based radiomics studies were identified. Integration of DTI maps offers the potential for improved organs at risk (OAR) sparing. MRSI metabolic maps are a promising technique for improving delineation accuracy in terms of heterogeneity and infiltration, with OAR sparing. No firm conclusions could be drawn regarding the integration of DWI metrics and PWI maps. Conclusions:Integration of qMRI metrics into RT planning offers the potential to improve delineation and OAR sparing. Clinical trials and consensus guidelines are required to demonstrate the clinical benefits of such approaches.

Background: Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials. Purpose: To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use. Methods: MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and 12 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites. Results: T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R-2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions. Conclusions: The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials. (C) 2021 The Author(s). Published by Elsevier B.V.

Abstract Background Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular (CV) mortality. Sodium–glucose-co transporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalisation for HF in T2D patients with high cardiovascular risk, despite only a modest improvement in glycemic 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. 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. Conclusions For the first time, we demonstrate that empagliflizon improves myocardial energetics and function, reduces myocardial cellular volume, and reduces NT-proBNP levels in patients with T2D. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation PCr/ATPLVEF