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OBJECTIVE Sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS Liraglutide (mean −1,144 steps/day; 95% CI −2,069 to −220), empagliflozin (−1,132 steps/day; −1,739, −524), and sitagliptin (−852 steps/day; −1,625, −78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D (n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls (n = 25). T2D remission was associated with a lower leptin–adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.

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

Objectives This study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA). Background The impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain. Methods A total of 1,236 consecutive patients (age: 60 ± 9 years; 41% female) who underwent serial CCTA at an interval of ≥2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta. Results With increasing luminal HU ( 500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P Conclusions Low tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411 )

Highlights • Activated platelets are associated with AS. • Platelets are a player in bioprosthetic valve dysfunction. • Randomized trials have assessed clinical outcomes with various antiplatelet/anticoagulation strategies in patients undergoing TAVR., Summary Aortic stenosis (AS) is the most common heart valve disease requiring surgery in developed countries, with a rising global burden associated with aging populations. The predominant cause of AS is believed to be driven by calcific degeneration of the aortic valve and a growing body of evidence suggests that platelets play a major role in this disease pathophysiology. Furthermore, platelets are a player in bioprosthetic valve dysfunction caused by their role in leaflet thrombosis and thickening. This review presents the molecular function of platelets in the context of recent and rapidly evolving understanding the role of platelets in AS, both of the native aortic valve and bioprosthetic valves, where there remain concerns about the effects of subclinical leaflet thrombosis on long-term prosthesis durability. This review also presents the role of antiplatelet and anticoagulation therapies on modulating the impact of platelets on native and bioprosthetic aortic valves, highlighting the need for further studies to determine whether these therapies are protective and may increase the life span of surgical and transcatheter aortic valve implants. By linking molecular mechanisms through which platelets drive disease of native and bioprosthetic aortic valves with studies evaluating the clinical impact of antiplatelet and antithrombotic therapies, we aim to bridge the gaps between our basic science understanding of platelet biology and their role in patients with AS and ensuing preventive and therapeutic implications., Central Illustration

We present a case of subclavian artery perforation with mediastinal hematoma following elective percutaneous coronary intervention. A conservative approach was preferred over invasive correction. Although no outcome data exist specifically for subclavian artery injury, registry data in patients with iatrogenic aortic dissection suggest that long-term outcomes are good without vascular repair. (Level of Difficulty: Advanced.), Central Illustration

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS. We pooled data (n = 148) from three randomised trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison to sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies on accelerometer-assessed physical activity. RESULTS: Liraglutide (-1144 steps/day; 95% CI -2069, -220), empagliflozin (-1132 steps/day; -1739, -524) and sitagliptin (-852 steps/day; -1625, -78) resulted in reduced total daily physical activity after 6 months (p< 0.01 vs. control). Moderate-to-vigorous intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS: The initiation of all glucose lowering therapies was associated with reduced physical activity, warranting further investigation.

Ischemic heart disease is the most common cause of mortality worldwide. The pathophysiology of myocardial infarction relates to temporal changes of atherosclerotic plaque culminating in plaque rupture, erosion or hemorrhage and the subsequent thrombotic response. Coronary computed tomographic angiography (CCTA) provides the ability to visualize and quantify plaque, and plaque progression can be measured on a per-patient basis by comparing findings of serial CCTA. The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry was established with the objective of identifying patterns of plaque progression in a large population. The registry comprises over 2000 patients with multiple CCTA scans performed at least two years apart. Unlike previous CCTA registries, a semi-automated plaque quantification technique permitting detailed analysis of plaque progression was performed on all patients with interpretable studies. Since the registry was established, 19 peer-reviewed publications were identified, and all are reviewed and summarized in this article.

To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D.Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D.At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training.Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.

Left ventricular (LV) strain measurements can be derived using cardiac MRI from routinely acquired balanced steady-state free precession (bSSFP) cine images.To compare the interfield strength agreement of global systolic strain, peak strain rates and artificial intelligence (AI) landmark-based global longitudinal shortening at 1.5 T and 3 T.Prospective.A total of 22 healthy individuals (mean age 36 ± 12 years; 45% male) completed two cardiac MRI scans at 1.5 T and 3 T in a randomized order within 30 minutes. FIELD STRENGTH/SEQUENCE: bSSFP cine images at 1.5 T and 3 T.Two software packages, Tissue Tracking (cvi42, Circle Cardiovascular Imaging) and QStrain (Medis Suite, Medis Medical Imaging Systems), were used to derive LV global systolic strain in the longitudinal, circumferential and radial directions and peak (systolic, early diastolic, and late diastolic) strain rates. Global longitudinal shortening and mitral annular plane systolic excursion (MAPSE) were measured using an AI deep neural network model.Comparisons between field strengths were performed using Wilcoxon signed-rank test (P value 0.05 considered statistically significant). Agreement was determined using intraclass correlation coefficients (ICCs) and Bland-Altman plots.Minimal bias was seen in all strain and strain rate measurements between field strengths. Using Tissue Tracking, strain and strain rate values derived from long-axis images showed poor to fair agreement (ICC range 0.39-0.71), whereas global longitudinal shortening and MAPSE showed good agreement (ICC = 0.81 and 0.80, respectively). Measures derived from short-axis images showed good to excellent agreement (ICC range 0.78-0.91). Similar results for the agreement of strain and strain rate measurements were observed with QStrain.The interfield strength agreement of short-axis derived LV strain and strain rate measurements at 1.5 T and 3 T was better than those derived from long-axis images; however, the agreement of global longitudinal shortening and MAPSE was good.2 TECHNICAL EFFICACY: Stage 2.

Obesity is associated with the development of heart failure and is a major risk factor for heart failure with preserved ejection fraction (HFpEF). Epicardial adipose tissue (EAT) is a unique visceral fat in close proximity to the heart and is of particular interest to the study of cardiac disease. Small poorly differentiated adipocytes with altered lipid:water content are associated with a proinflammatory secretome and may contribute to the pathophysiology observed in HFpEF. Multimodality imaging approaches can be used to quantify EAT volume and characterise EAT composition. Current research studies remain unclear as to the magnitude of effect that EAT plays on myocardial dysfunction and further work using multimodality imaging techniques is ongoing. Pharmacological interventions, including glucagon-like peptide 1 receptor agonists and sodium-dependent glucose linked transporter 2 inhibitors have shown promise in attenuating the deleterious metabolic and inflammatory changes seen in EAT. Clinical studies are ongoing to explore whether these therapies exert their beneficial effects by modifying this unique adipose deposit.

Background Type 2 diabetes (T2D) and hypertension commonly coexist and are associated with subclinical myocardial structural and functional changes. We sought to determine the association between blood pressure (BP) and left ventricular (LV) remodeling, systolic/diastolic function, and coronary microvascular function, among individuals with T2D without prevalent cardiovascular disease. Methods Participants with T2D and age-, sex-, and ethnicity-matched controls underwent comprehensive cardiovascular phenotyping including fasting bloods, transthoracic echocardiography, cardiovascular magnetic resonance imaging with quantitative adenosine stress/rest perfusion, and office and 24-h ambulatory BP monitoring. Multivariable linear regression was performed to determine independent associations between BP and imaging markers of remodeling and function in T2D. Results Individuals with T2D (n = 205, mean age 63 ± 7 years) and controls (n = 40, mean age 61 ± 8 years) were recruited. Mean 24-h systolic BP, but not office BP, was significantly greater among those with T2D compared to controls (128.8 ± 11.7 vs 123.0 ± 13.1 mmHg, p = 0.006). Those with T2D had concentric LV remodeling (mass/volume 0.91 ± 0.15 vs 0.82 ± 0.11 g/mL, p Conclusion 24-h ambulatory systolic BP, but not office BP, is independently associated with cardiac remodeling, coronary microvascular dysfunction, and diastolic dysfunction among asymptomatic individuals with T2D. (Clinical trial registration. URL: https://clinicaltrials.gov/ct2/show/NCT03132129 Unique identifier: NCT03132129).

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.

The role of cardiac magnetic resonance (CMR) in the evaluation and management of patients with frequent premature ventricular complexes (PVCs) of unknown etiology remains unclear.This study evaluated the prevalence and prognostic significance of myocardial abnormalities detected with CMR among patients with frequent PVCs and no known structural heart disease.This prospective cohort study included consecutive patients with frequent PVCs and a negative initial diagnostic work-up who underwent CMR with late gadolinium enhancement imaging. The clinical outcome was a composite of mortality, ventricular fibrillation, sustained ventricular tachycardia, or reduction in left ventricular ejection fraction of ≥10%.A total of 255 patients were included, of whom 35 (13.7%) had evidence of myocardial abnormality on CMR. Age ≥60 years (odds ratio [OR]: 6.96; 95% CI: 1.30-37.18), multifocal PVCs (OR: 10.90; 95% CI: 3.21-36.97), and non-outflow tract left ventricular PVC origin (OR: 3.00; 95% CI: 1.00-8.95) were independently associated with the presence of a myocardial abnormality on CMR. After a median follow-up of 36 months, the composite outcome occurred in 15 (5.9%) patients. The presence of a myocardial abnormality on CMR was independently associated with the composite outcome (HR: 4.35; 95% CI: 1.34-14.15; P = 0.014).One in 7 patients with frequent PVCs with no known structural heart disease had myocardial abnormality detected on CMR, and these abnormalities were associated with adverse clinical outcomes. These findings highlight the important role of CMR in the evaluation of patients with frequent PVCs.

Tenascin-C is a marker of interstitial fibrosis. We assessed whether plasma Tenascin-C differed between heart failure with preserved ejection fraction (HFpEF) and asymptomatic controls and related to clinical outcomes. Prospective, observational study of 172 age- and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, males 50%) who underwent phenotyping with 20 plasma biomarkers, echocardiography, cardiac MRI and 6-minute-walk-testing. The primary endpoint was the composite of all-cause death/HF hospitalisation. Tenascin-C was higher in HFpEF compared to controls (13.7 [10.8–17.3] vs (11.1 [8.9–12.9] ng/ml, p p During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations). In multivariable Cox regression analysis, Tenascin-C (adjusted hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.305–2.360; p p = 0.039) were independently associated with adverse outcomes. In HFpEF, plasma Tenascin-C is higher compared to age- and sex-matched controls and a strong predictor of adverse outcomes. Trial registration: ClinicalTrials.gov: NCT03050593

OBJECTIVE To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s−1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.

Aims To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. Methods and results One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case–control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P 4 were associated with larger infarcts [>10% left ventricular (LV) mass]. Conclusion The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.

Coronary CT angiography (CCTA) has emerged as a powerful noninvasive tool for characterizing the presence, extent, and severity of coronary artery disease (CAD) in patients with stable angina. Recent technological advancements in CT scanner hardware and software have augmented the rich information that can be derived from a single CCTA study. Beyond merely identifying the presence of CAD and assessing stenosis severity, CCTA now allows for the identification and characterization of plaques, lesion length, and fluoroscopic angle optimization, as well as enables the assessment of the physiologic extent of stenosis through CT-derived fractional flow reserve, and may even allow for the prediction of the response to revascularization. These and other features make CCTA capable of not only guiding invasive coronary angiography referral, but also give it the unique ability to help plan coronary intervention. This review summarizes current and future applications of CCTA in procedural planning for percutaneous coronary intervention, provides rationale for wider integration of CCTA in the workflow of the interventional cardiologist, and details how CCTA may help improve patient care and clinical outcomes. Keywords: CT Angiography © RSNA, 2022

Introduction: Type 2 diabetes (T2D) confers a higher relative risk of heart failure in women than men. Women also have a greater prevalence of heart failure with preserved ejection fraction (HFpEF), linked to microvascular dysfunction. We hypothesize that sex-specific differences are present in the pathophysiological alterations of myocardial structure, function, and perfusion associated with T2D. Methods: Cross-sectional case-control study. Participants underwent comprehensive cardiac phenotyping with echocardiography and cardiac magnetic resonance with adenosine stress/rest perfusion. Global myocardial perfusion was derived as a mean of three short axis slices. Image analysis was performed by two observers blinded to all participant information. Statistical analysis was performed with independent-sample T-tests or Mann-Whitney test. Results: Individuals with T2D (n=287, 41% female) were compared with age-matched controls (n=87, 41% female). Women with T2D were more obese than men (body mass index 35.7±7.2 vs 32.4±5.3 kg/m 2 , p Conclusions: In asymptomatic people with T2D, women have increased LV mass index and lower myocardial perfusion reserve than men, driven primarily by increased resting perfusion. These findings support the growing evidence that microvascular dysfunction partly explains the greater risk of HFpEF in women with T2D.

Introduction: The accumulation of excess epicardial adipose tissue (EAT) is associated with the onset of specific heart failure phenotypes. Subsets of adipocytes in EAT produce an inflammatory secretome which alters the extracellular matrix of the epicardium and impairs myocardial contractility. Lipid-laden adipocytes have a low computed tomography (CT) attenuation and can be readily identified using cardiac CT. Objective: This study sought to identify the clinical and biomarker determinants of low attenuation EAT in participants with Type 2 diabetes (T2D) at risk of heart failure. Methods: Participants with T2D and non-diabetic controls were prospectively recruited to an observational multi-modality cardiovascular imaging study. Deep learning analytics (QFAT, Cedars-Sinai) measured EAT volume and CT attenuation from cardiac CT datasets. Adipose tissue with CT attenuation values of -90 to -190 Hounsfield Units (HU) were classified as low attenuation EAT regions. Comparison was made with anthropometric and blood biomarkers to evaluate determinants of low attenuation EAT. Results: Type 2 diabetic (n=151, median age 64 (59, 69) years, 65% male) and non-diabetic individuals (n=39, median age 59 (54, 66.5) years, 59% male) were recruited. Total EAT volume indexed to body surface area was 1.6-fold higher in diabetics (62.4 (49.1, 77.7) cm 3 /m 2 vs 38.8 (29.6, 51.9) cm 3 /m 2 , p 2 = 0.2003, p Conclusions: In patients with T2D, indexed EAT volumes are 1.6-fold higher with a lower mean CT attenuation. Age, white ethnicity and waist circumference are associated with low attenuation EAT. Prospective studies are required to determine whether interventions to reduce low attenuation EAT will prevent the onset of heart failure.