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Aims We aimed to compare renal sinus fat volume assessed by MRI between patients with type 2 diabetes and healthy volunteers, and investigate the association between renal sinus fat and metabolic traits.Methods In this cross-sectional study, renal sinus fat and parenchyma volumes measured on abdominal MRI were compared between patients and controls using analysis of covariance. Associations of renal parameters with clinical characteristics were analyzed using linear regression analysis.Results A total of 146 participants were enrolled, consisting of 95 type 2 diabetes patients (57.2 +/- 8.8 years, 49.5% male) and 51 controls (54.0 +/- 9.2 years, 43.1% male). Patients with diabetes demonstrated larger sinus fat volumes (15.4 +/- 7.5 cm(3) vs. 10.3 +/- 7.1 cm(3), p < 0.001) and sinus fat-parenchyma ratio than controls. In the total population, renal sinus fat was positively associated with HbA1c, abdominal VAT, cholesterol and triglycerides, after adjustment for age, sex, ethnicity and type 2 diabetes. In type 2 diabetes patients, increased sinus fat volume was significantly associated with urinary albumin-to-creatinine ratio.Conclusion Renal sinus fat volume is positively associated with several metabolic risk factors including HbA1c level and urinary albumin-to-creatinine ratio in type 2 diabetes patients, indicating a potential role of renal sinus fat in the development of diabetic nephropathy. Future studies are needed to investigate whether sinus fat volume can serve as an early biomarker for diabetic nephropathy.

Background Pediatric hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular disease later in life. As HSCT survival has significantly improved, with a growing number of HSCT indications, tailored screening strategies for HSCT-related late effects are warranted. Little is known regarding the value of cardiovascular magnetic resonance (CMR) for early identification of high-risk patients after HSCT, before symptomatic cardiovascular disease manifests. This study aimed to assess CMR-derived left ventricular (LV) systolic and diastolic function, aortic stiffness and myocardial tissue characteristics in young adults who received HSCT during childhood. Methods Sixteen patients (22.1 ± 1.5 years) treated with HSCT during childhood and 16 healthy controls (22.1 ± 1.8 years) underwent 3 T CMR. LV systolic and diastolic function were measured as LV ejection fraction (LVEF), the ratio of transmitral early and late peak filling rate (E/A), the estimated LV filling pressure (E/Ea) and global longitudinal and circumferential systolic strain and diastolic strain rates, using balanced steady-state free precession cine CMR and 2D velocity-encoded CMR over the mitral valve. Aortic stiffness, myocardial fibrosis and steatosis were assessed with 2D velocity-encoded CMR, native T1 mapping and proton CMR spectroscopy (1H-CMRS), respectively. Results In the patient compared to the control group, E/Ea (9.92 ± 3.42 vs. 7.24 ± 2.29, P = 0.004) was higher, LVEF (54 ± 6% vs. 58 ± 5%, P = 0.055) and global longitudinal strain (GLS) ( -20.7 ± 3.5% vs. -22.9 ± 3.0%, P = 0.063) tended to be lower, while aortic pulse wave velocity (4.40 ± 0.26 vs. 4.29 ± 0.29 m/s, P = 0.29), native T1 (1211 ± 36 vs. 1227 ± 28 ms, P = 0.16) and myocardial triglyceride content (0.47 ± 0.18 vs. 0.50 ± 0.13%, P = 0.202) were comparable. There were no differences between patients and controls in E/A (2.76 ± 0.92 vs. 2.97 ± 0.91, P = 0.60) and diastolic strain rates. Conclusion In young adults who received HSCT during childhood, LV diastolic function was decreased (higher estimated LV filling pressure) and LV systolic function (LVEF and GLS) tended to be reduced as compared to healthy controls, whereas no concomitant differences were found in aortic stiffness and myocardial tissue characteristics. When using CMR, assessment of LV diastolic function in particular is important for early detection of patients at risk of HSCT-related cardiovascular disease, which may warrant closer surveillance.

Aims: Data on the effect of liraglutide on glycemic endpoints in people with T2DM using multiple daily insulin injections (MDI) are scarce, especially in the context of ethnicity. Methods: This is a secondary analysis of the placebo-controlled randomized clinical “MAGNA VICTORIA” trials in Western European (WE) and South Asian (SA) people with T2DM. Participants had inadequate glycemic control despite using metformin and/or sulfonylurea derivatives and/or insulin. Participants were assigned to liraglutide (1.8 mg) or placebo for 6 months, in addition to standard care. The primary endpoint number of participants reaching target HbA1c was compared for liraglutide versus placebo in the complete dataset and MDI-treated participants using Chi-square test. Liraglutide’s efficacy in WE and SA was compared using a generalized linear model. Results: Forty-five subjects were randomized to liraglutide and 51 to placebo. In each group, one participant did not complete the study. Liraglutide-treated patients reached target HbA1c more frequently: 23/45 (51%) vs 11/51 (22%), relative probability 2.4 (1.3–4.3), p = 0.002. Subgroup analysis in 43 MDI participants showed that the proportion reaching target HbA1c using liraglutide was significantly higher than in placebo: 9/22 (41%) vs 1/21 (5%), p = 0.005. There was no difference between WE and SA in terms of liraglutide efficacy (p = 0.18). Conclusions: Liraglutide treatment resulted in increased chance of reaching target HbA1c as compared to placebo. Liraglutide efficacy was sustained in participants using MDI regimens and those of SA descent. Liraglutide should be considered for T2DM people with inadequate glycemic control despite MDI.

Objective: Ectopic lipid accumulation in the kidney (fatty kidney) is a potential driver of diabetic kidney disease, and tight glycemic control can reduce risk of diabetic nephropathy. We assessed whether glycemic control influences renal triglyceride content (RTGC). Furthermore, we compared glucagon-like peptide-1 receptor agonist liraglutide versus standard glucose-lowering therapy. Design andMethods: In this single-center parallel-group trial, patients with type 2 diabetes mellitus were randomized to liraglutide or placebo added to standard care (metformin/sulfonylurea derivative/insulin). Changes in RTGC after 26 weeks of glycemic control measured by proton spectroscopy and difference in RTGC between treatment groups were analyzed.Results: Fifty patients with type 2 diabetes mellitus were included in the baseline analysis (mean age, 56.5 +/- 9.1 years; range, 33-73 years; 46% males). Seventeen patients had baseline and follow-up measurements. Mean glycated hemoglobin was 7.8 +/- 0.8%, which changed to 7.3 +/- 0.9% after 26 weeks of glycemic control irrespective of treatment group (P = .046). Log-transformed RTGC was -0.68 +/- 0.30% and changed to -0.83 +/- 0.32% after 26 weeks of glycemic control irrespective of treatment group (P = .049). A 26-week-to-baseline RTGC ratio (95% confidence interval) was significantly different between liraglutide (-0.30 [-0.50, -0.09]) and placebo added to standard care (-0.003 [-0.34, 0.34]) (P = .04).Conclusion: In this exploratory study, we found that 26 weeks of glycemic control resulted in lower RTGC, in particular for liraglutide; however, larger clinical studies are needed to assess whether these changes reflect a true effect of glycemic control on fatty kidney. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.

Background and aims: The separate cardiovascular effects of type 2 diabetes and adiposity remain to be examined. This study aimed to investigate the role of insulin resistance in the relations of visceral (VAT), abdominal subcutaneous (aSAT) adipose tissue and total body fat (TBF) to cardiovascular remodeling.Methods and results: In this cross-sectional analysis of the population-based Netherlands Epidemiology of Obesity study, 914 middle-aged individuals (46% men) were included. Participants underwent magnetic resonance imaging. Standardized linear regression coefficients (95%CI) were calculated, adjusted for potential confounding factors. All fat depots and insulin resistance (HOMA-IR), separate from VAT and TBF, were associated with lower mitral early and late peak filling rate ratios (E/A): -0.04 (-0.09;0.01) per SD (54 cm(2)) VAT; -0.05 (-0.10;0.00) per SD (94 cm(2)) aSAT; -0.09 (-0.16;-0.02) per SD (8%) TBF; -0.11 (-0.17;-0.05) per 10-fold increase in HOMA-IR, whereas VAT and TBF were differently associated with left ventricular (LV) end-diastolic volume: -8.9 (-11.7;-6.1) mL per SD VAT; +5.4 (1.1;9.7) mL per SD TBF. After adding HOMA- IR to the model to evaluate the mediating role of insulin resistance, change in E/A was -0.02 (-0.07;0.04) per SD VAT; -0.03 (-0.08;0.02) per SD aSAT; -0.06 (- 0.13;0.01) per SD TBF, and change in LV end-diastolic volume was -7.0 (-9.7;-4.3) mL per SD VAT. In women, adiposity but not HOMA-IR was related to higher aortic arch pulse wave velocity.Conclusion: Insulin resistance was associated with reduced diastolic function, separately from VAT and TBF, and partly mediated the associations between adiposity depots and lower diastolic function. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Background and aims: Several studies have shown that glucagon-like peptide-1 (GLP1) analogues can affect resting energy expenditure, and preclinical studies suggest that they may activate brown adipose tissue (BAT). The aim of the present study was to investigate the effect of treatment with liraglutide on energy metabolism and BAT fat fraction in patients with type 2 diabetes.Methods and results: In a 26-week double-blind, placebo-controlled trial, 50 patients with type 2 diabetes were randomized to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after treatment for 4, 12 and 26 weeks, we assessed resting energy expenditure (REE) by indirect calorimetry. Furthermore, at baseline and after 26 weeks, we determined the fat fraction in the supraclavicular BAT depot using chemical-shift water-fat MRI at 3T. Liraglutide reduced REE after 4 weeks, which persisted after 12 weeks and tended to be present after 26 weeks (week 26 vs baseline: liraglutide -52 +/- 128 kcal/day; P = 0.071, placebo +44 +/- 144 kcal/day; P = 0.153, between group P = 0.057). Treatment with liraglutide for 26 weeks did not decrease the fat fraction in supraclavicular BAT (-0.4 +/- 1.7%; P = 0.447) compared to placebo (-0.4 +/- 1.4%; P = 0.420; between group P = 0.911).Conclusion: Treatment with liraglutide decreases REE in the first 12 weeks and tends to decrease this after 26 weeks without affecting the fat fraction in the supraclavicular BAT depot. These findings suggest reduction in energy intake rather than an increase in REE to contribute to the liraglutide-induced weight loss. (C) 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Background Advanced renal disease is characterized by adverse changes in renal structure; however, noninvasive techniques to diagnose and monitor these changes are currently lacking. Purpose To evaluate the reproducibility of native T1 mapping for renal tissue characterization. Study type Reproducibility study. Population Fifteen healthy volunteers (mean age 31 years, range 19-63 years), and 11 patients with diabetic nephropathy (mean age 57 years, range 51-69 years). Field strength/sequence 3T, modified Look-Locker imaging (MOLLI) 5(3)3. Assessment Intra- and interexamination reproducibility of voxel-based T1 relaxation times of renal cortex and medulla was assessed in healthy human volunteers and diabetic nephropathy patients. Statistical tests Reproducibility was evaluated using Bland-Altman and intraclass correlation coefficients (ICCs). Results Intra- and interexamination reproducibility of renal native T1 mapping showed good-strong ICCs (0.83-0.89) for renal cortex and medulla, and moderate-good ICCs (0.62-0.81) for cortex-medulla ratio in both healthy volunteers and diabetic nephropathy patients. Intra- and interexamination limits of agreement were respectively (-124 msec, + 82 msec) and (-134 msec, + 98 msec) for renal cortex and (-138 msec, + 107 msec) and (-118 msec, + 151 msec) for medulla. Overall T1 values for renal cortex (P = 0.277) and medulla (P = 0.973) were not significantly different between healthy volunteers and diabetic nephropathy patients, in contrast to the cortex-medulla ratio (P = 0.003). Data conclusion Renal native T1 mapping is a technique with good-strong intra- and examination reproducibility in both healthy volunteers and diabetic nephropathy patients. Level of evidence 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:588-596.

In this review, current imaging techniques and their future perspectives in the field of cardiac metabolic imaging in humans are discussed. This includes a range of noninvasive imaging techniques, allowing a detailed investigation of cardiac metabolism in health and disease. The main imaging modalities discussed are magnetic resonance spectroscopy techniques for determination of metabolite content (triglycerides, glucose, ATP, phosphocreatine, and so on), MRI for myocardial perfusion, and single-photon emission computed tomography and positron emission tomography for quantitation of perfusion and substrate uptake.

Background Myocardial tissue characterization by MR T1 and extracellular volume (ECV) mapping has demonstrated clinical value. The modified Look–Locker inversion recovery (MOLLI) sequence is a standard mapping technique, but its quality can be negatively affected by motion. Purpose To develop a robust motion correction method for T1 and ECV mapping. Study Type Retrospective analysis of clinical data. Population Fifty patients who were referred to cardiac MR exam for T1 mapping. Field Strength/Sequence 3.0T cardiac MRI with precontrast and postcontrast MOLLI acquisition of the left ventricle (LV). Assessment A groupwise registration method based on principle component analysis (PCA) was developed to register all MOLLI frames simultaneously. The resulting T1 and ECV maps were compared to those from the original and motion-corrected MOLLI with pairwise registration, in terms of standard deviation (SD) error. Statistical Test Paired variables were compared using the Wilcoxon signed-rank test. Results The groupwise registration method demonstrated improved registration performance compared to pairwise registration, with the T1 SD error reduced from 31 ± 20 msec to 26 ± 15 msec (P < 0.05), and ECV SD error reduced from 4.1 ± 3.6% to 2.8 ± 2.0% (P < 0.05). In LV segmental analysis, the performance was particularly improved in lateral segments, which are most affected by motion. The running time of groupwise registration was significantly shorter than that of the pairwise registration, 17.5 ± 3.0 seconds compared to 43.5 ± 2.2 seconds (P < 0.05). Data Conclusion We developed an automatic, robust motion correction method for myocardial T1 and ECV mapping based on a new groupwise registration scheme. The method led to lower mapping error compared to the conventional pairwise registration method in reduced execution time. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

At present, most of the cardiac magnetic resonance imaging (MRI) examinations rely on contrast-enhanced protocols, but noncontrast alternatives are emerging. Late gadolinium enhancement (LGE) imaging for the detection of myocardial scar can be considered the main cause for the embedding of cardiac MRI into the clinical routine. The novel noncontrast technique of native T1 mapping shows promise for tissue characterization in ischemic and nonischemic cardiomyopathy and may provide additional information over conventional LGE imaging. Technical issues, including measurements variability, still need to be resolved to facilitate a wide clinical application. Ischemia detection can be performed with contrast-based stress perfusion and contrast-free stress wall motion imaging. For coronary magnetic resonance angiography (MRA), protocols with and without contrast material have been developed. Research on coronary atherosclerotic plaque characterization has introduced new applications of contrast material. For MRA of the aorta, which traditionally relied on contrast administration, several noncontrast protocols have become available. This review provides an overview of when to use contrast material in cardiac and cardiac-related vascular MRI, summarizes the major imaging building blocks, and describes the diagnostic value of the available contrast-enhanced and noncontrast techniques. Contrast material in cardiac MRI should be used for LGE imaging for tissue characterization in ischemic or nonischemic cardiomyopathy and may be used for stress perfusion imaging for the detection of ischemia. In cardiac-related vascular MRI, use of contrast material should be avoided, unless high-quality angiography is required that cannot be obtained with noncontrast protocols. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1551–1572.

Contains fulltext : 220645.pdf (Publisher’s version ) (Open Access) BACKGROUND: The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide may be beneficial in the regression of diabetic cardiomyopathy. South Asian ethnic groups in particular are at risk of developing type 2 diabetes. PURPOSE: To assess the effects of liraglutide on left ventricular (LV) diastolic and systolic function in South Asian type 2 diabetes patients. STUDY TYPE: Prospective, double-blind, randomized, placebo-controlled trial. POPULATION: Forty-seven type 2 diabetes patients of South Asian ancestry living in the Netherlands, with or without ischemic heart disease, who were randomly assigned to 26-week treatment with liraglutide (1.8 mg/day) or placebo. FIELD STRENGTH/SEQUENCE: 3T (balanced steady-state free precession cine MRI, 2D and 4D velocity-encoded MRI, (1) H-MRS, T1 mapping). ASSESSMENT: Primary endpoints were changes in LV diastolic function (early deceleration peak [Edec], ratio of early and late peak filling rate [E/A], estimated LV filling pressure [E/Ea]) and LV systolic function (ejection fraction). Secondary endpoints were changes in aortic stiffness (aortic pulse wave velocity [PWV]), myocardial steatosis (myocardial triglyceride content), and diffuse fibrosis (extracellular volume [ECV]). STATISTICAL TESTS: Data were analyzed according to intention-to-treat. Between-group differences were reported as mean (95% confidence interval [CI]) and were assessed using analysis of covariance (ANCOVA). RESULTS: Liraglutide (n = 22) compared with placebo (n = 25) did not change Edec (+0.2 mL/s(2) x 10(-3) (-0.3;0.6)), E/A (-0.09 (-0.23;0.05)), E/Ea (+0.1 (-1.2;1.3)) and ejection fraction (0% (-3;2)), but decreased stroke volume (-9 mL (-14;-5)) and increased heart rate (+10 bpm (4;15)). Aortic PWV (+0.5 m/s (-0.6;1.6)), myocardial triglyceride content (+0.21% (-0.09;0.51)), and ECV (-0.2% (-1.4;1.0)) were unaltered. DATA CONCLUSION: Liraglutide did not affect LV diastolic and systolic function, aortic stiffness, myocardial triglyceride content, or extracellular volume in Dutch South Asian type 2 diabetes patients with or without coronary artery disease. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1679-1688.

Aims/hypothesis The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. Methods This study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m2) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported. Results The trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (n = 23) vs placebo (n = 26) significantly reduced body weight (liraglutide 98.4 ± 13.8 kg to 94.3 ± 14.9 kg; placebo 94.5 ± 13.1 kg to 93.9 ± 13.2 kg; estimated treatment effect −4.5 [95% CI −6.4, −2.6] kg). HbA1c declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 ± 11.5 mmol/mol to 55.0 ± 13.2 mmol/mol [8.4 ± 1.1% to 7.3 ± 1.2%]; placebo 64.7 ± 10.2 mmol/mol to 56.9 ± 6.9 mmol/mol [8.2 ± 1.0% to 7.5 ± 0.7%]; estimated treatment effect −2.9 [95% CI −8.1, 2.3] mmol/mol or −0.3 [95% CI −0.8, 0.2]%). VAT did not change significantly between groups (liraglutide 207 ± 87 cm2 to 203 ± 88 cm2; placebo 204 ± 63 cm2 to 200 ± 55 cm2; estimated treatment effect −7 [95% CI −24, 10] cm2), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 ± 142 cm2 to 339 ± 131 cm2; placebo 329 ± 107 cm2 to 333 ± 125 cm2; estimated treatment effect −29 [95% CI −51, −8] cm2). Epicardial fat did not change significantly between groups (liraglutide 8.9 ± 4.3 cm2 to 9.1 ± 4.7 cm2; placebo 9.6 ± 4.1 cm2 to 9.6 ± 4.6 cm2; estimated treatment effect 0.2 [95% CI −1.5, 1.8] cm2). Change in HTGC was not different between groups (liraglutide 18.1 ± 11.2% to 12.0 ± 7.7%; placebo 18.4 ± 9.4% to 14.7 ± 10.0%; estimated treatment effect −2.1 [95% CI −5.3, 1.0]%). MTGC was not different after treatment with liraglutide (1.5 ± 0.6% to 1.2 ± 0.6%) vs placebo (1.3 ± 0.5% to 1.2 ± 0.6%), with an estimated treatment effect of −0.1 (95% CI −0.4, 0.2)%. There were no adjudicated serious adverse events. Conclusions/interpretation Compared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study. Trial registration ClinicalTrials.gov NCT01761318. Funding This study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark).

BackgroundThe pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans.MethodsT2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model.ResultsA total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [− 0.20 (− 0.36; − 0.03),P = 0.021] and Europeans [− 0.20 (− 0.36; − 0.04),P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30),P Pfor interaction by ethnicity = 0.005) with a lower extracellular volume fraction [− 1.9% (− 3.4; − 0.4),P = 0.013] (Pfor interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84),P = 0.001] (Pfor interaction = 0.002) than their control group.ConclusionsDiabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.

Background Impaired left ventricular (LV) contraction and relaxation may further promote adverse remodeling and may increase the risk of ventricular arrhythmia (VA) in ischemic cardiomyopathy. We aimed to examine the association of cardiovascular magnetic resonance (CMR)-derived circumferential strain parameters for LV regional systolic function, LV diastolic function and mechanical dispersion with the risk of VA in patients with prior myocardial infarction and primary prevention implantable cardioverter defibrillator (ICD). Methods Patients with an ischemic cardiomyopathy who underwent CMR prior to primary prevention ICD implantation, were retrospectively identified. LV segmental circumferential strain curves were extracted from short-axis cine CMR. For LV regional strain analysis, the extent of moderately and severely impaired strain (percentage of LV segments with strain between − 10% and − 5% and > − 5%, respectively) were calculated. LV diastolic function was quantified by the early and late diastolic strain rate. Mechanical dispersion was defined as the standard deviation in delay time between each strain curve and the patient-specific reference curve. Cox proportional hazard ratios (HR) (95%CI) were calculated to assess the association between LV strain parameters and appropriate ICD therapy. Results A total of 121 patients (63 ± 11 years, 84% men, LV ejection fraction (LVEF) 27 ± 9%) were included. During a median (interquartile range) follow-up of 47 (27;69) months, 30 (25%) patients received appropriate ICD therapy. The late diastolic strain rate (HR 1.1 (1.0;1.2) per − 0.25 1/s, P = 0.043) and the extent of moderately impaired strain (HR 1.5 (1.0;2.2) per + 10%, P = 0.048) but not the extent of severely impaired strain (HR 0.9 (0.6;1.4) per + 10%, P = 0.685) were associated with appropriate ICD therapy, independent of LVEF, late gadolinium enhancement (LGE) scar border size and acute revascularization. Mechanical dispersion was not related to appropriate ICD therapy (HR 1.1 (0.8;1.6) per + 25 ms, P = 0.464). Conclusions In an ischemic cardiomyopathy population referred for primary prevention ICD implantation, the extent of moderately impaired strain and late diastolic strain rate were associated with the risk of appropriate ICD therapy, independent of LVEF, scar border size and acute revascularization. These findings suggest that disturbed LV contraction and relaxation may contribute to an increased risk of VA after myocardial infarction. Electronic supplementary material The online version of this article (10.1186/s12968-019-0536-5) contains supplementary material, which is available to authorized users.

Background Liraglutide is an antidiabetic agent with cardioprotective effect. The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease. Methods Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks. Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR. Intention-to-treat analysis of between-group differences was performed using ANCOVA. Mean estimated treatment differences (95% confidence intervals) are reported. Results 23 patients were randomized to liraglutide and 26 to placebo. As compared with placebo, liraglutide significantly reduced E (− 56 mL/s (− 91 to − 21)), E/A ratio (− 0.17 (− 0.27 to − 0.06)), Edec (− 0.9 mL/s2 * 10−3 (− 1.3 to − 0.2)) and E/Ea (− 1.8 (− 3.0 to − 0.6)), without affecting A (3 mL/s (− 35 to 41)) and Ea (0.4 cm/s (− 0.9 to 1.4)). Liraglutide reduced stroke volume (− 9 mL (− 16 to − 2)) and ejection fraction (− 3% (− 6 to − 0.1)), but did not change cardiac output (− 0.4 L/min (− 0.9 to 0.2)), cardiac index (− 0.1 L/min/m2 (− 0.4 to 0.1)) and peak ejection rate (− 46 mL/s (− 95 to 3)). Conclusions Liraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle. LV systolic function reduced and remained within normal range. Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages. Trial registration ClinicalTrials.gov: NCT01761318.

Purpose To develop a deep learning-based method for fully automated quantification of left ventricular (LV) function from short-axis cine MR images and to evaluate its performance in a multivendor and multicenter setting. Materials and Methods This retrospective study included cine MRI data sets obtained from three major MRI vendors in four medical centers from 2008 to 2016. Three convolutional neural networks (CNNs) with the U-NET architecture were trained on data sets of increasing variability: (a) a single-vendor, single-center, homogeneous cohort of 100 patients (CNN1); (b) a single-vendor, multicenter, heterogeneous cohort of 200 patients (CNN2); and (c) a multivendor, multicenter, heterogeneous cohort of 400 patients (CNN3). All CNNs were tested on an independent multivendor, multicenter data set of 196 patients. CNN performance was evaluated with respect to the manual annotations from three experienced observers in terms of (a) LV detection accuracy, (b) LV segmentation accuracy, and (c) LV functional parameter accuracy. Automatic and manual results were compared with the paired Wilcoxon test, Pearson correlation, and Bland-Altman analysis. Results CNN3 achieved the highest performance on the independent testing data set. The average perpendicular distance compared with manual analysis was 1.1 mm ± 0.3 for CNN3, compared with 1.5 mm ± 1.0 for CNN1 (P < .05) and 1.3 mm ± 0.6 for CNN2 (P < .05). The LV function parameters derived from CNN3 showed a high correlation (r2 ≥ 0.98) and agreement with those obtained by experts for data sets from different vendors and centers. Conclusion A deep learning-based method trained on a data set with high variability can achieve fully automated and accurate cine MRI analysis on multivendor, multicenter cine MRI data. © RSNA, 2018 See also the editorial by Colletti in this issue.

Background South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South Asian patients with type 2 diabetes. Methods In a placebo-controlled trial, 47 South Asian patients with type 2 diabetes were randomly assigned to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after 26 weeks of treatment we assessed abdominal subcutaneous, visceral, epicardial and paracardial adipose tissue volume using MRI. Furthermore, myocardial and hepatic triglyceride content were examined with proton magnetic resonance spectroscopy. Results In the intention-to-treat analysis, liraglutide decreased body weight compared to placebo (− 3.9 ± 3.6 kg vs − 0.6 ± 2.2 kg; mean change from baseline (liraglutide vs placebo): − 3.5 kg; 95% CI [− 5.3, − 1.8]) without significant effects on the different adipose tissue compartments. HbA1c was decreased in both groups without between group differences. In the per-protocol analysis, liraglutide did decrease visceral adipose tissue volume compared to placebo (− 23 ± 27 cm2 vs − 2 ± 17 cm2; mean change from baseline (liraglutide vs placebo): − 17 cm2; 95% CI [− 32, − 3]). Furthermore, HbA1c was decreased by liraglutide compared to placebo (− 1.0 ± 0.8% (− 10.5 ± 9.1 mmol/mol)) vs (− 0.6 ± 0.8% (− 6.1 ± 8.8 mmol/mol)), with a between group difference (mean change from baseline (liraglutide vs placebo): − 0.6% (− 6.5 mmol/mol); 95% CI [− 1.1, − 0.1 (− 11.5, − 1.5)]). Interestingly, the decrease of visceral adipose tissue volume was associated with the reduction of HbA1c (β: 0.165 mmol/mol (0.015%) per 1 cm2 decrease of visceral adipose tissue volume; 95% CI [0.062, 0.267 (0.006, 0.024%)]). Conclusions While the intention-to-treat analysis did not show effects of liraglutide on ectopic fat and HbA1c, per-protocol analysis showed that liraglutide decreases visceral adipose tissue volume, which was associated with improved glycaemic control in South Asians. Trial registration NCT02660047 (clinicaltrials.gov). Registered 21 January 2016

Objectives This study proposed entropy as a new late gadolinium enhanced cardiac magnetic resonance–derived parameter to evaluate tissue inhomogeneity, independent of signal intensity thresholds. This study hypothesized that entropy within the scar is associated with ventricular arrhythmias (VAs), whereas entropy of the entire left ventricular (LV) myocardium is associated with mortality. Background In patients after myocardial infarction, the heterogeneity of fibrosis determines the substrate for VA. Fibrosis in remote areas has been associated with heart failure and mortality. Late gadolinium-enhanced cardiac magnetic resonance has been used to delineate fibrosis, but available methods depend on signal intensity thresholds and results have been inconsistent. Methods Consecutive post–myocardial infarction patients undergoing late gadolinium enhanced cardiac magnetic resonance prior to implantable cardioverter-defibrillator implantation were included. From cardiac magnetic resonance imaging, total scar size, scar gray zone, scar transmurality, and tissue entropy were derived. Patients were followed for appropriate implantable cardioverter-defibrillator therapy and mortality. Results A total of 154 patients (age 64 ± 10 years, 84% male, LV ejection fraction 29 ± 10%, 47% acute revascularization) were included. During a median follow-up of 56 (interquartile range: 40 to 73) months, appropriate implantable cardioverter-defibrillator therapy occurred in 46 patients (30%), and 41 patients (27%) died. From multivariable analysis, higher entropy of the scar (hazard ratio [HR]: 1.9; 95% confidence interval [CI]: 1.0 to 3.5; p = 0.042) was independently associated with VA, after adjusting for multivessel disease, acute revascularization, LV ejection fraction, scar gray zone, and transmurality. Entropy of the entire LV was independently associated with mortality (HR: 3.2; 95% CI: 1.1 to 9.9; p = 0.038). Conclusions High entropy within the scar was associated with VA and may indicate an arrhythmogenic scar. High entropy of the entire LV was associated with mortality and may reflect a fibrosis pattern associated with adverse remodeling.

Liraglutide is an antidiabetic agent with cardioprotective effect. The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease.Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks. Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR. Intention-to-treat analysis of between-group differences was performed using ANCOVA. Mean estimated treatment differences (95% confidence intervals) are reported.23 patients were randomized to liraglutide and 26 to placebo. As compared with placebo, liraglutide significantly reduced E (- 56 mL/s (- 91 to - 21)), E/A ratio (- 0.17 (- 0.27 to - 0.06)), Edec (- 0.9 mL/sLiraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle. LV systolic function reduced and remained within normal range. Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages. Trial registration ClinicalTrials.gov: NCT01761318.