BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis.

Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance.

Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT. Mice subjected to permanent ligation of the left coronary artery were imaged with MRI 6 weeks later. T2 weighted MRI of BAT volume and blood oxygen level dependent MRI of BAT function were performed. T2 * maps of BAT were obtained at multiple time points before and after administration of the ß3 adrenergic agonist CL 316 243 (CL). Blood flow to BAT was studied after CL injection using the flow alternating inversion recovery (FAIR) approach. Excised BAT tissue was analyzed for lipid droplet content and for uncoupling protein 1 (UCP1) mRNA expression. BAT volume was significantly lower in heart failure (51 ± 1 mm(3) versus 65 ± 3 mm(3) ; p < 0.05), and characterized by a reduction in lipid globules and a fourfold increase in UCP1 mRNA (p < 0.05). CL injection increased BAT T2 * in healthy animals but not in mice with heart failure (24 ± 4% versus 6 ± 2%; p < 0.01), consistent with an increase in flow in control BAT. This was confirmed by a significant difference in the FAIR response in BAT in control and heart failure mice. Heart failure results in the chronic activation of BAT, decreased BAT lipid stores and decreased BAT volume, and it is associated with a marked decrease in ability to respond to acute physiological stimuli. This may have important implications for substrate utilization and overall metabolic homeostasis in heart failure. Copyright © 2016 John Wiley & Sons, Ltd.

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy.

Quantification of myocardial extracellular volume fraction with cardiac MR imaging for early detection of left ventricle involvement in systemic sclerosis.

PURPOSE: To determine whether extracellular volume fraction (ECV) quantification at cardiac magnetic resonance (MR) imaging can demonstrate subclinical left ventricle (LV) abnormalities in a cohort of consecutive systemic sclerosis (SS) patients, and to investigate the relationship between ECV and diastolic and systolic LV function. MATERIALS AND METHODS: All subjects gave their written informed consent. The protocol was approved by the ethics committee. ECV quantification with cardiac MR imaging was prospectively performed in 33 consecutive SS patients with normal echocardiography results and no late gadolinium chelate enhancement at MR imaging. Left ventricular and atrial volumes and peak circumferential strain were measured at cardiac MR imaging. Diastolic function was assessed at echocardiography. The results were compared with those of 16 age-matched healthy control subjects by using Mann-Whitney and Kruskal-Wallis tests. RESULTS: SS patients had significantly higher global ECV (P < .001) and higher local ECV for all basal and midventricular LV segments. Global ECV significantly correlated with left atrial volume (P = .002) and with the grade of diastolic dysfunction (P = .016). The majority of SS patients (63%; 21 of 33 patients) had a high global ECV and a low global systolic circumferential strain. CONCLUSION: ECV quantification can identify LV abnormalities at an early stage in SS patients. These abnormalities may reflect increase in diffuse myocardial fibrosis and are associated with diastolic LV dysfunction.

Systolic myocardial dysfunction in patients with type 2 diabetes mellitus: identification at MR imaging with cine displacement encoding with stimulated echoes.

PURPOSE: To determine if cine displacement encoding with stimulated echoes (DENSE) can help to identify and determine the patterns of subclinical myocardial systolic dysfunction in patients with type 2 diabetes mellitus (DM) when compared with cine DENSE in control patients. MATERIALS AND METHODS: After obtaining approval from the institutional ethics committee and written informed consent from the patients, 37 patients with type 2 DM without overt heart disease and 23 age-matched control patients were prospectively included in the study. The patients underwent standard cine magnetic resonance (MR) imaging with two-dimensional cine DENSE acquisitions. Circumferential (Ecc) and radial (Err) systolic strains were measured on short-axis views at basal, mid, and apical left ventricular levels. Longitudinal strain (Ell) was measured on four- and two-chamber views. Statistical testing included the intraclass correlation coefficient and multiple linear regression analysis. RESULTS: The intraobserver intraclass correlation coefficient values were 0.85, 0.95, and 0.90, and the interobserver intraclass correlation coefficient values were 0.79, 0.91 and 0.80 for Ecc, Err, and Ell, respectively. The left ventricular ejection fraction was in the reference range and similar between the groups, and the patients with DM showed a decrease in Ecc (-14.4%±1.6 vs -17.0%±1.6, P<.001), Err (36.2%±10.9 vs 44.4%±9.9, P=.006) and Ell (-12.9%±2.1 vs -15.5%±1.6, P<.001) compared with the control patients. Finally, DM was independently associated with Ecc (P<.001), Err (P=.05) and Ell (P=.01) after adjustment for age, sex, hypertension, body mass index, and left ventricular mass. CONCLUSION: Cine DENSE, a motion-encoding MR imaging technique for myocardial strain assessment with high spatial resolution, appears to be useful in the identification of subclinical myocardial dysfunction in patients with DM.

Impact of cardiac resynchronization therapy optimization inside a heart failure programme: a real-world experience.

AIMS: This study sought to describe and evaluate the impact of a routine in-hospital cardiac resynchronization therapy (CRT) programme, including comprehensive heart failure (HF) evaluation and systematic echo-guided CRT optimization. METHODS AND RESULTS: CRT implanted patients were referred for optimization programme at 3 to 12 months from implantation. The program included clinical and biological status, standardized screening for potential cause of CRT non-response and systematic echo-guided atrioventricular and interventricular delays (AVd and VVd) optimization. Initial CRT-response and improvement at 6 months post-optimization were assessed with a clinical composite score (CCS). Major HF events were tracked during 1 year after optimization. A total of 227 patients were referred for CRT optimization and enrolled (71 ± 11 years old, 77% male, LVEF 30.6 ± 7.9%), of whom 111 (48.9%) were classified as initial non-responders. Left ventricular lead dislodgement was noted in 4 patients (1.8%), and loss or ≤90% biventricular capture in 22 (9.7%), mostly due to arrhythmias. Of the 196 patients (86%) who could undergo echo-guided CRT optimization, 71 (36.2%) required VVd modification and 50/144 (34.7%) AVd modification. At 6 months post-optimization, 34.3% of the initial non-responders were improved according to the CCS, but neither AVd nor VVd echo-guided modification was significantly associated with CCS-improvement. After one-year follow-up, initial non-responders maintained a higher rate of major HF events than initial responders, with no significant difference between AVd/VVd modified or not. CONCLUSIONS: Our study supports the necessity of a close, comprehensive and multidisciplinary follow-up of CRT patients, without arguing for routine use of echo-guided CRT optimization.

The role of hyperglycaemia in the development of diabetic cardiomyopathy.

Diabetes mellitus is a metabolic disorder with a chronic hyperglycaemic state. Cardiovascular diseases are the primary cause of mortality in patients with diabetes. Increasing evidence supports the existence of diabetic cardiomyopathy, a cardiac dysfunction with impaired cardiac contraction and relaxation, independent of coronary and/or valvular complications. Diabetic cardiomyopathy can lead to heart failure. Several preclinical and clinical studies have aimed to decipher the underlying mechanisms of diabetic cardiomyopathy. Among all the co-factors, hyperglycaemia seems to play an important role in this pathology. Hyperglycaemia has been shown to alter cardiac metabolism and function through several deleterious mechanisms, such as oxidative stress, inflammation, accumulation of advanced glycated end-products and upregulation of the hexosamine biosynthesis pathway. These mechanisms are responsible for the activation of hypertrophic pathways, epigenetic modifications, mitochondrial dysfunction, cell apoptosis, fibrosis and calcium mishandling, leading to cardiac stiffness, as well as contractile and relaxation dysfunction. This review aims to describe the hyperglycaemic-induced alterations that participate in diabetic cardiomyopathy, and their correlation with the severity of the disease and patient mortality, and to provide an overview of cardiac outcomes of glucose-lowering therapy.

Rest and low-dose dobutamine Tc-99m-mibi gated-SPECT for early prediction of left ventricular remodeling after a first reperfused myocardial infarction.

BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters. METHODS AND RESULTS: This prospective study tested the value of rest and low-dose dobutamine (LDD) Tc-99m-mibi gated-SPECT for early prediction of LV remodeling in patients treated by PCI in the acute phase of a first MI. Infarct size, infarct severity, regional wall motion abnormality (RWMA), and wall thickening score (WTs) were assessed at rest and on LDD by SPECT 6 +/- 2 days after MI in 40 patients. LV remodeling was defined as 20% increase at 6 months in LV end-diastolic volume assessed by MRI. Infarct severity at rest showed the best predictive values for left remodeling (PPV: 86%, NPV: 88%, accuracy: 88%; AUC: 0.750). Functional parameters at neither rest nor LDD study further improved predictive values of the SPECT imaging. CONCLUSIONS: Infarct severity assessed by Tc-99m-sestamibi gated-SPECT performed in the subacute phase of a first STEMI predicts LV remodeling with high accuracy without incremental value nor of functional parameters nor of LDD. Therefore, our results suggest that LDD should not be used in this setting.

Influence of afterload on left ventricular radial and longitudinal systolic functions: a two-dimensional strain imaging study.

AIMS: This study aimed to assess the influence of afterload alteration on radial (R) and longitudinal (L) left ventricular (LV) systolic regional functions. METHODS AND RESULTS: We analysed systolic myocardial function by two-dimensional strain (2D-S) and sonomicrometry (SS) in an experimental pig model of aortic banding. Both radial and longitudinal functions were analysed in six open-chest pigs under various loading conditions: baseline and graded aortic banding (subsequent increase in LV pressure of 10, 20, and 40 mmHg). Both systolic 2D-S(long) and 2D-S(rad) were significantly correlated with SS(long) and SS(rad) (r = 0.63, P < 0.001 and r = 0.65, P < 0.01, respectively). At a low increase in LV afterload, 2D-S(rad) was still preserved whereas 2D-S(long) significantly decreased. When LV afterload was subsequently increased, both 2D-S(rad) and 2D-S(long) significantly decreased. Difference in dependence to wall stress might explain these different behaviours. CONCLUSION: 2D-S shows a different response in longitudinal and radial functions to increased afterload. Longitudinal function is early impaired, whereas radial function remains preserved. This finding justifies the combined assessment of both radial and longitudinal regional myocardial functions to characterize myocardial dysfunction and might help to better identify the transition to heart failure in pressure-overload cardiomyopathy.

Imaging of myocarditis and inflammatory cardiomyopathies.

Myocarditis encompasses a wide range of myocardial inflammatory diseases, including acute myocarditis, chronic myocarditis and inflammatory cardiomyopathies, and myocardial inflammation associated with other cardiomyopathies. Because of this heterogeneity in clinical presentation, and the infrequent use of endomyocardial biopsy, cardiac imaging has gradually acquired a key role in the non-invasive detection of myocardial inflammation, the assessment of aetiology and the management of specific therapies. This article summarizes the issue of myocarditis and myocardial inflammation in clinical practice, and reviews the role of different non-invasive imaging techniques in the exploration of myocardial inflammation.

Interobserver Variability in Applying American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 Guidelines for Estimation of Left Ventricular Filling Pressure.

BACKGROUND: Assessment of left ventricular (LV) filling pressure is among the important components of a comprehensive echocardiographic report. Previous studies noted wide limits of agreement using 2009 American Society of Echocardiography/European Association of Echocardiography guidelines, but reproducibility of 2016 guidelines update in estimating LV filling pressure is unknown. METHODS: Echocardiographic and hemodynamic data were obtained from 50 patients undergoing cardiac catheterization for clinical indications. Clinical and echocardiographic findings but not invasive hemodynamics were provided to 4 groups of observers, including experienced echocardiographers and cardiology fellows. Invasively acquired LV filling pressure was the gold standard. RESULTS: In group I of 8 experienced echocardiographers from the guidelines writing committee, sensitivity for elevated LV filling pressure was 92% for all observers, and specificity was 93±6%. Fleiss κ-value for the agreement in group I was 0.80. In group II of 4 fellows in training, sensitivity was 91±2%, and specificity was 95±2%. Fleiss κ-value for the agreement in group II was 0.94. In group III of 9 experienced echocardiographers who had not participated in drafting the guidelines, sensitivity was 88±5%, and specificity was 91±7%. Fleiss κ-value for the agreement in group III was 0.76. In group IV of 7 other fellows, sensitivity was 91±3%, and specificity was 92±5%. Fleiss κ-value for the agreement in group IV was 0.89. CONCLUSIONS: There is a good level of agreement and accuracy in the estimation of LV filling pressure using the American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 recommendations update, irrespective of the experience level of the observer.

Adverse impact of diabetes mellitus on left ventricular remodelling in patients with chronic primary mitral regurgitation.

BACKGROUND: Diabetes mellitus (DM) has an impact on left ventricular (LV) geometry and function, and is associated with worsening of pressure-overload LV remodelling; however, its impact on volume-overload LV remodelling is unknown. AIM: The objective of the study was to examine the association between DM and LV remodelling in patients with chronic mitral regurgitation (MR) caused by mitral valve prolapse. METHODS: During a median follow-up of 3.26 [interquartile range 1.59-6.06] years, we evaluated the evolution of echocardiographic variables in 375 consecutive patients, including 61 (16%) patients with DM. The main endpoint was LV remodelling evaluated by LV end-diastolic diameter (LVEDD) and LV mass index increase. LV end-systolic diameter (LVESD) and ejection fraction (LVEF) were also evaluated. RESULTS: Patients with DM increased their LVEDD more than patients without DM (1.98±4.1 vs 0.15±4.54mm/year of follow-up; P=0.002). LVEF remained stable in the two groups. After adjustment for potential confounders, including age, sex, hypertension, body mass index, MR severity, medications and follow-up duration, DM remained independently associated with LVEDD increase (ß=2.30; P<0.001). When comparing patients with DM with patients without DM matched for age, sex and LVEDD at baseline, DM was independently associated with increased LVEDD (ß=2.14; P=0.002), LV mass index (ß=10.7; P=0.004) and LVESD (ß=2.07; P=0.01). CONCLUSION: DM is associated with worsening of LV remodelling in patients with moderate or severe chronic MR caused by mitral valve prolapse.

Diastolic function deterioration in type 2 diabetes mellitus: predictive factors over a 3-year follow-up.

Aims: Diastolic dysfunction is frequent in patients with type 2 diabetes mellitus (DM2) and associated with a poor prognosis. This study aimed to describe diastolic function changes over time in DM2 patients and to identify predictive factors of diastolic function deterioration. Methods and results: Diastolic function was assessed by echocardiography according to the EACVI/ASE recommendations at baseline and 3-year follow-up in a prospective cohort of 310 DM2 patients without overt heart disease. Predictors of diastolic function deterioration were identified using logistic regression analysis. During the 3-year follow-up, prevalence of diastolic dysfunction increased from 49% to 67% (P = 0.001). Only 32% of the patients had a normal diastolic function both at baseline and 3 years and 27% of the patients presented diastolic function deterioration. At multivariable analysis, age (OR = 1.05 [1.01-1.09], P < 0.01), retinopathy (OR = 2.00 [1.10-3.63], P = 0.02), and increase in systolic blood pressure during follow-up (OR = 1.03 [1.01-1.04], P < 0.01) were predictive of diastolic function deterioration. Conclusion: Age, retinopathy, and increase in blood pressure over time are associated with an increased risk of diastolic function deterioration in DM2 patients. The presence of these co-factors might help to early identify patients at risk of heart failure.

Short-term high-fat diet compromises myocardial function: a radial strain rate imaging study.

AIM: Long-term high-fat diet (HFD) induces both cardiac remodelling and myocardial dysfunction in murine models. The aim was to assess the time course and mechanisms of metabolic and cardiac modifications induced by short-term HFD in wild-type (WT) mice. METHODS AND RESULTS: Thirty-three WT mice were subjected to HFD (60% fat, n = 16) and chow diet (CD, 13% fat, n = 17). Metabolic and echocardiographic data were collected at baseline and every 5 weeks for 20 weeks. Invasive haemodynamic data and myocardial samples were collected at 5 and 20 weeks. Echocardiographic data included left ventricular (LV) diameters and thickness, and systolic function using radial strain rate (SR). Histological assessment of cardiomyocyte and adipocyte sizes, interstitial fibrosis, and apoptosis index were performed. During follow-up, body weight, and glycaemia levels were higher in HFD than in CD mice, in association with an early adipose tissue remodelling. Despite no difference between both groups in blood pressure and LV mass at 5 weeks, an early LV dysfunction was observed in HFD mice as assessed by radial SR (21 ± 0.8 vs. 27 ± 0.8 unit/s, P < 0.001) and haemodynamic assessment. During follow-up, both groups demonstrated a progressive systolic and diastolic LV dysfunction and remodelling including dilatation and hypertrophy, which were more severe in HFD mice. Compared with CD mice, the early LV impairment in HFD mice was coupled with a higher cardiomyocyte apoptosis level (0.95 vs. 0.02%, P < 0.05) associated with an interstitial fibrosis process (2.3 vs. 0.2%, P < 0.05), which worsen during follow-up. CONCLUSION: The HFD promoted early metabolic and cardiac dysfunctions, and adipose and myocardial tissues remodelling.

Clinical Implications of Echocardiographic Phenotypes of Patients With Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may alter cardiac structure and function, but obesity, hypertension (HTN), or aging can induce similar abnormalities. OBJECTIVES: This study sought to link cardiac phenotypes in T2DM patients with clinical profiles and outcomes using cluster analysis. METHODS: Baseline echocardiography and a composite endpoint (cardiovascular mortality and hospitalization) were evaluated in 842 T2DM patients from 2 prospective cohorts. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed. RESULTS: Three clusters were identified. Cluster 1 patients had the lowest left ventricular (LV) mass index and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') ratio, had the highest left ventricular ejection fraction (LVEF), and were predominantly male with the lowest rate of obesity or HTN. Cluster 2 patients had the highest strain and highest E/e' ratio, were the oldest, were predominantly female, and had the lowest rate of isolated T2DM (without HTN or obesity). Cluster 3 patients had the highest LV mass index and volumes and the lowest LVEF and strain, were predominantly male, and shared similar age and rate of obesity and HTN as cluster 1 patients. After follow-up of 67 months (interquartile range: 40 to 87), the composite endpoint occurred in 56 of 521 patients (10.8%). Clusters 2 (hazard ratio: 2.37; 95% confidence interval: 1.15 to 4.88) and 3 (hazard ratio: 2.19; 95% confidence interval: 1.00 to 4.82) had a similar outcome, which was worse than cluster 1. CONCLUSIONS: Cluster analysis of echocardiographic variables identified 3 different echocardiographic phenotypes of T2DM patients that were associated with distinct clinical profiles and highlighted the prognostic value of LV remodeling and subclinical dysfunction.

Standardization of adult transthoracic echocardiography reporting in agreement with recent chamber quantification, diastolic function, and heart valve disease recommendations: an expert consensus document of the European Association of Cardiovascular Imaging.

AIMS: This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases. METHODS AND RESULTS: Demographic data (age, body surface area, blood pressure, and heart rhythm and rate), type (vendor and model) of ultrasound system used and image quality need to be reported. In addition, measurements should be normalized for body size. Reference normal values, derived by ASE/EACVI recommendations, shall always be reported to differentiate normal from pathological conditions. This Expert Consensus document suggests avoiding the surveillance of specific variable using different ultrasound techniques (e.g. in echo labs with high expertise in left ventricular ejection fraction by 3D and not by 2D echocardiography). The report should be also tailored in relation with different cardiac pathologies, quality of images, and needs of the caregivers. CONCLUSION: The conclusion should be concise reflecting the status of left ventricular structure and function, the presence of left atrial and/or aortic dilation, right ventricular dysfunction, and pulmonary hypertension, leading to an objective communication with the patient health caregiver. Variation over time should be considered carefully, taking always into account the consistency of the parameters used for comparison.

Multimodality Imaging in Restrictive Cardiomyopathies: An EACVI expert consensus document In collaboration with the "Working Group on myocardial and pericardial diseases" of the European Society of Cardiology Endorsed by The Indian Academy of Echocardiography.

Restrictive cardiomyopathies (RCMs) are a diverse group of myocardial diseases with a wide range of aetiologies, including familial, genetic and acquired diseases and ranging from very rare to relatively frequent cardiac disorders. In all these diseases, imaging techniques play a central role. Advanced imaging techniques provide important novel data on the diagnostic and prognostic assessment of RCMs. This EACVI consensus document provides comprehensive information for the appropriateness of all non-invasive imaging techniques for the diagnosis, prognostic evaluation, and management of patients with RCM.

Young community of EACVI: the transition from EACVI Club 35 to Heart Imagers of Tomorrow: a promising yet challenging step.

The purpose of this review is to summarize the activity and potential of the young community of European Association of Cardiovascular Imaging and to highlight the transition from Club 35 to 'Heart Imagers of tomorrow'.

Relationship of brown adipose tissue perfusion and function: a study through ß2-adrenoreceptor stimulation.

Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by ß2-adrenoreceptor (ß2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during ß2-AR stimulation using salbutamol infusion in mice (P= 0.003). ß2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of ß2-AR agonist on brown adipocytes. Finally, ß2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively,P= 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.