scholarly journals 3266 Understanding epicardial adipose biology by imaging, transcriptomic, and lipidomic profiling

2019 ◽  
Vol 3 (s1) ◽  
pp. 157-158
Author(s):  
Jadranka Stojanovska ◽  
Alex Tsodikov ◽  
Carey Lumeng ◽  
Charles Burant ◽  
Thomas Chenevert

OBJECTIVES/SPECIFIC AIMS: The study aims to understand if pro inflammatory epicardial white adipose phenotype is positively associated with coronary atherosclerosis, while the brown adipose phenotype is negatively associated. Primary outcome is association between epicardial fat fraction and coronary atherosclerosis and cardiac function. Secondary outcome is transcriptomic and lipidomic profiling between epicardial, extra pericardial, and subcutaneous depots and how these profiles correlate with fat fraction. METHODS/STUDY POPULATION: Recruited patients undergoing open-heart surgery provided informed consent at their second visit and underwent laboratory testing and imaging (cardiac magnetic resonance including water-fat imaging and coronary calcium computed tomography) prior to their surgery. Cardiac function such as cardiac chamber volume, mass, function, and strain, and depo-specific fat fraction were calculated from cardiac MR and Agatston calcium score and epicardial adipose volume from CT images. At the time of surgery, a tissue specimens from the epicardial, extrapericardial, and subcutaneous depots were obtained for transcriptomic and lipidomic analysis. Linear and logistic regression analyses adjusted for other variables were performed to evaluate significance level between variables. RESULTS/ANTICIPATED RESULTS: 37 subjects were enrolled in the study, 13 (35%) of which were women. Cardiac function and fat fraction was quantified in all patients, whereas tissue analyses were performed in 22 patients. Epicardial and extrapericardial fat fraction were independently associated with coronary atherosclerosis (p-value 0.01 and 0.04 respectively) Only epicardial fat fraction was negatively associated with global circumferential shortening of the left ventricle (0.03), while neither the extrapericardial fat fraction nor epicardial adipose volume were not (p =0.33 and 0.97 respectively) All three adipose depots have unique gene signatures with differentially expressed genes and pathways. RNA sequencing of epicardial, extrapericardial, and subcutaneous depots demonstrated tight clustering of epicardial and subcutaneous signatures based on PCA analysis (Figure 2). 19 lipid classes and 59 lipids showed differential expression between at least 2 of the fat depots (Figure 3). Hierarchal clustering of the lipids showed that epicardial and extrapericardial depots were more closely related than subcutaneous adipose. Plasmenyl-phosphatidylcholines, with an ether-linked fatty acid at the sn-1 position of the lipid, were higher in subcutaneous fat while most other lipids were higher in epicardial fat per tissue weight, such as ceramides (p=0.002). DISCUSSION/SIGNIFICANCE OF IMPACT: Epicardial, extrapericardial, and subcutaneous adipose depots express different lipidome and transcriptome signatures and different pathways. GSEA analysis demonstrated enrichment of genes related to antigen presentation and B cell immunity in epicardial compared to subcutaneous adipose tissue. Epicardial fat fraction is associated with coronary atherosclerosis and decreased left ventricular global circumferential shortening as an early predictor of decreased left ventricular stroke volume. Epicardial fat fraction is also associated with cermides which may play role in the development of coronary atherosclerosis and decreased cardiac function.

2020 ◽  
Vol 33 (9) ◽  
pp. 837-845
Author(s):  
Phillip D Levy ◽  
Michael J Burla ◽  
Michael J Twiner ◽  
Alexander L Marinica ◽  
James J Mahn ◽  
...  

Abstract BACKGROUND Subclinical hypertensive heart disease (SHHD) is a precursor to heart failure. Blood pressure (BP) reduction is an important component of secondary disease prevention in patients with SHHD. Treating patients with SHHD utilizing a more intensive BP target (120/80 mm Hg), may lead to improved cardiac function but there has been limited study of this, particularly in African Americans (AAs). METHODS We conducted a single center, randomized controlled trial where subjects with uncontrolled, asymptomatic hypertension, and SHHD not managed by a primary care physician were randomized to standard (<140/90 mm Hg) or intensive (<120/80 mm Hg) BP therapy groups with quarterly follow-up for 12 months. The primary outcome was the differences of BP reduction between these 2 groups and the secondary outcome was the improvement in echocardiographic measures at 12 months. RESULTS Patients (95% AAs, 65% male, mean age 49.4) were randomized to the standard (n = 65) or the intensive (n = 58) BP therapy groups. Despite significant reductions in systolic BP (sBP) from baseline (−10.9 vs. −19.1 mm Hg, respectively) (P < 0.05), no significant differences were noted between intention-to-treat groups (P = 0.33) or the proportion with resolution of SHHD (P = 0.31). However, on post hoc analysis, achievement of a sBP <130 mm Hg was associated with significant reduction in indexed left ventricular mass (−6.91 gm/m2.7; P = 0.008) which remained significant on mixed effect modeling (P = 0.031). CONCLUSIONS In post hoc analysis, sBP <130 mm Hg in predominantly AA patients with SHHD was associated with improved cardiac function and reverse remodeling and may help to explain preventative effects of lower BP goals. CLINICAL TRIALS REGISTRATION Trial Number NCT00689819.


Author(s):  
Peter Wolf ◽  
Benjamin Marty ◽  
Khaoula Bouazizi ◽  
Nadjia Kachenoura ◽  
Céline Piedvache ◽  
...  

Abstract Context Cardiovascular disease is the leading cause of death in patients with Cushing’s syndrome. Cortisol excess and adverse metabolic profile could increase cardiac fat, which can subsequently impair cardiac structure and function. Objective We aimed to evaluate cardiac fat mass and distribution in patients with Cushing’s syndrome. Design In this prospective cross-sectional study 23 patients with Cushing’s syndrome and 27 control subjects of comparable age, sex and body-mass-index were investigated by cardiac magnetic resonance imaging and proton spectroscopy. Patients were explored before and after biochemical disease remission. Outcome measures Myocardial fat measured by the Dixon method was the main outcome measure. The intramyocardial triglyceride/water ratio measured by spectroscopy and epicardial and pericardial fat volumes were secondary outcome measures. Results No difference was found between patients and controls in intramyocardial lipid content. Epicardial fat mass was increased in patients compared to controls (30.8g/m 2 [20.4;34.8] vs 17.2g/m 2 [13.1;23.5], p<0.0001). Similarly, pericardial fat mass was increased in patients compared to controls (28.3g/m 2 [17.9;38.0] vs 11.4g/m 2 [7.5;19.4], p=0.0035). Sex, HbA1c and presence of hypercortisolism were independent determinants of epicardial fat. Pericardial fat was associated with sex, impaired glucose homeostasis and left ventricular wall thickness. Disease remission decreased epicardial fat mass without affecting pericardial fat. Conclusions Intramyocardial fat stores are not increased in patients with Cushing’s syndrome, despite highly prevalent metabolic syndrome, suggesting increased cortisol-mediated lipid consumption. Cushing’s syndrome is associated with marked accumulation of epicardial and pericardial fat. Epicardial adiposity may exert paracrine proinflammatory effects promoting cardiomyopathy. Trial registration ClinicalTrials.gov, NCT02202902.


2017 ◽  
Vol 20 (1) ◽  
pp. 026 ◽  
Author(s):  
Nan Cheng ◽  
Liuquan Cheng ◽  
Rong Wang ◽  
Lin Zhang ◽  
Changqing Gao

Objective: The aim of this study was to quantify left ventricular torsion by newly applied cardiovascular magnetic resonance feature tracking (CMR-FT), and to evaluate the clinical value of the ventricular torsion as a sensitive indicator of cardiac function by comparison of preoperative and postoperative torsion.Methods: A total of 54 volunteers and 36 patients with previous myocardial infarction (MI) and LV ejection fraction (EF) between 30%-50% were screened preoperatively or postoperatively by MRI. The patients’ short axis views of the whole heart were acquired, and all patients had a scar area >75% in at least one of the anterior or inferior segments. Their apical and basal rotation values were analyzed by feature tracking, and the correlation analysis was performed for the improvement of LV torsion and ejection fraction after CABG. The intra- and inter-observer reliabilities of torsion measured by CMR-FT were assessed.Results: In normal hearts, the apex rotated counterclockwise in the systolic period with the peak rotation as 10.2 ± 4.8°, and the base rotated clockwise as the peak value was 7.0 ± 3.3°. There was a timing hiatus between the apex and base untwisting, during which period the heart recoils and its suction sets the stage for the following rapid filling period. The postoperative torsion and rotation significantly improved compared with preoperative ones. However, the traditional indicator of cardiac function, ejection fraction, didn’t show significant improvement.Conclusion: Left ventricular torsion derived from CMR-FT, which does not require specialized CMR sequences, was sensitive to patients with low ejection fraction whose cardiac function significantly improved after CABG. The rapid acquisition of this measurement has potential for the assessment of cardiac function in clinical practice. 


2010 ◽  
Vol 13 (1) ◽  
pp. 31 ◽  
Author(s):  
Federico Benetti ◽  
Ernesto Pe�herrera ◽  
Teodoro Maldonado ◽  
Yan Duarte Vera ◽  
Valvanur Subramanian ◽  
...  

Background: End-stage heart failure (HF) is refractory to current standard medical therapy, and the number of donor hearts is insufficient to meet the demand for transplantation. Recent studies suggest autologous stem cell therapy may regenerate cardiomyocytes, stimulate neovascularization, and improve cardiac function and clinical status. Although human fetal-derived stem cells (HFDSCs) have been studied for the treatment of a variety of conditions, no clinical studies have been reported to date on their use in treating HF. We sought to determine the efficacy and safety of HFDSC treatment in HF patients.Methods and Results: Direct myocardial transplantation of HFDSCs by open-chest surgical procedure was performed in 10 patients with HF due to nonischemic, nonchagasic dilated cardiomyopathy. Before and after the procedure, and with no changes in their preoperative doses of medications (digoxin, furosemide, spironolactone, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, betablockers), patients were assessed for New York Heart Association (NYHA) class, performance in the exercise tolerance test (ETT), ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) via transthoracic echocardiography, performance in the 6-minute walk test, and performance in the Minnesota congestive HF test. All 10 patients survived the operation. One patient had a stroke 3 days after the procedure, and although she later recovered, she was unable to perform the follow-up tests. Another male patient experienced pericardial effusion 3 weeks after the procedure. Although it resolved spontaneously, the patient abandoned his control tests and died 5 months after the procedure. An autopsy of the myocardium suggested that new young cells were present in the cardiomyocyte mix. At 40 months, the mean (SD) NYHA class decreased from 3.4 0.5 to 1.33 0.5 (P = .001); the mean EF increased 31%, from 26.6% 4% to 34.8% 7.2% (P = .005); and the mean ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic equivalents, from 2.46 to 5.63) (P < .0001); the mean LVEDD decreased 15%, from 6.85 0.6 cm to 5.80 0.58 cm (P < .001); mean performance in the 6-minute walk test increased by 43.2%, from 251 113.1 seconds to 360 0 seconds (P = .01); the mean distance increased 64.4%, from 284.4 144.9 m to 468.2 89.8 m (P = .004); and the mean result in the Minnesota test decreased from 71 27.3 to 6 5.9 (P < .001).Conclusion: Although these initial findings suggest direct myocardial implantation of HFDSCs is feasible and improves cardiac function in HF patients at 40 months, more clinical research is required to confirm these observations.


2013 ◽  
Vol 118 (4) ◽  
pp. 796-808 ◽  
Author(s):  
Pornswan Ngamprasertwong ◽  
Erik C. Michelfelder ◽  
Shahriar Arbabi ◽  
Yun Suk Choi ◽  
Christopher Statile ◽  
...  

Abstract Background: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal–fetal hemodynamic instability and fetal myocardial depression. The authors’ preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal–fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. Methods: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. Results: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6–21.4; P &lt; 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P &lt; 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. Conclusion: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.


2003 ◽  
Vol 9 (5) ◽  
pp. S1
Author(s):  
Patrick I. McConnell ◽  
Louis Astra ◽  
E.William Schneeberger ◽  
Doug Jacoby ◽  
Jonathan Dinsmore ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Leon-Justel ◽  
Jose I. Morgado Garcia-Polavieja ◽  
Ana Isabel Alvarez-Rios ◽  
Francisco Jose Caro Fernandez ◽  
Pedro Agustin Pajaro Merino ◽  
...  

Abstract Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.


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