Diffuse Primary Malignant Pericardial Mesothelioma With Myocardial involvement: A Comprehensive Assessment Using Multimodel Echocardiography.

Diffuse primary malignant pericardial mesothelioma (PMPM) is an extremely rare and highly invasive tumor of pericardium. The tumor can infiltrate myocardium in part of cases, and will contribute to grave prognosis. Herein, we reported a 58-year-old man of diffuse PMPM with myocardial involvement, and summarized 39 cases of diffuse PMPM. Multimodal echocardiography, which combined conventional, tissue Doppler and speckle tracking echocardiography, was applied to diagnose diffuse PMPM with myocardial involvement, and assess the myocardial function. The common features were pericardial effusion, pericardial masses and thickened pericardium. The other echocardiographic characteristics were extensive and heterogenous echo, adhesion with pericardium and myocardium, reduced motion of adhered myocardium, and constriction performance. Diffuse PMPM with myocardial involvement revealed decreased LV diastolic function, and decreased LV and RV systolic function. Especially in systolic function, the unique strain features were reduced longitudinal strains from segmental to global and from epicardial to endocardial, relative 'septal sparing' pattern, and decreased transmural gradient of longitudinal strain. Our findings suggested that multimodal echocardiography not only can identify this disease, but also can provide detailed information of myocardial dysfunction, which provides a reference for clinicians to develop an optimal individualized treatment.

Assessment of the epi-pericardial fibrotic substrate by collagen-targeted probes.

The identification of the fibrotic arrhythmogenic substrate as a means of improving the diagnosis and prediction of atrial fibrillation has been a focus of research for many years. The relationship between the degree of atrial fibrosis as a major component of atrial cardiomyopathy and the recurrence of arrhythmia after AF ablation can correlate. While the focus in identification and characterisation of this substrate has been centred on the atrial wall and the evaluation of atrial scar and extracellular matrix (ECM) expansion by late gadolinium-enhancement (LGE) on cardiac magnetic resonance imaging (CMRI), LGE cannot visualise diffuse fibrosis and diffuse extravasation of gadolinium. The atrial pericardium is a fine avascular fibrous membranous sac that encloses the atrial wall, which can undergo remodelling leading to atrial disease and AF. Nevertheless, little attention has been given to the detection of its fibrocalcification, impact on arrhythmogenesis and, most importantly, on the potential prothrombotic role of epi-pericardial remodelling in generation of emboli. We have recently reported that tracers against collagen I and IV can provide a direct assessment of the ECM, and thus can estimate fibrotic burden with high sensitivity. Here, we show the ability of these optical tracers to identify epi-pericardial fibrosis, as well as to demonstrate subtle interstitial fibrosis of the atrial wall in a mouse model of beta-2-adrenergic receptor (ß2-AR) cardiac overexpression.

Assessment of Pericardial Disease with Cardiovascular MRI.

Disorders of the pericardium are common and can result in significant morbidity and mortality. Advances in multimodality imaging have enhanced our ability to diagnose and stage pericardial disease and improve our understanding of the pathophysiology of the disease. Cardiovascular MRI (CMR) can be used to define pericardial anatomy, identify the presence and extent of active pericardial inflammation, and assess the hemodynamic consequences of pericardial disease. In this way, CMR can guide the judicial use of antiinflammatory and immune modulatory medications and help with timing of pericardiectomy. CMR can also be used to diagnose congenital disorders of the pericardium. Furthermore, CMR can be used to define pericardial masses and understand their malignant potential.

Assessment of arterial stiffness and epicardial adipose tissue thickness in predicting the subclinical atherosclerosis in patients with ankylosing spondylitis.

OBJECTIVE: Atherosclerosis is a chronic, progressive, inflammatory disease. Recognition of subclinical atherosclerotic vascular changes before clinical manifestation in an asymptomatic population is important for risk stratification and optimal management, which finally leads to the prevention of cardiovascular disease. We aimed to determine the risk of premature subclinical atherosclerosis by evaluating epicardial adipose tissue thickness (EATT) and arterial stiffness parameters in patients with ankylosing spondylitis (AS). METHODS: We performed a prospective study of 60 consecutive patients meeting modified New York criteria for AS compared to 60 controls matched for age and sex. Patients with traditional cardiovascular risk factors were excluded. Arterial stiffness parameters and EATT (examined via echocardiography) values of all patients and control groups were measured. RESULTS: There was no difference between basal characteristic and echocardiographic parameters in patients with AS and in the control group. EATT and pulse wave velocity (PWV) were higher in the AS patients compared to the control group. EATT was 5.74 ± 1.22 mm and 4.91 ± 1.21 mm (p < .001) and PWV was 9.90 ± 0.98 m/s and 6.46 ± 0.83 m/s (p = .009) in the AS and control groups, respectively. Also, PWV was significantly correlated with EATT, age, and central blood pressure in patients with AS. CONCLUSIONS: EATT and PWV, markers of atherosclerosis and cardiovascular disease, were significantly higher in patients with AS than the control group. In addition, in this study, it has been shown that there is a significant relationship between PWV and EATT in patients with AS.

Toxicological assessment and developmental abnormalities induced by butylparaben and ethylparaben exposure in zebrafish early-life stages.

Toxicological effects of butylparaben (BuP) and ethylparaben (EtP) on zebrafish (Danio rerio) early-life stages are not well established. The present study evaluated, using zebrafish embryos and larvae, the toxicity of BuP and EtP through benchmark dose (BMD) approach. BuP was more toxic than EtP to zebrafish larvae. In fact, Lethal Concentration 50 (LC50) values at 96 h post-fertilization (hpf) for BuP and EtP were 2.34 mg/L and 20.86 mg/L, respectively. Indeed, BMD confidence interval (lower bound (BMDL) - upper bound (BMDU) was 0.91-1.92 mg/L for BuP and 10.8-17.4 mg/L for EtP. Zebrafish embryos exposed to 1 mg/L, 2.5 mg/L of BuP and 5 mg/L, 10 mg/L, 20 mg/L, 30 mg/L of EtP showed several developmental abnormalities and teratological effects compared to negative control. Exposed zebrafish developed reduced heartbeat, reduction in blood circulation, blood stasis, pericardial edema, deformed notochord and misshaped yolk sac. Embryos exposed to the highest concentrations of the chemicals (2.5 mg/L of BuP, 10 mg/L, 20 mg/L and 30 mg/L of EtP) showed the developmental abnormalities at 48 hpf while those treated with 1 mg/L of BuP and 10 mg/L of EtP reported behavioral changes at 72 hpf, including trembling of head, pectoral fins and spinal cord. This research identified the lethal and sublethal effects of BuP and EtP in zebrafish early-life stages and could be helpful to elucidate the developmental pathways of toxicity of parabens.

Assessment of Epicardial Adipose Tissue Thickness in Children with Familial Mediterranean Fever.

BACKGROUND: Familial Mediterranean fever (FMF) is suggested to be associated with increased risk of atherosclerosis. Epicardial adipose tissue (EAT) thickness is used in prediction of atherosclerotic risk. The aim of our study was to evaluate EAT thickness in FMF patients for early detection of risk of atherosclerosis and to be compared with its level in healthy controls. METHODS: Thirty 6- to 18-year-old children with FMF and 30 age- and sex-matched children (control group) were included in the study. Disease characteristics, disease severity and Mediterranean fever gene mutations were recorded. EAT thicknesses was measured by echocardiography. RESULTS: EAT in patients' group was significantly greater than that of controls (5.21 ± 2.3 vs. 2.81 ± 2.96 mm, p = 0.001) and was correlated with cholesterol level and platelets count (p = 0.047 and 0.018, respectively). CONCLUSION: This study concluded that EAT thickness was statistically increased in FMF patients than controls with a positive correlation with cholesterol level and platelet count. This finding suggests a higher risk for atherosclerosis in these patients. Follow-up study is needed to verify the effect of treatment of FMF on the EAT thickness. Further studies with larger number of patients following-up EAT are needed to verify this finding.

Pericardial fat versus BMI in the assessment of coronary atherosclerotic burden in patients with diabetes mellitus.

AIMS: To investigate the association of obesity measured by body mass index (BMI) versus pericardial fat volume (PFV) measured by multi-detector computed tomography (MDCT) with coronary atherosclerotic markers (coronary artery calcium score (CAC), coronary stenosis severity and coronary plaque presence) in patients with type 2 diabetes mellitus (DM). METHODS: Among 496 patients with suspected coronary artery disease who underwent 64-slice MDCT angiography to exclude occlusive coronary artery disease, 102 patients with DM were enrolled in the present study. RESULTS: PFV showed a significant association with CAC (r = 0.2, P = 0.01) and significant coronary artery stenosis [PFV median (IQR) = 75 (51-136) in patients with coronary stenosis < 50% versus PFV median (IQR) = 113 (68-140) in patients with coronary stenosis ≥ 50%, P = 0.01] while there was no significant association of PFV with coronary plaque presence (PFV median (IQR) = 84 (56-140) in patients without plaque versus PFV median (IQR) = 109 (70-136) in patients with plaque presence, P = 0.4). The association between PFV with CAC persisted after adjustment for conventional cardiac risk factors. BMI showed no significant association with CAC, coronary stenosis severity and coronary plaque presence (P > 0.05). CONCLUSIONS: PFV was independently associated with CAC in diabetic patients. PFV, rather than obesity measured by BMI, could be used as an imaging biomarker for assessing coronary atherosclerotic burden in patients with DM.

Comparison of the dose on specific 3DCT images and the accumulated dose for cardiac structures in esophageal tumors radiotherapy: whether specific 3DCT images can be used for dose assessment?

BACKGROUND: Cardiac activity could impact the accuracy of dose assessment for the heart, pericardium and left ventricular myocardium (LVM). The purpose of this study was to explore whether it is possible to perform dose assessment by contouring the cardiac structures on specific three-dimensional computed tomography (3DCT) images to reduce the impact of cardiac activity. METHODS: Electrocardiograph-gated 4DCT (ECG-gated 4DCT) images of 22 patients in breath-hold were collected. MIM Maestro 6.8.2 (MIM) was used to reconstruct specific 3DCT images to obtain the Maximal intensity projection (MIP) image, Average intensity projection (AIP) image and Minimum intensity projection (Min-IP) image. The heart, pericardium and LVM were contoured in 20 phases of 4DCT images (0, 5%... 95%) and the MIP, AIP and Min-IP images. Then, a radiotherapy plan was designed at the 0% phase of the 4DCT images, and the dose was transplanted to all phases of 4DCT to acquire the dose on all phases, the accumulated dose of all phases was calculated using MIM. The dose on MIP, AIP and Min-IP images were also obtained by deformable registration of the dose. The mean dose (Dmean), V5, V10, V20, V30 and V40 for the heart, pericardium and LVM in MIP, AIP and Min-IP images were compared with the corresponding parameters after dose accumulation. RESULTS: The mean values of the difference between the Dmean in the MIP image and the Dmean after accumulation for the heart, pericardium and LVM were all less than 1.50 Gy, and the dose difference for the pericardium and LVM was not statistically significant (p > 0.05). For dose-volume parameters, there was no statistically significant difference between V5, V10, and V20 of the heart and pericardium in MIP, AIP, and Min-IP images and those after accumulation (p > 0.05). For the LVM, only in the MIP image, the differences of V5, V10, V20, V30 and V40 were not significant compared to those after dose accumulation (p > 0.05). CONCLUSIONS: There was a smallest difference for the dosimetry parameters of cardiac structures on MIP image compared to corresponding parameters after dose accumulation. Therefore, it is recommended to use the MIP image for the delineation and dose assessment of cardiac structures in clinical practice.

Assessment of the relationship between serum paraoxonase activity and epicardial adipose tissue in hemodialysis patients.

PURPOSE: Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL) enzyme, which has been shown to reduce susceptibility to low-density lipoprotein (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of atherosclerosis. The aim of this study was to determine the relationship between PON-1 activity and EAT in hemodialysis (HD) patients. METHODS: This is a cross-sectional study conducted on 72 (43 males) HD patients with end-stage renal disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate, and parathyroid hormone were measured. PON-1 activity was also measured and compared to the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. Echocardiography was used to measure EAT thickness (EATT). The correlation between PON-1 and EATT was assessed, while independent predictors of EATT in HD patients were similarly assessed using multivariate regression analysis. RESULTS: There was a significant low mean value of PON-1 activity in HD patients compared with the control group (82.1 ± 31.6 vs. 164.3 ± 61.5 U/l, p = 0.0001) and significant high mean value of EATT in HD patients, compared with controls (6.2 ± 1.7 vs. 3.9 ± 1.1 mm, p = 0.0001). In addition, there was a significant negative correlation between PON-1 activity and EATT (r = -0.484, p = 0.0001) and a significant positive correlation between PON-1 activity and HDL-C (r = 0.417, p = 0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass index were found to be independent predictors of EATT. CONCLUSION: Our study demonstrated that PON-1 activity was significantly lower in HD patients compared with healthy controls and that PON-1 activity was inversely correlated with EATT in this population.

Does masked hypertension impact left ventricular deformation?

Our aim was to compare left ventricular (LV) deformation in subjects with masked hypertension (MH) to normotensive and sustained hypertensive patients. This cross-sectional study included 185 untreated subjects who underwent 24-hour ambulatory blood pressure (BP) monitoring and complete two-dimensional echocardiographic (2DE) examination including multilayer strain analysis. MH was diagnosed if clinic BP was normal (<140/90 mm Hg), and 24-hour BP was increased (≥130/80 mm Hg). 2DE LV longitudinal and circumferential strains gradually and significantly decreased from normotensive controls across MH individuals to sustained hypertensive patients. 2DE radial strain was not different between groups. 2DE longitudinal and circumferential endocardial and midmyocardial layer strains progressively decreased from normotensive control to sustained hypertensive individuals. Longitudinal and circumferential epicardial layer strains were lower in sustained hypertensive patients than in normotensive controls. Clinic and 24-hour systolic BP were associated with 2DE LV longitudinal endocardial strain, midmyocardial strain, and 2DE circumferential endocardial strain in the whole-study population independent of LV structure and diastolic function. MH significantly affect LV deformation assessed by 2DE traditional strain and 2DE multilayer strain. Clinic and 24-hour systolic BP were associated with LV mechanics evaluated with comprehensive 2DE strain analysis independent of LV structure and diastolic function.

Assessment of epicardial adipose tissue thickness in patients with resistant hypertension.

OBJECTIVE: Recent studies have shown that epicardial adipose tissue (EAT) thickness is increased in patients with hypertension. In this study, we aimed to investigate the relation of EAT thickness with resistant hypertension (RHT). PARTICIPANTS AND METHODS: Study participants (n=150) were classified into three groups according to their office and ambulatory blood pressure measurements: RHT (n=50), controlled hypertension (CHT, n=50), and normotension (NT, n=50). All patients underwent a transthoracic echocardiographic examination to measure EAT thickness. RESULTS: Clinical and biochemical characteristics of the groups were similar, except the CRP level, which was significantly increased in hypertensive patients compared with patients with NT (P<0.001). EAT thickness differed significantly between groups (P<0.001). The highest values were obtained in the RHT group (4.64±1.24 cm), followed by the CHT (3.3±0.82 cm) and NT (2.6±0.76 cm) groups. Multivariate analysis indicated age, physical activity level, and EAT thickness as independent predictors of RHT. The optimal cut-off value of EAT thickness for detection of RHT was found to be 3.42 cm, with a sensitivity and specificity of 82 and 77%, respectively (AUC=0.87, 95% confidence interval 0.81-0.92, P<0.000). CONCLUSION: EAT can be effective on blood pressure by several mechanisms. In this study, for the first time in the literature, the association of EAT with RHT is reported.

Invasive assessment of the coronary microcirculation in the catheter laboratory.

Historically much of our understanding of the coronary circulation has been centered towards the epicardial vessels. However, recent work has highlighted the importance of the coronary microcirculation across a broad spectrum of clinical conditions in influencing patient outcomes. Therefore an ability to measure microvascular function is most valuable. While evaluation of the epicardial coronary circulation is widely understood, interrogation of the coronary microcirculation is more complex. Many methods are available to assess the integrity of the microcirculation in the catheter laboratory. This review will discuss the physiology of the coronary microcirculation and evaluate the utility of available invasive techniques.

Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term Serial SPECT Imaging of Sodium Iodide Symporter Expression.

Heart failure is a leading cause of morbidity and mortality, and cardiac gene delivery has the potential to provide novel therapeutic approaches. Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, but cardiotropism, immune tolerance, and optimal delivery strategies in large animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide symporter (NIS) was administered to adult immunocompetent dogs via epicardial injection, coronary infusion without and with cardiac recirculation, or endocardial injection via a novel catheter with curved needle and both end- and side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression was tracked by single-photon emission computerized tomography (SPECT) imaging in addition to Western blot and immunohistochemistry. Direct epicardial or endocardial injection resulted in strong cardiac expression, whereas expression after intracoronary infusion or cardiac recirculation was undetectable. A threshold myocardial injection dose that provides robust nonimmunogenic expression was identified. The extent of transmural myocardial expression was greater with the novel catheter versus straight end-hole needle delivery. Furthermore, the authors demonstrate that cardiac NIS reporter gene expression and duration can be quantified using serial noninvasive SPECT imaging up to 1 year after vector administration. These data are relevant to efforts to develop cardiac gene delivery as heart failure therapy.

Assessment of epicardial adipose tissue thickness and the mean platelet volume in children with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an inflammatory disease, which is suggested to be associated with increased risk of atherosclerosis. Epicardial adipose tissue (EAT) thickness and the mean platelet volume (MPV) are parameters used in prediction of atherosclerotic risk in various conditions. These parameters were evaluated in children with FMF and compared with healthy controls. METHODS: Forty-five patients with FMF and 54 age- and gender-matched healthy controls were assessed. Duration of symptoms, age at diagnosis, duration of delay in diagnosis, frequency and duration of FMF attacks, disease severity scores, response to colchicine therapy, MEditerraneanFeVer (MEFV) gene mutations, and MPV values were recorded. EAT thicknesses were measured by echocardiography. RESULTS: Epicardial adipose tissue thicknesses of the children with FMF were found to be significantly greater than that of controls (5.1 ± 1.4 vs. 4.5 ± 0.9 mm, p=0.036). FMF patients had significantly higher MPV values compared with the controls (7.8 ± 1.1 vs. 7.3 ± 1.4 fl, p=0.044). Age at diagnosis, duration of delay in diagnosis, and MPV values were found to be correlated with EAT thickness in the patient group (r=0.49, p=0.001 for the former parameters and r=0.32, p=0.04 for MPV). CONCLUSION: Epicardial adipose tissue thickness and MPV values seem to be increased in children with FMF. These findings may indicate an increased risk of atherosclerosis in FMF patients.

Cardiac MR imaging in constrictive pericarditis: multiparametric assessment in patients with surgically proven constriction.

To assess the utility of cardiac magnetic resonance (MR) imaging in the diagnosis of constrictive pericarditis (CP). This study was approved by the institutional review board, with a waiver of informed consent. A total of 42 consecutive patients (mean age, 55 ± 16 years; 3 women, 39 men) with CP treated with pericardiectomy who had undergone cardiac MR before surgery were evaluated retrospectively. An additional 21 patients were evaluated as a control group; of these, 10 consecutive patients received cardiac MR for reasons other than suspected pericardial disease, and 11 consecutive patients had a history of pericarditis but no clinical suspicion of pericardial constriction. MR imaging parameters were analyzed independently and with a decision tree algorithm for usefulness in the prediction of CP. Catheterization data were also reviewed when available. A model combining pericardial thickness and relative interventricular septal (IVS) excursion provided the best overall performance in prediction of CP (C statistic, 0.98, 100% sensitivity, 90% specificity). Several individual parameters also showed strong predictive value in the assessment of constriction, including relative IVS excursion (sensitivity, 93%; specificity, 95%), pericardial thickness (sensitivity, 83%; specificity, 100%), qualitative assessment of pathologic coupling (sensitivity, 88%; specificity, 100%), diastolic IVS bounce (sensitivity, 90%; specificity, 85%), left ventricle area change (sensitivity, 86%; specificity, 100%), and eccentricity index (sensitivity, 86%; specificity, 90%; all P < 0.001). Strong agreement was observed between catheterization and surgical findings of constriction (97%). Cardiac MR provides robust quantitative and qualitative analysis for the diagnosis of CP.

Automated quantification of epicardial adipose tissue (EAT) in coronary CT angiography; comparison with manual assessment and correlation with coronary artery disease.

BACKGROUND: Epicardial adipose tissue (EAT) is emerging as a risk factor for coronary artery disease (CAD). OBJECTIVE: The aim of this study was to determine the applicability and efficiency of automated EAT quantification. METHODS: EAT volume was assessed both manually and automatically in 157 patients undergoing coronary CT angiography. Manual assessment consisted of a short-axis-based manual measurement, whereas automated assessment on both contrast and non-contrast-enhanced data sets was achieved through novel prototype software. Duration of both quantification methods was recorded, and EAT volumes were compared with paired samples t test. Correlation of volumes was determined with intraclass correlation coefficient; agreement was tested with Bland-Altman analysis. The association between EAT and CAD was estimated with logistic regression. RESULTS: Automated quantification was significantly less time consuming than automated quantification (17 ± 2 seconds vs 280 ± 78 seconds; P < .0001). Although manual EAT volume differed significantly from automated EAT volume (75 ± 33 cm(³) vs 95 ± 45 cm(³); P < .001), a good correlation between both assessments was found (r = 0.76; P < .001). For all methods, EAT volume was positively associated with the presence of CAD. Stronger predictive value for the severity of CAD was achieved through automated quantification on both contrast-enhanced and non-contrast-enhanced data sets. CONCLUSION: Automated EAT quantification is a quick method to estimate EAT and may serve as a predictor for CAD presence and severity.

Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment.

BACKGROUND: Contact force (CF) is an important determinant of lesion formation for atrial endocardial radiofrequency ablation. There are minimal published data on CF and ventricular lesion formation. We studied the impact of CF on lesion formation using an ovine model both endocardially and epicardially. METHODS AND RESULTS: Twenty sheep received 160 epicardial and 160 endocardial ventricular radiofrequency applications using either a 3.5-mm irrigated-tip catheter (Thermocool, Biosense-Webster, n=160) or a 3.5 irrigated-tip catheter with CF assessment (Tacticath, Endosense, n=160), via percutaneous access. Power was delivered at 30 watts for 60 seconds, when either catheter/tissue contact was felt to be good or when CF>10 g with Tacticath. After completion of all lesions, acute dimensions were taken at pathology. Identifiable lesion formation from radiofrequency application was improved with the aid of CF information, from 78% to 98% on the endocardium (P<0.001) and from 90% to 100% on the epicardium (P=0.02). The mean total force was greater on the endocardium (39±18 g versus 21±14 g for the epicardium; P<0.001) mainly because of axial force. Despite the force-time integral being greater endocardially, epicardial lesions were larger (231±182 mm(3) versus 209±131 mm(3); P=0.02) probably because of the absence of the heat sink effect of the circulating blood and covered a greater area (41±27 mm(2) versus 29±17 mm(2); P=0.03) because of catheter orientation. CONCLUSIONS: In the absence of CF feedback, 22% of endocardial radiofrequency applications that are thought to have good contact did not result in lesion formation. Epicardial ablation is associated with larger lesions.