Sara Shimoni

Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease : Echocardiographic and tissue doppler imaging assessment

Nonalcoholic fatty liver disease (NAFLD) is linked to the metabolic syndrome. The aim of the present study is to determine the effect of the metabolic syndrome on left ventricular (LV) geometry and function using as a model patients with NAFLD. Thirty-eight patients with NAFLD, less than 55 years of age and with a normal exercise test, were compared with an age and sex-matched control group. Patients with diabetes mellitus, hypertension, and body mass index>40 were excluded. A complete echocardiographic study including tissue Doppler imaging (TDI) was performed. The following parameters were assessed by echo Doppler: peak velocities of early (E) and late (A) diastolic filling, E/A ratio, flow propagation velocity (Vp). Using TDI early diastolic velocity (E′), and systolic velocity (S′) of mitral annulus were obtained. The patients with NAFLD had a significantly higher body mass index (31.4±5 vs. 26.4±4u2009kg/m2, P=0.01), higher glucose (100.6±13 vs. 83.0±10u2009mg/dL, P=0.01), and triglyceride levels (126.5±44 vs. 206.5±67u2009mg/dL, P<0.001). Increased thickness of the intraventricular septum, posterior wall (11.03±2.2 vs. 8.9±2.9u2009mm, P=0.001; 8.5±1.7 vs. 9.7±2.3u2009mm, P=0.04), and larger LV mass and LV mass/height (160.7±58.7 vs.115.3±35.4u2009g, P=0.001 and 92.6±29.5 vs. 69.2±19.8u2009g/m, P=0.001, respectively) were found in NAFLD group. LV systolic function was similar in both groups. Patients with NAFLD had a lower E (73.6±11.0 vs. 86.4±20.0u2009cm/s, P<0.006) and E/A ratio (1.0±0.3 vs. 1.76±0.8 P<0.0001). Moreover, the Vp and the E′ on TDI were significantly lower compared with the control group (49.0±9.7 vs. 74.7±18.4u2009cm/s, P<0.0001 and 10.3±2.0 vs. 13.8±1.7u2009cm/s, P<0.0001, respectively). On multivariate analysis the E′ on TDI was the only independent parameter associated with NAFLD. In conclusion, patients with NAFLD in the absence of morbid obesity, hypertension, and diabetes have mildly altered LV geometry and early features of left ventricular diastolic dysfunction. Early diastolic velocity on TDI was found to be the only index that could identify the patients with NAFLD and metabolic syndrome.

Layer-specific strain analysis by speckle tracking echocardiography reveals differences in left ventricular function between rats and humans

The rat heart is commonly used as an experimental model of the human heart in both health and disease states, assuming that heart function of rats and humans is alike. When studying a rat model, echocardiography is usually performed on sedated rats, whereas standard echocardiography on adult humans does not require any sedation. Since echocardiography results of sedated rats are usually inferred to alert humans, in the present study, we tested the hypothesis that differences in left ventricular (LV) function may be present between rats sedated by a low dose of ketamine-xylazine and alert humans. Echocardiography was applied to 110 healthy sedated rats and 120 healthy alert humans. Strain parameters were calculated from the scans using a layer-specific speckle tracking echocardiography program. The results showed that layer longitudinal strain is equal in rats and humans, whereas segmental strain is heterogeneous (P < 0.05) in a different way in rats and humans (P < 0.05). Furthermore, layer circumferential strain is larger in humans (P < 0.001), and the segmental results showed different segmental heterogeneity in rats and humans (P < 0.05). Radial strain was found to be homogeneous at the apex and papillary muscle levels in humans and heterogeneous in rats (P < 0.001). Additionally, whereas LV twist was equal in rats and humans, in rats the rotation was larger at the apex (P < 0.01) and smaller at the base (P < 0.001). The torsion-to-shortening ratio parameter, which indicates the transmural distribution of contractile myofibers, was found to be equal in rats and humans. Thus, when evaluating LV function of sedated rats under ketamine-xylazine, it is recommended to measure the global longitudinal strain, LV twist, and torsion-to-shortening ratio, since no scaling is required when converting these parameters and inferring them to humans.

Experimental myocardial infarction induces altered regulatory T cell hemostasis, and adoptive transfer attenuates subsequent remodeling.

Background Ischemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling. Methods and Results The number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling. Conclusion Treg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling.

Head-up tilt table testing in syncope: Safety and efficiency of isosorbide versus isoproterenol in pediatric population

BACKGROUNDnThe aim of this study was to compare the diagnostic value and safety of sublingual isosorbid dinitrate (ISDN) with intravenous isoproterenol (ISOP) during head-up tilt table testing (HUTT) in pediatric patients with suspected neurocardiogenic syncope.nnnMETHODSnOne hundred thirty-six consecutive pediatric patients complaining of presyncope or syncope were submitted to HUTT for the first time. Those who did not develop syncope or presyncope during passive HUTT for 20 minutes underwent repeated HUTT with either 1.25 to 2.5 mg sublingual ISDN or intravenous ISOP (1-3 mug/min) for 20 minutes. There were 54 boys and 82 girls, aged 10 to 18 years with an average of 15.5 +/- 2.4 years and a median of 16 years. Among the patients with cardioinhibition or mixed responses, the severity of the bradyarrhythmia was scored 1 to 3 (restoration of effective rhythm within 10 seconds, 10-20 seconds, and >20 seconds while back to supine position, respectively).nnnRESULTSnDuring the passive period, 24 (17.6%) of 136 patients had a positive response to HUTT. Syncope was observed in another 44 patients during either ISDN or ISOP period (14/58 [24.1%] and 30/54 [55.5%] with ISDN vs ISOP, respectively, P < .05). The time to symptoms was shorter with both ISDN and ISOP compared with passive period (6.5 +/- 2.9, 6.3 +/- 5.9, and 10.3 +/- 4.4, minutes, respectively, P < .05). The severity score for cardioinhibition response was significantly higher with ISDN compared with the passive period and ISOP (2 +/- 0.8, 1.25 +/- 0.45, and 1.26 +/- 0.45, respectively, P < .01).nnnCONCLUSIONSnSublingual ISDN is less sensitive and less safe compared to intravenous ISOP in assessing pediatric age patients with suspected neurocardiogenic syncope and with a negative result in tilt test without provocation. The simplicity of ISDN use should be weighed against the risk of longer symptoms with ISDN.

Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy PatientsCLINICAL PERSPECTIVE

Background—Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM. Methods and Results—Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th–75th percentile]; 149.57, [63.14–177.89] versus 20.29, [15.00–53.89] pg/mL, P<0.001) and significantly decreased vascular endothelial growth factor/sFlt1 ratio (P=0.012) compared with controls, with a trend toward lower concentration of circulating CD34+/KDR+ levels. In addition, patients with PPCM had lower early velocities E′ septal (9.9±2.1 versus 11.0±1.5 cm/s, P=0.02), with a significantly lower systolic velocity S′ septal (7.6±1.2 versus 8.5±1.2 cm/s, P=0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (−19.1±3.3 versus −22.7±2.2%, P<0.001) and apical circumferential 2D strain (−16.6±4.9 versus −21.2±7.9, P=0.02) were present in patients with PPCM compared with controls. Conclusions—Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.

Circulating CD14+ monocytes in patients with aortic stenosis

Background Calcific aortic stenosis (AS) is an active process sharing similarities with atherosclerosis and chronic inflammation. The pathophysiology of AS is notable for three cardinal components: inflammation, fibrosis and calcification. Monocytes play a role in each of these processes. The role of circulating monocytes in AS is not clear. The aim of the present study was to study an association between circulating apoptotic and non apoptotic CD14+ monocytes and AS features. Methods We assessed the number of CD14+ monocytes and apoptotic monocytes in 54 patients with significant AS (aortic valve area 0.74 ± 0.27 cm2) and compared them to 33 patients with similar risk factors and no valvular disease. The level of CD14+ monocytes and apoptotic monocytes was assessed by flow cytometry. Results There was no difference in the risk factor profile and known coronary or peripheral vascular diseases between patients with AS and controls. Patients with AS exhibited increased numbers of CD14+ monocytes as compared to controls (9.9% ± 4.9% vs. 7.7% ± 3.9%, P = 0.03). CD14+ monocyte number was related to age and the presence and severity of AS. In patients with AS, both CD14+ monocytes and apoptotic monocytes were inversely related to aortic valve area. Conclusions Patients with significant AS have increased number of circulating CD14+ monocytes and there is an inverse correlation between monocyte count and aortic valve area. These findings may suggest that inflammation is operative not only in early valve injury phase, but also at later developed stages such as calcification when AS is severe.

Autoantibodies to oxidized low-density lipoprotein in patients with aortic regurgitation: association with aortic diameter size.

Background: Aortic regurgitation (AR) is a condition associated with volume overload, causing left-ventricular (LV) remodeling, eccentric LV hypertrophy and eventually heart failure. LV remodeling associated with AR is regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress. Since anti-oxidized low-density lipoprotein (LDL) antibodies (Abs) are a measurable marker of oxidative stress, we hypothesized that an increased level of circulating oxidized LDL (oxLDL) Abs may be related to remodeling of the left ventricle in patients with significant AR. Methods: We assessed IgG anti-oxLDL Abs in 31 patients with significant AR and compared them to 30 patients with similar risk factors and no valvular disease. Abs to oxLDL were determined by ELISA. Results: The 2 groups had similar clinical characteristics. There was no difference between patients with AR and patients with no AR in the level of anti-oxLDL Abs. However, in all patients and controls, anti-oxLDL Abs correlated positively with the diameter of the ascending aorta (AA; r = 0.32, p = 0.016) and the level of oxLDL Abs was significantly higher in patients with an AA diameter ≥39 mm. On multivariate analysis, only white blood cell count and AA diameter were related to anti-oxLDL Abs in all patients. Conclusions: We did not find a difference in the level of anti-oxLDL Abs between patients with AR and controls; however, there was a strong correlation between anti-oxLDL Abs and AA diameter.

An unusual case of endocarditis.

The Case: A 31-year-old woman, an immigrant from Ethiopia, was admitted to hospital with a 2-week history of general weakness, cough and fever. She denied recent dental treatment or intravenous drug use and had not undergone any invasive procedures. She had a temperature of 38.8° C, with a pulse of

Circulating autoantibodies to endothelial progenitor cells: binding characteristics and association with risk factors for atherosclerosis.

Objective Endothelial progenitor cells (EPC) are committed to transform into EC promoting vasculogenic ischemic repair. Anti-endothelial cells (AECA) have been described in various disorders with an associated vascular damage. Herein, we explored a novel circulating population of IgG reactive with EPC, in patients with differential risk profile for atherosclerotic vascular disease. Approach and Results A novel cyto-ELISA system was established where the coated cells were late outgrowth EPC. Levels of anti-EPC antibodies were determined in 100 subjects and differential risk score for atherosclerosis, as well as to circulating EPC levels and the inflammatory markers IL-6 and C-reactive protein. To study endothelial cell (EC) activating properties, sera were tested for their ability to induce VCAM-1 expression in a cell ELISA system. Detectable levels of anti-EPC antibodies, that correlated with age, Framingham risk score and CRP concentrations but did not associate with levels of LDL, HDL, hypertension or diabetes, were detected. Anti-EPC antibodies were distinct from EC binding antibodies as shown by competitive inhibition studies, and have been positively correlated with the extent of EC activation manifested by in vitro VCAM-1 expression. Conclusion This is the first study showing a newly defined subgroup of self-antibodies binding EPC and associating positively with the Framingham risk score. Further studies are required to characterize and test this interesting subset of EPC binding autoantibodies and their potential significance.

Is It Time to Revise the Guidelines and Recommendations for Digital Echocardiography

The first comprehensive recommendations for digital echocardiography were published in 2005. They had a huge impact on the entire development of echocardiography and contributed to an early transition from videotape to an all-digital solution. Since then, there have been no recommendations for digital echocardiography, despite the dramatic development of computer technology and echocardiography machines. For example, the typical echocardiographic video frame rate increased from 30 fps to 40-120 fps, network speed increased from 100 Mbps to 1,000 Mbps and more, CD-ROMs disappeared, and so on.