Haim Shmilovich

Transfer of Endothelial Progenitor and Bone Marrow Cells Influences Atherosclerotic Plaque Size and Composition in Apolipoprotein E Knockout Mice

Objectives—Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell– or spleen cell–derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model. Methods and Results—ApoE KO mice aged 10 weeks served as recipients. Labeled BM cells and spleen cell–derived EPCs from age-matched apoE KO mice were injected intravenously to 2 groups of recipient mice each. Additional mice served as controls receiving saline. Both protocols were repeated 3 times at 2 weekly intervals. On killing, plaque size and character were studied, lipid profile analyzed, and serum and aortic cytokines assayed. Spleen cell–derived cells contained a significantly larger number of endothelial cell precursors. Labeled EPCs and BM cells were found abundantly in the spleens, yet also in the lesions of the recipient mice. Aortic sinus lesion size was significantly increased in mice receiving BM cells (n=10) in the EPC-treated group (n=10) compared with controls (n=10; a 54% and a 34% increase in aortic sinus plaque area, respectively). Mice receiving EPCs exhibited plaques with larger lipid cores and thinner fibrous caps and a higher number of infiltrating CD3 cells. RT-PCR analysis of aortas revealed reduced expression of mRNA for interleukin-10 (IL-10) in both cell transfer groups. Higher serum concentrations of IL-6 and monocyte chemoattractant protein-1 were found in sera from BM recipients, whereas lower IL-10 levels were found in mice transfused with spleen-derived EPCs. Conclusions—Transfer of BM cells and EPCs may result in an increase in atherosclerotic lesion size, whereas EPC transfer could also potentially influence plaque stability.

Circulating Endothelial Progenitor Cells in Patients with Cardiac Syndrome X

Background: Cardiac syndrome X (CSX) encompasses the constellation of anginal chest pain in the presence of a pathological functional test and a normal coronary angiogram. Endothelial progenitor cells (EPCs) in the peripheral circulation contribute to tissue vascularisation. Objective: To investigate the number and functional properties of circulating EPCs in patients with CSX. Methods: 17 patients with CSX and a referent population (n = 20) were matched for age, atherosclerotic risk factors and use of drugs. Numbers of EPCs were studied by FACS, and their functional properties, including their proliferative capacity, adherence to matrix and mature endothelial cells as well as their ability to support in vitro tube formation, were investigated. Levels of soluble markers that associate with peripheral mobilisation and homing were studied in the serum samples of all subjects. Results: Patients with CSX had significantly increased numbers of circulating EPCs as compared with the referent population (both CD34+/KDR and CD34+/CD133+). The proliferative capacity of EPCs and their ability to support in vitro tube formation were significantly impaired in patients with CSX as compared with the referent population. However, adhesiveness of EPCs from patients with CSX to fibronectin and cultured mature endothelial cells was enhanced as compared with the referent population. Serum vascular endothelial growth factor correlated with peripheral CD34+/KDR cell numbers, whereas serum concentration of erythropoietin correlated with the number of circulating CD34+/CD133+ cells Conclusion: Patients with CSX have a significantly altered circulating EPC phenotype that could potentially aid in understanding the complex pathogenesis of the syndrome.

Coronary ostium—straight tube or funnel–shaped? A computerized tomographic coronary angiography study

Background: The 3D configuration of the aortic‐coronary junction is decisive in stenting ostial coronary lesions. We hypothesized that it varies between straight to funnel–shaped tubes and studied arterial orifices using computerized tomographic coronary angiography (CTCA). Methods and Results: Axial and sagittal 2‐D and volumetric 3‐D reconstructions of the aorto‐coronary junction were performed in 25 patients who underwent CTCA. The following measurements of the left main (LM) and right coronary (RCA) arteries ostia were obtained: the coronary orifice broad base diameter, the diameter of the coronary vessel most proximal segment, the distance between them, and the angles of the aortic‐coronary junction. All patients exhibited a funnel–shaped aortic‐coronary junction in at least one plane, and none had an entirely straight tube shape. The RCA take–off had symmetric angling in both the axial and sagittal planes in only one patient, while the LM did not have a symmetric origin in either plane in any patient. The mean coronary orificial funnel depth and ostial cross–sectional diameters were measured. Conclusion: The frequency of funnel‐shaped and asymmetry of the aortic‐coronary junction configuration needs to be considered in designing stents for aortic–ostial coronary lesions in order to achieve optimal results and reduce restenosis.

Shift Work and the Risk of Coronary Artery Disease: A Cardiac Computed Tomography Angiography Study

Aims: Shift work disrupts the normal circadian rhythm and is associated with risk factors for coronary artery disease (CAD) and a higher incidence of CAD morbidity and mortality. Cardiac computed tomography angiography (CCTA) is a robust noninvasive modality for assessing the presence, extent, and severity of CAD. We sought to investigate whether shift workers are prone to a higher burden of CAD compared to non-shift workers. Methods: We conducted a historically prospective study in consecutive patients who underwent CCTA and answered a telephonic questionnaire. Due to significant differences in age and gender, we compared 89 well-matched pairs of shift workers and non-shift workers with the use of propensity scores. Results: Our cohort consisted of 349 participants, of whom 94 (26.9%) were shift workers. The mean age was 50.7 years, and 62.5% were males. After pairing, we showed that shift workers had a higher prevalence of CAD than non-shift workers (74.2 vs. 53.9%, respectively, p = 0.01), and a lower prevalence of coronary calcium scores of zero (46.8 vs. 63.4%, respectively, p = 0.034). Stenosis >50% was more prevalent in shift workers than in non-shift workers (20.2 vs. 11.2%, respectively, p = 0.006), and the extent of CAD (defined as the presence of ≥1-vessel disease) tended to be higher in shift workers than in non-shift workers (25.8 vs. 13.5%, respectively, p = 0.06). Conclusions: In this CCTA study, we showed in a well-matched cohort of consecutive patients that shift workers had a higher prevalence and extent of CAD than non-shift workers.

Aortoventricular annulus shape as a predictor of pacemaker implantation following transcatheter aortic valve replacement

Aims Conduction abnormalities following transcatheter aortic valve replacement (TAVR) are caused by damage of the aortoventricular conduction tissue during positioning of the valve. Therefore, our aim was to assess whether a higher difference between the long and short diameters of the elliptic aortoventricular annulus will possess higher forces on the annulus, and thus will be a predictor of pacemaker need following TAVR. Methods We retrospectively analyzed 123 patients who had the aortoventricular annulus measured by computed tomography angiography. The difference between maximal (Dmax) and minimal (Dmin) diameters of the annulus was considered the elliptic factor (ELFA), which was analyzed using t test to evaluate whether it differs between the group who received a pacemaker and the group without the need for a pacemaker. Then, using univariate and multivariate models adjusted for other confounders predicting the need for a pacemaker, we sought to evaluate whether a higher ELFA is a predictor of pacemaker implantation. Results Mean age was 82.2 ± 6.4 years, and 62.6% were women. Average Dmax, Dmin and ELFA were 25.8, 20.8 and 5 mm, respectively. Fourteen patients (11.4%) underwent pacemaker implantation. Those patients had an ELFA of 5.9 mm compared with 4.9 mm in those who did not receive a pacemaker (P < 0.01). In multivariate analysis, a higher ELFA remained a statistically significant and independent predictor for the need of a pacemaker (P = 0.046). Conclusion A high ELFA is an independent and significant predictor of the need for pacemaker implantation after TAVR and suggests further investigation whether it should be considered as a factor in managing TAVR patients.