Search

Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The "omics" tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls) by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells) as well as by circulating cells (monocytes, platelets) or novel biomarkers present in plasma. [ABSTRACT FROM AUTHOR] more...

Severe mitral regurgitation (MR) following mitral balloon valvuloplasty is a major complication of this procedure. We recently described a new echocardiographic score that can predict the development of severe MR following mitral valvuloplasty with the double balloon technique. The present study was designed to test the usefulness of this score for predicting severe MR in patients undergoing the procedure using the Inoue balloon technique. From 117 consecutive patients who underwent mitral valvuloplasty using the Inoue technique, 14 (11.9%) developed severe MR after the procedure. A good quality echocardiogram before mitral valvuloplasty was available in 11 patients. These 11 patients were matched by age, sex, mitral valve area, and degree of MR before valvuloplasty with 69 randomly selected patients who did not develop severe MR after Inoue valvuloplasty. The total MR-echocardiographic (MR-echo) score was significantly greater in the severe MR group (10.5 +/- 1.4 vs 8.2 +/- 1.1; p <0.001). In addition, the component grades for the anterior leaflet (2.9 +/- 0.5 vs 2.2 +/- 0.4; p <0.001), posterior leaflet (2.6 +/- 0.7 vs 1.9 +/- 0.8), commissures (2.4 +/- 0.8 vs 2.0 +/- 0.5; p <0.05) and subvalvular apparatus (2.6 +/- 0.5 vs 1.9 +/- 0.4; p <0.001) were also higher in the MR group. Using a total score of > or = 10 as a cut-off point for predicting severe MR with the Inoue technique, a sensitivity of 82%, specificity of 91%, accuracy of 90%, and negative predictive value of 97% were obtained. Stepwise logistic regression analysis identified the MR-echo score as the only independent predictor for developing severe MR with the Inoue technique (p <0.0001). Thus, the MR-echo score can also predict the development of severe MR following mitral balloon valvuloplasty using the Inoue technique. [ABSTRACT FROM AUTHOR] more...

Background: Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) represent two scarce blood populations that are thought to play important roles in tissue vascularization. They have also been proposed as potential markers for more than a dozen pathologies. Moreover, EPCs have arisen as a new therapeutic option for cardiovascular disease. However nowadays there is certain controversy about their roles and a better understanding of EPC biology is required to develop new strategies for forthcoming therapies., Methods: Flow cytometry analysis was performed on freshly isolated mononuclear cells from control subjects and Acute Coronary Syndrome (ACS) patients. EPCs and CECs for both groups were isolated and quantified. Statistical analyses were performed to test the potential biomarker usefulness of both populations in ACS together with the first "in vivo" proteomic characterizations of these populations., Results: Our results do not show statistical differences in the quantification of CECs and EPCs in control subjects and ACS patients. The proteomic characterization allowed us to identify 673 proteins associated to CECs (389 in controls and 462 in ACS patients), and another 502 proteins in EPCs (350 in controls and 274 in ACS patients)., Conclusions: Our data show the necessity to obtain a more accurate and specific phenotype of CECs and EPCs cells as well as a flow cytometry "golden standard" protocol, before they can be considered useful clinical markers., General Significance: The proteomic data suggest a potential effect of ACS in the protein profiles of these cells., (Copyright © 2012 Elsevier B.V. All rights reserved.) more...

Although aortic root dilation has etiologic and prognostic significance in patients with chronic aortic regurgitation (AR), no information is available regarding changes over time in aortic root size in patients with the entire spectrum of AR severity or how such changes relate to progression of the AR or to left ventricular (LV) overload. To analyze this, a total of 127 patients with chronic AR who had more than 6 months of follow-up by two-dimensional and Doppler echocardiography were included in the study (69 men and 58 women; mean age 59.3 +/- 21.2 years [range 14 to 94 years]; 67 cases of mild, 45 moderate, 15 severe, and 21 bicuspid aortic valve disease). The aortic anulus, sinuses of Valsalva, supraaortic ridge, and ascending aorta were measured in the parasternal long-axis view, LV volumes were calculated (biplane Simpson's approach), and the severity of AR was quantified based on proximal jet size and graded according to an algorithm that takes into account major color Doppler criteria. At entry to the study, significant differences between patients with mild, moderate, and severe AR were noted only in supraaortic ridge size (1.46 +/- 0.29 cm/m2 vs 1.63 +/- 0.33 cm/m2 [p < 0.006]; vs 1.67 +/- 0.43 cm/m2 [p < 0.03]). A significant increase in aortic root size at all levels was observed during the follow-up period in all three groups of severity of AR. The rate of change of the supraaortic ridge, the upper support structure of the anulus and cusps, was faster in patients with more severe degrees of AR (p = 0.013); this was not the case at the other aortic levels. No differences were observed in aortic root size or rate of progression between patients with bicuspid or tricuspid aortic valves. Patients were considered "progressive" if they lay on the steepest positive segment of the curve representing the rank order in the rate of aortic root progression. Compared with "nonprogressive" patients, patients who were progressive in supraaortic ridge size (rate >0.12 cm/yr; n = 23) had a faster rate of progression in the degree of regurgitation as assessed by the regurgitant jet area/LV outflow tract area ratio measured in the parasternal short-axis view (0.48 +/- 0.45 vs 0.24 +/- 0.5/yr; p < 0.03) and a foster rate of progression of LV end-diastolic volume (30 +/- 22.8 vs 14.4 +/- 15.6 ml/yr; p < 0.0002) and LV mass (70.8 +/- 74.4 vs 16.8 +/- 19.2 gm/yr; p < 0.0004). In conclusion, there is progressive dilation of the aortic root at all levels, even in patients with mild AR. More rapid progression in aortic root size is associated with more rapid progression of the underlying aortic insufficiency, as well as more rapid increases in LV volume and mass. more...

The rate of progression of the degree of chronic aortic regurgitation (AR) is unknown. Furthermore, although left ventricular (LV) dilation has been studied in patients with severe AR, its rate and determining factors, and specifically, its relation to the degree of regurgitation remain to be established and have not previously been studied for mild and moderate AR. The purpose of this study was to explore the progression of chronic AR by 2-dimensional and Doppler echocardiography, and the relation of LV dilation to the fundamental regurgitant lesion and its progression in patients with a full spectrum of initial AR severity. We studied 127 patients with AR by 2-dimensional and Doppler echocardiography (69 men; 59 +/- 21 years; 67 with mild, 45 with moderate, 15 with severe AR). AR increased in 38 patients (30%) (25% of mild, 44% of moderate, and 50% of moderate to severe lesions; p <0.006). The ratio of proximal AR jet height to LV outflow tract height also increased (30.3 +/- 17.5% vs 35.2 +/- 19.7%; p <0.0001). Initial LV volumes and mass were larger in patients with more severe AR and increased significantly during follow-up (138 +/- 53 to 164 +/- 70 ml; 59 +/- 32 to 71.7 +/- 42 ml; 203 +/- 89 to 241 +/- 114 g; p <0.0001). LV volumes and mass increased faster in patients with more severe AR, and in those in whom the degree of AR progressed more rapidly. Finally, patients with bicuspid aortic valve (n = 21) had a higher prevalence of severe AR than patients with tricuspid aortic valves (52% vs 4%; p <0.001). In conclusion, AR is a progressive disease not only in patients with severe AR but also in those with mild and moderate regurgitation. Patients with more severe AR have larger left ventricles that also dilate more rapidly. more...

Quantitative assessment of aortic stenosis (AS) is subject to the limitations of all current noninvasive and invasive methods. The ability to obtain a direct measure of aortic valve area with high resolution by intracardiac echocardiography (ICE) could be of great benefit to catheterized patients. To provide a fixed AS area as an ideal standard for comparison, we performed ICE in 12 sheep hearts with experimentally created AS and five human AS hearts from autopsies. ICE catheters were passed retrograde across the aortic valve, and the minimal orifice area on pullback was planimetered and compared with calibrated video imaging. The entire orifice circumference could be successfully recorded in 16 (94%) hearts. Orifice area from ICE correlated well with actual values (r=0.98; standard error of the estimate [SEE] = 0.06 cm2). To illustrate the applicability in vivo, two canine models and 10 patients with AS were studied. The limiting orifice could be imaged in both animals and in 8 of 10 patients, in whom values agreed well with invasive data (r= 0.95; SEE = 0.04 cm2). ICE can therefore accurately measure AS orifice area in vitro; it can be applied in vivo as well. These validation studies laid the foundation for subsequent clinical studies and applications. more...

Objectives: Using two-dimensional echocardiography, we sought to identify features that are associated with severe mitral regurgitation after percutaneous mitral valvulotomy and combine them into a predictive score., Background: Severe mitral regurgitation after percutaneous mitral valvulotomy is a major complication carrying an adverse prognosis that, to date, has not been predictable in advance., Methods: In a consecutive series of 566 patients who underwent percutaneous mitral valvulotomy, 37 (6.5%) developed severe mitral regurgitation (assessed by angiography) after the procedure, 31 of whom had an echocardiogram available before percutaneous mitral valvulotomy. These 31 patients were matched by age, gender, mitral valve area and degree of mitral regurgitation before valvulotomy with 31 randomly selected patients who did not develop severe mitral regurgitation after percutaneous mitral valvulotomy. An echocardiographic score was developed on the basis of the pathologic studies of valves of patients who developed severe regurgitation after percutaneous mitral valvulotomy (leaflet rupture of relatively thin portions of nonhomogeneously thickened leaflets in the presence of commissural and subvalvular calcification) and evaluated uneven distribution of thickness in the anterior and posterior mitral leaflets, degree of commissural disease and subvalvular disease involvement, with each component graded from 0 to 4 (total, 0 to 16). Intraobserver and interobserver variability for score assessment were 6% and 7%, respectively., Results: The total mitral regurgitation echocardiographic score was significantly greater in the severe mitral regurgitation group (11.7 +/- 1.9 [mean +/- SD] vs. 8.0 +/- 1.2, p < 0.001). In addition, the component grades for the anterior leaflet (3.2 +/- 0.7 vs. 2.3 +/- 0.6, p < 0.001), commissures (2.6 +/- 0.7 vs. 1.6 +/- 0.6, p < 0.001) and subvalvular apparatus (3.2 +/- 0.6 vs. 2.3 +/- 0.7, p < 0.001) were also higher in the mitral regurgitation group. With a total score > or = 10 as a cutoff point for predicting severe mitral regurgitation after percutaneous mitral valvulotomy, a sensitivity of 90 +/- 5% and a specificity of 97 +/- 3% were obtained. Stepwise logistic regression analysis identified the mitral regurgitation echocardiographic score as the only independent predictor for developing severe mitral regurgitation after percutaneous mitral valvulotomy (p < 0.0001)., Conclusions: This new mitral regurgitation echocardiographic score can predict the development of severe mitral regurgitation after percutaneous mitral valvulotomy and can be useful in the selection of patients for this technique. more...

To determine the feasibility and accuracy of intracardiac ultrasonography (ICUS) for the measurement of right ventricular (RV) volumes and function, a 10 MHz ICUS catheter was used in an in vitro and in vivo model. In the in vitro study, 16 sheep hearts were imaged. Sequential cross-sectional images from RV apex to base were recorded during a calibrated pullback. Volumes were calculated by applying Simpson's algorithm. ICUS-obtained volumes correlated well with actual volumes (standard error of estimate [SEE] = 2.3 ml, r = 0.98). For the in vivo study, a beating-heart canine model was used (31 hemodynamic stages in six dogs). Actual volumes were measured by an intracavitary balloon connected to an external column. Sequential cross-sectional images were recorded during the ICUS catheter pullback from apex to base of the RV, and volumes calculated by Simpson's algorithm. Good correlations were observed between ICUS and actual values for diastolic (SEE = 4.1 ml, r = 0.97), systolic (SEE = 3.4 ml, r = 0.96), and ejection fraction (SEE = 3.1%, r = 0.87) values. This new technique can accurately quantitate RV volumes, can function both in vitro and in vivo, and has the potential for increasing applications to questions of clinical and research interest. more...

Assessment of atrial septal defect (ASD) size and shape is important for planning and guiding its transcatheter occlusion and can potentially be achieved by intracardiac ultrasonography (ICUS). ICUS accuracy, however, must first be established against stable standards and technical imaging requirements defined. We therefore used 10, 20, and 30 MHz ICUS catheters to examine 17 ASDs that were 0.16 to 6.7 cm2 in area and were surgically created in excised ovine hearts with 10, 20, and 30 MHz ICUS catheters. ASD shape and area by ICUS were compared with direct video images of the actual ASD. In all instances minimal area by ICUS pullback agreed well with actual values (y = 1.04x + 0.2, SEE = 0.23 cm2, r = 0.99) and corresponded well with defect shapes. The maximum angle between ultrasonography beam and septal plane allowing for complete ASD visualization was 20 degrees. The angle depended on transducer frequency and septal thickness. This new technique has potential value for the accurate assessment of ASD shape and size and may be especially useful in the setting of transcatheter occlusion. more...

The purpose of this study was to determine in an in vitro model the effect of pulsatile pressure on the decay of echocardiographic contrast agents. Use of contrast agents for quantitative assessment of perfusion requires understanding of the factors controlling their rates of disappearance. Prior studies have shown that constant pressure affects the rate of disappearance of these agents. It is not known whether pulsatile pressure influences the rate of decay of contrast agents. In an in vitro chamber, three contrast agents (Albunex, hand-agitated saline solution, and hand-agitated Angiovist) were exposed to pulses of pressure at three rates (30, 60, and 120 pulsations/min), keeping pressure characteristics (peak, nadir, and mean) within a narrow range. Five injections were performed for each agent at each rate. Two-dimensional echocardiographic images of the effects of contrast material were recorded from injection until total disappearance. Videointensity was measured and time-intensity curves were generated. These curves of intensity decay were fitted to an exponential decay function (I = Ae-lambda t) and the velocity of decay (lambda) was used for comparisons. For all agents, intensity of contrast decreased over time. Saline solution and Angiovist, but not Albunex, showed pulsatile decreases in intensity of contrast with each peak pressure and partial recovery of contrast intensity with each nadir pressure. (ABSTRACT TRUNCATED AT 250 WORDS) more...

Objectives: The aim of this study was to investigate the association between the pattern of incomplete tricuspid valve closure and the presence of tricuspid regurgitation and to identify factors that determine the severity of regurgitation associated with this pattern., Background: The incomplete tricuspid valve closure pattern (defined as apical displacement of the leaflets) has been described by two-dimensional echocardiography. However, whether this pattern is universally associated with tricuspid regurgitation and the determinants of severity of regurgitation in its presence have not been studied by Doppler color flow mapping., Methods: We identified 109 consecutive patients (mean age 62 +/- 17 years) with incomplete tricuspid valve closure who were studied by Doppler color flow mapping. We measured the linear apical displacement of the coaptation point from the tricuspid annulus and the area of displacement between the leaflets and annulus. Right atrial, ventricular and annular dimensions were measured and compared with those in a group of normal subjects., Results: Tricuspid regurgitation was present in all patients with the incomplete closure pattern; it was mild in 14%, moderate in 19% and severe in 67%. Apical displacement was significantly greater (p < 0.02) in those with severe regurgitation than in those with mild regurgitation or in normal subjects. Tricuspid annulus dilation was the only independent predictor of severity of regurgitation. The right ventricle was not significantly dilated in 32% of patients, and right ventricular systolic pressure was not correlated with the severity of regurgitation and was < 30 mm Hg in 11% of patients., Conclusions: Tricuspid regurgitation was associated with incomplete tricuspid valve closure in all patients studied and was moderate to severe in 86%. Impaired coaptation is best reflected by the displacement area between the leaflets and the annulus. High pulmonary pressure and significant right ventricular dilation are not prerequisites for functional tricuspid regurgitation. Annular dilation is the most consistent and important determinant of this lesion. more...