Search

Aortic valve calcification (AVC) is the main culprit lesion of calcific aortic valve stenosis (AS) and is a strong determinant of AS severity and powerful risk factor for mortality [(1,2)][1]. Multidetector computed tomography (MDCT) provides accurate, reproducible quantitation of AVC. Recent

The published version of this article incorrectly lists the authors’ affiliations. The correct affiliations are given below. The Publisher regrets this mistake.

ObjectivesThe aim of this study was to verify the hypothesis that multidetector computed tomography (MDCT) is superior to echocardiography for measuring the left ventricular outflow tract (LVOT) and calculating the aortic valve area (AVA) with regard to hemodynamic correlations and survival outcome prediction after a diagnosis of aortic stenosis (AS).BackgroundMDCT demonstrated that the LVOT is noncircular, casting doubt on the AVA measurement by 2-dimensional (2D) echocardiography.MethodsA total of 269 patients (76 ± 11 years of age, 61% men) with isolated calcific AS (mean gradient 44 ± 18 mm Hg; ejection fraction 58 ± 15%) underwent Doppler echocardiography and MDCT within the same episode of care. AVA was calculated by echocardiography (AVAEcho) and by MDCT (AVACT) using each technique measurement of LVOT area. In the subset of patients undergoing dynamic 4-dimensional MDCT (n = 135), AVA was calculated with the LVOT measured at 70% and 20% of the R-R interval and measured by planimetry (AVAPlani).ResultsPhasic measurements of the LVOT by MDCT yielded slight differences in eccentricity and size (all p < 0.001) but with excellent AVA correlation (r = 0.92, p < 0.0001) and minimal bias (0.05 cm2), whereas the AVAPlani showed poor correlations with all other methods (all r values

Background Aortic valve calcification (AVC) load measures lesion severity in aortic stenosis (AS) and is useful for diagnostic purposes. Whether AVC predicts survival after diagnosis, independent of clinical and Doppler echocardiographic AS characteristics, has not been studied. Objectives This study evaluated the impact of AVC load, absolute and relative to aortic annulus size (AVCdensity), on overall mortality in patients with AS under conservative treatment and without regard to treatment. Methods In 3 academic centers, we enrolled 794 patients (mean age, 73 ± 12 years; 274 women) diagnosed with AS by Doppler echocardiography who underwent multidetector computed tomography (MDCT) within the same episode of care. Absolute AVC load and AVCdensity (ratio of absolute AVC to cross-sectional area of aortic annulus) were measured, and severe AVC was separately defined in men and women. Results During follow-up, there were 440 aortic valve implantations (AVIs) and 194 deaths (115 under medical treatment). Univariate analysis showed strong association of absolute AVC and AVCdensity with survival (both, p < 0.0001) with a spline curve analysis pattern of threshold and plateau of risk. After adjustment for age, sex, coronary artery disease, diabetes, symptoms, AS severity on hemodynamic assessment, and LV ejection fraction, severe absolute AVC (adjusted hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.04 to 2.92; p = 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; p = 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, p ≤ 0.04) and a net reclassification index of 12.5% (p = 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; p = 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; p = 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI. Conclusions This large-scale, multicenter outcomes study of quantitative Doppler echocardiographic and MDCT assessment of AS shows that measuring AVC load provides incremental prognostic value for survival beyond clinical and Doppler echocardiographic assessment. Severe AVC independently predicts excess mortality after AS diagnosis, which is greatly alleviated by AVI. Thus, measurement of AVC by MDCT should be considered for not only diagnostic but also risk-stratification purposes in patients with AS.

Objectives With concomitant Doppler echocardiography and multidetector computed tomography (MDCT) measuring aortic valve calcification (AVC) load, this study aimed at defining: 1) independent physiologic/structural determinants of aortic valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best associated with severe aortic stenosis (AS); and 3) whether, in AS with discordant MG, severe calcified aortic valve disease is generally detected. Background Aortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies. Methods Patients (n = 646) with normal left ventricular ejection fraction AS underwent Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed-to-body surface area (AVAi) and MG, patients were categorized as concordant severity grading (CG) with moderate AS (AVAi >0.6 cm²/m², MG 2 /m 2 , MG 0.6 cm 2 /m 2 , MG ≥40 mm Hg). Results The MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (p 35 ml/m 2 ). The AVC-load, absolute or indexed, identified severe AS accurately (area under the curve ≥0.89, sensitivity ≥86%, specificity ≥79%) in men and women. Upon application of these criteria to DG-low MG, at least one-half of the patients were identified as severe calcified aortic valve disease, irrespective of flow. Conclusions Among patients with AS, MG is often discordant from AVA and is determined by multiple factors, valvular (AVC) and non-valvular (arterial compliance) independently of flow. The AVC-load by MDCT, strongly associated with AS severity, allows diagnosis of severe calcified aortic valve disease. At least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease, emphasizing the clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients.

Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for harvest of EPC in human cell therapy studies. In addition the therapeutic effects of paracrine factors secreted by these cells was evaluated in vitro and in vivo. Intracoronary injection of autologous porcine EPC was associated with increased infarct territory mass and improved regional ventricular systolic function at 2 months compared to control. Treatment with conditioned media derived from autologous EPC was associated with similar improved effects on infarct territory mass and function. Histologic analysis of the infarct territory revealed significantly increased cardiomyocyte size in EPC and conditioned media treated groups, when compared to controls. A paracrine EPC effect was also verified in a pure myocardial preparation in which cardiomyocytes devoid of fibroblast, neuronal and vascular elements directly responded by increasing cell mass when exposed to the same conditioned media. Analysis of conditioned media revealed elevated levels of TGFbeta1 (human 267.3+/-11.8 pg/ml, porcine 57.1+/-6.1 pg/ml), a recognized mediator of hypertrophic signaling in the heart. Neutralizing antibodies to TGFbeta1 attenuated the pro-hypertrophic effect of conditioned media, and use of recombinant TGFbeta1 added to fresh media replicated the pro-hypertrophic effects of conditioned media in vitro. These data demonstrate the potential of paracrine factors secreted from endothelial progenitor cells to induce cardiomyocyte hypertrophy contributing to increased infarct territory LV mass, with favorable medium term effects on regional function following myocardial infarction.

We appreciate the interest of Dr. Habis and colleagues in our study [(1)][1] and their contribution to this research area. In response to their first issue, there is indeed a difference in the elliptic shape of the left ventricular outflow tract (LVOT) between systole and diastole by

With concomitant Doppler echocardiography and multidetector computed tomography (MDCT) measuring aortic valve calcification (AVC) load, this study aimed at defining: 1) independent physiologic/structural determinants of aortic valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best associated with severe aortic stenosis (AS); and 3) whether, in AS with discordant MG, severe calcified aortic valve disease is generally detected.Aortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies.Patients (n = 646) with normal left ventricular ejection fraction AS underwent Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed-to-body surface area (AVAi) and MG, patients were categorized as concordant severity grading (CG) with moderate AS (AVAi0.6 cm²/m², MG 40 mm Hg), severe AS (AVAi ≤0.6 cm²/m², MG ≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAi ≤0.6 cm(2)/m(2), MG 40 mm Hg), or high-MG (AVAi0.6 cm(2)/m(2), MG ≥40 mm Hg).The MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (p 0.0001) and systemic arterial compliance (p 0.0001). The AVC-load (median [interquartile range]) was similar within patients with DG (low-MG: 1,619 [965 to 2,528] arbitrary units [AU]; high-MG: 1,736 [1,209 to 2,894] AU; p = 0.49), higher than CG-moderate-AS (861 [427 to 1,519] AU; p 0.0001) but lower than CG-severe-AS (2,931 [1,924 to 4,292] AU; p 0.0001). The AVC-load thresholds separating severe/moderate AS were defined in CG-AS with normal flow (stroke-volume-index35 ml/m(2)). The AVC-load, absolute or indexed, identified severe AS accurately (area under the curve ≥0.89, sensitivity ≥86%, specificity ≥79%) in men and women. Upon application of these criteria to DG-low MG, at least one-half of the patients were identified as severe calcified aortic valve disease, irrespective of flow.Among patients with AS, MG is often discordant from AVA and is determined by multiple factors, valvular (AVC) and non-valvular (arterial compliance) independently of flow. The AVC-load by MDCT, strongly associated with AS severity, allows diagnosis of severe calcified aortic valve disease. At least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease, emphasizing the clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients.

Late enhancement magnetic resonance imaging (MRI) was compared with thallium-201 rest-redistribution single photon emission computed tomography (SPECT) in patients with reduced left ventricular (LV) function and prior myocardial infarction (MI).Hyperenhancement on contrast cardiac MRI using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) has been reported to identify nonviable myocardium. Comparisons of MRI and thallium-201 SPECT have recently been reported. This study focuses on the comparison of these modalities specifically in patients with ischemic heart failure, where viability determination is most clinically relevant.Fifteen patients with LV dysfunction and prior MI [mean ejection fraction (EF) 35 +/- 11%] underwent thallium-201 rest-redistribution scintigraphy and contrast MRI on separate days. Each short axis slice was divided into six 60-degree segments, and correlations between MRI and scintigraphy were made on viability detection for each segment. For SPECT, the mean uptake score was calculated from the average of all percent relative activity values throughout each segment. Areas with50% of maximal thallium uptake were considered nonviable. On MRI, regions with increased signal intensity after an injection of 0.1 mmol/kg Gd-DPTA were considered nonviable.A total of 558 segments were analyzed. Overall, there was a strong inverse relationship between the area of hyperenhancement on MRI and diminished thallium-201 uptake on SPECT (r = -0.51, P0.001). There was a significant correlation between the imaging methods for each individual segment, except for the inferior-septal segment (r = -0.38, P0.08).In patients with LV dysfunction and prior MI, our data suggest MRI hyperenhancement significantly correlates with myocardial nonviability by thallium-201 SPECT. Correlations were weaker in the inferior-septal region, which may be due to SPECT attenuation artifact.