Abstract 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.
Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS ...is controversial and that with AVC is unknown.
We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm(2); mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC-AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P=0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm(2)/m(2); P=0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P<0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P<0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P<0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r>0.67; P<0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P≤0.01).
In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women.
Little is known about transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve stenosis, which usually represents a contraindication. The aim of this study was to assess ...the feasibility and the results of TAVI in this patient subset. Of 316 high-risk patients with severe aortic stenosis who underwent TAVI from January 2009 to January 2012, 15 (5%) had documented bicuspid aortic valves. They were treated using a transarterial approach, using the Medtronic CoreValve system. Patients were aged 80 ± 10 years, in New York Heart Association functional classes III and IV. The mean aortic valve area was 0.8 ± 0.3 cm2 , and the mean gradient was 60 ± 19 mm Hg. The mean calcium score, calculated using multislice computed tomography, was 4,553 ± 1,872 arbitrary units. The procedure was successful in all but 1 patient. Major adverse events, according to Valvular Academic Research Consortium definitions, were encountered in 1 patient (death). The mean postimplantation prosthetic gradient was 11 ± 4 mm Hg, and ≤1+ periprosthetic leaks were observed in all but 2 patients. The mean prosthetic ellipticity index was 0.7 ± 0.2 at the level of the native annulus and 0.8 ± 0.2 at the level of the prosthetic leaflets. After a mean follow-up period of 8 ± 7 months, 1 patient had died from aortic dissection; there were no additional adverse events. All but 2 hospital survivors were in New York Heart Association class I or II. In conclusion, the present series suggests that transarterial Medtronic CoreValve implantation is feasible in selected patients with bicuspid aortic valve and may lead to short-term hemodynamic and clinical improvement.
Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We ...hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.
We sought to evaluate the relationship among left ventricular outflow tract diameter (LVOTd), gender, and body surface area (BSA) and to evaluate the usefulness of size-adjusted LVOTd reference ...values in patients with aortic stenosis (AS). AS grading is based on the echocardiographic calculation of the aortic valve area (AVA) and requires LVOTd measurements, one main potential source of error. Transesophageal echocardiography (TEE) is reputed to be more accurate than transthoracic echocardiography (TTE), but validation studies are rare. A safeguard for LVOTd measurements is thus desirable.
Since January 2006, 3 subsets of patients have been prospectively and concurrently enrolled: 1) TEE group: In 120 patients with and without AS, we prospectively measured LVOTd during both TTE and TEE. 2) Validation set: In 382 patients without aortic valve or ascending aorta diseases, we evaluated the relationship among LVOTd, gender, and BSA. 3) Testing set: In 173 patients with AS, we compared the AVA obtained using measured LVOTd (AVA(MEAS)) and calculated LVOTd derived from a regression determined in the validation set (AVA(CALC)).
TTE did not differ from and correlated well with TEE measurements overall (23 +/- 2 mm vs 23 +/- 2 mm, P = .26; r = 0.95, P < .0001) and in patients with AS (N = 43) (24 +/- 2 mm vs 24 +/- 3 mm, P = .15; r = 0.92, P < .0001). LVOTd was linearly correlated to BSA independently of gender (LVOTd = 5.7 * BSA+12.1; r = 0.55, P < .0001). In the testing set, AVA(CALC) did not differ from and correlated well with AVA(MEAS) (1.20 +/- 0.42 cm2 vs 1.23 +/- 0.40 cm2; P = .08; r = 0.89; P < .0001).
TTE and TEE measurements of the LVOTd provided similar results. LVOTd was significantly associated to BSA and LVOTd, derived from a linear regression linked to BSA independently of gender, provided an acceptable approximation of the AVA. Thus, although accurate measurement of LVOTd is a crucial part of the echocardiographic evaluation of AS severity, the present equation may be used as a safeguard when this measurement is difficult or not possible with TTE.
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 <40 mm Hg), severe AS (AVAi ≤0.6 cm²/m², MG ≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAi ≤0.6 cm2 /m2 , MG <40 mm Hg), or high-MG (AVAi >0.6 cm2 /m2 , 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 < 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-index >35 ml/m2 ). 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.
Transcatheter aortic valve replacement is currently used off-label for noncalcified aortic valve regurgitation and therefore is restricted to selected cases. In this setting we describe a rare ...complication of Sapien 3 (Edwards Lifesciences, Irvine, California) embolization from the left ventricle to the descending aorta. Given their technical challenges, such procedures require specific considerations and management. (Level of Difficulty: Advanced.)
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In patients with mitral stenosis (MS) in sinus rhythm (SR), guidelines recommend anticoagulation if the left atrium is enlarged based on diameter measurements. We sought to compare the association of ...left atrial (LA) diameter and LA volume with markers of thromboembolic risk (peak LA appendage emptying velocity LAAv and LA spontaneous contrast density) measured during transesophageal echocardiography in 152 patients with moderate to severe MS. High thromboembolic risk was defined by a peak LAAv <25 cm/s and/or dense spontaneous contrast. Mean LA diameter (50 ± 7 mm, 32 to 77) and LA volume (152 ± 70 ml, 67 to 720) were significantly correlated (r = 0.71, p <0.0001), but the relation was curvilinear and the 95% confidence interval increased with LA diameter. In the subset of 80 patients in SR who underwent clinically indicated transesophageal echocardiography, body surface area (BSA)-indexed LA volume but not LA diameter differentiated patients with normal from those with low LAAv (86 ± 17 vs 71 ± 17 ml/m2 , p <0.01, and 50 ± 6 vs 48 ± 6 mm, p = 0.13, respectively) and patients with dense spontaneous contrast from those with no or mild spontaneous contrast (81 ± 16 vs 63 ± 15 ml/m2 , p <0.01, and 49 ± 6 vs 46 ± 5 mm, p = 0.11, respectively). BSA-indexed LA volume provided the highest area under the curve (0.85) for high thromboembolic risk and LA diameter the lowest (0.65). A BSA-indexed LA volume >60 ml/m2 provided an excellent 90% sensitivity despite 44% specificity, 76% positive predictive value, and 70% negative predictive value. Use of this threshold instead of 50 or 55 mm would have changed the indication for anticoagulation in 51% to 77% of patients. In conclusion, LA volume was more strongly associated with markers of thromboembolic risk than LA diameter, which poorly reflected LA size. Our results support the use of BSA-indexed LA volume to guide the decision for anticoagulation in patients with MS in SR, which may lead to significant change in the management of those patients. We suggest a threshold of 60 ml/m2 , which has good sensitivity, albeit with low specificity.
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