Changes In Aortic Valve Area Research Articles

Chronic kidney disease is a key risk factor for aortic stenosis progression.

Rapid progression of aortic stenosis (AS) has been observed in patients undergoing dialysis, but existing cross-sectional evidence is contradictory in non-dialysis-dependent chronic kidney disease (CKD). The present study sought to evaluate whether CKD is associated with the progression of AS over time in a large cohort of patients with AS. We retrospectively studied all consecutive patients diagnosed with AS [peak aortic jet velocity (Vmax) ≥2.5m/s] and left ventricular ejection fraction ≥50% in the echocardiography laboratories of two tertiary centers between 2000 and 2018. The estimated glomerular filtration rate (eGFR) (mL/min/1.73m2) was calculated from serum creatinine values. Patients were divided into five CKD stages according to the baseline eGFR. Annual rates of change in the aortic valve area (AVA) were determined by a linear mixed-effects model. Among the 647 patients included, 261 (40%) had CKD. After a median follow-up of 2.9 (interquartile range 1.8-4.8) years, the mean overall rate of change in AVA was -0.077 (95% confidence interval -0.082; -0.073) cm2/year. There was an inverse relationship between the progression rate and kidney function. The more severe the CKD stage, the greater the AVA narrowing (P<.001). By multivariable linear regression analysis, the eGFR was also negatively associated (P<.001) with AS progression. An eGFR strata below 45mL/min/1.73m2 was associated with higher odds of rapid progression of AS than normal kidney function. During the clinical follow-up, event-free survival (patients free of aortic valve replacement or death) decreased as CKD progressed. Rapid progression of AS in patients with kidney dysfunction was associated with worse outcomes. Patients with CKD exhibit more rapid progression of AS over time and require close monitoring. The link between kidney dysfunction and rapid progression of AS is still unknown and requires further research.

Medium-Term Outcomes of the Different Antithrombotic Regimens After Transcatheter Aortic Valve Implantation

Bioprosthetic valve thrombosis is associated with accelerated bioprosthesis degeneration and valve re-replacement. Whether 3-month warfarin use after transcatheter aortic valve implantation (TAVI) protects against such consequences is unknown. We aimed to investigate if 3-month warfarin treatment after TAVI is associated with better outcomes than dual antiplatelet therapy (DAPT) and single antiplatelet therapy (SAPT) at medium-term follow-up. Adults who underwent TAVI were identified retrospectively (n = 1,501) and classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen received. Patients with atrial fibrillation were excluded. Outcomes and valve hemodynamics were compared between the groups. Annualized change from baseline in mean gradients and effective orifice area at last follow-up echocardiography was calculated. Overall, 844 patients were included (mean age: 80 ± 9 years, 43% women; 633 receiving warfarin, 164 DAPT, and 47 SAPT). Median time to follow-up was 2.5 (interquartile range 1.2 to 3.9) years. There were no differences in the adjusted outcome end points of ischemic stroke, death, valve re-replacement/intervention, structural valve degeneration, or their composite end point at follow-up. Annualized change in aortic valve area was significantly higher in DAPT (−0.11 [0.19] cm2/year) than warfarin (−0.06 [0.25] cm2/y, p = 0.03), but annualized change in mean gradients was not different (p >0.05). In conclusion, antithrombotic regimen, including warfarin, after TAVI was associated with marginally lower decrease in aortic valve area but no difference in medium-term clinical outcomes compared with DAPT and SAPT. Bioprosthetic valve thrombosis is associated with accelerated bioprosthesis degeneration and valve re-replacement. Whether 3-month warfarin use after transcatheter aortic valve implantation (TAVI) protects against such consequences is unknown. We aimed to investigate if 3-month warfarin treatment after TAVI is associated with better outcomes than dual antiplatelet therapy (DAPT) and single antiplatelet therapy (SAPT) at medium-term follow-up. Adults who underwent TAVI were identified retrospectively (n = 1,501) and classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen received. Patients with atrial fibrillation were excluded. Outcomes and valve hemodynamics were compared between the groups. Annualized change from baseline in mean gradients and effective orifice area at last follow-up echocardiography was calculated. Overall, 844 patients were included (mean age: 80 ± 9 years, 43% women; 633 receiving warfarin, 164 DAPT, and 47 SAPT). Median time to follow-up was 2.5 (interquartile range 1.2 to 3.9) years. There were no differences in the adjusted outcome end points of ischemic stroke, death, valve re-replacement/intervention, structural valve degeneration, or their composite end point at follow-up. Annualized change in aortic valve area was significantly higher in DAPT (−0.11 [0.19] cm2/year) than warfarin (−0.06 [0.25] cm2/y, p = 0.03), but annualized change in mean gradients was not different (p >0.05). In conclusion, antithrombotic regimen, including warfarin, after TAVI was associated with marginally lower decrease in aortic valve area but no difference in medium-term clinical outcomes compared with DAPT and SAPT.

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

Background:Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis.Methods:In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events.Results:From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225–326 AU) and 292 AU (95% CI, 246–338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, –86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, –0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, –0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (–212 pmol/L versus 45 pmol/L; P<0.001).Conclusions:In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03243890.

New Evidence About Aortic Valve Stenosis and Cardiovascular Hemodynamics.

Aortic stenosis (AS) is the most common degenerative valvular disease in western word. In patients with severe AS, small changes in aortic valve area can lead to large changes in hemodynamics. The correct understanding of cardiac hemodynamics and its interaction with vascular function is of paramount importance for correct identification of severe AS and to plan effective strategies for its treatment. In the current review with highlight the importance of pressure recovery phenomenon and valvular arterial impedance as novel tools in the evaluation of patients with aortic stenosis.

Effect of General Endotracheal Anesthesia and Mechanical Ventilation on the Echocardiographic Measurements in Severe Aortic Stenosis

Introduction: We measured the peak pressure gradient (pPG) and mean pressure gradient (mPG) obtained by transesophageal echocardiography (TEE) after induction of anesthesia and compared it with the preoperative pPG and mPG by transthoracic echocardiography (TTE) in adults with aortic stenosis (AS). We also compared the aortic valve area (AVA) measurements as obtained preoperatively by TTE versus those by TEE following induction of general endotracheal anesthesia (GETA) during the inspiratory phase, expiratory phase of the ventilatory cycle and with incremental increases in tidal volume. Materials and Methods: All patients had preoperative TTE within 1 month of surgery and was reviewed 1 day before the surgery. After anesthetic induction, precardiopulmonary bypass (CPB) TEE evaluation was done to measure mPG and pPG across AV, under steady-state conditions. Three different controlled tidal volumes: 8 ml, 10 ml, and 12 ml per kg body weight were utilized during the TEE measurements. Results: A total of 90 adults underwent aortic valve replacement from 2017 to 2018. The preoperative pPG and mPG across the AV by TTE was 96.7 ± 23.27 mmHg and 60.7 ± 18.1 mmHg, respectively. Compared to preoperative TTE, pre-CPB TEE pressure gradient during both phases of ventilation under GETA was significantly lower. The pPG and mPG were higher during inspiration as compared to those in the expiratory cycle during mechanical ventilation under GETA (pPG during inspiration = 66.63 ± 22.15 mmHg; mPG during inspiration = 38.24 ± 13.65 mmHg; pPG during expiration = 52.49 ± 19.10 mmHg; mPG during expiration = 30.76 ± 12.66 mmHg). There were no significant changes in AVA between TTE/TEE and inspiration/expiration. Conclusions: The findings of this study demonstrate that the TEE pre-CPB PGs underestimated the severity of AS; hence, the severity of AS must be interpreted with caution during GETA and mechanical ventilation (MV). In addition, PGs must be done at similar points in the respiratory cycle.

TCT-150 Impact of Physiological and Molecular Markers on the Progression of Calcific Aortic Valve Stenosis as Measured by Change in Aortic Valve Area: A Meta-Analysis and Meta-Regression

Identification of physiological and molecular markers is paramount in identifying patients at risk of faster progression of calcific aortic valve stenosis (pCAVS). A systematic review was conducted in accordance with the PRISMA guidelines. A search was performed using the PubMed, Cochrane library,

Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells.

Calcification of the aortic valve leads to increased leaflet stiffness and consequently to the development of calcific aortic valve disease. However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes calcific aortic valve disease progression. We obtained the aortic valve tissues from humans and murine models (wild-type and endothelial nitric oxide synthase-deficient-mice) and cultured the valvular interstitial cells (VICs) and valvular endothelial cells from the cusps. We induced osteogenic differentiation in the primary cultured VICs and examined the effects of the DPP-4 inhibitor on the osteogenic changes in vitro and aortic valve calcification in endothelial nitric oxide synthase-deficient-mice. We also induced calcific aortic stenosis in male New Zealand rabbits (weight, 2.5-3.0 kg) by a cholesterol-enriched diet+vitamin D2 (25 000 IU, daily). Echocardiography was performed to assess the aortic valve area and the maximal and mean transaortic pressure gradients at baseline and 3-week intervals thereafter. After 12 weeks, we harvested the heart and evaluated the aortic valve tissue using immunohistochemistry. We found that nitric oxide depletion in human valvular endothelial cells activates NF-κB in human VICs. Consequently, the NF-κB promotes DPP-4 expression, which then induces the osteogenic differentiation of VICs by limiting autocrine insulin-like growth factor-1 signaling. The inhibition of DPP-4 enzymatic activity blocked the osteogenic changes in VICs in vitro and reduced the aortic valve calcification in vivo in a mouse model. Sitagliptin administration in a rabbit calcific aortic valve disease model led to significant improvements in the rate of change in aortic valve area, transaortic peak velocity, and maximal and mean pressure gradients over 12 weeks. Immunohistochemistry staining confirmed the therapeutic effect of Sitagliptin in terms of reducing the calcium deposits in the rabbit aortic valve cusps. In rabbits receiving Sitagliptin, the plasma insulin-like growth factor-1 levels were significantly increased, in line with DPP-4 inhibition. DPP-4-dependent insulin-like growth factor-1 inhibition in VICs contributes to aortic valve calcification, suggesting that DPP-4 could serve as a potential therapeutic target to inhibit calcific aortic valve disease progression.

Resting Aortic Valve Area at Normal Transaortic Flow Rate Reflects True Valve Area in Suspected Low-Gradient Severe Aortic Stenosis

ObjectivesThis study sought to assess the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow, low-gradient aortic stenosis but normal resting transvalvular flow rate. BackgroundSE may help to distinguish between true severe aortic stenosis and pseudosevere aortic stenosis in patients with low aortic valve area (AVA) and mean gradient. However, if rest flow rate is normal, then SE may not confer any additional diagnostic value, irrespective of resting left ventricular ejection fraction (LVEF) and indexed stroke volume (SVi). MethodsSixty-seven patients with suspected low-flow, low-gradient aortic stenosis who underwent SE were retrospectively studied. Following stratification by rest LVEF, SVi, and flow rate—using cutoffs of 50%, 35 ml/m2, and 200 ml/s, respectively—we tested for significant changes in AVA during SE. ResultsMean age was 77 ± 9 years and 60% of patients were male. Mean values for rest variables were as follows: AVA: 0.77 ± 0.12 cm2; mean gradient: 27 ± 7 mm Hg; flow rate: 182 ± 37 ml/s; SVi: 32 ± 8 ml/m2; and LVEF: 45 ± 15%. During SE, significant increases in AVA were observed regardless of resting LVEF and SVi state. In patients with rest flow rate ≥200 ml/s, AVA did not increase significantly during stress (rest AVA: 0.90 cm2 vs. stress AVA: 0.97 cm2; p = 0.11), and positive predictive value for confirming underlying true severe aortic stenosis was 84%. In adjusted analyses, rest flow rate was the only parameter associated with severe AS (odds ratio: 1.05, 95% confidence interval: 1.0 to 1.1; p = 0.002). ConclusionsRest AVA measured under normal flow rate conditions is likely to reflect the true severity of AS and unlikely to change significantly with SE. Flow normalization may only be required in patients with AVA <1 cm2 and mean gradient <40 mm Hg when the rest flow rate is <200 ml/s.

96 Resting Aortic Valve Area at Normal Transaortic Flow Rate but not at Normal Stroke Volume Reflects the True Valve Area in PTS with Low Gradient Severe Aortic Stenosis: Implications for Obviating the Need for Stress Echocardiography in such PTS

<h3>Objectives</h3> The purpose of this study was to compare the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow low-gradient aortic stenosis (LFLGAS) but normal resting transvalvular flow rate. <h3>Background</h3> SE may help to distinguish between true LFLGAS, and pseudo severe stenosis in patients with low aortic valve area (AVA) and mean gradient (MG). However, if rest flow rate is normal then SE may not confer any additional diagnostic value, irrespective of resting left ventricular ejection fraction (LVEF) and indexed stroke volume (SVi). <h3>Methods</h3> Thirty-nine patients with suspected LFLGAS who underwent SE in a single institution were retrospectively studied. Following stratification by rest LVEF, SVi and flow rate – using cut-offs of 40%, 35 ml/m² and 200 ml/sec respectively – we tested for significant changes in AVA during SE. <h3>Results</h3> Mean age was 77 ± 8 years and 72% were male. Mean values for rest variables were: AVA 0.79 ± 0.13 cm²; MG 26 ± 6 mmHg; flow rate 186 ± 37 ml/s; SVi 33 ± 8 ml/m² and LVEF 44 ± 15%. During stress, significant increases in AVA were observed regardless of resting LVEF and SVi status, and only in patients with low rest flow rate. In patients with rest flow rate &gt;200 ml/s, AVA did not increase significantly during stress (rest AVA 0.90 cm² vs stress 0.97 cm², p = 0.11). In adjusted analyses, rest flow rate was the only parameter associated with severe AS (OR=0.94, p = 0.01). <h3>Conclusions</h3> Rest AVA measured under normal flow rate conditions is likely to reflect the true severity of AS – and unlikely to change significantly with SE. Flow rate normalisation during stress may only be required in patients with AVA &lt; 1 cm² and transvalvular mean gradient &lt; 40 mmHg when the flow rate is &lt;200 ml/s.

LIPOPROTEIN(A) AND PROGRESSION RATE OF AORTIC VALVE STENOSIS - THE PROGRESSA STUDY

Recent studies have reported a single nucleotide polymorphism (i.e. rs10455872) at the LPA gene locus, encoding the lipoprotein(a) [Lp(a)], associated with the presence of aortic valve calcification and the incidence of clinical aortic stenosis (AS). The objectives of this study was to examine the association of rs10455872 and Lp(a) plasma levels with the progression rate of AS. 246 consecutive patients with AS were prospectively recruited in the PROGRESSA study and underwent a comprehensive Doppler-echocardiography annually. Blood-DNA and plasma samples were collected to genotype the rs10455872 polymorphism and to measure Lp(a) plasma levels. Hemodynamic progression rate of AS severity was assessed by measuring the annualized increase in peak aortic jet velocity (Vpeak). Among the 246 patients included in the study, 38 (16%) patients carried at least one rs10455872 risk allele and 47 (19%) had high Lp(a) plasma level (i.e. >50mg/dL). Carriers of the risk allele had higher Lp(a) levels (58±24 vs. 20±38 mg/dL; p<0.0001). Baseline AS severity was similar in carriers and non-carriers (Vpeak: 2.8±0.4 vs. 2.9±0.7 m/s; p=0.33), as well as in patients with high vs. low Lp(a) levels (2.9±0.5 vs. 2.9±0.6 m/s; p=0.97). There was a borderline significant association for lower AS progression rate in carriers compared to non-carriers (annualized change in Vpeak: +0.07±0.17 vs. +0.15±0.21 m/s/yr; p=0.05), whereas patients with high Lp(a) levels had similar stenosis progression rate (+0.12±0.21 vs. +0.14±0.20 m/s/yr; p=0.46). Similar results were obtained with the analysis of baseline and annualized change in aortic valve area. This prospective study shows that neither LPA gene variant nor Lp(a) plasma levels are associated with faster AS progression rate. These findings suggest that Lp(a) lowering therapy may not be efficient to delay or stop stenosis progression in patients with AS.

Do Bisphosphonates Slow the Progression of Aortic Stenosis?

The aim of this study was to investigate the impact of bisphosphonates on the progression of aortic stenosis. Valvular calcification is associated with the development and progression of aortic stenosis. Bisphosphonates have been suggested to slow this progression. Female patients older than the age of 60 years with an aortic valve area (AVA) between 1.0 and 2.0 cm(2) were identified and studied retrospectively. Only those who had follow-up echocardiograms at least a year apart were included. Primary outcomes were the change in AVA and valvular gradients over time. Mortality and freedom from aortic valve replacement were also studied. A propensity-matching method was applied for the probability of the use of bisphosphonates. The study included 801 female patients (mean age, 76 ± 7.6 years) with a mean follow-up of 5.1 ± 2.4 years. The mean duration of bisphosphonate use was 3.1 ± 2.6 years. At the time of the initial echocardiogram, 323 patients (38%) were taking bisphosphonates. The mean ejection fraction at baseline was 56.7 ± 9.6% with a mean AVA of 1.32 ± 0.25 cm(2). Peak and mean gradients were 28.4 ± 11 mm Hg and 15.6 ± 6.8 mm Hg, respectively. Propensity matching was successfully performed for 438 patients. On follow-up, there were no differences in the rate of change in AVA or peak and mean gradients when patients were stratified based on the use of bisphosphonates. Bisphosphonates also had no impact on survival or freedom from aortic valve replacement. In this retrospective analysis of older female patients, bisphosphonates do not have a significant impact on the hemodynamic or clinical progression of aortic stenosis.

Validation of Conventional and Simplified Methods to Calculate Projected Valve Area at Normal Flow Rate in Patients With Low Flow, Low Gradient Aortic Stenosis: The Multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) Study

It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal transvalvular flow rate (AVA(proj)), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVA(proj) in a large series of patients and to propose a new clinically applicable simplified method to estimate AVA(proj). AVA(proj) was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVA(proj) = AVA(rest) + slope x (250 - Q(rest)). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q. There was a strong correlation between AVA(proj) calculated by the two methods (r = 0.95, P < .0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVA(proj) demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVA(proj) < or = 1 cm(2), 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVA(proj) correlated well with valve weight (r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVA(proj) < or = 1.2 cm(2) (hazard ratio, 1.65; P = .02) and simplified AVA(proj) < or = 1.2 cm(2) (hazard ratio, 2.70; P < .0001) were independent predictors of mortality. Traditional dobutamine stress echocardiographic indices were not predictive. In patients with low-flow AS, AVA(proj) better predicts underlying AS severity and patient outcomes than traditional dobutamine stress echocardiographic indices. Simplified AVA(proj) is easier to calculate than conventional AVA(proj), facilitating the use of AVA(proj) in clinical practice.

Osteoporosis Treatment and Progression of Aortic Stenosis

A decrease in bone mineral density has been reported to be associated with increased progression of aortic stenosis (AS). We hypothesized that osteoporosis treatment (OT) is associated with decreased progression of AS. We performed an observational study of patients with AS from our echocardiographic database comparing 18 patients on OT (bisphosphonates, calcitonin, or estrogen receptor modulators) with 37 patients not on OT. All patients had serial echocardiograms. Patients with mitral stenosis, aortic valve replacement, renal failure, calcium disorders, or left ventricular ejection fraction <40% were excluded. Aortic valve area (AVA) was calculated using the continuity equation. There was no significant difference in age, gender, renal function, hypertension, statin use, diabetes, or calcium level between the 2 groups. Mean baseline AVA was 1.33 cm(2) and not significantly different between groups. After a mean of 2.4 +/- 1.0 years, mean annual changes in AVA were -0.22 +/- 0.22 cm(2) in those not on OT and -0.10 +/- 0.18 cm(2) in patients receiving OT (p = 0.025). There was a graded association between AS progression rate and OT. In a multivariable analysis including age, gender, and statin use, only OT was associated with a change in AVA. In conclusion, OT is strongly and independently associated with decreased progression of AS. This association warrants investigation in a larger, prospective study.

Does diabetes accelerate progression of calcific aortic stenosis?

Calcific aortic valve stenosis (CAS) is an active disease like atherosclerosis. Effect of diabetes (D) on severity of CAS is not well documented. We retrospectively analysed 166 consecutive patients with CAS and multiple echocardiograms from January 1997 to March 2005. Aortic valve area (AVA) was measured using the continuity equation. CAS severity was categorized using AVA. D and non-D patients were compared for differences in sex, hypertension, smoking, statin use using chi(2) tests. Comparisons between D and non-D for changes in AVA per year were performed using ANOVA. Study cohort included 166 males with age 70 +/- 9 years, of which 72 (43%) had D. Baseline CAS was mild in 66 subjects, moderate in 75, and severe in 25. D subjects smoked less (P = 0.02), but all other variables were similar (P > 0.05). The interaction between D and baseline CAS severity was significant (P = 0.0191), indicating comparisons should be viewed by baseline CAS severity. D had significantly larger change in AVA than non-D (P = 0.0016) for those with moderate CAS at baseline only. Adjusting for statin use did not alter the results. CAS severity progresses faster in D than in non-D in subjects with moderate CAS at baseline. Statins do not affect progression of CAS.

Abstract 4693: Osteoporosis Treatment Associated with Decreased Progression of Aortic Stenosis

A decline in bone mineral density has been reported to be associated with progression of aortic stenosis (AS). We hypothesized that osteoporosis treatment (OT) is associated with decreased progression of AS. We performed a retrospective chart review of patients with mild and moderate aortic stenosis from our echocardiographic database comparing 18 patients on OT (bisphosphonates, calcitonin or estrogen receptor modulators) to 37 patients not on OT. All patients had serial echocardiograms. Patients with mitral stenosis, aortic valve replacement, renal failure, calcium disorders, or LVEF&lt;40% were excluded. Aortic valve area (AVA) was calculated using the continuity equation. There was no significant difference in age (mean of 82 years), gender (76% female), renal function, hypertension, statin use, diabetes or calcium level between the two groups. The mean baseline aortic valve area was 1.33 cm 2 and was not significantly different between the two groups. After a mean of 2.4 ± 1.0 years, the mean annual change in AVA was −0.10 ± 0.18 cm 2 in patients receiving OT and −0.22 ± 0.22 cm 2 in those not on OT (p=0.025). There was a graded association between AS progression rate and OT (Figure ). Age, gender, hypertension, renal function and statin use were not significantly associated with change in AVA. In a relatively small population of patients, osteoporosis treatment is strongly associated with decreased progression of aortic stenosis. This association warrants investigation in a larger, prospective study.

Determinants of an abnormal response to exercise in patients with asymptomatic valvular aortic stenosis

Patients with asymptomatic aortic stenosis (AS) and abnormal haemodynamic responses to exercise testing are at increased risk of cardiac events. This study assesses the Doppler echocardiographic determinants of a positive exercise test in a cohort of asymptomatic patients with AS. One hundred and twenty-eight patients with AS underwent quantitative Doppler echocardiographic measurements at rest and during exercise test. Of these patients, 60 had an abnormal response to exercise. Two independent determinants of an abnormal exercise response were selected in multivariate analysis: a larger increase in mean transaortic pressure gradient (P = 0.00014) and a limited contractile reserve-latent left ventricular dysfunction-as indicated by smaller changes in ejection fraction (P = 0.0002). Limiting symptoms were associated with greater increase in mean transaortic pressure gradient, smaller changes in systolic blood pressure and a lower ejection fraction at peak exercise. The increase in pressure gradient was associated with smaller exercise-induced changes in aortic valve area and in ejection fraction and new or worsening mitral regurgitation during exercise. Abnormal responses to exercise in asymptomatic AS patients are mediated by a larger increase in mean transaortic pressure gradient and/or a limited contractile reserve characterized by an inadequate increase in ejection fraction at exercise.

Rosuvastatin Affecting Aortic Valve Endothelium to Slow the Progression of Aortic Stenosis

The objective of this study was to test the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor on the progression of moderate to severe aortic stenosis as measured by echocardiography. Recent retrospective studies support the hypothesis that statins slow the progression of aortic stenosis. We performed an open-label, prospective study evaluating 121 consecutive patients with asymptomatic moderate to severe aortic stenosis (aortic valve area > or = 1.0 cm2; mean age 73.7 +/- 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months. Sixty-one patients (50.4%) with elevated LDL (159.7 +/- 33.4 mg/dl), aortic valve velocity (3.65 +/- 0.64 m/s), and aortic valve area (1.23 +/- 0.42 cm2) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 +/- 37.4 mg/dl), aortic valve velocity (3.62 +/- 0.61 m/s), and aortic valve area (1.20 +/- 0.35 cm2) received no statin. During a mean follow-up of 73 +/- 24 weeks, the change in aortic valve area in the control group was -0.10 +/- 0.09 cm2/year versus -0.05 +/- 0.12 cm2/year in the rosuvastatin group (p = 0.041). The increase in aortic valve velocity was 0.24 +/- 0.30 m/s/year in the control group and 0.04 +/- 0.38 m/s/year in the rosuvastatin group (p = 0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group. Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/NCT00114491?order = 1; NCT0014491).

Association of cholesterol levels, hydroxymethylglutaryl coenzyme-a reductase inhibitor treatment, and progression of aortic stenosis in the community

ObjectivesThis study was designed to analyze the association among cholesterol levels, lipid-lowering treatment, and progression of aortic stenosis (AS) in the community. BackgroundAortic stenosis is a progressive disease for which there is no known medical treatment to prevent or slow progression. Despite plausible pathologic mechanisms linking hypercholesterolemia to AS progression, clinical studies have been inconsistent and affected by referral bias, and the role of lipid-lowering therapy is uncertain. MethodsWe determined the association between blood cholesterol levels and progression of native AS (assessed by Doppler echocardiography at baseline and at least six months later; mean interval, 3.7 ± 2.3 years) in a community-based study of 156 patients (age 77 ± 12 years; 90 men). Thirty-eight patients received statin treatment during follow-up. ResultsIn untreated subjects, mean gradient increased from 22 ± 12 mm Hg to 39 ± 19 mm Hg, and aortic valve area (AVA) decreased from 1.20 ± 0.35 cm2to 0.91 ± 0.33 cm2(both p < 0.001). The annualized change in AVA was −0.09 ± 0.17 cm2/year (−7% ± 13%/year). Neither total cholesterol (r = −0.01, p = 0.92) nor low-density lipoprotein cholesterol (r = 0.01; p = 0.88) showed a significant correlation to AS progression. Nevertheless, progression of AS was slower in patients receiving statins compared with untreated patients (decrease in AVA −3 ± 10% vs. −7 ± 13% per year, respectively; p = 0.04), even when adjusted for age, gender, cholesterol, and baseline valve area (p = 0.04). The association of statin treatment with slower progression was confirmed when analysis was restricted to patients coming for a systematic follow-up (p=0.02). The odds ratio of AS progression with statin treatment was 0.46 (95% confidence interval, 0.21 to 0.96). ConclusionsIn the community, progression of AS shows no trend of association with cholesterol levels. Statin treatment, however, is associated with slower progression, suggesting that the effects of statin treatment on progression of AS should be pursued with appropriate clinical trials.

Can instantaneous changes in aortic valve area during ejection predict valve area response to dobutamine testing in valvular aortic stenosis?

Can instantaneous changes in aortic valve area during ejection predict valve area response to dobutamine testing in valvular aortic stenosis?

Hemodynamic-induced changes in aortic valve area: implications for Doppler cardiac output determinations.

Monitoring cardiac output (CO) by transesophageal echocardiography involves measurements of ascending aortic flow and an initial measurement of aortic valve area (AVA). Hemodynamic-induced changes in AVA are a potential source of error for this simplified method. Our goal was to quantify these changes in AVA and their effects on CO calculations. In 17 anesthetized patients, a dobutamine infusion was titrated to achieve a 50% increase in ascending aortic flow velocity (V(max)). Hemodynamic and echocardiographic variables, including V(max) and planimetry of AVA, were determined at baseline and at maximal dobutamine dose. Dobutamine produced a 3.0 +/- 1.4 L/min increase in CO, a 54.5% +/- 19.6% increase in V(max), and a 50.6% +/- 34.2% increase in systolic blood pressure. AVA increased by 4.3% +/- 2.6% during dobutamine infusion (P < 0.001). The simplified CO method, which does not account for increases in AVA, produced a 0.32 +/- 0.24 L/min underestimation of CO. This investigation demonstrates hemodynamic-induced changes in AVA. The use of a single AVA measurement for all subsequent CO calculations introduces a clinically acceptable degree of error, supporting a simplified CO protocol requiring less probe manipulation and reduced procedural time. An intraoperative dobutamine infusion was used to increase aortic blood flow and demonstrate hemodynamic-induced changes in aortic valve area. These valve-area changes affect the accuracy of Doppler cardiac output determinations.