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Objective: This study assessed whether apolipoprotein CIII-lipoprotein(a) complexes (ApoCIII-Lp(a)) associate with progression of calcific aortic valve stenosis (AS)., Methods: Immunostaining for ApoC-III was performed in explanted aortic valve leaflets in 68 patients with leaflet pathological grades of 1-4. Assays measuring circulating levels of ApoCIII-Lp(a) complexes were measured in 218 patients with mild-moderate AS from the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. The progression rate of AS, measured as annualised changes in peak aortic jet velocity (V peak ), and combined rates of aortic valve replacement (AVR) and cardiac death were determined. For further confirmation of the assay data, a proteomic analysis of purified Lp(a) was performed to confirm the presence of apoC-III on Lp(a)., Results: Immunohistochemically detected ApoC-III was prominent in all grades of leaflet lesion severity. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), oxidised phospholipids on apolipoprotein B-100 (OxPL-apoB) or on apolipoprotein (a) (OxPL-apo(a)) with annualised V peak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualised V peak (p<0.001) and risk of AVR/cardiac death (p=0.03). Similar results were noted with OxPL-apoB and OxPL-apo(a). There was no association between autotaxin (ATX) on ApoB and ATX on Lp(a) with faster progression of AS. Proteomic analysis of purified Lp(a) showed that apoC-III was prominently present on Lp(a)., Conclusion: ApoC-III is present on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild-moderate AS who display rapid progression of AS and higher rates of AVR/cardiac death., Trial Registration: NCT00800800., Competing Interests: Competing interests: J-PD has served as a speaker for Abbott Laboratories, AstraZeneca, Solvay Pharma, GlaxoSmithKline, and Pfizer Canada, Inc.; has received research funding from Eli Lilly Canada; and has served on the advisory boards of Novartis, Theratechnologies, Torrent Pharmaceuticals Ltd., and Sanofi-Aventis. PM has a patent application on the use of Lp-PLA2 inhibitors in the treatment of AS. BA has received research funding from Ionis Pharmaceuticals, Merck and Pfizer. ST and JLW are co-inventors and receive royalties from patents owned by UCSD on oxidation-specific antibodies and of biomarkers related to oxidised lipoproteins and are co-founders of Oxitope, Inc. ST is a consultant to Boston Heart Diagnostics, a co-founder of Oxitope, Inc. and has a dual appointment at UCSD and Ionis Pharmaceuticals. JLW is a consultant to Ionis Pharmaceuticals and a co-founder of Oxitope, Inc., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objective of this study was to determine the prognostic value of combined measures of B-type natriuretic peptide (BNP) and high-sensitivity cardiac troponin T (hsTnT) in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) who had either a preserved or reduced left ventricular ejection fraction (LVEF)., Background: An elevated BNP level is associated with increased risk of mortality in patients with LF-LG AS. The incremental prognostic value of hsTnT in these patients is unknown., Methods: Ninety-eight patients (74 ± 10 years; 75% men) with LF-LG AS (LVEF <50% and/or stroke volume index <35 ml/m 2 , mean gradient <40 mm Hg, indexed aortic valve area <0.6 cm 2 /m 2 ) who were prospectively enrolled in the TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study were included. The cohort was divided into 3 groups according to BNP and hsTnT levels: group A: BNP <550 pg/ml and hsTnT <15 ng/l; group B: BNP ≥550 pg/ml or hsTnT ≥15 ng/l; and group C: BNP ≥550 pg/ml and hsTnT ≥15 ng/l. The primary endpoint was all-cause mortality., Results: Twenty-seven patients (27%) were in group A, 39 (40%) were in group B, and 32 (33%) were in group C. During a median follow-up of 2.8 years, 43 patients died. Two-year mortality was higher in group C (41 ± 9%) than in group B (23 ± 7%) and group A (5 ± 4%) (p = 0.002). In group B, there was no significant difference in 2-year mortality rates between the subgroup with hsTnT ≥15 ng/l (n = 29) and the subgroup with BNP ≥550 pg/ml (n = 10) (26 ± 9% vs. 11 ± 10%, respectively; p = 0.21). In multivariable analysis adjusted for age, type of treatment (aortic valve replacement vs. conservative therapy), coronary artery disease, and LVEF, being in group C remained independently associated with an increased risk of mortality (hazard ratio [HR]: 4.25; p = 0.023), and group B tended to have higher mortality (HR: 3.63; p = 0.058) compared with group A., Conclusions: This study demonstrated the usefulness of combined measures of BNP and hsTnT to enhance risk stratification in patients with LF-LG AS. Patients with elevation of both BNP and hsTnT had a markedly increased risk of mortality. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies reported that middle-aged patients with atherogenic lipoprotein-lipid profile exhibit faster progression of aortic valve stenosis (AS). The ratio of apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) reflects the balance between atherogenic and anti-atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA-I ratio and AS hemodynamic progression and to determine whether this association varies according to age., Methods and Results: A total of 159 patients (66±13 years, 73% men) with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of AS was determined by the change in peak aortic jet velocity (V peak ) measured by Doppler-echocardiography between baseline and 2-year follow-up. Patients in the top tertile of apoB/apoA-I ratio (≥0.62) had a faster progression rate of AS compared with those in the bottom/mid tertiles (V peak progression: 0.30 [0.09-0.49] versus 0.16 [0.01-0.36] m/s, P =0.02). There was a significant interaction ( P =0.007) between apoB/apoA-I ratio and age. Among younger patients (ie, aged <70 years; median value of the cohort), those in the top tertile of apoB/apoA-I ratio had a 3.4-fold faster AS progression compared with those in the bottom/mid tertiles (V peak progression: 0.34 [0.13-0.69] versus 0.10 [-0.03-0.31] m/s, P =0.002), whereas there was no significant difference between tertiles in the subgroup of older patients ( P =0.83). After comprehensive adjustment, higher apoB/apoA-I ratio was significantly associated with faster AS progression in the subset of younger patients (all, standardized β≥0.36; P ≤0.01)., Conclusions: Higher apoB/apoA-I ratio is significantly associated with faster hemodynamic progression of AS in the younger patients. These findings suggest that atherogenic lipid factors may play a crucial role in the pathogenesis of AS in younger patients, but may be are less important in older patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01679431., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: Elevated levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict the progression of pre-existing mild-to-moderate calcific aortic valve stenosis (CAVS). Whether indirect markers of oxidation-specific epitopes (OSE) are also predictive is not known. The association between IgG and IgM autoantibodies and malondialdehyde-modified low density lipoprotein (MDA-LDL) and IgG and IgM apolipoprotein B immune complexes (apoB-IC), and the hemodynamic progression rate of CAVS was determined in the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin, NCT00800800) trial., Methods: Plasma levels of IgG and IgM MDA-LDL and apoB-IC were measured in 220 patients with mild-to-moderate CAVS from the ASTRONOMER trial. The endpoint of this study was the progression rate of CAVS, measured by the annualized increase in peak aortic jet velocity (V peak ) over a median follow-up of 3.5 [2.9-4.5] years., Results: There was no difference in the progression rate of CAVS across tertiles of IgG and IgM MDA-LDL and apoB-IC levels (all p > 0.05). After multivariable analysis, no marker reached significance level to predict faster CAVS progression or need for aortic valve replacement (all p > 0.05). There was no interaction between the OSE antibody titers and plasma levels of Lp(a) or OxPL-apoB, as well as age, with regards to the progression rate of CAVS., Conclusions: Autoantibody titers to MDA-LDL and apoB-IC, which are an indirect measurement of OSE, unlike direct measurements of OxPL-apoB or their major lipoprotein carrier Lp(a), do not predict the progression of CAVS or need for AVR., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS., Methods and Results: The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile-75th percentile]: +370 [126-824] vs. +157 [58-303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVC density : +96 [34-218] vs. +45 [14-82] AU/cm 2 , P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVC density (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3-199] vs. +41 [0-156] AU, P = 0.88)., Conclusion: This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objective: To evaluate the effect of age and aortic valve anatomy (tricuspid (TAV) vs bicuspid (BAV) aortic valve) on the relationship between the aortic valve calcification (AVC) and the haemodynamic parameters of aortic stenosis (AS) severity., Methods: Two hundred patients with AS and preserved left ventricular ejection fraction were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study and underwent a comprehensive Doppler echocardiography and multidetector CT (MDCT). Mean transvalvular gradient (MG) measured by Doppler echocardiography was used to assess AS haemodynamic severity and AVC was evaluated by MDCT using the Agatston method and indexed to the left ventricular outflow tract area to obtain AVC density (AVCd). All analyses were adjusted for sex., Results: Thirty-nine patients had a BAV and 161 a TAV. Median age was 51 and 72 years for BAV and TAV patients, respectively. There was a modest correlation between MG and AVCd (ρ=0.51, p<0.0001) in the whole cohort. After dichotomisation for valve anatomy, there was a good correlation between AVCd and MG in the TAV group (ρ=0.61, p<0.0001) but weak correlation in the BAV group (ρ=0.32, p=0.046). In the TAV group, the strength of the AVCd-MG correlation was similar in younger (<72 years old; ρ=0.59, p<0.0001) versus older (≥72 years old; ρ=0.61, p<0.0001) patients. In the BAV group, there was no correlation between AVCd and MG in younger patients (<51 years old; ρ=0.12, p=0.65), whereas there was a good correlation in older patients (≥51 years old; ρ=0.55, p=0.009). AVCd (p=0.005) and age (p=0.02) were both independent determinants of MG in BAV patients while AVCd (p<0.0001) was the only independent determinant of MG in TAV patients., Conclusions: In patients with TAV as well as in older patients with BAV, AVCd appears to be the main factor significantly associated with the haemodynamic severity of AS and so it may be used to corroborate AS severity in case of uncertain or discordant findings at echocardiography. However, among younger patients with BAV, some may have a haemodynamically significant stenosis with minimal AVCd. The results of MDCT AVCd should thus be interpreted cautiously in this subset of patients., Trial Registration Number: NCT01679431; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: This study sought to assess the survival benefit associated with aortic valve replacement (AVR) according to different strata of echocardiographic parameters of aortic stenosis (AS) severity, and especially in patients with an aortic valve area (AVA) comprised between 0.8 cm(2) and 1 cm(2)., Background: Discordant findings between AVA (≤1.0 cm(2)) and mean gradient (MG) (<40 mm Hg) raise uncertainty regarding the actual severity of AS. Some studies suggested that the AVA threshold value to define severe AS should be decreased to 0.8 cm(2) to reconcile these discordances., Methods: A total of 1,710 patients with documented moderate to severe AS by Doppler echocardiography were separated into 4 strata of AS severity based alternatively on AVA, indexed AVA, MG, or peak aortic jet velocity (Vpeak). We compared the survival rates of medically versus surgically treated patients. To eliminate covariate differences that may lead to biased estimates of treatment effect, a propensity matching with a greedy 5-to-1 digit-matching algorithm was used., Results: Mean AVA was 0.9 ± 0.3 cm(2), mean MG 33 ± 18 mm Hg, and mean Vpeak 3.6 ± 0.9 m/s. A total of 1,030 (60%) patients underwent AVR within 3 months following echocardiographic evaluation. During a mean follow-up of 4.4 ± 3.0 years there were 469 deaths. Patients with an AVA between 0.8 cm(2) and 1.0 cm(2) had a significant observed survival benefit with AVR (hazard ratio: 0.37 [95% confidence interval: 0.21 to 0.63]; p = 0.0002). AVR was also associated with improved survival in patients with MG between 25 mm Hg and 40 mm Hg or Vpeak between 3 m/s and 4 m/s, but only in patients with concomitant AVA ≤1 cm(2) (p = 0.001 vs. p = 0.46 in patients with AVA >1 cm(2))., Conclusions: These results do not support decreasing the AVA threshold value for severity to 0.8 cm(2) and they confirm that AVR is associated with improved survival in a substantial number of patients with discordant aortic grading., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The study purpose was to assess the usefulness of echocardiographic parameters of aortic stenosis (AS) severity and left ventricular (LV) systolic function to predict mortality in AS. The main hypothesis is that parameters of LV systolic function are the most important independent predictors of mortality, whereas parameters of stenosis severity are not., Methods: 1065 consecutive patients with AS referred to the echocardiography laboratory and meeting the inclusion/exclusion criteria were included and followed during 5.7 years. The end points were aortic valve replacement (AVR) (n=584), composite of AVR or death (n=932), all-cause mortality (n=550) and cardiovascular mortality (n=398)., Results: The most powerful echocardiographic predictors of valve-related events were parameters of AS severity, such as peak aortic jet velocity (VPeak), mean gradient (MG) and aortic valve area (AVA) (all p<0.001). Regarding mortality, the main predictors were LV ejection fraction (LVEF) and stroke volume index (SVi) (p<0.05). After multivariable adjustment, LVEF (p<0.001) and SVi (p=0.02) remained the only echocardiographic predictors of mortality, even after adjustment for symptomatic status. AVA was also associated with mortality, whereas VPeak and MG were not., Conclusions: The most powerful echocardiographic predictors of mortality are low LVEF and low flow, whereas AS severity parameters predict valve-related events but not overall mortality. Hence, low flow should be integrated in the risk stratification and therapeutic decision-making in patients with AS., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a)., Objectives: This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events., Methods: OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up., Results: AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death., Conclusions: Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cusp calcification is the main mechanism leading to bioprosthetic heart valve (BPV) failure. Recent studies suggest that BPV calcification is an active rather than passive process probably modulated by several mechanisms including lipid-mediated inflammation and dysfunctional phosphocalcic metabolism., Objective: To identify the clinical and metabolic determinants of BPV calcification assessed by multidetector CT (MDCT)., Methods and Results: Presence of BPV calcification was assessed by MDCT in 194 patients who had undergone aortic valve replacement. A calcification score was individually calculated and expressed in mm(3). Patients also underwent a clinical evaluation, a Doppler echocardiographic exam, and a plasma lipid and phosphocalcic profile. 46 patients (24%) had BPV calcification (cusp calcification score >0 mm(3)). After adjustment for age, gender, and time interval since BPV implantation, increased calcium-phosphorus product (OR 1.11, 95% CI 1.01 to 1.23 per 1 unit; p=0.02) and the presence of prosthesis-patient mismatch (OR 3.67, 95% CI 1.25 to 10.6; p=0.01) were the strongest independent factors associated with BPV calcification. Calcium supplement intake, age and female gender were independently associated with increased calcium-phosphorus product., Conclusions: This study suggests that higher calcium-phosphorus product and prosthesis-patient mismatch promote BPV calcification. Furthermore, this study reports that calcium supplements, which are extensively prescribed in elderly patients, are independently associated with higher calcium-phosphorus product., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims: We reported that patients with small aortic valve area (AVA) and low flow despite preserved left ventricular ejection fraction (LVEF), i.e. 'paradoxical' low flow (PLF), have worse outcomes compared with patients with normal flow (NF), although they generally have a lower mean gradient (MG). The aortic valve weight (AVW) excised at the time of valve replacement is a flow-independent marker of stenosis severity. The objective of this study was to compare the AVW of patients with PLF and MG<40 mmHg with the AVW of patients with NF and MG≥40 mmHg., Methods and Results: We recruited 250 consecutive patients undergoing valve replacement (Cohort A) for severe stenosis. Among them, 33 (13%) were in PLF [LVEF > 50% but stroke volume index (SVi) ≤ 35 mL/m(2)] with MG < 40 mmHg (PLF-LG group) and 105 (42%) were in NF (LVEF > 50% and SVi > 35 mL/m(2)) with MG ≥ 40 mmHg (NF-HG group). Despite a much lower MG (29 ± 7 vs. 53 ± 10 mmHg; P < 0.0001), patients in the PLF-LG group had a similar AVA (0.73 ± 0.12 vs. 0.69 ± 0.13; P = 0.19) compared with those in the NF-HG group. The AVW [median (interquartile): 1.90 (1.63-2.50) vs. 2.60 (1.66-3.32)] and prevalence of bicuspid phenotype (15 vs. 42%) were lower in the PLF-LG group than in the NF-HG group. However, AVWs analysed separately in the tricuspid and bicuspid valves were similar in both groups [tricuspid valves: 1.80 (1.63-2.50) vs. 2.30 (1.58-3.00) g; P = 0.26 and bicuspid valves: 2.72 (1.73-3.61) vs. 2.60 (2.10-3.55) g; P = 0.93]. When using cut-point values of AVW established in another series of non-consecutive patients (n = 150, Cohort B) with NF and concordant Doppler-echocardiographic findings, we found that the percentage of patients with evidence of severe stenosis in Cohort A was 70% in patients with PLF-LG and 86% in patients with NF-HG., Conclusion: The aortic valve weight data reported in this study provide evidence that a large proportion of patients with PLF and low-gradient have a severe stenosis and that the gradient may substantially underestimate stenosis severity in these patients. A multi-parametric approach including all Doppler-echocardiographic parameters of valve function as well as other complementary diagnostic tests may help correctly identify these patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

The objective of this study was to examine the value of stress-echocardiography in patients with paradoxical low-flow, low-gradient (PLFLG) aortic stenosis (AS). The projected aortic valve area (AVAProj) at a normal flow rate was calculated in 55 patients with PLFLG AS. In the subset of patients (n = 13) who underwent an aortic valve replacement within 3 months after stress echocardiography, AVA(Proj) correlated better with the valve weight compared to traditional resting and stress echocardiographic parameters of AS severity (AVA(Proj): r = -0.78 vs. other parameters: r = 0.46 to 0.56). In the whole group (N = 55), 18 (33%) patients had an AVA(Proj) >1.0 cm(2), being consistent with the presence of pseudo severe AS. The AVA(Proj) was also superior to traditional parameters of stenosis severity for predicting outcomes (hazard ratio: 1.32/0.1 cm(2) decrease in AVA(Proj)). In patients with PLFLG AS, the measurement of AVA(proj) derived from stress echocardiography is helpful to determine the actual severity of the stenosis and predict risk of adverse events., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this case match study was to compare the outcome of patients with paradoxical low-flow (left ventricular ejection fraction [LVEF] ≥50% but stroke volume index <35 ml/m(2)), low-gradient (mean gradient [MG] <40 mm Hg), a priori severe (aortic valve area [AVA] ≤1.0 cm(2)) aortic stenosis (AS) (PLG-SAS group) with that of patients with a severe AS (AVA ≤1.0 cm(2)) and consistent high-gradient (MG ≥40 mm Hg) (HG-SAS group) and with that of patients with a moderate AS (AVA >1.0 cm(2) and MG <40 mm Hg) (MAS group)., Background: In patients with preserved LVEF, a discordance between the AVA (in the severe range) and the gradient (in the moderate range) raises uncertainty with regard to the actual severity of the stenosis and thus the therapeutic management of the patient., Methods: In a prospective cohort of AS patients with LVEF ≥50%, we identified 187 patients in the PLG-SAS group. These patients were retrospectively matched: 1) according to the gradient, with 187 patients with MAS; and 2) according to the AVA, with 187 patients with HG-SAS., Results: Patients with PLG-SAS had reduced overall survival (1-year: 89 ± 2%; 5-year: 64 ± 4%) compared with patients with HG-SAS (1-year: 96 ± 1%; 5-year: 82 ± 3%) or MAS (1-year: 96 ± 1%; 5-year: 81 ± 3%). After adjustment for other risk factors, patients with PLG-SAS had a 1.71-fold increase in overall mortality and a 2.09-fold increase in cardiovascular mortality compared with the 2 other groups. Aortic valve replacement was significantly associated with improved survival in the HG-SAS group (hazard ratio: 0.18; p = 0.001) and in the PLG-SAS group (hazard ratio: 0.50; p = 0.04) but not in the MAS group., Conclusions: Prognosis of patients with paradoxical low-flow, low-gradient severe AS was definitely worse than those with high-gradient severe AS or those with moderate AS. The finding of a low gradient cannot exclude the presence of a severe stenosis in a patient with a small AVA and preserved LVEF and should mandatorily prompt further investigation., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aim of the Study: The optimal timing of aortic valve replacement (AVR) in patients with severe aortic stenosis (AS) is a source of debate. Moreover, it has been shown previously that prosthesis-patient mismatch (PPM) is an independent predictor of operative mortality after AVR. The study aim was to assess the effect of the preoperative severity of AS and its interaction with PPM with respect to operative mortality after AVR., Methods: The data were analyzed from 2,104 consecutive patients who had undergone AVR for severe AS. The patients were allocated to tertiles according to their preoperative indexed aortic valve area (AVAi) as: < 0.35 cm2/m2, 0.35 to 0.43 cm2/m2, and > 0.43 cm2/m2. PPM was defined as a projected postoperative indexed effective orifice area (EOAi) of the implanted prosthesis < 0.85 cm2/m2., Results: The operative mortality was 5.7% (n = 120). On multivariate analysis, an independent association was identified between the preoperative severity of AS and operative mortality (odds ratio [OR] = 2.00, p = 0.03 for AVAi < 0.35 cm2/m2; OR = 1.39, p = 0.32 for AVAi 0.35-0.43 cm2/m2). Notably, the impact of PPM was more important in patients with more severe AS (p = 0.046 for AVAi x EOAi interaction)., Conclusion: The study results confirmed that very severe AS (AVAi < 0.35 cm2/m2) is independently associated with operative mortality after AVR. The results also emphasized the importance of avoiding PPM in these patients.

Objectives: The objectives were to compare different Doppler echocardiographic methods for the measurement of prosthetic valve effective orifice area (EOA) following transcatheter aortic valve implantation (TAVI) and to determine the factors influencing the EOA of transcatheter balloon expandable valves., Background: Previous studies have used different methods for the measurement of the valve EOA following TAVI. Factors influencing the EOA of transcatheter valves are unknown., Methods: A total of 122 patients underwent TAVI with the use of the Edwards-SAPIEN valve (Edwards Lifesciences, Irvine, California). The EOA was measured by transthoracic echocardiography at hospital discharge, 6 months and 1 year after TAVI with the use of 2 methods as described in previous studies. In Method #1 (EOA(1)), LVOT diameter (LVOTd) entered in the continuity equation was measured at the base of prosthesis cusps whereas, in Method #2 (EOA(2)), LVOTd was measured immediately proximal to the prosthesis stent., Results: The average EOA(2) (1.57 ± 0.41 cm(2)) was larger (p < 0.01) than the EOA(1) (1.21 ± 0.38 cm(2)). Accordingly, incidence of severe PPM (indexed EOA ≤0.65 cm(2)/m(2)) was 3-fold lower with the use of EOA(2) than with EOA(1) (9% vs. 33%; p < 0.001). Mean transprosthetic gradient correlated better (p = 0.03) with indexed EOA(2) (r = -0.70, p < 0.0001) than with indexed EOA(1) (r = -0.58, p < 0.0001). Intraobserver and interobserver variability were lower for EOA(2) compared to EOA(1) (intra: 5% vs. 7%, p = 0.06; inter: 6% vs. 14%; p < 0.001). Aortic annulus size was the sole independent determinant (p = 0.01) of prosthetic valve EOA(2). The average EOA varied from 1.37 ± 0.23 cm(2) for aortic annulus size <19 mm up to 1.90 ± 0.17 cm(2) for size >23 mm., Conclusions: When estimating the EOA of Edwards-SAPIEN valves by Doppler-echocardiography, it is recommended to use the LVOT diameter and velocity measured immediately proximal to the stent. The main determinant of the EOA of transcatheter valves is the patient's annulus size and these valves provide excellent hemodynamics even in patients with a small aortic annulus., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A substantial proportion of patients with severe aortic stenosis may paradoxically have low transvalvular flow and a low gradient, despite the presence of normal left ventricular (LV) ejection fraction. These patients are characterized by pronounced LV concentric remodeling with small LV cavity size, impaired LV filling, altered myocardial function, and worse prognosis. This frequent clinical entity is often misdiagnosed, which may lead to an underestimation of aortic stenosis severity and thereby to underutilization or inappropriate delay of surgery. It is important to recognize this entity so we do not deny surgery to a symptomatic patient with small aortic valve area and low gradient. Thus, when there is a discordance between the valve area (in the severe range) and the gradient (in the moderate range) in patients with preserved LV ejection fraction, a more comprehensive Doppler echocardiographic evaluation and potentially other diagnostic tests may be required to confirm disease severity and guide therapeutic management.

Background: Bicuspid aortic valve (BAV) is the leading cause of aortic stenosis in patients younger than the age of 50. A classification scheme of BAVs is based upon leaflet orientation: Type I (fusion of right and left coronary cusps) and Type II (fusion of right and noncoronary cusps). The correlation between BAV leaflet orientation and aortic root pathology however remains ill defined., Objective: The objective was to describe a potential relationship between BAV leaflet morphology and aortic root measurements in the ASTRONOMER study, a multicenter study to assess the effect of rosuvastatin on the progression of AS., Methods: BAV morphology was classified as Type I or Type II orientation based on the parasternal short-axis view. Echo measurements including left ventricular and aortic root dimensions were obtained., Results: The study population included 89 patients (56 +/- 11 years; 44 males). There were 63 patients with Type I and 26 patients with Type II BAV. Baseline demographics, hemodynamics, and left heart dimensions were similar between both groups. Patients with Type I BAV had larger aortic annulus and ascending root dimensions compared to those patients with Type II BAV (P < 0.05)., Conclusion: In patients with mild to moderate aortic stenosis due to a BAV, the presence of Type I valve orientation was associated with significantly greater aortic root parameters compared to Type II valve orientation.

Objectives: This study was designed to evaluate the effect of valve prosthesis-patient mismatch (PPM) on late survival after aortic valve replacement (AVR) and to determine if this effect is modulated by patient age, body mass index (BMI), and pre-operative left ventricular (LV) function., Background: We recently reported that PPM is an independent predictor of operative mortality after AVR, particularly when associated with LV dysfunction., Methods: The indexed valve effective orifice area (EOA) was estimated in 2,576 patients having survived AVR and was used to define PPM as not clinically significant if it was >0.85 cm(2)/m(2), as moderate if >0.65 and < or =0.85 cm(2)/m(2), and severe if < or =0.65 cm(2)/m(2)., Results: After adjustment for other risk factors, severe PPM was associated with increased late overall mortality (hazard ratio [HR]: 1.38; p = 0.03) and cardiovascular mortality (HR: 1.63; p = 0.0006) in the whole cohort. Severe PPM was also associated with increased overall mortality in patients <70 years old (HR: 1.77; p = 0.002) and in patients with a BMI <30 kg/m(2) (HR: 2.1; p = 0.006), but had no impact in older patients or in obese patients. Moderate PPM was a predictor of mortality in patients with LV ejection fraction <50% (HR: 1.21; p = 0.01), but not in patients with preserved LV function., Conclusions: Moderate PPM is associated with increased late mortality in patients with LV dysfunction, but with normal prognosis in those with preserved LV function. Notwithstanding the previously demonstrated deleterious effect of severe PPM on early mortality, this factor appears to increase late mortality only in patients <70 years old and/or with a BMI <30 kg/m(2) or an LV ejection fraction <50%.

Aims: Mitral annular calcification (MAC) is characterized by calcium and lipid deposition in the annular fibrosa of the mitral valve. Although individuals with MAC are at increased risk of cardiovascular events, little is known about the significance of this finding in patients with concurrent aortic stenosis (AS). The aim of this study was to describe the association of baseline MAC and aortic valve morphology in asymptomatic patients enrolled in the ASTRONOMER study, a multicentre study to assess the effect of Rosuvastatin on the progression of AS., Methods and Results: At baseline, transthoracic echocardiography was performed with two-dimensional and Doppler imaging following a standardized protocol. Echo measurements including left ventricular (LV) dimensions and aortic root dimensions were obtained according to the ASE recommendations. MAC was identified by bright echoes at the base of the mitral leaflets or annulus on 2D imaging, and aortic valve calcification by visualization of bright echoes on the aortic valve leaflets. The degree of calcification was semi-quantitated from absent to severe. The study population included 219 patients (57 +/- 14 years; 129 males), divided into two pre-specified categories; bicuspid (n = 133) and tricuspid (n = 86) aortic valves. Baseline LV dimensions, aortic valve haemodynamics, and cholesterol profiles were similar between the two groups at baseline. Individuals with tricuspid aortic valves were older, more hypertensive, with higher degrees of MAC and AV calcification (P < 0.001). The higher degree of MAC persisted in patients with tricuspid AV after adjustment for age and systolic blood pressure (P = 0.004)., Conclusion: In patients with asymptomatic mild to moderate AS, MAC is more prevalent in those individuals with tricuspid AV, independent of age, and systolic blood pressure. Whether the degree of MAC may be a surrogate for atherosclerosis, and predict the subset of patients who will respond to statin therapy in preventing the progression of AS, remains to be determined.

Background and Aim of the Study: Certain theoretical arguments suggest that a stentless bioprosthetic valve may be less subject to calcification and degeneration compared to an equivalent stented bioprosthesis. The study aim was to define the long-term clinical outcomes, including freedom from structural valve deterioration (SVD), among relatively younger patients after aortic valve replacement (AVR) with the Freestyle aortic bioprosthesis., Methods: A total of 725 patients at eight study sites underwent AVR with the Freestyle stentless aortic bioprosthesis. Of these patients, 57 (7.9%) were aged < or = 60 years at the time of surgery. All clinical data were recorded prospectively., Results: The total follow up for the group was 4,900 patient-years; the mean follow up per patient was 6.8 +/- 3.6 years; median 7.2 years; range: 0 to 13.3 years). Survival at 12 years was 65.0 +/- 11.6% for patients aged < or = 60 years at implant, and 33.1 +/- 5.3% for those aged > or = 61 years. Freedom from cardiac death was 94.6 +/- 6.6% and 70.7 +/- 7.5%, respectively. Freedom from SVD at 12 years was 92.4 +/- 8.0% for patients aged < or = 60 years at implant, and 92.3 +/- 5.0% for those aged > or = 61 years (p = 0.58). There was no significant difference in freedom from reoperation at 12 years between the younger and older age groups (p = 0.16)., Conclusion: The Freestyle stentless aortic bioprosthesis was associated with excellent clinical outcomes through 12 years of follow up. Freedom from cardiac death was excellent. Measures of bioprosthesis durability remained outstanding through 12 years, with no difference in freedom from SVD or from reoperation between patients aged < or = 60 years and those aged > or = 61 years at the time of implant. Inasmuch as valve durability may influence decisions between a tissue and a mechanical valve in younger patients, these data help to support use of the Freestyle valve in patients aged < or = 60 years.

Aortic valve stenosis (AS) is the third-most frequent heart disease after coronary artery disease and arterial hypertension, and it is associated with a high incidence of adverse outcomes. Recent data support the notion that AS is not an isolated disease uniquely limited to the valve. Indeed, AS is frequently associated with abnormalities of the systemic arterial system, and, in particular, with reduced arterial compliance, which may have important consequences for the pathophysiology and clinical outcome of this disease. Moreover, AS may also be associated with left ventricular systolic dysfunction and reduced transvalvular flow rate, which pose important challenges with regards to diagnostic evaluation and clinical decision making in AS patients. Hence, the assessment of AS severity, as well as its therapeutic management, should be conducted with the use of a comprehensive evaluation that includes not only the aortic valve, but also the systemic arterial system and the left ventricle because these three entities are tightly coupled from both a pathophysiological and a hemodynamic standpoint.

Prosthesis-patient mismatch (PPM) is present when the effective orifice area of the inserted prosthetic valve is too small in relation to body size. Its main haemodynamic consequence is to generate higher than expected gradients through normally functioning prosthetic valves. This review updates the present knowledge about the impact of PPM on clinical outcomes. PPM is common (20-70% of aortic valve replacements) and has been shown to be associated with worse haemodynamic function, less regression of left ventricular hypertrophy, more cardiac events, and lower survival. Moreover, as opposed to most other risk factors, PPM can largely be prevented by using a prospective strategy at the time of operation.

Objectives: This study sought to examine the association between the metabolic syndrome (MS) and the progression of aortic stenosis (AS)., Background: It has been suggested that aortic valve sclerosis and its progression to AS are caused by an atherosclerotic process. Metabolic syndrome is associated with a higher risk of vascular atherosclerosis. Thus, we hypothesized that the atherogenic features of MS could negatively influence disease progression and prognosis in patients with AS., Methods: We retrospectively analyzed the data of 105 consecutive patients (age 69 +/- 12 years, 64 men) with at least moderate AS. Of these patients, 40 (38%) had MS identified according to the modified clinical criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. The hemodynamic progression of AS was assessed by the measurement of the annualized decrease in valve area during the follow-up period of the study, which averaged 28 +/- 13 months. Event-free survival was defined as the absence of death or aortic valve replacement during follow-up., Results: The hemodynamic progression of the stenosis was twice as fast (-0.14 +/- 0.13 cm2/year vs. -0.08 +/- 0.08 cm2/year, p = 0.008) and the three-year event-free survival was markedly lower (44 +/- 8% vs. 69 +/- 6%, p = 0.002) among patients with MS. In multivariate analysis, MS was found to be a strong independent predictor of both stenosis progression (p = 0.006) and event-free survival (odds ratio 3.85, 95% CI 1.96 to 7.58, p < 0.001)., Conclusions: The present study is the first to report that MS is associated with a faster disease progression and worse outcome in patients with AS. Such findings open new avenues of research and provide a strong impetus for the elaboration of additional prospective studies focusing on this association.

Objectives: We sought to determine whether the flow-dependent changes in Doppler-derived valve effective orifice area (EOA) are real or due to artifact., Background: It has frequently been reported that the EOA may vary with transvalvular flow in patients with aortic stenosis. However, the explanation of the flow dependence of EOA remains controversial and some studies have suggested that the EOA estimated by Doppler-echocardiography (EOA(Dop)) may underestimate the actual EOA at low flow rates., Methods: One bioprosthetic valve and three rigid orifices were tested in a mock flow circulation model over a wide range of flow rates. The EOA(Dop) was compared with reference values obtained using particle image velocimetry (EOA(PIV))., Results: There was excellent agreement between EOA(Dop) and EOA(PIV) (r2 = 0.94). For rigid orifices of 0.5 and 1.0 cm2, no significant change in the EOA was observed with increasing flow rate. However, substantial increases of both EOA(Dop) and EOA(PIV) were observed when stroke volume increased from 20 to 70 ml both in the 1.5 cm2 rigid orifice (+52% for EOA(Dop) and +54% for EOA(PIV)) and the bioprosthetic valve (+62% for EOA(Dop) and +63% for EOA(PIV)); such changes are explained either by the presence of unsteady effects at low flow rates and/or by an increase in valve leaflet opening., Conclusions: The flow-dependent changes in EOA(Dop) are not artifacts but represent real changes in EOA attributable either to unsteady effects at low flow rates and/or to changes in valve leaflet opening. Such changes in EOA(Dop) can be relied on for clinical judgment making.

Background: The effective orifice area (EOA) is the standard parameter for the clinical assessment of aortic stenosis severity. It has been reported that EOA measured by Doppler echocardiography does not necessarily provide an accurate estimate of the cross-sectional area of the flow jet at the vena contracta, especially at low flow rates. The objective of this study was to test the validity of the Doppler-derived EOA., Methods: Triangular and circular orifice plates, funnels, and bioprosthetic valves were inserted into an in vitro aortic flow model and were studied under different physiologic flow rates corresponding to cardiac outputs varying from 1.5 to 7 L/min. For each experiment, the EOA was measured by Doppler and compared with the catheter-derived EOA and with the EOA derived from a theoretic formula. In bioprostheses, the geometric orifice area (GOA) was estimated from images acquired by high-speed video recording., Results: There was no significant difference between the EOA derived from the 3 methods with the rigid orifices (Doppler vs catheter: y = 0.97x +0.18 mm(2), r(2) = 0.98; Doppler vs theory: y = 1.00x -3.60 mm(2), r(2) = 0.99). Doppler EOA was not significantly influenced by the flow rate in rigid orifices. As predicted by theory, the average contraction coefficient (EOA/GOA) was around 0.6 in the orifice plates and around 1.0 in the funnels. In the bioprosthetic valves, both EOA and GOA increased with increasing flow rate whereas contraction coefficient was almost constant with an average value of 0.99. There was also a very good concordance between EOA and GOA (y = 0.94x +0.05 mm(2), r(2) = 0.88)., Conclusions: In rigid aortic stenosis, the Doppler EOA is much less flow dependent than generally assumed. Indeed, it depends mainly on the GOA and the inflow shape (flat vs funnel-shaped) of the stenosis. The flow dependence of Doppler EOA observed in clinical studies is likely a result of a variation of the valve GOA or of the valve inflow shape and not an inherent flow dependence of the EOA derived by the continuity equation.

Objectives: We sought to obtain more coherent evaluations of aortic stenosis severity., Background: The valve effective orifice area (EOA) is routinely used to assess aortic stenosis severity. However, there are often discrepancies between measurements of EOA by Doppler echocardiography (EOA(Dop)) and those by a catheter (EOA(cath)). We hypothesized that these discrepancies might be due to the influence of pressure recovery., Methods: The relationship between EOA(cath) and EOA(Dop) was studied as follows: 1) in an in vitro model measuring the effects of different flow rates and aortic diameters on two fixed stenoses and seven bioprostheses; 2) in an animal model of supravalvular aortic stenosis (14 pigs); and 3) based on catheterization data from 37 patients studied by Schöbel et al., Results: Pooling of in vitro, animal, and patient data showed a good correlation (r = 0.97) between EOA(cath) (range 0.3 to 2.3 cm(2)) and EOA(Dop) (range 0.2 to 1.7 cm(2)), but EOA(cath) systematically overestimated EOA(Dop) (24 +/- 17% [mean +/- SD]). However, when the energy loss coefficient (ELCo) was calculated from EOA(Dop) and aortic cross-sectional area (A(A)) to account for pressure recovery, a similar correlation (r = 0.97) with EOA(cath) was observed, but the previously noted overestimation was no longer present., Conclusions: Discrepancies between EOA(cath) and EOA(Dop) are largely due to the pressure recovery phenomenon and can be reconciled by calculating ELCo from the echocardiogram. Thus, ELCo and EOA(cath) are equivalent indexes representing the net energy loss due to stenosis and probably are the most appropriate for quantifying aortic stenosis severity.

Background: The Ross procedure and aortic homografts have both been shown to have superior hemodynamic performance after valve replacement, but there have been few comparisons., Methods: Sequential Doppler echocardiograms were performed up to 5 years after aortic valve replacement in 132 patients with the Ross procedure and 111 patients with an aortic homograft (AH). Measurements included assessment of valvular regurgitation and calculations of valve effective orifice area (EOA) and mean transvalvular gradients; the same measurements were also performed at the level of the pulmonary homograft in the Ross patients as well as during maximum exercise in 20 Ross patients and 14 AH patients., Results: Aortic valve hemodynamics were stable during follow-up for both procedures and values at 1 year showed larger indexed EOAs (1.77+/-0.45 versus 1.42+/-0.35 cm(2)/m(2), P<0.001) and lower gradients (2+/-3 versus 4+/-3 mm Hg) for the Ross procedure; similar findings were also observed during exercise (1.99+/-0.44 versus 1.36+/-0.39 cm(2)/m(2), P<0.001 and 7+/-3 versus 17+/-11 mm Hg). Prevalence and severity of aortic regurgitation were low in both groups, although 4 patients (1 Ross, 3 AH) underwent a second operation for this reason. Also, various degrees of pulmonary homograft stenosis were found in 20% of Ross patients, 4 of which underwent a second operation., Conclusion: Both procedures provide continued excellent hemodynamics of the aortic valve. The Ross procedure has a slight advantage, but this is somewhat counterbalanced by the deterioration of the pulmonary homograft in up to 20% of patients. Further studies aimed at clarifying longer-term outcomes as well as preventing pulmonary homograft stenosis with the Ross operation are clearly needed.

Although stentless aortic bioprostheses are associated in general with excellent hemodynamics, a subset of patients exhibit high early postoperative gradients. The present study was performed to evaluate the prevalence and impact of suboptimal hemodynamics early after stentless tissue aortic valve replacement. The early postoperative peak transvalvular to peak left ventricular (LV) outflow tract velocity ratio was > or = 3.0 in 44 (6.7%) of 658 patients in the multicenter, long-term study of the Freestyle stentless aortic valve. Mean gradient, effective orifice area (EOA), and LV mass index were compared between these patients and a control group of 44 patients matched for age, sex, valve size, and implant technique. High velocity ratio was associated with female sex (63.6% v 42.8%, P =.01), smaller valve size (77.3% v 45.3%, < or = 23 mm, P =.0004), and use of the modified subcoronary rather than full root implant technique (90.9% v 70.2% modified subcoronary, P =.01). Mean gradient was significantly higher (P <.05) and EOA lower (P <.05) early postoperative and throughout follow-up among patients with high velocity ratio. LV mass index decreased across time among both groups; patients with high velocity ratio tended to have higher LV mass index with less complete LV mass regression, although the difference did not reach statistical significance. In conclusion, there was a 6.7% incidence of hemodynamics suggestive of significant aortic stenosis early after implantation of a Freestyle stentless aortic valve. Gradients decreased and EOA increased in the first months after surgery, although they remained less favorable. Multiple factors likely play a role in early suboptimal hemodynamics following stentless tissue aortic valve replacement, including factors related to patient population, valve size, implant modality, and implant technique., (Copyright 2001 by W.B. Saunders Company)

Stentless bioprostheses show excellent early hemodynamic performance. However, longevity still remains unknown. This study reports midterm follow-up in 419 patients in which a Freestyle bioprosthesis (Medtronic Heart Valves, Minneapolis, MN) was inserted between January 1993 and January 2000 at the Quebec Heart Institute (Ste-Foy, Québec, Canada). Mean age at implantation was 68.0 +/- 8.2 years. Implantation was subcoronary in 81.9% of the patients, as a root replacement in 16.5%, and as a root inclusion in 1.7%. Mortality at 30 days was 6.2% for the whole cohort (2.8% for isolated subcoronary aortic valve replacement). Female gender, root implantation, valve sizes 19 to 21 mm, previous surgery, a history of stroke and diabetes were identified as predictors of 30-day mortality. Actuarial freedom from all death causes was 81.5% at 7 years; freedom from valve-related deaths 97.0%, and freedom from cardiac deaths 92.7%. Freedom from thromboembolic events was 86.1% at 7 years (55.1% of events were < 30 days). Freedom from endocarditis and hemorrhagic complications were respectively 98.5% and 95.6% at 7 years. Six patients required reoperations for valve explantation: 2 for endocarditis, 2 for structural dysfunction, and 2 for nonstructural dysfunction. Incidence of moderate or severe valve insufficiency at annual echocardiographic follow-up was: discharge: 0.6%; year 1: 0.7%; year 2: 1.3%; year 3: 3.3%; year 4: 3.7%; year 5: 2.6%; year 6: 0%. At 6 years after implantation, mean transvalvular gradient and effective valve orifice area were comparable to the year 1 values. This single center experience with the Medtronic Freestyle prosthesis shows preserved hemodynamic performance and low valve-related complications at midterm., (Copyright 2001 by W.B. Saunders Company)

Aortic valve resistance has been proposed to represent the severity of aortic stenosis because some studies observed that it was less affected by change in flow than the valve-effective orifice area, but this issue remains controversial. The objective of this study was to systematically analyze the theoretical and practical determinants of these parameters in relation to changes in flow. Valve area and resistance in different valves were studied in vitro in a pulse duplicator system at different flow rates and in vivo in 90 subjects referred to either exercise or dobutamine infusion. Theoretical analysis and experimental results both demonstrated a unique relation between resistance (RES), valve-effective orifice area (EOA), and flow rate (Q): RES = K x (Q/EOA(2)). Accordingly, in fixed stenoses or in mechanical valves, resistance increased markedly with flow rate both in vitro (+0.88 +/- 0.26%/% of flow increase) and in vivo (mechanical valves: +2.09 +/- 4.61, fixed stenotic valves: +0.59 +/- 0.32%/%), whereas valve area did not change significantly (<0.2%/%). In contrast, in valves with a flexible orifice (bioprostheses and some patients with aortic stenosis), resistance was less increased due to the increase in valve area. Thus, both from a theoretical and a practical standpoint, valve resistance is much more flow dependent than valve area, particularly in fixed stenoses. Situations in which resistance does not increase with flow rate are unpredictable and are found in flexible valves when there is a concomitant increase in valve area.

Background: Patient-prosthesis mismatch is a frequent cause of high postoperative gradients in normally functioning prostheses. The objective of this study was to determine whether mismatch can be predicted at the time of operation., Methods: Indices used to predict mismatch were valve size, indexed internal geometric area, and projected indexed effective orifice area (EOA) calculated at the time of operation, and results were compared with indexed EOA and mean gradients measured by Doppler echocardiography after operation in 396 patients., Results: The sensitivity and specificity of these indices to detect mismatch, defined as a postoperative indexed EOA of 0.85 cm2/m2 or less, were respectively: 35% and 84% for valve size, 46% and 85% for indexed internal geometric area, and 73% and 80% for projected indexed EOA. Projected indexed EOA also correlated best with resting (r = 0.67) and exercise (r = 0.77) postoperative gradients., Conclusions: The projected indexed EOA calculated at the time of operation accurately predicts mismatch as well as resting and exercise postoperative gradients, whereas valve size and indexed internal geometric area cannot be used for this purpose.

Background: The midterm clinical and hemodynamic performance of the Medtronic Mosaic porcine bioprosthesis was evaluated in a regulatory trial., Methods: In nine Canadian centers, 802 bioprostheses (560 aortic and 242 mitral) were implanted between September 1994 and April 1999 in patients with a mean age of 70 years., Results: Survival for aortic valve replacement at 4 years was 84.4%+/-3.1%. Freedom from valve-related or unexplained death was 95.6%+/-1.9%; structural valve deterioration, 100.0%; reoperation, 96.2%+/-1.7%; major thromboembolism, 96.1%+/-1.8%; and major antithrombotic-related hemorrhage, 96.4%+/-1.7%. Echocardiographic derived mean systolic gradient was 13.4 mm Hg at 4 years with an indexed effective orifice area of 0.7 to 0.8 cm2/m2. A significant decrease in left ventricular mass was shown over time in all valve sizes. Survival for mitral valve replacement at 4 years was 79.2%+/-6.8%. Freedom from valve-related or unexplained death was 96.5%+/-3.4%; structural valve deterioration, 100%; reoperation, 97.0%+/-3.2%; major thromboembolism, 95.7%+/-3.8%; and major antithrombotic-related hemorrhage, 95.0%+/-4.2%. Echocardiographically measured averaged mean diastolic gradient was 4.5 mm Hg., Conclusions: The Medtronic Mosaic bioprosthesis is safe and effective in both the aortic and mitral positions. The valve has low gradients in both positions and excellent left ventricular mass regression in the patients with aortic valve replacement.

Background: The pulmonary autograft (Ross) operation is an attractive treatment for aortic valve disease, but hemodynamic follow-up is not well defined., Methods and Results: One hundred thirty-two consecutive patients (62% male, mean age 40+/-11 years) were followed up to 5 years after the Ross operation. Echocardiography was performed early (within 30 days), 3 to 6 months, and yearly after surgery. The valve effective orifice area (EOA) and mean transvalvular gradient of both aortic and pulmonary valves were measured, and transvalvular regurgitation was assessed by using color Doppler echocardiography. EOA was indexed for body surface area. The hemodynamic performance was excellent for both the aortic and pulmonary valves early after surgery (gradient, 3+/-4 and 3+/-4 mm Hg, respectively). It remained stable thereafter for the aortic valve, whereas there was a significant deterioration of the EOA (-0. 74+/-0.82 cm(2)) and gradient (+6+/-8 mm Hg) for the pulmonary valve, which occurred mostly during the first 6 months after surgery. This hemodynamic deterioration resulted in suboptimal (defined as an EOA index <0.85 cm(2)/m(2)) hemodynamics in 19.3% of the patients, to the extent that 3 (2%) of the 132 patients eventually had to be subjected to further surgery for severe pulmonary valve stenosis., Conclusions: The pulmonary autograft provides continued excellent hemodynamics in the aortic position, whereas moderately high gradients can be found across the pulmonary homograft in some patients. Further studies are necessary to identify the factors responsible for the deterioration of the hemodynamic performance of the homograft in the pulmonary position and to determine its impact on right ventricular function and clinical status.

This study examines the resting and exercise hemodynamic performance of the pulmonary autografts in the aortic position as well as of the homografts used for right ventricular outflow reconstruction in patients undergoing the Ross operation. Previous studies have reported excellent resting hemodynamics in patients who underwent aortic valve replacement with a pulmonary autograft. However, there are very few studies of their hemodynamic performance during exercise. Twenty adult subjects who underwent the Ross operation and 12 normal control subjects were submitted to maximum romp bicycle exercise. The valve effective orifice areas and transvalvular gradients of both aortic (autograft) and pulmonary (homograft) valves were measured at rest and at peak of maximum exercise using Doppler echocardiography. Valve areas were indexed for body surface area. The hemodynamics of the aortic valve were very similar in Ross subjects and in control subjects at rest and during exercise. However, the indexed valve area of the pulmonary valve at rest was significantly (p < 0.001) lower in the Ross subjects (1.10 +/- 0.46 cm2/ m2) than in the control subjects (1.95 +/- 0.41 cm2/m2), resulting in higher (p = 0.004) mean gradients at rest (Ross: 9 +/- 7 mm Hg vs control: 2 +/- 1 mm Hg) and at peak exercise (Ross: 21 +/- 14 mm Hg vs control: 7 +/- 2 mm Hg). The pulmonary autograft provided excellent hemodynamics in the aortic position either at rest or during maximum exercise, whereas moderately high gradients were found during exercise across the homograft implanted in the pulmonary valve position. Future improvement of the Ross procedure should be oriented toward the search of new methods to prevent the deterioration of the homografts.

Background: The objective of this study is to assess the clinical and hemodynamic performance of a stentless porcine bioprosthesis, the Freestyle aortic root bioprosthesis., Methods: Consenting patients requiring isolated aortic valve or aortic root replacement received the Freestyle bioprosthesis. Clinical follow-up and echocardiographic data were obtained at discharge, 3 to 6 months, 1 year, and annually thereafter., Results: Two hundred seventy-six patients received a Freestyle aortic root bioprosthesis between January 1993 and July 1997. The mean age was 67.7 years. Preoperatively, 86.3% were either New York Heart Association class III or IV. Two hundred thirty-eight patients underwent valve (subcoronary) replacement, 36 underwent aortic root replacement, and 2 underwent valve replacement using the root-inclusion technique. The early mortality was 5.4%, with 3.3% mortality for the subcoronary technique and 19.4% mortality for aortic root replacement. The mean gradient decreased significantly between discharge and the 3- to 6-month follow-up and stabilized thereafter. The effective orifice area increased significantly from discharge to 3 to 6 months' follow-up. At 3 years, 84.4% of the patients had either no or trivial regurgitation., Conclusions: The Freestyle bioprosthesis has good clinical performance and good short-term hemodynamic performance. The majority of the regurgitation identified is not clinically significant.