Degree Of Aortic Valve Calcification Research Articles

Use of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis

Abstract Objective Assessment of flow is important in grading of aortic valve stenosis (AS). Sex-specific thresholds for low flow were recently proposed (stroke volume index <40 ml/m² in men and <32 ml/m² in women, respectively). We tested the prognostic association of these cut-offs in AS patients with concordantly and discordantly graded AS based on pressure recovery adjusted aortic valve area. Methods Data from 1353 patients (38.6% women) with asymptomatic mild-moderate AS and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. Discordantly graded AS (DGASEL) was defined as combined pressure recovery adjusted aortic valve area (energy loss) <1.0 cm² and mean aortic gradient <40 mmHg and concordantly graded mild-moderate AS as combined EL ≥1.0 cm² and mean aortic gradient <40mmHg. Patients were further grouped into normal and low flow. Outcome was assessed using both Kaplan-Meier curves and Cox regression analyses with concordantly graded AS with normal flow as comparator. Results In the total study population, mild-moderate AS with normal flow was present in 915 patients, mild-moderate AS with low flow in 253 patients, DGASEL with normal flow in 57 patients and DGASEL with low flow in 126 patients. During a median of 4.3 years follow-up, survival free of death and/or hospitalization for heart failure was significantly lower in patients with DGASEL irrespective of flow compared to those with mild-moderate AS with normal flow (both P<0.05, Figure). In Cox regression analysis, after adjustment for hypertension, age, sex, heart rate, randomized study treatment, aortic valve replacement and degree of aortic valve calcification, DGASEL with normal or low flow were both associated with increased risk of combined death and hospitalization for heart failure (P<0.05) (Table). However, no prognostic difference was found between groups with normal vs. low flow within groups of discordantly or concordantly graded AS. Conclusions Identification of low flow by the proposed sex-specific thresholds of stroke volume index <40 ml/m² in men and <32 ml/m² in women needs more validation before inclusion in clinical guidelines. Figure. Kaplan-Meier plot of event-free survival from combined death and heart failure hospitalization in groups of patients with mild-moderate AS normal flow, mild-moderate AS low flow, DGASEL with normal flow and DGASEL with low flow. Table. Association of combined death and hospitalization for heart failure in groups of concordantly and discordantly graded AS with normal and low flow. Multivariable Cox analysis.

Association of aortic valve size with the degree of aortic valve calcification in patients with severe aortic stenosis

Abstract Background The development and progression of aortic valve calcification (AVC) is a major contributor to the severity of aortic stenosis (AS). Currently, the 2021 ESC/EACTS Guidelines recommend the use of the Agatston AVC score to predict the likelihood of severe AS in patients with unclear echocardiographic AS severity. It has been shown that AS in women is associated with less AVC, thus lower AVC thresholds for the diagnosis of severe AS in women are recommended. It has furthermore been demonstrated that women generally have smaller hearts. However, whether small aortic valve (AV) size, independent from sex, is associated with less AVC in patients with severe AS has not been explored. Purpose The aim of this study was to assess the association of AV dimension and the degree of AVC in severe AS. Methods AVC was assessed on computed tomography using the Agatston score in consecutive patients with severe AS. AV diameter and indexed AV annulus area adjusted for body surface area were measured. To analyze the association with AVC, Spearman rank correlation as well as multivariate linear regression models adjusted for age, sex, left ventricular ejection fraction and cardiovascular risk factors were performed. Results In total 446 patients (mean age 81±6 years, 45% female) were included. Median Agatston Score was 2949 AU [2135-3986] in men and 1755 AU [1303-2571] in women. Mean AV diameter was 24±2mm and mean indexed annulus area was 248±43mm2. We observed a significant correlation between AV Agatston score and AV diameter (r=0.6; p<0.001 Figure 1 Panel A) as well as between AV Agatston score and indexed annulus area (r=0.5; p <0.001; Figure 1 Panel B). On multivariate analysis AV diameter (β=273; p<0.001), indexed annulus area (β=13; p<0.001) and sex (β=396; p<0.001) were independently associated with AVC by the Agatston score. In addition, separate regression analyses in men and women showed a significant association of AV diameter (β(men)=265; β(women)=275; both p<0.001) and indexed annulus area (β(men)=13; β(women)=11; both p<0.001) with the AV Agatston score. Hypertension, dyslipidemia, diabetes mellitus, smoking and chronic kidney disease showed no statistically significant association with the amount of AVC. Conclusion Our results indicate that patients with severe AS and larger AV dimensions present with more AVC on Agatston scoring, independent from sex. From surgical data, it is known that smaller aortic bioprostheses cause higher gradients, consequently we hypothesize here, that less calcification is required in small valves to cause significant narrowing. Thus, AVC cut-offs for the diagnosis of AS should be indexed for AV size rather than sex.

Sex discrepancies in pathophysiology, presentation, treatment, and outcomes of severe aortic stenosis.

This review gives an overview of sex-based differences in aortic valve stenosis, spanning from pathophysiological mechanisms and disease progression, clinical presentation, presence of comorbidities, and diagnostic assessment, to treatment and outcomes. In particular, sex-related differences in the degree of aortic valve calcification, the response of the left ventricle to pressure overload, as well as in the referral to procedures, with women being less frequently referred for surgical aortic valve replacement and experiencing longer waiting times for transcatheter procedures, will be discussed. Sex-related differences are also particularly evident in outcomes of patients with severe aortic stenosis undergoing surgical or transcatheter procedures. The apparent sex paradox seen in women undergoing transcatheter aortic valve implantation refers to the phenomenon of women experiencing higher rates of short-term mortality and bleeding events, but demonstrating improved long-term survival as compared to men. Women who undergo surgical aortic valve replacement have generally worse outcomes as compared to men, which is reflected by the inclusion of female sex in surgical risk calculation scores. Hence, a thorough understanding of sex-related differences in aortic valve stenosis is important to provide optimal and personalized patient care.

Clinical outcomes after aortic valve replacement with severe stenosis of trileaflet aortic valve and low valve calcium score

BackgroundSome patients have severe aortic valve stenosis (AS) despite a lower degree of aortic valve calcification (AVC). This study compared the clinical features and prognosis of patients undergoing aortic valve...

Combined CT Coronary Artery Assessment and TAVI Planning

Computed tomography angiography (CTA) of the aorta and the iliofemoral arteries is crucial for preprocedural planning of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS), because it provides details on a variety of aspects required for heart team decision-making. In addition to providing relevant diagnostic information on the degree of aortic valve calcification, CTA allows for a customized choice of the transcatheter heart valve system and the TAVI access route. Furthermore, current guidelines recommend the exclusion of relevant coronary artery disease (CAD) prior to TAVI. The feasibility of coronary artery assessment with CTA in patients scheduled for TAVI has been established previously, and accumulating data support its value. In addition, fractional flow reserve determined from CTA (CT-FFR) and machine learning-based CT-FFR were recently shown to improve its diagnostic yield for this purpose. However, the utilization of CTA for coronary artery evaluation remains limited in this specific population of patients due to the relatively high risk of CAD coexistence with severe AS. Therefore, the current diagnostic work-up prior to TAVI routinely includes invasive catheter coronary angiography at most centers. In this article, the authors address technological prerequisites and CT protocol considerations, discuss pitfalls, review the current literature regarding combined CTA coronary artery assessment and preprocedural TAVI evaluation, and provide an overview of unanswered questions and future research goals within the field.

Aortic valve calcium score in prediction of post-TAVI complications in an Egyptian cohort

BackgroundSevere symptomatic aortic stenosis is a common disorder in the elderly and is associated with high morbidity and mortality rate. Traditionally, surgical aortic valve replacement has been considered the most effective treatment for advanced disease. Transcatheter aortic valve implantation (TAVI) has been established as a valuable alternative treatment option for inoperable and high-risk patients with symptomatic severe aortic stenosis. Pre-procedure ECG-gated CT aortography study is important in planning the procedure. The aim of the study was to correlate the aortic valve calcium score with the post-TAVI complications.ResultsThirty patients who were candidates for TAVI procedure were enrolled for ECG-gated CT aortic valve calcium score and CT aortography. The calcium score was calculated. The patients were followed up both clinically and by echocardiography every 3 months for 1 year. Those who developed complications were enrolled for another CT study. Fourteen out of 30 patients (46.7%) presented with post-TAVI complications [9 cases (30%) presented with paravalvular leak (PVL) and 5 cases (16.7%) presented with major adverse cardiac events (MACE), while 16 cases (53.3%) had no complications]. There was a strong correlation between the calcium score and post-procedure complications.ConclusionsThe degree of aortic valve calcification can be considered as a predictor of post-TAVI complications: PVL and MACE.

Haemodynamic performance and clinical outcomes of transcatheter aortic valve replacement with the self-expanding ACURATE neo2.

Transcatheter aortic valve replacement (TAVR) with the ACURATE neo device has been associated with a non-negligible incidence of paravalvular aortic regurgitation (AR). The new-generation ACURATE neo2 has been designed to mitigate this limitation. The aim of the study was to compare TAVR with the ACURATE neo and neo2 devices. The NEOPRO and NEOPRO-2 registries retrospectively included patients undergoing transfemoral TAVR with self-expanding valves at 24 and 20 centres, respectively. Patients receiving the ACURATE neo and neo2 devices (from January 2012 to December 2021) were included in this study. Predischarge and 30-day VARC-3 defined outcomes were evaluated. The primary endpoint was predischarge moderate or severe paravalvular AR. Subgroup analyses per degree of aortic valve calcification were performed. A total of 2,026 patients (neo: 1,263, neo2: 763) were included. Predischarge moderate or severe paravalvular AR was less frequent for the neo2 group (2% vs 5%; p<0.001), resulting in higher VARC-3 intended valve performance (96% vs 90%; p<0.001). Furthermore, more patients receiving the neo2 had none/trace paravalvular AR (59% vs 38%; p<0.001). The reduction in paravalvular AR with neo2 was mainly observed with heavy aortic valve calcification. New pacemaker implantation and VARC-3 technical and device success rates were similar between the 2 groups; there were more frequent vascular and bleeding complications for the neo device. Similar 1-year survival was detected after TAVR (neo2: 90% vs neo: 87%; p=0.14). TAVR with the ACURATE neo2 device was associated with a lower prevalence of moderate or severe paravalvular AR and more patients with none/trace paravalvular AR. This difference was particularly evident with heavy aortic valve calcification.

P905Association of ionized serum magnesium with progression of aortic valve calcification

Abstract Background Calcific aortic valve disease (CAVD) is the most common heart valve disease among adults. It is a progressive disease whose final step leads to severe aortic stenosis (AS). Pharmacotherapeutic strategies aimed to limit the progression of valve leaflet calcification could be beneficial to slow-down the CAVD progression and to preserve left ventricular function. Several recent clinical studies demonstrated that lower serum magnesium (Mg) level is associated with vascular calcification. Whether serum magnesium is a determinant of aortic calcific stenosis progression remains unkwown. Methods In an ongoing prospective cohort of AS patients (COFRASA/GENERAC) we studied the association between serum Mg with the aortic valve calcification prevalence and progression. Serum Mg was measured at baseline in both its ionized (iMg) and total (tMg) forms. AS stenosis severity was evaluated at baseline and yearly thereafter using mean pressure gradient (MPG), the aortic valve area indexed to body surface (AVAi) assessed by echocardiography and the degree of aortic valve calcification (AVC) assessed by computed tomography. Annual progression was calculated as: (final measurement − baseline measurement)/follow-up duration. Results We enrolled 356 patients (73.1±10 years, 73% men), the mean follow-up duration was 2.5±2 years. There was a highly significant correlation between iMg and t Mg concentrations values (r=0.85, p&lt;0.0001). Approximately 37% and 25% of patients have respectively iMg values ≤0.45 mmol/L (normal range 0.45–0.60 mmol/L) and t Mg ≤0.80 mmol/L (normal range 0.80–0.95 mmol/L). At baseline, lower i Mg and t Mg were significantly associated with sex, diabètes, lower heamoglobin and hypertension but not with AVC neither with MPG or AVAi. After mean follow-up of 2.5±2 years, the annual mean Log AVC progression was significantly greater (p=0.01) in patients with values of iMg ≤0.45 mmol/L (2,04±0.73) as compared to patients with iMg &gt;0,45 mmol/L (1.78±0.94). Annual Mean MGP and AVAi also progressed greater in patients with low iMg but without reaching a significant level. Similar association was not found with tMg. In multivariate analysis, iMg remained significantly associated with the progression of AVC (odds ratio per 0.1 mmol/L increment [95% confidence interval] = 0.36 [0.15–0.83]; p=0.015) independently of age, tMg, glucose, type 2 diabetes, Tobacco use, baseline AVC, MPG and AVAi. Conclusion In a prospective cohort of asymptomatic patients with a wide range of AS severity, low serum ionized Mg but not low total Mg was independently associated with AVC progression. Acknowledgement/Funding ANR -RHU-STOPAS

P4660Lipoprotein particle profiles compared with standard lipids in the association with sub-clinical aortic valve calcification in apparently healthy Japanese men

Abstract Introduction Calcific aortic valve disease (CAVD) is one of the most common heart diseases worldwide, and its prevalence has increased in developed countries along with aging populations. Subclinical CAVD is characterized by aortic valve calcification (AVC) that may lead to aortic stenosis. AVC shares the same risk factors with atherosclerotic disease. Recently, nuclear magnetic resonance (NMR)-based lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease. It has been unclear, however, whether NMR-based particles are associated with AVC. Purpose To examine cross-sectional association of NMR-based lipoprotein particles, standard lipids with AVC, and compare their strengths of association. Methods We studied a community-based random sample of Japanese men aged 40–79 years examined in 2006–08 in Japan. We excluded participants with history of myocardial infarction, stroke, aortic valve surgery, serum triglyceride concentration ≥400 mg/dl, estimated glomerular filtration rate (eGFR) &lt;30 (ml/min/1.73m2), and use of lipid-lowering medication. We scored the degree of AVC according to Agatston's method, and defined prevalent AVC as the score &gt;0. Lipoprotein particles were measured using NMR spectroscopy. In our main analysis, we obtained multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) of prevalent AVC in the top quartile (Q4) for each lipid index in reference to the lowest quartile (Q1). Adjusting covariates include age, smoking, drinking, systolic blood pressure, glycated hemoglobin, medications for hypertension and/or for diabetes, eGFR, C-reactive protein. For sensitivity analysis, we repeated similar analyses presenting ORs per 1 standard deviation (SD) higher NMR-lipoproteins particles or standard lipids. Results Of 874 participants we analyzed, 153 (17.5%) men had AVC. The average (SD) age was 63.3 (10.0) years. Those with AVC tended to be older, likely to have clustering of atherosclerotic risk factors. Multivariable-adjusted ORs of prevalent AVC for Q4 versus Q1 were significantly positive for LDL-p [OR, 2.21 (95% CI: 1.24, 3.95] and low-density lipoprotein cholesterol (LDL-c) [2.17 (1.24, 3.80)]. In contrast, neither HDL-p nor high-density lipoprotein cholesterol (HDL-c) was significantly associated with AVC. In sensitivity analyses, however, the corresponding ORs per 1SD higher lipids/lipoprotein particles were smaller in LDL-p [1.33 (1.09, 1.63)] than LDL-c [1.41 (1.15, 1.73)]. The association of HDL-p became significant [1.28 (1.02, 1.61)] (per 1SD decrement) in the sensitivity analysis. Conclusion The overall associations of AVC with NMR-based lipoprotein particles (i.e. LDL-p, HDL-p) are comparable to those of standard lipids. This finding is parallel to the association between atherosclerotic cardiovascular diseases with NMR-based lipoproteins.

Impact of Fetuin-A on progression of calcific aortic valve stenosis - The COFRASA - GENERAC study

BackgroundAortic stenosis (AS) is an active disease, but the determinants of AS progression remain largely unknown. Low levels of Fetuin-A, a powerful inhibitor of ectopic calcification, have been linked to ectopic calcium tissue deposition but its role in AS progression has not been clearly evaluated. MethodsIn our ongoing prospective cohort (COFRASA/GENERAC), serum Fetuin-A level was measured at baseline and AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification (AVC)). Annual progression was calculated as [(final measurement-baseline measurement)/follow-up duration] for both MPG and AVC measurements. ResultsWe enrolled 296 patients (74 ± 10 years,73% men); mean follow-up duration was 3.0 ± 1.7 years. No correlation was found between baseline serum Fetuin-A (0.55 ± 0.15 g/L) and baseline AS severity (r = 0.25, p = 0.87 for MPG; r = 0.06, p = 0.36 for AVC). More importantly, there was no correlation between baseline serum Fetuin-A level and AS progression either assessed using MPG or AVC (both r = 0.01, p = 0.82). In bivariate analysis, after adjustment for age, gender, baseline AS severity, or valve anatomy, Fetuin-A was not associated with AS progression (all p > 0.20). The absence of link with AS progression was further confirmed by the absence of link betwen serum Fetuin-A and the occurrence of AS-related events (p = 0.17). ConclusionsIn a large prospective cohort of AS patients, serum Fetuin-A was not associated to hemodynamic or anatomic AS progression. Despite its capacity to inhibit ectopic calcium deposition, Fetuin-A serum level seemed to have minor influence on AS progression.

Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis

BackgroundDeterminants of the progression of aortic stenosis (AS) remained unclear. Metabolic syndrome (MetS) and diabetes are suspected to play an active role but literature is scarce and results conflicting. We sought to assess their impact in an ongoing prospective cohort of asymptomatic patients with at least mild AS. MethodsWe enrolled 203 patients (73±9years, 75% men) with at least 2years of follow-up. Risk-factors assessment was performed at baseline. Annual progression was calculated as [(final-baseline measurements)/follow-up duration] for both mean pressure gradient (MPG) and degree of aortic valve calcification (AVC) measurements. ResultsNinety-nine patients (49%) had MetS and 50 (25%) had diabetes (including 39 with MetS). After a mean follow-up of 3.2±1.2years, AS progression was not different between patients with and without MetS either using MPG (+3±3 vs. +4±4mmHg/year, p=0.25) or AVC (+211±231 vs. +225±222AU/year, p=0.75). Same results were obtained for patients with diabetes (3±3 vs. 4±4mmHg/year p=0.53, 187±140 vs. 229±248AU/year p=0.99). MetS had no impact on AS progression in all tested subgroups based on age, statin prescription, valve anatomy and AS severity (all p≥0.10). ConclusionIn our prospective cohort of AS patients, we found no impact of MetS or diabetes on AS progression. Although MetS and diabetes should be actively treated, no impact on AS progression should be expected. Our results support the theory that if cardiovascular risk-factors may play a role at the early phase of AS disease they have no or limited influence on AS progression.

Cerebral white matter lesion burden is associated with the degree of aortic valve calcification and predicts peri-procedural cerebrovascular events in patients undergoing transcatheter aortic valve implantation (TAVI).

To investigate the impact of aortic valve calcification and brain morphology on acute peri-procedural cerebrovascular events (CVEs) in patients undergoing transcatheter aortic valve implantation (TAVI). Aortic valve calcification and stenosis can be assessed with echocardiography. Cerebral magnetic resonance imaging (MRI) depicts and quantifies morphological signs of hypoperfusion and vascular embolism, which is of special interest in patients with severe aortic stenosis. Furthermore, subjects who undergo TAVI are prone to suffer of clinically silent peri-procedural CVEs. A total of 119 patients referred to TAVI were investigated for aortic valve calcification using trans-esophageal echocardiography. Cerebral MRI prior to and immediate after implantation was performed in all patients using a dedicated scan protocol. Prior to TAVI, brain morphology was characterized. Post TAVI, brains were investigated for the onset of acute peri-procedural CVEs using diffusion weighted imaging (DWI). Seventy-eight patients (65.5%) revealed acute peri-procedural CVEs on MRI after TAVI with a favor of the left hemisphere (57.5%). The degree of valve calcification was associated with peri-procedural CVEs. Patients with a high WML burden had an increased risk for CVEs ((OR) 2.36 (95% CI: 1.09-5.15; P = 0.037)), especially when distributed periventricular ((OR: 3.27; 95% CI: 1.47-7.26; P = 0.0038)). In patients undergoing TAVI, the degree of aortic valve calcification and periventricular WML burden were correlated with acute peri-procedural CVEs. Future studies are needed to evaluate their independent value for the long-term clinical outcome.

P650Influence of fetunin-a level on progression of calcific aortic valve stenosis The COFRASA - GENERAC Study.

In recent years, pathophysiology of aortic stenosis (AS) has been considered as a possibly active inflammatory process, but its determinants remain unclear. Calcium tissue deposition observed in dilaysis patients have been linked to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is thus suspected to play a role in development of aortic stenosis. To assess correlation between Fetuin-A level and AS progression in a prospective cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC (clinicalTrial.gov_number_NCT00647088). A comprehensive clinical evaluation and Fetuin-A plasma level measurement was performed at baseline. AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification or AVC). Annual progression was calculated as [(final measurement - baseline measurement)/follow-up duration] for both MPG and AVC measurements. We enrolled 296 patients with at least 1 year of follow-up. Mean age was 74±10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55±0.15 g/L. After a mean follow-up of 3.0±1.7 years, no correlation was found between AS progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC (r=0.014, p=0.82). This was also true when comparing patients with lower level of Fetuin-A (≤0.53 g/L, the median in our cohort) with patients with higher level(+3±5 mmHg/year (median 2, [0-5] vs +4±4 mmHg/year (median 2, [1-6]) p=0.06, and +205±290 AUC/year (median 122, [32-269]) vs +240±310 AUC/year (median 145, [50-313], p=0.24). This was true also after adjustment for baseline severity and valve antomy. In our prospective cohortot of AS patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS progression. Despite strong capacity to inhibit ectopic calcium deposition, Fetuin-A plasma level seems to have minor influence on AS progression.

Abstract 14003: Prognosis Value of Aortic Valve Calcium Scoring After Transcatheter Aortic Valve Implantation performed With New Generation Prosthesis

Introduction: The degree of aortic valve calcification has been shown to be associated with paravalvular aortic regurgitation (AR) and mortality after transcatheter aortic valve implantation (TAVI). Hypothesis: Calcium scoring of the aortic valve might no longer be a prognosis factor of adverse events after implantation of new devices designed to reduce paravalvular leaks. Methods: In a prospective monocentric study, Agatson calcium score (CS) was evaluated on multislice computed tomography (MSCT) before TAVI in consecutive patients who had TAVI with balloon expandable SAPIEN XT (n=61) or self expandable CoreValve (n=57) (group 1, n=118), and in patients who received the new generation balloon expandable SAPIEN 3 valve (n=142). Major adverse clinical events were evaluated at 1-month follow-up (VARC-2 criteria) Results: Main clinical characteristics did not significantly differ between the 2 groups excepted concerning logistic Euroscore (20.1% in group 1 vs 15.1% in group 2; p=0.001). Pre procedural CS value was 4092+/- 2176 in group 1 vs 4209+/- 2204 in group 2 (p=0.9). At follow-up incidence of more-than-mild AR was significantly higher in group 1 vs group 2 (n=27; 22.9% and n=10; 7.1 % respectively, p &lt;0.01). CS was associated with occurrence of AR in group 1 (3429 +/- 1505 without AR vs 6234 +/- 2711 with AR; p&lt;0.001), but not in group 2 (4663+/- 3057 vs 4176+/- 2149 respectively; p=0.9). Similarly, CS was associated with adverse clinical events only in group 1 (table 1). A CS value &gt; 6000 was a major predictor of adverse events in group 1 (OR: 106; IC 95: 15.5-727.6; p&lt;0.0001) but not in group 2 (p=0.4). Conclusions: Severe calcifications of the aortic valve evaluated on MSCT appear to be an major prognostic parameter after TAVI performed with the second generation prosthesis but not with the new designed SAPIEN 3 valves. Impact of CS on patient selection before TAVI need probably to be reconsidered with the new generation devices .

Impact of Different Iterations of Devices and Degree of Aortic Valve Calcium on Paravalvular Regurgitation After Transcatheter Aortic Valve Implantation

The iterations of the SAPIEN prosthesis might impact the incidence and grade of paravalvular regurgitation (PVR). The aim of this study was to assess the impact of iterations of balloon-expandable valves (SAPIEN, SAPIEN XT, and SAPIEN 3) and degree of aortic valve calcification (AVC) on the severity of PVR after transcatheter aortic valve implantation (TAVI). Comprehensive echocardiographic examinations and multidetector computed tomography (MDCT) were performed in 272 patients (127 men, 81 ± 7years old, logistic EuroScore of 21 ± 13%) who underwent TAVI with 23- and 26-mm balloon-expandable valves. The degree of AVC was assessed with MDCT. PVR grade was assessed with echocardiography. The cover index was calculated as (prosthesis area- MDCT annulus area)/prosthesis area. SAPIEN, SAPIEN XT, and SAPIEN 3 prostheses were implanted in 103 patients (38%), 105 patients (38.5%), and 64 patients (23.5%), respectively. Significant PVR (≥moderate) occurred in 14%, 10%, and 0% of patients receiving the SAPIEN, SAPIEN XT, and SAPIEN 3, respectively (p= 0.010). Across the groups, the aortic annulus size, degree of calcification, and cover index were comparable. Larger burden of AVC was independently associated with significant PVR (odds ratio 3.48, p= 0.006) after adjusting for age, body surface area, gender, aortic annulus area, coverindex, and prosthesis iteration. SAPIEN 3 was associated with lower frequency of significant PVR (odds ratio 0.31, p= 0.002). In conclusion, the incidence of significant PVR significantly decreased over time with improvement in valve design. SAPIEN 3 wasassociated with less significant PVR after TAVI independently of the AVC burden.

Dysregulation of ossification-related miRNAs in circulating osteogenic progenitor cells obtained from patients with aortic stenosis.

CAVD (calcific aortic valve disease) is the defining feature of AS (aortic stenosis). The present study aimed to determine whether expression of ossification-related miRNAs is related to differentiation intro COPCs (circulating osteogenic progenitor cells) in patients with CAVD. The present study included 46 patients with AS and 46 controls. Twenty-nine patients underwent surgical AVR (aortic valve replacement) and 17 underwent TAVI (transcatheter aortic valve implantation). The number of COPCs was higher in the AS group than in the controls (P<0.01). Levels of miR-30c were higher in the AS group than in the controls (P<0.01), whereas levels of miR-106a, miR-148a, miR-204, miR-211, miR-31 and miR-424 were lower in the AS group than in the controls (P<0.01). The number of COPCs and levels of osteocalcin protein in COPCs were positively correlated with levels of miR-30a and negatively correlated with levels of the remaining miRNAs (all P<0.05). The degree of aortic valve calcification was weakly positively correlated with the number of COPCs and miR-30c levels. The number of COPCs and miR-30c levels were decreased after surgery, whereas levels of the remaining miRNAs were increased (all P<0.05). Changes in these levels were greater after AVR than after TAVI (all P<0.05). In vitro study using cultured peripheral blood mononuclear cells transfected with each ossification-related miRNA showed that these miRNAs controlled levels of osteocalcin protein. In conclusion, dysregulation of ossification-related miRNAs may be related to the differentiation into COPCs and may play a significant role in the pathogenesis of CAVD.

Lipoprotein(a) Levels Are Associated With Subclinical Calcific Aortic Valve Disease in White and Black Individuals: The Multi-Ethnic Study of Atherosclerosis.

Lipoprotein(a) [Lp(a)] is a risk factor for calcific aortic valve disease (CAVD) but has not been evaluated across multiple races/ethnicities. This study aimed to determine whether Lp(a) cutoff values used in clinical laboratories to assess risk of cardiovascular disease identify subclinical CAVD and its severity and whether significant relations are observed across race/ethnicity. Lp(a) concentrations were measured using a turbidimetric immunoassay, and subclinical CAVD was measured by quantifying aortic valve calcification (AVC) through computed tomographic scanning in 4678 participants of the Multi-Ethnic Study of Atherosclerosis. Relative risk and ordered logistic regression analysis determined cross-sectional associations of Lp(a) with AVC and its severity, respectively. The conventional 30 mg/dL Lp(a) clinical cutoff was associated with AVC in white (relative risk: 1.56; confidence interval: 1.24-1.96) and was borderline significant (P=0.059) in black study participants (relative risk: 1.55; confidence interval: 0.98-2.44). Whites with levels ≥50 mg/dL also showed higher prevalence of AVC (relative risk: 1.72; confidence interval: 1.36-2.17) than those below this level. Significant associations were observed between Lp(a) and degree of AVC in both white and black individuals. The presence of existing coronary artery calcification did not affect these associations of Lp(a) and CAVD. There were no significant findings in Hispanics or Chinese. Lp(a) cutoff values that are currently used to assess cardiovascular risk seem to be applicable to CAVD, but our results suggest race/ethnicity may be important in cutoff selection. Further studies are warranted to determine whether race/ethnicity influences Lp(a) and risk of CAVD incidence and its progression.

Calcification of Aortic Valve Is Not Associated with Neurologic Events or Need for Pacemaker Implantation in TAVI Patients

Objectives: Trans-catheter aortic valve implantation (TAVI) is frequently used for patients with valvular aortic stenosis and high perioperative risk, but postoperative neurologic events and the need for pacemaker implantation are common problems. Our aim was to investigate if the degree of aortic valve calcification is associated with these complications.

Abstract 15338: Determinants of Significant Paravalvular Regurgitation After Transcatheter Aortic Valve Implantation: Impact of Different Iterations of Devices and Degree of Valve Calcification

Objectives: The aim of this study is to assess the impact of iterations of balloon expandable valves (Sapien, Sapien XT and Sapien 3) and degree of aortic valve calcification (AVC) on the severity of paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI). Hypothesis: The iterations of the Sapien prosthesis might impact the frequency and grade of PVR. Methods: Multidetector computed tomography (MDCT) and echocardiographic examinations were performed in 262 patients (127 men, 81±7 years old, logistic EuroScore of 21±13%) who underwent TAVI with 23- and 26-mm balloon expandable valves. Patients receiving a 29-mm valves or undergoing valve-in-valve procedure were excluded. The degree of AVC was calculated with MDCT. PVR grade was assessed with echocardiography. The cover index was calculated as (prosthesis area- MDCT annulus area)/prosthesis area. Results: Sapien, Sapien XT and Sapien 3 prostheses were implanted in respective 103 (39%), 105 (40%) and 54 (21%) patients. Significant PVR (≥moderate) occurred in 14% of patients receiving the Sapien prosthesis and 10% receiving a Sapien XT prosthesis but none in patients of the Sapien 3 group (p=0.019) (Figure 1). Across the groups (Sapien vs. Sapien XT vs. Sapien 3) the aortic annulus size (4.4±0.8 cm2 vs. 4.4±0.7cm2 vs. 4.3±0.7cm2, respectively; p=0.2), degree of calcification (7.7±0.6 Au vs. 7.8±0.7 Au vs. 8.0±0.6 Au, respectively; p=0.1) and cover index (88±16% vs. 90±11% vs. 90±10%, respectively; p=0.4) were comparable. Significant PVR was independently associated with higher degree of AVC (OR 2.89 p=0.02)and cover index (OR 1.08, p=0.03) after adjusting for age, body surface area, gender, aortic annulus area and prosthesis iteration. Conclusions: The incidence of ≥moderate PVR significantly decreased over time with improvement in valve design. Significant PVR after TAVI remains independently associated with degree of AVC and cover index independently of the prosthesis iteration.

Abstract 18449: Apolipoprotein B/Apolipoprotein A-I Ratio and Progression of Aortic Valve Stenosis - Results From the PROGRESSA Study

Introduction: Calcific aortic stenosis (AS) is an active and complex disorder, which involves atherosclerotic-like processes. However, previous studies reported that the association between atherosclerotic risk factors and AS progression appears to be stronger in younger middle-aged patients compared to elderly ones. Hypothesis: Apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio reflects the balance between proatherogenic versus antiatherogenic lipid profile. The objective of this study was to examine the association between apoB/apoA-I ratio and progression of AS according to patient’s age. Methods: One hundred sixty five patients with AS were prospectively recruited in the PROGRESSA study. AS progression was assessed by increase in peak aortic jet velocity (Vpeak) measured by Doppler echocardiography between baseline and 2-year follow-up. Blood samples were collected to measure plasma levels of apoB and apoA-I. Results: The mean age was 66±13 years and 72% were male. During the 2-year follow-up, AS progression was similar in younger patients (age &lt;69 y.o. [median age for the whole cohort]; n=82) and older patients (Vpeak: +0.24±0.04 vs +0.25±0.03 m/s; p=0.82). There was a significant interaction (p&lt;0.01) between patient’s age and baseline apoB/apoA-I ratio for AS progression. Younger patients with high baseline apoB/apoA-I ratio (i.e. apoB/apoA-I ≥0.53; n=41) had faster AS progression compared to those with lower apoB/apoA-I ratio (Vpeak: +0.32±0.06 vs +0.16±0.04 m/s; p=0.03). In older patients, there was no significant association between apoB/apoA-I ratio and AS progression (Vpeak: +0.23±0.05 vs +0.27±0.04 m/s; p=0.55). After adjustment for sex, hypertension, dyslipidemia, diabetes, metabolic syndrome, creatinine level, degree of aortic valve calcification and baseline Vpeak, higher apoB/apoA-I ratio remained independently associated with faster progression of AS in younger patients (p=0.003). Conclusions: This prospective study shows for the first time that higher apoB/apoA-I ratio is a powerful and independent predictor of faster AS progression in younger patients. These findings suggest that the pathological processes involved in the progression of AS are different in younger versus older patients.