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      The Association between Aortic Valve Weight, Echocardiographic Indices, and All-Cause Death in 1,046 Patients Undergoing Surgical Aortic Valve Replacement for Aortic Stenosis

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          Abstract

          Background: Aortic valve weight (AVW), a flow independent measure of aortic stenosis (AS) severity, is reported to have heterogeneous associations with the echocardiographic variables used for AS evaluation. Controversy exists regarding its impact on survival after aortic valve replacement (AVR). Objective: We sought to determine the association between AVW with echocardiographic measures of AS severity and all-cause mortality after surgical AVR. Methods: One thousand and forty-sixconsecutive patients underwent surgical AVR for AS, the excised valves were weighed, and an echocardiogram was done before surgery. Results: Males had heavier valves than females, for both absolute and body surface are (BSA)-indexed values (2.78 ± 1.23 vs. 2.08 ± 0.68 g, p < 0.001; and 1.38 ± 0.61 vs. 1.19 ± 0.41 g/m<sup>2</sup>, p < 0.001, respectively). In a restricted cohort of 634 patients with isolated severe AS and normal ejection fraction, the correlations of AVW with echocardiographic variables of AS were modest, the strongest being with the dimensionless index ( r = 0.27 and 0.26 for male and female, both p < 0.01). Stratified by stroke volume index and mean gradient (MG), no associations were found in the low-gradient groups (i.e., MG <40 mmHg). At a median follow-up of 3.5 years, there were only 244 deaths in the entire cohort. Mortality was not related to AVW, except in females who displayed an inverse relationship (HR = 0.67; 95% CI 0.47 0.95) only when it was analyzed as a continuous variable. Conclusions: The weak correlation between AVW with the echocardiographic indices of AS may reflect its complex pathophysiology, heterogeneous hemodynamics, and possible pitfalls in the current echocardiographic methods used in clinical practice. The prognostic value of AVW after AVR warrants further evaluation.

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          Most cited references25

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          Is Open Access

          Principles of confounder selection

          Selecting an appropriate set of confounders for which to control is critical for reliable causal inference. Recent theoretical and methodological developments have helped clarify a number of principles of confounder selection. When complete knowledge of a causal diagram relating all covariates to each other is available, graphical rules can be used to make decisions about covariate control. Unfortunately, such complete knowledge is often unavailable. This paper puts forward a practical approach to confounder selection decisions when the somewhat less stringent assumption is made that knowledge is available for each covariate whether it is a cause of the exposure, and whether it is a cause of the outcome. Based on recent theoretically justified developments in the causal inference literature, the following proposal is made for covariate control decisions: control for each covariate that is a cause of the exposure, or of the outcome, or of both; exclude from this set any variable known to be an instrumental variable; and include as a covariate any proxy for an unmeasured variable that is a common cause of both the exposure and the outcome. Various principles of confounder selection are then further related to statistical covariate selection methods.
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            Genetic associations with valvular calcification and aortic stenosis.

            Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis. One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P=1.5×10(-8) and P=1.8×10(-8), respectively), but the findings were not replicated consistently. Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.).
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              A classification system for the bicuspid aortic valve from 304 surgical specimens.

              In general, classification of a disease has proven to be advantageous for disease management. This may also be valid for the bicuspid aortic valve, because the term "bicuspid aortic valve" stands for a common congenital aortic valve malformation with heterogeneous morphologic phenotypes and function resulting in different treatment strategies. We attempted to establish a classification system based on a 5-year data collection of surgical specimens. Between 1999 and 2003 a precise description of valve pathology was obtained from operative reports of 304 patients with a diseased bicuspid aortic valve. Several different characteristics of bicuspid aortic valves were tested to generate a pithy and easily applicable classification system. Three characteristics for a systematic classification were found appropriate: (1) number of raphes, (2) spatial position of cusps or raphes, and (3) functional status of the valve. The first characteristic was found to be the most significant and therefore termed "type." Three major types were identified: type 0 (no raphe), type 1 (one raphe), and type 2 (two raphes), followed by two supplementary characteristics, spatial position and function. These characteristics served to classify and codify the bicuspid aortic valves into three categories. Most frequently, a bicuspid aortic valve with one raphe was identified (type 1, n = 269). This raphe was positioned between the left (L) and right (R) coronary sinuses in 216 (type 1, L/R) with a hemodynamic predominant stenosis (S) in 119 (type 1, L/R, S). Only 21 patients had a "purely" bicuspid aortic valve with no raphe (type 0). A classification system for the bicuspid aortic valve with one major category ("type") and two supplementary categories is presented. This classification, even if used in the major category (type) alone, might be advantageous to better define bicuspid aortic valve disease, facilitate scientific communication, and improve treatment.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2020
                11 March 2020
                : 145
                : 4
                : 178-188
                Affiliations
                [_a] aSt. Francis Hospital, The Heart Center, Roslyn, New York, USA
                [_b] bStony Brook University (SUNY), Stony Brook, New York, USA
                Author notes
                *Dr. Eddy Barasch, MD, St. Francis Hospital, The Heart Center/SUNY at Stony Brook, 100 Port Washington Blvd, Roslyn, NY 11576 (USA), Eddy.Barasch@chsli.org
                Author information
                https://orcid.org/0000-0002-6847-8057
                Article
                505870 Cardiology
                10.1159/000505870
                32160622
                7a9b52b8-01a5-4e77-8a6c-7474da64e9d2
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 28 August 2019
                : 12 December 2019
                Page count
                Figures: 3, Tables: 6, Pages: 11
                Categories
                Valvular Heart Disease: Research Article

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Survival,Aortic valve weight,Aortic stenosis,Aortic valve replacement

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