<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02241109</url>
  </required_header>
  <id_info>
    <org_study_id>087/14</org_study_id>
    <nct_id>NCT02241109</nct_id>
  </id_info>
  <brief_title>Predicting Aortic Stenosis Progression by Measuring Serum Calcification Propensity</brief_title>
  <acronym>PASP</acronym>
  <official_title>Predicting Aortic Stenosis Progression by Measuring Serum Calcification Propensity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aortic stenosis is the most common valvular heart disease and an important public-health&#xD;
      problem. Surgical or interventional aortic valve replacement are based on symptoms and&#xD;
      measures of valvular and ventricular function using echocardiography.There is no uniform&#xD;
      pattern of progression. Instead, marked differences not only between individuals, but also&#xD;
      during the time course of the disease can be observed.&#xD;
&#xD;
      Several prospective studies have been performed to enhance the predictability of disease&#xD;
      behavior. Individually it is still prone to large errors and hard to predict aortic stenosis&#xD;
      progression. Therefore, in patients with aortic sclerosis without severe stenosis, it is&#xD;
      desirable to find a strong predictor of rapid disease progression. This would allow&#xD;
      anticipating cardiovascular deterioration by identifying individuals at particular risk.&#xD;
&#xD;
      Study Hypothesis&#xD;
&#xD;
      In patients with aortic sclerosis, increased serum calcification propensity, as measured by&#xD;
      the T50-Test, is related to the amount of stenosis progression in one year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Clinical Background&#xD;
&#xD;
      Aortic stenosis is the most common valvular heart disease and an important public-health&#xD;
      problem. It is present in approximately 25% of all adults aged &gt;65 years. Decisions about&#xD;
      surgical or interventional aortic valve replacement are based on symptoms and measures of&#xD;
      valvular and ventricular function using echocardiography. Such valvular affections are the&#xD;
      result of a chronic progressive disease, usually starting with hemodynamically&#xD;
      non-significant aortic sclerosis, and then progressing to severe stenosis over years. There&#xD;
      is no uniform pattern of progression. Instead, marked differences not only between&#xD;
      individuals, but also during the time course of the disease can be observed. Aortic sclerosis&#xD;
      progresses to mild aortic stenosis in &lt;15% of patients over 2 to 7 years. Once moderate&#xD;
      stenosis is present (jet velocity &gt;3 m/s), the average progression is 0.3 m/s per year, but&#xD;
      still highly variable. When peak jet velocity exceeds 4 m/s, survival free from symptoms and&#xD;
      valve replacement is significantly reduced.&#xD;
&#xD;
      In the past, several prospective studies have been performed to enhance the predictability of&#xD;
      disease behavior. Some determinants of rapid progression and adverse outcome have been&#xD;
      identified, such as: age, gender, cardiovascular risk factors, B-natriuretic peptide,&#xD;
      stenosis severity, degree of valvular calcification and others. Although it appears that&#xD;
      progression is more rapid in degenerative calcific disease than congenital or rheumatic&#xD;
      disease, predicting progression individually is still prone to large errors even when&#xD;
      considering these determinants. Therefore, regular clinical follow-up is mandatory in&#xD;
      patients with asymptomatic aortic valve affections. In patients with aortic sclerosis without&#xD;
      severe stenosis, it is desirable to find a strong predictor of rapid disease progression.&#xD;
      This would allow anticipating cardiovascular deterioration by identifying individuals at&#xD;
      particular risk.&#xD;
&#xD;
      Background of Tissue Calcification&#xD;
&#xD;
      From a biochemical and histological point of view, aortic sclerosis is a valvular disease&#xD;
      characterized by focal plaque-like lesions containing microscopic calcifications. Because&#xD;
      calcium and phosphate concentrations in serum are near supersaturation, the balance of&#xD;
      inhibitors and promoters critically influences the development of calcification. The serum&#xD;
      protein fetuin-A is a major systemic inhibitor of calcification. Together with additional&#xD;
      blood components, fetuin-A prevents the supersaturated calcium and phosphate from&#xD;
      precipitating by forming soluble colloidal protein-mineral nanoparticles and is therefore an&#xD;
      integral part of the defense system preventing calcifications. Low serum concentrations of&#xD;
      fetuin-A are associated with a reduced capacity to inhibit calcification in vitro.&#xD;
      Calcification takes place when this humoral line of defense is overwhelmed.&#xD;
&#xD;
      Koos et al. showed that serum levels of the calcification inhibitor fetuin-A are associated&#xD;
      with the progression of aortic valve calcifications and major adverse clinical events,&#xD;
      independent of the renal function and inflammation.&#xD;
&#xD;
      A novel in vitro blood test developed by Pasch et al. provides an overall measure of&#xD;
      calcification propensity by monitoring the maturation time (T50) of calciprotein particles.&#xD;
      First published clinical data indicate that the T50 test is a helpful biomarker for the&#xD;
      prediction of future vascular calcifications.&#xD;
&#xD;
      Study Endpoints&#xD;
&#xD;
        -  Index test (parameter to be evaluated): T50-Test&#xD;
&#xD;
        -  Comparator tests (tests to define disease status):&#xD;
&#xD;
      Primary:&#xD;
&#xD;
      Progression of peak aortic jet velocity over one year (m/s per year)&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
      Progression of peak aortic jet velocity &gt;20% in one year (dichotomized primary comparator)&#xD;
      Combined endpoint: death, hospitalizations, aortic-valve replacement, heart failure, angina,&#xD;
      syncope&#xD;
&#xD;
      Inclusion Criteria&#xD;
&#xD;
        -  Patient referred to routine clinical echocardiography at the Department of Cardiology,&#xD;
           Inselspital Bern&#xD;
&#xD;
        -  Aortic sclerosis with or without stenosis&#xD;
&#xD;
        -  Written informed consent&#xD;
&#xD;
      Exclusion Criteria&#xD;
&#xD;
      The goal is to recruit a population comprising a large variety of clinical conditions.&#xD;
      Exclusion criteria are:&#xD;
&#xD;
        -  Age &lt;18 years&#xD;
&#xD;
        -  Aortic valve replacement scheduled within 1 year after inclusion&#xD;
&#xD;
        -  Any aortic valvular disease other than degenerative sclerotic, bi- or unicuspid valves&#xD;
&#xD;
        -  Known disease with expected survival &lt;1 year&#xD;
&#xD;
        -  Known malignant tumor&#xD;
&#xD;
        -  Subvalvular obstruction (in LVOT) with mean pressure gradient &gt;10mmHg&#xD;
&#xD;
      Echocardiography&#xD;
&#xD;
      Patients will be examined by standard echocardiography including a comprehensive assessment&#xD;
      of cavity and wall dimensions, ventricular and valvular function, morphologic appraisal and&#xD;
      pressure predictions. In particular, peak aortic jet velocity will be recorded using CW&#xD;
      Doppler from the window yielding the highest velocity signal. Aortic stenosis severity will&#xD;
      be measured using peak flow velocity (m/s). Progression will be expressed as peak flow&#xD;
      velocity change per year (m/s per year). Aortic valve sclerosis will be assessed visually&#xD;
      from a short axis according to Rosenhek: 1, no calcification; 2, mildly calcified (small&#xD;
      isolated spots); 3, moderately calcified (multiple larger spots); and 4, heavily calcified&#xD;
      (extensive thickening and calcification of all cusps).&#xD;
&#xD;
      T50-Test The addition of calcium and phosphate to serum triggers the formation of primary&#xD;
      calciprotein particles (CPP, see figures 2 and 3). As nano-suspension of calcium-phosphate,&#xD;
      these particles represent a defense mechanism of the serum against calcification. Primary&#xD;
      CPPs undergo spontaneous transition to secondary CPPs. The formation of these particles&#xD;
      represents calcification. In the T50-Test, the time elapsed for the transformation of 50% of&#xD;
      the particles is measured and is specific for individual sera.&#xD;
&#xD;
      The blood-sample will be taken immediately after completion of the echocardiographic exam.&#xD;
&#xD;
      Objective&#xD;
&#xD;
      The purpose of this study in patients with aortic sclerosis with and without stenosis is to&#xD;
      establish an independent predictor of progression of aortic valve obstruction using a new&#xD;
      calcification propensity measure in the serum.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Recruitment 200 consecutive patients referred for a routine clinical echocardiographic exam&#xD;
      showing varying degrees of aortic sclerosis will be included.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 30, 2014</start_date>
  <completion_date type="Actual">February 28, 2017</completion_date>
  <primary_completion_date type="Actual">January 31, 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression of peak aortic jet velocity over one year (m/s per year)</measure>
    <time_frame>One year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression of peak aortic jet velocity &gt;20% in one year</measure>
    <time_frame>One year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Combined endpoint: death, hospitalizations, aortic-valve replacement, heart failure, angina, syncope</measure>
    <time_frame>One year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Aortic Valve Sclerosis</condition>
  <condition>Aortic Valve Stenosis</condition>
  <condition>Stenosis Progression</condition>
  <condition>Valvular Heart Disease</condition>
  <arm_group>
    <arm_group_label>All patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Compare patients with high calcification propensity do have faster valve-stenosis progression</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>no intervention</intervention_name>
    <description>progression monitoring by echocardiography</description>
    <arm_group_label>All patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient referred to routine clinical echocardiography&#xD;
&#xD;
          -  Aortic sclerosis with or without stenosis&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Age &lt;18 years&#xD;
&#xD;
          -  Aortic valve replacement scheduled within 1 year after inclusion&#xD;
&#xD;
          -  Any aortic valvular disease other than degenerative sclerotic, bi- or unicuspid valves&#xD;
&#xD;
          -  Known disease with expected survival &lt;1 year&#xD;
&#xD;
          -  Known malignant tumor&#xD;
&#xD;
          -  Subvalvular obstruction (in left ventricular outflow tract) with mean pressure&#xD;
             gradient &gt;10mmHg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stefano de Marchi, Senior Consultant</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept. of Cardiology, University Hospital Bern, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dep. of Cardiology, Bern University Hospital</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999 Jul 15;341(3):142-7. doi: 10.1056/NEJM199907153410302.</citation>
    <PMID>10403851</PMID>
  </reference>
  <reference>
    <citation>Manning WJ. Asymptomatic aortic stenosis in the elderly: a clinical review. JAMA. 2013 Oct 9;310(14):1490-7. doi: 10.1001/jama.2013.279194.</citation>
    <PMID>24104373</PMID>
  </reference>
  <reference>
    <citation>Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005 Jun 21;111(24):3316-26. doi: 10.1161/CIRCULATIONAHA.104.486738. No abstract available.</citation>
    <PMID>15967862</PMID>
  </reference>
  <reference>
    <citation>Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, Healy NL, Kraft CD, Miyake-Hull CY, Schwaegler RG. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997 May 6;95(9):2262-70. doi: 10.1161/01.cir.95.9.2262.</citation>
    <PMID>9142003</PMID>
  </reference>
  <reference>
    <citation>Koos R, Brandenburg V, Mahnken AH, Muhlenbruch G, Stanzel S, Gunther RW, Floege J, Jahnen-Dechent W, Kelm M, Kuhl HP. Association of fetuin-A levels with the progression of aortic valve calcification in non-dialyzed patients. Eur Heart J. 2009 Aug;30(16):2054-61. doi: 10.1093/eurheartj/ehp158. Epub 2009 May 8.</citation>
    <PMID>19429630</PMID>
  </reference>
  <reference>
    <citation>Pasch A, Farese S, Graber S, Wald J, Richtering W, Floege J, Jahnen-Dechent W. Nanoparticle-based test measures overall propensity for calcification in serum. J Am Soc Nephrol. 2012 Oct;23(10):1744-52. doi: 10.1681/ASN.2012030240. Epub 2012 Sep 6.</citation>
    <PMID>22956818</PMID>
  </reference>
  <reference>
    <citation>Smith ER, Ford ML, Tomlinson LA, Bodenham E, McMahon LP, Farese S, Rajkumar C, Holt SG, Pasch A. Serum calcification propensity predicts all-cause mortality in predialysis CKD. J Am Soc Nephrol. 2014 Feb;25(2):339-48. doi: 10.1681/ASN.2013060635. Epub 2013 Oct 31.</citation>
    <PMID>24179171</PMID>
  </reference>
  <reference>
    <citation>Rosenhek R, Klaar U, Schemper M, Scholten C, Heger M, Gabriel H, Binder T, Maurer G, Baumgartner H. Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography. Eur Heart J. 2004 Feb;25(3):199-205. doi: 10.1016/j.ehj.2003.12.002.</citation>
    <PMID>14972419</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>March 27, 2023</last_update_submitted>
  <last_update_submitted_qc>March 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>aortic stenosis progression</keyword>
  <keyword>aortic valve sclerosis progression</keyword>
  <keyword>calcification propensity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
    <mesh_term>Calcinosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02241109
org study id: 087/14
nct id: NCT02241109
lead sponsor: 
has dmc: No
Aortic stenosis is the most common valvular heart disease and an important public-health
      problem. Surgical or interventional aortic valve replacement are based on symptoms and
      measures of valvular and ventricular function using echocardiography.There is no uniform
      pattern of progression. Instead, marked differences not only between individuals, but also
      during the time course of the disease can be observed.

      Several prospective studies have been performed to enhance the predictability of disease
      behavior. Individually it is still prone to large errors and hard to predict aortic stenosis
      progression. Therefore, in patients with aortic sclerosis without severe stenosis, it is
      desirable to find a strong predictor of rapid disease progression. This would allow
      anticipating cardiovascular deterioration by identifying individuals at particular risk.

      Study Hypothesis

      In patients with aortic sclerosis, increased serum calcification propensity, as measured by
      the T50-Test, is related to the amount of stenosis progression in one year.
Background

      Clinical Background

      Aortic stenosis is the most common valvular heart disease and an important public-health
      problem. It is present in approximately 25% of all adults aged >65 years. Decisions about
      surgical or interventional aortic valve replacement are based on symptoms and measures of
      valvular and ventricular function using echocardiography. Such valvular affections are the
      result of a chronic progressive disease, usually starting with hemodynamically
      non-significant aortic sclerosis, and then progressing to severe stenosis over years. There
      is no uniform pattern of progression. Instead, marked differences not only between
      individuals, but also during the time course of the disease can be observed. Aortic sclerosis
      progresses to mild aortic stenosis in <15% of patients over 2 to 7 years. Once moderate
      stenosis is present (jet velocity >3 m/s), the average progression is 0.3 m/s per year, but
      still highly variable. When peak jet velocity exceeds 4 m/s, survival free from symptoms and
      valve replacement is significantly reduced.

      In the past, several prospective studies have been performed to enhance the predictability of
      disease behavior. Some determinants of rapid progression and adverse outcome have been
      identified, such as: age, gender, cardiovascular risk factors, B-natriuretic peptide,
      stenosis severity, degree of valvular calcification and others. Although it appears that
      progression is more rapid in degenerative calcific disease than congenital or rheumatic
      disease, predicting progression individually is still prone to large errors even when
      considering these determinants. Therefore, regular clinical follow-up is mandatory in
      patients with asymptomatic aortic valve affections. In patients with aortic sclerosis without
      severe stenosis, it is desirable to find a strong predictor of rapid disease progression.
      This would allow anticipating cardiovascular deterioration by identifying individuals at
      particular risk.

      Background of Tissue Calcification

      From a biochemical and histological point of view, aortic sclerosis is a valvular disease
      characterized by focal plaque-like lesions containing microscopic calcifications. Because
      calcium and phosphate concentrations in serum are near supersaturation, the balance of
      inhibitors and promoters critically influences the development of calcification. The serum
      protein fetuin-A is a major systemic inhibitor of calcification. Together with additional
      blood components, fetuin-A prevents the supersaturated calcium and phosphate from
      precipitating by forming soluble colloidal protein-mineral nanoparticles and is therefore an
      integral part of the defense system preventing calcifications. Low serum concentrations of
      fetuin-A are associated with a reduced capacity to inhibit calcification in vitro.
      Calcification takes place when this humoral line of defense is overwhelmed.

      Koos et al. showed that serum levels of the calcification inhibitor fetuin-A are associated
      with the progression of aortic valve calcifications and major adverse clinical events,
      independent of the renal function and inflammation.

      A novel in vitro blood test developed by Pasch et al. provides an overall measure of
      calcification propensity by monitoring the maturation time (T50) of calciprotein particles.
      First published clinical data indicate that the T50 test is a helpful biomarker for the
      prediction of future vascular calcifications.

      Study Endpoints

        -  Index test (parameter to be evaluated): T50-Test

        -  Comparator tests (tests to define disease status):

      Primary:

      Progression of peak aortic jet velocity over one year (m/s per year)

      Secondary:

      Progression of peak aortic jet velocity >20% in one year (dichotomized primary comparator)
      Combined endpoint: death, hospitalizations, aortic-valve replacement, heart failure, angina,
      syncope

      Inclusion Criteria

        -  Patient referred to routine clinical echocardiography at the Department of Cardiology,
           Inselspital Bern

        -  Aortic sclerosis with or without stenosis

        -  Written informed consent

      Exclusion Criteria

      The goal is to recruit a population comprising a large variety of clinical conditions.
      Exclusion criteria are:

        -  Age <18 years

        -  Aortic valve replacement scheduled within 1 year after inclusion

        -  Any aortic valvular disease other than degenerative sclerotic, bi- or unicuspid valves

        -  Known disease with expected survival <1 year

        -  Known malignant tumor

        -  Subvalvular obstruction (in LVOT) with mean pressure gradient >10mmHg

      Echocardiography

      Patients will be examined by standard echocardiography including a comprehensive assessment
      of cavity and wall dimensions, ventricular and valvular function, morphologic appraisal and
      pressure predictions. In particular, peak aortic jet velocity will be recorded using CW
      Doppler from the window yielding the highest velocity signal. Aortic stenosis severity will
      be measured using peak flow velocity (m/s). Progression will be expressed as peak flow
      velocity change per year (m/s per year). Aortic valve sclerosis will be assessed visually
      from a short axis according to Rosenhek: 1, no calcification; 2, mildly calcified (small
      isolated spots); 3, moderately calcified (multiple larger spots); and 4, heavily calcified
      (extensive thickening and calcification of all cusps).

      T50-Test The addition of calcium and phosphate to serum triggers the formation of primary
      calciprotein particles (CPP, see figures 2 and 3). As nano-suspension of calcium-phosphate,
      these particles represent a defense mechanism of the serum against calcification. Primary
      CPPs undergo spontaneous transition to secondary CPPs. The formation of these particles
      represents calcification. In the T50-Test, the time elapsed for the transformation of 50% of
      the particles is measured and is specific for individual sera.

      The blood-sample will be taken immediately after completion of the echocardiographic exam.

      Objective

      The purpose of this study in patients with aortic sclerosis with and without stenosis is to
      establish an independent predictor of progression of aortic valve obstruction using a new
      calcification propensity measure in the serum.

      Methods

      Recruitment 200 consecutive patients referred for a routine clinical echocardiographic exam
      showing varying degrees of aortic sclerosis will be included.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Progression of peak aortic jet velocity over one year (m/s per year)
time frame: One year
measure: Progression of peak aortic jet velocity >20% in one year
time frame: One year
measure: Combined endpoint: death, hospitalizations, aortic-valve replacement, heart failure, angina, syncope
time frame: One year
arm group label: All patients
arm group type: Other
description: Compare patients with high calcification propensity do have faster valve-stenosis progression
intervention type: Other
intervention name: no intervention
description: progression monitoring by echocardiography
arm group label: All patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stefano de Marchi, Senior Consultant
role: Principal Investigator
affiliation: Dept. of Cardiology, University Hospital Bern, Switzerland
facility: 
country: Switzerland
citation: Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999 Jul 15;341(3):142-7. doi: 10.1056/NEJM199907153410302.
PMID: 10403851
citation: Manning WJ. Asymptomatic aortic stenosis in the elderly: a clinical review. JAMA. 2013 Oct 9;310(14):1490-7. doi: 10.1001/jama.2013.279194.
PMID: 24104373
citation: Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005 Jun 21;111(24):3316-26. doi: 10.1161/CIRCULATIONAHA.104.486738. No abstract available.
PMID: 15967862
citation: Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, Healy NL, Kraft CD, Miyake-Hull CY, Schwaegler RG. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997 May 6;95(9):2262-70. doi: 10.1161/01.cir.95.9.2262.
PMID: 9142003
citation: Koos R, Brandenburg V, Mahnken AH, Muhlenbruch G, Stanzel S, Gunther RW, Floege J, Jahnen-Dechent W, Kelm M, Kuhl HP. Association of fetuin-A levels with the progression of aortic valve calcification in non-dialyzed patients. Eur Heart J. 2009 Aug;30(16):2054-61. doi: 10.1093/eurheartj/ehp158. Epub 2009 May 8.
PMID: 19429630
citation: Pasch A, Farese S, Graber S, Wald J, Richtering W, Floege J, Jahnen-Dechent W. Nanoparticle-based test measures overall propensity for calcification in serum. J Am Soc Nephrol. 2012 Oct;23(10):1744-52. doi: 10.1681/ASN.2012030240. Epub 2012 Sep 6.
PMID: 22956818
citation: Smith ER, Ford ML, Tomlinson LA, Bodenham E, McMahon LP, Farese S, Rajkumar C, Holt SG, Pasch A. Serum calcification propensity predicts all-cause mortality in predialysis CKD. J Am Soc Nephrol. 2014 Feb;25(2):339-48. doi: 10.1681/ASN.2013060635. Epub 2013 Oct 31.
PMID: 24179171
citation: Rosenhek R, Klaar U, Schemper M, Scholten C, Heger M, Gabriel H, Binder T, Maurer G, Baumgartner H. Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography. Eur Heart J. 2004 Feb;25(3):199-205. doi: 10.1016/j.ehj.2003.12.002.
PMID: 14972419
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Aortic Valve Stenosis
mesh term: Heart Valve Diseases
mesh term: Calcinosis
mesh term: Sclerosis
mesh term: Constriction, Pathologic
mesh term: Disease Progression