Trial document




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  DRKS00005623

Trial Description

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Title

BOchum heaRt failurE in Aortic Stenosis study - Prospective diagnostic study to investigate the hemodynamic and cell biological basis of an irreversible left ventricular failure in severe aortic stenosis

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Trial Acronym

BOREAS

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URL of the Trial

[---]*

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Brief Summary in Lay Language

An accompanying heart failure can be caused by pressure overload of the left ventricle in aortic stenosis. A replacement of the diseased aortic valve eliminates the pressure load of the left ventricle and the performance of the heart recovers.
Heart failure can, however, also be due to an intrinsic damage to the heart muscle. Although a replacement of the diseased aortic valve reduces the pressure load on the heart, but the function of the heart becomes not normal. In these patients, the usefulness of the valve replacement with respect to the improvement of symptoms and normalization of the life expectancy is questionable.
The mechanisms and the differences between the two forms of heart failure in aortic stenosis are not fully understood. In particular, it remains unclear why the cardiac insufficiency in some cases, is reversible and irreversible in others.
Until now, there is no precise hemodynamic analysis of the different forms of heart failure in aortic stenosis. In addition, the specific histopathological and cell biological basis of reversible or irreversible myocardial contraction disorder have not yet been investigated.
The aim of the study is therefore to investigate the pathophysiology of heart failure in aortic stenosis. 30 patients are examined with severe aortic valve stenosis and heart failure, which are submitted to aortic valve replacement.
During the aortic valve replacement, a small amount of heart muscle tissue is removed for histological and cytological examination. To investigate the myocardial properties of the aortic stenosis with heart failure more accurately, a control group is examined.
As control groups serve 10 patients with severe aortic stenosis without heart failure . Analysis of cardiac proteins that are important for the function of the heart, direct measurements of the force of the heart muscle cells and hemodynamic studies of the entire heart are performed.

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Brief Summary in Scientific Language

The aim of the present study is to analyze the pathophysiology of irreversible left ventricular dysfunction in aortic stenosis.
For this purpose, 30 patients with symptomatic, severe aortic stenosis and left ventricular dysfunction (left ventricular ejection fraction ≤ 40%) are investigated. Patients are differentiated by their transaortic pressure gradient in a group with "low-flow, low-gradient" and a group with "low-flow, high-gradient" aortic stenosis.
Both study groups are subjected to extensive clinical and echocardiographic studies.
During the cardiac surgical aortic valve replacement, the removal of a small amount of left ventricular muscle tissue for histological and cytological examination is performed. It is carried out the analysis of the expression ratio and the titin N2BA/N2B-Isoform Titinphosphorylierung, the active contraction of the cardiomyocyte and the degree of myocardial fibrosis.
To delineate the myocardial properties of aortic stenosis with left ventricular failure against other forms of aortic stenosis and left ventricular failure, a control groups is formed. As control groups serve 10 patients with severe aortic stenosis without left ventricular failure.
The primary endpoint is the normalization of left ventricular ejection fraction of ≥ 50% three months after aortic valve replacement. Secondary endpoints include all-cause mortality, cardiovascular mortality and hospitalization due to heart failure.

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Organizational Data

  •   DRKS00005623
  •   2014/01/09
  •   [---]*
  •   yes
  •   Approved
  •   4379-12, Ethik-Kommission der Medizinischen Fakultät der Ruhr-Universität Bochum
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Secondary IDs

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Health Condition or Problem studied

  •   I35.0 -  Aortic (valve) stenosis
  •   I42.8 -  Other cardiomyopathies
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Interventions/Observational Groups

  •   Hemodynamic, histopathological and cell biological analyzes in patients with severe aortic stenosis (valve area <1 cm ²) with a left ventricular dysfunction (left ventricular ejection fraction ≤ 40%) and a transaortic gradient of > 40 mmHg.
  •   Hemodynamic, histopathological and cell biological analyzes in patients with severe aortic stenosis (valve area <1 cm ²) with a left ventricular dysfunction (left ventricular ejection fraction ≤ 40%) and a transaortic gradient of ≤ 40 mmHg.
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Diagnostic
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

The primary endpoint is the normalization of left ventricular ejection fraction of ≥ 50% three months after aortic valve replacement.

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Secondary Outcome

Comparison of reversible and irreversible left ventricular failure:
- N2BA/N2B-Isoform titin expression ratio and phosphorylation
- Active contraction of the cardiomyocytes
- The degree of myocardial fibrosis
- All-cause mortality (one-year)
- Cardiovascular mortality (one-year)
- Hospitalization for heart failure (within the first year after aortic valve replacement)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2014/09/17
  •   30
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Inclusion criteria study group aortic stenosis and left ventricular failure
- Severe aortic stenosis ( valve area < 1 cm ²)
- Left ventricular dysfunction (left ventricular ejection fraction ≤ 40%)
- Symptoms of heart failure (NYHA II -IV)
- Age ≥ 18 years
- Life expectancy > 1 years
- Consent to participate in the study

Inclusion criteria control group aortic stenosis without left ventricular failure
- Severe aortic stenosis ( valve area < 1 cm ²)
- Received left ventricular ejection fraction ( ≥ 50%)
- Symptoms of heart failure (NYHA II -IV)
- Age ≥ 18 years
- Life expectancy > 1 years
- Consent to participate in the study

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Exclusion Criteria

- Active endocarditis
- Previous myocardial infarction
- Previous heart surgery
- Concurrent serious stenosis or insufficiency of the mitral valve
- Concurrent serious insufficiency of the aortic valve
- Pregnancy, lactation

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Addresses

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    • Medizinische Klinik II, Kardiologie und AngiologieBG-Universitätsklinikum Bergmannsheil, Ruhr-Universität Bochum
    • Mr.  PD Dr. med.  Michael  Gotzmann 
    • Bürkle-de-la-Camp-Platz 1
    • 44789  Bochum
    • Germany
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    • Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH
    • Mr.  PD Dr.med.  Michael  Gotzmann 
    • Bürkle-de-la-Camp-Platz 1
    • 44789  Bochum
    • Germany
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    • Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH
    • Mr.  PD Dr. med.   Michael   Gotzmann 
    • Bürkle-de-la-Camp-Platz 1
    • 44789  Bochum
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Stiftung für Herzforschung
    • Mr.  Prof. Dr. med.  Udo  Sechtem 
    • Vogtstraße 50
    • 60322  Frankfurt am Main
    • Germany
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.