Effect of Angiotensin II Receptor Blockers (ARB) on Left Ventricular Reverse Remodelling After Aortic Valve Replacement in Severe Valvular Aortic Stenosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00294775
Recruitment Status : Unknown
Verified June 2009 by Odense University Hospital.
Recruitment status was:  Active, not recruiting
First Posted : February 22, 2006
Last Update Posted : June 30, 2009
Information provided by:
Odense University Hospital

Brief Summary:

The consequence of aortic valve stenosis (AVS) is increased pressure load on the left ventricle which causes left ventricular (LV) hypertrophy, and myocardial stretch will cause activation of cardiac peptides and activation of the renin angiotensin aldosterone system (RAAS). The consequence of LV hypertrophy is increased chamber-stiffness and delayed active LV relaxation which initially will cause diastolic and later systolic dysfunction. In heart failure (HF) and ischemic heart disease the degree of diastolic dysfunction has been demonstrated to correlate with functional class, neurohormonal activation and prognosis which also recently have been suggested for AVS.

With longstanding elevated filling pressures the left atrium (LA) will dilate. Only limited data are available on the degree and importance of LA dilatation in AVS.

When apparent, symptoms of HF in AVS are associated with high mortality rates. If LV systolic dysfunction also is present prognosis will deteriorate further. In these cases aorta valve replacement (AVR) is recommended. AVR will normalize pressure overload and thereby decreases LV hypertrophy. Previously it was believed that in time LV hypertrophy regressed towards normal and even normalized. Recent studies however have demonstrated that LV hypertrophy regression mainly happens during the first year after AVR, and little subsequent changes are seen during the remaining 10 years. Furthermore, patients that experience most regression of hypertrophy have more favourable outcome and better functional class than patients with less regression of hypertrophy. Thus absence of reverse remodelling is associated with poor outcome after AVR. Importantly the regression of LV hypertrophy is closely paralleled by decreasing RAAS hyperactivity.

RAAS hyperactivity may be attenuated pharmacologically with angiotensin II receptor blockers (ARB) which in systemic hypertension with LV hypertrophy has been associated with reverse remodelling.

The hypothesis is that in patients undergoing AVR for symptomatic AVS, 12 months post operative blockade of the angiotensin II receptor will accelerate LV and LA reverse remodelling, reduce filling pressures and suppress neurohormonal activation compared with conventional therapy. This will lead to improved exercise tolerance and due to improved left atrial function reducing the risk of atrial arrythmias.

Condition or disease Intervention/treatment Phase
Aortic Valve Stenosis Left Ventricular Hypertrophy Atrial Fibrillation Drug: Candesartan Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Left Ventricular Reverse Remodelling After Aortic Valve Replacement in Severe Valvular Aortic Stenosis - Effect of Blockade of the Angiotensin-II Receptor
Study Start Date : February 2006
Estimated Primary Completion Date : January 2009
Estimated Study Completion Date : June 2009

Primary Outcome Measures :
  1. LV mass index
  2. LA volume index
  3. Plasma nt-pro BNP concentration

Secondary Outcome Measures :
  1. Diastolic E/e' ratio
  2. Overall LV function assessed by the Doppler echocardiographic Tei Index
  3. Regional LV function assessed with tissue Doppler imaging
  4. LV end systolic and end diastolic volume index
  5. Atrial arrhythmias assessed with 48h Holter after 12 months
  6. Exercise capacity after 12 months
  7. Serial changes in LV diastolic, overall LV function and regional LV systolic function
  8. Assess serial changes in plasma nt-pro BNP, ANP, and renin

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Symptomatic severe AVS referred for valve replacement (mechanic prosthesis or bioprosthesis) at Odense University Hospital
  2. Signed informed consent

Exclusion Criteria:

  1. Severe renal failure (s-creatinine >300 mmole/l)
  2. Moderate or severe hepatic failure
  3. Moderate or severe LV systolic dysfunction (LVEF<40%)
  4. Patients already treated with ACE-I or ARB
  5. Known intolerance for ARB
  6. Unwilling to participate in the study
  7. Poor echocardiographic window
  8. Pregnant women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00294775

Cardiology Department, Odense University hospital
Odense, Fyn, Denmark, 5000
Sponsors and Collaborators
Odense University Hospital
Study Director: Torben Haghfelt, Md, DMSc Kardiologisk forskningsenhed, OUH
Principal Investigator: Jordi S Dahl, MD, MMSci Kardiologisk forskningsenhed, OUH
Study Chair: Henrik Nissen, MD, PhD Kardiologisk forskningsenhed, OUH
Study Chair: Jacob E Moller, Md, Ph.D Kardiologisk forskningsenhed, OUH
Study Chair: Lars Videbæk, MD, Ph.d Kardiologisk forskningsenhed, OUH
Study Chair: Lars I Andersen, MD, DMSc Department of thoracic surgery, OUH

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00294775     History of Changes
Other Study ID Numbers: EudraCT number 2005-001930-34
First Posted: February 22, 2006    Key Record Dates
Last Update Posted: June 30, 2009
Last Verified: June 2009

Keywords provided by Odense University Hospital:
diastolic dysfunction
Reverse Remodelling

Additional relevant MeSH terms:
Aortic Valve Stenosis
Atrial Fibrillation
Constriction, Pathologic
Hypertrophy, Left Ventricular
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Pathological Conditions, Anatomical
Heart Valve Diseases
Ventricular Outflow Obstruction
Angiotensin Receptor Antagonists
Angiotensin II
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors