Effect of Angiotensin II Receptor Blockers (ARB) on Left Ventricular Reverse Remodelling After Aortic Valve Replacement in Severe Valvular Aortic Stenosis
Recruitment status was: Active, not recruiting
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.
|Aortic Valve Stenosis Left Ventricular Hypertrophy Atrial Fibrillation||Drug: Candesartan||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: 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|
- LV mass index
- LA volume index
- Plasma nt-pro BNP concentration
- Diastolic E/e' ratio
- Overall LV function assessed by the Doppler echocardiographic Tei Index
- Regional LV function assessed with tissue Doppler imaging
- LV end systolic and end diastolic volume index
- Atrial arrhythmias assessed with 48h Holter after 12 months
- Exercise capacity after 12 months
- Serial changes in LV diastolic, overall LV function and regional LV systolic function
- Assess serial changes in plasma nt-pro BNP, ANP, and renin
|Study Start Date:||February 2006|
|Estimated Study Completion Date:||June 2009|
|Estimated Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00294775
|Cardiology Department, Odense University hospital|
|Odense, Fyn, Denmark, 5000|
|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|