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

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.

Timeline

Start

2006-02

Primary completion

2009-01

Completion

2009-06

Publications

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• Background Walther T, Schubert A, Falk V, Binner C, Walther C, Doll N, Fabricius A, Dhein S, Gummert J, Mohr FW. Left ventricular reverse remodeling after surgical therapy for aortic stenosis: correlation to Renin-Angiotensin system gene expression. Circulation. 2002 Sep 24;106(12 Suppl 1):I23-6.
• Background Walther T, Schubert A, Falk V, Binner C, Kanev A, Bleiziffer S, Walther C, Doll N, Autschbach R, Mohr FW. Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression. Circulation. 2001 Sep 18;104(12 Suppl 1):I54-8. doi: 10.1161/hc37t1.094777.
• Background Giorgi D, Di Bello V, Talini E, Palagi C, Delle Donne MG, Nardi C, Verunelli F, Mariani MA, Di Cori A, Caravelli P, Mariani M. Myocardial function in severe aortic stenosis before and after aortic valve replacement: a Doppler tissue imaging study. J Am Soc Echocardiogr. 2005 Jan;18(1):8-14. doi: 10.1016/j.echo.2004.08.012.
• Background Lund O, Emmertsen K, Dorup I, Jensen FT, Flo C. Regression of left ventricular hypertrophy during 10 years after valve replacement for aortic stenosis is related to the preoperative risk profile. Eur Heart J. 2003 Aug;24(15):1437-46. doi: 10.1016/s0195-668x(03)00316-6.
• Sabino-Carvalho JL, Li S, Mekonnen E, Mammino K, Nocera JR, Park J. Aerobic Cycling Exercise Training Does Not Improve Impaired Vagal Reactivation in Patients with Chronic Kidney Disease. Med Sci Sports Exerc. 2025 Dec 1;57(12):2621-2629. doi: 10.1249/MSS.0000000000003824. Epub 2025 Jul 16.
• Dahl JS, Barros-Gomes S, Videbaek L, Poulsen MK, Issa IF, Carter-Storch R, Christensen NL, Kumme A, Pellikka PA, Moller JE. Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis. JACC Cardiovasc Imaging. 2016 May;9(5):519-28. doi: 10.1016/j.jcmg.2015.06.029. Epub 2016 Apr 13.
• Dahl JS, Christensen NL, Videbaek L, Poulsen MK, Carter-Storch R, Hey TM, Pellikka PA, Steffensen FH, Moller JE. Left ventricular diastolic function is associated with symptom status in severe aortic valve stenosis. Circ Cardiovasc Imaging. 2014 Jan;7(1):142-8. doi: 10.1161/CIRCIMAGING.113.000636. Epub 2013 Oct 30.
• Dahl JS, Moller JE, Videbaek L, Poulsen MK, Rudbaek TR, Pellikka PA, Scott Argraves W, Rasmussen LM. Plasma fibulin-1 is linked to restrictive filling of the left ventricle and to mortality in patients with aortic valve stenosis. J Am Heart Assoc. 2012 Dec;1(6):e003889. doi: 10.1161/JAHA.112.003889. Epub 2012 Dec 19.
• Dahl JS, Videbaek L, Poulsen MK, Rudbaek TR, Pellikka PA, Moller JE. Global strain in severe aortic valve stenosis: relation to clinical outcome after aortic valve replacement. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):613-20. doi: 10.1161/CIRCIMAGING.112.973834. Epub 2012 Aug 6.
• Dahl JS, Videbaek L, Poulsen MK, Pellikka PA, Veien K, Andersen LI, Haghfelt T, Moller JE. Noninvasive assessment of filling pressure and left atrial pressure overload in severe aortic valve stenosis: relation to ventricular remodeling and clinical outcome after aortic valve replacement. J Thorac Cardiovasc Surg. 2011 Sep;142(3):e77-83. doi: 10.1016/j.jtcvs.2011.01.032. Epub 2011 Feb 25.

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