European Heart Journal Advance Access originally published online on February 17, 2009
European Heart Journal 2009 30(7):805-812; doi:10.1093/eurheartj/ehp012
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The impact of left ventricular assist device-induced left ventricular unloading on the myocardial renin–angiotensin–aldosterone system: therapeutic consequences?
1 Department of Thoracic and Cardiovascular Surgery, University Hospital Muenster, Germany
2 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
3 Pharmacology, Vascular, and Metabolic Medicine Sector, Department of Internal Medicine, Erasmus Medical Center, Room EE1418b, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Received 8 November 2008; revised 20 November 2008; accepted 24 December 2008; online publish-ahead-of-print 17 February 2009.
* Corresponding author. Tel: +31 10 7043540, Fax: +31 10 7044733, Email: a.danser{at}erasmusmc.nl
Aims: Angiotensin-converting enzyme inhibitors (ACE-Is) prevent the rise in myocardial angiotensin II that occurs after left ventricular assist device (LVAD) implantation, but do not fully normalize cardiac function. Here, we determined the effect of LVAD implantation, with or without ACE-Is, on cardiac renin, aldosterone, and norepinephrine, since these hormones, like angiotensin II, are likely determinants of myocardial recovery during LVAD support.
Methods and results: Biochemical measurements were made in paired LV myocardial samples obtained from 20 patients before and after LVAD support in patients with and without ACE-I therapy. Pre-LVAD renin levels were 100x normal and resulted in almost complete cardiac angiotensinogen depletion. In non-ACE-I users, LVAD support, by normalizing blood pressure, reversed this situation. Cardiac aldosterone decreased in parallel with cardiac renin, in agreement with the concept that cardiac aldosterone is blood-derived. Cardiac norepinephrine increased seven-fold, possibly due to the rise in angiotensin II. Angiotensin-converting enzyme inhibitor therapy prevented these changes: renin and aldosterone remained high, and no increase in norepinephrine occurred.
Conclusion: Although LV unloading lowers renin and aldosterone, it allows cardiac angiotensin generation to increase and thus to activate the sympathetic nervous system. Angiotensin-converting enzyme inhibitors prevent the latter, but do not affect aldosterone. Thus, mineralocorticoid receptor antagonist therapy during LVAD support may play a role in further promoting recovery.
Key Words: Left ventricular assist device • Renin–angiotensin–aldosterone system • Catecholamine • Collagen • Heart failure • Reverse remodelling