Author + information
- Received July 21, 2006
- Revision received October 4, 2006
- Accepted October 9, 2006
- Published online March 20, 2007.
- Stefan Klotz, MD⁎,
- A.H. Jan Danser, PhD‡,
- Robert F. Foronjy, MD⁎,
- Mehmet C. Oz, MD†,
- Jie Wang, MD, PhD⁎,§,
- Donna Mancini, MD⁎,
- Jeanine D’Armiento, MD, PhD⁎ and
- Daniel Burkhoff, MD, PhD⁎,§,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Daniel Burkhoff, Jack H. Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, 8 Corporate Drive, Orangeburg, New York 10962.
Objectives We hypothesized that angiotensin-converting enzyme inhibition (ACE-I) during left ventricular assist device (LVAD) support in patients with end-stage heart failure prevents potentially deleterious effects on the extracellular matrix.
Background Left ventricular assist device-induced mechanical unloading increases myocardial collagen and stiffness and may contribute to the low rate of recovery.
Methods Heart samples obtained before and after LVAD implantation were divided into groups depending on whether the patients received (n = 7) or did not receive (control; n = 15) ACE-I. At transplant, ex vivo pressure-volume relationships were measured and chamber and myocardial stiffness constants determined. Myocardial tissue content of angiotensin (Ang) I and II, matrix metalloproteinase (MMP)-1, tissue inhibitor of MMPs (TIMP)-1, and total and cross-linked collagen was measured.
Results Duration of support was comparable between ACE-I and control subjects (96 ± 65 days vs. 109 ± 22 days). Pre-LVAD Ang I and II and total and cross-linked collagen were similar between groups. Post-LVAD, Ang II was reduced in the ACE-I group but increased in control subjects (181 ± 7 fmol/g vs. 262 ± 41 fmol/g; p < 0.05). Similarly, cross-linked collagen decreased during LVAD support in the ACE-I group. Left ventricular (LV) mass and myocardial stiffness were lower in the ACE-I group. ACE-I normalized the LV and right ventricular (RV) MMP-1/TIMP-1 ratio. Collagen content and characteristics of the RV were not affected by ACE-I.
Conclusions ACE-I therapy was associated with decreased Ang II, myocardial collagen content, and myocardial stiffness during LVAD support. This is the first demonstration of a pharmacologic therapy that can impact myocardial properties during mechanical unloading, and it could foster new lines of investigation in strategies of enhancing myocardial recovery during LVAD support.
- Received July 21, 2006.
- Revision received October 4, 2006.
- Accepted October 9, 2006.
- American College of Cardiology Foundation