The Impact of Angiotensin-Converting Enzyme Inhibitor Therapy on the Extracellular Collagen Matrix During Left Ventricular Assist Device Support in Patients With End-Stage Heart Failure
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*,,*
* Department of Medicine
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York
Department of Pharmacology, Erasmus Medical Center, Rotterdam, the Netherlands
The Jack H. Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, New York
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Figure 1 MMP1- and TIMP-1 Protein Expression
Matrix metalloproteinase (MMP)-1 (A), MMP-9 (B), and tissue inhibitor of MMP (TIMP)-1 (C) protein levels in normal (open bars), chronic heart failure (CHF) + angiotensin-converting enzyme inhibition (ACE-I) (solid bars), and left ventricular assist device (LVAD)-supported hearts without ACE-I (blue bars) and with ACE-I (red bars). Whereas MMP-1 protein levels are slightly reduced in LV samples after LVAD support and ACE-I, TIMP-1 protein levels are significantly elevated in this group compared with CHF hearts without LVAD support. The MMP-1/TIMP-1 ratio (D) shows a trend toward better normalization after LVAD support if patients received ACE-I. *p < 0.05 versus normal hearts; p < 0.05 versus CHF + ACE-I (analysis of variance). LV = left ventricle; RV = right ventricle.
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Figure 2 EDPVRs With and Without ACE-I
Grouped end-diastolic pressure-volume relationships (EDPVR) measured ex vivo from whole hearts. The average EDPVR from patients with LVAD support receiving ACE-I (LVAD ACE-I, open circles) tended to be shifted to the left toward lower volumes compared with the EDPVR from patients with LVAD support without ACE-I (LVAD Control, solid circles). X = nonfailing hearts; solid squares = failing hearts without LVAD support. *p < 0.05 versus CHF without LVAD (analysis of variance). Abbreviations as in Figure 1.
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Figure 3 Impact of ACE-I on LV and RV Volume and LV Mass
(Left) LV (black bars) and RV (green bars) ex vivo volume at the pressure of 30 mm Hg. With ACE-I therapy, LV volume was almost significantly lower compared with the control group. (Right) LV mass was significantly lower in the ACE-I group (open bar) compared with the control group (solid bar). *p < 0.05 versus LV control group; p < 0.062 versus control group (Student t test). Abbreviations as in Figure 1.
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Figure 4 Developed Force Measured From Isolated Myocardial Trabeculae
Developed force (mN/mm2) at baseline (open bars) and during ß-stimulation with isoproterenol (solid bars) in the control and ACE-I groups. Whereas isoproterenol significantly increases developed force, there is no difference between the control and the ACE-I groups. *p < 0.001 versus baseline (Student t test). Abbreviations as in Figure 1.
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