Abstract 16103: Effects of Left Ventricular Assist Device Placement on Biomarkers of Cardiovascular Stress, Fibrosis, Fluid Homeostasis, Mitochondrial Function, Metabolism, and Endothelial Dysfunction
Background: End stage heart failure (HF) is characterized by excessive hemodynamic demands on the failing ventricle and dysregulation of molecular pathways that induce further myocardial damage. Left ventricular assist device (LVAD) therapy may relieve these stressors and even result in myocardial recovery. Corresponding changes in markers of myocardial stress, injury and metabolism are unknown.
Methods: The study population consisted of 41 consecutive patients undergoing LVAD implantation. NTproBNP, galectin-3, ST2, proADM, and copeptin were measured using ELISA and 69 metabolites (free fatty acids, acylcarnitines, and amino acids) were measured using mass spectrometry with isotope labeled standards in plasma collected prior to LVAD implantation and ≥80 days following placement. Unadjusted paired Student T-tests were used to assess temporal changes in individual biomarkers.
Results: The average age of patients was 62 (±16) years, 68% had ischemic HF, and post-LVAD blood collection was performed at a mean of 149 (±66) days. LVAD therapy was associated with significant decreases in biomarkers of myocardial stress (NTproBNP, ST2; P=0.01), fibrosis (galectin-3, P=0.03), fluid homeostasis (copeptin, P=0.03), but not endothelial dysfunction (proADM, P=0.28). Despite improvement over time, absolute values of each biomarker remained abnormal. Metabolomic profiling revealed that short-chain long-chain dicarboxylacylcarnitines decreased significantly after LVAD placement (P≤0.05). Fatty acids and their catabolic byproducts decreased with LVAD placement (P≤0.05), possibly indicating a return towards normal myocardial fatty acid utilization in the face of decreased myocardial demand.
Conclusions: LVAD therapy is associated with improvements but continued abnormalities in biomarkers of myocardial stress, fibrosis, and fluid homeostasis. Metabolites previously shown to portend poor longer term cardiovascular outcomes decreased after left ventricular unloading with LVAD. Our results suggest the need for targeted therapeutic interventions to mitigate continued myocardial injury and possibly increase rates of recovery.
- Mitochondrial energetics, heart failure, arrhythmias
- Cardiac metabolism
- Artificial heart/Cardiac support devices
- Heart failure
- © 2013 by American Heart Association, Inc.