Date Published: April 1, 2013
Publisher: Public Library of Science
Author(s): Lindsay B. Weitzel, Amrut V. Ambardekar, Andreas Brieke, Joseph C. Cleveland, Natalie J. Serkova, Paul E. Wischmeyer, Brian D. Lowes, Shahab A. Akhter. http://doi.org/10.1371/journal.pone.0060292
Heart failure patients have inadequate nutritional intake and alterations in metabolism contributing to an overall energy depleted state. Left ventricular assist device (LVAD) support is a common and successful intervention in patients with end-stage heart failure. LVAD support leads to alterations in cardiac output, functional status, neurohormonal activity and transcriptional profiles but the effects of LVADs on myocardial metabolism are unknown. This study set out to measure cardiac metabolites in non-failing hearts, failing hearts, and hearts post-LVAD support.
The study population consisted of 8 non-ischemic failing (at LVAD implant) and 8 post-LVAD hearts, plus 8 non-failing hearts obtained from the tissue bank at the University of Colorado. NMR spectroscopy was utilized to evaluate differences in myocardial energy substrates. Paired and non-paired t-tests were used to determine differences between the appropriate groups.
Glucose and lactate values both decreased from non-failing to failing hearts and increased again significantly in the (paired) post-LVAD hearts. Glutamine, alanine, and aromatic amino acids decreased from non-failing to failing hearts and did not change significantly post-LVAD. Total creatine and succinate decreased from non-failing to failing hearts and did not change significantly post-LVAD.
Measured metabolites related to glucose metabolism are diminished in failing hearts, but recovered their values post-LVAD. This differed from the amino acid levels, which decreased in heart failure but did not recover following LVAD. Creatine and the citric acid cycle intermediate succinate followed a similar pattern as the amino acid levels.
Patients with chronic heart failure often have inadequate intake of calories and protein and diminished energy availability . Likewise, it has been hypothesized that the failing heart is in a chronic energy starved state ,  and that abnormalities in metabolism contribute to myocardial dysfunction.  There are also considerable data to support an obesity paradox in heart failure with BMI’s between 30–35 associated with lower mortality than BMI’s closer to 25 . Together, these ideas would seem to argue that patients with heart failure are energy depleted and it is plausible they could benefit from targeted nutrition therapy. Historically, nutritional interventions in this population focus on limiting sodium intake and maximizing intake of minerals such as calcium and magnesium , while little is known about metabolic substrates and metabolism in the failing heart.
Patient characteristics are found in Table 1. There were no statistically significant demographic differences between the failing/post-LVAD group and the non-failing group. Patients in the failing and post-LVAD group had a mean age of 40, and those in the non-failing group were on average 48 years old.
Our data indicates that significant changes in myocardial metabolism occur in the failing heart and some, but not all of these changes, are improved by LVAD placement. The amino acid levels in this study indicate that these substrates decrease significantly in cardiac tissue from non-failing to failing hearts and they do not recover during LVAD support. These data seem to support the hypothesis that the heart is depleting its amino acid stores and that unloading the heart through LVAD support does not allow replenishment of these losses.