Left Ventricular Assist Device: Morphological, Molecular And Genetic Changes After Mechanical Support

Left ventricular assist devices (LVADs) are currently used to either "bridge" patients with terminal congestive heart failure (CHF) to cardiac transplantation or optionally for patients with contraindications for transplantation ("destination therapy"). Mechanical support is associated with a marked decrease of cardiac dilation and hypertrophy as well as numerous cellular and molecular changes ("reverse cardiac remodeling"), which can be accompanied by improved cardiac function ("bridge to recovery") in a relatively small subset of patients. In these patients, heart transplantation is no longer necessary even after removal of the device ("weaning"). In the recent past, novel pharmacological strategies have been developed and are combined with mechanical support, which has increased the percentage of patients with improved clinical status and cardiac performance. Gene expression profiles have demonstrated that individuals who recover after LVADs show different gene expression compared to individuals who do not respond to unloading. This chapter focuses on signal transduction, transcriptional regulation, and aspects of neurohormonal activation in the failing human heart before and after ventricular unloading.