Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure

Abstract

LVAD therapy is an effective rescue in acute and especially chronic cardiac failure. In several scenarios, it provides a platform for regeneration and sustained myocardial recovery. While unloading seems to be a key element, pharmacotherapy may provide powerful tools to enhance effective cardiac regeneration. The synergy between LVAD support and medical agents may ensure satisfying outcomes on cardiomyocyte recovery followed by improved quality and quantity of patient life. This review summarizes the previous and contemporary strategies for combining LVAD with pharmacotherapy and proposes new therapeutic targets. Regulation of metabolic pathways, enhancing mitochondrial biogenesis and function, immunomodulating treatment, and stem-cell therapies represent therapeutic areas that require further experimental and clinical studies on their effectiveness in combination with mechanical unloading.

Assessment of Autophagy Markers Suggests Increased Activity Following LVAD Therapy

“…Previous clinical studies have shown that renin-angiotensin-aldosterone system blockade, including with ACE inhibitors, improves reported quality of life, heart failure class, and LV function for patients with LVADs. 28 Our data showing that ACE inhibitor use in this patient population is associated with restored proteostasis (ie, reduction of ubiquitinated protein levels) may provide mechanistic insight into the underlying biology. It is therefore important to note that the high prevalence of ACE inhibitors used on our patient cohort post-LVAD may be a contributing factor to the molecular features observed.…”