Bridge to recovery: understanding the disconnect between clinical and biological outcomes.

Left ventricular (LV) assist devices (LVADs) are increasingly used in everyday clinical practice either as a bridge for end-stage heart failure (HF) patients to heart transplantation or as a permanent (destination) therapy.1,2 Yet, there is still significant uncertainty about the consequences of this intervention both at the level of the detailed myocardial biology (ie, biological outcomes) and at the functional cardiovascular response of the patient at the organ level (ie, clinical outcomes). The LVAD patient population presents a series of significant advantages as far as research is concerned. First, LVAD therapy offers the ability to acquire paired human myocardial tissue at LVAD implantation and again on LVAD removal. The ability to obtain human tissue and the possibility for its serial examination before and after any therapeutic investigational therapy combined with LVADs provide an important opportunity for in-depth study of the changes in the structure and function of the diseased human heart caused by the specific investigational therapy. Second, this population represents a relatively safe investigational platform because the hemodynamic support provided by VADs makes these patients significantly less vulnerable to any arrhythmic3 or hemodynamic adverse events potentially associated with new aggressive investigational therapies. Third, the volumes of potential study subjects for these investigations (ie, patients who receive LVADs) are rapidly increasing; because of a lack of donor organs and incremental progress in device design and durability, the number of advanced HF patients with LVADs has been continuously increasing.1,2 These 3 research advantages create an ideal setting for various new HF therapies to test their potential efficacy in LVAD patients. Fourth, this population offers an opportunity to investigate the effects of the LVAD-induced removal of excess mechanical load, which drives the vicious cycle of myocardial remodeling and eventually leads to the clinical HF syndrome.4 Increasing evidence suggests that a significant degree of improvement in myocardial structure and function can be observed after LVAD-induced mechanical unloading,5 to the point that some of these advanced HF patients can eventually be weaned from mechanical support and achieve sustained myocardial recovery.6,7 These important research advantages may transform this LVAD patient population into a precious translational research vehicle for investigating new antiremodeling and regenerative therapies for HF. However, for these promises to be fulfilled, we must first establish the baseline and better understand the fundamental impact of LVAD-induced unloading on the failing human heart.