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Left ventricular assist devices (LVADs) are an established treatment modality for advanced heart failure (HF). It has been shown that through volume and pressure unloading they can lead to significant functional and structural cardiac improvement, allowing LVAD support withdrawal in a subset of patients. In the first part of this review, we discuss the historical background, current evidence on the incidence and assessment of LVAD-mediated cardiac recovery, and out-comes including quality of life after LVAD support withdrawal. In the second part, we discuss current and future opportunities to promote LVAD-mediated reverse remodeling and improve our pathophysiological understanding of HF and recovery for the benefit of the greater HF population. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders. Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was −0.6 cm (interquartile range [IQR], −1.1 to −0.1 cm; nonresponders), −1.1 cm (IQR, −1.8 to −0.4 cm; partial responders), and −1.9 cm (IQR, −2.9 to −1.1 cm; responders). Similarly, the median change in LVEF was −2% (IQR, −6% to 1%), 9% (IQR, 6%–14%), and 27% (IQR, 23%–33%), respectively. Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations. [ABSTRACT FROM AUTHOR]

By unloading the failing heart, left ventricular (LV) assist devices (LVADs) provide a favorable environment for reversing adverse structural and functional cardiac changes. Prior reports have suggested that an improved native LV function might contribute to the development of LVAD thrombosis. We used the Interagency Registry for Mechanically Assisted Circulatory Support and found that LV functional improvement is associated with a lower risk for device thrombosis. The risk for cerebrovascular accident and transient ischemic attack was comparable across post-LVAD LV function subgroups, while the risk of hemolysis was lower in subgroups of patients with better LV function on LVAD support. [ABSTRACT FROM AUTHOR]

Background: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)-induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R.Methods: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy.Results: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery.Conclusions: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading. [ABSTRACT FROM AUTHOR]