Purpose of review Myocardial remodeling driven by excess pressure and volume load is believed to be responsible for the vicious cycle of progressive myocardial dysfunction in chronic heart failure. Left ventricular assist devices (LVADs), by providing significant volume and pressure unloading, allow a reversal of stress-related compensatory responses of the overloaded myocardium. Herein, we summarize and integrate insights from studies which investigated how LVAD unloading influences the structure and function of the failing human heart. Recent findings Recent investigations have described the impact of LVAD unloading on key structural features of cardiac remodeling – cardiomyocyte hypertrophy, fibrosis, microvasculature changes, adrenergic pathways and sympathetic innervation. The effects of LVAD unloading on myocardial function, electrophysiologic properties and arrhythmias have also been generating significant interest. We also review information describing the extent and sustainability of the LVAD-induced myocardial recovery, the important advances in understanding of the pathophysiology of heart failure derived from such studies, and the implications of these findings for the development of new therapeutic strategies. Special emphasis is given to the great variety of fundamental questions at the basic, translational and clinical levels that remain unanswered and to specific investigational strategies aimed at advancing the field. Summary Structural and functional reverse remodeling associated with LVADs continues to inspire innovative research. The ultimate goal of these investigations is to achieve sustained recovery of the failing human heart.

Non-invasive imaging techniques are highly desirable as an alternative to conventional biopsy for characterizing remodeling of tissues associated with disease progression, including end-stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for characterizing myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be systematically investigated. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end-stage heart failure due to idiopathic dilated cardiomyopathy (n=14) and from normal donors (n=5). Scalar DTI parameters, including fractional anisotropy (FA), mean (MD), primary (D1), secondary (D2), and tertiary (D3) diffusivities, were correlated to collagen content measured by digital microscopy. Compared to hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D2 and D3 increased by 12%, 14%, and 24% respectively (P < 0.01). No significant change was detected for D1 between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e., fibrosis). Pearson's correlation coefficient (r) between collagen content and either FA, MD, D2, and D3 was -0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D1 and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for noninvasive assessment of diffuse fibrosis in failing hearts.