Hold or fold-Proteins in advanced heart failure and myocardial recovery

Advanced heart failure (AHF) describes the subset of heart failure patients refractory to conventional medical therapy. For some AHF patients, the use of mechanical circulatory support (MCS) provides an intermediary "bridge" step for transplant-eligible patients or an alternative therapy for transplant-ineligible patients. Over the past 20 years, clinical observations have revealed that approximately 1% of patients with MCS undergo significant reverse remodeling to the point where the device can be explanted. Unfortunately, it is unclear why some patients experience durable, sustained myocardial remission, while others redevelop heart failure (i.e. which hearts "hold" and which hearts "fold"). In this review, we outline unmet clinical needs related to treating patients with MCS, provide an overview of protein dynamics in the reverse-remodeling process, and propose specific areas where we expect MS and proteomic analyses will have significant impact on our understanding of disease progression, molecular mechanisms of recovery, and provide new markers with prognostic value that can positively impact patient care. Complimentary perspectives are provided with the goal of making this important topic accessible and relevant to both a clinical and basic science audience, as the intersection of these disciplines is required to advance the field.