title: Therapeutic targets in heart failure: refocusing on the myocardial interstitium.
abstract: New therapeutic targets, agents, and strategies are needed to prevent and treat heart failure (HF) after a decade of failed research efforts to improve long-term patient outcomes, especially in patients after hospitalization for HF. Conceptually, an accurate assessment of left ventricular structure is an essential step in the development of novel therapies because heterogeneous pathophysiologies underlie chronic HF and hospitalization for HF. Improved left ventricular characterization permits the identification and targeting of the intrinsic fundamental disease-modifying pathways that culminate in HF. Interstitial heart disease is one such pathway, characterized by extracellular matrix (ECM) expansion that is associated with mechanical, electrical, and vasomotor dysfunction and adverse outcomes. Previous landmark trials that appear to treat interstitial heart disease were effective in improving outcomes. Advances in cardiovascular magnetic resonance now enable clinicians and researchers to assess the interstitium and quantify ECM expansion using extracellular volume fraction measures and other derangements in cardiovascular structure. These capabilities may provide a mechanistic platform to advance understanding of the role of the ECM, foster the development of novel therapeutics, and target specific disease-modifying pathways intrinsic to the ventricle. Refocusing on the interstitium may potentially improve care through the identification and targeted treatment of key patient subgroups.
authors.affiliation: Heart & Vascular Institute Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: schelberteb@upmc.edu.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schelbert
authors.affiliation: Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan-UCLA Medical Center, Los Angeles, California.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Bonow
authors.affiliation: Division of Cardiology, Emory University, Atlanta, Georgia.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D005109:Extracellular Matrix / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents
keywords: extracellular matrix; extracellular volume fraction; heart failure; myocardial fibrosis