Therapeutic Targets in Heart Failure: Refocusing on the Myocardial Interstitium.
J Am Coll Cardiol. 2014 Mar 6;
Authors: Schelbert EB, Fonarow GC, Bonow RO, Butler J, Gheorghiade M
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 following hospitalization for heart failure (HHF). Conceptually, an accurate assessment of left ventricular (LV) structure is an essential step in the development of novel therapies because heterogeneous pathophysiologies underlie chronic HF and HHF. Improved LV 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" have been 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 (ECV) 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.
PMID: 24657693 [PubMed - as supplied by publisher]