Integrating the Myocardial Matrix Into Heart Failure Recognition and Management

Abstract

In contrast to public perception, the morbidity and mortality and the resultant healthcare costs associated with chronic heart failure (HF) are increasing and arguably reaching epidemic proportions. Although basic research efforts have provided unique insights into fundamental processes that govern myocardial extracellular matrix (ECM) growth and function, the translation of these findings to improved diagnostics and therapeutics for HF has not been as forthcoming. The factors that contribute to this relative paucity of new clinical tools for HF are multifactorial but likely include the need to recognize and differentiate HF phenotypes and to couple the use of biomarkers and multimodality imaging in early translational research studies. Recognizing the classification scheme of HF with a reduced ejection fraction (EF) to that of HF with a preserved EF and incorporating unique and differential measurements of ECM remodeling to these specific disease processes are warranted. For example, profiling pathways of ECM degradation such as the matrix metalloproteinases in patients with ischemic heart disease and HF with a reduced EF can provide prognostic information in terms of risk of progression to HF. In patients with chronic hypertensive disease and HF with a preserved EF, plasma profiling indexes of ECM synthesis and turnover, as well as advances in ECM imaging, have been shown to provide diagnostic and prognostic use. In terms of therapeutics, strategies to stabilize the ECM in HF with a reduced EF hold potential, whereas in contradistinction, selective antifibrotic agents may hold promise for HF with a preserved EF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT 00946231