Pathways of the Heart

Abstract

Disease heterogeneity presents a formidable challenge for clinical medicine. We are unlikely to develop successful, targeted treatments unless diagnostic schemes begin to reflect the biological complexity underlying superficially similar disease phenotypes. To address heterogeneity, there is an increasing recognition that realistic disease models need to be built on a foundation of quantitative molecular information.1 Such a “systems medicine” approach should ultimately allow classification into biologically more homogeneous groups, with similar prognosis and treatment response. Article see p 371 Oncology has been among the first specialties to embrace molecular profiling to improve clinical decision making. Today, a wealth of expression profiling information exists for tumors, and early efforts are being made to classify patients into likely treatment responders for specific chemotherapeutics.2 The investigation of complex multisystem pathologies, such as cardiovascular disease, has been slower to incorporate molecular profiling, in part, because of the involvement of multiple tissues, many of which are not readily accessible. Moreover, cardiovascular disease, unlike cancer, is not clonal in origin, making experimental analyses more challenging. It is clear, however, that broadly defined diseases such as the cardiomyopathies are the product of diverse genetic and environmental agents3; one can expect that quantitative molecular profiling will shed light on distinct, pathological activities underlying these conditions, thus allowing more meaningful classification schemes beyond those that are solely based on anatomic or hemodynamic considerations. The article by Barth et al4 in this issue of Circulation: Cardiovascular Genetics represents such a broadened search for molecular correlates of cardiovascular disease. The authors focus on the problem of heart failure with mechanical dyssynchrony (DHF) and its treatment by cardiac resynchronization therapy (CRT). Clinically, CRT has been a remarkable success, with significant gains in quality of life and mortality.5 Multiple studies have investigated the physiological consequences of dyssynchrony and …