Systolic and Diastolic Heart Failure Are Overlapping Phenotypes Within the Heart Failure Spectrum

Should chronic heart failure (HF) be subdivided into 2 distinct phenotypes? Current knowledge supports the view that the complexity of HF cannot be captured by answering this question with a yes or a no. Recent developments in the biosciences, particularly systems biology approaches and studies of phenotypic disease networks, have indicated that such questions are becoming obsolete, and perhaps even irrelevant.Response by Borlaug and Redfield on p 2005Chronic HF is a complex, multifactorial syndrome consisting of many overlapping phenotypes. A unifying hypothesis to explain the development and progressive character of HF has not withstood the test of time (Figure 1). Despite improvements in clinical management, the incidence and mortality of chronic HF remain high. Attempts to further improve its prognosis have failed, and conceptual progress seems to stagnate.Figure 1. Evolving paradigms of heart failure progression. Each of the paradigms highlights a different aspect of the syndrome. In the vicious circle paradigm of heart failure ( left ), the pernicious, progressive, and irreversible character is emphasized as propelled by endothelial dysfunction and (mal)adaptive activation of neurohormones and cytokines. In the time progression paradigm ( middle ), the progressive nature of heart failure is equally emphasized, but focus is on the consecutive stages of failing cardiac performance: failure of the heart first as a muscular suction pump, then as a hemodynamic compression pump, and finally of the whole cardiovascular system, with drop in stroke volume (SV), cardiac index (CI), and eventually of arterial blood pressure (Part). The spectrum paradigm of heart failure ( right ) visualizes the manner in which each patient follows a unique disease trajectory during heart failure progression. The trajectories depend on the relative contribution of the patient's traits and comorbidities (coined disease modifiers ), are thus patient specific, and hence create a spectrum of phenotypes throughout the entire population of heart failure patients. CV …