Abstract
BackgroundMultiple circulatory factors are increased in heart failure (HF). Many have been linked to cardiac and/or skeletal muscle tissue processes, which in turn might influence physical activity and/or capacity during HF. This study aimed to provide a better understanding of the mechanisms linking HF with the loss of peripheral function.Methods and resultsPhysical capacity measured by maximum oxygen uptake, myocardial function (measured by echocardiography), physical activity (measured by accelerometry), and mortality data was collected for patients with severe symptomatic heart failure an ejection fraction < 35% (n = 66) and controls (n = 28). Plasma circulatory factors were quantified using a multiplex immunoassay. Multivariate (orthogonal projections to latent structures discriminant analysis) and univariate analyses identified many factors that differed significantly between HF and control subjects, mainly involving biological functions related to cell growth and cell adhesion, extracellular matrix organization, angiogenesis, and inflammation. Then, using principal component analysis, links between circulatory factors and physical capacity, daily physical activity, and myocardial function were identified. A subset of ten biomarkers differentially expressed in patients with HF vs controls covaried with physical capacity, daily physical activity, and myocardial function; eight of these also carried prognostic value. These included established plasma biomarkers of HF, such as NT-proBNP and ST2 along with recently identified factors such as GDF15, IGFBP7, and TfR, as well as a new factor, galectin-4.ConclusionsThese findings reinforce the importance of systemic circulatory factors linked to hemodynamic stress responses and inflammation in the pathogenesis and progress of HF disease. They also support established biomarkers for HF and suggest new plausible markers.Graphic abstract
Highlights
Heart failure (HF) is manifested by an inability of the heart to supply the peripheral tissues with the necessary volume of blood to meet their metabolic demands [73]
heart failure (HF) is usually diagnosed by echocardiography assessment of systolic and diastolic cardiac function [65, 85], the prognostic value of this measurement is considerably smaller than peak oxygen uptake (VO2peak) [5, 23]
Patients with moderate to severe and stable chronic HF, defined as functional New York Heart Association (NYHA) class III disease, with no acute hospital admission within the last 8 weeks and with a left ventricular ejection fraction (LVEF) < 35% were eligible for inclusion
Summary
Heart failure (HF) is manifested by an inability of the heart to supply the peripheral tissues with the necessary volume of blood to meet their metabolic demands [73]. The combination of physical capacity (VO2peak), systolic function expressed as the left ventricular ejection fraction (LVEF), blood pressure, and heart rate has repeatedly shown the ability to identify patients with a poor prognosis [1, 48, 64] These variables constitute the cornerstone of several well-established prognostic models for patients with HF. A subset of ten biomarkers differentially expressed in patients with HF vs controls covaried with physical capacity, daily physical activity, and myocardial function; eight of these carried prognostic value These included established plasma biomarkers of HF, such as NT-proBNP and ST2 along with recently identified factors such as GDF15, IGFBP7, and TfR, as well as a new factor, galectin-4. They support established biomarkers for HF and suggest new plausible markers
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