Circulatory factors associated with function and prognosis in patients with severe heart failure

Abstract

Background Multiple 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 results Physical 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. Conclusions These 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

Compared with matched controls, patients with postoperative atrial fibrillation (POAF) have increased long-term AF after CABG, and POAF is further associated with increased ischemic stroke, heart failure and mortality even after adjustment for AF

“…Mechanistically, AF is a common cause of tachycardia-induced cardiomyopathy, and neurohormonal and structural changes in heart failure can in turn trigger and maintain AF [ 16 , 17 ], but overall it is not possible to specify which condition causes which. It has been suggested that AF and heart failure are different expressions of the same underlying systemic disease, and inflammation is significantly involved in both conditions [ 16 – 19 ].…”

“…Furthermore, AF promotes different levels of vessel wall damage [ 15 ]. Regarding AF and heart failure, it has been suggested that they are different expressions of the same underlying systemic disease, where inflammation is significantly involved in both conditions and in many of their shared comorbidities [ 16 – 19 ]. In short, in the context of primary AF there are several identified mechanisms regarding associations with outcome.…”

GDF-15 como Biomarcador em Doenças Cardiovasculares

“…Este resultado se manteve significativo após ajuste para outros fatores de risco como o consumo de oxigênio de pico (VO2 pico), idade e taxa de filtração glomerular. 35 O primeiro grande estudo que avaliou o valor prognóstico do GDF-15 na ICFEr foi realizado utilizando-se a base de dados do ensaio clínico Val-HeFT (Valsartan Heart Failure Trial), que avaliou o uso de valsartan em pacientes com IC. O GDF-15 foi avaliado no início do estudo (n=1734) e após 12 meses de seguimento (n=1517).…”

Exercise as a Therapeutic Strategy for Sarcopenia in Heart Failure: Insights into Underlying Mechanisms

“…A decrease in peak VO 2 in HF may be largely due to complications in the central region, including reduced carbon monoxide (CO), impaired respiratory gas exchange, and insufficient blood flow [ 56 ]. In addition, systemic oxygen delivery to locomotor muscles is significantly reduced during exercise because of impaired endothelium-dependent vasodilation [ 57 ], muscle capillarization [ 58 ], systemic inflammation, oxygen unloading [ 59 ], and oxidative stress [ 60 ]. These cardiovascular impairments mainly limit exercise capacity in HF.…”