The cardiosplenic axis: the prognostic role of the spleen in heart failure

Abstract

Despite the number of available methods to predict prognosis in patients with heart failure, prognosis remains poor, likely because of marked patient heterogeneity and varied heart failure etiologies. Thus, identification of novel prognostic indicators to stratify risk in patients with heart failure is of paramount importance. The spleen is emerging as a potential novel prognostic indicator for heart failure. In this article, we provide an overview of the current prognostic tools used for heart failure. We then introduce the spleen as a potential novel prognostic indicator, before outlining the structure and function of the spleen and introducing the concept of the cardiosplenic axis. This is followed by a focused discussion on the function of the spleen in the immune response and in hemodynamics, as well as a review of what is known about the usefulness of the spleen as an indicator of heart failure. Expert insight into the most effective spleen-related measurement indices for the prognostication of patients with heart failure is provided, and suggestions on how these could be measured in clinical practice are considered. In future, studies in humans will be required to draw definitive links between specific splenic measurements and different heart failure manifestations, as well as to determine whether splenic prognostic measurements differ between heart failure classes and etiologies. These contributions will provide a step forward in our understanding of the usefulness of the spleen as a prognostic predictor in heart failure.

Keywords: Cardiosplenic axis; Heart failure; Hemodynamics; Immunity; Prognosis; Spleen.

Fig. 1

Proposed mechanisms of the cardiosplenic axis in heart failure. The cardiosplenic axis can be described as a cycle involving hemodynamic and immune processes. Heart failure is caused by reversible or irreversible damage to cardiac muscle. This tissue damage leads to immune cell recruitment from the circulation, triggering inflammation through cross-talk with the spleen. In terms of hemodynamic changes, the spleen holds a significant amount of the increased intravascular blood volume and regulates fluid distribution. As a result, splenomegaly and increased spleen stiffness are often observed in heart failure. This structural remodeling of the spleen is accompanied by functional remodeling, with changes in the composition of spleen-derived immune cells. Splenic immune cells, such as splenic macrophages, are released into the blood and migrate to the heart. This can lead to cardiac remodeling at the macroscopic and microscopic levels, which may be maladaptive or adaptive. The former can lead to cardiac fibrosis, while the latter is associated with suppression of inflammation in myocardial tissue via cardiac macrophage activity, which supports normalization of cardiac rhythm and suppression of arrhythmia development. These seemingly contradictory mechanisms have antagonistic effects, and their balance may affect cardiac function and prognosis. Owing to these wide-ranging changes, the spleen may be a clinical prognostic indicator in heart failure. For example, changes at the macroscopic level (spleen size and stiffness), as well as at the microscopic level (specific subsets of circulating spleen-derived immune cells), could be utilized as biomarkers to predict the prognosis of patients with heart failure