Hypersplenism: an independent risk factor for myocardial remodeling in chronic heart failure patients

During the progression of chronic heart failure (CHF), decreased cardiac functioning is often associated with congestion in the inferior vena vein, which in turn induces splenomegaly and subsequent hypersplenism. Hypersplenism has been shown to exacerbate endothelial dysfunction and adverse cardiac remodeling in HF mice. However, it is unknown whether this effect also occurs in CHF patients with hypersplenism. Here, we compared different patterns of myocardial remodeling between patients with and without hypersplenism.

33 CHF patients with hypersplenism were selected and carefully examined. Clinical data and baseline hemogram measurements were included in the evaluation. Another 35 CHF patients were randomly chosen as controls. All patients received formal HF treatment to ameliorate their symptoms and to preserve heart structure and functioning. Peripheral blood-derived endothelial progenitor cells (EPCs) were cultured, and the experimenters were blinded to the patients' clinical characteristics. The biological properties of the cells were then compared. The groups were also compared in terms of the free plasma hemoglobin and heme levels, endothelial adhesion molecule expression, left ventricular ejection fraction (LvEF) and cardiovascular events (re-PCI, re-myocardial infarction, stent thrombosis, stroke and death due to cardiovascular or vascular causes).

The free plasma hemoglobin and heme levels were significantly higher in the CHF patients with hypersplenism compared with the controls (P<0.001). Additionally, the CHF patients with hypersplenism had increased levels of VCAM-1, ICAM-1, P-selectin and E-selectin (P<0.001). Echocardiography revealed a significant reduction in the LVEF in these patients compared with the controls at the 24(th) month (P=0.013). During a mean follow-up period of 24±1 months, cardiovascular events were observed in 16 patients in the CHF with hypersplenism group and 9 patients in the control group. Univariate Kaplan-Meier analysis further revealed a significant difference between the groups (P=0.021). The mRNA levels of endothelial NO synthase enzyme (eNOS) in EPCs from the CHF patients with hypersplenism were significantly lower than those in the control subjects (P<0.001). We also observed decreased proliferation potential of EPCs from the CHF patients with hypersplenism (P<0.001). Further, a significant increase in TUNEL(+) EPCs was observed in the CHF patients with hypersplenism after 6 h of stimulated ischemia compared with the control subjects (P<0.001).

CHF patients with hypersplenism are susceptible to myocardial remodeling. Increased oxidative stress and endothelial dysfunction caused by excess free plasma hemoglobin and heme may partially explain this causality.