Impact of a durable left ventricular assist device on inflammation and cardiac remodelling in subjects with advanced heart failure.

BACKGROUND

This study aimed to explore the association of long-term left ventricular assist device (LVAD) support with changes in inflammation and cardiac remodelling in subjects with advanced heart failure (HF).

METHODS

A single-centre prospective observational trial was conducted in 16 consecutive subjects with advanced HF who were indicated for implantation of HeartMate 3 LVAD. Blood samples were collected both during the procedure (V1) and 12 months postoperatively (V2) for comprehensive analysis. Additionally, in a subgroup of seven LVAD subjects listed for heart transplantation (HTx), a histological examination was performed on myocardial samples obtained during LVAD implantation and from the explanted heart following HTx.

RESULTS

LVAD implantation was associated with reductions in brain natriuretic peptide (324.7±47.0 vs 124.6±50.3 pg/mL) and C reactive protein (15.2±3.8 vs 6.0±1.3 mg/L) levels. Decreased inflammation markers coincided with reduced levels of lymphocyte- and macrophage-derived cytokines and their stimulating factors. LVAD implantation was associated with modulation of circulating biomarkers related to negative cardiac remodelling processes, including reductions in fibrosis- and remodelling-associated mediators (Extracellular Matrix Metalloproteinase Inducer, fibroblast growth factor (FGF)-2, FGF-19, receptor for advanced glycation endproducts, suppression of tumourigenicity 2, interleukin 27) and angiogenesis-related factors (stromal cell-derived factor-1α, growth differentiation factor (GDF)-15, somatotropin, vascular endothelial growth factor, angiopoietin 1, hepatocyte growth factor). In parallel, markers of metabolism and systemic catabolic state were significantly modulated, with decreases in GDF-15, somatotropin, trefoil factor 3 and resistin and increases in leptin levels. Histological analysis of myocardial samples available from a subgroup of subjects showed reduced macrophage infiltration following LVAD implantation.

CONCLUSIONS

Long-term LVAD support was associated with improved biochemical and haematological profiles and with coordinated changes in circulating markers of inflammation, metabolism and cardiac remodelling. These exploratory findings provide further insight into the biological changes associated with durable mechanical unloading in subjects with advanced HF.