Abstract 16561: Mechanical Unloading via Left Ventricular Assist Device Implantation Ameliorates Systemic and Adipose Tissue Inflammation and Increases Adipocyte Size in Patients With Advanced Heart Failure
Introduction: Heart failure (HF) is a complex multi-organ syndrome characterized by systemic inflammation, insulin resistance (IR) and peripheral hypoperfusion. Recent studies have implicated local adipose tissue hypoxia and macrophage infiltration in contributing to systemic inflammation, while reductions in adipocyte size have been linked to IR. The effects of advanced HF on adipose tissue have not been characterized.
Hypothesis: We hypothesized that advanced HF would be associated with similar alterations in adipose tissue biology and that hemodynamic correction through implantation of a left ventricular assist device (VAD) would reverse these changes.
Methods: Serum was collected from 36 subjects with advanced HF before and after VAD implantation and 10 control subjects. Adipose tissue was collected from 8 control subjects (mean BMI: 33.9) and 8 subjects before and after VAD implantation (mean BMI: 26.5). IR was calculated by HOMA-IR and adipose tissue macrophages detected by immunostaining against CD68.
Results: Compared with controls, patients with HF (mean age: 59±10 yrs, ejection fraction: 17±5%) had increased fasting plasma glucose (5.1±0.9 vs.6.5±1.9 mM; p<0.05), HOMA-IR (1.0±0.6 vs.6.3±5.8; p<0.05) and TNFa levels (1.0±0.1 vs. 4.6±0.9 pg/ml; p<0.05). VAD implantation (mean duration 129±99 days) did not change BMI, but normalized IR by HOMA-IR (3.6±2.9, p<0.05), reduced fasting plasma glucose (5.5±1.2 mmol/L; p<0.05) and TNFa levels (2.3±0.4 pg/ml; p<0.05). Compared to controls, adipocytes in patients with HF had increased macrophage infiltration (6.4±0.9 vs. 8.2±0.7 per high power field; p<0.01). VAD implantation reduced macrophage infiltration (-33%; p<0.05), increased adipocyte area 29% and increased cell size heterogeneity.
Conclusion: Our data show that adipose tissue inflammation and IR develop in advanced HF and these alterations are partially reversible after hemodynamic correction via VAD implantation. These findings suggest a novel and reversible role of adipose tissue inflammation and IR in the pathogenesis of systemic metabolic derangements in patients with advanced HF.
- © 2011 by American Heart Association, Inc.