Objective: To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression.
Methods: Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor α (TNFα), interleukin (IL) -1β, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM.
Results: Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFα, IL-1β, and IL-6 gene expression was detected in both groups. However, TNFα gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFα gene expression. In patients with AS there was a strong inverse relation between circulating TNFα and TNFα gene expression (r = −0.685, p = 0.014), between circulating TNFα and IL-1β gene expression (r = −0.664, p = 0.018), and between soluble TNF receptor 2 and TNFα gene expression (r = −0.685, p = 0.020). Myocardial gene expression of TNFα was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFα gene expression than were patients with well compensated DCM (p = 0.011).
Conclusion: TNFα gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFα gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.
Keywords: cardiomyopathy, cytokines, gene expression, heart failure