Inflammasome and pro-inflammatory cytokines in the pathophysiology of idiopathic dilated cardiomyopathy before and after ventricular assist device (VAD) insertion

Dilated cardiomyopathy (DCM) represents the most common cardiomyopathy worldwide. The familial type, named “idiopathic”, account for 20-48% of all cases. An accumulating body of literature indicates that the pathophysiologic mechanism of genetic DCM may be much more complex than expected involving the finely tuned mechanism of protein homeostasis. Intracellular proteins aggregation seems to be at the base of the activation of the inflammasome bringing to the release of inflammatory cytokines, such as IL1ß, IL 4 and IL 6 and may be involved in the clinical deterioration of patients affected by idiopathic DCM. For this purpose the cytokine levels of surgical patients affected by idiopathic terminal DCM were compared with healthy controls to assess the hypothesis that pro inflammatory status plays a role on the natural history of the DCM and to see if the VAD insertion was related to a reduction of the inflammasome activation. 10 idiopathic DCM affected patients who underwent VAD insertion were admitted to the study. The mean follow up was 377 days. The analysis of the circulatory biomarkers showed statistically significant higher concentrations of IL1ß, IL4, IL6 and of IL1ß/ IL1RA ratio in the DCM group. The follow up analysis of the circulatory BNP levels showed that after the VAD insertion there was a BNP non-significant augmentation during the first post-operatory week and then a reduction during the long-term follow-up while IL 1 and the IL4 levels did not show significant variation. The correlation analysis between the different biomarkers found that BNP significantly correlate in a negative way to IL1ß (P=0.0462; Spearman r = -0.4292), IL4 (P=0.004; Speerman r = -0,692), and Leptin (P=0.026; Speerman r = -0,462) and in a positive way to IL 6 (P=0.026; Speerman r = 0,475). Taken together, these results suggest that in end stage heart failure idiopathic DCM patients there is a higher concentration of pro inflammatory cytokines that can play a role on the progression of the disease. The reduction of the volume overload done by the VAD does not reverse the mechanisms of chronic inflammation