Influence of Left Ventricular Unloading on Activated Macrophages and Cardiac Remodeling

A minor proportion of dilated cardiomyopathy patients on long-term VAD support for end stage heart failure can be weaned from mechanical assistance after functional recovery of the native heart. Although underlying pathophysiological mechanisms implicated in reverse remodeling remain unclear, it is known that elevated levels of interstitial fibrosis (IF) often correlate with deterioration of left ventricular function and levels of interstitial macrophages often correlate with the level of interstitial fibrosis (IF).

We investigated the effect of a subset of macrophages, including those known to promote chronic (ongoing) inflammation (stabilin-1), and the immunohistochemical phenotype of freshly infiltrating macrophages (CD14) on the level of IF and therefore on the level of cardiac remodeling.

We investigated formalin-fixed paraffin-embedded left apical endomyocardial tissue samples obtained from patients at time of VAD implantation and explantation of 12 patients (age range 1-60 years) between 01/2010 and 10/2013 for level of macrophages and fibrosis levels.

Results showed the level of macrophages supporting chronic inflammation and freshly infiltrating macrophages to decrease consistently following left ventricular mechanical unloading, although statistical significance was closely missed. IF showed increaed levels (p=0.007).

In conclusion, macrophages appear to promote cardiac remodeling. Probably due to the small subset of patients, this study failed to identify a specific macrophage subtype suitable to predict the outcome of VAD therapy, but our findings merit further investigation in this field.