Background: Heart failure, arrhythmia and other clinical cardiac complications with dilated cardiomyopathy (DCM) are considered to be associated with the severity of ventricular fibrosis regardless of the potential causes of DCM. Recent reports have provided some evidences that persistent myocardial inflammation may contribute to the progression of ventricular fibrosis. Purpose of this study is to investigate which type of inflammatory cells is the most responsible for the ventricular fibrotic development in patients with DCM.
Method: 182 consecutive patients with DCM, who underwent right ventricular endomyocardial biopsy in 2005 and 2009 at our institution, were enrolled. We stained their biopsy samples with antibodies specific for CD3 (T lymphocytes), CD68 (macrophages), CD163 (M2 macrophages), and CD209 (dendritic cells) to count the number of infiltrating cells. Myocardial collagen area fraction (CAF) was semi-quantitatively measured in Masson’s trichrome-stained sections. We also obtained each patient’s clinical data in medical records for up to 9 years.
Results: Median (interquartile range) numbers of myocardial CD3, CD68, CD163 and CD209 positive cells infiltrates were 8.1 (4.0-14.2)/mm2, 22.3 (12.1-36.0)/mm2, 6.5 (2.0-14.0)/mm2 and 18.0 (8.3-30.0)/mm2 respectively. CAF ranged from 2.7% to 39.8% (mean±SD, 15.1±6.8 %). Kaplan-Meier survival curves demonstrated that CAF above the cut off values (> 18%) was associated with poor long term prognosis in terms of cardiovascular death and heart transplantation (log-lank p=0.002). CAF was correlated with the count of CD163 and CD209 positive cells (p<0.0001, r=0.32, and p<0.0001, r=0.30), although it was not correlated with the count of CD3 and CD68 positive cells (p=0.14, p=0.60). Multiple regression analysis revealed that the CD163 positive cell count was an independent determinant of CAF (p <0.001). Furthermore, the count of CD209 positive cells was strongly correlated with that of CD163 positive cells (p<0.0001, r=0.71).
Conclusions: Long-term outcome of DCM patients with high CAF was significantly poor. Increased infiltration of M2 macrophage was independently associated with CAF. There was a strong association between the counts of M2 macrophages and dendritic cells.