Impact of cellular myocardial infiltration on clinical outcome in non-ischaemic heart failure

Abstract

AimsSo far, little has been known on whether myocardial inflammatory infiltration influences heart failure (HF) progression. Thus, the aim of this study was to test the impact of intramyocardial infiltration on clinical outcomes.MethodsBiopsy samples from 358 patients with stable HF secondary to dilated cardiomyopathy were studied. Immunohistochemistry for lymphocyte (CD3) and macrophage (CD68) markers was performed and counted. After a 1-year follow-up, patients were classified as improved based on the predefined definition of improvement. The clinical data were collected from 324 patients (90.5%).ResultsAccording to the predefined definition of improvement, 133 patients improved (41.0%) but 191 remained unchanged or deteriorated (58.9%). After a 12-month follow-up, the OR with 95% CI of counts of myocardial inflammatory CD68-positive ≥4 cell/high power field (HPF) compared with CD68-positive <4 cell/HPF for lack of improvement was 1.91 (1.65–2.54). However, the number of CD3 positive cell infiltration had no impact on clinical outcome after a 1-year follow-up. In the baseline study, a reasonably negative correlation was found between the number of CD68 positive cells and troponin T (r=−0.39; p<0.001 by Spearman’s r). This was corroborated with a low negative correlation between these cells and myocardial form of creatine kinase (CK-MB) fraction (r=−0.27; p=0.006). There was no correlation between CD3 and CD68 positive cells (Spearman’s r; r=−0.17, p=0.16).ConclusionsThe current results provide evidence that high macrophage counts may be a predisposing factor for HF progression.

Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy

“…It has generally been assumed that chronic immune response may play an important role in the development and disease progression [2,4]. Accordingly, we recently reported that a higher number of CD68-positive macrophages in biopsy specimens signi cantly predicted clinical progression of HF due to DCM in patients after one-year follow-up [5]. These observations con rmed the previously reported impact of macrophages on the prognosis in DCM [6].…”

“…the rst was characterized by their presence in the interstitial space, without direct contact with the surrounding cardiomyocytes and the second showed macrophages attached to injured cardiomyocytes using immunohistochemistry. Both of these forms were inversely proportional to cTnT serum levels, which suggested insu cient clearance of phagocytic activity of these cells in DCM patients [5].…”

“…On the other hand, myocyte injury per se is a pathophysiological heterogeneous mechanism, including local ischemia as a major cause [22,23,24]. Other authors and our previous paper recently reported that a higher number of CD68-positive macrophages in biopsy specimens signi cantly predicted clinical progression of HF due to DCM in patients after one-year follow-up [5,6]. Moreover, accumulated clinical and experimental data suggest that chronic in ammation may be responsible for the development and disease progression in at least some of them [4].…”