title: Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome.
abstract: OBJECTIVE
  Intramyocardial inflammation is considered an adverse prognostic factor in inflammatory cardiomyopathy (CMi). However, the precise nature of immune system factors relevant for the prediction of long-term course remains elusive. The aim of this study was to analyse the prognostic relevance of perforin in a large cohort of patients with CMi.
  
  
  RESULTS
  We investigated 495 consecutive patients with suspected CMi, undergoing endomyocardial biopsies (EMBs), and examined haemodynamic measurements after a long follow-up period (interquartile range 10.2-37.1 months). In EMBs, myocardial inflammation was assessed by histology and immunohistology. At follow-up, 388 patients (Group I) showed stable mild dysfunction or significant improvement, with LVEF rising from 46.2 ± 14.8% to 64.3 ± 12.3% (P < 0.0001). Lack of improvement of LV function or significant deterioration of LVEF from 42.1 ± 14.2% to 32.3 ± 11.6% (P < 0.0001) was observed in 107 patients (Group II). Multivariable statistical analysis of LVEF and immunohistochemical parameters in all patients revealed that the single most important predictor of LVEF development was detection of perforin in EMBs, with an odds ratio (OR) of 7.922 [95% confidence interval (CI) 4.380-14.326; P < 0.001] for deteriorating LVEF. Importantly, baseline LVEF (OR 0.962), LV end-diastolic diameter (OR 1.847), and other immmunohistochemical parameters (CD3, Mac-1, CD45R0, LFA-1, HLA-1, and ICAM-1) made minor or insignificant contributions to LVEF course in these 495 patients.
  
  
  CONCLUSIONS
  In this EMB-based analysis of the long-term course of CMi we identified, for the first time, that detection of perforin in the myocardium is a key predictor of LVEF course.
authors.affiliation: Department of Cardiology and Pneumology, CBF, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Escher
authors.forename: Uwe
authors.initials: U
authors.lastname: Kühl
authors.forename: Dirk
authors.initials: D
authors.lastname: Lassner
authors.forename: Andrea
authors.initials: A
authors.lastname: Stroux
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.forename: Carsten
authors.initials: C
authors.lastname: Skurk
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D054353:Perforin / Q000032:analysis / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology
chemical_list: D054353:Perforin
keywords: Cardiomyopathy; Inflammatory; Perforin; Prognosis