Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome
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Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome. / Escher, Felicitas; Kühl, Uwe; Lassner, Dirk; Stroux, Andrea; Westermann, Dirk; Skurk, Carsten; Tschöpe, Carsten; Poller, Wolfgang; Schultheiss, Heinz-Peter.
In: EUR J HEART FAIL, Vol. 16, No. 10, 10.2014, p. 1066-1072.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome
AU - Escher, Felicitas
AU - Kühl, Uwe
AU - Lassner, Dirk
AU - Stroux, Andrea
AU - Westermann, Dirk
AU - Skurk, Carsten
AU - Tschöpe, Carsten
AU - Poller, Wolfgang
AU - Schultheiss, Heinz-Peter
N1 - © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.
PY - 2014/10
Y1 - 2014/10
N2 - AIMS: 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.METHODS AND 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.
AB - AIMS: 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.METHODS AND 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.
KW - Adult
KW - Aged
KW - Biopsy
KW - Cardiomyopathies/diagnosis
KW - Female
KW - Hemodynamics
KW - Humans
KW - Inflammation/metabolism
KW - Male
KW - Middle Aged
KW - Myocardium/metabolism
KW - Perforin/analysis
KW - Predictive Value of Tests
KW - Prognosis
KW - Ventricular Dysfunction, Left/diagnosis
U2 - 10.1002/ejhf.148
DO - 10.1002/ejhf.148
M3 - SCORING: Journal article
C2 - 25163698
VL - 16
SP - 1066
EP - 1072
JO - EUR J HEART FAIL
JF - EUR J HEART FAIL
SN - 1388-9842
IS - 10
ER -
