1IKDT - Institut Kardiale Diagnostik und Therapie GmbH Berlin, Deutschland; 2Deutsches Herzzentrum der Charite (DHZC) Klinik für Kardiologie, Angiologie und Intensivmedizin | CVK Berlin, Deutschland
Background:
The diagnosis of unexplained heart failure (HF) is challenging. Despite advances in treatment, heart failure patients remain at high risk of death, and the course of the disease is often insidious and uncertain. The aim of this study was to assess the prognostic relevance of advanced and differentiated diagnostics in endomyocardial biopsies (EMB) in a large cohort of consecutive patients with virus-negative inflammatory cardiomyopathy (CMi). Intramyocardial inflammation is considered an unfavorable prognostic factor in CMi. However, precise and standardized EMB-based diagnostics for the prediction of long-term course remains elusive.
Methods and Results:
Total cohort included n=3072 patients, n=478 patients were identified with unexplained heart failure and clinical follow-up analyses undergoing EMBs with mean follow-up period of 26 (10-49) months. The median age (interquartile range) was 51 [40.00, 60.00] years, and 67% were males. Coronary artery disease and other possible causes of myocardial dysfunction (valvular heart disease) had been excluded by angiography and echocardiography prior to EMB in all patients. In EMBs myocardial inflammation was assessed and quantified by histology and immunohistology (IH).
Based on calculated cut off values for high risk, Cox regression analysis showed that CD3+ t-cells and MAC-1+ macrophages phenotypes were the leading predictor for mortality and failure to improve, with a Hazard odds ratio (HR) of 1.037 (95% confidence interval CI 0.005-8.035; p<0.001) and a HR of 1.010 (95% confidence interval CI 0.002-4.238; p<0.001), respectively. Importantly, LV-function improvement was attenuated in both, patients with elevated CD3+ levels, and patients with CD3 negative results but increased values of CD45R0+, LFA-1+ and/or MAC-1+, when compared with inflammation negative patients (p<0.0001). Therefore, 26.1% of patients would not have been classified as inflammation-positive according to the conventional definition. Moreover, long-term prognosis was incrementally associated with quantitative inflammatory cell count (CD3+-high ≥20/mm2 group revealed the worst outcome (p<0.0001)).
Conclusions:
Accurate diagnostic quantitative assessment of infiltrate density and characterization of the different infiltrate phenotypes is relevant for predicting of outcome and is a prerequisite for future personalized management and treatment options. The finding of specific inflammatory cells as a prognostic marker and adaptations of new thresholds of diverse phenotypes of infiltrates could be useful in establishing new definitions of cardiac inflammation.