Genomics of Myocardial Recovery in Patients with Mechanical Circulatory Support

• Published in: The Journal of heart and lung transplantation Vol. 32; no. 4; p. S229
• Main Authors: Milting, H, Kassner, A, Oezpeker, C, Morhuis, M, Bohms, B, Boergermann, J, Gummert, J
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2013
• Subjects: Surgery
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2013.01.582

Purpose Ventricular assist devices (VAD) are implanted in patients for bridging to heart transplantation (BTT) or nowadays in an increasing number of cases for destination therapy. However, about 2% of the patients develop spontaneously myocardial recovery for unknown reasons (BTR). Currently, myocardial recovery is not predictable, since reliable biomarkers are lacking. The aim of our study was the identification of novel biomarkers for myocardial recovery. Methods and Materials Total-RNA from left ventricular (LV) samples of 7 rejected donor hearts (NF), and LV-apex samples of 7 BTR- and 7 BTT-patients from VAD-implantation were isolated. NF-, BTR-, BTT-patients were matched according to age, gender and etiology. We analysed the myocardial transcriptome using Affymetrix-chips for the identification of secretory proteins. Differentially expressed transcripts were confirmed by real time RT-PCR. Expression profiling was evaluated by principal component analysis (PCA) and target gene identification. Transcripts of secretory proteins were analysed by enzyme linked immunosorbant assay (ELISA) for differences in the plasma at the time VAD-implantation. Results The principal component analysis (PCA) did not reveal clear separation of the HF samples. However, transcripts related to the immune system like plasma TNF-alpha stimulated gene 14 (TSG14) and interferon inducible protein 10kD (CXCL10) are by trend increased in BTR-samples compared to controls. Of note, TSG14 and CXCL10 were not different between BTR and BTT patients. However, both proteins were significantly elevated in VAD-patients before device implantation. Conclusions Molecular differences in the myocardium of patients with and without myocardial recovery are small. However, the identified transcripts such as TSG14 or CXCL14 related to immune-modulatory functions may indicate an uncomplete cardiac remodelling in patients weaned from the device. Both markers are significantly increased in heart failure patients.