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Aims: Accumulation of extracellular matrix (ECM) is known to play a crucial role in the pathophysiology of heart failure (HF). However, its prognostic relevance is poorly investigated., Methods and Results: A total of 73 HF patients who underwent LV endomyocardial biopsy were enrolled in our study. ECM area was quantified by TissueFAXS and ImageJ software. Patients were followed-up at 6-month intervals. The study endpoint was defined as hospitalization for a cardiac reason and/or cardiac death. Furthermore, the influence of the ECM on invasively measured haemodynamic parameters was tested. During a median follow-up period of 9.0 months, 34 patients (46.6%) reached the combined endpoint. Median ECM area was 30.5%. Patients with ECM area ≥30.5% experienced significantly more events (67.6% vs. 25.0%, P < 0.001) in comparison with patients with an ECM area <30.5%. ECM area was independently associated with outcome in the total HF cohort [hazard ratio (HR) 1.041, 95% confidence interval (CI) 1.017-1.066, P = 0.001] as well as in HF patients with preserved (HR 1.079, 95% CI 1.001-1.163, P =0 .046) or reduced ejection fraction (HR 1.149, 95% CI 1.036-1.275, P = 0.009). Positive correlations were found between ECM area and LV end-diastolic pressure (P = 0.021, R = 0.303), pulmonary artery wedge pressure (P = 0.042, R = 0.249), mean pulmonary arterial pressure (P = 0.035, R = 0.258), as well as right atrial pressure (P = 0.003, R = 0.353)., Conclusion: ECM area within the LV myocardium correlates with left and right heart haemodynamics and is associated with clinical course in various non-ischaemic HF types., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are beneficial in patients with heart failure, yet their role after heart transplantation (HTx) remains ambiguous. Particularly, the effects of ACEis on plasma and cardiac metabolites of the "classical" and "alternative" renin-angiotensin system (RAS) in HTx patients are unknown., Methods: This cross-sectional study used a novel mass spectrometry-based approach to analyze plasma and tissue RAS regulation in homogenates of heart biopsy specimens from 10 stable HTx patients without RAS blockade and in 15 patients with ACEi therapy. Angiotensin (Ang) levels in plasma and Ang formation rates in biopsy tissue homogenates were measured., Results: Plasma Ang II formation is exclusively ACE dependent, whereas cardiac Ang II formation is primarily chymase dependent in HTx patients. ACEi therapy substantially increased plasma Ang-(1-7), the key effector of the alternative RAS, leaving plasma Ang II largely intact. Importantly, neprilysin and prolyl-carboxypeptidase but not angiotensin converting enzyme 2 are essential for cardiac tissue Ang-(1-7) formation., Conclusion: ACE is the key enzyme for the generation of plasma Ang II, whereas chymase is responsible for cardiac tissue production of Ang II. Furthermore, our findings reveal that neprilysin and prolyl-carboxypeptidase are the essential cardiac enzymes for the alternative RAS after HTx. These novel insights into the versatile regulation of the RAS in HTx patients might affect future therapeutic avenues, such as chymase and neprilysin inhibition, beyond classical Ang II blockade., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF-1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6-h observation period, ATG (1 mg/kg BW) was given intravenously. After 45 min, the donor hearts were removed. Proinflammatory markers IL-2 and IL-6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL-2 expression (BD Control vs. BD ATG, P = 0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL-2 levels in the myocardium. We observed a reduction of IL-6 deposition in media cells in ATG-treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL-2-directed inflammatory response and possible reduction of IL-6-mediated vascular changes., (© 2016 Steunstichting ESOT.)