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Background:Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF. Methods and results:We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair. Conclusion:CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous left ventricular assist devices in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) is evolving. The aim of the study was to assess the long-term outcome of patients with AMICS depending on early initiation of Impella CP ® support prior to a percutaneous coronary intervention (PCI)., Methods: We retrospectively reviewed all patients who underwent PCI and Impella CP ® support between 2014 and 2016 for AMICS at our institution. We compared survival to discharge between those with support initiation before (pre-PCI) and after (post-PCI) PCI., Results: A total of 73 consecutive patients (69±12 years old, 27.4% female) were supported with Impella CP ® and underwent PCI for AMICS (34 pre-PCI vs . 39 post-PCI). All patients were admitted with cardiogenic shock, and 58.9% sustained cardiac arrest. Survival at discharge was 35.6%. Compared with the post-PCI group, patients in the pre-PCI group had more lesions treated ( p =0.03), a higher device weaning rate ( p =0.005) and higher survival to discharge as well as to 30 and 90 days after device implantation, respectively (50.0% vs . 23.1%, 48.5% vs . 23.1%, 46.9 vs . 20.5%, p < 0.05). Kaplan-Meier analysis showed a higher survival at one year (31.3% vs . 17.6%, log-rank p -value=0.03) in the pre-PCI group. Impella support initiation before PCI was an independent predictor of survival up to 180 days after device implantation., Conclusions: In this small, single-centre, non-randomized study Impella CP ® initiation prior to PCI was associated with higher survival rates at discharge and up to one year in AMICS patients presenting with high risk for in-hospital mortality.

Background: Monocytes (Mo) are the most important mediators in arteriogenesis. Previous results from our group demonstrated the great potential of allogenic Mo transplantation for improving collateral vessel growth, which appeared to be due to a considerable host vs. graft reaction. To prove this hypothesis and introduce this new method in clinical practice, we performed transplantation of human Mo (HuMo) in a mouse model. Methods and results: We ligated the femoral artery of BALB/c mice and transplanted Mo via the tail vein. Perfusion was measured by laser Doppler perfusion imaging (LDPI). We also performed clinical scoring based on behavior, wound healing, signs of inflammation and mobility of the ligated extremity. Finally, arteriogenesis and angiogenesis were examined histologically and by quantitative RT-PCR of the hind limb musculature. LDPI increased within one week after ligation when HuMo were transplanted and increased further up to day 21 (0.63±0.12 (n=12) in HuMo vs. 0.50±0.12 (n=17) in the control group (P<0.01)). A histological evaluation showed significantly more collateral arteries within the adductor muscles after HuMo transplantation. The promotion of collateral vessel growth after HuMo transplantation resulted in better clinical scores (0.33±0.26 (n=12) vs. 3.3 (n=9), SEM; P<0.01). Conclusions: Transplantation of HuMo improves collateral vessel growth and clinical outcomes in mice. These results verify our hypothesis that controlled triggering of the inflammatory mechanism resulted in collateral vessel growth by a local host vs. a graft reaction in the ischemic hind limbs and could represent a further step in the development of a clinical strategy for promoting arteriogenesis., Competing Interests: None.

Serine proteases and G-protein-coupled receptors have been studied extensively as effectors of cell death. However, their roles in myocardial infarction have not been determined. In this study, we investigated the influence of the plasminogen activator system involving urokinase and urokinase receptor on necrosis after acute myocardial infarction. Myocardial infarction and reperfusion were induced in mouse hearts using the in vitro Langendorff model. DNA fragmentation and cleaved caspase-3 activity in urokinase- (uPA -/- ) and urokinase receptor-knockout mice (uPAR -/- ) were determined and compared with those in wild-type mice using in situ nick-end DNA labeling (TUNEL) and enzyme-linked immunosorbent assays, respectively. Infarct sizes were determined using propidium iodide and fluorescent microspheres. Following regional ischemia and reperfusion, a significant increase in the number of TUNEL-positive nuclei was observed in the ischemic zone in mouse hearts and to a lesser degree in regions remote from the ischemic area in wild-type, uPAR -/- , and uPA -/- groups compared with those in directly removed hearts. No significant differences were observed between uPAR -/- and wild-type mice. Conversely, a significant reduction in DNA fragmentation was observed in ischemic and nonischemic regions after acute myocardial infarction in uPA -/- mice when compared with that in wild-type and uPAR -/- groups. The resulting infarct sizes were significantly smaller in uPA -/- mice than in uPAR -/- and wild-type mice. These data demonstrated the involvement of uPA, but not uPAR, in protecting against necrosis during acute myocardial infarction., Competing Interests: None.