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Background Clinical relevant cerebrovascular events (CVE) following transcatheter aortic valve implantation (TAVI) still remain a devastating complication associated with mortality and severe impairments. Therefore, identification of particularly modifiable predictors of this complication is clinically relevant and an important step for planning preventive strategies. Methods A total of 985 patients who underwent trans-femoral TAVI for aortic valve stenosis in our institution from February 2008 to January 2015 were considered. The influence of demographics, clinical and procedural data on the occurrence of CVE was assessed with a competing risk model with death as competing event. Clinical events were defined according to VARC-2 criteria. Results At a median follow-up of 838days, 95% CI 807–892, 59 patients experienced any CVE (5.9%) and the overall cumulative mortality rate was 46.1%. CVEs mainly occur later than 30days after TAVI (47.5%), 88.1% of them were of ischemic origin and 52.5% were disabling events. Independent predictors of CVEs were age (hazard ratio 1.05; 95% CI 1.01 to 1.09), history of CVE (hazard ratio 2.54; 95% CI 1.39 to 4.63) and use of balloon post-dilation (hazard ratio 1.85; 95% CI 1.08 to 3.18). Conclusion In patients undergoing TAVI incidence of clinically relevant CVEs is frequent with half of the events occurring after the first 30days post-TAVI. Identification of balloon post-dilation as the only modifiable predictor of CVE risk at mid-term, urges its cautious performance after prosthesis implantation. ClinicalTrials.gov identifier NCT02289339.

Objective In animal models, G-CSF based progenitor cell mobilization combined with a DPP4 inhibitor leads to increased homing of bone marrow derived progenitor cells to the injured myocardium via the SDF1/CXCR4 axis resulting in improved ejection fraction and survival after acute myocardial infarction (AMI). Research design and methods After successful revascularization in AMI, 174 patients were randomized 1:1 in a multi-centre, prospective, placebo-controlled, parallel group, double blind, phase III efficacy and safety trial to treatment with G-CSF and Sitagliptin (GS) or placebo. Diabetic and non-diabetic patients were included in our trial. The primary efficacy endpoint hierarchically combined global left and right ventricular ejection fraction changes from baseline to 6months of follow-up (Δ LVEF , Δ RVEF ), as determined by cardiac MRI. Results At follow-up Δ LVEF as well as Δ RVEF did not differ between the GS and placebo group. Patients in the placebo group had a similar risk for a major adverse cardiac event within 12months of follow-up as compared to patients under GS. Conclusion Progenitor cell therapy comprising the use of G-CSF and Sitagliptin after successfully revascularized acute myocardial infarction fails to show a beneficial effect on cardiac function and clinical events after 12months. (EudraCT: 2007–003,941-34; ClinicalTrials.gov: NCT00650143, funding: Heinz-Nixdorf foundation).

Aims The aims of this trial were to investigate the effect of granulocyte colony-stimulating factor (G-CSF) on left-ventricular ejection fraction and event-free survival in patients suffering from sub-acute myocardial infarction (STEMI). Methods We enrolled 44 patients suffering from sub-acute STEMI with late revascularization achieved by percutaneous coronary intervention (PCI). Patients were randomized to receive either G-CSF (Filgrastim) at a dose of 10 μg/kg body weight/day subcutaneously or placebo. Changes of global and regional cardiac function from baseline (1 week after PCI) over 1 and 3 months to 12 months of follow-up were analyzed by magnetic resonance imaging. Results Ejection fraction improved in G-CSF treated patients from 41.1±11.9% to 47.1±11.9% (3 months) and decreased slightly to 45.7±15.1% after 1 year. Ejection fraction also improved in the placebo group from 43.8±9.0% to 49.5±11.8% (3 months) and decreased slightly to 42.9±15.4% after 1 year (1 year MRI follow-up was performed in 23 out initial 44 patients). There was no significant difference between the two groups at any time point. Other parameters such as infarct size, myocardial perfusion, left ventricular end-diastolic and end-systolic volumes were not different between the two groups. Event-free survival of such as death, (re) myocardial infarction or acute coronary syndromes, coronary artery bypass grafting and target lesion revascularization was not significantly different between both groups. Conclusions G-CSF administration after sub-acute STEMI is feasible and safe but does not improve myocardial function or survival when used as a single substance.

Aims Our pre-clinical studies demonstrated that G-CSF based stem cell mobilization in combination with genetic or pharmaceutical CD26/DPP-IV inhibition after acute myocardial infarction leads to improved cardiac homing of stem cells, enhanced heart function and increased survival. Thereupon, we initiated a phase III, multi-centre, randomised, placebo-controlled efficacy and safety study ( n =100) analyzing the effect of combined application of G-CSF and Sitagliptin, which is a clinically admitted, anti-diabetic DPP-IV-inhibitor, after acute myocardial infarction ("SITAGRAMI-Trial"; EudraCT Number: 2007-003941-34). Methods The primary objective of the study is to assess myocardial regeneration by improved myocardial homing of mobilized stem cells, as measured by cardiac function using MRI analysis. In this paper, we report on the study design and a planned first interim-analysis on safety issues without unblinding. Results During the first 6weeks of follow-up, only two major adverse cardiac events occurred (one de novo stenosis and one instent-restenosis) in the first 36 patients. Presumably, they were not related to any study medication. No other side effects like headache, bone pain, hypoglycaemias etc. were observed. Furthermore, no myocardial infarction or death occurred in any patient. Thus, the rate of serious adverse events lay within the expected range. Conclusions Our data demonstrate that the combined application of Sitagliptin and G-CSF seems to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future.