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OBJECTIVES The acquired von Willebrand syndrome (AvWS), which is associated with left ventricular assist device support, is caused by the loss of the von Willebrand factor (vWF) high molecular weight multimers (HMWMs). We investigated whether the implantation of the left ventricular assist device HeartMate 3 (HM 3) is superior to the HeartWare ventricular assist device (HVAD) in preserving the multimeric structure of vWF. METHODS In total, 70 patients with implanted HM 3 (n = 35) or HVAD (n = 35) were retrospectively investigated. HMWMs, intermediate molecular weight multimers and low molecular weight multimers were quantified by using a densitometric methodology. vWF antigen, vWF activity and vWF collagen-binding activity, as well as demographic and clinical data, were analysed. RESULTS AvWS, which is characterized by a decrease in vWF HMWMs, was found in 97.1% of patients in the HM 3 group and 100% of patients in the HVAD group. Compared to normal pooled plasma, HM 3 induced a reduction in HMWMs (40.7 ± 8.2% vs 26.7 ± 7.5%, P < 0.01) and an increase in low molecular weight multimers (31.3 ± 11.8% vs 42.7 ± 9.8%, P < 0.01), whereas HVAD patients exhibited an increase in the percentage of intermediate molecular weight multimers (28.0 ± 5.0% vs 38.4 ± 7.7%, P < 0.01) in addition to a decrease in the percentage of HMWM (23.0 ± 11.0%, P < 0.01). A comparison of both left ventricular assist device types showed a difference in vWF multimeric structure (HMWMs: P < 0.01, intermediate molecular weight multimer: P = 0.05, low molecular weight multimer: P = 0.03). Furthermore, vWF activity was elevated in patients with an implanted HM 3 device (153.7 ± 54.4%) compared to those with an HVAD device (126.3 ± 39.7%, P = 0.02). CONCLUSIONS Patients with an implanted HM 3 had more intact HMWMs and a higher vWF activity during device support. This may reduce the manifestation of AvWS in HM 3 patients and could thus lead to a lower bleeding complication rate.

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In our pilot study, we showed different stimulatory effects of ECP on pDCs and cytokines among prophylactic and therapeutic ECP therapy after HTx. Immunological monitoring should be included in a larger clinical study of ECP treatment following HTx and to identify predictable parameters for ECP efficacy.

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Chronic pressure overload due to aortic valve stenosis leads to pathological cardiac hypertrophy and heart failure. Hypertrophy is accompanied by an increase in myocyte surface area, which requires a proportional increase in the number of cell-cell and cell-matrix contacts to withstand enhanced workload. In a proteomic analysis we identified nerve injury-induced protein 1 (Ninjurin1), a 16kDa transmembrane cell-surface protein involved in cell adhesion and nerve repair, to be increased in hypertrophic hearts from patients with aortic stenosis. We hypothesised that Ninjurin1 is involved in myocyte hypertrophy. We analyzed cardiac biopsies from aortic-stenosis patients and control patients undergoing elective heart surgery. We studied cardiac hypertrophy in mice after transverse aortic constriction and angiotensin II infusions, and performed mechanistic analyses in cultured myocytes. We assessed the physiological role of ninjurin1 in zebrafish during heart and skeletal muscle development. Ninjurin1 was increased in hearts of aortic stenosis patients, compared to controls, as well as in hearts from mice with cardiac hypertrophy. Besides the 16kDa Ninjurin1 (Ninjurin1-16) we detected a 24kDa variant of Ninjurin1 (Ninjurin1-24), which was predominantly expressed during myocyte hypertrophy. We disclosed that the higher molecular weight of Ninjurin1-24 was caused by N -glycosylation. Ninjurin1-16 was contained in the cytoplasm of myocytes where it colocalized with stress-fibers. In contrast, Ninjurin1-24 was localized at myocyte membranes. Gain and loss-of-function experiments showed that Ninjurin1-24 plays a role in myocyte hypertrophy and myogenic differentiation in vitro . Reduced levels of ninjurin1 impaired cardiac and skeletal muscle development in zebrafish. We conclude that Ninjurin1 contributes to myocyte growth and differentiation, and that these effects are mainly mediated by N -glycosylated Ninjurin1-24.