AIMS: Recipients of left ventricular assist devices (LVAD) are exposed to increased risk of adverse clinical events. One of the potential contributing factors is non-pulsatile flow generated by LVAD. We evaluated the association of flow patterns in carotid arteries and of increased arterial stiffness with death and cerebrovascular events in LVAD recipients. METHODS AND RESULTS: We analysed data from 83 patients [mean age 54 ± 15 years; 12 women; HeartMate II (HMII), n = 34; HeartMate 3 (HM3), n = 49]. Pulsatile and resistive indexes, atherosclerotic changes in carotid arteries (measured by duplex ultrasound), and arterial stiffness [measured by Endo-PAT 2000 as the augmentation index standardized for heart rate (AI@75)] were evaluated 3 and 6 months after LVAD implantation. Sixteen patients died during follow-up (27.3 months; interquartile range 15.7-44.3). After adjusting for the main variables examined, the pulsatility index measured at 3 months was positively associated with increased hazard ratios (HR) for death and cerebrovascular events [HR 9.8, 95% confidence interval (CI) 1.62-59.42], with HR increasing after adding AI@75 to the model (HR 18.8, 95% CI 2.44-145.50). In HM3 recipients, HR was significantly lower than in HMII recipients (HR 0.31, 95% CI 0.11-0.91), but the significance disappeared after adding AI@75 to the model (HR 0.33, 95% CI 0.09-1.18). CONCLUSIONS: The risk of death and cerebrovascular events in LVAD recipients is associated with increased pulsatility index in carotid arteries and potentiated by increased arterial stiffness. The same risk is attenuated by HM3 LVAD implantation, but this effect is weakened by increased arterial stiffness.

• Klíčová slova
• Clinical events, Mechanical circulatory support, Pulsatility index,
• MeSH
• ateroskleróza * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• podpůrné srdeční systémy * MeSH
• senioři MeSH
• srdeční selhání * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Studying the long-term impact of continuous-flow left ventricular assist device (CF-LVAD) offers an opportunity for a complex understanding of the pathophysiology of vascular changes in aortic tissue in response to a nonphysiological blood flow pattern. Our study aimed to analyze aortic mRNA/miRNA expression changes in response to long-term LVAD support. Paired aortic samples obtained at the time of LVAD implantation and at the time of heart transplantation were examined for mRNA/miRNA profiling. The number of differentially expressed genes (Pcorr < 0.05) shared between samples before and after LVAD support was 277. The whole miRNome profile revealed 69 differentially expressed miRNAs (Pcorr < 0.05). Gene ontology (GO) analysis identified that LVAD predominantly influenced genes involved in the extracellular matrix and collagen fibril organization. Integrated mRNA/miRNA analysis revealed that potential targets of miRNAs dysregulated in explanted samples are mainly involved in GO biological process terms related to dendritic spine organization, neuron projection organization, and cell junction assembly and organization. We found differentially expressed genes participating in vascular tissue engineering as a consequence of LVAD duration. Changes in aortic miRNA levels demonstrated an effect on molecular processes involved in angiogenesis.

• Klíčová slova
• aorta, left ventricular assist device, mRNA, mechanical circulatory support, microRNA,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• messenger RNA genetika   metabolismus   MeSH
• mikro RNA genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• onemocnění aortální chlopně etiologie   metabolismus   patologie   MeSH
• podpůrné srdeční systémy škodlivé účinky   MeSH
• regulace genové exprese * MeSH
• senioři MeSH
• srdeční selhání patologie   chirurgie   MeSH
• stanovení celkové genové exprese MeSH
• transplantace srdce škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA MeSH
• mikro RNA MeSH

INTRODUCTION: Changes in circulating CD34+CD45low stem cells (SC) and CD34+CD45low+KDR+ endothelial progenitor cells (EPC) may reflect pathological endothelial activation. Non-pulsatile/continuous-flow left ventricular assist devices (CF-LVAD) can enhance this process. The aim of this study was to analyse the impact of 12-month CF-LVAD treatment on SC and EPC. METHODS: We analysed changes in SC and EPC from the pre-implantation period up until 12 months after implantation over 3-month intervals in 14 patients. Data from 12 patients with heart failure (HF) and from 13 healthy volunteers were used as controls. RESULTS: Baseline EPC were significantly higher in CF-LVAD and HF patients than in healthy controls, substantially decreasing 3 months after CF-LVAD implantation and then returning to high baseline values at 12 months. CONCLUSIONS: Changes in circulating SC and EPC may reflect pathological endothelial activation after CF-LVAD implantation.

• Klíčová slova
• continuous flow, endothelial damage, endothelial progenitor cells, mechanical circulatory support, stem cells,
• Publikační typ
• časopisecké články MeSH