Because the first generation of pulsatile-flow devices was primarily used to bridge the sickest patients to transplantation (bridge-to-transplant therapy), the current generation of continuous-flow ...ventricular assist devices qualifies for destination therapy for patients with advanced heart failure who are ineligible for transplantation. The first-generation devices were associated with frequent adverse events, limited mechanical durability, and patient discomfort due device size. In contrast, second-generation continuous-flow devices are smaller, more quiet, and durable, thus resulting in less complications and significantly improved survival rates. Heart transplantation remains an option for a limited number of patients only, and this fact has also triggered the discussion about the optimal timing for device implantation. The increasing use of continuous-flow devices has resulted in new challenges, such as adverse events during long-term support, and high hospital readmission rates. In addition, there are a number of device-related complications including mechanical problems such as device thrombosis, percutaneous driveline damage, as well as conditions such as hemolysis, infection, and cerebrovascular accidents. This review provides an overview of the evolution of mechanical circulatory support systems from bridge to transplantation to destination therapy including technological advances and clinical improvements in long-term patient survival and quality of life. In addition, recent changes in device implant strategies and current trials are reviewed and discussed. A brief glimpse into the future of mechanical circulatory support therapy will summarize the innovations that may soon enter clinical practice.
It has recently been shown that treatment of animals with antibodies to CD154 (CD40L), allows for prolongation of cardiac allograft survival, but does not inhibit development of graft vasculopathy. ...CD8
+ T cells have been implicated in this effect. In this study we assess the role of CD40–CD154 interactions and CD40-independent CD8
+ T cells in the permanent and complete absence of CD40 by using donors and recipients genetically deficient in CD40.
Hearts from BALB/c CD40
−/− donors were transplanted into C57BL/6 CD40
−/− recipients in the presence or absence of CD8
+ T-cell depletion. At Day 60, hearts were examined for vasculopathy using quantitative morphometry and numbers of infiltrating T cells were counted. The intragraft expression of interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1), interleukin-4 (IL-4), eotaxin and CCR3 was assessed using competitive reverse transcription–polymerase chain reaction (RT-PCR).
In the absence of CD8
+ T-cell depletion, the mean percent intimal occlusion was 28% (with 50% of vessels showing no intimal occlusion). This figure was reduced significantly to 12% and 80% of vessels showing no intimal occlusion in mice receiving anti-CD8 antibody. Depletion of CD8
+ T cells was associated with significantly reduced intragraft IFN-γ, TGF-β1 and CCR3 expression, whereas mRNA production of IL-4 and eotaxin was increased.
Vascular intimal occlusion progresses in the complete absence of CD40–CD154 interactions, albeit to quite a small degree. The residual disease is significantly reduced by anti CD8
+ T-cell treatment, confirming the importance of CD40–CD154-independent CD8
+ T cells in the genesis of this disease.
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