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The temporary total artificial heart (TAH-t) has emerged as an effective bridge to transplantation for individuals with biventricular failure. Implantation of a TAH-t creates a hypercoagulable state requiring a multidrug approach that includes low-dose unfractionated heparin (UFH) in order to minimize thromboembolism. A concern with UFH is the development of heparindependent antibodies, which develop in up to 50% of patients receiving the drug as part of cardiopulmonary bypass. If UFH therapy continues postoperatively, the risk of heparin-induced thrombocytopenia approaches 3%. Small investigations have demonstrated that bivalirudin, given as a bolus of 0.75-1 mg/kg followed by an infusion at 1.75-2.5 mg/kg/hour, is an effective alternative to UFH for therapeutic anticoagulation during coronary artery bypass surgery, valve replacement, or both. We describe a series of five adults (age range 24-58 yrs) who received bivalirudin as an alternative to low-dose UFH after TAH-t implantation. None of the patients had documented heparin-induced thrombocytopenia. Treatment was started at the discretion of the treating physician, and adjustments were based principally on the results of thromboelastography. Additional general monitoring included activated partial thromboplastin time, prothrombin time, international normalized ratio, fibrinogen, D-dimer, platelet count, hemoglobin, hematocrit, and platelet aggregation studies. Bivalirudin therapy was continued until successful warfarin implementation. All five patients received bivalirudin in addition to standard antithrombotic therapy. Bivalirudin treatment started at a dosage of 0.005 or 0.01 mg/kg/hour with titration to maintain normocoagulability, which occurred (without concomitant warfarin therapy) within the dosage range of 0.01-0.02 mg/kg/hour. Duration of TAH-t implantation was a mean of 38.8 days (range 25-60 days), and bivalirudin was continued for a mean of 15.2 days (range 7-24 days). No major hemorrhagic events occurred during treatment, and all patients successfully transitioned to warfarin therapy. Low-dose bivalirudin, as an alternative to UFH, maintained normocoagulability after TAH-t implantation. Further investigation is warranted to define the role and dosing of bivalirudin in this situation. [ABSTRACT FROM AUTHOR]

Mast-cell expressed membrane protein-1 (MCEMP1) is higher in patients with idiopathic pulmonary fibrosis (IPF) with an increased risk of death. Here we aimed to establish the mechanistic role of MCEMP1 in pulmonary fibrosis. We identified increased MCEMP1 expression in classical monocytes and alveolar macrophages in IPF compared with controls. MCEMP1 is upregulated by transforming growth factor beta (TGFβ) at the mRNA and protein levels in monocytic leukemia THP-1 cells. TGFβ-mediated MCEMP1 upregulation results from the cooperation of SMAD3 and SP1 via concomitant binding to SMAD3/SP1 cis- regulatory elements within the MCEMP1 promoter. We also found that MCEMP1 regulates TGFβ-mediated monocyte chemotaxis, adhesion, and migration. Our results suggest that MCEMP1 may regulate the migration and transition of monocytes to monocyte-derived alveolar macrophages during pulmonary fibrosis development and progression. NEW & NOTEWORTHY MCEMP1 is highly expressed in circulating classical monocytes and alveolar macrophages in IPF, is regulated by TGFβ, and participates in the chemotaxis, adhesion, and migration of circulating monocytes by modulating the effect of TGFβ in RHO activity.

This study found significant improvements in heart transplant outcomes and survival in patients with hepatitis C virus., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.

Background: The total artificial heart (TAH) consists of two implantable pneumatic pumps that replace the heart and operate at a fixed ejection rate and ejection pressure. We evaluated the blood pressure (BP) response to exercise and exercise performance in patients with a TAH compared to those with a with a continuous-flow left ventricular assist device (LVAD)., Methods: We conducted a single-center, retrospective study of 37 patients who received a TAH and 12 patients implanted with an LVAD. We measured the BP response during exercise, exercise duration and change in tolerated exercise workload over an 8-week period., Results: In patients with a TAH, baseline BP was 120/69 ± 13/13, exercise BP was 118/72 ± 15/10 and post-exercise BP was 120/72 ± 14/12. Mean arterial BP did not change with exercise in patients with a TAH (88 ± 10 vs 88 ± 11; p = 0.8), but increased in those with an LVAD (87 ± 8 vs 95 ± 13; p < 0.001). Although the mean arterial BP (MAP) was negatively correlated with metabolic equivalents (METs) achieved during exercise, the association was not statistically significant (β = -0.1, p = 0.4). MAP correlated positively with METs achieved in patients with LVADs (MAP: β = 0.26, p = 0.04). Despite the abnormal response to exercise, patients with a TAH participated in physical therapy (median: 5 days; interquartile range [IQR] 4 to 7 days) and treadmill exercise (19 days; IQR: 13 to 35 days) early after device implantation, with increased exercise intensity and duration over time., Conclusions: During circulatory support with a TAH, the BP response to exercise was blunted. However, aerobic exercise training early after device implantation was found to be safe and feasible in a supervised setting., (2011 International Society for Heart and Lung Transplantation. All rights reserved.)