The implantable continuous hemodynamic monitor-guided care did not significantly reduce total HF-related events compared with optimal medical management. Additional trials will be necessary to establish the clinical benefit of implantable continuous hemodynamic monitor-guided care in patients with advanced HF.

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Molecular testing has emerged as a new tool to distinguish rejection from quiescence in cardiac allograft recipients. Although corticosteroids are important participants in immunosuppressive management, their unwanted side effects prompt dose decreases over time posttransplant. We investigated the influence of steroid dose weaning on the alloimmune molecular signature and assessed whether molecular testing monitors a patient's response to steroid treatment.Adult cardiac allograft recipients were enrolled in an eight center protocol at the time of transplant and followed during their first years post transplant. Peripheral blood mononuclear (PBMC) samples were obtained from patients at the time of biopsy. 184 samples from 124 patients (62 grade 3A, 122 grade 0 as judged by a panel of 3 expert cardiopathologists blinded to clinical data) were prospectively analyzed using a 20 gene RT-PCR test (AlloMap).The AlloMap score (AS) was found to significantly differ between rejection (R, high AS) and quiescence (Q, low AS) samples at all times post transplant (pϭ0.0001). A time-dependent increase of the AS threshold indicating rejection during the first 180 days post-transplant was noted. In addition, several AlloMap genes representing monocyte/ neutrophil as well as megakaryocyte markers showed significant correlations with steroid dose which were reflected in the AS, with high steroid doses associated with lower AS (rϭϪ0.53, pϭ10 Ϫ8 for Q-samples, and rϭϪ0.36, pϭ0.006 for R-samples). Consequently, the observed increase in the AS threshold appears largely explained by steroid weaning post-transplant. However, for similar doses of steroids and across all dose levels, R-samples were separable from Q-samples by AS.Steroid weaning was found to have an important influence on the AlloMap test scores. We conclude that the gene expression based AlloMap test, besides distinguishing rejection from quiescence, can also be used for monitoring the functional response of patients to corticosteroid treatment.

Purpose: Although in vitro data exist demonstrating an association of Fas and perforin (pfp) with rejecting cardiac allografts, the actual in vivo effector mechanism required for acute rejection is unknown. As the CD4 T-cell is required and sufficient for cardiac allograft rejection, the purpose of this study was to demonstrate the required effector molecule(s) for in vivo CD4 T-cell mediated cardiac allograft rejection. In vitro data strongly suggest a primary role for CD4 T-cell killing via Fas and therefore our hypothesis was that CD4-mediated rejection would require Fas. Procedures: Wild type (Wt) C3H (h-2 k ) and Fas-deficient C3Hlpr (h-2 k ) mice were used as heart donors into immunodeficient Bl/ 6rag Ϫ/Ϫ (h-2 b ) mice reconstituted with naïve Bl/6 CD4 T-cells or naïve Bl/6 pfp Ϫ/Ϫ CD4 T-cells. Mixed lymphocyte reactions were performed with Wt C3H and C3Hlpr gamma-irradiated splenocyte stimulators and Wt Bl/6 or Bl/6 pfp Ϫ/Ϫ CD4 T-cells as responders. Results: Removal of Fas from the donor heart or removal of perforin from the naive CD4 ϩ T-cells did not abrogate rejection individually. In contrast, removal of both donor Fas and CD4 T-cell perforin simultaneously completely abrogated rejection (pϭ0.012 vs C3H ϩ CD4 ϩ

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