Preformed donor HLA-specific antibodies are a known indicator for poor patient survival after cardiac transplantation. The role of de novo donor-specific antibodies (DSA) formed after cardiac transplantation is less clear. Here we have retrospectively analyzed 243 cardiac transplant recipients, measuring HLA antibody production every year after transplantation up to 13 years post-transplant. Production of de novo DSA was analyzed in patients who had been negative for DSA prior to their transplant. DSA including transient antibodies were associated with poor patient survival (p = 0.0018, HR = 3.198). However, de novo and persistent DSA was strongly associated with poor patient survival (p = 0.0001 HR = 4.351). Although complement fixing persistent DSA correlated with poor patient survival, this was not increased compared to noncomplement fixing persistent DSA. Multivariable analysis indicated de novo persistent DSA to be an independent predictor of poor patient survival along with HLA-DR mismatch and donor age. Only increasing donor age was found to be an independent risk factor for earlier development of CAV. In conclusion, patients who are transplanted in the absence of preexisting DSA make de novo DSA after transplantation which are associated with poor survival. Early and regular monitoring of post-transplant DSA is required to identify patients at risk of allograft failure.

The standard method to detect pretransplant antibodies has been the complement dependent cytotoxicity (CDC) test of donor leukocytes. Solid phase assays to detect HLA antibodies in pretransplant serum reveal a greater number of sensitized patients, but their clinical impact is less certain. Here we have developed a method of detecting C4d fixing HLA antibodies on Luminex beads. Pretransplant serum from 565 cardiac transplant patients was retrospectively tested for the presence of HLA antibodies using CDC, HLA coated Luminex beads and C4d deposition on Luminex beads, and the results correlated with graft survival. Whereas 5/565 patients had CDC positive donor specific antibodies (DSA) before their transplant, this number was increased by 19 using Luminex beads. The 1-year survival of CDC -ve/Luminex +ve patients with DSA (n = 19) was 42% compared with 77% for CDC -ve/Luminex +ve without DSA (n = 39, p = 0.0039). Fixation of C4d (22/67 Luminex positive sera) had a negative effect on graft outcome; 1-year graft survival was, C4d +ve/DSA +ve (n = 11) 20%, C4d +ve/DSA -ve (n = 11) 91%, C4d -ve DSA +ve (n = 13) 54%, C4d -ve DSA -ve (n = 32) 75%, compared with 75% for antibody-negative patients (p = 0.0002). In conclusion, detection of Luminex +ve DSA in pretransplant serum provides a powerful negative predictor of graft survival, especially if they bind C4d.

The incidence of CKD increased with time and was not influenced by the CsA regimen. Some risk factors are not modifiable but measures to reduce the incidence of post-operative ARF may help to reduce CKD.

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The yield of BPAR was low in the AZA group and very low in the MMF group. The incidence of complications was also low, but repeated biopsies led to a higher rate per patient. Routine surveillance EMBs and the frequency of such biopsies should be reevaluated in the light of their low yield with current immunosuppression.

Little is known about the effect of MICA antibodies (Abs) on cardiac allograft function and survival. Pretransplant and posttransplant serum from 491 and 196 adult cardiac allograft recipients, respectively, has been investigated for MICA Abs, donor specificity and the effect of MICA Abs on graft survival, acute rejection episodes (AR) and cardiac allograft vasculopathy (CAV). Patients with HLA Abs (11.6%) were excluded from the analysis. A total of 11.8% of patients had MICA Abs, without HLA Abs, before their transplant. Actuarial graft survival demonstrated slightly better survival of patients with donor-specific MICA Abs at 1 and 5 years (88.9% and 83.3%) than patients negative for MICA Abs (72% and 63.7%, p = 0.051). After transplantation, 15.8% of patients produced MICA Abs, and in 17 patients these were produced de novo. There was no effect of pretransplant or posttransplant production of MICA Abs on numbers of AR episodes in year 1, or CAV assessed at years 3 and 5. Immunocytochemistry of cardiac biopsies from 11 patients did not demonstrate a presence of MICA. Sera from only 4/69 patients with MICA Abs fixed complement prior to transplantation and from 7/38 patients following transplantation. In conclusion, this study suggests that MICA Abs do not adversely affect the outcome of cardiac transplantation.

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BackgroundHeart failure (HF) patients derive a dose‐dependent clinical benefit from medications that are part of guideline‐directed medical therapy (GDMT). The widespread underdosing of these medications and the clinical implications of the lack of titration have been well documented. There is paucity of data on design and outcomes of pharmacist‐led HF clinics.AimThe aim of this study is to describe the establishment of the first pharmacist‐led HF pharmacotherapy clinic (HFPC) in the Middle East gulf region.MethodsThis is a retrospective study of patients seen by the HF pharmacotherapy clinic. We determined the percentage of patients on target doses of GDMT at baseline and at the end of follow‐up in the subgroup of patients with HF with reduced ejection fraction (HFrEF). All baseline self‐care behaviors and interventions performed were examined.ResultsThe first 100 patient referrals and 193 visits were included in this analysis for an average of 1.9 ± 1.4 visits per patient and a mean follow‐up period of 51 ± 36.1 days. Most patients (94%) had HFrEF and were referred to from the outpatient clinics (72%). Many patients (76%) had at least one inadequacy in medication adherence or self‐care behaviors at baseline, and none were on simultaneous target doses of all GDMTs. At the end of follow‐up, more patients with HFrEF were on target doses when compared with baseline (beta‐blockers 31.9% vs 40.4%, P = .032, angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin II receptor blocker neprilysin inhibitor 7.4% vs 25.5%, P < .001, mineralocorticoid receptor antagonist 37.2% vs 39.4% P = .46, all three target GDMTs 0% vs 6.4%, P = .093). Significantly, more patients were on any dose of all three GDMTs.ConclusionsPharmacist‐led HF medication optimization clinic establishment can contribute to longitudinal medication titration, successful transition of care, and correcting noncompliance and indiscretions. Pharmacists are in an ideal position to fill gaps and help evolve the current HF care model.