Review Form First Author, Year: ___________________ Ref ID #__________ Abstractor Initials: ___ ___ ___ Primary Inclusion/Exclusion Criteria 1. Relevant to SER topic Yes No Cannot Determine 2. Attempts internal or external validation Yes No Cannot Determine 3. Published in English Yes No Cannot Determine 4. Original research (exclude reviews, editorials, commentaries, letters to editor, etc.) Yes No Cannot Determine 5. Eligible Study types a. Randomized controlled trials b. Controlled clinical trials

Systematic Review of Cardiovascular Disease Risk Assessment Tools

Cyclosporin was introduced into clinical practice in the early 1980s and has since been shown to prolong survival for transplant recipients. Because cyclosporin is a narrow therapeutic index drug and there are significant consequences associated with ‘subtherapeutic’ and ‘supratherapeutic’ concentrations, cyclosporin therapy is monitored as part of routine patient follow-up. However, the optimal method for the therapeutic drug monitoring of cyclosporin has yet to be defined. Currently, the most common method involves monitoring pre-dose trough concentrations, but this method is less than ideal. Other methods of monitoring cyclosporin therapy include monitoring the area under the concentration-time curve, limited sampling strategies, monitoring of single concentrations other than troughs and pharmacodynamic monitoring. Bayesian forecasting has been used successfully in clinical practice with other drugs with narrow therapeutic indices. However, few studies are available regarding Bayesian forecasting and cyclosporin. Existing studies are preliminary in nature and involve the old Sandimmun® formulation rather than the Neoral® formulation. Although these methods show promise, they have not gained widespread acceptance. This is because of their impracticality and the lack of prospective studies comparing other monitoring methods with trough concentration monitoring. Further comparative studies evaluating the impact of the specific monitoring method on definite patient outcomes are warranted.

Methods for Clinical Monitoring of Cyclosporin in Transplant Patients

Recent years have seen a rising awareness of the significance of cardiac antibody-mediated rejection (AMR) as a result of its formal recognition by the International Society for Heart and Lung Transplantation. New insights on the pathology and clinical behavior of cardiac AMR are at odds with current diagnostic guidelines. This perspective examines some of the contentious and unresolved issues in cardiac AMR as the transplant community makes concrete steps towards updating its defining criteria.

Controversies in defining cardiac antibody-mediated rejection: Need for updated criteria

Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy

/pdf/cardiac-allograft-vasculopathy-diagnosis-therapy-and-539xg8oz7a.pdf

Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis.

Cardiac allograft vasculopathy (CAV) is a significant factor impacting outcomes after heart transplant. We performed a systematic review of risk factors for the development of CAV. A search of electronic databases was performed. The eligibility criteria included cohort and case-control studies with more than 50 adult patients submitted to a heart transplant. The outcome should be CAV diagnosed by angiography and/or intravascular ultrasound (IVUS). Two reviewers performed study selection, data abstraction, and quality assessment. Of 2514 citations, 66 articles were included--46 had 200 participants or less; 61 were single-center; and 44 were retrospective cohorts. The most used definition of CAV using angiography was the detection of any degree of abnormality (21 studies of 58). In studies using IVUS, an intimal thickness ≥0.5 mm was the most used definition (five of eight studies). Quality assessment revealed an inadequate description of patient selection, attrition, and accounting of potential confounders. Donor age, recipient age, recipient gender, etiology of heart failure, ischemic time, human leukocyte antigen matching, cytomegalovirus, lipid profile, and rejection episodes were the most studied factors. Our review indicates that the current evidence is not consistent across different studies. The definite contribution of risk factors for the development of CAV is still to be determined.

Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies.

A procoagulant microvasculature is associated with accelerated development of coronary artery disease (CAD) and failure in heart transplant patients. This study was performed to evaluate how changes in natural anticoagulation within cardiac allografts affect outcome. We prospectively studied 141 consecutive cardiac allograft recipients who underwent transplantation between 1988 and 1997. Serial endomyocardial biopsy specimens (6.5 ± 0.1 biopsy specimens/patient) obtained during the first 3 months after transplantation were studied immunohistochemically to evaluate vascular antithrombin, and annual coronary angiograms (3.8 ± 0.2 angiograms/patient) were studied to evaluate CAD. Antithrombin was present in arteries and veins, but not in capillaries, of all donor heart biopsy samples. Allografts that maintained vascular antithrombin had the best prognosis. Allografts with early and persistent loss of vascular antithrombin (n = 21) developed CAD earlier (p <0.001), developed more severe disease (p <0.001), showed more disease progression (p <0.001), and failed more often (p = 0.003) and earlier (p <0.001) than allografts retaining normal vascular antithrombin (n = 45). However, allografts that lost and recovered vascular antithrombin while developing unusual capillary antithrombin binding (n = 75) had less CAD, developed CAD later, had less severe disease and less disease progression (p <0.01), and failed less often (p = 0.01) and later (p = 0.03) than allografts with persistent loss of vascular antithrombin. The persistent lack of a thromboresistant microvasculature increases risk of subsequent CAD and graft failure. However, recovery of vascular antithrombin and development of unusual capillary antithrombin binding improves allograft outcome.

Vascular antithrombin and clinical outcome in heart transplant patients.

Immunohistochemical model to predict risk for coronary artery disease and failure in heart transplant patients.

Immunologic monitoring of the cardiac transplant patient.

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Vascular antithrombin and clinical outcome in heart transplant patients.

Immunohistochemical model to predict risk for coronary artery disease and failure in heart transplant patients.

Immunologic monitoring of the cardiac transplant patient.