Multicenter evaluation of a national organ sharing policy for highly sensitized patients listed for heart transplantation in Canada.

Background: Transplantation of sensitized recipients has been associated with increased risk of post-transplant complications. In 2010, the Canadian Cardiac Transplant Network (CCTN) created a unique status listing for highly sensitized heart transplant candidates. Status 4S listing requires calculated panel-reactive antibody (cPRA) level >80% as the sole listing criteria and enables geographic expansion of the donor pool by providing national access.

Cardiac signaling molecules and plasma biomarkers after cardiac transplantation: impact of tacrolimus versus cyclosporine.

Background: We investigated cardiac proinflammatory, mitogenic, and apoptotic signaling events, and plasma biomarkers of inflammation and oxidative stress in de novo adult cardiac transplant (CTX) patients receiving tacrolimus (TAC) or cyclosporine A (CsA).

Methods: One hundred CTX recipients were randomized 1:1 to TAC/CsA in a prospective, randomized open-label multicenter study. Biomarkers of inflammation, immunity, oxidative stress, and cardiac signaling underlying growth and inflammation (extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase, mitogen-activated protein kinase kinases [MEK] 1/2 and 3/6, c-Src), and apoptosis and survival (c-Jun NH2-terminal kinases [JNK], Bax/Bcl2, Akt) were assessed at 2, 4, 12, 26, and 52 weeks post-CTX.

Early and late outcomes after cardiac retransplantation.

Background: Cardiac retransplantation remains the most viable option for patients with allograft heart failure; however, careful patient selection is paramount considering limited allograft resources. We analyzed clinical outcomes following retransplantation in an academic, tertiary care institution.

Methods: Between 1981 and 2011, 593 heart transplantations, including 22 retransplantations were performed at our institution.

Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant.

Aims: Familial amyloid polyneuropathy (FAP) is a dominantly inherited multi-system disease associated with transthyretin (TTR) mutations. Previous series have predominantly described patients with the TTR variant Val30Met (V30M), which is the most prevalent cause of FAP worldwide. Here, we report the dominant cardiac phenotype and outcome of FAP associated with TTR Thr60Ala (T60A), the most common UK variant.

Reduction of cyclosporine following the introduction of everolimus in maintenance heart transplant recipients: a pilot study.

Data are scarce concerning the calcineurin inhibitor dose reduction required following introduction of everolimus in maintenance heart transplant recipients to maintain stable renal function. In a 48-week, multicenter, single-arm pilot study in heart transplant patients >12 months post-transplant, everolimus was started at 1.5 mg/day (subsequently adjusted to target C(0) 5-10 ng/ml).

Increased morbidity in diabetic cardiac transplant recipients.

Background: Diabetes currently affects more than 7% of the Canadian population, and heart failure is a well-documented complication of diabetes. The medical management of heart failure is often limited by disease progression, and cardiac transplantation is a key therapeutic option in end-stage disease. However, both American and Canadian guidelines continue to list diabetes as a relative contraindication to cardiac transplantation.

Cyclosporine reduction in the presence of everolimus: 3-month data from a Canadian pilot study of maintenance cardiac allograft recipients.

Background: Concentration-controlled everolimus with concomitant cyclosporine (CsA) dose reduction in renal transplantation permits preservation of kidney function without loss of efficacy. Data are lacking regarding everolimus with reduced-dose CsA in maintenance cardiac transplant patients.

Methods: In a multicenter, open-label, single-arm pilot study, concentration-controlled everolimus was initiated in patients receiving CsA microemulsion (Neoral) with/without mycophenolate mofetil (MMF) or azathioprine, and with/without corticosteroids.

Subclinical inflammation and prothrombotic state in heart transplant recipients: impact of cyclosporin microemulsion vs. tacrolimus.

Background: Subclinical inflammation is related to adverse events in patients with coronary artery disease. In the present study, we determined the changes in hemostatic parameters and inflammatory markers in a large cohort of dyslipidemic cardiac transplant recipients compared with dyslipidemic healthy controls, and the effect of cyclosporin microemulsion (CsA) vs. tacrolimus immunoprophylaxis on these parameters.

Angiographic, pathologic, and clinical relationships in coronary artery disease in cardiac allografts.

Background: To date, the etiologic factors involved in the development of allograft coronary disease remain speculative and the treatment uncertain. The purpose of this study was to review the relationship of clinical, angiographic, and pathologic features of cardiac allograft vascular disease in a large population of heart transplant recipients followed for up to 15 years.

Methods: From 1981 to 1996, 789 angiograms from 255 cardiac allografts were reviewed to determine the prevalence and severity of coronary artery disease.

Conversion from cyclosporine microemulsion to tacrolimus-based immunoprophylaxis improves cholesterol profile in heart transplant recipients with treated but persistent dyslipidemia: the Canadian multicentre randomized trial of tacrolimus vs cyclosporine microemulsion.

Background: Tacrolimus improves lipid profile in renal and liver transplant recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported.

Methods: One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion-treated heart transplant recipients with low-density lipoprotein cholesterol >2.

Validation of a three-dimensional intravascular ultrasound imaging technique to assess atherosclerotic burden: potential for improved assessment of cardiac allograft coronary artery disease.

Background: Serial analysis of intracoronary ultrasound images is limited by difficulty with spatial registration and inability to assess the full extent of vascular disease. Three-dimensional (3D) imaging of coronary arteries can potentially overcome these limitations.

Objectives: To assess the feasibility of using a PC-based 3D rendering technique to assess atherosclerotic burden.