mycophenolic-acid and Cardiomyopathies

Elevated panel reactive antibody (PRA) may be considered a risk factor precluding pediatric orthotopic heart transplantation. We retrospectively reviewed our management strategy and outcome data for children undergoing heart transplantation with high PRA (> 10%).. Sixty consecutive children (median age = 130.5 days) underwent heart transplantation. Diagnoses included hypoplastic left heart syndrome (HLHS) (30 patients), cardiomyopathy (18 patients), and postoperative complex congenital heart disease (CCHD) (12 patients). Standard induction immunosuppressive therapy included pulse steroids, gamma globulin, and polyclonal rabbit antithymocyte globulin. Initial immunosuppression is a calcinurin inhibitor and an antiproliferative agent. Eight children exhibited elevated PRA (group P). Fifty-two exhibited nonelevated PRA (group N). Immunosuppression was modified in group P as follows: preoperative intravenous immunoglobulin G (IVIG) and/or cyclophosphamide or mycophenolate mofetil and preoperative and postoperative exchange transfusions or plasmapheresis. In group P, cyclophosphamide was the initial antiproliferative agent.. Group P = 4 HLHS patients (all status post [s/p] prior cardiac surgery) and 4 postoperative CCHD patients. Group N = 26 HLHS patients (4 patients s/p prior cardiac surgery), 18 cardiomyopathy patients, and 8 postoperative CCHD patients. Group P patients were older and weighed more than group N patients. Waiting time for donor heart, cardiac ischemic time, and length of hospital stay were similar in both groups. Thirty-day mortality for group P was 25% and for group N it was 7.9% (p = 0.178). Overall mortality for group P was 50% and for group N it was 15.4% (p = 0.043).. Although heart transplantation can offer children with end-stage heart failure and elevated PRA their only chance of survival, these patients remain high risk despite aggressive immunosuppression.

Topics: Adolescent; Antilymphocyte Serum; Cardiomyopathies; Child; Child, Preschool; Cyclophosphamide; Exchange Transfusion, Whole Blood; Female; Florida; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Histocompatibility Testing; Humans; Immunoglobulins, Intravenous; Immunosuppression Therapy; Immunosuppressive Agents; Infant; Infant, Newborn; Isoantibodies; Length of Stay; Male; Mycophenolic Acid; Plasmapheresis; Postoperative Complications; Retrospective Studies; Risk Factors; T-Lymphocytes; Treatment Outcome

To assess the clinical characteristics, diagnosis, and outcome of cardiac sarcoidosis in a single institution sarcoidosis clinic.. Patients with cardiac sarcoidosis were identified using refined World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria of highly probable and probable. Patient demographics, local and systemic treatments, and clinical outcome were collected.. Of the 1,815 patients evaluated over a 6-year period, 73 patients met the WASOG criteria for cardiac sarcoidosis. The median age at diagnosis was 46 years, with a median follow-up of 8.8 years. Reduced left ventricular ejection fraction (LVEF) was the most common manifestation (54.8%). Patients with arrhythmias experienced ventricular tachycardia or severe heart block, (35.6% and 19.2%, respectively) with or without reduced LVEF. A total of 45 (61.6%) patients underwent cardiac PET scan and/or MRI, with 41 (91.1%) having a positive study. During follow-up, 10 patients (13.7%) either underwent transplant (n = 3) or died (n = 7) from sarcoidosis. Kaplan-Meier survival curves revealed 5- and 10-year survival rates of 95.5% and 93.4%, respectively. Univariate factors of age at diagnosis < 46 years, implantation of pacemaker or defibrillator, mycophenolate treatment, or LVEF > 40% were associated with improved survival. Cox regression analysis demonstrated that age ≥ 46 years and lack of an implanted pacemaker or defibrillator were the only independent predictors of mortality.. The new WASOG criteria were able to characterize cardiac involvement in our sarcoidosis clinic. Age and lack of pacemaker or defibrillator were the significant predictors of mortality for cardiac sarcoidosis, and reduced LVEF < 40% was associated with worse prognosis.. ClinicalTrials.gov; No.: NCT02356445; URL: www.clinicaltrials.gov.

Topics: Adult; Antibiotics, Antineoplastic; Cardiomyopathies; China; Defibrillators, Implantable; Female; Follow-Up Studies; Heart Transplantation; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Mycophenolic Acid; Positron-Emission Tomography; Prognosis; Sarcoidosis; Stroke Volume; Tachycardia, Ventricular; Ventricular Dysfunction, Left

A 45-year-old male with cardiac sarcoidosis verified by cardiac biopsy presented with multiple coexisting arrhythmias, including ventricular tachycardia of more than 1000 episodes per 24 h, paroxysmal atrial fibrillation, and third-degree atrioventricular block. He did not respond to corticosteroids dose of 20-60 mg once daily and mycophenolate mofetil dose of 1 g twice daily for 6 months. Cardiac magnetic resonance (CMR) demonstrated inflammation and late gadolinium enhancement on right ventricular wall and interventricular septum. Positron emission tomography-computed tomography (PET-CT) showed multifocal

Topics: Adalimumab; Arrhythmias, Cardiac; Atrioventricular Block; Cardiomyopathies; Contrast Media; Fluorodeoxyglucose F18; Gadolinium; Humans; Inflammation; Male; Middle Aged; Mycophenolic Acid; Myocarditis; Positron Emission Tomography Computed Tomography; Sarcoidosis

Topics: Adult; Antibodies, Monoclonal, Humanized; Cardiomyopathies; Fatty Acids; Female; Fibrosis; Humans; Iodobenzenes; Mycophenolic Acid; Myocardium; Scleroderma, Systemic

Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality.. We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics.. Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; American Indian or Alaska Native; Antilymphocyte Serum; Black or African American; Cardiomyopathies; Cause of Death; Diabetes Mellitus; Educational Status; Female; Glucocorticoids; Graft Rejection; Healthcare Disparities; Heart Defects, Congenital; Heart Transplantation; Hispanic or Latino; Histocompatibility; Humans; Immunosuppressive Agents; Insurance, Health; Interleukin-2; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Mycophenolic Acid; Proportional Hazards Models; Registries; Sex Factors; Tacrolimus; White People; Young Adult

Data on the incidence, timing, and risk factors for herpes zoster (HZ) in heart transplant (HT) recipients are limited.. We determined HZ incidence rates and actuarial estimates of time to first HZ episode in 314 HT recipients at our institution from 1995 to 2010. We developed Cox models to assess potential risk factors for HZ in HT.. Median age at HT was 54 (range, 17-71) years; 237 (76%) were male. There were 60 episodes of HZ in 51 patients, with an overall incidence rate of 31.6 cases (95% confidence interval [CI], 23.5-41.6)/1000 person-years. Although most cases occurred during the first post-HT year, cumulative HZ incidence was 0.078 at 1, 0.15 at 5, and 0.20 at 10 years. Many patients had substantial HZ morbidity, including 14% with HZ ophthalmicus and 45% with post-herpetic neuralgia. Adjusting for age, gender, and acute cellular rejection episodes, exposure to mycophenolate mofetil (MMF) was an independent risk factor for HZ (adjusted hazard ratio [HR] 2.18; 95% CI, 1.20-3.96; P = 0.01), while ganciclovir-based cytomegalovirus prophylaxis reduced HZ risk (adjusted HR 0.09; 95% CI, 0.01-0.71; P = 0.02). Although age and female gender increased HZ risk, the magnitude of their effect was not statistically significant in Cox models.. HZ is common and morbid after HT, particularly with MMF exposure. Ganciclovir prophylaxis is effective in reducing the short-term risk of HZ, but the steady incidence of cases for years post HT makes long-term HZ prevention challenging. Augmenting varicella zoster virus immunity post HT with vaccines warrants further exploration.

Topics: Adolescent; Adult; Age Factors; Aged; Antiviral Agents; Cardiomyopathies; Cohort Studies; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Male; Middle Aged; Mycophenolic Acid; Neuralgia, Postherpetic; Proportional Hazards Models; Retrospective Studies; Risk Factors; Sex Factors; Time Factors; Young Adult

The use of C2 levels for therapeutic drug monitoring (TDM) of cyclosporine microemulsion (CsA) has been clinically validated. Routine TDM of tacrolimus and mycophenolate mofetil (MMF) is based on trough (C0) levels and side effects, respectively. The purpose of the present study was to determine the best single time points to assess the area-under-the-curve (AUC(0-12 hours)) in long-term heart transplant patients being treated with MMF in combination with CsA or tacrolimus.. We studied the AUC(0-12 hours) in long-term (>1 year), adult heart transplant patients being treated with CsA and MMF (14 patients) and with tacrolimus and MMF (9 patients).. C2 is the best surrogate (r2 = 0.87) of CsA AUC(0-12 hours). Tacrolimus C1 (r2 = 0.78), C2 (r2 = 0.83), C3 (r2 = 0.89) and C4 (r2 = 0.92) correlate better than C0 (r2 = 0.51) with the AUC(0-12 hours). When MMF is combined with CsA, there is poor correlation (r2) of MPA at all measured time points (C0 = 0.49, C2 = 0.09, C3 = 0.23, C4 = 0.44, and C6 = 0.60). When MMF is combined with tacrolimus, MPA C2 (r2 = 0.72), C4 (r2 = 0.86), C6 (r2 = 0.85), and C8 (r2 = 0.93) are better surrogates of the AUC(0-12 hours) compared with C0 (r2 = 0.69).. Our results suggest that in long-term heart transplant patients, the calcineurin inhibitor used in combination with MMF affects the correlation between MPA single time points and the AUC(0-12 hours). Future studies should determine the clinical benefit of TDM of tacrolimus and MPA with C2 or C4 compared with C0 and determine the therapeutic ranges. As for CsA-treated patients, CsA TDM should be performed with C2, and the TDM of MMF may be clinically irrelevant.

Topics: Adult; Aged; Area Under Curve; Calcineurin Inhibitors; Cardiomyopathies; Cyclosporine; Drug Interactions; Drug Monitoring; Enzyme Inhibitors; Heart Diseases; Heart Neoplasms; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Tacrolimus; Time Factors