tacrolimus and Cardiomyopathies

TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome.. Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly.. In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis.. In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy.. This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

Topics: Adolescent; Aged; Bone Marrow; Calcineurin Inhibitors; Cardiomyopathies; Castleman Disease; Cyclosporine; Edema; Female; Fever; Fibrosis; Glucocorticoids; Hepatomegaly; Humans; Interleukin-6; Male; Primary Myelofibrosis; Renal Insufficiency; Splenomegaly; Syndrome; Tacrolimus; Thrombocytopenia; Treatment Outcome

We contacted and analyzed the data of 18 lung transplant recipients who had had children. The complications we detected included: hypertension (50%), diabetes mellitus (21%), preeclampsia (13%), infection (21%), rejection (30%), loss of graft function (23%) and a lower percentage of live births than in transplant recipients of other organs. Other aspects to keep in mind are: the potential risk for fetal alterations (caused by drugs used as prophylaxis against rejection crossing the placental barrier); greater risk for infection and alterations in drug levels due to changes in metabolism typical of pregnancy and postpartum period. We describe the two cases in Spain of female lung transplant recipients who have had children after transplantation. Although pregnancy in these cases can have a similar evolution as in non-transplanted women, doctors should recommend their transplanted patients to avoid becoming pregnant, while explaining the high risk of both fetal and maternal morbidity and mortality after transplantation.

Topics: Adult; Cardiomyopathies; Female; Graft Rejection; Heart Defects, Congenital; Heart-Lung Transplantation; Humans; Hypertension; Hypertension, Pulmonary; Immunosuppressive Agents; Infant, Newborn; Infant, Premature, Diseases; Lung Diseases, Interstitial; Lung Transplantation; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy, High-Risk; Spain; Survivors; Tacrolimus

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

A 69-year-old Japanese woman was admitted to our hospital with progressive muscle weakness and dysphagia. She was taking pitavastatin for dyslipidemia. Her serum creatine kinase was 6,300 U/L. Pitavastatin was stopped, but her symptoms deteriorated, and cardiac congestion appeared. A muscle biopsy showed necrotizing myopathy (NM), and anti-signal recognition particle (SRP) antibody was positive.

Topics: Aged; Autoantibodies; Biopsy; Cardiomyopathies; Contrast Media; Echocardiography; Female; Gadolinium; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Magnetic Resonance Imaging; Multimodal Imaging; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Positron Emission Tomography Computed Tomography; Signal Recognition Particle; Tacrolimus

Tacrolimus-induced cardiomyopathy (TICM) is a rare but serious adverse effect of tacrolimus, which has been described primarily in pediatric non-renal transplant recipients. We describe a case of TICM in an adult renal transplant recipient that resulted in allograft dysfunction and multiple hospital admissions for heart failure exacerbation. Prompt and complete reversal of TICM occurred after tacrolimus discontinuation. Although tacrolimus-induced cardiomyopathy is reversible, availability of alternative immunosuppressants is limited, particularly in the setting of renal dysfunction. Available studies and patient-specific factors must be considered when determining an alternative maintenance immunosuppression regimen. We chose to use belatacept as alternative immunosuppression in this patient with TICM. Over the next 3 years, the patient remained free of hospital admissions and acute rejection, and demonstrated superior renal allograft function than was observed before her first heart failure admission. We believe that belatacept is an acceptable alternative to tacrolimus therapy for resolution of TICM.

Topics: Cardiomyopathies; Diagnosis, Differential; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Tacrolimus; Ultrasonography

Topics: Cardiomyopathies; Fusion Proteins, bcr-abl; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocyte Count; Male; Middle Aged; Philadelphia Chromosome; Platelet Count; Postoperative Complications; Tacrolimus

Induction with rabbit antithymocyte immunoglobulins (RATG) for cardiac transplantation allows reduction of calcineurin inhibitor and reduces the incidence of acute rejection episodes (ARE). We compared induction with RATG combined with either cyclosporine (CsA) or tacrolimus (FK) in regard to the number of ARE in the first year after transplantation. We transplanted 111 patients from 2000 to 2008 including 61 who received CsA-RATG, and 19, FK-RATG. At 3 months and 1 year the CsA group displayed 3.29 +/- 1.66 and 7.44 +/- 2.45 ARE per patient of grade at least 1R respectively. The FK group showed 3.21 +/- 1.71 and 8.13 +/- 2.07 episodes per patient (P = .86 at 3 months; P = .32 at 1 year). Among ARE 2R or greater, the CsA group displayed 0.51 +/- 0.70 and 0.91 +/- 0.95 episodes per patient at 3 months and 1 year, while the FK group showed 0.15 +/- 0.38 and 0.31 +/- 0.63 episodes, respectively (P = .09 at 3 months; P = .016 at 1 year). Among type 3R ARE, the CsA group showed 0.11 +/- 0.32 and 0.13 +/- 0.34 episodes, whereas the FK group experienced 0.05 +/- 0.23 and 0.05 +/- 0.23 episodes at 3 months and 1 year, respectively (P = .44 at 3 months, P = .35 at 1 year). The freedom rate from 1R, 2R, and 3R ARE was therefore similar between the two groups (P = .76, P = .14, and P = .23, respectively). Induction with FK-RATG tended to reduce the number of type 2R and greater rejection episodes per patient at 1 year after transplantation compared to CsA-RATG.

Topics: Adult; Animals; Antilymphocyte Serum; Calcineurin Inhibitors; Cardiomyopathies; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Rabbits; Retrospective Studies; Tacrolimus; Time Factors

Pediatric heart transplantation is entering its third decade, allowing for the first time an analysis of a large group of true long-term survivors, specifically children who have survived > or =10 years post-transplantation.. Fifty-two patients < or =18 years, who had undergone heart transplantation at Stanford between August 1974 and June 1993 and survived > or =10 years, were retrospectively reviewed.. Forty (77%) patients are currently alive. Thirteen survived >15 years and 5 >20 years (the longest being 26 years). Actuarial survival was 79.4% at 14 years and 53.1% at 20 years. Cardiomyopathy was the reason for transplantation in 71% and congenital heart disease (CHD) in 29%. At last evaluation, 71% were on a cyclosporine-based regimen and 23% a tacrolimus-based regimen; 33% were steroid-free. Twenty-seven percent were totally free from treatable rejection, 44% developed serious infections, 69% were receiving anti-hypertensives, and 8% required renal transplantation. Neoplasms occurred in 23%, graft coronary artery disease (CAD) in 31%, and 15% required re-transplantation. Of the 12 deaths, CAD was the most common cause (n = 4), followed by non-specific late graft failure (n = 3), infection (n = 2), rejection (n = 1), non-lymphoid cancer (n = 1) and lymphoid cancer (n = 1). Physical rehabilitation and return to normal lifestyle has been nearly 100%.. Heart transplantation in pediatric patients is compatible with true long-term survival with a growing cohort of children approaching their second and third decades. The gradual constant-phase decrease in survival noted in earlier studies appears to be continuing. Rejection and infection are low but persistent risks after the first years. Graft CAD and non-specific late graft dysfunction are the leading causes of death after 10 years. Rehabilitation is excellent.

Topics: Actuarial Analysis; Adolescent; Bacterial Infections; Cardiomyopathies; Child; Child, Preschool; Coronary Artery Disease; Cyclosporine; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Lymphoproliferative Disorders; Male; Reoperation; Retrospective Studies; Survival Analysis; Survivors; Tacrolimus

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

Topics: Actuarial Analysis; Adolescent; Age Factors; Cardiomyopathies; Cause of Death; Child; Child, Preschool; Cyclosporine; Europe; Forecasting; Glucocorticoids; Heart Defects, Congenital; Heart Transplantation; Heart-Lung Transplantation; Hospitalization; Humans; Immunosuppressive Agents; Infant; Logistic Models; Lung Transplantation; Multivariate Analysis; Odds Ratio; Patient Readmission; Prednisone; Registries; Risk Factors; Societies, Medical; Survival Analysis; Tacrolimus; United States

Topics: Adult; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Graft Rejection; Heart; Humans; Liver Transplantation; Male; Middle Aged; Tacrolimus

The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14%) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67%. In children with congenital heart disease (> 6 months of age) the perioperative (30 day) mortality was 66% before mid-1988 (n = 10) and 0% since mid-1988 (n = 11). The late mortality (> 30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66% (n = 14) and 7% since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82% in children with congenital heart disease and 90% in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82% at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60% at 3 and 6 months after transplantation versus 20% and 12%, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p < 0.001, Mantel-Cox and Breslow). Twenty of 24 children (83%) in the FK 506 group are receiving no steroids. The prevalence of posttransplantation hypertension was 4% in the FK 506 group versus 70% in the cyclosporine group (p < 0.001, Fisher). Renal toxicity in children treated with FK 506 has been mild. Additionally, eight children have been switched to FK 506 because of refractory rejection and drug toxicity. FK 506 has not produced hirsutism, gingival hyperplasia, or abnormal facial bone growth. The absence of these debilitating side effects, together with the observed immune advantage and steroid-sparing effects of FK 506, hold tremendous promise for the young patient facing cardiac transplantation and a future wedded to immunosuppression.

Topics: Adolescent; Cardiomyopathies; Child; Child, Preschool; Cyclosporine; Extracorporeal Membrane Oxygenation; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Infections; Kidney; Lymphoproliferative Disorders; Male; Postoperative Complications; Tacrolimus