Adverse Effects of Immunosuppression: Nephrotoxicity, Hypertension, and Metabolic Disease.

The use of Immunosuppression has led to the tremendous improvement in graft survival. However, immunosuppressants have been found to cause a variety of metabolic derangements including but not limited to: insulin resistance and diabetes, hyperlipidemia, hypertension, and weight gain after transplantation. This combination of metabolic risk factors may be associated with increased cardiovascular disease (Grundy et al., Circulation 112(17):2735, 2005). In addition many transplant recipients may have many of these risk factors pre-transplant that are exacerbated by immunosuppression. These facts emphasize the need for rigorous follow-up and management of these risk factors post-transplant.The most common immune suppressant regimens may include different combinations of these agents: Corticosteroids, Calcineurin inhibitors (CNIs), Mammalian Target of Rapamycin (mTOR) Inhibitors, Antimetabolite.

Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates.

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established. In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions to guide DSA treatment post-transplant. Although these findings have to be confirmed in a larger prospective study, our data suggest that serum dilutions can serve as a predictive biomarker to guide peri-operative desensitization and post-transplant immunologic management.

Time Is a Precious Commodity: 2018 OPTN Policy Change and the Potential to Lower Heart Transplant Waitlist Time in the Sickest Patients.

PURPOSE OF REVIEW: Heart transplantation is the gold standard therapy for end-stage heart failure; however, the donor pool is limited, making this a scarce resource that must be allocated to the sickest patients in an efficient, fair, and equitable manner. The allocation policies have been constantly revised over the years to refine the process. We will explore the new heart allocation system, OPTN-Policy 6, as well as, review why these changes were necessary. RECENT FINDINGS: Over the past decade, the number of active heart transplant candidates nearly doubled, with a dramatic increase in the number of status 1A and 1B (high priority) candidates. Candidates have also faced increased waitlist times with geographic variances. The allocation policy changes will attempt to alleviate these problems as well as adapt to advances in technology. The new allocation policy is designed to adapt to the present day reality of expanded mechanical support use, increased candidate acuity, increasing waiting times, and geographical disparities in transplant rates. Though the implementation of the new allocation policy will require some change in practice, the transplant community, as knowledge is gained, is accustomed to change and refinement in practice, in an effort to improve outcomes for patients with end-stage heart failure.

The Initial Evaluation and Management of a Patient with Heart Failure.

PURPOSE OF REVIEW: The goal of this review is to summarize and discuss a thorough and effective manner in the evaluation of the patient with heart failure. RECENT FINDINGS: Heart failure is a prevalent disease worldwide and while the diagnosis of heart failure has remained relatively unchanged via a careful history and physical examination, identification of the etiology of the heart failure and treatment has made significant advances. Mechanical circulatory support (MCS), neprilysin inhibitors, and chronic resynchronization therapy (CRT) are just some of the relatively recent therapies afforded to assist heart failure patients. Heart failure is a complicated, multifactorial diagnosis that requires a careful history and physical for diagnosis with the support of laboratory tests. While the prognosis for heart failure patients remains poor in comparison to other cardiovascular disease and even certain cancers, new advancements in therapy have shown survival and quality of life improvement.