E. Kransdorf

Heart Transplantation for Chagas Cardiomyopathy in the United States

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Chagas disease in solid organ and heart transplantation.

Purpose of review The diagnosis and management of acute and chronic infections with the microorganism Trypanosoma cruzi, which causes Chagas disease, is important in solid organ transplantation in both endemic and nonendemic countries. In this review, we examine recently published data on the topic of Chagas disease in solid organ transplantation, with an emphasis on data relevant to heart transplantation. Recent findings Most people with chronic T. cruzi infection have the intermediate form of disease, but approximately 2% of infected persons will progress to Chagas cardiomyopathy per year. The risk of T. cruzi transmission with liver or kidney transplantation appears to be substantially less than that with heart transplantation. For patients with Chagas cardiomyopathy undergoing heart transplant, a structured clinical and laboratory monitoring protocol is necessary to monitor for T. cruzi reactivation. Recent data indicate that laboratory monitoring of peripheral blood with polymerase chain reaction testing can identify reactivation prior to the occurrence of symptoms and allograft injury. Summary Transplant clinicians should exercise vigilance in surveillance for Chagas disease in both organ donors and recipients. Although Chagas disease may seem uncommon, it is pervasive in endemic and several nonendemic countries, including the United States and Spain.

Racial and ethnic disparities in outcomes after heart transplantation: A systematic review of contributing factors and future directions to close the outcomes gap

The demographics of patients undergoing heart transplantation in the United States have shifted over the last 10 years, with an increasing number of racial and ethnic minorities undergoing heart transplant. Multiple studies have shown that survival of African American patients after heart transplantation is lower compared with other ethnic groups. We review the data supporting the presence of this outcome disparity and examine the multiple mechanisms that contribute. With an increasingly diverse population in the United States, knowledge of these disparities, their mechanisms, and ways to improve outcomes is essential.

Early Denervation and Later Reinnervation of the Heart Following Cardiac Transplantation: A Review

Heart transplantation (HTx) surgically interrupts the parasympathetic vagal neurons and the intrinsic postganglionic sympathetic nerve fibers traveling from the stellate ganglia to the myocardium, causing axonal Wallerian degeneration and thus extrinsic cardiac denervation.[1][1], [2][2], [3][3], [4

Dissecting the “CHF admission”: An evidence‐based review of the evaluation and management of acute decompensated heart failure for the hospitalist

Acute decompensated heart failure (ADHF) is one of the most common conditions managed by hospitalists. Here we review the most recent evidence applicable to hospitalists for the diagnosis, risk stratification, and management of patients presenting with ADHF. By following a structured approach based on the patients symptoms, history, physical examination, and laboratory testing, the clinician can make the diagnosis of heart failure efficiently. Because patients exhibit a wide spectrum of risk for adverse outcomes, both in the hospital and after discharge, assessing for clinical factors associated with these outcomes is essential. Congestion should be managed primarily with diuretics, and vasodilators may be helpful in certain patients. Given high rates of readmission, hospitalists should ensure that patients received evidence-based therapy, heart failure education is performed, and follow-up is in place before discharge.

Pathology of Chronic Chagas Cardiomyopathy in the United States: A Detailed Review of 13 Cardiectomy Cases.

OBJECTIVES The pathologic features of chronic Chagas cardiomyopathy may not be widely appreciated in the United States. We sought to describe the gross, microscopic, immunohistochemical, and molecular pathology features useful to diagnose chronic Chagas cardiomyopathy. METHODS The features from a case series of cardiectomy specimens of patients undergoing heart transplantation (12 patients) or mechanical circulatory support device implantation (one patient) for chronic Chagas cardiomyopathy at three institutions in the United States are reported and analyzed. RESULTS Gross findings included enlarged and dilated ventricles (100% of cases), mural thrombi (54%), epicardial plaques (42%), and left ventricular aneurysm (36%). Microscopic evaluation revealed myocarditis (100% of cases) characterized by mononuclear cell infiltration, fibrosis (100%), nonnecrotizing granulomas (62%), and giant cells (38%). Two specimens (15%) showed rare intracellular amastigotes. Immunohistochemical assays for Trypanosoma cruzi organisms were negative in all cardiectomy specimens, whereas tissue polymerase chain reaction was positive in six (54%) of 11 cases. CONCLUSIONS The gross and microscopic features of chronic Chagas cardiomyopathy in the United States appear similar to those reported in endemic countries. Importantly, tissue polymerase chain reaction may be useful to confirm the diagnosis.

Calculated panel-reactive antibody predicts outcomes on the heart transplant waiting list

BACKGROUND Sensitized heart transplant candidates spend more time and have higher mortality on the waiting list. Although the calculated panel-reactive antibody (CPRA) value is used to assign allocation priority to kidney transplant candidates in the United States, the relationship between CPRA and outcomes on the heart transplant waiting list is unknown. METHODS A data set of patients listed for heart transplant with unacceptable human leukocyte antigens (HLA) entered was obtained from the United Network for Organ Sharing. The study cohort was composed of 3,855 adult candidates listed for heart transplant between 2006 and 2013 with active waiting time. The cohort was divided into 5 groups by increasing CPRA. Outcomes were assessed using competing risks and sub-hazard regression analyses. RESULTS In each group of successively higher CPRA, the percentage of candidates who received a transplant decreased, whereas the percentage of those who were still waiting for a transplant increased, as did the percentage of those removed from the waiting list or had died. The group of candidates with a CPRA >80% displayed a markedly decreased incidence of transplantation (hazard ratio 0.37) and an increased risk of removal from the waiting list or death (hazard ratio 2.18) as compared to those with CPRA of ≤10%. CONCLUSIONS Sensitized heart transplant candidates are at high risk of adverse outcomes on the heart transplant waiting list. Clinicians should strive to minimize the CPRA by maximizing specificity in the selection of HLA antigens to exclude. The optimal clinical approach for candidates with high CPRA requires further study.

HLA Population Genetics in Solid Organ Transplantation

Abstract HLAs are fundamental to the adaptive immune response and play critical roles in the cellular and humoral response in solid organ transplantation. The genes encoding HLA proteins are the most polymorphic within the human genome, with thousands of different allelic variants known within the population. Application of the principles of population genetics to the HLA genes has resulted in the development of a numeric metric, the calculated panel-reactive antibody (CPRA) that predicts the likelihood of a positive crossmatch as a function of a transplant candidate’s unacceptable HLA antigens. The CPRA is an indispensible measure of access to transplantation for sensitized candidates and is used as the official measure of sensitization for allocation of points in the US Kidney Allocation System and Eurotransplant. Here, we review HLA population genetics and detail the mathematical basis of the CPRA. An understanding of these principles by transplant clinicians will lay the foundation for continued innovation in the care of sensitized patients.

ISHLT transplant registry: Youthful investment – The path to progress

Cite this article as: Evan P. Kransdorf, Hirsch S. Mehta, Keyur B. Shah, Darko Vucicevic, Eugene DePasquale, Livia Goldraich, Agnieszka Ciarka, Marco Masetti, Jong-Chan Youn, Claire Irving, Feras Khaliel, Martin Schweiger, Patricia Uber, Mandeep R. Mehra and Josef Stehlik, ISHLT transplant registry: Youthful investment – The path to progress, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2017.07.024

Prediction Model For Cardiac Allograft Vasculopathy: Comparison of Three Multivariable Methods

Cardiac allograft vasculopathy (CAV) remains an important cause of graft failure after heart transplantation (HT). Although many risk factors for CAV have been identified, there are no clinical prediction models that enable clinicians to determine each recipients risk of CAV.