A nationwide analysis of 16 year trends in cardiac transplantation for acute myocarditis

Background Orthotopic heart transplant (OHT) is indicated in 1–8% of patients with myocarditis. However, national trends in the utilization of transplantation and outcomes in myocarditis across the United States are not well established. Purpose Our objective was to study the trends and baseline characteristic of myocarditis patients undergoing heart transplant in the United States using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) from 1999 to 2014. Methods Using NIS data, we identified patients older than 18 years with myocarditis using codes ICD9 codes of 422.0 and 422.9. Among these patients, we identified those who underwent cardiac transplantation using ICD9 procedure codes 37.5 and 33.6. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results We identified a total of 62,264 hospitalizations for myocarditis from 1999–2014. 430 (0.69%) myocarditis patients underwent OHT which consisted of 0.82% of all 29990 cardiac transplants identified in the same period. The trends in OHT for myocarditis is as shown in Figure 1. The mean age was 32.9±2.4 years and 51.1% (n=219) were females. 235 (54.6%) were Caucasians and 60 (13.9%) were Hispanic. Majority of the transplants were performed at medium (16%) and large sized hospitals (80.4%). Cardiac transplants were mainly done at teaching hospitals (98.9%). Further, with regards to the geographical distribution of transplant procedure, most were done in the West (37.2%) followed by South (25.3%), Northeast (21.4%) and Mid-west (16%) of the United States. Private insurance was the major payor source which covered 245 (58%) patients followed by Medicaid covering 112 (26%) patients. A total of 26 (6%) myocarditis patients died during the same hospitalization for OHT. In terms of discharge following OHT in myocarditis 85.8% (n=369) were discharged home and 8.1% (n=35) to short term hospitalization. The average length of stay for OHT for myocarditis was 64.3±6.3 days. Also, the mean cost of hospitalization for heart transplant in myocarditis when adjusted for inflation was 789,566±93,108 dollars. In-patient mortality following OHT was not significantly different in large sized hospital compared to small and medium sized hospitals (7.6% vs 5.7%, p=0.54). However, the cost of hospitalization was significantly lesser in small and medium sized hospitals (588,363±154,349 vs 826,864±106,110 dollars, p<0.0001). Conclusions Only a small percentage of OHT is done for myocarditis with high proportion done in female when compared to OHT for other etiologies. Further studies need to be done to compare long term outcomes of heart transplant in myocarditis. Funding Acknowledgement Type of funding source: None

RISK FACTORS OF SMOKING AFTER HEART TRANSPLANTATION

While cessation of smoking is a requirement for cardiac transplantation prior to listing, some patients return to smoking after recovery. Since 1993, we have covertly tested the smoking habits of our recipients of cardiac transplants (with ethical approval) by calculating urinary cotinine: a level of > 500 ng / mL suggesting continuing tobacco use. Survival, causes of death and the occurrence of graft coronary artery disease (GCAD) were retrospectively analyzed in terms of the amount of positive and negative levels of cotinine. At some point after transplantation, one hundred and four out of 380 (27.4 percent) patients tested positive for active smoking, and 57 (15.0 percent) tested positive repeatedly. Because of GCAD (21.2 percent vs. 12.3 percent, p<0.05), and because of malignancy (16.3 percent vs. 5.8 percent, p<0.001), smokers experienced slightly more deaths. Smoking after heart transplantation reduced median survival from 16.28 years to 11.89 years in the univariate study. After accounting for the impact of pretransplant smoking in a time-dependent multivariate study, the most relevant determinant of total mortality remained posttransplant smoking (p < 0.00001). We conclude that by accelerating the production of graft vasculopathy and malignancy, cigarette smoking after cardiac transplantation has a substantial effect on survival. We hope that this information will prevent recipients of cardiac transplants from relapsing and will intensify efforts to increase the rate of cessation. Keywords: heart transplantation, Cardiac allograft vasculopathy, smoking, malignancy

Hyaluronan Synthesis Inhibition Impairs Antigen Presentation and Delays Transplantation Rejection

A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection.

Cardiac Transplants

Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It provides comprehensive information about cardiac structure and function and may be of interest during cardiac biopsy. Precluded by a brief summary of orthotopic and heterotopic cardiac transplantation, this chapter highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. Normal echocardiographic findings in a transplanted heart are summarized alongside echocardiographic indicators of rejection.