Heart Transplant Recipients Research Articles

Role of Angiopoietins in Pediatric Heart Transplant Recipients with and without Kidney Dysfunction

Role of Angiopoietins in Pediatric Heart Transplant Recipients with and without Kidney Dysfunction

TCT-963 Age-Based Cardiovascular Outcomes of Heart Transplant Recipients: National Readmission Analysis

TCT-963 Age-Based Cardiovascular Outcomes of Heart Transplant Recipients: National Readmission Analysis

The Implementation-Effectiveness of a Mindfulness-Based Retreat for Mothers of Pediatric Heart Transplant Recipients: A Pilot Hybrid Mixed Methods Study

The Implementation-Effectiveness of a Mindfulness-Based Retreat for Mothers of Pediatric Heart Transplant Recipients: A Pilot Hybrid Mixed Methods Study

Importance of optimizing routine immunization schedules in pediatric heart transplantation

ObjectiveVaccination is the most effective preventive measure to reduce the risk of infection in patients receiving immunosuppressive treatment, such as heart transplant (HT) patients. The objectives of this study are to describe and evaluate the vaccination status of a group of pediatric HT recipients. Material and methodsRetrospective descriptive study of 75 pediatric patients who underwent HT at a tertiary hospital between January 2000 and September 2020. Demographic, clinical (immunization before and after HT, and attendance to vaccination counselling consultation), and analytical (hepatitis A and B serology before and after HT) variables were collected. ResultsPatients >12 months reached the HT with better vaccination coverage than those <12 months: 78.9 % versus 60.7 % had a complete vaccination schedule (P=.15). Post-HT vaccination update rate is low; only 13.3 % of patients had a complete schedule according to their age. The post-HT vaccination update of the human papillomavirus vaccine is higher in women (P=.02). We did not find statistical differences between other vaccines according to sex. A total of 13.3 % of patients attended post-HT vaccination counselling consultation, being better immunised than those who did not (P=.01). ConclusionsThe evaluation and optimization of vaccination schedules of patients with HT remains suboptimal. A follow-up of these patients and their relatives in vaccination specialised consultations can improve the immunization status of pediatric HT recipients.

Clostridium Limosum Lung Abscess in a Heart Transplant Recipient: A Rare Case Report

We report a case of Clostridium limosum lung abscess in a 71-year-old male heart transplant recipient. The patient presented with a week-long history of productive cough and confusion. His medical history included nonischemic dilated cardiomyopathy, chronic renal disease, and past Klebsiella pneumoniae bacteremia, among others. Imaging revealed a thick-walled cavitary lesion in the right lung, initially suspected to be a pulmonary abscess. Lung biopsy culture confirmed the presence of Clostridium limosum, a rare pathogen in humans, typically associated with farm animals. Following six weeks of Piperacillin/Tazobactam treatment, the patient showed significant clinical improvement. This case emphasizes the importance of considering zoonotic pathogens in immunosuppressed patients, especially those with occupational exposure.

Regional disparities in heart transplant mortality in the United States.

Mortality after heart transplantation can be influenced by multiple factors. This study analyzed its variation across 4 regions of the United States. Analyze the differences in mortality among patients receiving a heart transplant across 4 regions of the United States. Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) registry was analyzed for adult heart transplant recipients from 1987-2023. They were divided into 4 regions according to heart transplant recipients' residence: the Northeast, Midwest, South, and West. The endpoint was all-cause mortality. A total of 33,482 heart transplant recipients were included in the analysis. Baseline characteristics differed by region. The median survival (years) was lower in the South [Northeast 12.9 (6.1-17.9), Midwest 13.1 (6.5-18.1), South 11.6 (5.3-16.8), West 13.6 (7.0-18.6); p<0.0001]. Mortality incidence rate was greater in the South. When compared to the Northeast, in the unadjusted analysis, mortality was higher in the South [HR 1.13 (95%CI 1.07-1.19), p<0.001] and lower in the West [HR 0.89 (95%CI 0.83-0.94), p<0.001]. After adjusting for demographic and clinical variables, only the South retained significant differences [HR 1.17 (95%CI 1.10-1.24), p<0.001]. Mortality significantly increased in all regions after 2018. Mortality of heart transplant recipients varies across region of residence in the United States. A significant increase in adjusted mortality was observed in the South. These findings suggest that there are regional disparities in the mortality rates of heart transplant recipients.

Review of Association Between Urinary Tract Infections and Immunosuppressive Drugs after Heart Transplantation.

Management of infections in heart transplant recipients is complex and crucial. In this population, there is a need for a better understanding of immunosuppressive trough levels (C0), infectious complications, and urinary tract infections (UTIs). The purpose of this review was to understand the association between immunosuppressive trough levels and UTIs after heart transplantation. A review of scientific literature (n= 100) was conducted based on the topic of interest by searching PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. The analysis of bacterial pulmonary infection required the occurrence of new or deteriorating pulmonary infiltrates and the development of organisms in cultures of sputum specimens. The diagnosis of UTIs was based on the result of related signs, pyuria, and a positive urine culture. The incidence of UTIs was reported as 0.07 episodes/1000 regarding heart transplantation days. An eightfold increase in the rate of rejection was noted in heart transplant recipients with higher variability in tacrolimus C0. There are associations between C0 of immunosuppressive drugs and clinical presentation of infection complications. Recipients with a low metabolism of immunosuppressive drugs are more susceptible to infectious complications. Attention to the biology of herpes viruses, Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa, and Staphylococcus saprophyticus after heart transplantation are important, in which some of them are the most common pathogens responsible for UTIs. Pneumocystis and cytomegalovirus affect all transplant recipients. Pneumonia due to bacterial, viral, protozoa, and fungal infections, in addition to UTIs, are more specific reported types of infections in heart transplant recipients. Bacterial infections produced by extensively drug-resistant Enterobacteriaceae, vancomycin-resistant enterococci, and non-fermenting gramnegative bacteria were reported to increase after transplantation.

Association Between High Sensitivity Troponin I and NTproBNP With Rejection and Graft Loss in Pediatric Heart Transplant Recipients.

Troponin I is a blood biomarker of cardiac injury and levels measured using a high-sensitivity assay after pediatric heart transplantation (HT) have not been described. We sought to assess the association between high-sensitivity troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NTproBNP) with treated acute rejection (AR) and graft loss in pediatric heart transplant (HT) recipients. Serum was collected and banked from pediatric HT recipients prior to cardiac catheterization. Patients with samples drawn within 365 days post-HT were included and followed for up to 5 years. Generalized linear mixed-effect models examined the association between hsTnI and treated AR using a random intercept per patient. Cox proportional hazards models tested the association between maximal hsTnI and NT-proBNP and death/graft loss. HsTnI and NTproBNP values decline in the weeks following HT, after which these biomarkers stabilize. HsTnI was higher in AR versus no AR (6.2 vs. 3.5 ng/L, p < 0.001); doubling of hsTnI increased the odds of AR by 33% (p = 0.004). HsTnI showed moderate discrimination for AR with an AUC of 0.811 (95% CI 0.76, 0.87) and a NPV of 96.4% (95% CI 93.0, 98.1). Elevation in NT-proBNP was not associated with AR. In multivariable Cox modeling, a doubling of maximal NT-proBNP was associated with graft loss (HR 8.96, p = 0.014). In this pediatric HT cohort, HsTnI was moderately discriminative for AR and higher maximal NT-proBNP was associated with graft loss. HsTnI may add value in pediatric HT non-invasive AR surveillance, and elevated NTproBNP could suggest an increased risk of graft loss.

Association of early post-transplant hyperglycaemia and diabetes mellitus on outcomes following heart transplantation.

Early post-transplant hyperglycaemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5-year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre-transplant T2DM with adverse transplant-related outcomes. Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia. A total of 141 patients were included, of whom 25 had pre-existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre-existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5-year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre-existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three-fold increased likelihood of death compared to patients that remained free from diabetes. EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre-existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5-year survival compared to patients who remained free from diabetes during follow-up.

The Association Between Pulmonary Vascular Resistance and Posttransplant Outcomes Differs by Left Ventricular Assist Device Status.

Elevated pulmonary vascular resistance (PVR) is a risk factor for mortality after heart transplantation (HT), but whether this association differs for patients with and without left ventricular assist device (LVAD) support before HT is unknown. We analyzed adult first-time HT recipients from the United Network for Organ Sharing (UNOS) registry transplanted between 2010 and 2021. We quantified the association between PVR and the outcomes of 30 day graft failure and 1 year mortality using multivariable logistic regression, stratified by LVAD support status at the time of HT. Pulmonary vascular resistance was modeled using restricted cubic splines to identify clinically relevant risk thresholds. We also examined the association with 10 year survival using multivariable Cox proportional hazards regression. For PVR values less than approximately 2 WU, higher PVR was independently associated with a higher risk of early graft failure (odds ratio [OR] = 1.58, 95% CI: 1.06-2.36) and a higher risk of 1 year mortality (OR = 1.32, 95% CI: 1.10-1.59) among LVAD patients only (interaction p = 0.023 and 0.03, respectively). However, for patients surviving at least 1 year, PVR was not associated with long-term mortality among either subgroup. Whether more aggressive reduction of PVR among HT candidates supported with LVADs can mitigate these risks requires further study.

Assessing the cost-effectiveness of replacing antimetabolites with mTOR inhibitors in heart transplant immunosuppression in China: a network meta-analysis-based economic evaluation.

Although several pharmacoeconomic studies have assessed the cost-effectiveness of maintenance immunosuppressive regimens for heart transplant recipients, economic comparisons between various combination drug therapies remain sparse. This study used an economic evaluation based on network meta-analysis to assess the cost-effectiveness of four immunosuppressive regimens for adult heart transplant recipients in China. We conducted a systematic search for clinical trials in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP database. A validated Markov model was adapted to reflect the Chinese medical landscape. Four maintenance immunosuppression regimens were considered: tacrolimus/mycophenolate mofetil (TAC/MMF), cyclosporine/mycophenolate mofetil (CSA/MMF), everolimus/cyclosporine (EVL/CSA), and sirolimus/tacrolimus (SRL/TAC). The probabilities of health events were derived from a comprehensive literature review. Direct medical costs, adjusted for 2022 values, were from public documents and websites, while utilities for quality-adjusted life-years (QALYs) were taken from previous studies. Primary outcomes were mean lifetime cost, QALYs, and cost-effectiveness, with a willingness-to-pay (WTP) threshold set at three times China's GDP per capita in 2022. Sensitivity analyses were conducted to test the robustness of the results. The base case analysis identified TAC/MMF as the most cost-effective regimen, producing a mean of 6.31 QALYs per patient at a cost of Chinese Yuan (CNY) 534,182.89. Sensitivity analyses consistently reinforced TAC/MMF as the most cost-effective and robust choice. TAC/MMF is the most cost-effective maintenance immunosuppressive regimen for heart transplant recipients within the Chinese health system. The study findings are reinforced by sensitivity analyses, affirming their robustness amid various uncertainties.

Exercise as a modality to improve heart transplantation-related functional impairments: An article review.

Heart transplantation (HT), the treatment choice of advanced heart failure patients, is proven effective in increasing the survival and functional status of the recipients. However, compared to normal controls, functional status is lower in HT recipients. Exercise given in cardiac rehabilitation has been shown to improve exercise capacity as measured with peak oxygen uptake (VO2 peak) and muscle strength after completion of the program and cessation of exercise results in loss of exercise benefits. Several factors related to cardiac denervation and the use of immunosuppressive agents in HT recipients result in functional impairments including cardiovascular, pulmonary, exercise capacity, psychological, and quality of life (QoL) problems. High-intensity interval training (HIIT) is the most common type of exercise used in HT recipients and given as a hospital-based program. Improvement of functional impairments was found to have occurred due to primarily musculoskeletal adaptations through improvement of muscle structure and aerobic capacity and cardiovascular adaptations. In general, exercise given after transplantation improved VO2 peak significantly and improvement was better in the HIIT group compared to moderate intensity continuous training or no-exercise groups. Improvement of QoL was ascribed to improvement of exercise capacity, symptoms, pulmonary function, physical capacity improvement, anxiety, and depression.

Comparative Analysis of the Health Status of Heart Transplant Patients with Different Levels of Physical Activity

This study’s goals were to determine the health status of a group of heart transplant recipients (HTRs) and their level of physical activity and to compare the health status among them and with a group of healthy sedentary individuals. Fifty-four HTRs and eighteen sedentary individuals (S) were assigned to four groups, according to their level of physical activity (determined with the International Physical Activity Questionnaire); patients with a low, moderate, and high level of physical activity (HTRL, HTRM, and HTRH, respectively) and S participants underwent a basic blood analysis and several tests to assess their cardiovascular, neuromuscular, and functional mobility condition and their quality of life. The S and HTRH were very similar in terms of BP, HR, and blood analysis while HTRM and HTRL differed from both S and HTRH in these parameters. Regarding the cardiovascular, neuromuscular, functional mobility, and quality of life variables assessed in this study, HTRH showed the best results across all of them, followed by S, HTRM, and HTRL. It is suggested that the weekly level of physical activity of HTRs should be high, which might help them to enhance their health and quality of life.

Donor-derived Cell-free DNA Evaluation in Pediatric Heart Transplant Recipients: A Single-center 12-mo Experience.

Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients. Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information. The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 and P < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%. Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.

The Impact of Age and Body Composition on the Agreement between Estimated and Measured GFR in Heart Transplant Recipients

Plain Language SummaryAssessing kidney function in heart transplant recipients is paramount to adjust immunosuppressive, antibacterial, and antiviral therapy. An estimate of the kidney function from plasma creatinine measurements is less expensive and time-consuming than a direct measure of kidney function but may be inaccurate in heart transplant recipients. We compared estimated and measured kidney function in 150 heart transplanted patients with a total of 723 kidney function measurements. We find that the kidney function improved the first year after transplantation, which was not detected by the estimate of the kidney function. One year after transplantation, the estimate of the kidney function was, on average, accurate and not affected by body composition, but for the individual patient the estimate was very imprecise, especially in younger patients. The results suggest that kidney function in heart transplanted patients should be measured and not estimated, especially during the first year following transplantation and in younger patients.

Impact of New-Onset Diabetes after Transplantation on Cardiovascular Risk and Mortality in Korea: A Nationwide Population-Based Study.

Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL. Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis. A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment. NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.

Association between pre-heart transplant kidney function and post-transplant outcomes in Black and White adults.

It remains unknown whether estimated glomerular filtration rate (eGFR) using the refit Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without a term for race is associated with mortality and the need for kidney replacement therapy (KRT) differentially between Black and White heart transplant recipients. We studied 25,900 adults included in the Scientific Registry of Transplant Recipients. We classified recipients into six categories of eGFR (< 30, 30 to < 45, 45 to < 60, 60 to < 90, 90 to < 120, ≥ 120ml/min/1.73 m2) using the race-neutral CKD-EPI refit equation, and assessed survival with multivariable adjusted Cox proportional hazards regression. The association between pre-transplant race-neutral eGFR and mortality varied by race (Pinteraction = 0.006). Compared to White patients with an eGFR of 90-120ml/min/1.73 m2, the mortality rates were 57% (95% CI 1.25, 1.98), 29% (95% CI 1.11, 1.51), 34% (95% CI 1.19, 1.52), and 19% (95% CI 1.06, 1.33) higher in Black patients with an eGFR less than 30, 30-45, 45-60, and 60-90ml/min/1.73m2, respectively; and 53% (95% CI 1.28, 1.82), 49% (95% CI 1.33, 1.66), and 23% (95% CI 1.11, 1.35) higher among White patients with an eGFR less than 30, 30-45, and 45-60ml/min/1.73 m2, respectively. The association between pre-transplant eGFR and the need for KRT during follow-up was similar between Black and White patients (Pinteraction = 0.57). Worsening pre-transplant eGFR using the new race-neutral CKD-EPI refit equation was associated with a higher rate of post-heart transplant mortality and KRT in Black and White recipients. The racial disparity in post-heart transplant mortality was narrower in the setting of severe kidney dysfunction.

Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients

ObjectiveGut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in...

Hospital volume does not mitigate the impact of area socioeconomic deprivation on heart transplantation outcomes.

While structural socioeconomic inequity has been linked with inferior health outcomes, some have postulated reduced access to high-quality care to be the mediator. We assessed whether treatment at high-volume centers(HVC) would mitigate the adverse impact of area deprivation on heart transplantation(HT) outcomes. All HT recipients ≥18years were identified in the 2005-2022 Organ Procurement and Transplantation Network. Neighborhood socioeconomic deprivation was assessed using the previously validated Area Deprivation Index. Recipients with scores in the highest quintile were considered Most Deprived (others: Less Deprived). Hospitals in the highest quartile by cumulative center volume (≥21 transplants/year) were classified as HVC. The primary outcome was post-transplant survival. Of 38,022 HT recipients, 7,579 (20%) were considered Most Deprived. Following risk adjustment, Most Deprived demonstrated inferior survival at 3(hazard ratio[HR] 1.14, 95%confidence interval[CI] 1.06-1.21) and 5 years following transplantation (HR 1.13, CI 1.07-1.20). Similarly, Most Deprived faced greater graft failure at 3(HR 1.14, CI 1.06-1.22) and 5 years (HR 1.13, CI 1.07-1.20). Evaluating patients transplanted at HVC, Most Deprived continued to face greater mortality at 3(HR 1.10, CI 1.01-1.21) and 5 years (HR 1.10, CI 1.01-1.19). The interaction between Most Deprived status and care at HVC was not significant, such that transplantation at HVC did not ameliorate the survival disparity between Most and Less Deprived. Area socioeconomic disadvantage is independently associated with inferior survival. Transplantation at HVC did not eliminate this inequity. Future efforts are needed to increase engagement with longitudinal follow-up care and address systemic root causes to improve outcomes.

P.040: Association CYP3A5 gene polymorphisms with tacrolimus blood concentration in heart transplant recipients.

P.040: Association CYP3A5 gene polymorphisms with tacrolimus blood concentration in heart transplant recipients.