Risk Factors of Post-Traumatic Stress in Pediatric Solid Organ Transplant Recipients.

BACKGROUND: Life with end-stage organ failure is accompanied by an accumulation of traumatic medical or surgical experiences. Despite recovery after solid organ transplantation (SOT), many children and adolescents develop post-traumatic stress symptoms (PTSS). PTSS remain underappreciated as a major comorbidity in SOT programs, despite their association with decreased quality of life. METHODS: We conducted a retrospective, cross-sectional study of 86 pediatric SOT recipients (17 heart, 44 kidney, and 25 liver) to evaluate potential determinants of PTSS. Trauma symptoms were measured by the Child Trauma Screening Questionnaire (CTSQ). Demographic, baseline, and contemporaneous factors were tested for independent association with CTSQ scores. RESULTS: The median post-transplant CTSQ score was 2 (IQR 1-4), and 22% were identified as high risk (score ≥5) for PTSD. Higher CTSQ scores were independently associated with the number of ICU days within the previous 12 months, the number of medications (complexity), and involvement with foster care in the primary model (R2 [adj.] = 0.26). The addition of the Family Impact Module improved the overall model (R2 [adj.] = 0.33), wherein higher family functioning was independently associated with lower CTSQ scores. An exploratory analysis of pre-transplant patients (n = 34) found a median pre-transplant CTSQ of 2 (IQR 1-6), suggesting that PTSS are onset before transplant and persist afterward. CONCLUSIONS: PTSS are highly prevalent in the SOT population. Risk factors include recent adverse medical experiences and complexity, whereas family stability may be protective. Additional research is needed to improve early ascertainment and support for patients at high risk of developing PTSS throughout their transplant journey.

Early Outcomes in Heart Transplantation using Donation after Circulatory Death Donors in Patients Bridged with Durable Left Ventricular Assist Devices.

OBJECTIVE: Donation after circulatory death (DCD) heart transplantation potentially increases donor allografts, especially for patients with lower listing status. We assessed outcomes of DCD heart transplantation in patients bridged with durable left ventricular assist devices (LVAD). METHODS: The United Network for Organ Sharing (UNOS) database was queried for adult heart transplants utilizing DCD donors from 2019-2022. Patients were stratified between those with durable LVAD versus those with intra-aortic balloon pump, inotropic, or no bridging support (control group). Primary outcome was 1-year mortality. Secondary endpoints were hospital length of stay, stroke, pacemaker implantation, dialysis, and acute rejection before discharge. RESULTS: 160 LVAD recipients and 311 control recipients met study inclusion criteria. Recipients bridged with LVAD were younger (55 vs. 58 years, p<0.001) with lower BMI (28.3 vs. 30.3, p<0.001), longer waitlist times (112 vs. 34 days, p<0.001), longer out of body times (5.7 vs 4.6 hours, p<0.001), and less frequent normothermic regional perfusion (31% vs 40%, p=0.049). LVAD patients were commonly transplanted at UNOS status 3-4 (92%), while control patients were transplanted at status 2 (27%), status 3 (10%), status 4 (30%), or status 6 (30%). Kaplan-Meier analysis showed no difference in 1-year mortality between groups (p=0.34). However, acute rejection was higher in the unadjusted LVAD cohort (26% vs. 13%, p<0.001). On multivariable logistic regression, LVAD was an independent predictor of acute rejection (OR: 2.21, 95% CI:1.32-3.69, p=0.002). CONCLUSIONS: Durable LVAD may be associated with higher risk of developing an early inflammatory response in DCD heart transplantation; however, 1-year survival was similar between groups.

Natural recovery of cardiac allograft diastolic function, a retrospective longitudinal report.

Cardiac allografts suffer diastolic dysfunction early post-heart transplantation (HTx) due to ischemic injury, however the natural course of diastology recovery post HTx remains unknown (Tallaj et al., 2007 [1]). We retrospectively reviewed 60 adult HTx patients between 2015 and 2021 at a single site. Invasive hemodynamics and echocardiograms were obtained at 2 weeks and 1, 3, 6, and 12 months post-HTx. RA strain by 2D feature tracking was compared to intracardiac pressure measurements. In all patients, we observed normalization of RV and RA filling pressures by post-operative week 12 and recovery of diastolic dysfunction by month 6. There was an inverse correlation between RV end-diastolic pressure and RA contractile (r = -0.192, p < 0.05) and reservoir (r = -0.128, p < 0.05) functions in the allograft. As the post-transplant care paradigm shifts away from invasive procedures, right atrial indices should be included in imaging-based allograft surveillance studies.

Highly Sensitized Patients Listed for Heart After Liver Transplantation With or Without Domino.

For patients with end stage heart disease and borderline hemodynamics, high HLA allosensitization presents a barrier for heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant (HALT-D) on a single patient without liver disease. We describe this patient's course to date as well as four subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.

Effect of CMV Mismatch on Heart Transplant Outcomes Using a Surveillance and Preemptive Strategy.

PURPOSE: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R-) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. METHODS: A review of patient records from January 2010 to December 2020 with follow-up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. RESULTS: Two hundred and twenty-one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty-six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). CONCLUSIONS: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation.

Clinical Outcomes After a Biopsy Diagnosis of Antibody-mediated Rejection in Pediatric Heart Transplant Recipients.

BACKGROUND: Extending graft survival after heart transplant (HT) is of paramount importance to achieve survival well into adulthood for childhood recipients. Acute rejection is a significant adverse event, and biopsy remains the most specific means for diagnosing acute cellular rejection (ACR) versus antibody-mediated rejection (AMR). METHODS: All children in the Pediatric Heart Transplant Society (PHTS) Registry who underwent HT between 1/2015 and 6/2022 and had ≥1 episode of treated rejection were included. Survival after rejection was compared between those with AMR and those with ACR-only. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) were assessed. Risk factors for graft loss after AMR were identified using Cox proportional hazard modeling. RESULTS: Among 906 children treated for rejection during follow-up through 12/2022, 697 (77%) with complete biopsy information were included. AMR was present on biopsy in 261 (37%) patients; ACR-only was present in 436 (63%) patients. Time to treated rejection was earlier in those with AMR, median time from HT to rejection 0.11 versus 0.29 years, p=0.0006. When rejection occurred within the 1st year, survival after AMR was lower than survival after ACR-only. Predictors of graft loss after AMR were younger age at HT, diagnosis of congenital heart disease, and rejection with hemodynamic compromise. There was no difference in time to CAV, infection, or malignancy after treated rejection between groups. CONCLUSIONS: The largest analysis of pediatric HT recipients treated for rejection with biopsy data to identify AMR underscores the continued importance of AMR on survival. AMR is associated with higher graft loss versus ACR when occurring in the first-year post HT. Predictors of graft loss after AMR identify patients who may benefit from increased surveillance, more aggressive rejection treatment, or augmented maintenance immunosuppression.

Single-center experience of extended brain-death donor heart preservation with the organ care system.

BACKGROUND: The Organ Care System (OCS) (Transmedics, Andover, MA) reduces cold ischemic time of donor hearts by producing a normothermic beating state during ex vivo perfusion, enabling extended ex situ intervals, which potentially increases donor pool. We aimed to compare outcomes in utilization of OCS and conventional cold storage technique. METHODS: Consecutive heart transplants following brain death at our institution between May 2022 and July 2023 were analyzed. Recipients were divided into those receiving hearts preserved with OCS [N = 15] and those with conventional cold storage (Control, N = 27), with OCS utilization when anticipated ischemic time was more than 4 h. Pre-transplant characteristics and transplant outcomes were compared. RESULTS: OCS utilization allowed a significant increase in distance traveled for heart retrieval (OCS, 624 ± 269 vs. Control, 153 ± 128 miles, p < 0.001), with longer mean total preservation times (6.2 ± 1.1 vs 2.6 ± 0.6 h, p < 0.001). All but one patient displayed a general decrease or plateau in lactate throughout perfusion time by OCS. Both groups experienced similar rates of severe primary graft dysfunction (OCS, 6.7% [N = 1] vs. Control, 11.1% [N = 3], p = 0.63), with 100% in-hospital survival in the OCS group compared to 96.3% in the Control group (p = 0.34). Kaplan-Meier survival analysis showed that estimated one-year survival were comparable (OCS, 93.3 ± 6.4% vs. Control, 88.9 ± 6.0%, p = 0.61). CONCLUSION: With a mean preservation time of around 6 h and distance covered of over 600 miles, our results using OCS indicate a potential to safely increase the quantity and viability of accessible organs, thus broadening the donor pool without negatively affecting outcomes.

Feasibility of a Multidomain Resiliency Assessment in Patients with Advanced Heart Failure Requiring Surgery: A Pilot Study.

OBJECTIVE: The resiliency of patients who have advanced heart failure (HF) and undergo a physical stressor such as heart transplantation or left ventricular assist device implantation has yet to be studied in the physical, cognitive, and psychosocial domains. The primary aim of this pilot study was to assess the feasibility of a multidomain resiliency assessment in patients who have advanced HF and require surgery. METHODS: A battery of assessments in each of the domains was completed at baseline before surgical intervention, after intensive care discharge, and 3 and 6 months after surgery. Feasibility was assessed through completion rates, time required to complete the assessments, and qualitative feedback from assessors. RESULTS: Although various completion rates were noted at different time points, high completion rates were seen for grip strength, the modified Fried frailty phenotype, and the Montreal Cognitive Assessment. Additionally, when controlled for patients who were medically restricted from physical function, the Short Physical Performance Battery, gait speed, and the 30-second chair stand test also had high completion rates. A trend toward return to baseline status or an improvement in baseline status was observed in all physical and cognitive assessments and most psychosocial assessments at 3 and 6 months. Minimal change was noted in the Brief Resilience Scale questionnaire. CONCLUSION: This pilot study demonstrates that a multidomain assessment of resiliency is feasible in patients with advanced HF. Future studies are needed to help determine specific assessments or patient factors that would help predict positive postsurgical outcomes in this population. IMPACT: This study has implications for clinical practice on the most feasible assessments in multiple domains for patients who have advanced HF and are being evaluated for heart transplantation or left ventricular assist device.

Center and Individual Willingness to Consider Heart and Lung Offers From Donors With Hepatitis C.

INTRODUCTION: Transplants with hearts and lungs from donors with hepatitis C virus (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV + persists as a reason to decline organs. METHODS: We identified adult candidates listed January 1, 2015-March 8, 2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual-level and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework. RESULTS: Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5%-74.3%) and lung (7.8%-59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9%-91.1%) and lung (32.8%-82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively. CONCLUSIONS: Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients' transplant access.

Implantation of a permanent pacemaker following orthotopic heart transplantation: a systematic review and meta-analysis.

BACKGROUND: Orthotopic heart transplant (OHT) is among the final armamentariums for end-stage heart disease. Many patients who have had OHT require a post-transplant permanent pacemaker (PPM) implantation due to an abnormal conduction system. We aimed to evaluate the risk of mortality and acute rejection in patients with OHT who had received PPM compared to patients without PPM and to determine predictors for PPM placement in this population. METHODS: We comprehensively searched for studies from MEDLINE, EMBASE, and Cochrane databases from inception to September 2023. Inclusion criteria focused on patients who had undergone OHT and PPM implantation post-transplant. Data from each study were combined using a random-effects model. Results were expressed as relative risk (RR) or odd ratios (OR) with a 95% confidence interval (CI). RESULTS: A total of 9 studies were included in this meta-analysis incorporating a total of 54,848 patients (3.3% had PPM). The pooled all-cause mortality rate among patients with PPM post-OHT was 26% (95% CI: 19-33%, I2 = 1%). There were no differences between post-heart transplant patients with PPM and those without PPM in risk of all-cause mortality (RR 0.76, 95% CI: 0.43-1.34; I2 = 45%) and acute rejection (RR 1.22, 95% CI: 0.74-2.00, I2 = 59%). Bi-atrial anastomosis was associated with an increased risk of PPM implantation post-OHT (OR 7.74, 95% CI: 3.55-16.91, I2 = 0%), while pre-OHT mechanical circulatory support (MCS) was associated with a decreased risk of PPM implantation post-OHT (OR 0.45, 95% CI 0.27-0.76, I2 = 0%). CONCLUSION: There were no significant differences in all-cause mortality or acute rejection between post-OHT recipients who required PPM compared to those who did not receive PPM. Further, bi-atrial anastomosis portended the need for PPM implantation, while MCS was associated with a decreased occurrence of PPM.

Use of Evolocumab in Familial Hyperlipidemia With Isolated Heart Transplant.

We describe a novel use of evolocumab for successful postoperative lipid control in a patient with familial hyperlipidemia who underwent isolated heart transplantation. We believe that this case carries valuable lessons regarding post-transplant proprotein convertase subtilisin kexin 9 inhibitor use with implications for the future of combined organ allocation and transplantation waitlist times.

Indication for Pediatric Heart Transplant Affects Longitudinal Chronotropy on Cardiopulmonary Exercise Testing.

Studies have suggested that pediatric patients with heart transplants (HT) due to congenital heart disease (CHD) perform differently on cardiopulmonary exercise testing compared to pediatric patients with HT due to cardiomyopathy (CM). However, it is not known if this relationship changes over time. The aim of this study was to examine the differences in cardiopulmonary exercise test (CPET) parameters over time between patients with HT due to CHD versus CM. A large single-institution CPET database was used for this study. We conducted a retrospective cohort study of 250 total CPETs from 93 unique patients, examining how patients with HT due to CHD (109 CPETs, 40 unique patients) differed in CPET performance from patients with HT due to CM (141 CPETs, 53 unique patients) from < 2 years post-HT, 2 to < 6 years post-HT, and ≥ 6 years post-HT. There were no differences between patients with HT due to CHD compared to CM in CPETs performed < 2 years post-HT. In CPETs performed 2 to < 6 years post-HT, the CM group had higher maximal HR and percentage of age-predicted maximal heart rate (APMHR) achieved. At ≥ 6 years post-HT, the CM group continued to have higher maximal HR and percentage of APMHR achieved, but also improved HR recovery at one minute. Initial indication for transplant may affect performance on CPETs post-transplant. Patients with HT due to CM have improved chronotropic measures compared to patients with HT due to CHD and these differences are more pronounced with increased time post-HT.

Added prognostic value of visually estimated coronary artery calcium among heart transplant recipients.

BACKGROUND: Cardiac hybrid positron emission tomography/computed tomography (PET/CT) has become a valid screening modality for cardiac allograft vasculopathy (CAV) following heart transplantation (HT). Visually estimated coronary artery calcium (VECAC) can be quantified from CT images obtained as part of PET/CT and has been shown to be associated with adverse cardiovascular outcomes in coronary artery disease. We investigated the prognostic value of VECAC following HT. METHODS: A retrospective analysis of 430 consecutive adult HT patients who underwent 13N-ammonia cardiac PET/CT from 2016 to 2019 with follow-up through October 15, 2022, was performed. VECAC categories included: VECAC 0, VECAC 1-9, VECAC 10-99, and VECAC 100+. The association between VECAC categories and outcomes was assessed using univariable and multivariable proportional hazards regression. The primary outcome was death/retransplantation. RESULTS: The cohort was 73% male, 33% had diabetes, 67% had estimated glomerular filtration rate <60 ml/min, median age was 61 years, and median time since HT was 7.5 years. VECAC alone was insufficiently sensitive to screen for CAV. During a median follow-up of 4.2 years ninety patients experienced death or retransplantation. Compared with those with VECAC 0, patients VECAC 10-99 (HR 2.25, 95% CI 1.23-4.14, p = 0.009) and VECAC 100+ (HR 3.42, 95% CI 1.96-5.99, p < 0.001) experienced an increased risk of death/retransplantation. The association was similar for cardiovascular death and cardiovascular hospitalization. After adjusting for other predictors of death/retransplantation, VECAC 10-99 (VECAC 10-99: aHR 1.95, 95% CI 1.03-3.71 p = 0.04) and VECAC 100+ (VECAC 100+: aHR 2.33, 95% CI 1.17-4.63, p = 0.02) remained independently associated with death/retransplantation. CONCLUSIONS: VECAC is an independent prognostic marker of death/retransplantation following HT and merits inclusion as a part of post-HT surveillance PET/CT.

Dual immunoadsorption for ABO-incompatible heart transplantation in a 35 kg child.

Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible (ABOi) heart transplantation. Here we report the first case of a patient transplanted with ABO-IA, that was of an age and weight that required two ABO-IA columns run in parallel, to enable the reduction in antibody titres to a sufficiently low level in the time available during implantation of the donor organ.

LCP-Tacrolimus Extended-Release (Envarsus XR) Use in Adolescent and Young Adult Solid Organ Transplant Recipients.

INTRODUCTION: Limited published experience describes once daily, extended-release tacrolimus (LCP-Tac) use in pediatric solid organ transplantation (SOT), particularly nonrenal SOT. LCP-Tac can simplify immunosuppression (IS) regimens, minimize immediate release-tacrolimus (IR-Tac)-associated adverse effects, and promote adherence. This study describes the successful use of LCP-Tac in adolescent and young adult (AYA) SOT populations. METHODS: A single-center, retrospective chart review of AYA SOT recipients (age < 25 years) converted from IR-Tac to LCP-Tac. Graft survival, biopsy-proven acute rejection (BPAR), infection rates, estimated glomerular filtration rate (eGFR), and pill burden were assessed at five time points postconversion (1, 3, 6, 12, and 24 months). Intrapatient variability of tacrolimus, as assessed by coefficient of variability (CV%), was also analyzed. RESULTS: Twenty-nine AYA SOT recipients (19 heart, 6 kidney, and 4 liver) were converted to LCP-Tac, with a median age of 17.4 years at conversion. Conversion, mainly due to perceived or identified medication nonadherence, occurred at a median of 5.4 years posttransplant. No graft loss occurred within 24 months of conversion, and BPAR incidence rate was consistent with previous reports for these populations. Only one patient experienced CMV infection. Renal function remained stable postconversion. CONCLUSION: Successful conversion from IR-Tac to LCP-Tac was demonstrated in AYA heart, kidney, and liver transplant recipients. These AYA SOT recipients experienced reduced pill burden and improved tacrolimus trough concentration variability. However, the impact on medication adherence warrants further investigation. Future research should explore the targeted use of LCP-Tac to enhance IS tolerability and medication adherence in young SOT populations.

First worldwide use of the hybrid system for extracorporeal circulation in heart transplant.

BACKGROUND: This case report documents the first worldwide use of the Hybrid System from Spectrum Medical in a heart transplant procedure, focusing on its safety and efficacy. Traditional cardiopulmonary bypass systems often use an open reservoir, which increases the blood's exposure to air, thereby heightening the risk of an inflammatory response and gas embolism. In contrast, the Hybrid System is designed to improve surgical outcomes by significantly reducing the blood-air interface. This system utilizes a dual-chamber cardiotomy-venous reservoir with a collapsible soft bag, effectively minimizing blood contact with air and foreign materials. However, it is important to note that there is currently no evidence supporting the use of this methodology specifically in heart transplants. CASE PRESENTATION: A 41-year-old male managed with a left ventricular assist device because of dilated cardiomyopathy underwent a heart transplant using the Hybrid System. The perioperative and postoperative data provided evidence of the system's effectiveness. The selection of this patient was due to the absence of significant comorbidities unrelated to his primary cardiac condition, making him an ideal candidate to evaluate the system's performance. CONCLUSION: The Hybrid System is safe and efficient. The successful implementation in this case highlights its advantages over traditional cardiopulmonary bypass systems, suggesting a promising future in cardiac surgery. Further studies with routine cardiac surgery patients are required to validate these findings.

International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.