Cardiac Transplant Recipients Research Articles

6299107 Anaesthetic, maternal and neonatal outcomes in cardiac transplant recipients

6299107 Anaesthetic, maternal and neonatal outcomes in cardiac transplant recipients

D-43 | Restenosis and Outcomes Following PCI of Small Vessels in Cardiac Transplant Recipients

D-43 | Restenosis and Outcomes Following PCI of Small Vessels in Cardiac Transplant Recipients

(971) - Kaposi Sarcoma Due to Possible Donor-Derived Human Herpesvirus-8 Infection in a Cardiac Transplant Recipient

(971) - Kaposi Sarcoma Due to Possible Donor-Derived Human Herpesvirus-8 Infection in a Cardiac Transplant Recipient

(345) - Allosensitized Cardiac Transplant Recipients Treated with CD38-Antibody Daratumumab Show Histomorphologic Signs of PAMR in Biopsies without Clinical Signs of Rejection

(345) - Allosensitized Cardiac Transplant Recipients Treated with CD38-Antibody Daratumumab Show Histomorphologic Signs of PAMR in Biopsies without Clinical Signs of Rejection

Ten-year outcomes post percutaneous coronary intervention in cardiac transplant recipients

BackgroundCardiac allograft vasculopathy (CAV) is one of the major late causes of mortality in cardiac transplant recipients beyond the first year. Given the lack of longer term data for PCI in cardiac transplant recipients, we report ten year follow up of such cardiac transplant recipients who underwent PCI at Mayo Clinic. MethodsA retrospective observational study was conducted that included cardiac transplant recipients who underwent PCI at the Mayo Clinic. Continuous variables were presented as mean (SD) or median (IQR) and discrete variables were presented as frequency (percentage). ResultsThirty-eight consecutive cardiac transplant recipients underwent PCI from January 1, 1995, to June 30, 2023, at the Mayo Clinic. The median age of the cohort was 61.00 years (IQR:51.00–70.00) comprised predominantly of men (65.80%), and 47.40% of the cohort presented with an acute coronary syndrome. The antirejection therapy prior to the PCI included steroids (47.30%), cyclosporine (26.30%), tacrolimus (15.80%), mycophenolate (42.10%), azathioprine (13.10%), & sirolimus (31.57%). Intravascular ultrasound during PCI was utilized in 10.50% of the cases. The median time duration between heart transplant and PCI was 9.00 years (IQR:6.00–13.00 years). Two individuals needed repeat heart transplant for severe CAV. In hospital mortality was 5.20% and the long-term median survival was 7.20 years with a 10-year mortality rate of 65.70%. ConclusionsThis is the first publication reporting ten-year outcomes for PCI in cardiac transplant patients. The salient features for our cohort were a 65.70% mortality rate at 10 years and a median survival of 7.20 years.

Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study

AbstractPosttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus–infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein–specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vβT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.

Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study.

Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.

Comparative Analysis of Clinical Outcomes for COVID-19 and Influenza among Cardiac Transplant Recipients in the United States.

COVID-19 infections can lead to worse outcomes in an immunocompromised population with multiple comorbidities, e.g., heart transplant patients. We used the National Inpatient Sample database to compare heart transplant outcomes in patients with COVID-19 vs. influenza. A total of 2460 patients were included in this study: heart transplant with COVID-19 (n = 1155, 47.0%) and heart transplant with influenza (n = 1305, 53.0%) with the primary outcome of in-hospital mortality. In-hospital mortality (n = 120) was significantly higher for heart transplant patients infected with COVID-19 compared to those infected with influenza (9.5% vs. 0.8%, adjusted OR: 51.6 [95% CI 4.3-615.9], p = 0.002) along with significantly higher rates of mechanical ventilation, acute heart failure, ventricular arrhythmias, and higher mean total hospitalization cost compared to the influenza group. More studies are needed on the role of vaccination and treatment to improve outcomes in this vulnerable population.

Cardiac Allograft Rejection: Strategies for Success in the Face of Immune Challenges.

Heart transplantation for patients with end-stage heart failure refractory to medical therapy has remained definitive treatment with significant advances in posttransplant care. Despite improvement in postoperative morbidity and mortality, acute cellular rejection (ACR) and antibody-mediated rejection (AMR) remain substantial challenges that can lead to allograft failure and patient mortality. Immunosuppressive agents have been the mainstay of both prevention and treatment for ACR and AMR; however, many challenges exist with traditional therapies. There are a multitude of molecular pathways involved in mediating the humoral and cellular response to rejection, offering various targets for treatment. This review summarizes therapies used in the management of ACR and AMR as extrapolated from use in induction therapy and treatment of other solid-organ transplant rejection. Future studies focused on cardiac transplant recipients are needed to expand therapeutic options.

Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitised Cardiac Transplant Recipient

Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitised Cardiac Transplant Recipient

The COVID-19 Pandemic and Adult Cardiac Transplantation: Impact, Interventions, and Implications.

In this review, we provide a comprehensive overview of the impact of the COVID-19 pandemic on adult heart transplantation. We highlight the decline in the number of adult transplantations performed throughout the pandemic as a consequence of restrictions imposed on individual programs and hospitals. There were challenges to maintaining cardiac transplant activity at multiple levels, including organ donation in intensive care units, logistical difficulties with organ procurement, and rapidly changing resource considerations at health system and jurisdictional levels. We also review the impact of COVID-19 on cardiac transplant recipients. Despite the high rates of morbidity and mortality observed during the initial phases of the pandemic among heart transplant patients infected with COVID-19, the availability of effective vaccines, pre-exposure prophylaxis, and specific antiviral therapies have drastically improved outcomes over time. Vaccines have proven to be safe and effective in reducing infections and illness severity, but specific considerations in the immunocompromised solid organ transplant population apply, including the need for additional booster doses to achieve sufficient immunisation. We further outline the strong rationale for vaccination before transplantation wherever possible. Finally, the COVID-19 response created a number of barriers to safe and efficient post-transplantation care. Given the need for frequent evaluation and monitoring, especially in the first several months after cardiac transplantation, the pandemic provided the impetus to improve virtual care delivery and explore noninvasive rejection surveillance through gene expression profiling. We hope that lessons learned will allow us to prepare and pivot effectively during future pandemics and health care emergencies.

A035 Long Term Outcomes Following Bariatric Surgery in Cardiac and Lung Transplant Recipients

A035 Long Term Outcomes Following Bariatric Surgery in Cardiac and Lung Transplant Recipients

Animal Models for Heart Transplantation Focusing on the Pathological Conditions.

Cardiac transplant recipients face many complications due to transplant rejection. Scientists must conduct animal experiments to study disease onset mechanisms and develop countermeasures. Therefore, many animal models have been developed for research topics including immunopathology of graft rejection, immunosuppressive therapies, anastomotic techniques, and graft preservation techniques. Small experimental animals include rodents, rabbits, and guinea pigs. They have a high metabolic rate, high reproductive rate, small size for easy handling, and low cost. Additionally, they have genetically modified strains for pathological mechanisms research; however, there is a lacuna, as these research results rarely translate directly to clinical applications. Large animals, including canines, pigs, and non-human primates, have anatomical structures and physiological states that are similar to those of humans; therefore, they are often used to validate the results obtained from small animal studies and directly speculate on the feasibility of applying these results in clinical practice. Before 2023, PubMed Central® at the United States National Institute of Health's National Library of Medicine was used for literature searches on the animal models for heart transplantation focusing on the pathological conditions. Unpublished reports and abstracts from conferences were excluded from this review article. We discussed the applications of small- and large-animal models in heart transplantation-related studies. This review article aimed to provide researchers with a complete understanding of animal models for heart transplantation by focusing on the pathological conditions created by each model.

Evaluation of perivascular fat attenuation with coronary CT angiography in cardiac transplantation patients: an imaging biomarker candidate for prediction of cardiac mortality and re-transplantation

ObjectivesIn cardiac transplant recipients, non-invasive allograft surveillance for identifying patients at risk for graft failure remains challenging. The fat attenuation index (FAI) of the perivascular adipose tissue in coronary computed tomography angiography (CCTA) predicts outcomes in coronary artery disease in non-transplanted hearts; however, it has not been evaluated in cardiac transplant patients.MethodsWe followed 39 cardiac transplant patients with two or more CCTAs obtained between 2010 and 2021. We performed FAI measurements around the proximal 4 cm segments of the left anterior descending (LAD), right coronary artery (RCA), and left circumflex artery (LCx) using a previously validated methodology. The FAI was analyzed at a threshold of − 30 to − 190 Hounsfield units.ResultsFAI measurements were completed in 113 CCTAs, obtained on two same-vendor CT models. Within each CCTA, the FAI values between coronary vessels were strongly correlated (RCA and LAD R = 0.67 (p < 0.0001), RCA and LCx R = 0.58 (p < 0.0001), LAD and LCx R = 0.67 (p < 0.0001)). The FAIs of each coronary vessel between the patient’s first and last CCTA completed at 120 kV were also correlated (RCA R = 0.73 (p < 0.0001), LAD R = 0.81 (p < 0.0001), LCx R = 0.55 (p = 0.0069). Finally, a high mean FAI value of all three coronary vessels at baseline (mean ≥ − 71 HU) was predictive of cardiac mortality or re-transplantation, however, not predictive of all cause-mortality.ConclusionHigh baseline FAI values may identify a higher-risk cardiac transplant population; thus, FAI may support the implementation of CCTA in post-transplant surveillance.Key Point• Perivascular fat attenuation measured with coronary CT is feasible in cardiac transplant patients and may predict cardiac mortality or need for re-transplantation.

Cardiac transplant and exercise cardiac rehabilitation.

Cardiac transplantation is the final therapeutic option for patients with end-stage heart failure. Most patients experience a favorable functional ability post-transplant. However, episodes of acute rejection, and multiple comorbidities such as hypertension, diabetes mellitus, chronic kidney disease and cardiac allograft vasculopathy are common. The number of transplants has increased steadily over the past two decades with 3,817 operations performed in the United States in 2021. Patients have abnormal exercise physiologic responses related to surgical cardiac denervation, diastolic dysfunction, and the legacy of reduced skeletal muscle oxidative capacity and impaired peripheral and coronary vasodilatory reserve resulting from pre-transplant chronic heart failure. Cardiorespiratory fitness is below normal for most patients with a mean peak VO2 of approximately 60% of predicted for healthy persons. Cardiac transplant recipients are therefore excellent candidates for Exercise-Based Cardiac Rehabilitation (CR). CR is safe and is a recommendation of professional societies both before (pre-rehabilitation) and after transplantation. CR improves peak VO2, autonomic function, quality of life, and skeletal muscle strength. Exercise training reduces the severity of cardiac allograft vasculopathy, stroke risk, percutaneous coronary intervention, hospitalization for either acute rejection or heart failure, and death. However, there are deficits in our knowledge regarding CR for women and children. In addition, the use of telehealth options for the provision of CR for cardiac transplant patients requires additional investigation.

(756) Immunogenicity of COVID-19 Vaccination in Cardiac Transplant Recipients: 5 Months Follow-Up after the 3rd Dose

(756) Immunogenicity of COVID-19 Vaccination in Cardiac Transplant Recipients: 5 Months Follow-Up after the 3rd Dose

Stimulant Use for ADHD in a Cardiac Transplant Recipient: A Case Report

AbstractIntroductionMethylphenidate is a central nervous system stimulant used as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). CNS stimulant use is associated with increased risk of cardiovascular events such as increased resting heart rate and blood pressure, sudden cardiac death, arrhythmia, and stroke. Its safety profile in recipients of cardiovascular transplants is unknown, and more research is warranted to determine the risk of adverse cardiac events due to stimulant medication in this population.MethodsClinical case report, n=1Results/Clinical CaseA 19-year-old female with a history of restrictive cardiomyopathy, cardiac arrest, and orthotopic cardiac transplant has been treated with methylphenidate for ADHD for approximately 2 years without incident. The patient was diagnosed with ADHD between the ages of 8 and 10 and historically was treated with stimulant medication. At age 13, she experienced a cardiac arrest after a volleyball game with 4–6 minutes of pulselessness. She was successfully resuscitated and underwent defibrillator placement. It was concluded that the patient had restrictive cardiomyopathy undetected at birth, leading to the need for orthotopic cardiac transplantation at age 16. After her cardiac arrest, the patient’s memory and cognition worsened, and approximately 1 year after her transplant, she was prescribed amantadine. The patient remained untreated for her ADHD until approximately 1.5 years after her cardiac transplant, at which time she underwent neuropsychological testing that showed findings consistent with attention deficit disorder, and was restarted on stimulant medication. Her transplant cardiologist and psychiatrist have collaborated in her ongoing treatment with methylphenidate 40 mg daily and monitoring symptom response and cardiac stability. Because the patient had previously been stable on stimulant medication for many years, it is reasonable to conclude that stimulant medication did not lead to her cardiac arrest. The patient reports that methylphenidate has been helpful in improving her functioning as a college student, through reduction of her ADHD symptoms. The patient’s blood pressure and heart rate remain within an acceptable range and she has not experienced any adverse cardiac events to date while taking methylphenidate.ConclusionThis case sheds light on the potential to treat cardiac transplant recipients with stimulant medication for ADHD. Although a careful evaluation of risk factors must be undertaken in cooperation with cardiology and other specialists, a role exists for the safe use of stimulant medications in the cardiac transplant population.FundingNo Funding

(60) Impact of Donor Specific Antibodies in Cardiac Transplant Recipients after Acute Covid-19

(60) Impact of Donor Specific Antibodies in Cardiac Transplant Recipients after Acute Covid-19

(1016) Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitized Cardiac Transplant Recipient

(1016) Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitized Cardiac Transplant Recipient

Chicken or Egg: Tricuspid Regurgitation-The Cause or the Consequence of Post-Heart Transplant Allograft Dysfunction.

Tricuspid regurgitation (TR) is the most common valvular abnormality in cardiac transplant recipients.1 The causes of posttransplant TR are often obscure and can be multifactorial.2,3 The prognostic significance of posttransplant TR and the clinical implications of the severity of TR remain unclear and undefined.4-6 To clarify these questions, Bart et al7 conducted a retrospective study of their heart transplant patients over a 6-y period, examining transthoracic echocardiograms in 163 patients. Of these patients, 142 had a transthoracic echocardiograms before their first posttransplant endomyocardial biopsy (EMB). At month 0 posttransplant, 127 patients (78%) had no or mild TR before their first EMB, whereas 36 patients (22%) had moderate–severe TR.7 In patients with no or mild TR, 9 (7%) progressed to moderate–severe TR by 6 mo and 1 underwent tricuspid valve (TV) surgery.7 Of the patients with moderate–severe TR before the first biopsy, by 2 y, 3 had undergone TV surgery. Furthermore, in the moderate–severe TR before first biopsy group, postoperative extracorporeal membrane oxygenation (ECMO) use was significantly more common (78%; P < 0.05), as was rejection frequency (P = 0.02).7 Patients with late progressive moderate–severe TR had a significantly higher 2-y mortality than those who had moderate–severe TR immediately.7 Severe TR post–heart transplant is associated with a worse outcome8 although the clinical outcomes are otherwise variable.4 The consequences of severe TR can result in right ventricular dilatation with hepatic and renal congestion and subsequent dysfunction. Major causes of posttransplant TR include damage to the TV from the EMB and perioperative complications such as primary graft dysfunction (PGD), which often requires ECMO. This would explain the association of ECMO with moderate–severe TR. Additionally, rejection frequency was associated with greater severity of TR. This may be because of injury to the allograft from rejection as well as performing more EMB to make the diagnosis of rejection with concomitant damage to the TV. There has been some evidence that bicaval heart transplants are less likely to develop severe TR as opposed to the older biatrial transplant technique.9,10 However, the current study did not observe a difference. This retrospective study has significant limitations, which are clearly delineated by the authors. A retrospective, single-center study is likely not able to determine if there are specific factors that have causality in the development of TR, its severity, and its progression. The predominant use of the biatrial approach among this study’s patients would limit the ability to distinguish one surgical approach from another in terms of causality of TR. The increasing use of the bicaval approach may reduce the likelihood of developing TR or severe TR. The correlation of ECMO with the development of moderate–severe TR and worse prognoses would suggest that the presence of moderate–severe TR would be a consequence of severe allograft dysfunction posttransplant, necessitating resorting to ECMO for postoperative support. These patients would have worse prognoses on the basis of having PGD, and the severity of TR would, in essence, be an epiphenomenon and a surrogate marker of severe allograft dysfunction posttransplant, given the increased likelihood of developing hepatic and renal congestion and subsequent end-organ dysfunction with severe TR. We can conclude from the results of the current study that TR severity and progression are unsurprisingly associated with severe posttransplant allograft dysfunction with damage to the valve and allograft function. This and the concomitant TV valve damage would adversely affect posttransplant outcomes. The association of rejection frequency with TV severity could be associated with EMB-induced TR, which is also not surprising. What is missing from this study is a more prospective assessment of the relationship of pretransplant and posttransplant pulmonary hemodynamics and volume status to the development of and the severity of TR as well as the relationship with risk factors of PGD. This article serves as a starting point for future investigations. Ultimately, to resolve the questions raised by this article and to better understand the causes and risk factors of TR and prognostic factors of TR development and severity, a larger, prospective, multicenter study collecting echocardiographic information of TR severity, relationship of TR with type of transplant surgery performed, correlation of pulmonary hemodynamics with severity of TR, and prognosis and correlation of number of biopsies and rejection episodes with severity of TR should be performed. The care of transplant patients has changed with greater reliance on noninvasive biomarkers to assess the need for performing EMB, thus reducing the numbers of EMB. This may reduce the incidence and severity of TR. Given the large number of heart transplant programs in the United States that have switched to a biomarker-guided posttransplant strategy (donor-derived cell-free DNA, gene expression profiling) with biopsy minimization, it may be difficult to compare this approach with the more traditional biopsy-guided approach in terms of the impact on TR.