Post-heart Transplant Patients Research Articles

Evaluation of serum levels of sCD40, sCD40L and s4-1BB in advanced heart failure and after heart transplant

Abstract Heart failure is one of the most important problems in public health. Although big advances had been reached in treatment, the prognosis of advanced heart failure is still reserved and the heart transplant is the main therapy for this stage of disease. Allograft rejection is responsible for mortality in transplantation patients and the diagnosis of this complication is made through an invasive diagnostic method – the cardiac biopsy. The inflammatory response has been described in cardiovascular disease and in allograft rejection process. The objective of this study is to evaluate levels of sCD40, sCD40L and s4-1BB (inflammatory biomarkers) in advanced heart failure and post heart transplant with allograft rejection comparing to normal individuals and post heart transplant patients with no allograft rejection. The study population comprised 38 patients undergoing heart transplant in our center. Fifteen patients had biomarkers dosed before heart transplant and twenty three patients had dosed just after procedure. In this group, six patients were enrolled in the study for clinical suspicion of rejection. Nineteen health persons composed the control group with age between 18 and 49 years. Plasma dosage of sCD40, sCD40L e s4-1BB was made by enzyme linked immunosorbentassay (ELISA). Mann-Whitney test, Wilcoxon and t test were used to analyse dates. Statistical analysis used GraphPad®Prism6 and the value p< 0,05 was considered statistical significant. Allograft rejection occurred in 6,26% of studied patients. There was no statistical difference in age, sex, comorbities as hypertension, diabetes or etiology of cardiomyopathy. Serum levels of sCD40, sCD40L e s4-1BB were higher in patients with advanced heart failure comparing to controls (p< 0,0001). There was no difference in these levels of sCD40 (p = 0,74) e sCD40L (p = 0,44) between groups with and without rejection. Levels of s4-1BB were significantly lower in patients with allograft rejection (p= 0,02). The sCD40/PCR and s4-1BB/PCR indexs were significantly higher in the group of patients with allograft rejection (p =0,02 e p= 0,0001). We concluded that sCD40, sCD40L e s4-1BB are biomarkers of severe heart failure. The serum level of s4-1BB could be a potential biomarker of allograft rejection and the association of sCD40 and s4-1BB with PCR could be a better strategy to this.

Establishing normal global longitudinal strain values in heart transplant patients: a novel approach to enhancing detection of rejection and cardiac allograft vasculopathy

Abstract In the realm of heart transplantation, accurate cardiac monitoring is pivotal for patient outcomes. This study pioneers in filling a critical void by delineating the normative values of Global Longitudinal Strain (GLS), specifically tailored for heart transplant recipients, distinguishing them from the general population. We conducted a retrospective analysis on a cohort of 110 patients who underwent heart transplantation, meticulously compiling echocardiographic data over the first 18 months post-operation. Our research focused on two primary indicators of cardiac function: Ejection Fraction (EF) and Global Longitudinal Strain (GLS). The data indicated that EF values remained within the normal range and relatively stable throughout the monitoring period. In contrast, GLS values exhibited a gradual increase over time, suggesting a post-transplant myocardial adaptation process. However, these GLS values did not reach the established reference ranges for non-transplanted, healthy hearts, highlighting the distinctive physiological landscape of transplant recipients. Our study elucidates the superior sensitivity of GLS in detecting subtle myocardial changes that might precede clinically apparent dysfunction, advocating its utility as a crucial surveillance tool for this demographic. By pinpointing the modified GLS benchmarks applicable to post-heart transplant patients, our findings advocate for a recalibrated echocardiographic assessment protocol. Such a protocol can significantly enhance the surveillance for post-transplant complications, most notably graft rejection and the onset of cardiac allograft vasculopathy (CAV). The study posits that incorporating these refined GLS thresholds into routine post-transplant evaluations could facilitate early intervention, potentially mitigating adverse outcomes and improving the long-term prognosis for heart transplant recipients. Thus, our research underscores the need for updated clinical guidelines that integrate these novel echocardiographic insights, paving the way for improved patient-centric cardiac care in the transplant setting.

Pulmonary artery mass with PIK3CA mutation after orthotopic heart transplantation

BackgroundPatients can develop de novo malignancies following orthotopic heart transplantation. However, vascular tumors are not commonly described in this population.Case presentationWe present a 69-year-old female with a history of orthotopic heart transplantation for chemotherapy-induced cardiomyopathy who developed an incidental pulmonary artery mass six years after her transplantation. Given concerns for malignancy, the patient underwent an operative excisional biopsy through a left anterior mini-thoracotomy with femoral artery and vein cannulation for cardiopulmonary bypass. The mass was determined to be a non-malignant vascular overgrowth with PIK3CA mutation.ConclusionWe present the case of an unusual pulmonary artery mass with PIK3CA mutation found in a post heart transplant patient. We were able to spare her the morbidity of a redo-sternotomy by excising the mass via a minimally invasive left anterior thoracotomy approach.

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

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. 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). 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%). 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.

Prevalent Complications in Heart Transplantation: A Retrospective Cohort Analysis

Objectives: To identify the prevalent complications after heart transplantation. Methods: This is a quantitative retrospective cohort research with post-heart transplant patients from 2010 to 2022 through medical record analysis. Results: Forty-nine post-heart transplant patients participated in the study, six of whom died. The leading cause of heart failure before transplantation was idiopathic dilated heart failure (36.7%), followed by chagasic etiology (30.6%), with an average transplant waiting time of 7.4 months (standard deviation [SD] = 9.7). In the post-heart transplantation period, 95.9% of the population presented at least one complication, the most common being acute cellular rejection (81.6%), followed by cytomegalovirus infection (44.9%). Conclusion: The study provided relevant data to the literature to identify the prevalent complications in heart transplantation and implement nursing actions such as planning by nurses to improve self-management of care for transplant patients

Postoperative cognitive dysfunction in heart transplantation recipients.

This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation. Seventy-six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini-mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients. Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR=1.057, 95% CI 1.002-1.115), gender (OR=.200, 95% CI.044-.919), education level (OR=.728, 95% CI.600-.883), LVEF (OR=.891, 95% CI.820-.969), and history of diabetes (OR=7.674, 95% CI 1.317-44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P<.05). The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long-term outcomes.

Failing to Make the Grade: Conventional Cardiac Allograft Rejection Grading Criteria Are Inadequate for Predicting Rejection Severity.

Cardiac allograft rejection is the leading cause of early graft failure and is a major focus of postheart transplant patient care. While histological grading of endomyocardial biopsy samples remains the diagnostic standard for acute rejection, this standard has limited diagnostic accuracy. Discordance between biopsy rejection grade and patient clinical trajectory frequently leads to both overtreatment of indolent processes and delayed treatment of aggressive ones, spurring the need to investigate the adequacy of the current histological criteria for assessing clinically important rejection outcomes. N=2900 endomyocardial biopsy images were assigned a rejection grade label (high versus low grade) and a clinical trajectory label (evident versus silent rejection). Using an image analysis approach, n=370 quantitative morphology features describing the lymphocytes and stroma were extracted from each slide. Two models were constructed to compare the subset of features associated with rejection grades versus those associated with clinical trajectories. A proof-of-principle machine learning pipeline-the cardiac allograft rejection evaluator-was then developed to test the feasibility of identifying the clinical severity of a rejection event. The histopathologic findings associated with conventional rejection grades differ substantially from those associated with clinically evident allograft injury. Quantitative assessment of a small set of well-defined morphological features can be leveraged to more accurately reflect the severity of rejection compared with that achieved by the International Society of Heart and Lung Transplantation grades. Conventional endomyocardial samples contain morphological information that enables accurate identification of clinically evident rejection events, and this information is incompletely captured by the current, guideline-endorsed, rejection grading criteria.

Could the Cytomegalovirus Viral Load Be Correlated with Cellular Rejection in Asymptomatic Heart Transplant Recipients? A Brief Report

Abstract Introduction: Cytomegalovirus (CMV) infection is mainly associated with acute or chronic graft rejection in various solid organs. This study was conducted with the aim of evaluating the plasma viral load of CMV infection in postheart transplant patients and its correlation with the grading of cellular graft rejection in endomyocardial biopsies. Materials and Methods: In a cross-sectional study, 90 samples from 65 asymptomatic heart transplant recipients scheduled for routine endomyocardial biopsy were obtained. All the recipients had a history of positive serology for CMV infection before transplantation. Evaluation of their DNA was tracked using the polymerase chain reaction technique and the use of specific virus DNA primers, and based on this, the peak virus load (the number of virus copies per milliliter) was determined. A peak viral load &gt;10,000 copies/mL was considered positive. Graft rejection grading was determined based on the ISHLT grading system. Results: The mean (standard deviation) age of the patients (37 men) was 67 (37.3) years. The graft rejection grading was as follows: 22.2% grade 0, 38.9% Quilty effect (QE), 35.6% grade 1, and 3.3% grade 2. The mean plasma viral load level of CMV infection was 2197.4 (1256.2) μg/μL, 1970.4 (1150.3) μg/μL, and 4567.2 (1669.1) μg/μL in grades 0, QE, and 1 and/or 2, respectively (P &lt; 0.001). The virus load was significantly higher in those with higher grades of cellular rejection. Conclusion: The relationship between the plasma level of CMV viral load and the grading of cellular graft rejection in heart transplant patients could emphasize the role of CMV virus in the pathophysiology of graft rejection. A closer surveillance for CMV infection using the viral load is also recommended in particular in those who have higher grades of graft rejection.

Endomyocardial Biopsy Using Rigid Bioptome Technique and the Risk of Tricuspid Regurgitation after Heart Transplantation.

Endomyocardial biopsy (EB) is the preferred procedure for post-heart transplant rejection diagnosis. The rigid bioptome technique has been used due to its greater simplicity and has been criticized for the potential risk of tricuspid regurgitation (TR). We aimed to review all the EBs performed by this technique in a tertiary center and estimate the rate of complications and/or aggravation of TR. Cross-sectional, retrospective, anterograde study. Data were collected from 729 EBs performed in 55 post-heart transplant patients with a rigid Scholten Novatome™ bioptome between September 2012 to March 2022. All EBs were performed via the right jugular vein under local anesthesia and through micro-puncture and ultrasound guidance. A total of 729 procedures had an echocardiography performed before and after the procedures. The estimate of TR was categorized as absent, minimal, mild, moderate, and severe. McNemar's chi-square test was used to analyze the degree of pre- and post-EB TR. There was a worsening enough to become moderate or severe post-biopsy TR in two (0.27%) procedures, and there was a slight change in TR from minimal to mild TR in 25 (3.42%) procedures. In 729 percutaneous EBs performed with a rigid bioptome, there was no myocardial perforation, cardiac tamponade or pneumothorax. One death occurred within 24 hours after the procedure for an unknown reason. EB using a rigid bioptome is safe and has not been associated with worsening TR in a follow-up of 729 EBs performed after cardiac transplantation. The overall complication rate, including moderate to severe TR, was 0.81%. The mortality rate was 0.14%.

Abstract 15342: Outcomes of High-Intensity Interval Training Are Superior to Moderate Exercise Training Among Post-Heart Transplant Patients

INTRODUCTION: Heart failure patients who underwent heart transplantation (Htx) need to undergo cardiac rehabilitation (CR) to regain and improve their physical ability and functional capacity. To date, there is no established exercise regimen that optimizes this recovery. This study aims to compare the outcomes of High-Intensity Interval Training (HIIT) versus Moderate Exercise Training (MT) among Htx patients. Hypothesis: The outcomes of HIIT are superior to MT among Htx patients. Methods: A systematic review was conducted in multiple databases including PubMed, Embase, and Google Scholar from inception to 2022 following the PRISMA guidelines to look for randomized controlled trials that directly compare clinical outcomes of HIIT versus MT. Joanna Briggs Institute (JBI) critical assessment tool was used to assess the risk of bias. A meta-analysis was performed using a random effect model to calculate mean differences with 95% confidence intervals (CI). This study is registered on Prospero (CRD42023403954). Results: This study included four clinical trials (n=177 patients). The average age was 51 years ± 10.57, with a majority male (73%). On average, patients were overweight (BMI = 25.78 ± 4.08) with comorbidities including hypertension (81%) and diabetes (12%). Compared to baseline levels, the peak oxygen consumption (VO2 peak), maximal muscle strength extensors, maximal muscle endurance, body mass index, and FEV1 were statistically significantly increased after the intervention of either HIIT or MT. Of these, HIIT had higher percent changes in VO2 peak at 0.205 (95% CI: 0.007 to 0.417, p=0.0578), maximal muscle strength extensors at 0.100 (95% CI: 0.059 to 0.141, p&lt;0.001), and maximal muscle endurance at 0.263 (95% CI: 0.185 to 0.341, p&lt;0.001) compared to MT. CONCLUSION: Both exercise CR regimens significantly improved the physical ability and functional performance of Htx patients. However, HIIT was superior to MT in terms of VO2 peak, maximal muscle strength extensors, and maximal muscle endurance, which may be associated with higher survival.

Therapeutic potential role of vitamin C in prevention and control of heart transplant rejection and cardiac allograft vasculopathy. A need for consideration.

The burden of cardiovascular diseases is rising rapidly globally. Heart transplant is one of the most last resort medical option for patients with heart failure. Unfortunately, this surgical intervention is associated with several serious complications including heart transplant rejection (HTR) and Cardiac Allograft Vasculopathy (CAV) which can manifest just within few years'posttransplant. These complications affect significantly the prognosis and quality of life among postheart transplant patients. Several medications including immunosuppressant, antibiotics, antihypertensive,and statins have been used during posttransplant care so as to address such complications. Unfortunately, most of those drugs are expensive and pose a number of serious side effects to the patients enough to compromise patients'quality of life too.Several studies on Vitamin C are therapeutically suggestive that it can be used during postheart transplant care with more cost-effective benefits with less and minimized side effects compared to the current drugs in place. It should be considered pharmacologically that Vitamin C has a great potential role clinically in prevention and control of HTR and CAV development. On the light of such findings as described above, we recommend more studies especially clinical trials and molecular studies to determine whether Vitamin C can be repositioned to replace or to be used along the current drug regimens used in postheart transplant care for prevention and control of HTR and CAV.

Elevated Aortic Stiffness after Pediatric Heart Transplantation.

In adults, arterial stiffness has been linked to the development of target end-organ damage, thought to be related to abnormal transmission of pulse pressure. Increased arterial stiffness and endothelial dysfunction have been hypothesized to contribute to the development of microvascular dysfunction and coronary allograft vasculopathy (CAV), an important comorbidity after heart transplantation. However, little data exists regarding arterial stiffness in pediatric heart transplantation and its influence on development of coronary allograft vasculopathy is not well understood. We sought to assess aortic stiffness and distensibility in pediatric post-heart transplant patients. A prospective, observational study analyzing the ascending (donor tissue) and descending aorta (recipient tissue) using transthoracic echocardiographic M-mode measurements in patients aged < 21 years was conducted. Descending and ascending aorta M-modes were obtained from the subcostal long axis view, and the parasternal long axis view 3-5mm above the sinotubular junction, respectively. Two independent reviewers averaged measurements over 2-3 cardiac cycles, and Aortic Distensibility (AD) and Aortic Stiffness Index (ASI) were calculated using previously validated methods. We recruited 39 heart transplant (HT) patients and 47 healthy controls. Median end diastolic dimension of the ascending aorta (donor tissue) was significantly larger in the transplant group than the control group (1.92cm vs. 1.74cm, p = 0.01). Ascending aortic distensibility in post-transplant patients was significantly lower than in the control group (4.87 vs. 10.53, p < 0.001). Ascending aortic stiffness index was higher in the transplant patients compared to the controls (4.63 vs. 2.21, p < 0.001). There is evidence of altered ascending aortic distensibility and stiffness parameters in post-heart transplant patients. Further studies are required to assess its influence on complications like development of coronary artery vasculopathy.

Coronary allograft vasculopathy in post-heart transplant patients: pathogenesis and role of cardiac computed tomography in diagnosis-a comprehensive review.

Coronary allograft vasculopathy, often known as cardiac allograft vasculopathy (CAV), is a substantial source of morbidity and mortality in people who have had heart transplants. Early detection and monitoring of CAV are crucial for improving outcomes in this population. Although cardiac computed tomography (CT) has emerged as a possible method for finding and evaluating CAV, invasive coronary angiography has long been thought of as the gold standard for recognizing CAV. This study focuses on the utility of cardiac CT for CAV diagnosis and treatment in the post-heart transplant population. It provides an overview of recent studies on the application of cardiac CT in CAV and highlights the advantages and disadvantages of this imaging modality. The potential application of cardiac CT for CAV risk assessment and care is also examined in the study. Overall, the data point to a potential role for cardiac CT in the detection and treatment of CAV in post-heart transplant patients. It enables evaluation of the whole coronary tree and low-radiation, high-resolution imaging of the coronary arteries. Hence, further study is required to determine how best to employ cardiac CT in treating CAV in this group.

Case Report: COVID-19 Infection of a Transplanted Heart Simulating Cellular Rejection

Contemporary reports showed that solid organ transplantation patients who contract SARS-CoV-2 infection have a high mortality rate. There are sparse data about recurrent cellular rejections and the immune response to the SARS-CoV-2 virus in patients after heart transplantation. Herein, we report a case of a 61-year-old male post-heart transplant patient who tested positive for COVID-19 and developed mild symptoms 4 months after transplantation. Thereafter, a series of endomyocardial biopsies showed histologic features of acute cellular rejection despite optimal immunosuppression, good cardiac functions, and hemodynamic stability. Demonstration of SARS-CoV-2 viral particles by electron microscopy in the endomyocardial biopsy confirmed the presence of the virus in the foci of the cellular rejection, pointing to a possible immunologic reaction to the virus. To our knowledge, there is limited information regarding the pathology of COVID-19 infection in immunocompromised heart transplant patients, and there are no well-established guidelines for treating such patients. Based on the demonstration of SARS-CoV-2 viral particles within the myocardium, we concluded that myocardial inflammation visible on endomyocardial biopsy might be attributed to the host's immune response to the virus, which mimics acute cellular rejection in newly heart transplanted patients. We report this case to increase awareness of such events post-transplantation and to add to knowledge regarding the management of patients with ongoing SARS-CoV-2 infection that proved to be challenging.

Implications of Extra-cardiac Disease in Patient Selection for Heart Transplantation: Considerations in Cardiac Amyloidosis.

Disease-modifying therapies in both light chain and transthyretin amyloidosis have improved patient functional status and survival. Conceivably, as heart failure may progress despite amyloid therapies, more patients may be considered for heart transplantation. In earlier eras, extra-cardiac amyloid deposits significantly reduced post-heart transplant patient survival and functional status compared to the non-amyloid population. In the modern era, transplant centres have reported improved outcomes in amyloidosis as patient selection has grown more stringent. Importantly, systematic candidate evaluation should assess the degree of extra-cardiac involvement, the effectiveness of disease-modifying therapies and downstream effects on patients' nutrition and frailty. This review outlines such an overall approach while also considering that organ-specific selection criteria may vary between individual transplant centres. A methodical approach to patient evaluation will promote better understanding of the prevalence and severity of extra-cardiac disease in amyloidosis patients referred for heart transplantation and of any disparities in decision outcomes in this population.

Fluoride toxicity: A tale of two sources

The aim of this study was to identify the cause and source of two patients’ clinical manifestations. Case#1 was a 47-year-old male with diffuse bone pain and weakness aggravated by exertion. Past medical history revealed two surgeries for a left fibular fracture with eventual resection of installed hardware. Current medications included: oxycodone, montelukast, and vitamin D3. Magnetic resonance imaging and x-ray showed L5–6 fusion and diffuse trabecular thickening. A pelvic bone biopsy showed features consistent with severe skeletal fluorosis. Case#2 was a 61-year-old male post-heart transplant patient. His medications included: cyclosporine A, prednisone, rosuvastatin, amlodipine, and voriconazole. He complained of joint pain, his alkaline phosphatase was 222 U/L (reference range 40–129 U/L), and his bone density scan showed periostitis. Fluoride was measured in heparinized-plasma in both patients using a fluoride ion-selective-electrode on an Orion™ Dual Star pH/ISE meter (Thermo Scientific). The analytical measurement range is 4.0–21.0 μmol/L with an upper reporting limit of 105 μmol/L. Case#1 and case#2 had plasma fluoride concentrations of 11.3 and 17.5 μmol/L, respectively (reference-range < 4 μmol/L). Fluoride is often added to drinking water, toothpastes, and mouth rinses to prevent dental cavities. While food generally contains low levels of fluoride, tea and seafood have been found to have higher levels. Several medications containing fluorine are used for treating skin diseases and cancer. Following ingestion, plasma concentrations peak within an hour and up to 50% is stored in bones/teeth while the rest is primarily eliminated in the urine. The average person ingests ∼2–3 mg fluoride per day with a recommended daily intake of 3–4 mg/day by the United States Department of Agriculture. Chronic ingestion exceeding 20 mg/day can pose a risk to bone health leading to denser brittle bones, joint pain, and limited joint movement. In case#1, the source of fluoride was identified as excessive consumption of strong black tea (> 10 servings per day). In case#2, voriconazole (trifluorinated antifungal) was associated with the development of excess fluoride and periostitis. Plasma fluoride testing can be useful for diagnosing acute environmental toxicity, as well as, monitoring those taking fluorine-containing drugs. Detailed patient histories are required to identify common (voriconazole) or less-common (tea) sources. Patient#1 limited his tea consumption to one cup/day and his fluoride levels returned to normal on follow-up three months later. Patient#2 was switched from voriconazole to itraconazole (nonfluorinated triazole) and fluoride levels returned to normal. Pain resolution or improvement was also noted in both cases.

Severely Underweight: Is It a Risk Factor for Poor Outcomes in Post-Heart Transplant Patients?

<h3>Purpose</h3> Obesity has been noted as a risk factor for poor outcome after heart transplantation (HTx). Cardiac cachexia has also been reported to be a risk factor for poor outcome, however no threshold has been noted for this patient population. Body mass index (BMI) greater than 35 kg/m² is a noted threshold for declined patients for HTx, but a lower BMI has not been established. In this study, we reviewed the UNOS database to evaluate underweight patients awaiting HTx to assess whether there is a risk for poor outcomes post-HTx. <h3>Methods</h3> Between 2000 and 2020, we assessed 16,457 patients from the UNOS database and divided the patients according to BMI groupings below. Patients were divided by CDC BMI definitions: severely underweight (BMI less than 15.0 kg/m²), moderately underweight (15.0 to 16.0 kg/m²), mildly underweight (16.0 to 18.5 kg/m²), and healthy weight (18.5 to <25.0 kg/m²). Endpoints included 1-year survival and freedom from graft failure. <h3>Results</h3> There was no significant difference in BMI underweight groups compared to healthy weight group in 30-day, 6-month, and 1-year survival or freedom from graft failure. (see table) <h3>Conclusion</h3> There does not appear to be decreased post-heart transplant outcome for mild, moderate, or severely underweight patients. Being severely underweight should not be an absolute contraindication for heart transplant. However, larger number of severely underweight patients are needed to confirm these findings.

Effect of COVID-19 Infection on HeartCare, Data from the SHORE Multicenter Registry

PurposeTransplant patients represent a cohort in which COVID-19 (C19) may stimulate an unpredictable clinical course. The aim of this study was to evaluate the impact of C19 infection on AlloMap gene expression profiling (AM) and AlloSure donor derived cell free DNA (AS) results in patients post heart transplant.MethodsThe Surveillance Using HeartCare Outcomes Registry (SHORE) is a multicenter study for post heart transplant patients followed with AM/AS for 5 years. Patients enrolled were analyzed based on C19 . AM/AS were evaluated before, at the time and following infection. Both individual trends and the differences between the median AS and AS levels were studied. Nonparametric tests were used to assess categorical and longitudinal variables.Results21 patients developed C19 infection; 16 (76%) were males, median age 50 years. There was no significant difference in AM or AS in stable patients (no rejection, CAV, graft dysfunction, dnDSA) compared to the first AM/AS profile in the C19+ patients, Figure 1. Event rates in C19+ patients are described in Table 1. 12 C19+ patients had 28 biopsies, 2 of which were within 30 days of C19. 1 patient had ACR 2R and another AMR 1; all other biopsies were <ACR 2R/AMR1. Additionally, 5 patients developed dnDSA and 7 patients developed subsequent CMV viremia, a median of 67 and 158 days after C19 diagnosis, respectively. No CAV, graft dysfunction, or deaths were reported in this small group of C19+ patients.ConclusionThe presence of C19 infection is not associated with a significant increase in AS or AM scores, suggesting AS and AM are not confounded by C19 and can be used safely as non-invasive surveillance in this population.

Effect of CMV Viremia on HeartCare

<h3>Purpose</h3> CMV infection post-heart transplantation presents complex challenges affecting changes in immunosuppression and antiviral therapy that have both short- and long-term consequences. AlloMap gene expression profiling (AM), a non-invasive method to detect acute cellular rejection was affected by the presence of CMV infection. The aim of this study was to evaluate the impact of CMV infection on donor derived cell free DNA (AS) in patients post heart transplantation (HT). <h3>Methods</h3> The Surveillance Using HeartCare Outcomes Registry (SHORE) is a multicenter study for post-heart transplant patients followed with AM/AS for 5 years following heart transplantation. Patients enrolled in the SHORE registry were analyzed based on CMV infection. AM/AS were evaluated before, at the time, and following the viremic episodes. Both individual trends and the differences between the median AS and AS levels were studied. Nonparametric tests were used to assess categorical and longitudinal variables. <h3>Results</h3> 1702 patients were included, 1245 (73%) male, median age 57, 1156 (68%) white. CMV infection was diagnosed in 360 (21%) patients occurring at a mean time of 229 days after HT. CMV(-) patients had similar demographics to those patients CMV(+ve), but CMV(+) were older (p=0.025). CMV(+ve) patients had an increase in both AS (0.07% v. 0.05%, p<0.001) and AM (34 v. 30, p<0.001) compared to those without CMV [Figure 1a]. Levels returned to baseline within 5 weeks following the infection [Figure 1b]. The threshold to discriminate CMV infection with a NPV of 95% with GEP is 34 and dd-cfDNA is 0.12% . <h3>Conclusion</h3> AS does not seem to be confounded by CMV, but the presence of CMV infection may be associated with an elevated AS if there is allograft injury. Recovery from CMV infection was associated with normalization of AS and AM. This study points to the need to evaluate CMV in the presence of an increased AS, with further work to compare PCR titers and AS levels planned.

Circumstances surrounding end-of-life in pediatric patients pre- and post-heart transplant: a report from the Pediatric Heart Transplant Society.

Although mortality has decreased considerably in pediatric heart transplantation, waitlist and post-transplant death rates remain notable. End-of-life focused research in this population, however, is very limited. This Pediatric Heart Transplant Society study aimed to describe the circumstances surrounding death of pediatric heart transplant patients. A retrospective analysis of the multi-institutional, international, Pediatric Heart Transplant Society registry was conducted. Descriptive statistics and univariate analyses were performed to 1) describe end-of-life in pediatric pre- and post-heart transplant patients and 2) examine associations between location of death and technological interventions at end-of-life with demographic and disease factors. Of 9217 patients (0-18years) enrolled in the registry between 1993 and 2018, 2804 (30%) deaths occurred; 1310 while awaiting heart transplant and 1494 post-heart transplant. The majority of waitlist deaths (89%) occurred in the hospital, primarily in ICU (74%) with most receiving mechanical ventilation (77%). Fewer post-transplant deaths occurred in the hospital (22%). Out-of-hospital death was associated with older patient age (p<.01). ICU deaths with high use of technological interventions at end-of-life were common, particularly in patients awaiting heart transplant. In this high mortality population, findings raise challenging considerations for clinicians, families, and policy makers on how to balance quality of life amidst high risk for hospital-based death.