Heart Transplant Patients Research Articles

Afterload mismatch is associated with gender mismatch and negatively affect long-term outcome after heart transplant

Abstract Background Cardiac physiology changes after heart transplant (HT), resulting in a restrictive physiology with an increase in both arterial elastance (Ea) and ventricular elastance (Ees). This leads to a higher susceptibility to develop afterload mismatch, although the early identification of this phenomenon has not yet been explored. The aim of this study is to identify the presence of afterload mismatch after HT, its determinants, and its impact on cardiac mortality. Methods We conducted an observational, single-centre study based on the historical cohort of patients who underwent HT from 1985 to 2015 at our institution. We included patients who had survived the first year after HT with left ventricular ejection fraction (LVEF) ≥ 50%, International Society of Heart and Lung Transplantation (ISHLT) cardiac allograft vasculopathy of grade 0-1, and ISHLT acute cellular rejection of grade 0-1R at 1 year after HT. Ea and Ees were calculated using a non-invasive method based on blood pressure and end-systolic volume and end-diastolic volume measured at transthoracic echocardiography. Patients were grouped in 3 categories according to the presence of increased afterload and afterload mismatch as follows: low afterload (LA - Ea lower the median), matched high afterload (MHA - Ea higher of equal than the median, Ees higher or equal than the median), afterload mismatch (AM - Ea higher or equal than the median, Ees lower than the median). The impact of AM on long-term outcome, defined as cardiac mortality, was investigated, as well as predictors of AM. Results The study cohort consisted of 345 HT patients. The median of Ea and Ees were 4.0mmHg/mL and 6.75mmHg/mL, respectively. 49 patients (13%) developed AM, while LA and MHA groups accounted for 49% and 36% of the cohort, respectively. Patients with AM were mostly male (91%), with ischemic heart disease (45%) and a higher percentage of left ventricular assisted device prior to HT (8%). LVEF was lower in AM (57% vs 63% and 64% for LA and MHA respectively, p < 0.0001), while stroke volume was lower than LA and similar to MHA (27ml vs 35mL and 26mL for LA and MHA respectively, p = 0.0001). Predictors of AM were male recipient from male donor (Mr/Md) (β 015, p = 0.0067) and Mr from female donor (Mr/Fd) (β 0.6, p = 0.0078). After a median of 11.3-year follow-up, 59 (17%) HT recipients died. Cardiac mortality was higher in AM than in the other groups (AM median survival 17.2y vs 27.8y and 24.1y for LA and MHA respectively, log-rank p = 0.005). After adjusting for confounding variables, AM was a predictor of cardiac mortality (HR: 2.26; 95%CI 1.18 – 4.35), such as Mr/Fd (HR 2.94; 95%CI 1.18 – 4.35, p = 0.0358). Conclusion AM, in the context of a normal LVEF, is associated with male donor and sex mismatch, and negatively affects long-term outcome after HT.KM curvesCox proportional hazard model

Systematic Review of Case Manager Nurse in Heart Transplant and Heart Failure Consultation

ObjectiveTo analyze the functions and activities of the case manager nurse in the specialized practice of transplantation and heart failure. MethodThis systematic review is reported according to the PRISMA guidelines. Selected articles were subjected to a detailed critical reading and the evidence levels and recommendation grades of the Joanna Briggs Institute were verified. The field of documentation search was limited to the last 5 years. ResultsHealth education provided by nursing is key in patients with heart failure and heart transplants. It must be evidence-based and focuses primarily on promoting self-care and adherence to therapy, although it includes other aspects such as recognition of signs and symptoms by the patient. Both activities are essential to prevent decompensations of heart failure, thus reducing hospital readmissions and mortality rates. ConclusionNursing has an essential role in multidisciplinary programs for the care of heart failure and heart transplant patients. Case manager nurse role stands out for being cost effective, as well as for improving treatment compliance and reducing hospital stay and mortality rates. Nursing functions in this practice ensure continuity and coordination of care between the different health levels, increasing the patients’ quality of life.

Impact of biological sex on heart transplant patients admitted to cardiac rehabilitation: A 10-year retrospective cohort study

IntroductionHeart transplantation (HTx) serves as the gold-standard therapy for end-stage heart failure, yet patients often experience physical deconditioning and cognitive impairments post-surgery. Cardiac rehabilitation (CR) has shown promise in the HTx context. However, uncertainty surrounds the impact of biological sex. Accordingly, the aim of this paper was to investigate the impact of biological sex in a cohort of patients with HTx early admitted to a residential CR program. MethodsThis was a retrospective analysis involving patients who underwent HTx at Niguarda Hospital and who subsequently participated in a CR program at IRCCS Fondazione Don Gnocchi, Milan, Italy, between 2010 and 2022. The primary endpoint was time to event (in months), with an event defined as a composite outcome of whichever occurred first of death, allograft rejection, or cardiac allograft vasculopathy up to 30 months follow-up. ResultsIn a total of 129 patients, 60 % male, and 40 % female, baseline characteristics presented comparably between the sexes. At 6 months, no significant sex differences were observed for the primary composite outcome. However, at 30 months, females exhibited a significantly lower incidence of the primary composite outcome and an increased survival rate. Multivariable analysis confirmed a protective effect of female sex against mortality (F vs. M, HR 0.164, 95 % CI 0.038–0.716, P = 0.0161). ConclusionsDespite limitations, our findings emphasize that sex affects post-HTx long-term follow-up following CR discharge, with more favorable outcomes for female recipients. In an era of tailored management algorithms, it is imperative to take into account the gender gap even in cardiac rehabilitation.

Cause of death for heart transplant patients, an autopsy study

IntroductionHeart transplantations are lifesaving for patients with end-stage heart failure. It is pertinent for the multidisciplinary care team to understand how heart transplant patients succumbed to death and the complications that occurred. In this study, we performed a comprehensive retrospective review of all the autopsies performed in our institute for heart transplant patients and report the trend of demographic data, cause of death, and autopsy findings. Materials and methodsReports, photos, and slides of autopsies performed at our institute from 1990 to 2023 for heart transplant patients were reviewed. Pertinent demographic data (age, gender, pretransplant diagnosis), clinical data (clinical history of rejection, complication, time interval from transplant to death, clinical cause of death) and pathological findings (allograft pathology, infectious etiology, other findings related to cause of death) were reviewed, documented, and analyzed. ResultsWe identified 88 cases, consisting of 53 male and 35 female patients. The median age at transplant was 26 years, while 28.5 years was the median age at death. The median interval from transplant to death was 10 months. The cases were classified in three categories based on length of survival post-transplant: Superacute (<1 month, 21%), Early (1 month-12 months, 30%), and Late (> 12 months, 49%). Slides were unavailable for review in 15 cases, which were excluded from cause of death (COD) evaluation. We categorized 41.1% of cases as allograft-related COD and 58.9% as non-allograft-related COD. Six of the CODs were not perceived premortem. These unexpected CODs included moderate/severe acute cellular rejection in a patient with a recently negative biopsy, dehiscent suture caused by a fungal abscess, an aorto-bronchial fistula, CMV myocarditis, acute abdominal bleeding, and ruptured atherosclerotic plaques with acute myocardial infarction. ConclusionWe systematically reviewed 33 years of heart transplant autopsies. We found that 41.1% of deaths were allograft related, with infection being the most frequent COD. While the rate of unexpected findings was low, the findings demonstrate the continued utility of autopsy in patient evaluation.

Outcomes of Multiorgan Heart Transplant Between Donation After Circulatory Death and Brain Death.

There is insufficient data on the outcomes of donation after circulatory death (DCD) multiorgan transplant that includes heart. The primary objective of this study is to compare the overall survival outcomes of DCD and donation after brain death (DBD) multiorgan transplants. We identified all heart transplant patients from 2019 to June of 2023 using the United Network for Organ Sharing (UNOS) Database who also received an additional organ (kidney, liver, and lungs). A total of 1,844 DBD and 91 DCD multiorgan transplants occurred within the study period, the majority being combined heart-kidney transplantation. More patients were listed at a higher status in the DBD group (p < 0.05) and were in the intensive care unit (ICU) before transplant (p < 0.05). Despite the higher ischemia time in the DCD group (p < 0.05), the overall unmatched survival did not differ between the two groups (p < 0.05). Within the heart-kidney transplants, the overall survival between DBD and DCD heart-kidney transplants did not differ in either unmatched or matched groups (unmatched p = 0.5, matched p = 0.5). In conclusion, the data on the outcomes of DCD multiorgan transplants are limited. Still, our analysis of the currently available data suggests that the overall survival is comparable in the DCD multiorgan transplants.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients

Abstract Background Valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) infection and disease has provided an important advance in the management of pediatric solid organ transplantation (SOT) recipients over the past two decades. However, there remain significant questions regarding its relative safety and efficacy, optimal dosing strategies, and toxicities including neutropenia and lymphopenia. We performed a multi-center retrospective study of children post SOT who were to receive at least 3 months of valganciclovir. The primary outcomes were CMV DNAemia while receiving prophylaxis (breakthrough) and post-prophylaxis CMV DNAemia within the first year. Methods The study population included patients ≤ 20 years of age at the time of their first transplant between January 2016 and December 2019 from 8 US centers in PIDTRAN Network. Data for each patient was extracted from the electronic medical record and entered into a REDcap database hosted by St. Jude Children’s Research Hospital. Variables analyzed included demographics, donor/recipient CMV serostatus, immunosuppression, trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis use, rejection, other viral or bacterial infections and one-year survival. Statistics were performed using STATA software for univariate and multivariate models; p-value&amp;lt; 0.05 was considered statistically significant. Results 749 pediatric SOT patients were enrolled over the 3-year study period. Breakthrough DNAemia occurred in 85 (11.4%) patients and post-prophylaxis CMV DNAemia was documented in an additional 46 (6.9%) patients. CMV disease occurred in only 30 patients (4%). In univariate analysis, there were no differences in age, sex, race/ethnicity, or immunosuppression comparing those who experienced breakthrough or post-prophylaxis CMV DNAemia compared to those without CMV DNAemia, but there were differences based on transplanted organ (p&amp;lt; 0.001, liver and lung &amp;gt; heart &amp;gt; kidney) and CMV risk status (high and intermediate) (p&amp;lt;0.001). Neutropenia (p&amp;lt;0.001) and lymphopenia (p=0.003) as well as VGCV discontinuation or dose reduction for perceived toxicity (p&amp;lt;0.001) were associated with breakthrough CMV infection. Bacteremia (p=0.001), EBV viremia (p=0.02), and adenovirus viremia (p=0.002) were also documented more in those with breakthrough compared to those who never had CMV DNAemia. In an adjusted Cox regression hazard model using all significant univariate variables, transplanted organ, CMV risk status, toxicity related VGCV modification (p=0.005), and bacteremia (p=0.01) were independently associated with breakthrough CMV infection. Breakthrough CMV was also associated with rejection (p=0.01) in a separate logistic multivariable model. Both liver (p&amp;lt;0.001) and heart transplant (p&amp;lt;0.001) patients had a greater risk of rejection over the first year of transplantation, but only liver transplant patients had a greater risk of rejection with breakthrough CMV infection (p=0.004). Post prophylaxis CMV DNAemia was associated with mortality at 1 year in the univariate analysis in the full cohort (p=0.001). Conclusion Rates of CMV disease when using valganciclovir prophylaxis were low in this large, multicenter cohort of pediatric SOT recipients. However, breakthrough CMV infection continues to be a problem in intermediate- and high-risk CMV patients and is associated with significant morbidity and rejection, particularly in the liver transplant population. Alternative approaches to prevent breakthrough and post-prophylaxis CMV and with a better safety profile should be studied in pediatric SOT patients.

Optimization of Hypercholesterolemia Treatment after Heart Transplant: The Role of PCSK9 Inhibitors.

Previous studies have reported the benefit of statins after heart transplant (HT). However, the use of high-dose statins might be limited in some HT patients due to intolerance and interactions with immunosuppression or might not be enough to achieve low-density lipoprotein (LDL) cholesterol goals. Hyperlipidemia has been associated with coronary allograft vasculopathy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors might be a safe and effective option in HT patients with suboptimal lipid control. In a retrospective study, we identified HT patients in our center with LDL cholesterol >100 mg/dL, after diet modifications and up-titration of statins to maximum tolerated dose, treated with PCSK9i. The primary endpoint was LDL reduction one month after, and secondary endpoints were the development of donorspecific HLA antibodies (DSA) and the presence of coronary allograft vasculopathy or rejection. From January, 2018, to January, 2024, we identified five HT patients treated with PCSK9 inhibitors. In all cases, evolocumab was used. A significant reduction in LDL cholesterol was observed (151.6 ± 13.5 mg/dl to 72.4 ± 14.6 mg/dl; p = 0.04, mean reduction 75.7 ± 14.1 mg/dl), as well as in total cholesterol (231 ± 34.6 mg/dl to 152.2 ± 38.9 mg/dl; p < 0.01, mean reduction 78.8 ± 22.2 mg/dl). A significant increase in HDL cholesterol was not observed (45.4 ± 10.9 mg/dl to 46.2 ± 11.1 mg/dl; p = 0.60). One patient developed DSA five years after treatment onset. Rejection and coronary allograft vasculopathy were not observed. PCSK9 inhibitors are safe and effective in reducing LDL in HT patients. However, larger studies are needed to clarify if they can reduce the development of coronary allograft vasculopathy.

Short communications: Endothelin-1 in cardiac allograft vasculopathy

IntroductionCardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplant. Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide derived from the vascular endothelium with multiple biological actions known to be relevant for CAV. We assessed the trans-myocardial gradient (TMG: coronary sinus minus coronary artery concentration: negative = extraction, positive = secretion) of ET-1 in heart transplant patients to determine correlations with angiographic, Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) features of CAV. ResultsVessels with more severe CAV demonstrated significantly higher (more positive) ET-1 TMG (IVUS Stanford Grade IV: −0.05 [−0.21, 0.13] pg/ml versus Stanford Grade I-III: −0.31 [−0.64, −0.11] pg/ml, p = 0.01). ET-1 TMG was positively correlated with mean intimal thickness on both IVUS and OCT (IVUS: Kendall's tau-b = 0.254, p = 0.02 and OCT: Kendall's tau-b = 0.344, p < 0.0001). Patients who died had net ET-1 release compared with surviving patients (died: 0.21 [0.19–0.24] versus surviving: −0.28 [−0.52, −0.17], p = 0.01). ConclusionIn heart transplant patients, coronary arteries with more intimal thickening are associated with a higher (more positive) trans-myocardial gradient of ET-1, suggesting that up-regulated ET-1 release in the coronary circulation may be permissive for the development of CAV.

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era.

Pathologic antibody mediated rejection (pAMR) evaluation and donor specific antibody (DSA) testing are recommended in the first year after heart transplantation (HTx) in adult patients. Whether DSA testing adds prognostic information to contemporary pAMR surveillance has not been fully studied. This was a single center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether DSA testing contributes additional information to pAMR surveillance to better predict overall survival. Secondary endpoints included cardiac allograft dysfunction and loss. A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ group had significantly lower overall survival versus the pAMR-/DSA- group (hazard ratio [HR] = 2.63; 95% confidence interval [CI], 1.35-5.11; pc = 0.013). In the pAMR+/DSA+ group, patients with cardiac allograft dysfunction, compared to those without allograft dysfunction, had significantly lower overall and cardiac survival (pc < 0.001 for both). In contrast, pAMR+/DSA+ and pAMR-/DSA- patients without cardiac allograft dysfunction showed no difference in overall and cardiac survival. Primary graft dysfunction (PGD) was a novel risk factor for development of de novo DSAs (dnDSA) three weeks post-HTx (p = 0.007). DSA testing as the primary surveillance method can identify high-risk pAMR+/DSA+ patients. Surveillance pAMR testing in the contemporary era may need to be reevaluated. Earlier DSA testing at 10-14 days post-HTx should be considered in PGD patients.

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.

Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients. A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected.Patients who had simultaneous MOT were identified and included in this study.Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade≥2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0.The within-patient variability score of the dd-cfDNA was calculated by the variance/average. The study included 25 multiorgan transplant recipients: 13 heart-kidney (H-K), 8 heart-liver (H-Li), and 4 heart-lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5).The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001).Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection. Dd-cfDNA is chronically elevated in most MOT recipients.There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.

CytoSorb hemoadsorption of apixaban during cardio-pulmonary bypass for heart transplantation

IntroductionHeart transplantation is an emergency surgery requiring cardio-pulmonary bypass (CPB) and its timing is unpredictable. Patients on the transplant waiting list often have multiple reasons for being anticoagulated. Direct oral anticoagulants (DOACs) such as apixaban are very popular due to their well-known advantages. Intraoperative removal of apixaban using CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA), seems to be an interesting solution for patients on DOACs requiring an emergency CPB intervention. The aim of this short communication is to describe the perioperative effects of the use of the CytoSorb® hemoadsorption device during emergency CPB for a heart transplant patient Case presentationA 61-year-old male patient (75kg/173cm) wait-listed for heart transplantation was admitted to our hospital (Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France) to benefit from a heart transplantation. This patient, with many comorbidities, has an end-stage heart failure with multiple episodes of decompensation over the previous year. He was anticoagulated with a Vitamin K antagonist (VKA) due to atrial fibrillation and was switched to apixaban (5mg twice daily) 9 days before surgery based on poor clotting control. A NaCl 0.9% primed CytoSorb cartridge was inserted into the CPB circuit. Hemoadsorption was performed during the entire CPB duration. Anti-Factor Xa Activity (AFXaA) levels were taken at multiple time points before, during and after surgery in order to monitor anticoagulation. Results. Preoperatively, activated Clotting Time (ACT) was 146 seconds. The ACT reached 545 seconds after administration of 25,000IU of unfractionated heparin (UFH). Surgery consisted of an orthotopic heart transplantation with bi-caval anastomoses.CPB duration was 133 minutes with 83 minutes of aortic cross clamping. Total graft ischemic time was 249 minutes. At the time of anesthesia induction and after UFH administration, AFXaA levels were 330ng/mL and 317ng/mL, respectively. Thereafter, AFXaA decreased to 137ng/mL during CPB and to 57ng/mL after the end of CPB and 250mg (=25,000IU) of protamine administration.After surgery, AFXaA levels stabilized over 50ng/mL over the next 14 hours. Postoperative anticoagulation was performed with the use of UFH starting 6 hours after surgery.No primary graft dysfunction (PGD) was observed, and during the post-operative period of 72 hours, the patient did not have any bleeding events requiring reintervention or transfusion. ConclusionIn conclusion, we observed that CytoSorb® could be a potential solution to remove apixaban intraoperatively. If this efficacy is confirmed in larger trials, it would allow transplant candidates to be treated with DOACs without requiring a switch to VKAs.

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.

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.

Specific features of anesthesia management in a patient with a transplanted heart

Background. The number of heart transplant patients makes 1 per 100,000 in the Russian Federation, 1.2 per 100,000 population in the Tambov Region. The medical community is poorly informed about the specific features of managing such patients during non-cardiac surgical interventions. The article presents a case report of the management of a patient with a transplanted heart undergoing surgery for acute appendicitis. Preoperative preparation, anesthesia management, surgery, and postoperative care and rehabilitation were provided taking into account the presence of a transplanted heart in the patient, according to the Guidelines developed by the experts of the V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs where the heart transplant had been performed to the patient, and standard clinical recommendations.Case Report. An 18-year-old patient diagnosed with acute phlegmonous appendicitis with a heart transplanted in 2021 for dilated cardiomyopathy underwent laparoscopic appendectomy 3 years after heart transplantation. Anesthesia was provided taking into account the presence of a denervated donor heart, a high risk of myocardial ischemia and heart ailure (low cardiac output syndrome), and the need for a timely correction of hypovolemia and hypotension. Anesthesia management was a general combined multicomponent anesthesia.Conclusion. This clinical case has shown the possibility of providing medical care to a patient with a transplanted heart at a modern level in an urban multidisciplinary hospital. Non-cardiac surgery was performed in accordance with recommendations of specialists of V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs and clinical recommendations in order to achieve optimal results and the fastest possible rehabilitation in the postoperative period.

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.

Malignancies After Heart Transplantation.

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Cause-of-Death-Registry. A total of 664 patients were followed for a median of 7.7years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx (p = 0.53). During a median follow-up of 7.7years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx.

Evaluation of Serum Levels of CK-MB in Heart Transplant Patients and Their Relationship with Graft Rejection Grades

Background: Heart transplant rejection is a multifactorial phenomenon routinely assessed using endomyocardial biopsy. Recently, efforts have been made to identify less invasive and cost-effective biomarkers for predicting graft rejection. Objectives: This study evaluated serum CK-MB levels in heart transplant patients and examined their relationship with the grading of graft rejection. Methods: In a prospective cohort study, 92 biopsy specimens from heart transplant patients were analyzed at Tehran's Rajaie Cardiovascular Medical and Research Center during 2022. Rejection grades, plasma CK-MB levels, and their relationship were investigated. Results: The mean age (standard deviation) of the patients was 36.70 (9.59) years, with 60.9% being male. Regarding graft rejection grades, 16.3% were grade 0R, 46.7% had Quilty effect (QE), 32.6% were grade 1R, and 4.3% were grade 2R. The mean (standard deviation) serum CK-MB levels for grades 0R, QE, 1R, and 2R were 17.14 (16.46), 12.39 (7.52), 26.77 (22.97), and 29.50 (7.94) ng/L, respectively (P = 0.046). The sensitivity of CK-MB for detecting grade 1R and 2R graft rejection was 56.7% and 75%, respectively, while its specificity for detecting grade 0R was 80%. A significant correlation was observed between increased serum CK-MB levels and transplant rejection grades (P &lt; 0.001). Most cases of grade 0R had negative CK-MB serum levels (&lt; 24 IU/L), with a higher frequency of positive CK-MB in grade 1R compared to grade 0R and in grade 2R compared to grade 1R. Conclusions: While elevated serum CK-MB levels in heart transplant patients may indicate graft rejection, the inconsistency of CK-MB levels with graft rejection grades suggests that endomyocardial biopsy and histopathological examination remain the gold standard for determining graft rejection grades.

Early outcomes in heart transplantation using donation after circulatory death donors in patients bridged with durable left ventricular assist devices

ObjectiveDonation after circulatory death heart transplantation potentially increases donor allografts, especially for patients with lower listing status. We assessed the outcomes of donation after circulatory death heart transplantation in patients bridged with durable left ventricular assist devices. MethodsThe United Network for Organ Sharing database was queried for adult heart transplants using donation after circulatory death donors from 2019 to 2022. Patients were stratified between those with durable left ventricular assist devices and those with intra-aortic balloon pump, inotropic, or no bridging support (control group). Primary outcome was 1-year mortality. Secondary end points were hospital length of stay, stroke, pacemaker implantation, dialysis, and acute rejection before discharge. ResultsA total of 160 left ventricular assist device recipients and 311 control recipients met study inclusion criteria. Recipients bridged with left ventricular assist devices were younger (55 vs 58 years, P < .001) with lower body mass index (28.3 vs 30.3, P < .001), longer waitlist times (112 vs 34 days, P < .001), longer out of body times (5.7 vs 4.6 hours, P < .001), and less frequent normothermic regional perfusion (31% vs 40%, P = .049). Patients with left ventricular assist devices commonly underwent transplantation at United Network for Organ Sharing status 3 and 4 (92%), whereas control patients underwent transplantation 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 = .34). However, acute rejection was higher in the unadjusted left ventricular assist device cohort (26% vs 13%, P < .001). On multivariable logistic regression, left ventricular assist device was an independent predictor of acute rejection (odds ratio, 2.21, 95% CI, 1.32-3.69, P = .002). ConclusionsDurable left ventricular assist devices may be associated with a higher risk of developing an early inflammatory response in donation after circulatory death heart transplantation; however, 1-year survival was similar between groups.