Heart Transplant Patients Research Articles

Complete heart block and subsequent sudden cardiac death following transcatheter tricuspid valve replacement in a heart transplant patient: a case report

Abstract Background Tricuspid regurgitation (TR) is a common valvular complication following heart transplantation. Transcatheter tricuspid valve replacement exists as a novel treatment option. However, as with any procedure, important complications can occur and warrant discussion. Case Summary A 46 year old woman, status-post orthotopic heart transplant (HT), developed symptomatic severe TR. She underwent transcatheter tricuspid valve replacement (TTVR; EVOQUE System, Edwards Lifesciences) and subsequently represented to hospital following a syncopal event. She was found to be in cardiogenic shock with complete heart block on electrocardiogram that degenerated into sudden cardiac death. Although the valve was well seated, autopsy revealed areas of focal necrosis where the bioprosthetic valve was seated in the region of the atrioventricular node and His bundle. Discussion This is the first case report of a complication of transcatheter tricuspid valve replacement in a heart transplant patient resulting in complete heart block and sudden cardiac death. While TTVR may be a good treatment option for select patients in this high-risk group, conduction system damage is a potential complication given the anatomy of the region and requires very close monitoring. This case further highlights the unique physiology of HT patients and illustrates the fact that bradyarrhythmias are often poorly tolerated and potentially lethal.

Bleeding Risk of Anticoagulation Reversal Strategies Before Heart Transplantation: A Retrospective Comparative Cohort Study

Heart transplantation (HT) poses high bleeding risks, especially for patients on anticoagulation. This study evaluates the use of idarucizumab for dabigatran (DBG) reversal compared to vitamin K antagonist (VKA) strategies in HT. A retrospective analysis of HT patients from January 2018 to December 2022, excluding those requiring ECMO immediately before or after surgery, was conducted. Outcomes included transfusion needs, re-surgery due to bleeding, ICU stay lengths, and 30-day survival. A cost analysis compared the direct expenses of each strategy. Among 34 patients, 20 were on DBG and 14 on VKAs or not anticoagulated. Idarucizumab significantly reduced the number of patients requiring transfusion (p = 0.034) and ICU stay lengths (p = 0.014), with no significant impact on re-surgery rates (p = 0.259) or survival (p = 0.955). Despite higher initial costs, overall expenses for idarucizumab were comparable to VKA reversal due to reduced transfusion needs and shorter ICU stays. Idarucizumab offers a viable and potentially cost-neutral anticoagulation reversal option for HT patients on DBG, presenting an alternative to VKA strategies. However, due to the retrospective nature of the study and the small sample size, further prospective studies are needed to confirm these findings.

A contemporary simple risk score for prediction of severe acute kidney injury after heart transplantation

AbstractBackgroundThe aim of this study was to develop a simple risk score to estimate severe acute kidney injury (AKI) risk based on a large contemporary heart transplantation (HT) cohort.MethodsFrom 1 January 2015 to 31 December 2021, all consecutive HT recipients in our institute were included and analysed for the occurrence of AKI within the first seven postoperative days. Patients transplanted between 2015 and 2019 comprised the derivation cohort, and those transplanted between 2020 and 2021 formed the validation cohort. The primary endpoint was severe AKI (AKI stages 2–3). The impact of severe AKI on 90 day mortality was also evaluated.ResultsOverall, 430 HT patients were included in the derivation cohort, and 108 were included in the validation cohort. Postoperative AKI occurred in 388 (72%) patients, including 162 (30%) severe AKI. The risk of 90 day mortality significantly increased in patients with severe‐AKI. Seven independent predictors of severe AKI were found in the derivation cohort, including recipients' body mass index, history of diabetes, anaemia, preoperative inotropes, estimated glomerular filtration rate, cardiopulmonary bypass duration and intraoperative red blood cell transfusion. The occurrence of severe AKI increased gradually from the lowest to the highest of the four risk score groups in the derivation and validation cohort. The scoring prediction model showed a highly acceptable discriminating power for severe‐AKI [C statistic: 0.76, 95% confidence interval (CI): 0.71–0.80 for derivation cohort; C statistic: 0.79, 95% CI: 0.71–0.89 for validation cohort].ConclusionsA contemporary simple risk score based on available variables from patients undergoing HT can accurately discriminate the risk of severe AKI.

Abstract 4134309: From Heartache to Headache: Cryptococcal Meningitis Post-Heart Transplant in a Chronic Hepatitis B and Sarcoidosis Patient

Introduction: We report the case of a heart transplant patient on chronic immunosuppression diagnosed with cryptococcal meningitis. Up to 5% of solid organ transplant patients develop cryptococcosis, carrying a 50% mortality rate in central nervous system involvement. Case Presentation: This is a 57-year-old male with a past medical history of heart failure with reduced ejection fraction (HFrEF) status post orthotopic heart transplantation (on prednisone 7.5 mg daily, mycophenolate, tacrolimus and sirolimus), pulmonary sarcoid, and chronic hepatitis B (on tenofovir and entecavir) who presented with headache, nausea, vomiting and seizure-like activity. The patient’s heart rate was 129 beats per minute, blood pressure 188/92 mmHg, but was afebrile. He eventually underwent a lumbar puncture with the cerebrospinal fluid (CSF) positive for cryptococcal antigen (1:2560). The patient was started on liposomal amphotericin B and flucytosine. Mycophenolate and sirolimus were held in the setting of his infection. The patient’s hospital course was complicated by acute kidney injury likely secondary to elevated tacrolimus levels while on fluconazole. He was ultimately discharged with plans to repeat CSF studies as an outpatient. Discussion: Here we report a case of cryptococcal meningitis in a heart transplant patient in the context of pulmonary sarcoidosis, chronic hepatitis B and quadruple immunosuppression. Of note, as part of rejection surveillance, the patient undertook serial AlloSure and AlloMap testing. Sirolimus was added to his regimen due to persistently elevated AlloSure scores. Indeed, immunosuppressive agents are the leading risk factor for cryptococcosis in organ transplant patients. Our patient also has two important risk factors for cryptococcal infection. Firstly, sarcoidosis is associated with T-cell dysregulation, compromising cell-mediated immunity. Additionally, hepatitis B carriers have an increased predisposition for cryptococcal infections, notwithstanding that our patient had been on dual antiviral therapy. Conclusion: Quadruple immunosuppression in heart transplant patients, especially in the context of risk factors such as sarcoidosis and hepatitis B infection, can result in cryptococcal meningitis and should be considered in patients with suggestive symptoms. Effective prophylactic regimens for such higher risk patients may be a potential area for further investigation.

Abstract 4137449: Diagnostic Yield and Testing Characteristics of an Invasive Coronary Function Testing Program

Background: Angina, ischemia, or myocardial infarction in the absence of obstructive coronary artery disease (ANOCA, INOCA, or MINOCA) is common and underdiagnosed. Invasive coronary function testing (CFT) for microvascular disease through coronary thermodilution and for coronary vasospasm through coronary reactivity testing can provide definitive diagnoses and improve patient quality of life. Here, we describe a single site experience launching a CFT program and present the diagnostic yield and test characteristics of the first 66 patients. Methods: The first 66 patients who underwent invasive CFT at Mass General Hospital after the launch of the program in 2022 were included. Invasive CFT data and clinical characteristics before and after were entered into a registry. We used descriptive statistics to summarize patient characteristics, diagnostic yield and change in management with invasive CFT. We describe the dose-response and safety of incremental doses of acetylcholine. Results: Among 66 patients (mean age 61.73±11.02 years, 56% female), 17 patients underwent testing at the time of an index angiogram and 49 were scheduled after knowledge of coronary anatomy. Reasons for invasive coronary function testing were post-revascularization angina (n=30, 45.5%), ANOCA (n=21, 31.8%), INOCA (n=9, 13.6%), MINOCA (n=4, 6.1%), and heart transplant patients (n=2, 3%). 24 (36.3%) patients underwent coronary thermodilution only, 6 (9.1%) coronary reactivity testing only , and 36 (54.5%) both. CFT resulted in a definitive diagnosis in 45 (68.1%) of participants – 37.9% with coronary vasospasm only, 13.6% with microvascular dysfunction only, and 16.7% with both. There were 21 (31.8%) patients who remained negative after invasive CFT. Invasive CFT led to a change in management in 46 (70%) patients. For example, nitrate, calcium channel blocker and beta blocker prescriptions were modified in 47%, 50%, and 52.3% of patients, respectively. Among 42 patients who underwent coronary reactivity testing by provocation with intracoronary acetylcholine doses of 20, 100, and 200 mcg, there was a dose-response to angina (18.5%, 70.2%, and 95.2%), ischemic ECG changes (11.1%, 75.7%, and 95.2%), and vessel spasm of greater than 90% (3.7%, 27%, and 57.1%). There was only one safety event(PTCA to re-establish flow after spasm). Conclusions: We demonstrate the safe implementation of an invasive coronary function testing program with very high diagnostic yield and impact on management.

Abstract 4144529: Cardiac Allograft Hypertrophy (CAH) at 6 Months Post Transplant Is a Prognostic Marker of Long-Term Outcomes: Are We Missing a Simple Biomarker?

Introduction: Cardiac hypertrophy is a known adverse prognostic marker in various non-transplant pathologies. In heart transplant patients, due to many confounders, it has been controversial on the relevance and timing of cardiac hypertrophy as an adverse remodeling vs acute injury pattern in an immunologically hostile environment. Previous studies have shown prognostication of hypertrophy on echocardiogram at 1-year post-heart transplant. Research Questions: Does cardiac hypertrophy within a year after transplant have long-term prognostic implications? Methods: We collected relevant clinical variables for all heart transplants using EPIC EHR’s Clarity database. Hypertrophy was defined based on LV Mass Indexed to body surface area where LV Mass = 0.8 x (1.04 x (((LVIDD + IVSd + PWd) 3 - LVIDD 3 ))) + 0.6. Relative Wall Thickness was defined as RWT = 2 x PWd / LVIDD. We used a rule-based natural language processing program validated by correlation with manual readings by trained cardiologists (r=0.96, p=0.007) to abstract echo variables. Results: Inclusion criteria were heart transplants performed from 2015 to 2023 at our center, with an echocardiogram closest to 6 months (+/- 1 month). Ten percent (n=33) showed hypertrophy on echocardiograms at 6 months (Table 1). Of these, 20 (61%) had mild, 3 (9%) severe, and 10 (30%) moderate hypertrophy. Of 33 patients, 28 (85%) had concentric, and 5 (15%) had eccentric hypertrophy. Patients with hypertrophy at 6 months had significantly worse survival at 5 years (p=0.01) and 10 years (p=0.05) compared to patients without hypertrophy (Fig 1). Survival at 5 and 10 years was not statistically different for patients with hypertrophy at 3 months (5 yrs p=0.17, 10 yrs p=0.06), 12 months (5 yrs p=0.38, 10 yrs p=0.30), and 18 months (5 yrs p=0.15, 10 yrs p=0.08) compared to those without hypertrophy. Conclusion: Cardiac hypertrophy on echocardiogram at 6 months predicts adverse long-term survival, while other time points did not.

Abstract 4118641: Trend, Survival, and Disparity Analysis of Heart Transplantation in a Single Large Transplant Center

Background: In the landscape of organ transplantation, heart transplantation stands as a life-saving procedure for patients with end-stage heart failure. Comprehensive analyses of transplant programs are imperative to optimize outcomes and understand the complexities. Hypothesis: This study hypothesizes that an increasing trend of heart transplant service and short-term mechanical circulatory support (STMCS) is the bridge to transplant; the UNOS (United Network for Organ Sharing) guideline positively impacts STMCS utilization. Even with the standard of care, there might be a disparity in receiving care in terms of gender and race. Goal/ Aims: By examining this center's collective experience, this research provides valuable insights into the evolving landscape of heart transplantation, ultimately contributing to advancements in patient care and transplant policy. Methods: This retrospective cohort study includes heart transplant patients in a single large transplant center. For statistical analysis, Cox regression, Mann-Whitney test, Kruskal Wallis, and Chi-Square test were used in IBM SPSS 25. Result: Trends: This retrospective study covering 2010 to 2022 comprehensively analyzed 1513 heart transplant patients. The cohort consisted of 1071 (70.78%) males and 442 (29.21%) females, 31.9% were bridged through STMCS. 76.7% of Caucasian and 16.1% were African American.The mean utilization of STMCS was 20.08% before the UNOS policy change, increasing to 53.81% after that (p < 0.001). Disparity Analysis: There was a statistically significant difference in STMCS utilization between white and black patients (p= 0.008) but no difference in between obese and non-obese cohorts (P=0.362).Wait time was similar among the genders (p=0.161) and different races (p=0.302). Survival Analysis: There is a significant survival discrepancy between patients bridged through MCS and those without STMCS(p< 0.001). However, yearly trend analysis showed an evolving survival trajectory favoring STMCS users. There are statistically significant survival differences among whites and blacks (P =0.008) but similar among the genders (p=0.589). Summary: The study reveals significant changes in the trend of transplants regarding STMCS utilization since the UNOS guideline. There are substantial differences in survival between STMCS vs. non-STMCS groups and among the races.There was a significant difference in STMCS utilization among the races.

Abstract 4118018: Increased Risk of Post-Transplant Malignancy After Isolated Heart Transplant in Adult Patients with Congenital Heart Disease

Introduction: Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. Methods: Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. Outcomes were PTM and hematologic malignancy (either leukemia, lymphoma or post-transplant lymphoproliferative disorder). Multivariable Fine-Gray competing-risk regression adjusting for age, sex, race, prior cardiac surgery, smoking, diabetes, induction immunosuppression, recipient and donor cytomegalovirus and Ebstein-Bar virus status was used to estimate subhazard ratio (SHR). Results: Of the total of 29,717 patients with HT were included, 1,017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and more likely to have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with higher risk of PTM (aSHR 1.44, 95% CI 1.15 – 1.80) and hematologic malignancy (aSHR 2.09, 95% CI 1.28 – 3.42). Among patients < 45 years old, CHD had an unadjusted SHR of 1.55 (95% CI 1.11 – 2.16) of PTM, Figure. Conclusions: Among adult patients with HT, CHD was associated with increased risk of PTM and hematologic malignancy. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Global left ventricular relaxation index in predicting cardiac cellular rejection in paediatric heart transplant patients.

Endomyocardial biopsy remains the gold standard for cardiac cellular rejection surveillance after heart transplantation. We studied a novel non-invasive index of left ventricular relaxation to detect cardiac cellular rejection in paediatric heart transplant patients. This is a single-centre retrospective study of paediatric heart transplant patients who underwent endomyocardial biopsy from June 2014 to September 2021. Left ventricular relaxation index was calculated as the sum of diastolic tissue Doppler imaging velocities (E) of the left ventricular lateral, septal, and posterior walls divided by the percentage of the left ventricular posterior wall thinning by M-mode. Statistical analysis included t-tests and Mann-Whitney tests to compare means and medians between treatment and non-treatment groups. We used the cut-off with the maximum Youden index to compare the sensitivity and specificity of left ventricular relaxation index to detect rejection. The study included 65 patients who underwent 246 cardiac catheterizations and endomyocardial biopsies. Out of 246, 192 procedures were included and 54 were excluded due to recent transplants or lack of echocardiographic data. A total of 114 demonstrated Grade 0R, 68 Grade 1R, 8 Grade 2R, and 2 Grade 3R allograft rejection. The difference in mean left ventricular relaxation index between treatment versus non-treatment groups (2R, 3R vs. 0R, 1R) was not statistically significant (p = 0.917). A left ventricular relaxation index cut-off of 0.73 had the highest Youden index with good sensitivity (100%) and poor specificity (23%) for detecting rejections with grades 2R and 3R. Left ventricular relaxation index, a novel index of left ventricular relaxation, was not a sensitive or specific predictor of cardiac cellular rejection in paediatric heart transplants.

Heart Transplant Rejection in the Setting of Glyphosate Herbicide Exposure; A Case Report

Glyphosate is a common herbicide utilized worldwide with known exposure related toxicities. Numerous adverse effects related to glyphosate exposure have been documented, specifically in non-human models, however literature is lacking on cardiotoxic effects specific to heart transplant patients. Rejection is the most common post-transplant complication and the diagnosis of such is vital in order to guide immediate and appropriate treatment. In addition to the endomyocardial biopsy, noninvasive genetic testing can aid in rejection diagnosis and distinguish between cell-mediated and antibody-mediated rejection. We describe a case of glyphosate exposure in a post orthotopic heart transplant and the subsequent heart transplant rejection, patient’s clinical course, treatment, and follow up.

CYP3A5 pharmacogenetic testing for tacrolimus in pediatric heart transplant patients: a budget impact analysis.

Pharmacogenomic testing can optimize drug efficacy and minimize adverse effects. CYP3A5 polymorphisms affect the metabolism of tacrolimus. We sought to estimate the budget impact of preemptive pharmacogenomic testing for CYP3A5 in pediatric heart transplantation patients from an institutional perspective. A decision tree was constructed to estimate the budget impact of pediatric heart transplant patients (age ≤18 years) initiated on tacrolimus with and without CYP3A5 pharmacogenomic testing. The budget impact of preemptive pharmacogenomic testing versus no pharmacogenomic testing was calculated. One-way sensitivity analysis and alternative analyses were conducted to assess the robustness of results to changes in model parameters. CYP3A5 genotype-guided dosing provided savings of up to $17 225 per patient compared to standard dosing. These savings decreased to $11 759 when using another institution's data for the standard-dosing group. The time to achieve therapeutic concentration in the poor metabolizer genotype-guided dosing group had the largest impact on cost savings while the cost of the pharmacogenetic test had the smallest impact on cost savings. Implementing CYP3A5 testing could save $17 225 per pediatric heart transplant patient receiving tacrolimus. As pharmacogenomic testing becomes more widespread, institutions should track resource requirements and outcomes to determine the best implementation policies going forward.

Role of pericoronary adipose tissue inflammation at CCTA after heart transplantation as non-invasive diagnostic tool of cardiac rejection and predictor of major adverse cardiovascular events

Abstract Background Long-term survival of heart transplanted (HT) patients is challenged by cardiac rejection and cardiac allograft vasculopathy (CAV). Until now, there are no established biomarkers for graft dysfunction, and the conventional approach for cardiac rejection surveillance is through the endomyocardial biopsy (EMB), an invasive and costly procedure. Purpose This study investigates the prognostic value of the pericoronary Fat Attenuation Index (FAI) and its role as a marker of inflammation and rejection in HT recipients. Methods A double-center observational retrospective study was conducted on a cohort of HT patients who underwent coronary computed tomography angiography (CCTA) between January 2016 and December 2022. FAI was measured with dedicated software and using the cut-off described in literature, we considered each coronary as "inflamed" if FAI was ≥ - 70,1 HU and "not inflamed" if FAI was < - 70,1 HU. Then, based on the number of inflamed coronary arteries for each patient, we divided the population into two comparison groups: high inflammatory (high INF) phenotype (alle three coronary arteries inflamed) and low inflammatory (low INF) phenotype (at least one coronary artery not inflamed). The primary endpoint was a composite of all-cause mortality, acute myocardial infarction, urgent revascularization and heart failure hospitalization. Furthermore, we investigated the correlation between FAI and cardiac rejection by looking for T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR) through EMB performed no more than six months before or after CCTA. Results A total of 101 HT patients were included; of this group 58 patients underwent EMBs within six months after or before the CCTA. The median duration of follow-up was 28 months. The composite endpoint occurred in 17 patients (16.8%). We documented 26 significative cardiac rejection episodes, 14 TCMR ≥ 2R and 12 AMR. The composite endpoint was achieved in 37.9% of patients with high INF phenotype compared to 8.3% with low INF phenotype (p < 0.001). In the multivariate analysis, the high INF phenotype remained an independent predictor of the composite endpoint in our population (HR: 10.5; 95% CI: 1.88-58.71; p = 0.007). Patients with TCMR and AMR had significantly higher FAI values. High INF phenotype correlated with the presence of ACR ≥ 2R (55.0% vs 7.9%, p < 0.001) and AMR (55.0% vs 2.6%, p < 0.001). Conclusion In HT patients, FAI is an independent predictor of major cardiovascular events. It is also associated with TCMR and AMR within six months from CCTA. FAI, therefore, may offer a non-invasive approach to stratify the prognosis of HT patients and serve as a valuable inflammatory biomarker for early diagnosis of cardiac rejection, supporting the use of CCTA in this setting of patients.Correlation FAI and MACECorrelation FAI and cardiac rejection

Outcomes in patients with light chain cardiac amyloidosis undergoing heart transplantation: a single centre UK study

Abstract Background Light chain cardiac amyloidosis (AL-CA) results in restrictive cardiomyopathy associated with progressive heart failure and poor survival. Traditionally, outcomes following heart transplantation in patients with AL-CA have been worse than in other heart failure cohorts and consequently, many centres do not offer this population transplantation. Purpose and Methods This was a retrospective observational study of 18 patients with AL-CA (age 52.7years +/- 8.3, male 66%) referred to our centre in the UK for assessment for heart transplantation from 2008 to 2023. Seven patients (39%) were listed for transplant, and all received orthotopic heart transplantation (OHT). This study compared pre-transplantation characteristics in those offered cardiac transplantation with those not transplanted. We also examined post-transplantation outcomes in this group (n=7) compared with the overall heart transplantation population (n=95) at our centre. Results Patients with AL-CA who were not offered transplantation (n=11) were older (mean age 54.3 vs 50.3 years), were more likely male (72% vs 57%) but had similar baseline renal function to those transplanted (median eGFR 60.4 vs 54.2ml/min). Reasons against offering OHT included extensive multisystem or renal amyloid deposition (n=4), insufficient haematological response (n=2), heart failure not advanced enough for OHT (n=1) and malignancy (n=1). Pre-transplant right heart catheterisation of patients undergoing OHT demonstrated a mean transpulmonary gradient of 7.8mmHg (+/- 1.9) and cardiac output of 2.94/min (+/- 0.3). Five patients (71%) had a complete and two (29%) a partial haematological response to clonally directed chemotherapy. Three patients were bridged to transplant with biventricular assist devices for 9, 10 and 51 days, respectively. Five patients developed episodes of histologically confirmed rejection of grade 2R that resolved with medical management. One patient experienced first degree atrioventricular block and had a pulseless electrical activity arrest 19 days after transplantation before being fitted with a permanent pacemaker. Two patients went on to receive autologous stem cell transplantation. Patients with AL-CA undergoing OHT had a lower mortality rate compared with non-transplanted patients over a median follow up of 9 months (HR 0.3, 95%CI 0.07-1.3, p = 0.10). Two patients with AL-CA died at 42 days and 7.7 years after OHT. Five patients (71%) are alive under follow up at 4, 7.5, 9, 10 months and 7.7 years post OHT. There was no difference in survival between patients who underwent heart transplantation for AL-CA and patients who underwent heart transplantation for all other indications (HR 1.94, 95%CI 0.3 – 12, p=0.45). Conclusions In selected patients with AL-CA, OHT offers favourable outcomes. After clonally directed therapy to control the underlying plasma cell dyscrasia, heart transplantation should be considered in the absence of widespread systemic disease.

Home alone on milrinone: a novel way to deliver home inotropes as a bridge to heart transplantation

Abstract Continuous ambulatory intravenous inotropes can be successfully used as a bridge to decision or heart transplant in patients with end-stage heart failure. The traditional model at our institute involved the Hospital in the Home (HITH) team, with daily nurse-led visits to the patients’ home, to safely maintain this treatment, which is otherwise largely restricted to the intensive care setting. In response to the COVID-19 pandemic, delivery of healthcare underwent a paradigm shift. Our model was changed to a patient led continuous intravenous inotrope program at home which obviated the need for a daily nurse visit. We describe our process and our early outcomes. Fifteen patients were deemed suitable for the Independent at Home program. All patients needed to complete ambulatory intravenous inotrope education, pass competency testing and have implantable cardioverter-defibrillators inserted prior to discharge. Competencies included proficiency for troubleshooting the inotrope ambulatory delivery pump, monitoring of vital signs and ability to report decompensated heart failure symptoms. Weekly outpatient visits to our heart failure clinic with nursing, medical and pharmacy reviews were scheduled. Emergency action plans were provided to patients. 73.3% of our cohort were male. The average age was 51 years. 46.6% had a diagnosis of dilated cardiomyopathy. 53.3% were listed for heart transplant and were bridge to transplant (BTT) and 46.7% were bridge to decision (BTD) for heart transplant. Over a study period of 35 months, seven (46.7%) patients were weaned off inotropes, three (20.0%) were escalated to durable mechanical circulatory support (one due to decompensated heart failure and two due to persistently elevated pulmonary pressures), four (26.7%) were transplanted and one (6.7%) chose to be palliated. Six patients had one admission, five patients had two admissions. Five readmissions were due to decompensated heart failure, four admissions were planned to optimize pulmonary hypertension following a right heart catheterization, three had peripherally inserted central catheter (PICC) line complications and two had non-cardiac admissions (refer to table 1). The median length of days on the Independent at Home program was 112 days with an interquartile range of 120 days. A comparative group consisting of consecutive patients treated under the previous Hospital in the Home model are presented in table 2; the Independent at Home cohort shows reduced unplanned admissions. The independent at home inotrope program is an effective and safe option to bridge to decision or bridge to cardiac transplantation.HITH vs Independent admission reasonHITH vs Independent admissions

Challenging endomyocardial biopsies' gold standard status in rejection screening: a prospective blinded study on cardiovascular magnetic resonance in heart transplant patients

Abstract Background The detection of rejection is crucial for graft survival after heart transplantation. Endomyocardial biopsies (EMBs) serve as the gold standard for rejection surveillance despite its limitations, while cardiac magnetic resonance (CMR), in conjunction with donor-derived cell-free DNA (dd-cfDNA) analysis, holds promise as a non-invasive approach. Purpose In this prospective blinded study, our aim was to evaluate feasibility of CMR for rejection screening, validating it against EMB, dd-cfDNA, and clinical status. Methods We blindly analyzed 250 studies involving CMR, EMB, dd-cfDNA, and clinical data in 58 heart transplant recipients (17 children and 41 adults). Of these 250 studies, 239 (96%) were assessed within 1 to 28 months after transplantation, and 11 studies (4%) 3-14 years post-transplant. In CMR T1- and T2-mapping analyses, acute rejection was defined by T1 or T2 times exceeding the specified thresholds (T1 ≥ 1060 ms, T2 ≥ 55 ms) in at least 2/16 heart segments. EMB findings were graded according to the ISHLT criteria (2005 and 2013), and acute cellular rejection (ACR) grade ≥ 2 or antibody-mediated rejection (AMR) grade ≥ 1 were considered significant. The cutoff for abnormal dd-cfDNA was set at 0.2%. Solely clinical rejection included patients with absent or normal EMB (ACR grade 0-1 and AMR grade 0), but with symptoms or ECG/echocardiographic findings indicative of acute rejection. Results Our study revealed 22 acute rejections, with 15 confirmed through EMB and 7 diagnosed solely based on clinical indicators. Among the EMB-confirmed cases, 3/15 exhibited AMR grade 1, 10/15 demonstrated ACR grade 2 and 2/15 ACR grade 3. CMR identified rejection in 77% (17/22) of cases. Specifically, it successfully identified rejection in 67% (10/15) of EMB-confirmed cases and 100% (7/7) of solely clinically diagnosed cases. Examining the concordance between CMR findings and dd-cfDNA levels, 35% (6/17) of the CMR-identified rejection cases exhibited abnormal dd-cfDNA, while 30% (5/17) showed normal levels. Notably, in one case, despite normal CMR results, both EMB and dd-cfDNA indicated rejection. Conversely, in four instances where EMB indicated acute rejection, both CMR and dd-cfDNA levels were normal. These findings highlight a potential discrepancy in the diagnostic accuracy of EMB, suggesting its tendency to both over- and underdiagnose acute heart transplant rejection. The integration of CMR and dd-cfDNA in the diagnostic process may provide a more comprehensive and reliable assessment of rejection episodes, offering valuable insights for clinical decision-making in heart transplant recipients. Conclusions EMB presents challenges in both under- and overdiagnosing rejection in heart transplant surveillance. A strategy based on CMR, combined with dd-cfDNA analyses, shows promise as a new gold standard for rejection screening.Flowchart

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.

Efficacy and severity of side-effects of rosuvastatin compared to other statins post-heart-transplantation

Abstract Introduction The International Society of Heart and Lung Transplantation (ISHLT) 2022 guideline recommends statin therapy in heart transplantation (HTx) patients, with the therapeutic low-density lipoprotein (LDL) target being <2.5 mmol/L. Particularly pravastatin is recommended, given proven beneficial effects on long-term clinical outcome and the low prevalence of side effects. Yet, in the general population, rosuvastatin has been shown to be even more potent. Purpose We investigated the lipid-lowering effect and severity of side-effects of rosuvastatin compared to less potent statins in HTx patients. Methods In this before-after study, we included all HTx patients whom were prescribed a change from the statin they were using to rosuvastatin, for better cardiovascular risk management and/or because of side-effects, between February 2018 and February 2023. We evaluated the weight, lipid profile and side-effects (including myalgia, cramps, stiffness and weakness) of these patients up to one year prior to and after the statin change. At the same time, side-effects were measured in a visual analogue scale (VAS) ranging from 0-10, with the average score of side-effects utilized for analysis. We compared the differences using a Wilcoxon signed rank test. Results Out of 299 HTx patients, we included 114 patients, with a median age of 58 [IQR 50-67] years at switch of whom 31 (27%) were females. Median time since HTx was 9 [IQR 5-15] years. The distribution and dosage of prescribed statins before and after switch can be found in Table 1. Compared to statins used prior to therapy change, rosuvastatin was associated with lower total cholesterol, LDL- and triglyceride levels, with high density lipoprotein (HDL) levels remaining the same (Table 2). No difference in bodyweight was found (Table 2). Before switch, 41 (36%) patients achieved the target of LDL-levels below 2.5 mmol/L. After switch, 86 (75%) patients achieved the target of LDL levels below 2.5 mmol/L. Rosuvastatin shows a trend towards a lower prevalence of side-effects (Table 2). Conclusion In HTx patients that were prescribed a change of statin due to better cardiovascular risk management and/or complaints of side-effects, rosuvastatin is related to a more favorable lipid profile, without additional side-effects, compared to other statins. Furthermore, many more patients achieve the guideline recommended LDL-target. Ongoing research should determine whether this translates to a better clinical outcome.

The diagnostic value of endomyocardial biopsy in the era of precision medicine: data from over 8,000 patients with comprehensive biopsy diagnostics

Abstract Background Endomyocardial biopsy (EMB) is an important diagnostic tool for evaluating various cardiac diseases such as myocarditis and storage disorders as well as for the monitoring heart transplant patients. Despite advances in non-invasive imaging techniques to characterize myocardial tissue, EMB remains the gold standard for definitive diagnosis and initiation of specific therapy. Here we report EMB laboratory results from over 8,000 patients and demonstrate the diagnostic utility of EMB. Methods and results We retrospectively reviewed EMB analyses performed at our institution. EMBs for monitoring graft rejection were not included in this study. Clinical data, suspected clinical diagnoses and EMB-based laboratory results were collected. Histopathological, immunohistochemical and molecular biology biopsy findings were recorded and reviewed for degree of concordance with clinical diagnosis. In total, EMBs from N=8,085 consecutive patients with unexplained heart failure were analyzed. The comprehensive EMB analysis revealed that N=616 (7.6%) patients had cardiac storage disease, most of whom had cardiac amyloidosis (N=606). N=357 (4.4%) patients were diagnosed with acute forms of myocarditis, including N=95 cases with active myocarditis, N=148 cases with giant cell myocarditis, N=95 cases with sarcoidosis and N=19 cases with eosinophilic myocarditis. A total of N=3,392 (42%) patients were found to have inflammatory heart disease such as inflammatory cardiomyopathy and borderline myocarditis, whereby a differentiation of the inflammatory infiltrates revealed considerable differences in the quality of inflammation. Viral genomes were found in the myocardium of N=6,072 (75%) patients, with treatment-relevant viral infections detected in N=2,015 (25%) cases. The remaining N=1,705 (21%) patients were diagnosed with other cardiomyopathies, including dilated cardiomyopathy (N=1,252), heart failure with preserved ejection fraction (N=325), hypertrophic cardiomyopathy (N=117) and arrhythmogenic right ventricular cardiomyopathy (N=11). Conclusions This retrospective study of over 8,000 patients with heart failure clearly shows that a definitive diagnosis is only possible with a comprehensive EMB diagnosis and leads to specific therapy in 79% of the cases. In the remaining 21% of patients, infectious and inflammatory causes could be excluded in order to initiate standard heart failure therapy. It is important to emphasize here that the quality of the inflammation and therapy-relevant viral infections cannot be detected with imaging techniques, which underlines the clinical-therapeutic importance of endomyocardial biopsy.

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.

PIRCHE-II: a new tool to predict rejection in cardiac transplantation?

Abstract Aim This retrospective observational study aims to compare patients diagnosed with antibody-mediated or cell-mediated rejection with patients without episodes of rejection and study any predictors of rejection at follow-up with particular attention to PIRCHE-II scores. Materials and Methods We performed a retrospective evaluation of prospectively collected data of heart transplant patients from January 2022 to August 2023, at a single hospital. Preoperative, intraoperative and postoperative parameters are collected anonymously in our institutional database used for internal quality control. The primary endpoint was the incidence of rejection in one of three control endomyocardial biopsies. As pre-operative data, age, sex, BSA, blood group mismatch, risk such as dyslipidemia, hypertension, diabetes, peripheral vascular disease, COPD, previous cardiac surgery, PRA, ischemia time and post-operative infections. We evaluated patients at a mean follow-up of 106 (78 – 180) days. In patients who tested positive for cell-mediated or antibody-mediated rejection, the PIRCHE-II score was calculated. Results There were 45 patients with no diagnosis of rejection and they were aged 61 [50-65]; 22.2% were women, with a mean BSA of 1.87 ± 0.19. 22.2% had a blood type mismatch. They had a mean PIRCHE-II of 111.88 ± 43.6. There were 15 patients diagnosed with rejection and they were 63 years old [52 – 66]; 20.0% were women, with a mean BSA of 1.84 ± 0.23. 13.3% had a blood type mismatch. They had a mean PIRCHE-II of 113.70 ± 33.90. In multivariable analysis, the main predictors of rejection were plasma transfusions [OR 0.053, 95% CI, p=0.02], post-operative infections [OR 0.076, 95% CI, p=<0, 02] and the PIRCHE – II [OR 3.284, 95% CI, p=0.04]. The mean PIRCHE-II of patients who presented antibody-mediated or cell-mediated rejection was 113.70 ± 33.90 and that of patients who did not present any rejection was 111.88 ± 33.90; Conclusion According to the results obtained, the PIRCHE-II algorithm could be a tool in immunological risk stratification in patients undergoing cardiac transplantation. It is necessary, however, to apply PIRCHE-II to a larger number of patients and should also be considered in light of other factors such as the immunological status of the recipients, the immediate post-operative course (infections, CMV reactivation, blood component transfusions), which could constitute an immunological trigger and patient compliance in immunosuppressive therapy.Patients' featuresResuts