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The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review. © 2022 International Society for Heart and Lung Transplantation

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Objective : The aim of this study was to identify perioperative risk factors associated with intensive care unit readmission and in-hospital death after cardiac surgery. Design : Retrospective analysis using a multivariable regression model to identify independent risk factors for ICU readmission and in-hospital mortality. Setting : The study was carried out in a single tertiary-care hospital. Participants : This was an analysis of 2789 adult patients. Interventions : All patients underwent cardiac surgery and were admitted to the intensive care unit perioperatively at the General Hospital Vienna. Measurements and Main Results : Among the 2789 patients included in the analysis, 167 (6%) were readmitted to the intensive care unit during the same hospital stay. Preoperative risk factors associated with ICU readmission included end-stage renal failure (odds ratio (OR) 2.80, 95% CI: 1.126-6.964), arrhythmia (OR 1.59, 95% CI: 1.019-2.480), chronic obstructive pulmonary disease (OR 1.51, 95% CI: 1.018-2.237), age > 80 (OR 2.55, 95% CI: 1.189-5.466), and EuroSCORE II > 8 (OR 1.40, 95% CI: 1.013-1.940). Readmitted patients were more likely to die than non-readmitted patients (OR 5.3, 95% CI: 3.284-8.558). In-hospital mortality in readmitted patients was 19.2%, whereas that in the non-readmitted study population was 5.1%. Conclusion : Preoperative risk assessment is crucial for identifying cardiac surgery patients at risk of ICU readmission and in-hospital death. The potentially modifiable risk factors pinpointed by our study call for the optimization of care before surgery and after ICU discharge.

OBJECTIVE Tricuspid regurgitation (TR) in heart transplant patients is associated with poor outcome. The increased risk for surgical and post-operative complications might be reduced in these vulnerable patients by transcatheter therapies. METHODS All patients with prior heart transplantation (HTX) undergoing transcatheter edge-to-edge repair in tricuspid position (T-TEER) were prospectively enrolled in an institutional registry. RESULTS Seven transplanted patients (5/7 female) at a mean age of 53 [48; 64] and median TRI-SCORE of 14 [7; 22] underwent T-TEER to treat symptomatic TR ≥ IV in an elective (n = 6) and urgent (n = 1) setting, respectively. Median time from HTX to T-TEER was 13 years. A total of 2 (n = 4) and 3 (n = 3) clips were implanted with a technical success in 6/7 (one single device detachment). TR reduction was effective and durable within a median echocardiographic follow-up time of 10 months (TR baseline vs last follow-up: p = 0.03). Further, a significant right ventricular remodelling (right ventricular end-diastolic diameter: 50 mm to 36 mm, p = 0.02), decrease in the inferior vena cava diameter (24 mm to 18 mm, p = 0.04) and in the gamma-glutamyl-transferase (255 U/l to 159 U/l, p = 0.04) was found. Four of 7 patients were free of cardiovascular death (n = 1, 267 days after T-TEER), cardiac redo surgery (n = 1), heart failure hospitalization (n = 2) and had no further clinical signs of right heart failure. CONCLUSIONS T-TEER after HTX demonstrates to be feasible and effective regarding TR reduction in a short-term follow-up. The initial results may pave the way of a novel approach in TR management in HTX patients.

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

Controlled organ donation after circulatory determination of death is increasingly being used for the donation of organs also in thoracic transplantation. This document outlines the position of the International Society for Heart and Lung Transplantation on thoracic organ transplantation in circulatory determination of death. The document also includes a position regarding some of the methods applied to ensure the viability of Donation after Circulatory Death organs retrieved after certification of death.

BackgroundThe Molecular Microscope (MMDx) system classifies heart transplant endomyocardial biopsies as No-rejection (NR), Early-injury, T cell-mediated (TCMR), antibody-mediated (ABMR), mixed, and possible rejection (possible TCMR, possible ABMR). Rejection-like gene expression patterns in NR biopsies have not been described. We extended the MMDx methodology, using a larger data set, to define a new "Minor" category characterized by low-level inflammation in non-rejecting biopsies.MethodsUsing MMDx criteria from a previous study, molecular rejection was assessed in 1,320 biopsies (645 patients) using microarray expression of rejection-associated transcripts (RATs). Of these biopsies, 819 were NR. A new archetypal analysis model in the 1,320 data set split the NRs into NR-Normal (N = 462) and NR-Minor (N = 359).ResultsCompared to NR-Normal, NR-Minor were more often histologic TCMR1R, with a higher prevalence of donor-specific antibody (DSA). DSA positivity increased in a gradient: NR-Normal 24%; NR-Minor 34%; possible ABMR 42%; ABMR 66%. The top 20 transcripts distinguishing NR-Minor from NR-Normal were all ABMR-related and/or IFNG-inducible, and also exhibited a gradient of increasing expression from NR-Normal through ABMR. In random forest analysis, TCMR and Early-injury were associated with reduced LVEF and increased graft loss, but NR-Minor and ABMR scores were not. Surprisingly, hearts with MMDx ABMR showed comparatively little graft loss.ConclusionsMany heart transplants currently diagnosed as NR by histologic or molecular assessment have minor increases in ABMR-related and IFNG-inducible transcripts, associated with DSA positivity and mild histologic inflammation. These results suggest that low-level ABMR-related molecular stress may be operating in many more hearts than previously estimated. (ClinicalTrials.gov #NCT02670408).

For over 30 years, the International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant (TTX) Registry has gathered data regarding transplant procedures, donor and recipient characteristics, and outcomes from a global community of transplant centers. Almost 70,000 adult lung transplant procedures have been reported to the Registry since its inception, each one providing an opportunity for a recipient with end-stage lung disease to regain quality of life and longevity. With each year’s report, we provide more detailed analyses on a particular focus theme important to recipient outcomes. Since 2013, these have been donor and recipient age; retransplantation; early graft failure; indication for transplant; allograft ischemic time; multiorgan transplantation; and donor and recipient size matching.(1–7) In response to a changing regulatory environment, the ISHLT TTX Registry is undergoing an update in data acquisition, and the patient cohort examined in this report is therefore derived from the same data source or datasets as that examined in the 2019 annual reports.(2,8–10) We refer the reader to the 2019 and prior reports for a detailed description of the baseline characteristics of the cohort, and additional core analyses not directly related to the focus explored in this year’s report. To complement the 2020 report which focussed on donor characteristics, the goal of this year’s report was to focus entirely on changes in recipient factors over the past 3 decades and to identify important recipient characteristics and transplant processes that may influence post-transplant outcomes. Due to small numbers, heart-lung transplant recipient characteristics and transplant outcomes have not been included. This 38th annual adult lung transplant report is hence basedon data submitted to the ISHLT TTX Registry on 67,493 adult recipients of deceased recipient transplants between January 1, 1992 and June 30, 2018.

Previous studies indicate an association between reduced absolute lymphocyte count (ALC) and cytomegalovirus (CMV) infection after solid organ transplantation and have therefore highlighted the potential of ALC as a simple tool to predict CMV infection in transplant patients. This study aimed to examine the utility of ALC as a valuable marker for CMV infection in heart transplant patients.Clinical information and ALC data of all adult patients who received orthotopic heart transplantation at the Medical University of Vienna between January 2004 and May 2019 were collected. We performed a multivariable Cox regression model that incorporates repeated measurements of ALC as a time-varying continuous factor in 2 ways, first as continuous logarithmic factor considering a 50% decrease of ALC levels and second as binary factor using a threshold of 610 cells/μL.One hundred fifty-eight (39%) patients developed CMV infection over the course of 2 y. Patients with lymphopenia were shown to be at higher risk of developing CMV infection both in the continuous approach (HR [per 50% reduction] 1.29; confidence interval [CI], 1.09-1.53; P = 0.003) and the binary approach with a cutoff of 610 cells/μL (HR 1.74; CI, 1.20-2.51; P = 0.003).This study demonstrated a strong association between reduced ALC and the development of CMV infection after heart transplantation. ALC value monitoring could provide an additional tool to assess individualized CMV risk after solid organ transplantation.

Neurological complications after heart surgery are associated with tremendous morbidity and mortality. Nonconvulsive status epilepticus (NCSE), which can only be verified by EEG, may cause secondary brain damage. Its frequency and its impact on outcomes after cardiac surgery is still unclear. We collected the neurological files and clinical data of all our patients after heart surgery who, in the course of their ICU stay, had been seen by a neurologist who ordered an EEG. Within 18 months, 1457 patients had cardiac surgery on cardiopulmonary bypass. EEG was requested for 89 patients. Seizures were detected in 39 patients and NCSE was detected in 11 patients. Open heart surgery was performed in all 11 NSCE patients, of whom eight showed concomitant brain insults. None had a history of epilepsy. Despite the inhibition of seizure activity with antiseizure medication, clinical improvement was only noted in seven NCSE patients, three of whom were in cerebral performance category 2 and four in category 3 at hospital discharge. The four patients without neurological benefit subsequently died in the ICU. The occurrence of NCSE after open cardiac surgery is significant and frequently associated with brain injury. It seems prudent to perform EEG studies early to interrupt seizure activity and mitigate secondary cerebral injury.

The INTERHEART study (ClinicalTrials.gov #NCT02670408) used genome-wide microarrays to detect rejection in endomyocardial biopsies; however, many heart transplants with no rejection have late dysfunction and impaired survival. We used the microarray measurements to develop a molecular classification of parenchymal injury.In 1320 endomyocardial biopsies from 645 patients previously studied for rejection-associated transcripts, we measured the expression of 10 injury-induced transcript sets: 5 induced by recent injury; 2 reflecting macrophage infiltration; 2 normal heart transcript sets; and immunoglobulin transcripts, which correlate with time. We used archetypal clustering to assign injury groups.Injury transcript sets correlated with impaired function. Archetypal clustering based on the expression of injury transcript sets assigned each biopsy to 1 of 5 injury groups: 87 Severe-injury, 221 Late-injury, and 3 with lesser degrees of injury, 376 No-injury, 526 Mild-injury, and 110 Moderate-injury. Severe-injury had extensive loss of normal transcripts (dedifferentiation) and increase in macrophage and injury-induced transcripts. Late-injury was characterized by high immunoglobulin transcript expression. In Severe- and Late-injury, function was depressed, and short-term graft failure was increased, even in hearts with no rejection. T cell-mediated rejection almost always had parenchymal injury, and 85% had Severe- or Late-injury. In contrast, early antibody-mediated rejection (AMR) had little injury, but late AMR often had the Late-injury state.Characterizing heart transplants for their injury state provides new understanding of dysfunction and outcomes and demonstrates the differential impact of T cell-mediated rejection versus AMR on the parenchyma. Slow deterioration from AMR emerges as a major contributor to late dysfunction.

Background The myocardium exhibits an adaptive tissue-specific renin-angiotensin system (RAS), and local dysbalance may circumvent the desired effects of pharmacologic RAS inhibition, a mainstay of heart failure with reduced ejection fraction (HFrEF) therapy. Objectives This study sought to investigate human myocardial tissue RAS regulation of the failing heart in the light of current therapy. Methods Fifty-two end-stage HFrEF patients undergoing heart transplantation (no RAS inhibitor: n = 9; angiotensin-converting enzyme [ACE] inhibitor: n = 28; angiotensin receptor blocker [ARB]: n = 8; angiotensin receptor neprilysin-inhibitor [ARNi]: n = 7) were enrolled. Myocardial angiotensin metabolites and enzymatic activities involved in the metabolism of the key angiotensin peptides angiotensin 1-8 (AngII) and Ang1-7 were determined in left ventricular samples by mass spectrometry. Circulating angiotensin concentrations were assessed for a subgroup of patients. Results AngII and Ang2-8 (AngIII) were the dominant peptides in the failing heart, while other metabolites, especially Ang1-7, were below the detection limit. Patients receiving an ARB component (i.e., ARB or ARNi) had significantly higher levels of cardiac AngII and AngIII (AngII: 242 [interquartile range (IQR): 145.7 to 409.9] fmol/g vs 63.0 [IQR: 19.9 to 124.1] fmol/g; p Conclusions The failing heart contains considerable levels of classical RAS metabolites, whereas AngIII might be an unrecognized mediator of detrimental effects on cardiovascular structure. The results underline the importance of pharmacologic interventions reducing circulating AngII actions, yet offer room for cardiac tissue-specific RAS drugs aiming to limit myocardial AngII/AngIII peptide accumulation and actions.

Background Temporary epicardial pacing wires, implemented in patients during heart transplantation, are routinely removed before discharge. However, in some cases, these wires may remain in situ and are often considered as a contraindication for cardiovascular magnetic resonance (CMR) imaging in the future. Therefore, we aimed to provide data about safety and image quality of CMR in these patients. Methods This is a report on a subpopulation out of 88 patients after heart transplantation that were included in a prospective cohort study and underwent multiple CMR in their post-transplant course. During CMR, patients were monitored by electrocardiogram and all examinations were observed by a physician to document potential adverse events. Additionally, image quality was assessed by an imaging specialist. Results Nineteen of 88 patients included had temporary pacing wires in situ. These patients underwent a total of 51 CMR studies. No major adverse event and only one single, mild sensory event could be documented. All CMR studies showed preserved diagnostic image quality. Temporary pacing wires were visible in 100% of HASTE and cine sequences. In less than 50% of the examinations, temporary pacing wires were also visible in T1 and T2 mapping, short tau inversion recovery (STIR), and late gadolinium enhancement (LGE) sequences, without any impairment of image quality. Conclusions With a low event rate of only one mild adverse event during 51 CMR examinations (2%), CMR appears to be safe in patients with retained temporary epicardial pacing wires after heart transplantation. Moreover, image quality was not impaired by the presence of pacing wires.

Heart transplantation is advocated in selected patients with advanced heart failure in the absence of contraindications. Principal challenges in heart transplantation centre around an insufficient and underutilized donor organ pool, the need to individualize titration of immunosuppressive therapy, and to minimize late complications such as cardiac allograft vasculopathy, malignancy, and renal dysfunction. Advances have served to increase the organ donor pool by advocating the use of donors with underlying hepatitis C virus infection and by expanding the donor source to use hearts donated after circulatory death. New techniques to preserve the donor heart over prolonged ischaemic times, and enabling longer transport times in a safe manner, have been introduced. Mechanical circulatory support as a bridge to transplantation has allowed patients with advanced heart failure to avoid progressive deterioration in hepato-renal function while awaiting an optimal donor organ match. The management of the heart transplantation recipient remains a challenge despite advances in immunosuppression, which provide early gains in rejection avoidance but are associated with infections and late-outcome challenges. In this article, we review contemporary advances and challenges in this field to focus on donor recovery strategies, left ventricular assist devices, and immunosuppressive monitoring therapies with the potential to enhance outcomes. We also describe opportunities for future discovery to include a renewed focus on long-term survival, which continues to be an area that is under-studied and poorly characterized, non-human sources of organs for transplantation including xenotransplantation as well as chimeric transplantation, and technology competitive to human heart transplantation, such as tissue engineering.

Background and Objective: The number of adults with congenital heart disease (ACHD) is increasing worldwide. Almost all congenital cardiac lesions can be successfully treated due to the progress in neonatal surgery and pediatric cardiology with a high likelihood of surviving until adulthood. However, ACHD frequently develop sequelae related to the initial cardiac anomaly. Heart failure (HF) is one of the most common complications associated with a high morbidity and mortality.Methods: The authors did search the PubMed database regarding relevant content covering publications up to March 2022. Relevant manuscripts were classified according to the impact factor of the journal, being a guideline manuscript, a position paper by a society or a comprehensive review of the current literature. Key content and findings: Optimal HF treatment remains an unmet need in ACHD. In particular, advanced HF therapy with cardiac resynchronization therapy, ventricular assist devices or organ transplantation is still very different and more specific in ACHD compared to non-ACHD. This review aims to compile international views and evidence from the literatures on the treatment of advanced HF in ACHD. Current challenges, but also the success of different treatment strategies in ACHD are illustrated by clinical cases.Conclusions: The main finding of the review is that data is still scarce regarding ACHD with advanced HF and international efforts to collect data regarding these patients needed to improve the current standard of care.

The aim was to evaluate the association of molecular-level human leukocyte antigen (HLA) mismatching with post-transplant graft survival, rejection, and cardiac allograft vasculopathy (CAV). We retrospectively analyzed all primary cardiac transplant recipients between 01/1984-06/2016. 1167 patients fulfilled inclusion criteria and had HLA typing information available. In 312 donor-recipient pairs, typing at serological split antigen level was available. We used the Epitope MisMatch Algorithm to calculate the number of amino acid differences in antibody-verified HLA eplets (amino acid mismatch load (AAMM)) between donor and recipient. Patients with a higher HLA-DR AAMM load had inferior 1-year graft survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01-1.28). The HLA-AB AAMM load showed no impact on graft survival. In the subgroup with available split-level information, we observed an inferior graft survival for a higher HLA-DR AAMM load 3 months after transplantation (HR, 1.22; 95% CI, 1.04-1.44) and a higher risk for rejection for an increasing HLA-AB (HR, 1.70; 95% CI, 1.29-2.24) and HLA-DR (HR, 1.32; 95% CI, 1.09-1.61) AAMM load. No impact on the development of CAV was found. Molecular-level HLA mismatch analysis could serve as a tool for risk stratification after heart transplantation and might take us one step further into precision medicine.

In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8–10 ng/ml, months 1–6; 5–8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (n = 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.

Graphical Abstract

The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor (MC1R) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden.

Heart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established.We prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = -0.5,Multiplate