Perioperative Risk Factors of Acute Kidney Injury After Heart Transplantation and One-Year Clinical Outcomes: A Retrospective Cohort Study.

OBJECTIVES: This study aimed to identify perioperative risk factors of acute kidney injury after heart transplantation and to evaluate 1-year clinical outcomes. DESIGN: A retrospective single-center cohort study. SETTING: At a university hospital. PARTICIPANTS: All patients who underwent heart transplantation from January 2015 to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors recorded acute kidney injury after heart transplantation. One-year mortality and renal function also were recorded. Risk factors of acute kidney injury were evaluated using a multivariate logistic regression model. Long-term survival was compared between patients developing acute kidney injury and those who did not, using a log-rank test. Among 209 patients included in this study, 134 patients (64% [95% CI (58; 71)]) developed posttransplantation acute kidney injury. Factors independently associated with acute kidney injury were high body mass index (odds ratio [OR]: 1.18 [1.02-1.38] per kg/m2; p = 0.030), prolonged duration of cold ischemic period (OR: 1.11 [1.01-1.24] per 10 minutes; p = 0.039), and high dose of intraoperative dobutamine support (OR: 1.24 [1.06-1.46] per µg/kg/min; p = 0.008). At 1 year, patients who developed postoperative acute kidney injury had higher mortality rates (20% v 8%, p = 0.015). Among 172 survivors at 1 year, 82 survivors (48%) had worsened their renal function compared with preheart transplantation. CONCLUSIONS: This study highlighted the high incidence of acute kidney injury after heart transplantation and its impact on patient outcomes. Risk factors such as body mass index, prolonged cold ischemic period duration, and level of inotropic support with dobutamine were identified, providing insights for preventive strategies.

Prognosis of patients in end-stage heart failure with atrial fibrillation treated with ablation: Insights from CASTLE-HTx.

BACKGROUND: The CASTLE-HTx trial demonstrated the benefit of atrial fibrillation (AF) ablation compared with medical therapy in decreasing mortality, need for left ventricular assist device implantation, or heart transplantation (HTx) in patients with end-stage heart failure (HF). OBJECTIVE: This analysis aimed to identify risk factors related to adverse outcomes in patients with end-stage HF and to assess the impact of ablation. METHODS: The CASTLE-HTx protocol randomized 194 patients with end-stage HF and AF to ablation vs medical therapy. We identified left ventricular ejection fraction <30%, New York Heart Association class ≥III, and AF burden >50% as predictors for the primary end point. The CASTLE-HTx risk score assigned weights to these risk factors. Patients with a risk score ≥3 were identified as high risk. RESULTS: The patients were assigned to low-risk (89 [45.9%]) and high-risk (105 [54.1%]) groups. After a median follow-up of 18 months, a primary end point event occurred in 6 and 31 patients of the low- and high-risk groups (hazard ratio, 4.98; 95% confidence interval, 2.08-11.9). The incidence rate (IR) difference between ablation and medical therapy was much larger in high-risk patients (8/49 [IR, 11.4] vs 23/56 [IR, 36.1]) compared with low-risk patients (2/48 [IR, 2.6] vs 4/41 [IR, 6.3]). The IR difference for ablation was significantly higher in high-risk patients (24.69) compared with low-risk patients (3.70). CONCLUSION: The absolute benefit of ablation is more pronounced in high-risk patients, but low-risk patients may also benefit. The CASTLE-HTx risk score identifies patients with end-stage HF who will particularly benefit from ablation.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

The first case report of de novo Crohn's disease after heart transplantation successfully treated with ustekinumab.

Inflammatory bowel disease (IBD) is a complex chronic inflammatory intestinal disease. The development of de novo IBD after solid organ transplantation with immunosuppressive agents has been rarely reported. We present the case of a 65-year-old man with repeated colitis after heart transplantation (HTx) who was diagnosed with Crohn's disease (CD). The patient underwent HTx due to non-ischemic dilated cardiomyopathy. Six months after HTx, he developed serious diarrhea and a transient fever, which persisted for about 6 months. Valganciclovir or any antibiotic agents were not effective for his symptoms and longitudinal ulcers in colonoscopy aggravated during the course, so that we made a diagnosis of CD. We started 5-aminosalicylic acid and found improvement in his symptoms and colonoscopic findings. However, 7 months after improvement, CD worsened. We started ustekinumab by which his condition successfully went into remission again. While oral immunosuppressive drugs are thought to suppress autoimmune diseases in general, IBD should be included in the differential diagnoses for recurring enterocolitis after HTx. Poorly controlled CD can lead to serious and potentially fatal complications, but in this case, ustekinumab has been used safely and effectively for the treatment of CD. Learning objective: Colitis is a common complication after heart transplantation (HTx). Although cytomegalovirus colitis or posttransplant lymphoproliferative disorder are observed commonly, de novo inflammatory bowel disease (IBD) should be considered when serious refractory colitis occurs. Not only 5-aminosalicylic acid but also ustekinumab, which is a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, may be a safe and effective treatment for de novo IBD after HTx.

Macrophage-derived extracellular vesicles alter cardiac recovery and metabolism in a rat heart model of donation after circulatory death.

Conditions to which the cardiac graft is exposed during transplantation with donation after circulatory death (DCD) can trigger the recruitment of macrophages that are either unpolarized (M0) or pro-inflammatory (M1) as well as the release of extracellular vesicles (EV). We aimed to characterize the effects of M0 and M1 macrophage-derived EV administration on post-ischaemic functional recovery and glucose metabolism using an isolated rat heart model of DCD. Isolated rat hearts were subjected to 20 min aerobic perfusion, followed by 27 min global, warm ischaemia or continued aerobic perfusion and 60 min reperfusion with or without intravascular administration of EV. Four experimental groups were compared: (1) no ischaemia, no EV; (2) ischaemia, no EV; (3) ischaemia with M0-macrophage-dervied EV; (4) ischaemia with M1-macrophage-derived EV. Post-ischaemic ventricular and metabolic recovery were evaluated. During reperfusion, ventricular function was decreased in untreated ischaemic and M1-EV hearts, but not in M0-EV hearts, compared to non-ischaemic hearts (p < 0.05). In parallel with the reduced functional recovery in M1-EV versus M0-EV ischaemic hearts, rates of glycolysis from exogenous glucose and oxidative metabolism tended to be lower, while rates of glycogenolysis and lactate release tended to be higher. EV from M0- and M1-macrophages differentially affect post-ischaemic cardiac recovery, potentially by altering glucose metabolism in a rat model of DCD. Targeted EV therapy may be a useful approach for modulating cardiac energy metabolism and optimizing graft quality in the setting of DCD.

Advanced Respiratory Failure Requiring Tracheostomy-A Marker of Unfavourable Prognosis after Heart Transplantation.

Advanced respiratory failure with tracheostomy requirement is common in heart recipients. The aim of the study is to assess the tracheostomy rate after orthotopic heart transplantation and identify the subgroups of patients with the highest need for tracheostomy and these groups' association with mortality at a single centre through a retrospective analysis of 140 consecutive patients transplanted between December 2012 and July 2018. As many as 28.6% heart recipients suffered from advanced respiratory failure with a need for tracheostomy that was performed after a median time of 11.5 days post-transplant. Tracheostomy was associated with a history of stroke (OR 3.4; 95% CI) 1.32-8.86; p = 0.012), previous sternotomy (OR 2.5; 95% CI 1.18-5.32; p = 0.017), longer cardiopulmonary bypass time (OR 1.01; 95% CI 1.00-1.01; p = 0.007) as well as primary graft failure (OR 6.79; 95% CI2.93-15.71; p < 0.001), need of renal replacement therapy (OR 19.2; 95% 2.53-146; p = 0.004) and daily mean SOFA score up to 72 h (OR 1.50; 95% 1.23-1.71; p < 0.01). One-year mortality was significantly higher in patients requiring a tracheostomy vs. those not requiring one during their hospital stay (50% vs. 16%, p < 0.001). The need for tracheostomy in heart transplant recipients was 30% in our study. Advanced respiratory failure was associated with over 3-fold greater 1-year mortality. Thus, tracheostomy placement may be regarded as a marker of unfavourable prognosis.

Ten-Year Experience with Endomyocardial Biopsy after Orthotopic Heart Transplantation: Comparison between Trans-Jugular and Trans-Femoral Approach.

BACKGROUND: Endomyocardial biopsy (EMB) is considered the gold standard for monitoring allograft rejection after heart transplantation. EMB is an invasive procedure that may be performed via a trans-jugular or a trans-femoral approach with a complication rate reported as less than 6%. The aim of this study was to evaluate the complication rate after EMBs in heart recipients and to compare the results of EMBs performed via a trans-jugular or a trans-femoral approach. METHODS: Medical records of heart recipients undergoing EMBs between January 2012 and December 2022 were retrospectively reviewed. EMB-related complications were classified as major (death, pericardial effusion, hemopericardium, cardiac tamponade requiring a pericardiocentesis or an urgent cardiac surgery, ventricular arrythmias, permanent atrio-ventricular block requiring permanent pacing, hemothorax, pneumothorax and retroperitoneal bleeding) and minor (de novo tricuspid regurgitation, arrhythmias, coronary artery fistula, vascular access site complications). RESULTS: A total of 1698 EMBs were performed during the study period at our institution in 212 heart recipients. There were 927 (55%) EMBs performed through a trans-jugular approach (TJ group) and 771 (45%) EMBs performed through a trans-femoral approach (TF group). A total of 60 (3.5%) complications were recorded, including nine (0.5%) major complications (six cardiac tamponades, two pneumothorax and one retroperitoneal bleeding) and 51 (3%) minor complications (seven coronary fistulae, five de novo tricuspid regurgitation, four supraventricular arrythmias and thirty-five vascular access site complications). No difference was found in total (38 [4%] vs. 22 [3%]; p = 0.16) and major (6 [1%} vs. 3 [0.4%]; p = 0.65) complications (32 [3%] vs. 19 [2%]; p = 0.23) between the TJ group and the TF group. No difference was found in male sex, age at time of EMB and time from HT between complicated and not complicated EMBs. CONCLUSIONS: EMBs represent a safe procedure with a low risk of complications. In our experience, EMBs performed via a trans-jugular approach are as safe as the trans-femoral approach.

Special Considerations for Advanced Heart Failure Surgeries: Durable Left Ventricular Devices and Heart Transplantation.

Heart transplantation and durable left ventricular assist devices (LVADs) represent two definitive therapies for end-stage heart failure in the modern era. Despite technological advances, both treatment modalities continue to experience unique risks that impact surgical and perioperative decision-making. Here, we review special populations and factors that impact risk in LVAD and heart transplant surgery and examine critical decisions in the management of these patients. As both heart transplantation and the use of durable LVADs as destination therapy continue to increase, these considerations will be of increasing relevance in managing advanced heart failure and improving outcomes.

Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death.

BACKGROUND: Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects. METHODS AND RESULTS: Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω-nitro-L-arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω-nitro-L-arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels. CONCLUSIONS: HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts.

Management of incessant ventricular arrhythmias in a patient with left ventricular assist device: a case report.

BACKGROUND: The implantation of left ventricular assist devices (LVADs) as a bridge to transplantation or as destination therapy in end-stage heart failure patients is frequently complicated by the emergence of ventricular arrhythmias (VAs). These arrhythmias have been implicated in precipitating deleterious clinical outcomes, increased mortality rates and augmented healthcare expenditures. CASE PRESENTATION: We present a challenging case of a 49-year-old male with a history of dilated cardiomyopathy who received an LVAD. Post-implantation, the patient suffered from intractable VAs, leading to multiple rehospitalizations and hemodynamic deterioration. Despite exhaustive medical management and electrical cardioversion attempts, the patient's VAs persisted, ultimately necessitating prioritization for cardiac transplantation. DISCUSSION: This case highlights the challenges in managing VAs in LVAD patients and the importance of multidisciplinary collaboration. While pharmacological intervention is the initial strategy, catheter ablation may be considered in selected cases when medication is insufficient. In instances of intractable VAs, expeditious listing for heart transplantation as a high-priority candidate is advisable when feasible.

Semilunar valve growth and function 10 years after infant heart transplantation: Predicting long-term outcomes of partial heart transplants.

INTRODUCTION: Partial heart transplants are a new type of pediatric transplant that replace defective heart valves with the parts of matched donor hearts containing the necessary valves. Short-term outcomes of partial heart transplants are excellent, but long-term outcomes are unknown. In order to predict the long-term outcomes of partial heart transplants, we evaluated long-term growth and function of semilunar heart valves transplanted in infancy as part of a heart transplant. METHODS: All children who underwent infant heart transplantation at a single center from 1997 to 2014 were included in this study. Children in whom echocardiograms after heart transplantation and after 10 years were not available for review were excluded. The echocardiograms were reviewed by two authors to analyze semilunar valve annulus diameters, Z-scores, peak valve gradients, and valve regurgitation. Statistical difference was determined using two-tailed, paired sample t-tests with Bonferroni correction for multiple comparisons. RESULTS: Data from 15 patients were analyzed. The aortic valve annulus averaged 1.3 cm (range 0.7-1.8 cm) immediately after transplantation and grew to an average of 1.7 cm (range 1.4-2.3 cm) after 10 years (p < .001). After 10 years, the aortic valve peak gradient avereraged 5.1 mmHg (range 2.1-15.5 mmHg) and none of the valves had more than trivial regurgitation. The pulmonary valve annulus averaged 1.5 cm (range 1.1-2.5 cm) immediately after transplantation and grew to an average of 2.1 cm (range 1.0-2.9 cm) after 10 years (p < .001). After 10 years, the pulmonary valve peak gradient averaged 4.3 mmHg (range 1.1-13.8 mmHg), and 7% of valves had moderate regurgitation. DISCUSSION: Semilunar heart valves transplanted in infancy as part of a heart transplant demonstrate statistically significant growth and excellent function after 10 years. This predicts excellent long-term outcomes of partial heart transplants.

What are the main oral manifestations in heart transplant patients? A scoping review.

OBJECTIVE: The purpose of this scoping review is to evaluate the oral manifestations (OM) of heart transplant (HT) patients undergoing immunosuppressive therapy (IT). MATERIAL AND METHODS: A literature search was performed using keywords and MeSH terms related to OM and HT in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until June 2023. Studies that evaluated HT individuals who used any IT and who reported the occurrence of OM were considered eligible. The results from the search were imported to EndNote Web, and duplicates were removed followed by title/abstract and full-text analysis. RESULTS: A total of 402 nonduplicated studies were found and 13 fulfilled the criteria and were included in the present review: 10 cross-sectional, 2 cohorts, and 1 clinical trial. The most reported OM were periodontal diseases, including drug-induced gingival enlargement (DIGE), gingival bleeding, gingivitis, and periodontitis. Reported in a minority of studies are oral cancer, opportunistic infections (oral hairy leukoplakia and erythematous candidiasis), enamel defects, and burning mouth. CONCLUSION: Considering the methodological heterogeneity of the studies analyzed, DIGE is the most commonly observed oral manifestation in HT individuals.

Right Ventricular Function on Cardiovascular Magnetic Resonance Imaging and Long-Term Outcomes in Stable Heart Transplant Recipients.

BACKGROUND: In heart transplant recipients, right ventricular (RV) dysfunction may occur for a variety of reasons. Whether RV dysfunction in the stable phase after heart transplantation is associated with long-term adverse outcomes is unknown. We aimed to determine the long-term prognostic significance of RV dysfunction identified on cardiovascular magnetic resonance imaging (CMR) at least 1 year after heart transplantation. METHODS: In consecutive heart transplant recipients who underwent CMR for surveillance, we assessed 2 CMR measures of RV function: RV ejection fraction and RV global longitudinal strain (RVGLS). We investigated associations between RV dysfunction and a composite end point of death or major adverse cardiac events, including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization. RESULTS: A total of 257 heart transplant recipients (median age, 59 years; 75% men) who had CMR at a median of 4.3 years after heart transplantation were included. Over a median follow-up of 4.4 years after the CMR, 108 recipients experienced death or major adverse cardiac events. In a multivariable Cox regression analysis adjusted for age, time since transplantation, indication for transplantation, cardiac allograft vasculopathy, history of rejection, and CMR covariates, RV ejection fraction was not associated with the composite end point, but RVGLS was independently associated with the composite end point with a hazard ratio of 1.08 per 1% worsening in RVGLS ([95% CI, 1.00-1.17]; P=0.046). RVGLS provided incremental prognostic value over other variables in multivariable analyses. The association was replicated in subgroups of recipients with normal RV ejection fraction and recipients with late gadolinium enhancement imaging. A similar association was seen with a composite end point of cardiovascular death or major adverse cardiac events. CONCLUSIONS: CMR feature tracking-derived RVGLS assessed at least 1 year after heart transplantation was independently associated with the long-term risk of death or major adverse cardiac events. Future studies should investigate its role in guiding clinical decision-making in heart transplant recipients.

Effectiveness of Mechanical Circulatory Support Devices in Reversing Pulmonary Hypertension Among Heart Transplant Candidates: A Systematic Review.

BACKGROUND: Pulmonary hypertension (PH) poses a significant challenge in the selection of candidates for heart transplantation, impacting their eligibility and post-transplant outcomes. Mechanical circulatory support (MCS) devices, particularly left ventricular assist devices (LVADs), have emerged as a therapeutic option to manage PH in this patient population. This systematic review aims to evaluate the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates. METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify studies that evaluated the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates. Data on pulmonary vascular resistance, PH reversal, heart transplant eligibility, and post-transplant outcomes were extracted and synthesized. RESULTS: The review included studies that demonstrated the potential of MCS devices, especially LVADs, to significantly reduce pulmonary vascular resistance and reverse fixed pulmonary hypertension in heart transplant candidates. These findings suggest that MCS devices can improve transplant eligibility and may positively impact post-transplant survival rates. However, the literature also indicates a need for further comparative studies to optimize MCS device selection and treatment protocols. CONCLUSION: MCS devices, particularly LVADs, play a crucial role in the management of fixed pulmonary hypertension in heart transplant candidates, improving their eligibility for transplantation and potentially enhancing post-transplant outcomes. Future research should focus on comparative effectiveness studies to guide clinical decision-making and optimize patient care in this challenging clinical scenario.

Pediatric donor heart utilization variability among organ procurement organizations.

BACKGROUND: Organ procurement organizations (OPOs) are responsible for the medical management of organ donors. Given the variability in pediatric donor heart utilization among OPOs, we examined factors that may explain this variability, including differences in donor medical management, organ quality, and candidate factors. METHODS: The Organ Procurement and Transplant Network database was queried for pediatric (<18 years) heart donors and candidates receiving pediatric donor heart offers from 2010 to 2019. OPOs were stratified by pediatric donor heart utilization rate, and the top and bottom quintiles were compared based on donor management strategies and outcomes. A machine learning algorithm, combining 11 OPO, donor, candidate, and offer variables, was used to determine factors most predictive of whether a heart offer is accepted. RESULTS: There was no clinically significant difference between the top and bottom quintile OPOs in baseline donor characteristics, distance between donor and listing center, management strategies, or organ quality. Machine learning modeling suggested neither OPO donor management nor cardiac function is the primary driver of whether an organ is accepted. Instead, number of prior donor offer refusals and individual listing center receiving the offer were two of the most predictive variables of organ acceptance. CONCLUSIONS: OPO clinical practice variation does not seem to account for the discrepancy in pediatric donor heart utilization rates among OPOs. Listing center acceptance practice and prior number of donor refusals seem to be the important drivers of heart utilization and may at least partially account for the variation in OPO heart utilization rates given the regional association between OPOs and listing centers.

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs.

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

CD47 blockade reduces ischemia/reperfusion injury in murine heart transplantation and improves donor heart preservation.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction. We hypothesized that blocking the CD47-TSP-1 system would attenuate ischemia-reperfusion injury in the transplanted heart and, thus, improve the preservation of donor hearts. METHODS: We utilized a syngeneic mouse heart transplant model to assess the effect of CD47 monoclonal antibody (CD47mAb) to treat MIRI. Donor hearts were perfused with CD47mAb or an isotype-matched control immunoglobulin (IgG2a) and were implanted into the abdominal cavity of the recipients after being stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C for 4 h or 8 h. RESULTS: At both the 4-h and 8-h preservation time points, mice in the experimental group perfused with CD47mAb exhibited prolonged survival in the transplanted heart, reduced inflammatory response and oxidative stress, significantly decreased inflammatory cell infiltration, and fewer apoptosis-related biomarkers. CONCLUSION: The application of CD47mAb for the blocking of CD47 attenuates MIRI as well as improves the preservation and prognosis of the transplanted heart in a murine heart transplant model.

Advanced Heart Failure Therapies in The Eastern Mediterranean Region: Current Status, Challenges, and Future Directions.

While there has been a global decrease in rates of heart failure (HF) prevalence between 1990 and 2019, the Eastern Mediterranean region (EMR) is experiencing an increase. In 2019, approximately 1,229,766 individuals lived with moderate to severe HF in the EMR. Despite the growth in the utilization of advanced heart failure (AHF) therapies in the EMR in the past two decades, current volumes are yet to meet the growing AHF burden in the region. Heart Transplantation (HT) volumes in EMR have grown from 9 in the year 2000 to 179 HTs in 2019. However, only a few centers provide the full spectrum of AHF therapies, including durable mechanical circulatory support (MCS) and HT. Published data on the utilization of left ventricular assist devices (LVAD) in the EMR are scarce. Notably, patients undergoing LVAD implantation in the EMR are on average, 13 years younger, and have a higher likelihood of presenting with critical cardiogenic shock, as compared to their counterparts in the Western world. Furthermore, AHF care in the region is hampered by the paucity of multidisciplinary HF programs, inherent costs of AHF therapies, limited access to short and long-term MCS, organ shortage, and lack of public awareness and acceptance of AHF therapeutics. All stakeholders in the EMR should work together to strategize tackling the challenging AHF burden in the region.

Early Outcomes in Patients With LVAD Undergoing Heart Transplant via Use of the SherpaPak Cardiac Transport System.

BACKGROUND: Heart transplant (HT) in recipients with left ventricular assist devices (LVADs) is associated with poor early post-HT outcomes, including primary graft dysfunction (PGD). As complicated heart explants in recipients with LVADs may produce longer ischemic times, innovations in donor heart preservation may yield improved post-HT outcomes. The SherpaPak Cardiac Transport System is an organ preservation technology that maintains donor heart temperatures between 4 °C and 8 °C, which may minimize ischemic and cold-induced graft injuries. This analysis sought to identify whether the use of SherpaPak versus traditional cold storage was associated with differential outcomes among patients with durable LVAD undergoing HT. METHODS: Global Utilization and Registry Database for Improved Heart Preservation-Heart (NCT04141605) is a multicenter registry assessing post-HT outcomes comparing 2 methods of donor heart preservation: SherpaPak versus traditional cold storage. A retrospective review of all patients with durable LVAD who underwent HT was performed. Outcomes assessed included rates of PGD, post-HT mechanical circulatory support use, and 30-day and 1-year survival. RESULTS: SherpaPak (n=149) and traditional cold storage (n=178) patients had similar baseline characteristics. SherpaPak use was associated with reduced PGD (adjusted odds ratio, 0.56 [95% CI, 0.32-0.99]; P=0.045) and severe PGD (adjusted odds ratio, 0.31 [95% CI, 0.13-0.75]; P=0.009), despite an increased total ischemic time in the SherpaPak group. Propensity matched analysis also noted a trend toward reduced intensive care unit (SherpaPak 7.5±6.4 days versus traditional cold storage 11.3±18.8 days; P=0.09) and hospital (SherpaPak 20.5±11.9 days versus traditional cold storage 28.7±37.0 days; P=0.06) lengths of stay. The 30-day and 1-year survival was similar between groups. CONCLUSIONS: SherpaPak use was associated with improved early post-HT outcomes among patients with LVAD undergoing HT. This innovation in preservation technology may be an option for HT candidates at increased risk for PGD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04141605.