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The burden of chronic lymphocytic leukemia (CLL) in the prognosis of solid organ transplant (SOT) recipients seems non-negligible. Whether transplanting a patient with previous CLL is safe or what is the optimal monitoring and treatment management after transplantation is still unclear and only based on few case series and reports. Therefore, we aimed to contribute to this understanding by reporting the first documented case of a clinically significant CLL with biopsy-proven infiltration of the kidney allograft and its successful management with a Bruton tyrosine kinase inhibitor (BTKi). We then reviewed the related literature, with a focus on CLL and kidney transplantation. Our main message is that BTKi may represent a safe and effective intervention to prevent the hazardous patient and graft outcomes of CLL in SOT patients.

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Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the "gold standard" in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required.

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Acute cellular rejection (ACR) is a prevalent postoperative complication following liver transplantation (LT), exhibiting an increasing incidence of morbidity and mortality. However, the molecular mechanisms of ACR following LT remain unclear. To explore the genetic pathogenesis and identify biomarkers of ACR following LT, three relevant Gene Expression Omnibus (GEO) datasets consisting of data on ACR or non-ACR patients after LT were comprehensively investigated by computational analysis. A total of 349 upregulated and 260 downregulated differentially expressed genes (DEGs) and eight hub genes (ISG15, HELZ2, HNRNPK, TIAL1, SKIV2L2, PABPC1, SIRT1, and PPARA) were identified. Notably, HNRNPK, TIAL1, and PABPC1 exhibited the highest predictive potential for ACR with AUCs of 0.706, 0.798, and 0.801, respectively. KEGG analysis of hub genes revealed that ACR following LT was predominately associated with ferroptosis, protein processing in the endoplasmic reticulum, complement and coagulation pathways, and RIG-I/NOD/Toll-like receptor signaling pathway. According to the immune cell infiltration analysis, γδT cells, NK cells, Tregs, and M1/M2-like macrophages had the highest levels of infiltration. Compared to SIRT1, ISG15 was positively correlated with γδT cells and M1-like macrophages but negatively correlated with NK cells, CD4+ memory T cells, and Tregs. In conclusion, this study identified eight hub genes and their potential pathways, as well as the immune cells involved in ACR following LT with the greatest levels of infiltration. These findings provide a new direction for future research on the underlying mechanism of ACR following LT.

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Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade ≥ 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of ≥ 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 ≥ 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy.

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We present an exceptional case of a lung transplant recipient successfully treated by multiple courses of alemtuzumab for refractory acute cellular rejection (ACR). The patient experienced multiple episodes of ACR following the transplantation procedure. Alemtuzumab was initiated as a third-line rejection treatment and was repeated 6 times. Each treatment course resulted in complete recovery of the pulmonary function and depletion of T- and B-lymphocytes and natural killer cells (NK cells). The onset of rejection was consistently preceded by the recovery of NK cells, while T- and B-lymphocytes remained depleted. This suggests a rejection process mediated by NK cells. This case contributes to recent research findings suggesting that NK cells play a significant role in ACR in lung transplant recipients and stresses the importance to further investigate the role of NK cells in rejection. Furthermore, it demonstrates that ACR following lung transplantation can be repeatedly managed by treatment with alemtuzumab.

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BACKGROUND: T cells drive acute cellular rejection (ACR) and its progression to chronic lung allograft dysfunction (CLAD) following lung transplantation. International Society for Heart and Lung Transplantation grade A1 ACR without associated allograft dysfunction is often untreated, yet some patients develop progressive graft dysfunction. T-cell composition of A1 ACR lesions may have prognostic value; therefore, protein-level and epigenetic techniques were applied to transbronchial biopsy tissue to determine whether differential T-cell infiltration in recipients experiencing a first episode of stable grade A1 ACR (StA1R) is associated with early CLAD. METHODS: Sixty-two patients experiencing a first episode of StA1R were divided into those experiencing CLAD within 2 years (n = 13) and those remaining CLAD-free for 5 or more years (n = 49). Imaging mass cytometry (IMC) was used to profile the spectrum and distribution of intragraft T cell phenotypes on a subcohort (n = 16; 8 early-CLAD and 8 no early-CLAD). Immunofluorescence was used to quantify CD4+, CD8+, and FOXP3+ cells. Separately, CD3+ cells were fluorescently labeled, micro-dissected, and the degree of Treg-specific demethylated region methylation was determined. RESULTS: PhenoGraph unsupervised clustering on IMC revealed 50 unique immune cell subpopulations. Methylation and immunofluorescence analyses demonstrated no significant differences in Tregs between early-CLAD and no early-CLAD groups. Immunofluorescence revealed that patients who developed CLAD within 2 years of lung transplantation showed greater CD8+ T cell infiltration compared to those who remained CLAD-free for 5 or more years. CONCLUSIONS: In asymptomatic patients with a first episode of A1 rejection, greater CD8+ T cell content may be indicative of worse long-term outlook.

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BACKGROUND: Transbronchial cryobiopsy (TBCB) provides larger tissue samples and improved sampling depth, but its role in diagnosing acute cellular rejection (ACR) in lung transplant patients is unclear due to limitations in existing studies. To address this, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of TBCB. METHODS: A thorough literature review was conducted to evaluate TBCB in post-lung transplant surveillance, assessing the quality of studies and conducting a meta-analysis comparing diagnostic yields of TBCB and transbronchial forceps biopsy (TBFB), as well as evaluating procedural complications. RESULTS: Our meta-analysis, incorporating 11 studies with a total of 915 patients, showed that TBCB had a diagnostic rate of 38.27% (225/588) for ACR post-lung transplantation, notably higher than the 35.65% (251/704) for TBFB. The inverse-variance weighted odds ratio was calculated at 2.32 (95% confidence interval: 1.24-4.32; p=0.008). Funnel plot analysis indicated no major publication bias. Meta-analysis of 6 studies demonstrated that TBCB, compared to TBFB, significantly increased the diagnostic rate for chronic rejection post-transplantation (25.00% vs 10.93%, p=0.005). Our meta-analysis comparing the safety of TBCB and TBFB in post-lung transplant surveillance found no significant differences in moderate to severe bleeding (5.99% vs 6.31%, p=0.98), or pneumothorax incidence (3.90% vs 3.29%, p=0.75). CONCLUSIONS: Our study indicates that TBCB may enhance the diagnosis of acute and chronic rejection post-lung transplantation with a safety profile comparable to TBFB. Further research and the development of standardized procedures are warranted to ensure the safe and effective application of TBCB in broader clinical practice.

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BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.

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Intestinal transplantation is the standard treatment for patients with intestinal failure with severe complications due to parenteral nutrition; however, rejection leads to graft failure in approximately half of both adult and pediatric recipients within 5 years of transplantation. Although intensive immunosuppressive therapy is used in an attempt to reduce this risk, commonly used treatment strategies are generally practice- and/or expert-based, as head-to-head comparisons are lacking. In this ever-developing field, biologicals designed to prevent or treat rejection are used increasingly, with both infliximab and vedolizumab showing potential in the treatment of acute cellular rejection in individual cases and in relatively small patient cohorts. To help advance progress in clinical care, we review the current use of biologicals in intestinal transplantation, and we provide future perspectives to guide this progress.

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The traditional procedure for multivisceral transplant (MVT) is to transplant the stomach, pancreas, intestine, and liver en bloc. During surgery, the native spleen is routinely removed from the recipient, and it usually creates more space in the abdomen to insert the allogeneic graft. Thus, recipients often become asplenic after MVT. Considering all of the risks and benefits, we advocate that temporary transplant of the donor spleen could be the best option for MVT recipients; it could potentially reduce the rate of intestinal allograft rejection without increasing the risk for graft-versus-host disease.

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BACKGROUND: Current monitoring after heart transplantation (HT) employs repeated invasive endomyocardial biopsies (EMB). Although positive EMB confirms rejection, EMB fails to predict impending, subclinical, or EMB-negative rejection events. While non-human leukocyte antigen (non-HLA) antibodies have emerged as important risk factors for antibody-mediated rejection after HT, their use in clinical risk stratification has been limited. A systematic review of the role of non-HLA antibodies in rejection pathologies has the potential to guide efforts to overcome deficiencies of EMB in rejection monitoring. METHODS: Databases were searched to include studies on non-HLA antibodies in HT recipients. Data collected included the number of patients, type of rejection, non-HLA antigen studied, association of non-HLA antibodies with rejection, and evidence for synergistic interaction between non-HLA antibodies and donor-specific anti-human leukocyte antigen antibody (HLA-DSA) responses. RESULTS: A total of 56 studies met the inclusion criteria. Strength of evidence for each non-HLA antibody was evaluated based on the number of articles and patients in support versus against their role in mediating rejection. Importantly, despite previous intense focus on the role of anti-major histocompatibility complex class I chain-related gene A (MICA) and anti-angiotensin II type I receptor antibodies (AT1R) in HT rejection, evidence for their involvement was equivocal. Conversely, the strength of evidence for other non-HLA antibodies supports that differing rejection pathologies are driven by differing non-HLA antibodies. CONCLUSIONS: This systematic review underscores the importance of identifying peri-HT non-HLA antibodies. Current evidence supports the role of non-HLA antibodies in all forms of HT rejection. Further investigations are required to define the mechanisms of action of non-HLA antibodies in HT rejection.

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OBJECTIVES: The choice of the cardiac preservation solution for myocardial protection at time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm heart transplantation (HTx) outcomes. We retrospectively compared our adult HTx performed with 2 different solutions, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. METHODS: From January 2009 to December 2020, 154 consecutive HTx of adult patients, followed up in pre- and post-transplantation by 2 different tertiary centres, were performed at the University Hospital of Lausanne, Switzerland. From 2009 to 2015, the cardiac preservation solution used was exclusively St-Thomas, whereafter an institutional decision was made to use HTK-Custodiol only. Patients were classified in 2 groups accordingly. RESULTS: There were 75 patients in the St-Thomas group and 79 patients in the HTK-Custodiol group. The 2 groups were comparable in terms of preoperative and intraoperative characteristics. Postoperatively, compared to the St-Thomas group, the Custodiol group patients showed significantly lower inotropic scores [median (interquartile range): 35.7 (17.5-60.2) vs 71.8 (31.8-127), P < 0.001], rejection scores [0.08 (0.0-0.25) vs 0.14 (0.05-0.5), P = 0.036] and 30-day mortality rate (2.5% vs 14.7%, P = 0.007) even after adjusting for potential confounders. Microscopic analysis of the endomyocardial biopsies also showed less specific histological features of subendothelial ischaemia (3.8% vs 17.3%, P = 0.006). There was no difference in primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation. The use of HTK-Custodiol solution significantly improved midterm survival (Custodiol versus St-Thomas: hazard ratio = 0.20, 95% confidence interval: 0.069-0.60, P = 0.004). CONCLUSIONS: This retrospective study comparing St-Thomas solution and HTK-Custodiol as myocardial protection during heart procurement showed that Custodiol improves outcomes after HTx, including postoperative inotropic score, rejection score, 30-day mortality and midterm survival.

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Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation. By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11b-CD11c+), mature (CD11b-CD11c+MHCII+) and active (CD11b-CD11c+CD40+) DCs and cDC2 subset (CD11b+CD11c+ MHCII+) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.

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BACKGROUND: Simultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a "safety net" policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss. RESULTS: Sixty-six thousand seventy-nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan-Meier estimates .61 vs. .89 and .90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups. CONCLUSION: KALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK. BRIEF SUMMARY: Patients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

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Acute cellular rejection (ACR) is a significant immune issue among recipients following liver transplantation. Although diffusion-weighted magnetic resonance imaging (DWI) is widely used for diagnosing liver disease, it has not yet been utilized for monitoring ACR in patients after liver transplantation. Therefore, the aim of this study was to evaluate the efficacy of DWI in monitoring treatment response among recipients with ACR. This study enrolled 25 recipients with highly suspected ACR rejection, and all subjects underwent both biochemistry and DWI scans before and after treatment. A pathological biopsy was performed 4 to 24 h after the first MRI examination to confirm ACR and degree of rejection. All patients were followed up and underwent a repeated MRI scan when their liver function returned to the normal range. After data acquisition, the DWI data were post-processed to obtain the apparent diffusion coefficient (ADC) map on a voxel-by-voxel basis. Five regions of interest were identified on the liver parenchyma to measure the mean ADC values from each patient. Finally, the mean ADC values and biochemical markers were statistically compared between ACR and non-ACR groups. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the ADC and biochemical data in detecting ACR, and correlation analysis was used to understand the relationship between the ADC values, biochemical markers, and the degree of rejection. The histopathologic results revealed that 20 recipients had ACR, including 10 mild, 9 moderate, and 1 severe rejection. The results demonstrated that the ACR patients had significantly lower hepatic ADC values than those in patients without ACR. After treatment, the hepatic ADC values in ACR patients significantly increased to levels similar to those in non-ACR patients with treatment. The ROC analysis showed that the sensitivity and specificity for detecting ACR were 80% and 95%, respectively. Furthermore, the correlation analysis revealed that the mean ADC value and alanine aminotransferase level had strong and moderate negative correlation with the degree of rejection, respectively (r = -0.72 and -0.47). The ADC values were useful for detecting hepatic ACR and monitoring treatment response after immunosuppressive therapy.

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Intestinal allografts are the most immunologically complex and carry the highest risk of rejection among solid organ transplantation, necessitating complex immunosuppressive management. We evaluated the latest information regarding induction immunosuppression, with an emphasis on established, novel, and emergent therapies. We also reviewed classic and novel induction immunosuppression strategies for highly sensitized recipients. Comparable progress has been made in intestinal transplantation clinical outcomes since the implementation of induction strategies. This review shows a clear diversity of induction protocols can be observed across different centers. The field of intestinal transplantation is still in its early stages, which is further complicated by the limited number of institutions capable of intestinal transplantation and their geographical variation, which further hinders the development of adequately powered studies in comparison to other organs. As the implementation of institution-specific induction protocols becomes more refined and results are disseminated, future research efforts should be directed towards the development of efficacious induction strategies.

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BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

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Despite developments in circulating biomarker and imaging technology in the assessment of cardiovascular disease, the surveillance and diagnosis of heart transplant rejection has continued to rely on histopathologic interpretation of the endomyocardial biopsy. Increasing evidence shows the utility of molecular evaluations, such as donor-specific antibodies and donor-derived cell-free DNA, as well as advanced imaging techniques, such as cardiac magnetic resonance imaging, in the assessment of rejection, resulting in the elimination of many surveillance endomyocardial biopsies. As non-invasive technologies in heart transplant rejection continue to evolve and are incorporated into practice, they may supplant endomyocardial biopsy even when rejection is suspected, allowing for more precise and expeditious rejection therapy. This review describes the current and near-future states for the evaluation of heart transplant rejection, both in the settings of rejection surveillance and rejection diagnosis. As biomarkers of rejection continue to evolve, rejection risk prediction may allow for a more personalized approach to immunosuppression.