Search

Background Heart transplant (HTx) patients can develop graft dysfunction (GD) without biopsy evidence of cell or antibody mediated rejection. Cardiac MRI (CMR) can detect inflammatory or infiltrative causes of cardiomyopathy however CMR findings in HTx recipients with GD have not been previously described. Purpose We sought to identify CMR characteristics of HTx patients with GD, and evaluate its additive value in its diagnosis and prognosis. Methods CMR has been performed routinely to evaluate GD at our institutions. There were 37 HTx recipients who presented with acute decline in left ventricular ejection fraction (LVEF) of 10% from baseline, with no biopsy evidence of rejection between 2007 and 2018. Coronary angiogram with IVUS was done to rule out allograft vasculopathy. Treatment of GD was per discretion of the treating clinician. Responders were defined as those with LVEF improvement >10% at 180 days or greater post-presentation. LV and RV indices, the presence and pattern of late gadolinium enhancement (LGE) were determined by CMR. Results There were 34% females and mean age at transplant was 49±13 years. Median time from HTx to GD was 1.2 years. Presenting symptoms were heart failure (n=25), cardiogenic shock (n=1) and 11 patients were asymptomatic. Mean LVEF at presentation was 37±12% and donor specific antibodies were detected in 38% patients. Most patients were treated with steroid bolus (n=29), and/or plasmapheresis (n=23). There were no major changes made in immunosuppression in 6 patients. Delayed enhancement MRI was performed with standard inversion-recovery (IR) gradient echo sequences, between 5 and 20 minutes after institutional-standard protocol administration of IV gadolinium contrast. Biventricular LGE was present in 18/37 (49%) patients with GD and was more prevalent in responders (57%, 13 of 23) than non-responders (35%, 5 of 14), although not statistically significant (p=0.21). There were two patterns of LGE noted: 1) Diffuse epicardial (10 patients out which 9 were responders) and 2) Patchy pattern with non-specific distribution (8 patients out of which 4 were responders). Myocardial edema by triple IR sequencing was seen in 6 patients, all having diffuse epicardial pattern of enhancement matching the delayed enhancement pattern. When comparing different treatment groups, among those treated for GD (n=31), 12 of 21 (57%) responders had LGE and 4 of 10 (40%) non-responders had LGE (p=0.37), a pattern similar to the broader population. Among those not treated for GD (n=6), 1 of 2 responders had LGE and 1 of 4 non-responders had LGE (p=0.5). Conclusion CMR identified inflammation as a potential cause of GD in approximately 50% of HTx patients. There are 2 distinct patterns of LGE observed in GD, diffuse epicardial (56%) and patchy (44%). Although the presence of LGE in itself is not associated with myocardial recovery, 90% of patients with a diffuse epicardial pattern have recovery of GD. Funding Acknowledgement Type of funding source: None

Purpose HeartCare [dd-cfDNA (AlloSure) and gene expression profiling (GEP; AlloMap)] in heart transplantation (HT) surveillance provides a unique opportunity to assess allograft injury in conjunction with immune activity. This report describes our single center use of dd-cfDNA and GEP in HT. Methods A cohort of HT patients underwent dd-cfDNA and GEP testing between 1/2020 - 9/2020 (median months post-transplant 31). A GEP ≥34 and dd-cfDNA ≥0.15% were considered elevated. Patients were stratified into 4 groups based on high/low dd-cfDNA and GEP values. We performed an analysis of dd-cfDNA and DSA by Mann-Whitney for nonparametric values (p Results Among 101 HT patients there were 238 dd-cfDNA results (mean 2.4 per pt); 82% paired with GEP. Patients were median 59 years of age, 78% male, 72% Caucasian and 9% PRA >20%. Distribution of HeartCare results are reported. For aggregated groups with high dd-cfDNA there was a greater incidence of DSA (56%) compared to low dd-cfDNA groups (14%). Samples associated with detectable DSA, dd-cfDNA was significantly elevated (median 0.53%; IQR: 0.12-1.65%) compared to samples negative for DSA (median 0.12%; IQR: 0.12-0.14%) (p Conclusion Presence of DSA correlated with elevation in dd-cfDNA may reflect allograft injury. There may be potential immunologic effects of dd-cfDNA on innate and adaptive immunity, that hence contribute to development of DSA. The High dd-cfDNA/ Low GEP group should be evaluated for potential non-HLA DSA that may potentially impact allograft health. Further analyses regarding clinical events and long-term follow up would be valuable.

Introduction Antibody mediated rejection (AMR) may be suspected in Heart Transplant (HT) patients with biopsy negative rejection (BNR). Donor specific antibodies (DSA) can support this diagnosis. Molecular phenotyping of endomyocardial biopsies (EMB) has identified rejection associated transcripts which correlate with decreased left ventricular ejection fraction (EF) but not with AMR on EMB. BNR may respond to augmented immunosuppression. Thus, there is evidence that BNR may represent rejection. The pathophysiology of AMR involves complement activation. Eculizumab, a monoclonal antibody targeting C5a treats AMR in renal transplant patients. We present two cases of eculizumab use for BNR with presumed AMR in HT patients. Case Report A 22 year old male underwent HT in 2007 for non-ischemic cardiomyopathy (NICM). His post-operative course was complicated by grade 2 AMR and mild cardiac allograft vasculopathy (CAV1) with normal graft function. In 2018 he presented with EF 20%. Coronary angiography (CA) showed CAV1. EMB and DSA were negative. Following treatment for presumed AMR with steroids, IVIG, therapeutic plasma exchange (TPE) and extracorporeal photopheresis (ECP), EF improved to 54%. Three months later he developed symptomatic graft dysfunction (EF 35%). EMB, DSA were negative. CA was stable. Cardiac magnetic resonance imaging (MRI) showed mid myocardial late gadolinium enhancement (LGE). He underwent empiric AMR treatment, with addition of eculizumab. EF normalized with sustained improvement at 18 months. He is maintained on monthly ECP and eculizumab. Our second patient is a 27 year old male with HT in 2009 for NICM. He had recurrent cellular and AMR with re-transplantation in 2013 for recalcitrant CAV. In 2017 he presented in cardiogenic shock, EF 35%. CA showed CAV1. EMB showed grade 1 CMR, negative for AMR. Class I DSA was positive, low level MFI (1053). He was treated with steroids, TPE, IVIG and thymoglobulin. EF further declined to 25%. MRI showed subendocardial inferior LGE. Eculizumab was commenced. Side effects included mild headaches. EF normalized at 6 months. He continues with biweekly ECP and eculizumab. Summary In our patients with BNR and presumed refractory AMR, eculizumab resulted in improved graft function. Research is needed into the efficacy, dosing and duration of therapy. Eculizumab is a therapeutic prospect for HT patients with presumed AMR and BNR.

Purpose In patients with NYHA Class IV heart failure, renal disease may limit candidacy for heart transplantation. Combined heart-kidney transplantation has been effective in patients with multi-organ failure, thereby improving long-term cardiac graft function and overall patient survival. Donors with acute kidney injury (AKI) may limit available organs for transplantation. We aimed to report our experience using donor kidneys with AKI in combined heart-kidney transplantation. Methods From 2005-2020, a single institutional retrospective chart review of patients undergoing combined heart-kidney transplants was performed. The United Network for Organ Sharing (UNOS) database was used to collect data. Statistical analysis was done using a two-sample T-test and comparison of means test. Results were stratified by age, sex, post-operative length of stay (LOS), episodes of rejection, post-operative CRRT, post-operative delay in renal graft function, and cardiac function. Results 35 patients received combined heart-kidney transplants. Average age was 59.37 years. Average follow-up was 50.58 months. In our patient pool, 77.2% were male and 22.8% were female. 5 patients received kidneys from donors who had AKI, of which 1 had delayed graft function (20%). 14 patients who received donor kidneys without AKI had delayed graft function (43.3%) (p=0.88). Average LOS was not statistically different. Current eGFR was not statistically different. 3 patient deaths were not related to graft rejection. See Table 1. Conclusion This study demonstrates that combined heart-kidney transplantation can be done safely and effectively using donor kidneys with AKI. Our analysis shows no difference in post-operative delayed graft function of the kidney with AKI, LOS, and renal/cardiac function. Although our experience suggests safe use of donor kidneys with AKI, larger studies are necessary to define the short and long-term outcomes of combined heart-kidney transplantation with AKI donors.

Introduction Myocarditis is often an elusive diagnosis as the clinical presentation can be nonspecific and definitive diagnosis can be challenging due to the low sensitivity of endomyocardial biopsy. Additionally, treatment of myocarditis is controversial with no guidelines and limited data available regarding efficacy. Nevertheless, recent studies have demonstrated a treatment benefit with immunosuppression, particularly in giant cell myocarditis (GCM). This report highlights a unique case of histologically confirmed GCM in which the patient also had a significant peripheral hypereosinophilia, and examines the response of combined immunosuppression with rabbit anti-thymocyte globulin (RATG), corticosteroids, cyclosporine, and benralizumab–an interleukin-5 receptor antagonist–that resulted in rapid recovery. Case Report A 25 year old woman with a history of asthma for 3 years and a recent diagnosis of heart failure with reduced ejection fraction (40%) presented with acute chest pain and worsening left ventricular (LV) dysfunction with a reduction of her left ventricular ejection fraction (LVEF) to 25-30% within 2 weeks. Laboratory studies revealed a 40% peripheral eosinophilia. Further workup was negative for infection, eosinophilic granulomatosis with polyangiitis, or malignancy. A cardiac MRI showed late-gadolinium enhancement and an endomyocardial biopsy confirmed significant eosinophilic tissue infiltration, myocyte necrosis, and the presence of giant cells. She was treated with a combined immunosuppression regimen of RATG induction, corticosteroids, cyclosporine, and benralizumab. Despite this regimen, she had a recurrence of peripheral eosinophilia during the course of her hospitalization. Nevertheless, she had significant clinical improvement in symptomatology, functional status, and hemodynamics. Her peripheral eosinophilia resolved over the following days with increased corticosteroids and thereafter remained negligible. A repeat echocardiogram 3 weeks after initial initiation of immunosuppression demonstrated significant improvement in her LVEF to 53%, improvement of global strain, and reduction of left atrial dilatation. Discussion Emerging data suggests that treatment with immunosuppression can improve outcomes in patients with GCM. Indeed, this patient did have a marked improvement in LV function within 3 weeks of initiating treatment. Additionally, the use of benralizumab to treat her peripheral eosinophilia demonstrates potential implications for use in other hypereosinophilic syndromes. However, given that her serum eosinophila recurred despite being on a multi-drug immunosuppression regimen, including benralizumab, identifies potential focus areas of future research including further examination of the exact mechanism of action, the relevance of expanded use in other hypereosinophilic syndromes, and delineation of appropriate end points for measuring response.

Cardiac resynchronization therapy (CRT) reduces ventricular arrhythmia (VA) burden in some patients with heart failure, but its effect after left ventricular assist device (LVAD) implantation is unknown. We compared VA burden in patients with CRT devices in situ who underwent LVAD implantation and continued CRT (n = 39) to those who had CRT turned off before discharge (n = 26). Implantable cardioverter-defibrillator (ICD) shocks were significantly reduced in patients with continued CRT (1.5 ± 2.7 shocks per patient vs 5.5 ± 9.3 with CRT off, p = 0.014). There was a nonsignificant reduction in cumulative VA episodes per patient with CRT continued at discharge (42 ± 105 VA per patient vs 82 ± 198 with CRT off, p = 0.29). On-treatment analysis by whether CRT was on or off identified a significantly lower burden of VA (17 ± 1 per patient-year CRT on vs 37 ± 1 per patient-year CRT off, p

Emergent mechanical support with transfer of patients in acute cardiopulmonary shock to specialty centers for definitive management is often required at non-transplant centers. An alternative approach to the traditional "hub and spoke" model is presented. A team of health care specialists from our hospital is deployed to the community hospital for stabilization, possible implantation, and transfer of patients to our tertiary care facility. Patient assessment can be made with intervention, allowing stabilization and safe transfer by our team to our institution. This method provides tertiary level care at the referring hospital and may improve survival for a sub-set of patients in the community hospital setting.

Invasive fungal infections are a significant complication of solid organ transplantation. Here we report the first case of concurrent invasive pulmonary fungal infection caused by Aspergillus fumigatus and Mucor species in a heart transplant recipient. Polymicrobial mold infection is rare but should be considered in solid organ transplant recipients who fail to respond to initial antifungal therapy targeting a single organism. It is also of interest that in addition to potent immunosuppression and prolonged voriconazole therapy, possible airway fungal colonization following hurricane Katrina cleaning efforts might have contributed to this dual invasive mold infection.

A Novel Human Leukocyte Antigen Score Improves Prediction for Rejection After Heart Transplant E.P. Kransdorf ,1 L. Gragert,2 M. Cheng,3 D.E. Steidley,1 R.L. Scott,1 M.J. Pando,4 M. Maiers,2 O.E. Pajaro.5 1Division of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, AZ; 2Bioinformatics Research, National Marrow Donor Program/Be The Match, Minneapolis, MN; 3Division of Health Sciences Research, Mayo Clinic Arizona, Scottsdale, AZ; 4Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ; 5Division of Cardiothoracic Surgery, Mayo Clinic Arizona, Scottsdale, AZ.

max. 2880 mg/day or MMF max. 3g/day) and steroids (≤ 0.3 mg/kg). The primary objective is to assess whether a CNI-free regimen with Everolimus and MPA is associated with a better renal outcome (eGFR, MDRD) 12 months after randomization as compared to the CNI regimen. Key secondary objectives include: non-inferior efficacy (composite endpoint of BPAR of ISHLT 1990 grade ≥ 3A / ISHLT 2004 grade ≥ 2R, acute rejection, episodes of hemodynamic compromise, graft loss / re-transplant, death or loss to follow-up) and assessment of safety parameters as infections, hypertension, hyperlipidemia and diabetes. Results: As of September 2014, 144 patients have been randomized at 9 German heart transplant centers into the MANDELA study. Continuation of the study was well supported by a neutral data safety monitoring board. Conclusion: The MANDELA study might help to evaluate benefit on renal function of an EVR-based CNI-free regimen in HTxR after early conversion.

Purpose HLA mismatches (HLA-MM) have been shown to affect survival after heart transplantation (HTX). However, it is generally felt that current immunosuppressive therapies (IS) minimize the effects of HLA-MM. This study wishes to test the hypothesis that despite advances in IS, HLA-MM still plays a predictive role in determining outcomes. Methods and Materials We retrospectively analyzed survival and freedom from immunologic adverse events on all patients undergoing HTX at our institution between 2005 and 2012 (n=129). Groups were stratified by number of HLA-MM at HLA-A, B, DQ and DR (Group 1, 3-4 MM) (Group 2, 5-6 MM) (Group 3, 7-8 MM). Events considered as adverse were biopsy-proven rejection (BPR) (ISHLT grade > 2R), allograft dysfunction (EF Results 100% of patients had > 3 MM. Group 1-15/129, (12%), Group 2-59/129 (46%), Group 3-55/129 (43%). Freedom from adverse events and survival were significantly worse in patients with >4 MM (Group 2 and 3) (Figure 1). Conclusions Despite the use of triple-drug immunosuppression including tacrolimus in our patients, HLA-MM remains a significant predictor of adverse events and survival. Given this, novel immunologic strategies to abrogate the effect of HLA-MM are urgently needed.