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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.

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