No abstract

Introduction: Chimeric Antigen receptor T- Cells (CAR-T) are novel therapy for various malignancies, including lymphoma. Cardiotoxicity such as heart failure, arrhythmia, and acute coronary syndrome frequently occurs in the setting of cytokine release syndrome (CRS). Hypothesis: We aimed to investigate the changes in inflammatory cytokines in patients who develop cardiotoxicity after CAR-T therapy. Methods: This was a prospective observational cohort study involving patients diagnosed with lymphoma treated with CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel). Serum cytokines interleukin (IL)-2, IL-6, IL-15, IFN-gamma, TNF-alpha, GM-CSF, and angiopoietin 1 & 2 were tested before lymphodepletion and daily during index hospitalization. Cytokines were analyzed using the ELLA Immunoassay system (SimplePlex, Protein Simple) and reported in pg/mL. Cardiac events were adjudicated by a cardio-oncology team. Results: Fifty-three patients with a complete set of cytokine levels were analyzed. There were 9 cardiac events after CAR-T (8 atrial fibrillation and 1 cardiomyopathy). Patients with cardiac events were older and had higher baseline creatinine level and left atrial volume. All cardiac events occurred in patients who had low-grade CRS (5 Grade 1 and 4 Grade 2 CRS). Tocilizumab was given to seven patients. Pre-CAR-T baseline inflammatory cytokine levels were not different in the cardiac event group. However, median peak IFN-gamma, IL-6, and IL-15 levels were higher median in the cardiac event group (Figure 1). Conclusions: In the setting of CAR-T, the elevation of multiple pro-inflammatory pathways from cytokine release syndrome may be related to the adverse cardiac events, including atrial fibrillation. Further studies are needed to identify and investigate the role of specific inflammatory mediators in cardiac events after CAR-T therapy.

Introduction: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a feared complication. Right ventricle (RV) dysfunction by echocardiogram prior to LVAD implant is a significant risk factor for post-LVAD RVF. However, RV’s unique crescent shape makes it difficult for accurate assessment through echocardiogram. Cardiac MRI can image RV in its entirety and is the gold standard for evaluating RV size and function. Hypothesis: Our study aimed to assess RV comprehensively through cardiac MRI before LVAD implantation to predict severe RVF post-LVAD. Methods: This retrospective cohort study included 231 consecutive patients who underwent LVAD from January 2015 to July 2021. We utilized the commercially available QStrain Application (Medis Suite, the Netherlands) for feature-tracking myocardial strain using gated cine SSFP images. We also assessed for quantitative measurements of RV (systolic/ diastolic volume, stroke volume, and systolic function). Results: There were 12 patients with cardiac MRI before LVAD, of which 4 patients developed severe RVF after LVAD. There were 9 cardiac MRIs available for strain analysis (image quality and old studies before 2012). The RV end-systolic volume (ESV) was higher in severe RVF post-LVAD, but not RV ejection fraction. Endocardial and myocardial global longitudinal strain and global radial strain of RV were not different in severe RVF. Conclusions: In this small series investigating RV function before LVAD implant, we have shown that ESV was higher with severe RVF. Although feature tracking strain of RV was not different in patients with severe RVF, a larger cohort study is warranted to investigate this.

Introduction: Non-invasive quantification of donor-derived cell-free DNA (dd-cfDNA) has recently been shown to correlate with endomyocardial biopsy (EMB) for diagnosis of allograft rejection in heart transplant (HTx) patients. Hepatitis C virus-positive (HCV+) donor hearts are being more utilized with comparable survival outcomes. Hypothesis: The aim of this study is to evaluate the utility of dd-cfDNA monitoring in different types of rejections in recipients of HCV+ donor hearts. Methods: We performed a retrospective review of recipients of HCV+ donor hearts between 2018-2022 with paired dd-cfDNA/GEP and EMB results. The levels of dd-cfDNA/GEP were compared in different rejection types and no rejection for patients using non-parametric comparison. CMR ISHLT ≥ Grade 2R and AMR ≥ Grade 1 from histology were considered as allograft rejection. Results: There were 17 patients who underwent heart transplant from HCV+ donor heart. There was a total of 89 paired samples with dd-cfDNA and EMB. The reason for the biopsy was mostly for routine surveillance (N=68, 76.4%). There was a total of 1 case (1.1%) of grade 2 CMR and 16 cases of pAMR (18%; 10 cases of grade 1, 6 cases of grade 2). Levels of dd-cfDNA were elevated in cases of AMR when compared to no rejection (Median: 0.24% vs. 0.12%, respectively, P<0.001; Figure 1A). There were 57 samples (78%) with dd-cfDNA reference values of <0.12%. In patients with no rejection, dd-cfDNA levels were all below 0.25%. The AUC for elevation of dd-cfDNA and allograft rejection was 0.85 [95% C.I.: 0.72-0.97; P<0.001; Figure 1B]. Conclusions: Non-invasive quantitation of dd-cfDNA levels is elevated in allograft rejection as assessed by traditional microscopy from EMB. There was no false-positive rate of dd-cfDNA in allograft rejection at a threshold of 0.25%. Further studies are indicated to study whether dd-cfDNA levels transiently increase only in the setting of allograft rejection or active hepatitis C viremia at the time of biopsy.