Case report: CAR-T cell therapy-induced cardiac tamponade

CD19-specific chimeric antigen receptor T (CAR-T) cell therapy has recently been shown to improve the prognosis of refractory diffuse large B-cell lymphoma (DLBCL). However, CAR-T cells may induce numerous adverse events, in particular cytokine release syndrome (CRS) which is frequently associated with cardiovascular manifestations. Among the latter, acute pericardial effusion represents less than 1% of cases and cardiac tamponade has only been reported once. The management and outcome of these severe complications are not well established. We report here, a case of cardiac tamponade associated with CRS in a context of CAR-T cell therapy, which required urgent pericardiocentesis.Case summaryA 65-year-old man with refractory DLBCL was treated with CAR-T cell therapy. He had a history of dilated cardiomyopathy with preserved ejection fraction and transient atrial fibrillation. A pericardial localization of the lymphoma was observed on the second relapse. One day after CAR-T cell infusion the patient was diagnosed with grade 1 CRS. Due to hypotension, he was treated with tocilizumab and dexamethasone, and then transferred to intensive care unit (ICU). Echocardiography performed at ICU admission showed acute pericardial effusion with signs of right ventricular heart failure due to cardiac tamponade. It was decided to perform pericardiocentesis despite grade IV thrombocytopenia in a context of aplasia. Analysis of pericardial fluid showed a large number of lymphoma cells and 73% of CAR-T cells amongst lymphocytes, a level that was similar in blood. Hemodynamic status improved after pericardiocentesis, and no recurrence of pericardial effusion was observed. The presence of a high count of activated CAR-T cells in the pericardial fluid as well as the short interval between CAR-T cells injection and the symptoms appear as potential arguments for a direct action of CAR-T cells in the mechanism of this adverse event. The patient was discharged from ICU after two days and initially exhibited a good response to DLBCL treatment. Unfortunately, he died fifty days after starting CAR-T cell therapy due to a new DLBCL relapse.ConclusionPatients with a pericardial localization of DLBCL should be assessed for a risk of cardiac tamponade if receiving CAR-T cell therapy and presenting CRS. In this case, cardiac tamponade seems directly related to CAR-T cell expansion. Pericardiocentesis should be considered as a feasible and effective treatment if the risk of bleeding is well controlled, in association with anti-IL6 and corticosteroids

MR evaluation of pulmonary vein diameter reduction after radiofrequency catheter ablation of atrial fibrillation.

International audienceFifty consecutive patients aged 52+/-12 years suffering from drug refractory atrial fibrillation (AF) underwent baseline and post-ablation MR angiography (MRA) at a mean follow-up of 4+/-3.5 months. Pulmonary vein (PV) disconnection was performed with a maximum energy delivery of 30 W. MRA allowed a two-plane measurement of each PV ostium. After ablation, no significant stenosis was observed, and only 1/194 (0.5%) and 3/194 (2%) PVs had a diameter reduction of 31-40% in the coronal and axial planes, respectively. There was a significant overall post-procedural PV narrowing of 4.9% in the coronal plane and 6.5% in the axial plane (P=ns between both planes). MRA is an efficient technique that can be used in pre- and postoperative evaluation of AF patients. Using a maximal power delivery limited to 30 W, no significant PV stenosis was observed at mid-term follow-up. Late PV anatomical assessment is needed to confirm these results on long-term follow-up

Safety, feasibility, and outcome results of cardiac resynchronization with triple-site ventricular stimulation compared to conventional cardiac resynchronization.

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RVOT premature ventricular contractions induce significant anatomical displacement during 3D mapping: A cause of mid-term ablation failure?

International audienceBACKGROUND: Catheter ablation is a first-line treatment for symptomatic right ventricular outflow tract (RVOT) premature ventricular complexes (PVCs). There is evidence of displacement of the ablation target site during PVCs relative to the location in sinus rhythm (SR). AIM: To analyse the extent of displacement induced by RVOT PVCs and its effect on the ablation sites and the mid-term efficacy of ablation. METHODS: In this multicentre French study, we retrospectively included 18 consecutive adults referred for ablation of RVOT PVCs using a three-dimensional (3D) mapping system. PVC activation maps were performed conventionally (initial map), then each PVC activation point was manually reannotated considering the 3D location on a previous SR beat (corrected map). The ablation-site locations on the initial or the corrected area, including the 10 best activation points, were analysed. Mid-term efficacy was evaluated. RESULTS: The direction of map shift during PVCs relative to the map in SR occurred along a vertical axis in 16 of 18 patients. The mean activation-point displacement for each of the 18 mapped chambers was 5.6±2.2mm. Mid-term recurrence of RVOT PVCs occurred in 5 (28%) patients. In all patients with recurrences, no significant ablation lesion was located on the corrected (true) site of origin. CONCLUSIONS: RVOT PVCs induce a vertical anatomical shift that can mislead physicians about the true location of the arrhythmia’s site of origin. Our study highlights the association between mid-term PVC recurrence and the absence of spatial overlap between ablation points and the corrected site of origin

The cardiac blood transcriptome predicts de novo onset of atrial fibrillation in heart failure

Heart failure (HF) increases the risk of developing atrial fibrillation (AF), leading to increased morbidity and mortality. Therefore, better prediction of this risk may improve treatment strategies. Although several predictors based on clinical data have been developed, the establishment of a transcriptome-based predictor of AF incidence in HF has proven to be more problematic. We hypothesized that the transcriptome profile of coronary sinus blood samples of HF patients is associated with AF incidence. We therefore enrolled 192 HF patients who were selected for biventricular cardioverter defibrillator implantation. Both coronary sinus and peripheral blood samples were obtained during the procedure. Patients were followed-up during two years and AF occurrence was based on interrogation of the defibrillator. A total of 96 patients stayed in sinus rhythm (SR) during follow-up, 13 patients developed AF within 1 year and 10 patients developed AF during the second year of follow up. Gene expression profiling of coronary sinus samples led to the identification of 321 AF predictor genes based on their differential expression between patients developing AF within 1 year of blood sampling and patients remaining in SR. The expression levels of these genes were combined to obtain a molecular atrial fibrillation prediction score for each patient which was significantly different between both patient groups (Mann-Whitney, p = 0.00018). We conclude that the cardiac blood transcriptome of HF patients should be further investigated as a potential AF risk prediction tool