BackgroundMyocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST.MethodsThis case–control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca’s criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not.ResultsA total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005).ConclusionThe need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.

IntroductionApart from pulmonary vein isolation (PVI), several step-by-step procedures that aim to modify left atrial substrate have been proposed for the ablation of persistent atrial fibrillation (AF), yet the optimal strategy remains elusive. There are cumulative data suggesting an incremental benefit of adding vein of Marshall (VOM) ethanol infusion to PVI in patients with persistent AF. We sought to evaluate the feasibility and efficacy of a novel stepwise ablation approach, incorporating a VOM alcoholization step, for persistent AF.MethodsIn this single-center study, we prospectively enrolled 66 consecutive patients with symptomatic persistent AF and failure of at least one antiarrhythmic drug (ADD). The ablation procedure consisted of (i) PVI, (ii) left atrial segmentation with VOM ethanol infusion and the deployment of linear radiofrequency lesions across the roof and the mitral isthmus and (iii) electrogram-based ablation of dispersion zones. The first two steps were performed in all patients, whereas the third step was carried out only in those still in AF at the end of the second step. Atrial tachycardias during the procedure were mapped and ablated. At the end of the procedure, cavotricuspid isthmus ablation was additionally performed in all patients. The primary endpoint was 12-month freedom from AF and atrial tachycardia after a single procedure and an initial three-month blanking period.ResultsTotal procedure time was 153 ± 38.5 min. Fluoroscopy time was 16 ± 6.5 min and the radiofrequency ablation time was 26.14 ± 0.26 min. The primary endpoint occurred in 54 patients (82%). At 12 months, 65% of patients were off any AAD. In the univariate Cox regression analysis, left ventricular ejection fraction &lt; 40% was the only predictor of arrhythmia recurrence (HR 3.56; 95% CI, 1.04–12.19; p = 0.04). One patient developed a pericardial tamponade and another a minor groin hematoma.ConclusionA novel stepwise approach, including a step of ethanol infusion in the VOM, is feasible, safe and provides a high rate of sinus rhythm maintenance at 12 months in patients with persistent AF.