The spectrum of cardiovascular complications related to immune-checkpoint inhibitor treatment: Including myocarditis and the new entity of non inflammatory left ventricular dysfunction

Abstract

Background: The full range of cardiovascular complications related to the use of Immune checkpoint inhibitors (ICI) is not fully understood. We aim to describe the spectrum of cardiovascular adverse events (cvAEs) by presenting our real-world experience of the diagnosis and management of these complications. Methods: Two thousand six hundred and forty-seven (2647) patients were started on ICI treatment between 2014 and 2020. Data from 110 patients referred to the cardio-oncology service with a suspected cvAE was collected prospectively and analysed. Results: Eighty-ninepatients (3.4%) were confirmed to have cvAEs while on ICI therapy. Myocarditis was the most frequent event (33/89), followed bytachyarrhythmia (27/89), non-inflammatory left ventricular dysfunction (NILVD)(15/89) and pericarditis (7/89). Results from myocarditis and non-inflammatory left ventriculardysfunction cohorts were compared. Myocarditis and NILVD showed significantdifferences in respect tooftroponin elevation, cardiac magnetic resonance abnormalities and ventricularfunction. Dual ICI therapy and other immune related adverse events were morefrequently associated with myocarditis than NILVD. There was a significantdifference in the median time from starting ICI treatment to presentation withmyocarditis versus NILVD (12 vs 26 weeks p = 0.049). Through early recognitionof myocarditis, prompt treatment with steroids and interruption of ICI, therewere no cardiovascular in-hospital deaths. NILVD did notrequire steroid treatment and ICI could be restarted safely. Conclusions: The full spectrum of cardiovascular complicationsin patients with immune checkpoint inhibitors is much broader than initiallydescribed. Myocarditis remains the most frequent cvAE related to ICI treatment.A novel type of myocardial injury was observed anddefined as Atrial tachyarrhythmias and NILVDwere also frequent in this cohort. NILVD has a Thisdiffers fromdifferent presentation fromICI-related myocarditis, mainly usuallypresenting afterby the lack ofinflammatory features on CMR and biomarkers anda later presentation in time.