The spectrum of cardiovascular complications related to immune-checkpoint inhibitor treatment

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-nine patients (3.4%) were confirmed to have cvAEs while on ICI therapy. Myocarditis was the most frequent event (33/89), followed by tachyarrhythmia (27/89), non-inflammatory left ventricular dysfunction (NILVD) (15/89) and pericarditis (7/89). Results from myocarditis and non-inflammatory left ventricular dysfunction cohorts were compared. Myocarditis and NILVD showed significant differences in respect of troponin elevation, cardiac magnetic resonance abnormalities and ventricular function. Dual ICI therapy and other immune related adverse events were more frequently associated with myocarditis than NILVD. There was a significant difference in the median time from starting ICI treatment to presentation with myocarditis versus NILVD (12 vs 26 weeks p = 0.049). Through early recognition of myocarditis, prompt treatment with steroids and interruption of ICI, there were no cardiovascular in-hospital deaths. NILVD did not require steroid treatment and ICI could be restarted safely.Conclusions: The full spectrum of cardiovascular complication in patients with immune checkpoint inhibitors is much broader than initially described. Myocarditis remains the most frequent cvAE related to ICI treatment. Atrial tachyarrhythmias and NILVD were also frequent in this cohort. NILVD has a different presentation from ICI-related myocarditis, usually presenting after 6 months of treatment commencement and presents no inflammatory features.

Immune checkpoint inhibitor-induced cardiotoxicity in patients with lung cancer: a systematic review and meta-analysis

“…The United States Food and Drug Administration has also approved several ICIs including tremelimumab, nivolumab, atezolizumab, avelumab, ipilimumab, pembrolizumab, and durvalumab [4]. While the benefits reaped with ICIs play a pivotal role in the treatment of lung cancer, recent studies have shown that ICIs may precipitate serious cardiotoxic events, such as myocarditis, pericarditis, arrhythmias, myocardial infarction (MI), and non-inflammatory left ventricular dysfunction [5][6][7][8][9][10]. Concern over poor cardiac outcomes is heightened by the extensive use of ICIs in lung cancer therapy [5].…”