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 toof 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 complications in patients with immune checkpoint inhibitors is much broader than initially described. Myocarditis remains the most frequent cvAE related to ICI treatment. A novel type of myocardial injury was observed and defined as Atrial tachyarrhythmias and NILVD were also frequent in this cohort. NILVD has a This differs fromdifferent presentation from ICI-related myocarditis, mainly usually presenting afterby the lack of inflammatory features on CMR and biomarkers and a later presentation in time.

Immune-related cardiovascular toxicities of PD-1/PD-L1 inhibitors in solid tumors: an updated systematic review and meta-analysis

“…Clinical evidence has indicated that immunotherapy can cause myocarditis, which should be taken seriously. The severity of immune-associated myocarditis varies from mild cases without apparent inflammation to severe cases that may be associated with heart failure, cardiogenic shock, and a high mortality rate in the case of rapidly progressing fulminant myocarditis (98,99). Hu et al concluded that immunotherapy drastically increased the risk of myocardial disease compared with conventional antitumor therapy (100).…”

Early microvascular coronary endothelial dysfunction precedes pembrolizumab-induced cardiotoxicity. Preventive role of high dose of atorvastatin

“…Moreover, documentation of molecular pathways, involved in endothelial dysfunction, can enable the identification of novel druggable targets against endothelial-related functional deficits in cardiovascular diseases [39,76]. Identification and management of Pem-related early coronary endothelial dysregulation are of great clinical value, as in a recent clinical study on ICIinduced CVAEs, vascular-driven CVAEs, such as vasovagal syncope, acute myocardial infarction and microvascular dysfunction, were observed within the spectrum of ICI-induced cardiovascular complications [3]. Therefore, the pharmacological management of ICI-derived early coronary endothelial dysregulation might serve as a druggable target for the mitigation of both cardiac dysfunction and vascular-driven CVAEs by anti-PD-1 therapy.…”

Achilles’ Heel of currently approved immune checkpoint inhibitors: immune related adverse events

“…The estimated event rate of immune-related myocarditis was 1.05%, but the median time of development was delayed to 38 days. Another real-world investigation ( 158 ), that included 2647 patients treated with ICIs, revealed cardiovascular irAEs in 89 patients (3.4%), with myocarditis accounting for approximately. 37.1% of cases.…”