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

Maria Sol Andres; Sivatharshini Ramalingam; Stuart D Rosen; John Baksi; Rajdeep Khattar; Yulia Kirichenko; Kate Young; Nadia Yousaf; Alicia Okines; Robert Huddart; Kevin Harrington; Andrew J S Furness; Samra Turajlic; Lisa Pickering; Sanjay Popat; James Larkin; Alexander R Lyon

doi:10.1186/s40959-022-00147-w

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

Cardiooncology. 2022 Nov 24;8(1):21. doi: 10.1186/s40959-022-00147-w.

Authors

Maria Sol Andres¹, Sivatharshini Ramalingam², Stuart D Rosen^{2

3}, John Baksi², Rajdeep Khattar², Yulia Kirichenko^{2

4}, Kate Young⁵, Nadia Yousaf⁵, Alicia Okines⁵, Robert Huddart⁵, Kevin Harrington⁵, Andrew J S Furness⁵, Samra Turajlic⁵, Lisa Pickering⁵, Sanjay Popat^{3

5}, James Larkin⁵, Alexander R Lyon^{2

3}

Affiliations

¹ Cardio-Oncology Service, Royal Brompton Hospital, Guy's and St. Thomas' NHS Foundation Trust, Sydney Street, SW3 6NP, London, UK. m.andres@rbht.nhs.uk.
² Cardio-Oncology Service, Royal Brompton Hospital, Guy's and St. Thomas' NHS Foundation Trust, Sydney Street, SW3 6NP, London, UK.
³ National Heart and Lung Institute, Imperial College London, London, UK.
⁴ Department of Hospital Therapy N°1, Sechenov University, Moscow, Russia.
⁵ Royal Marsden Hospital Foundation Trust, London, UK.

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.

Keywords: Cancer survivorship; Cardiomyopathy; Immunotherapy; Myocarditis.

Abstract

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