Takotsubo syndrome in patients with cancer treated with immune checkpoint inhibitors: a new adverse cardiac complication

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

“…Myasthenia gravis frequently overlapped with myocarditis/myositis, with a 62.5% mortality rate Salem et al (2018); Vigibase [ 34 ] Cardiovascular toxicity Higher reporting of myocarditis, pericardial diseases, supraventricular arrhythmias, vasculitis (temporal arteritis, polymyalgia rheumatic) 0.4% (myocarditis), 0.3% (pericardial diseases, vasculitis) 50% (myocarditis), 21% (pericardial disease), 6% (vasculitis) TTO = 30 (myocarditis, pericardial disease), 55 (vasculitis). Myocarditis overreported with anti-PD-1/PD-L1, and combo; pericardial diseases with anti-PD-1/PD-L1; vasculitis with anti-CTLA-4 Fan et al (2019); FAERS [ 39 ] Myocarditis Higher reporting for all ICI monotherapies and two ICI combos 0.7% 51% (66% in combination) TTO = 23, earlier for combination vs. monotherapy (16.5 vs. 32) Ederhy et al (2019); Vigibase [ 55 ] TTS Higher reporting of TTS, especially with ipilimumab and pembrolizumab 0.03% 13% (1 patient) 1333 cases of stress cardiomyopathy; TTO = 6 (median) and 76 (mean); no cases in combo; use of positive (venlafaxine/adrenaline) and negative (paracetamol) controls; 3 patients did not recover Nguyễn et al (2020); Vigibase [ 56 ] Myositis Higher reporting with anti-PD-1/PD-L1 (vs. anti-CTLA-4) and combo; no myasthenia cases with anti-CTLA-4 0.6% (345 cases) 22.3% (51.3% with myocarditis) Median TTO = 33; 95% serious; myocarditis and myasthenia in 11.3% and 11.9%, respectively Oshima et al (2018); FAERS [ 43 ] IP Higher proportion of IP in nivolumab + EGFR TKIs 20,516 patients with NSCLC; 985 IP cases (18 exposed to nivolumab + EGFR TKIs) NA The statistically significant interaction effect supported the existence of the interaction Aggarwal (2019); FAERS [ 40 ] BP Consistent signal of BP across analyses 37 cases with pembrolizumab, 81 with nivolumab ...…”

Cardiotoxicity from immune checkpoint inhibitors

“…Few data is available on the feasibility of ICI rechallenge following takotsubo syndrome. Therefore, ICI rechallenge should be evaluated individually after recovery of LV function under intensified cardiac monitoring [26,47].…”

Immune checkpoint inhibitor-induced takotsubo syndrome and diabetic ketoacidosis: rare reactions

“…12 13 There have been reports in the literature of TS secondary to ICIs and a proportionality study found that there was an increased OR of TS when compared with positive and negative controls. [6][7][8] The precise pathophysiology of TS in the setting of ICIs is unclear and imaging studies have not consistently shown myocardial oedema. 7 8 The proposed mechanism of injury in ICI-induced myocarditis is lymphocyte (CD4+ and CD8+ T cells) and macrophage infiltration of the myocardium.…”

“…Four days after the ICI treatment, he re-presented with recurrent chest pain. Case report 6.6 mmol/L (range <1 mmol/L) and a pH of 7.12 (normal range 7.32-7.43). He was managed with nitrates, antiplatelet agents and enoxaparin once again together with intravenous rehydration, but an angiogram was not performed.…”

“…There are published case reports of ICI-triggered takotsubo syndrome (TS). [5][6][7][8] ICI-induced endocrinopathies are well described in the literature and these occur at a higher frequency with combination therapy. 9 This case report identifies a patient presenting with TS followed by ketoacidosis (associated with SGLT2 inhibitor) in the setting of combination ipilimumab and nivolumab (Ipi/Nivo) therapy for metastatic melanoma.…”