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. 2022 Dec:177:197-205.
doi: 10.1016/j.ejca.2022.07.018. Epub 2022 Aug 24.

Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry

Collaborators, Affiliations

Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry

Joseph Nowatzke et al. Eur J Cancer. 2022 Dec.

Abstract

Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis.

Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram.

Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057).

Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis.

Keywords: Acute coronary syndrome; Coronary revascularization; Immune checkpoint blockers; Immune-related adverse events; Myocarditis.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LL has served on the advisory board for Daiichi Sankyio, Senaca, Astra Zeneca and Servier, as an external expert for Astra Zeneca and received speakers' honoraria from Novartis and MSD. LL is receiving grants from the German Center for Cardiovascular Research (DZHK), German Reuter Foundation (DFG) LE3570/2-1; 3570/3-1 and grant 01KC2006B from the Federal Ministry for Education and Research (BMBF). DA received speakers’ honoraria from BMS, Ipsen and participated to ad-boards from Sanofi and AstraZeneca. KT has received honoraria from Bristol Myers Squibb, Pfizer, Ono Pharmaceutical, Merck BioPharma, Bayer, and grants from Otsuka, Daiichi, Sankyo and Takeda. JM has served on advisory boards for Bristol Myers Squibb, Takeda, Regeneron, Audentes, Deciphera, Ipsen, Janssen, ImmunoCore, Boston Biomedical, Amgen, Myovant, Triple Gene/Precigen, Cytokinetics and AstraZeneca and supported by NIH grants (R01HL141466, R01HL155990, R01HL156021). JES have received consultancy fees from BMS, BeiGene, AstraZeneca, Novartis, and grants from BMS, Novartis, French Agence Nationale de la Recherche, Fondation Coeur et Recherche, Fédération Française de Cardiologie. All other authors have nothing to declare.

Figures

Fig. 1.
Fig. 1.
A 75-year-old male with hypertension, atrial fibrillation, metastatic renal cell carcinoma treated with ipilimumab and nivolumab most recently 4 days prior presented with palpitations and found to be in ventricular tachycardia (A), which converted to atrial fibrillation with ST segment elevations in leads V3–V6 (B). Urgent coronary angiogram was performed demonstrating an 80% left anterior descending blockage (red arrow, C), which was treated with percutaneous coronary intervention (PCI) with a drug-eluting stent. Transthoracic echocardiogram demonstrated apical hypokinesis and dilated right ventricle, with 50–55% ejection fraction. The day after the intervention, the patient developed wide complex tachycardia treated by lidocaine bolus, which evolved to complete atrioventricular heart block associated with shock requiring vasopressor support, continuous renal replacement therapy and intubation for hypoxic respiratory failure. He was then started on 100 mg of intravenous methylprednisolone, ultimately increased to 1000 mg methylprednisolone for 3 days. Troponin-I peeked 2 days after initial PCI at 40.46 ng/ml (upper limit of normal 0.03 ng/ml). Endomyocardial biopsy on Day 5 was consistent with lymphocytic myocarditis (D). With no clinical improvement, the patient’s family decided to transition to comfort care measures and the patient was extubated and passed away 7 days after initial presentation.
Fig. 2.
Fig. 2.
Cumulative incidence of event curves by presence of coronary artery disease and revascularization assessing myocarditis-related death, irAE-death, and all-cause death at 90 days. Adjusted hazard ratio (aHR) and confidence interval (CI) represent the association of coronary revascularization (vs. no revascularization) adjusted on age and sex with the outcome of interest.

Comment in

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