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Background: Limited data are available regarding the optimal management and prognosis of patients with cancer who develop an acute myocardial infarction., Aim: The objective of this study was to analyse the characteristics and outcomes of patients according to cancer and myocardial infarction occurrence., Methods: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients seen in French hospitals in 2013, excluding those with a history of myocardial infarction. The population was divided into two groups according to their history of cancer. We studied the following outcomes: all-cause and cardiovascular mortality; acute myocardial infarction; and ischaemic stroke. Data were collected after a 5-year follow-up., Results: Between 2013 and 2019, 3,381,472 patients were seen in French hospitals; among them, 3,323,757 had no history of myocardial infarction. Patients with a history of cancer (n=497,593) had higher incidences of all-cause mortality (17.82%/year vs 3.79%/year), cardiovascular mortality (1.61%/year vs 1.17%/year), myocardial infarction (0.82%/year vs 0.61%/year) and ischaemic stroke (0.91%/year vs 0.62%/year) compared with patients without cancer (n=2,826,164). After performing an adjusted competing-risk analysis, the cumulative incidence of acute myocardial infarction, cardiovascular death and ischaemic stroke incidence was found to be lower in patients with a history of cancer, whereas death of non-cardiac origin was more prevalent in patients with a history of cancer., Conclusions: In this observational study, we have shown that patients with cancer have a higher incidence of all-cause mortality, cardiovascular mortality and myocardial infarction. However, multivariable analysis showed a lower cumulative incidence of these events., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Over the last decade or so, there has been a paradigm shift in the oncologic care of patients with a range of solid tumour and haematologic malignancies, away from traditional cytotoxic chemotherapy and towards personalized cancer treatments, using both targeted therapy and immunotherapy. This shift has contributed to the remarkable and sustained increase in the number of cancer survivors and the longevity of patients with a cancer diagnosis. This review will focus on the cardiovascular effects of immune checkpoint inhibitors and will present a background on immune checkpoint inhibition for cancer, the epidemiology, potential mechanisms, the potential insights into cardiovascular biology, and a diagnostic and therapeutic approach to potential cases. Our understanding of the cardiovascular effects of immune checkpoint inhibitors needs to improve. However, the evolution necessarily needs to be rapid. Initial observations noted that immune checkpoint inhibitor therapy can lead to a fulminant myocarditis. Recent reports have expanded the effect of immune checkpoint inhibitor therapy on the cardiovascular system to include an increase in cardiac dysfunction without myocarditis, arrhythmias, venous thromboembolic disease, accelerated atherosclerosis, and atherosclerosis-related cardiovascular events. The association between immune checkpoint inhibitor therapy and an increase in these cardiovascular events is not only limited to events occurring within the first few weeks after starting therapy but can also include events that occur months to years after therapy. The latter observation is especially of relevance in those treated with adjuvant or neoadjuvant therapy. There needs to be a shift from recognition of an increase in cardiovascular events to currently approved immune checkpoint inhibitor therapies to understanding the mechanisms that lead to adverse cardiovascular effects, understanding who is at risk, and understanding what we can do about it., Competing Interests: Conflict of interest: T.G.N. has received advisory fees from AbbVie, Amgen, C4 Therapeutics, H3-Biomedicine, Genentech, Sanofi, Roche, BMS, and Intrinsic Imaging. T.G.N. has received grant funding from AstraZeneca and BMS. J.N. has received advisory fees from AstraZeneca, Bristol Myers Squibb, Merck, Roche/Genentech, Amgen, Takeda, Pfizer, Daiichi Sankyo, NGM Pharmaceuticals, Kaleido Biosciences, and institutional research grant funding from Merck, AstraZeneca, Bristol Myers Squibb, and Mirati. J.N. is the principal investigator on grant funding from Merck, AstraZeneca, and Bristol Myers Squibb., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Cardiac MRI features are not well-defined in immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M), a severe complication of ICI therapy in patients with cancer. Purpose To analyze the cardiac MRI features of ICI-M and to explore their prognostic value in major adverse cardiovascular events (MACE). Materials and Methods In this retrospective study from May 2017 to January 2020, cardiac MRI findings (including late gadolinium enhancement [LGE], T1 and T2 mapping, and extracellular volume fraction [ECV] z scores) of patients with ICI-M were compared with those of patients with cancer scheduled to receive ICI therapy (pre-ICI group) and patients with viral myocarditis. As a secondary objective, the potential value of cardiac MRI for predicting MACE in patients with ICI-M by using Cox proportional hazards models was explored. Results Thirty-three patients with ICI-M (mean age ± standard deviation, 68 years ± 14; 23 men) were compared with 21 patients scheduled to receive to ICI therapy (mean age, 65 years ± 14; 14 men) and 85 patients with viral myocarditis (mean age, 32 years ± 13; 67 men). Compared with the pre-ICI group, patients with ICI-M showed higher global native T1, ECV, and T2 z scores (0.03 ± 0.85 vs 1.79 ± 1.93 [ P < .001]; 1.34 ± 0.57 vs 2.59 ± 1.97 [ P = .03]; and -0.76 ± 1.41 vs 0.88 ± 1.96 [ P = .002], respectively), and LGE was more frequently observed (27 of 33 patients [82%] vs two of 21 [10%]; P < .001). LGE was less frequent in patients with ICI-M than those with viral myocarditis (27 of 33 patients [82%] vs 85 of 85 [100%]; P < .001) but was more likely to involve the septal segments (16 of 33 patients [48%] vs 25 of 85 [29%]; P < .001) and midwall layer (11 of 33 patients [33%] vs two of 85 [2%]; P < .001). Septal LGE was the only cardiac MRI predictor of MACE at 1 year even after adjustment for peak troponin (adjusted hazard ratio, 2.7 [95% CI: 1.1, 6.7]; P = .03). Conclusion Cardiac MRI features of immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M) seem to differ from those in patients scheduled to receive ICIs and patients with viral myocarditis. Septal late gadolinium enhancement might be a predictor of major cardiovascular events in patients with ICI-M. Clinical trial registration no. NCT03313544 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Edelman and Pursnani in this issue.

Opinion Statement: Vascular events have become an important issue in the overall management of cancer patients. They usually result from a combination of (i) direct or indirect toxicity of anticancer treatments, (ii) a higher prevalence of cardiovascular risk factors in cancer patients, and (iii) prolonged exposure to treatments due to an increasing patient survival rate. In addition to conventional chemotherapies and radiotherapy, targeted therapies and immunotherapies have been developed which improve the prognosis of cancer patients but sometimes at the cost of vascular toxicity, which can lead to systemic or pulmonary hypertension and arterial/venous thromboembolic events. Endothelial dysfunction, a procoagulant state and metabolic disorders are the three main pathophysiological patterns leading to cancer treatment-related vascular toxicity. This issue is challenging because serious vascular adverse events can necessitate cancer treatment being put on hold or stopped, which could compromise patient survival. In addition to increasing the risk of thrombotic adverse events, cancer therapies may lead to an increased risk of bleeding, especially in treatments with vascular endothelial growth factor inhibitors. Therefore, we can define vasculo-oncology as a part of the cardio-oncology specialty; its aims are to predict, prevent, screen, and treat vascular toxicity related to cancer treatments. While the level of evidence is low regarding the management of vascular toxicity during cancer therapy, cardiologists and specialists in vascular diseases should closely collaborate with oncologists and hematologists to determine the optimal strategy for each patient., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE)., Objective: To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences., Design, Setting, and Participants: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included., Main Outcomes and Measures: The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge., Results: A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs., Conclusions and Relevance: This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.

Background: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs., Methods: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death., Results: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002)., Conclusion: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

How to organise cardiovascular management of cancer patients? Advances in cancer therapy have reduced cancer mortality. However, these results are sometimes achieved at the cost of cardiovascular adverse events that may limit the overall benefit of treatment. Cardio-oncology is a recent discipline that aims to prevent, screen and manage cardiovascular diseases associated with or secondary to cancer treatment without compromising its effectiveness. These goals must therefore be integrated into the patient care program at the time of cancer diagnosis. Therefore, a cardiovascular toxicity risk assessment should be conducted prior treatment to identify patients candidate for closer monitoring. In parallel with their oncologic follow-up, these high-risk patients should receive cardiovascular follow-up that should not be restricted to a solely measurement of the left ventricular ejection fraction. Indeed, toxicities can be multiple, so the assessment must be comprehensive and should include at least clinical examination, ECG, cardiac imaging, and sometimes biomarkers. In the case of cardiovascular events, this organisation will enable an earlier and coordinated management with oncologists, which will result in an improvement of the patients' overall prognosis., Competing Interests: F. Thuny déclare des interventions ponctuelles (essais cliniques, conférences) pour AstraZeneca, Novartis, Sanofi, Boston Scientific, Bristol- Myers Squibb. J. Cautela déclare des interventions ponctuelles (essais cliniques, conférences) pour MSD, Janssen, Merck, Novartis, AstraZeneca, Vifor Pharma. F. Thuny et J. Cautela déclarent avoir été pris en charge lors de congrès par AstraZeneca, Novartis, Sanofi, Boston Scientific, Bristol- Myers Squibb, St. Jude Medical, Abbott, LivaNova, Pfizer, Boehringer Ingelheim, Biotronik, Orion Pharma, Resmed, Philips, General Electric, Sorin Group, Lilly, Daiichi Sankyo, Genzyme, Mylan Medical, Medtronic, Bayer Healthcare, Vifor, Actelion, LEO Pharma.

Background: Cardiovascular toxicity has become a challenging issue during cancer therapy. Nonetheless, there is a lack of consensual guidelines for their management. We aimed to determine the current practices of oncologists regarding cardiovascular toxicity related to anthracyclines, trastuzumab and angiogenic inhibitors and to gather their opinions on the development of cardio-oncology programs., Methods: A cross-sectional declarative study was submitted to French oncologists in the form of an individual, structured questionnaire., Results: A total of 303 oncologists responded to the survey. Ninety-nine percent of oncologists prescribed cardiotoxic therapies, including anthracyclines (83%), trastuzumab (51%) and other angiogenic inhibitors (64%). The method adopted for managing cardiovascular toxicity was based on guidelines from expert oncology societies for only 35% of oncologists. None was aware of recommendations from expert cardiology societies. Prescription of pre-, peri- and post-therapy cardiovascular assessment was inconsistent and significantly less frequent for all classes of angiogenic inhibitors than for anthracyclines and trastuzumab (P<0.0001). Relative to pre-therapy assessment, post-therapy assessment was prescribed significantly less often for all cancer therapies (P<0.0001). Attitudes regarding the onset of left ventricular dysfunction were much more inconsistent when angiogenic inhibitors were involved. Additionally, the management of hypertension and QT prolongation was also inconsistent. Finally, 88% of oncologists supported projects of cardio-oncology programs development., Conclusions: Practices of oncologists are disparate in the field of cardiovascular toxicity. This finding underlines the complexity of managing many different situations and the need for distribution of formal guidelines from oncology and cardiology expert societies. The development of personalized cardio-oncology programs seems essential., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)