Coronary care unit CDK Cyclin-dependent kinase CHA 2 DS 2 -VASc Congestive heart failure, Hypertension, Age ≥ 75 years (2 points), Diabetes mellitus, Stroke (2 points)-Vascular disease, Age 65-74 years, Sex category (female) CIED Cardiac implantable electronic device CML Chronic myeloid leukaemia CMR Cardiac magnetic resonance COMPASS-CAT Prospective COmparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real-life patients-Cancer Associated Thrombosis CPET Cardiopulmonary exercise testing CrCl Creatinine clearance CRF Cardiorespiratory fitness CRS Cytokine release syndrome CS Cancer survivors CT Computed tomography CTLA-4 Cytotoxic T lymphocyte-associated antigen-4 cTn Cardiac troponin CTRCD Cancer therapy-related cardiac dysfunction CTR-CVT Cancer therapy-related cardiovascular toxicity CV Cardiovascular CVD Cardiovascular disease CVRF Cardiovascular risk factorsData derived from a single randomized clinical trial or large non-randomized studies.Consensus of opinion of the experts and/or small studies, retrospective studies, registries.©ESC 2022 ESC Guidelines © ESC 2022This table refers to anthracycline equivalence dose using doxorubicin as a reference. Note that these isoequivalent doses are derived from paediatric CS. CS, cancer survivors; CV, cardiovascular.a Data for idarubicin are based upon an estimated anticancer efficacy ratio, not derived from cardiotoxicity data. The CV toxicity dose ratio provides the value that should be used to multiply the dose of the anthracycline of interest to convert to isoequivalent doses of doxorubicin; e.g. to convert 125 mg/m 2 of epirubicin to doxorubicin isoequivalent, multiply the dose by 0.8 (125 mg/m 2 × 0.8 = 100 mg/m 2 of doxorubicin).

Although clinical trials reported a low incidence of immune-related cardiovascular adverse events,1 the number of published life-threatening cases of cardiotoxicity is increasing.2 In this descriptive observational analysis, we aimed to describe the clinical manifestations, management, and outcomes of patients who developed ICI-related cardiotoxicity.

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 MEASURESThe 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.

The considerable progress made in the field of cancer treatment has led to a dramatic improvement in the prognosis of patients with cancer. However, toxicities resulting from these treatments represent a cost that can be harmful to short‐ and long‐term outcomes. Adverse events affecting the cardiovascular system are one of the greatest challenges in the overall management of patients with cancer, as they can compromise the success of the optimal treatment against the tumor. Such adverse events are associated not only with older chemotherapy drugs such as anthracyclines but also with many targeted therapies and immunotherapies. Recognizing this concern, several American and European governing societies in oncology and cardiology have published guidelines on the cardiovascular monitoring of patients receiving potentially cardiotoxic cancer therapies, as well as on the management of cardiovascular toxicities. However, the low level of evidence supporting these guidelines has led to numerous discrepancies, leaving clinicians without a consensus strategy to apply. A cardio‐oncology expert panel from the French Working Group of Cardio‐Oncology has undertaken an ambitious effort to analyze and harmonize the most recent American and European guidelines to propose roadmaps and decision algorithms that would be easy for clinicians to use in their daily practice. In this statement, the experts addressed the cardiovascular monitoring strategies for the cancer drugs associated with the highest risk of cardiovascular toxicities, as well as the management of such toxicities.

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Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non-severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients.

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