Fradley, Michael G.

ABSTRACT Introduction and Methods Cancer therapy–related cardiac dysfunction (CTRCD) is a well established and potentially life‐threatening complication of contemporary oncologic treatment. Although comprehensive cardio‐oncology guidelines have been developed, their integration into routine hematology and oncology practice remains inconsistent. This consensus statement, developed by a multidisciplinary panel of cardio‐oncology experts, aims to provide practical, case‐based guidance to help oncology providers recognize, assess, and manage CTRCD across a spectrum of malignancies and cardiovascular presentations. Clinical Scenarios and Discussion We present representative clinical scenarios that illustrate real‐world challenges in cardio‐oncology and apply evidence‐based recommendations from current guidelines, including those from the European Society of Cardiology (ESC) and the International Cardio‐Oncology Society (ICOS)—to support informed decision‐making. Key areas of focus include baseline cardiovascular risk stratification prior to initiating potentially cardiotoxic therapies, with an emphasis on biomarker and imaging surveillance strategies tailored to individual risk profiles. Also, this document outlines the application of guideline‐directed medical therapy (GDMT) for cancer patients with heart failure. Conclusion By offering a structured, user‐friendly framework, this document seeks to bridge the implementation gap between oncology and cardiology disciplines. Our goal is to equip oncology providers with accessible tools that facilitate early recognition, consistent surveillance, and timely referral, thereby preserving cancer treatment intensity while minimizing cardiovascular morbidity.

Importance The introduction of immune checkpoint inhibitor (ICI) therapy has improved cancer outcomes but at the cost of adverse events, mainly related to the immune system. Cardiovascular (CV) toxic effects, and especially myocarditis, are of particular concern and are the subject of this position statement by the International Cardio-Oncology Society with representation of experts from oncology, hematology, and cardiology. Observations CV toxic effects of ICI therapies include inflammation-associated diseases, such as myocarditis, pericarditis, and vasculitis, as well as the aggravation of chronic inflammatory conditions, such as atherosclerosis with acute ischemic complications (myocardial infarction and stroke). Patients taking ICI therapies can also develop cardiac dysfunction, stress-induced cardiomyopathy (Takotsubo or apical ballooning syndrome), and heart failure without inflammatory cell infiltration of the myocardium. Atrial and ventricular arrhythmias can emerge in the setting of a systemic inflammatory milieu, myocarditis, or ischemia. Of all potential CV adverse effects, myocarditis remains of highest concern, although fatality rates have declined over time with a broadening spectrum of presentations ranging from troponin elevation of uncertain significance to smoldering, nonsevere, and severe or fulminant myocarditis. Conclusions and Relevance Concerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge. Ischemic heart disease constitutes the main differential diagnosis in these patients, while pericarditis can be concomitantly present, and atrial and ventricular arrhythmias can also complicate the clinical picture. Several gaps in knowledge are identified and require further research.

BACKGROUND: The association between breast cancer diagnosis, treatment, and the risk of incident ischemic stroke remains unclear. We aimed to investigate ischemic stroke risk among breast cancer survivors and evaluate the association by age, follow-up duration, and cancer treatments. METHODS: Using the Korean National Health Insurance Service database, we studied 113,232 women newly diagnosed with breast cancer (aged ≥18 years) without prior stroke history who underwent breast cancer surgery between January 2010 and December 2016. Each was matched 1:3 by birth year to a cancer-free female population (n=322,818). Subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) were estimated, accounting for death as a competing risk and adjusting for sociodemographic factors and cardiovascular and noncardiovascular comorbidities. RESULTS: Over a mean follow-up of 7.2 years, ischemic stroke occurred in 1,155 (1.0%) breast cancer surgery survivors. Overall, breast cancer survivors had a slightly lower risk of stroke than cancer-free women (sHR 0.94; 95% CI 0.88–1.00). However, stroke risk was elevated in the short term following diagnosis (sHR 1.59, 95% CI 1.34–1.89 at 1 year; sHR 1.17, 95% CI 1.05–1.30 at 3 years) across all age groups, with stronger associations observed at 3 and 6 months post-diagnosis. A reduced risk was observed after 1 year in a landmark analysis that included only individuals event-free at the 1-year follow-up (sHR 0.87, 95% CI 0.81–0.93). Among breast cancer survivors, treatment with anthracycline (sHR 1.25) and the combination of tamoxifen and aromatase inhibitors (sHR 1.49) were associated with increased stroke risk, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations weakened and became nonsignificant after 1 year. Stroke risk was also higher in breast cancer survivors with low income, hypertension, diabetes, or current smoking. CONCLUSION: The association between breast cancer and ischemic stroke risk is time-dependent, with increased short-term risk post-diagnosis and treatment, followed by a decline over time. These findings highlight the importance of proactive stroke risk management, including baseline cardiovascular assessments and ongoing monitoring for thromboembolic events.

ABSTRACT The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Abstract The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID‐19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID‐19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio‐oncology and outlines key modifications in the approach to this ever‐increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS–CoV‐2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.

Abstract This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.