[The Cardio-Oncology Guideline - A Comprehensive Approach to Managing Cardiovascular Risks in Cancer Patients]. / Update zur ESC-Leitlinie Kardioonkologie.

The emerging field of cardio-oncology addresses the critical need for specialized cardiovascular care in cancer patients, given the overlapping risk factors and potential cardiovascular complications of oncological therapies. In collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO), and the European Society of Cardiology (ESC), the first cardio-oncology guideline was developed and published in 2022. This guideline comprises 272 recommendations covering risk stratification before therapy initiation, monitoring during oncological treatment, and the diagnosis and treatment of therapy-associated cardiovascular side effects.A significant innovation in this guideline is the comprehensive risk stratification approach, which categorizes patients into low, moderate, and high-risk groups based on therapy-specific factors. This allows for tailored cardiovascular care during therapy, with varying frequencies of follow-up examinations depending on the patient's risk level. Notably, the guideline emphasizes the importance of interdisciplinary collaboration between oncologists and cardiologists to optimize patient outcomes.Overall, the cardio-oncology guideline represents a significant advancement in addressing the complex cardiovascular needs of cancer patients. Its comprehensive recommendations and emphasis on interdisciplinary care underscore the importance of optimizing cardiovascular health throughout the oncological treatment journey.This review provides an overview of the guidelines and updates on the risk stratification and therapy of patients with immune checkpoint inhibitor-associated myocarditis (ICIM), as well as the role of statins in protecting against anthracycline-associated cardiotoxicity.

Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort study.

Background: Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM). Methods: In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022 at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint. Findings: Overall, 137 patients (median age 60, range 20-83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02-4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03-2.38 years, IQR 0.79). A septal wall thickness above 11 mm (HR 2.48, 95%-CI = 1.10-5.67, p = 0.029) was associated with an increased risk of ACM, with a trend seen for reduced left ventricular ejection fraction prior to therapy (LVEF <40%; HR 9.17, 95%-CI = 1.30-183.11, p = 0.051). Secondary endpoint was reached by 93 patients while no baseline parameter was able to predict an elevated risk. However, hs-cTnT change from baseline of 50% or more during the first 14 days after CAR infusion predicted ACM (HR 3.81, 95%-CI = 1.58-9.45; p = 0.003). None of the baseline characteristics was able to predict the incidence of cardiac events. Interpretation: Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance. Funding: The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research.

Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

AIMS: Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient-related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all-cause mortality (ACM) and the development of cardiotoxicity. METHODS AND RESULTS: Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio-Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12-lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs-cTnT of ≥ 7 ng/L [odds ratio (OR) 1.82, P < 0.001] and NT-proBNP (OR 1.98, P < 0.001) were independent predictors of ACM, while reduced left ventricular ejection fraction was not associated with increased ACM (P = 0.85). The secondary endpoint was reached by 182 patients (9.2%) with a median of 793.5 [IQR 411.2, 1165.0] days. Patients with multiple CVRFs (defined as high risk, n = 886) had an increased risk of cardiotoxicity (n = 100/886, 11.3%; hazard ratio 1.57, P = 0.004). They showed elevated baseline values of hs-cTnT (OR 1.60, P = 0.006) and NT-proBNP (OR 4.00, P < 0.001) and had an increased risk of ACM (OR 1.43, P = 0.031). CONCLUSIONS: In cancer patients, CVRF accumulation predicts cardiotoxicity whereas elevated hs-cTnT or NT-proBNP levels are associated with ACM. Accordingly, less intensive surveillance protocols may be warranted in patients with low cardiac biomarker levels and absence of CVRFs.

High-sensitivity cardiac troponin T determines all-cause mortality in cancer patients: a single-centre cohort study.

AIMS: Cardio-oncology is a growing interdisciplinary field which aims to improve cardiological care for cancer patients in order to reduce morbidity and mortality. The impact of cardiac biomarkers, echocardiographic parameters, and cardiological assessment regarding risk stratification is still unclear. We aimed to identify potential parameters that allow an early risk stratification of cancer patients. METHODS AND RESULTS: In this cohort study, we evaluated 930 patients that were admitted to the cardio-oncology outpatient clinic of the University Hospital Heidelberg from January 2016 to January 2019. We performed echocardiography, including Global Longitudinal Strain (GLS) analysis and measured cardiac biomarkers including N-terminal pro brain-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T levels (hs-cTnT). Most patients were suffering from breast cancer (n = 450, 48.4%), upper gastrointestinal carcinoma (n = 99, 10.6%) or multiple myeloma (n = 51, 5.5%). At the initial visit, we observed 86.7% of patients having a preserved left ventricular ejection fraction (LVEF >50%). At the second follow up, still 78.9% of patients showed a preserved LVEF. Echocardiographic parameters or elevation of NT-proBNP did not significantly correlate with all-cause mortality (ACM) (logistic regression LVEF <50%: P = 0.46, NT-proBNP: P = 0.16) and failed to identify high-risk patients. In contrast, hs-cTnT above the median (≥7 ng/L) was an independent marker to determine ACM (multivariant logistic regression, OR: 2.21, P = 0.0038) among all included patients. In particular, hs-cTnT levels before start of a chemotherapy were predictive for ACM. CONCLUSIONS: Based on our non-selected cohort of cardio-oncological patients, hs-cTnT was able to identify patients with high mortality by using a low cutoff of 7 ng/L. We conclude that measurement of hs-cTnT is an important tool to stratify the risk for mortality of cancer patients before starting chemotherapy.