Immune Checkpoint Inhibitors and Cardiovascular Adverse Events

ESC Heart Failure, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract In the last years, we assisted to a tremendous increase in therapeutic options for management of cancers, with immunotherapy at forefront this innovation. Immune checkpoint inhibitors (ICIs) have been developed enhance activity immune system against cancer cells (1) and number approvals ICIs has rapidly increased. also associated disinhibited cytotoxic T that damage healthy tissue multiple organs, causing immune‐related adverse events (AEs). Cardiovascular AEs (CVAe) are increasingly reported: myocarditis, Takotsubo syndrome, pericarditis pericardial effusion, worsening atherosclerosis, acute coronary syndromes, non‐inflammatory heart failure, ischaemic stroke. They classified into five grades, based on presenting symptoms, level cardiac biomarkers, imaging. Even though myocarditis occurs more frequently than previously thought, clinically relevant is rare irAE compared other (0.5–1.2%). The clinical manifestations range from mild symptoms such as chest pain, cardiogenic shock. prognosis severe, mortality rates ranging 25% 50%. It concomitant use combination inhibitors. treatment strategies tripartite: (i) holding ICI prevent further toxicity, (ii) immunosuppression alleviate inflammatory changes, (iii) supportive therapy address complications. Glucocorticoids represent first‐line treatment. hemodynamically unstable patients, high‐dose steroids should be initiated (intravenous methylprednisolone 1000 or 1250 mg oral during 4 days). ICI‐associated can accompanied by no/mild effusion up tamponade. made nonsteroidal anti‐inflammatory drugs colchicine, corticosteroids if needed, pericardiocentesis large effusions. could continued Grade 1 pericarditis, while temporary suspension warranted severe cases. There significant potential accelerated atherosclerosis long‐term effect, but atherosclerosis‐related CVAEs not frequent, especially treatment; increasing evidence associates progression increased atherosclerotic cardiovascular disease. lead arrhythmias: atrial fibrillation, supraventricular ventricular tachycardias. Non‐inflammatory failure syndrome observed ICI‐treated patients. seem involved development right dysfunction pulmonary arterial hypertension. outmost importance improve collaboration among different medical figures, cardiologists, oncologists, endocrinologists, immunologists, both practice basic science research, better recognize these events, understand their pathophysiological mechanisms, overall survival quality life affected

Language: Английский

The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Abstract Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain cornerstones of oncological treatment. However, each carries risk cardiotoxicity, though molecular mechanisms underlying these adverse effects differ. Common include DNA damage response, increased reactive oxygen species, mitochondrial dysfunction, which are key areas ongoing research for potential cardioprotective strategies. Since also essential effective tumor cytotoxicity, we explore tumor-specific effects, particularly hereditary breast linked to BRCA1 BRCA2 mutations. These genetic variants impair repair mechanisms, increase tumorigenesis possibly cardiotoxicity from treatments such as anthracyclines antagonists. Novel therapies, including immune checkpoint inhibitors, used clinic triple-negative improve outcomes patients. This review discusses BRCA dysfunction associated pathological pathways. It gives an overview preclinical models genetically engineered mouse models, syngeneic murine humanized various vitro ex vivo systems study cardiovascular side therapies. Understanding mechanism developing strategies improving treatment reducing long-term risks

Language: Английский

Changes in tumor and cardiac metabolism upon immune checkpoint

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Cardiovascular disease and cancer are the leading causes of death in Western world. The associated risk factors increased by smoking, hypertension, diabetes, sedentary lifestyle, aging, unbalanced diet, alcohol consumption. Therefore, study cellular metabolism has become increasing importance, with current research focusing on alterations adjustments patients. This may also affect efficacy tolerability anti-cancer therapies such as immune-checkpoint inhibition (ICI). review will focus metabolic adaptations their consequences for various cell types, including cells, cardiac myocytes, immune cells. Focusing ICI, we illustrate how interact metabolism. In addition to desired tumor response, highlight that ICI can lead a variety side effects impact or vice versa. With regard cardiovascular system, ICI-induced cardiotoxicity is increasingly recognized one most life-threatening adverse events mortality up 50%. As such, significant efforts being made assess specific interactions changes ICIs improve both management effects.

Language: Английский