Cardiovascular safety outcomes of chronic lymphocytic leukemia treatments: A systematic and targeted literature review.

Chronic lymphocytic leukemia (CLL) treatments, such as targeted agents, chemotherapies, and immunotherapies, may be associated with adverse cardiovascular (CV) outcomes. To understand the extent to which CV outcomes are driven by treatment and potential differences among treatments, we conducted a systematic literature review (SLR) of interventional trials and a targeted literature review (TLR) of observational studies indexed in Embase and MEDLINE from January 2012-June 2023. CV outcomes data were sparse and heterogeneous in the SLR trials (n = 55).

Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.

Heart disease and cancer share common risk factors, genetic predispositions, and metabolic and inflammatory components. Metabolic reprogramming can drive disease progression in both, with cardiometabolic syndrome-marked by obesity, insulin resistance, dyslipidemia, and hypertension-contributing to cancer development. Studies link around 20% of cancer cases to obesity, while elevated glucose and triglyceride levels increase the risk of liver, thyroid, and respiratory cancers.

Immune checkpoint inhibitor-associated myocarditis: a novel risk score.

Background And Aims: Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this 'cardiomyotoxicity' are lacking.

Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis.

In this Review, we present a comprehensive analysis of preclinical models used to study immune checkpoint inhibitor-associated myocarditis (hereafter ICI-myocarditis), a potentially lethal immune-related adverse event. We begin by providing an overview of immune checkpoint inhibitors, highlighting how their efficacy in cancer treatment is counterbalanced by their predisposition to cause immune-related adverse events. Next, we draw from human data to identify disease features that an effective mouse model should ideally mimic.

Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood.

Objectives: The aim of this study was to identify factors associated with LVEF <50% vs ≥50% at the time of hospitalization for ICI-M.

Cardiovascular Safety in Oncology Clinical Trials: JACC: CardioOncology Primer.

The development of novel treatments has improved cancer outcomes but may result in cardiovascular toxicities. Traditional approaches to clinical trial safety evaluation have limitations in their ability to detect signals of cardiovascular risk. Mechanisms to increase power and specificity to clarify cardiovascular safety are required.

Successful treatment of immune checkpoint inhibitor-associated fulminant myocarditis with abatacept and ruxolitinib: a case report.

Background: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy with growing indications for treatment of various malignancies. Immune checkpoint inhibitors are monoclonal antibodies that block inhibitory pathways in immune cells, including cytotoxic T lymphocyte antigen-4 (CTLA4), programmed death 1 receptor (PD1), and programmed cell death ligand-1 (PDL1), to activate the immune system. However, these agents can disrupt self-tolerance and lead to immune-related adverse events.

Cardio-Oncology: A New Clinical Frontier and Novel Platform for Cardiovascular Investigation.

In the past 20 years, cardio-oncology has emerged as a new cardiovascular subspeciality. Older, non-specific chemotherapies (such as anthracyclines) and radiation had been well-described cardiotoxic agents, with anthracycline-associated heart failure initially extensively studied in the pediatric population by Drs. Steven Lipshultz (a cardiologist) and Stephen Sallan (an oncologist).

Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart.

Immune-checkpoint inhibitors (ICIs) have revolutionized oncology, with nearly 50% of all patients with cancer eligible for treatment with ICIs. However, patients on ICI therapy are at risk for immune-related toxicities that can affect any organ. Inflammation of the heart muscle, known as myocarditis, resulting from ICI targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) is an infrequent but potentially fatal complication.

Unveiling Cellular Identities and Gene Expression Pathways in Overlapping Myocarditis and Myositis.

Immune checkpoint therapies can drive antitumor responses and benefit patients but can also induce life-threatening immune-related adverse events such as myocarditis and myositis. These immune-related adverse events are rare but carry substantial morbidity and mortality. In this issue, Siddiqui and colleagues use single-cell RNA and T-cell receptor sequencing to identify novel cellular subsets and propose various mechanisms that could contribute to the pathogenesis of immune checkpoint inhibitor-associated myocarditis and myositis.

Autoimmune Myocarditis, Old Dogs and New Tricks.

Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood.

Clonal hematopoiesis and inflammation in the vasculature: CHIVE, a prospective, longitudinal clonal hematopoiesis cohort and biorepository.

Clonal hematopoiesis (CH) is an age-associated phenomenon leading to an increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery of CH clinically common yet evidence-based guidelines and effective management strategies to prevent adverse CH health outcomes are lacking. To address this gap, the prospective CHIVE (clonal hematopoiesis and inflammation in the vasculature) registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and refine taxonomy and standards of practice for CH risk mitigation.