Circulating factors in heart failure:Biomarkers, markers of co-morbidities and disease factors

Heart failure (HF) is a clinical syndrome characterized by typical signs and symptoms caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intra-cardiac pressures at rest or during stress. The lifetime risk to develop HF at age 55 is 33% for men and 28% for women. In the Netherlands, every day more than 100 patients die of cardiovascular disease, and every year over 7500 patients die of HF. One of the key processes in the pathophysiology of HF is cardiac remodeling, a generally unfavorable process in which the myocardium is converted into a, mostly irreversible, changed structural and functional state. Circulating molecules, released during this process and also known as biomarkers, might aid physicians to better understand the pathophysiology of HF and to better treat and tailor therapy for specific patients. In this thesis, we investigate the utility of biomarkers in different clinical settings and whether biomarkers can provide insights in the interplay between different disease entities. We explore whether biomarkers could be used to identify subjects at low-risk for adverse events. Furthermore, we provide insight in the biological variation of biomarkers, to help clinicians to better interpret biomarkers levels over time. Biomarkers could also be used as a target for therapy. In a review article we discuss the possibilities of anti-galectin-3 therapy and the possible clinical consequences. Lastly, we demonstrate that biomarkers secreted by the failing heart have a direct effect on cancer development and growth. This interplay and possible other mechanisms involved are discussed within this thesis. Future studies need to further explore this interplay of the cardiac secretome with other organs and diseases

Cardio-Immuno-Oncology.

Applying novel technology developed in immuno-oncology to cardiovascular biology and disease may be transformative

OCP acquires FTTH player

PURPOSE OF REVIEW: In this review, we highlight the most important cellular and molecular mechanisms that contribute to cardiac inflammation and fibrosis. We also discuss the interplay between inflammation and fibrosis in various precursors of heart failure (HF) and how such mechanisms can contribute to myocardial tissue remodelling and development of HF. RECENT FINDINGS: Recently, many research articles attempt to elucidate different aspects of the interplay between inflammation and fibrosis. Cardiac inflammation and fibrosis are major pathophysiological mechanisms operating in the failing heart, regardless of HF aetiology. Currently, novel therapeutic options are available or are being developed to treat HF and these are discussed in this review. A progressive disease needs an aggressive management; however, existing therapies against HF are insufficient. There is a dynamic interplay between inflammation and fibrosis in various precursors of HF such as myocardial infarction (MI), myocarditis and hypertension, and also in HF itself. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the inflammatory and fibrotic pathways are essential, and specific drugs that target these pathways need to be evaluated

Cancer and heart disease:associations and relations

Emerging evidence supports that cancer incidence is increased in patients with cardiovascular (CV) disease and heart failure (HF), and patients with HF frequently die from cancer. Recently, data have been generated showing that circulating factors in relation to HF promote tumour growth and development in murine models, providing proof that a causal relationship exists between both diseases. Several common pathophysiological mechanisms linking HF to cancer exist, and include inflammation, neuro-hormonal activation, oxidative stress and a dysfunctional immune system. These shared mechanisms, in combination with risk factors, in concert may explain why patients with HF are prone to develop cancer. Investigating the new insights linking HF with cancer is rapidly becoming an exciting new field of research, and we herein review the most recent data. Besides insights in mechanisms, we call for clinical awareness, that is essential to optimize treatment strategies of patients having developed cancer with a history of HF. Finally, ongoing and future trials should strive for comprehensive phenotyping of both CV and cancer end points, to allow optimal usefulness of data, and to better describe and understand common characteristics of these two lethal diseases

The role of immune checkpoints in cardiovascular disease

Immune checkpoint inhibitors (ICI) are monoclonal antibodies which bind to immune checkpoints (IC) and their ligands to prevent inhibition of T-cell activation by tumor cells. Currently, multiple ICI are approved targeting Cytotoxic T-lymphocyte antigen 4 (CTLA-4), Programmed Death Protein 1 (PD-1) and its ligand PD-L1, and Lymphocyte-activation gene 3 (LAG-3). This therapy has provided potent anti-tumor effects and improved prognosis for many cancer patients. However, due to systemic effects, patients can develop immune related adverse events (irAE), including possible life threatening cardiovascular irAE, like atherosclerosis, myocarditis and cardiomyopathy. Inhibition of vascular IC is associated with increased atherosclerotic burden and plaque instability. IC protect against atherosclerosis by inhibiting T-cell activity and cytokine production, promoting regulatory T-cell differentiation and inducing T-cell exhaustion. In addition, PD-L1 on endothelial cells might promote plaque stability by reducing apoptosis and increasing expression of tight junction molecules. In the heart, IC downregulate the immune response to protect against cardiac injury by reducing T-cell activity and migration. Here, inhibition of IC could induce life-threatening T-cell-mediated-myocarditis. One proposed purpose behind lymphocyte infiltration is reaction to cardiac antigens, caused by decreased self-tolerance, and thereby increased autoimmunity because of IC inhibition. In addition, there are several reports of ICI-mediated cardiomyopathy with immunoglobulin G expression on cardiomyocytes, indicating an autoimmune response. IC are mostly known due to their cardiotoxicity. However, t his review compiles current knowledge on mechanisms behind IC function in cardiovascular disease with the aim of providing an overview of possible therapeutic targets in prevention or treatment of cardiovascular irAEs