HELPFul

Heart failure is a severe syndrome formed by two entities, systolic heart failure and diastolic heart failure. Currently the term ‘heart failure with reduced ejection fraction (HFREF)’ is used for systolic heart failure and ‘heart failure with preserved ejection fraction (HFPEF)’ for diastolic heart failure. Until recently it was thought that diastolic heart failure had a better prognosis because the pump function of the heart was maintained. Most research has therefore been in the area of systolic heart failure resulting in good biomarkers, such as BNP, and better treatment options. Recent literature has pointed out the severity of diastolic heart failure, for which current biomarkers are not optimal and treatment options remain inadequate. New medicine for diastolic heart failure is in phase II clinical trial setting, which brings hope for better treatment options. To treat the correct type of patient good diagnostic modalities are necessary. For diastolic heart failure echocardiography is the golden standard, though there is much debate concerning the cutoff value for the ejection fraction (a value for the pomp function of the heart) and which combination of echocardiographic abnormalities should classify diastolic dysfunction or heart failure. Wall motions of the left ventricle, together with the volume of the left atrium, are viewed as the most important parameters. The addition of a biomarker to this echo for improvement of the diagnosis would be of great value. This is the goal of HELPFul, to discover and validate a biomarker in the diagnosis of diastolic dysfunction and HFPEF. Recent data shows that the causes of HFPEF are different from HFREF. HFPEF mostly affects women, with persistent high blood pressure and diabetes. These risk factors appear to damage the endothelium (lining of the vascular wall) in the small blood vessels of the heart (microvasculature). As a result these small vessels will collaps, causing regional oxygen deficiency and thereby thickening and stiffening of the heart. Another hypothese is that micro-embolia (small clots) let go of artery sclerosis (erosion) and cause the small vessels to get clogged. This could also result in thickening and stiffening of the heart. For the biomarker discovery we will aim for these two hypothese which centre around the endothelium and the coagulation. We will study the transcriptoma (information) of cells released from the smalls vessels of the heart for information on the presence of diastolic dysfunction or HFPEF. Furthermore we will study the blood for information suggestion the presence of micro-embolia. Our biomarker discovery is mostly aimed at the endothelium and blood coagulation. Promising biomarkers will be validated.

Sex differences in cardiovascular disease (CVD) have been widely acknowledged. Diastolic dysfunction of the heart, eventually evolving into heart failure with preserved ejection fraction (HFpEF) is common in women and has been neglected in cardiovascular research. Currently, it is hypothesized to originate from microvascular dysfunction in the small vessels of the heart leading to stiffness and filling problems. Diastolic dysfunction and HFpEF in women is associated with marked increase of all-cause mortality, yet the disease is often unrecognized because of insufficient diagnostic tools. To be able to effectively prevent diastolic dysfunction and treat HFpEF patients in the future, development of screening tools for (early) diagnosis is crucial.

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