Blood, tissue and imaging biomarkers in calcific aortic valve stenosis: past, present and future

Calcific aortic valve stenosis is the most prevalent valvular heart disease in the high-income countries. To this date, no medical therapy has been proven to prevent or to stop the progression of aortic valve stenosis. The physiopathology of aortic valve stenosis is highly complex and involves several signalling pathways, as well as genetic related factors, which delay the elaboration of effective pharmacotherapies. Moreover, it is difficult to predict accurately the progression of the valve stenosis and finding the optimal timing for aortic valve replacement remains challenging. Therefore, the present review makes an inventory of the most recent and promising circulating and imaging biomarkers related to the underlying mechanisms involved in the physiopathology of aortic valve stenosis, as well as the biomarkers associated with the left ventricular (LV) remodelling and subsequent dysfunction in patients with aortic valve stenosis.

Over the last decade, several blood, tissue and imaging biomarkers have been investigated in aortic valve stenosis patients. At the aortic valve level, these biomarkers are mostly associated and/or involved with processes such as lipid infiltration and oxidation, chronic inflammation and fibrocalcific remodelling of the valve. Moreover, recent findings suggest that aging and sex hormones might interact with these multiple processes. Several studies demonstrated the usefulness of circulating biomarkers such as lipoprotein(a), brain natriuretic peptides and high-sensitivity cardiac troponin, which are very close to clinical routine. Furthermore, noninvasive imaging biomarkers including positron emission tomography and cardiac magnetic resonance, which provide a detailed view of the disease activity within the aortic valve and its repercussion on the left ventricle, may help to improve the understanding of aortic valve stenosis physiopathology and enhance the risk stratification. Other biomarkers such as von Willebrand factor and microRNAs are promising but further studies are needed to prove their additive value in aortic valve stenosis.

Most of the biomarkers are used in research and thus, are still being investigated. However, some biomarkers including plasma level of lipoprotein(a), F-sodium fluoride, brain natriuretic peptides and high-sensitivity cardiac troponin can be or are very close to be used for the clinical management of patients with aortic valve stenosis. Moreover, a multibiomarker approach might provide a more global view of the disease activity and improve the management strategies of these patients.