Emerging biomarkers Many new players are emerging and biomarkers of cardiac remodelling could provide additional information to natriuretic peptides testing and help to develop more tailor-based strategies for treatment . 2 , 3 As previously mentioned , the remodelling and fibrosis of the heart plays an important role in the progression of HF . Biomarkers related to cardiac hypertrophy , cardiac fibrosis and remodeling of the extracellular matrix could provide valuable information for the risk stratification of HF patients . Soluble ST2 and fibroblast growth factor 23 ( FGF-23 ) are two good examples of biomarkers related to remodelling , and automated assays are emerging to facilitate their measurement in clinical laboratories . 4 – 8
Soluble ST2 Interleukin 33 ( IL-33 ) is a member of the IL-1 cytokine family acting both as a cytokine and as an intracellular nuclear factor with transcriptional regulatory properties . IL-33 prevents the apoptosis of cardiomyocytes and improves cardiac function and survival after myocardial infarction through ST2 signalling . 4 , 7 ST2 is a receptor encoded by IL1RL1 and for which differential splicing of the gene can produce a functional membrane-bound receptor ( ST2L ) or a soluble decoy receptor ( sST2 ) able to quench the biological activity of IL-33 . The increase of circulating sST2 levels is related to cardiac remodelling , fibrosis and HF , and measurement of sST2 could facilitate the risk stratification and treatment of HF with reduced ejection fraction as well as the diagnosis and prognosis of HF with preserved ejection fraction . 4 , 7 , 9
FGF-23 FGF-23 , a key regulator of the phosphorus homeostasis , is produced by osteocytes and binds to renal and parathyroid FGF-Klotho receptor heterodimers , resulting in phosphate excretion , decreased 1-a-hydroxylation of 25-hydroxyvitamin D and decreased parathyroid hormone ( PTH ) secretion . 5 , 6 As for PTH , impaired homeostasis of cations and decreased glomerular filtration rate might contribute to the rise of FGF-23 . The amino-terminal portion of FGF-23 ( amino acids 1 – 24 ) may serve as a signal peptide allowing the secretion into the blood , and the carboxylterminal portion ( amino acids 180 – 251 ) participates in its biological action . FGF-23 is also related to the risk of cardiovascular diseases and mortality . 5 , 6 FGF-23 levels are independently associated with left ventricular mass index and hypertrophy as well as mortality in patients with chronic kidney disease . Increased circulating concentrations of FGF-23 are independently associated with the risk of developing HF in the community and with poor clinical outcome in HF patients , and assays for the measurement of circulating concentrations of the intact hormone ( iFGF-23 ) and some against the C-terminal fragments of FGF-23 ( Ct-FGF-23 ) are available .
Perspectives from emerging technologies Progress around point of care testing ( POCT ) technologies is enormous , contributing to increasing their reliability and the number of tests available . 2 , 7 , 10 The added value of POCT is increasingly evident for rapid diagnosis and might add value in primary care and pre-hospital settings . An example is illustrated by the integration of tele-cardiology units and central laboratories through cardiac markers performed with POCT technologies in the ambulance . 10 These procedures can play an important role in the early diagnosis and treatment of acute coronary syndrome patients related to the pre-hospital phase . The performances of some POCT assays are now compatible with the enquiries of physicians for the management and monitoring of HF , and both BNP and NT-proBNP can be determined by POCT assays . The implementation of POCT will of course rely on interactions between laboratory specialists and users to respect the requirements of accreditation standards and to maximise the efficiency of POCT-based protocols . 7 , 10
Beside the shift of paradigm for biomarker testing , recent progress in the area of mobile Health ( mHealth ) is also spectacular . 10 MHealth describes the use of portable electronic devices with software applications to provide health services and manage patient information . With approximately five billion mobile phone users globally , mHealth technologies have the potential to greatly impact health research , health care , and health outcomes . Mobile phones , smartphones , and tablets are therefore exceptional means for the empowerment of patients with chronic illness . The use of mHealth technologies decreases the number of disease-related health outcomes in
Beside the shift of paradigm for biomarker testing , recent progress in the area of mobile health ( mHealth ) is also spectacular
patients suffering from chronic diseases compared with regular care . 10 In HF patients , mHealth aid in decreasing the length of stay in hospitals and in maintaining the activities of daily living . Studies involving patients with hypertension also demonstrated the ability of mHealth to reduce systolic and / or diastolic blood pressure . 10
Innovations are also coming from the field of data mining and integration , which will allow the combination of clinical and biological features for a more accurate management of patients and will facilitate the identification of clusters of patients at higher risk or more suitable for selection for clinical trials .
Conclusions To reach maximum potential , innovative biomarkers and emerging technologies will require a multidisciplinary assessment of technical , clinical and economical outcomes , meaning that the communication between specialists in laboratory medicine and other healthcare professionals will be needed to ensure an efficient translation into daily practice .
18 HHE 2018 | hospitalhealthcare . com
References 1 Timmis A et al . European Society of Cardiology : Cardiovascular Disease Statistics 2017 . Eur Heart J 2018 ; 39 ( 7 ): 508 – 79 . 2 Gruson D , Thys F , Verschuren F . Diagnosing destabilized heart failure in the emergency setting : current and future biomarker tests . Mol Diagn Ther 2011 ; 15 ( 6 ): 327 – 40 . 3 Gruson D , Ko G . Galectins testing : new promises for the diagnosis and risk stratification of chronic diseases ? Clin Biochem 2012 ; 45 ( 10-11 ): 719 – 26 . 4 Gruson D et al . Increased soluble ST2 is a stronger predictor of long-term cardiovascular death than natriuretic peptides in heart failure patients with reduced ejection fraction . Int J Cardiol 2014 ; 172 ( 1 ): e250 – 2 . 5 Gruson D et al . Comparison of fibroblast growth factor 23 , soluble ST2 and Galectin-3 for prognostication of cardiovascular death in heart failure patients . Int J Cardiol 2015 ; 189:185 – 7 . 6 Gruson D et al . Head to head comparison of intact and C-terminal fibroblast growth factor 23 in heart failure patients with reduced ejection fraction . Int J Cardiol 2017 ; 248:270 – 3 . 7 Gruson D et al . Testing for soluble ST2 in heart failure patients : Reliability of a point of care method . Clin Lab 2017 ; 63 ( 1 ): 141 – 5 . 8 Lepoutre T et al . Measurement Nt-proBNP circulating concentrations in heart failure patients with a new point-ofcare assay . Clin Lab 2013 ; 59 ( 7-8 ): 831 – 5 . 9 Gruson D et al . Increased soluble ST2 is a stronger predictor of long-term cardiovascular death than natriuretic peptides in heart failure patients with reduced ejection fraction . Int J Cardiol 2014 ; 172 ( 1 ): e250 – 2 . 10 Gruson D , Ko G . Laboratory medicine and mobile health technologies at crossroads : Perspectives for the management of chronic diseases . Crit Rev Clin Lab Sci 2016 ; 53 ( 5 ): 352 – 7 .