ST2Based Precision Medicine in Device Management

Authors: Antoni BayesGenis

Publish Date: 2016/10/24

Volume: 9, Issue: 5-6, Pages: 419-420

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Abstract

“The Precision Medicine Initiative is an innovative approach that aims to develop and consolidate a medical model based on the ‘customization’ of healthcare with medical decisions practices and/or products being tailored to the individual patient” President Barack Obama Announcement of the Precision Medicine Initiative in the State of the Union Address January 20 2015On January 20 2015 President Obama announced the Precision Medicine Initiative PMI in his State of the Union address Through advances in research technology and policies that empower patients the PMI aims to enable a new era of medicine in which researchers providers and patients work together to develop individualized care https//wwwwhitehousegov/precisionmedicine The cancerfocused component of this initiative will be designed to address some of the obstacles that have already been encountered in “precision oncology” unexplained drug resistance genomic heterogeneity of tumors insufficient means for monitoring responses and tumor recurrence and limited knowledge about the use of drug combinations 1Heart disease killer number 1 in western countries and one of the most serious emerging threats in developing countries cannot afford sitting and waiting to follow the path of cancer but instead the cardiovascular field needs to be audacious to promote specific cardiovascular precision medicine programs The challenge is enormous but the benefits greatly outweigh inactivity In the past three decades cardiovascular research has been the driving force behind the lengthened life expectancy Indeed from 1980 to 2009 life expectancy at birth in Spain increased by more than 6 years for both sexes The contribution of the decrease in cardiovascular mortality to the total increase in life expectancy at birth was 63  among women and 53  among men Among the ≥65yearold age group this contribution was 93  among women and 87  among men 2 If this was achieved with imprecision medicine the potential of cardiovascular research in the era of precision medicine has no limitsBiomarkers now have an established role in aiding with diagnosis and prognostication in a number of cardiovascular diseases nevertheless their role in patient monitoring and personalized care is at present illdefined Although a large number of candidate biomarkers have been evaluated to help fill this gap few have survived the rigorous studies that are a prerequisite to translation into the clinical realm ST2 is recently emerging as a bona fide biomarker for patient careST2 is a member of the IL1 receptorlike family of proteins Through alternative splicing ST2 is found in multiple isoforms including a transmembrane form ST2 ligand or ST2L and a soluble circulating form sST2 In response to mechanical stress cardiomyocytes and fibroblasts express both ST2L and sST2 hereafter referred to simply as “ST2” Soluble ST2 is thought to act as a decoy receptor for IL33 The presence of high levels of ST2 blocks the favorable effects of IL33 by limiting activation of the cascade triggered by the IL33/ST2L interaction Higher levels of ST2 are thereby associated with increased myocardial fibrosis adverse cardiac remodeling and worse cardiovascular outcomes 3Whether ST2 may be valuable in predicting sudden death and arrhythmia is uncertain Indeed the prediction and prevention of sudden death remains a major challenge in the management of patients with chronic heart failure HF Sudden death is the cause of 50  of all HF deaths mainly affecting patients with mildtomoderate symptoms and the number of patients with HF at risk is increasing The challenge lies in identifying patients with HF who are at significant risk of sudden death Severe left ventricular systolic dysfunction has long been recognized as a risk factor for sudden death yet left ventricular ejection fraction LVEF lacks enough sensitivity and specificity by itselfIn the present study Skali et al 4 provide data on a biomarker substudy of the MADITCRT Trial The authors report that both baseline and serial elevated ST2 levels ≥35 ng/mL were predictive of an increasing risk of death HF or ventricular arrhythmic events This study shows that for every 10  increase in ST2 levels at 1 year there was an increased risk of ventricular arrhythmias or death during followup regardless of randomization arm in MADITCRTPreviously PascualFigal et al found in an ambulatory HF population that elevation of ST2 and NTproBNP above the cutoff values was associated with a very high rate 71  of sudden death and interestingly a very low rate 4  of sudden death existed when both markers were below the cutoff thresholds 5 Given the increased risk of sudden death and ventricular arrhythmias found in these two studies in HF patients with elevated ST2 it is conceivable that action should be taken at the individual patient levelWe have been quite successful in the past decades using imprecise medicine Incorporation of precision medicine tools will likely be beneficial for our patients and moreover it will make us better doctors Biomarkers such as ST2 and other ie natriuretic peptides troponins are already FDA/CE approved and are ready for incorporation in personalized decision algorithms

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