Project: Development of a novel test for the diagnosis, monitoring and prognosis of cardiac ischemia
This project aims to develop a novel early stage diagnostic and prognostic test for Cardiac Ischemia (CI) in patients before myocardial damage has occurred. The test will also be able to monitor treatment response. This tool will be based on a unique set of biomarkers that was recently discovered by Dr. Duckers. Cardiovascular diseases (CVDs) are the number one cause of death in the world. In 2008, an estimated 17.3 million people died from CVDs, which represents 30% of all global deaths. CVDs are projected to reCO the leading cause of death with an estimated 23.6 million deaths in 2030(1). The costs in 2010 for CVD in the US were estimated to be 444 billion US dollars(2). The costs related to CVD in Europe were 169 billion Euros in 2003 and is continuously increasing(3). More than 50% of CVD patients suffer from CI, which is a term for conditions of decreased blood supply to the heart by the constriction or occlusion by the atherosclerotic plaques of coronary blood vessels (Fig. 1). CI is the most common manifestation of CVD that eventually leads to myocardial damage due to irreversible loss of cardiomyocytes._x000D__x000D_In 50% of the cases of CI, the first manifestation is an acute myocardial infarction, whereas the other 50% experiences transient episodes of chest pain without actual myocardial necrosis, also referred to as Angina Pectoris (AP). If patients would be diagnosed with CI before the occurrence of myocardial damage, immediate medical intervention would be simple and effective, either by timely pharmacotherapy or surgical percutaneous intervention to re-open a narrowed artery. Early diagnosis also allows preventive measures, including lifestyle adjustment and pharmacological regimen. The current procedures to diagnose chest pain are laborious, time-consuming and expensive, and usually involve a standard exercise test combined with an electrocardiogram (ECG) and blood-based assays. If no conclusive diagnosis is obtained, patients require expensive and invasive imaging techniques to evaluate perfusion and function of the heart muscle. Unfortunately, the current practice has limited diagnostic value (sensitivity 71%). An ECG only shows signs of ischemia during an actual ischemic period, whereas blood-based tests are only able to detect myocardial damage. A significant number of patients is unable to achieve the minimal exercise intensity for a reliable diagnosis of CI, due to poor exercise tolerance. As a result, about 50% of all AP patients cannot be reliably diagnosed and require additional assessment by nuclear imaging or multislice CT imaging, which is laborious, cost intensive and requires specialized infrastructure and expertise. There is a clear need for accurate, reliable and rapid diagnostics that can detect CI to allow early diagnosis and medical intervention to prevent severe complications. _x000D__x000D_Recent exciting discoveries of Dr. Duckers of the University Medical Centre Utrecht (UMCU) revealed that expression of specific novel genes involved in vasculogenesis (new vessel development) is indicative for ischemia(4). Duckers has shown that Endothelial Progenitor Cells (EPCs) become activated under conditions of ischemia to initiate new vessel formation to restore oxygen transport to the heart muscle. As a result of their activation, EPCs present a unique gene expression profile. EPCs are present in peripheral blood and are essential for blood vessel formation and ischemic damage repair in the heart. Genes that are specifically expressed in activated EPCs can thus serve as biomarkers for CI. 80 novel biomarkers have been identified and will be used to develop a diagnostic tool for AP patients that will also be capable of monitoring the course of disease and therapy response. This will allow timely adjustment of medical intervention and prevention of the occurrence of late stage conditions, including chronic ischemia, acute myocardial infarction and heart failure. This tool would be a major step forward in the field of CI diagnostics and treatment._x000D__x000D_To develop this diagnostic test, the 80 biomarkers will be assessed and validated for diagnostic and prognostic use, using the strong expertise of two leading SMEs (CardioGenx and Firalis) in biomarker discovery and validation. From these biomarkers, the most discriminating and clinically relevant diagnostic and prognostic markers will be identified to be developed into a diagnostic assay. For biomarker selection and validation, well-characterized patient samples are required, which will be provided by University Medical Center Utrecht (UMCU) and the University of Strasbourg (NHC). After selection of the biomarker profile and optimization and validation of the sample preparation procedure by CardioGenx, Firalis will use their specific expertise to develop a prototype multiplex PCR assay for these specific marker sets. The prototype diagnostic multiplex PCR assay will be validated in patient cohorts at UMCU and UoS to achieve Proof of Principle._x000D_
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Acronym
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DIACARDIS
(Reference Number: 7964)
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Duration
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01/04/2013 - 31/03/2016
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Project Topic
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Cardiovascular diseases (CVD) are the global number 1 cause of death. Most of these CVD patients suffer from Cardiac Ischemia (CI). This project aims to develop a novel blood test for accurate, rapid and cost-effective diagnosis, monitoring and prognosis of CI before myocardial damage has occurred.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 9
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Project partner
