Heart Disease

Evaluating Cardiovascular Phenotypes Using Induced Pluripotent Stem Cells

Coronary Artery Disease (CAD) – the most significant cause of death and disability in the developed world – offers an example of a paradox in translational genomics. Heritability estimates reveal a significant contribution made by an individual’s genetic makeup to the risk of developing CAD. Yet extensive genome-wide scans have so far not provided a simple path from a personal genome to customized therapies.

At the Scripps Translational Science Institute (STSI), researchers are investigating whether this gap exists due to the lack of appropriate tools to analyze genetic findings in an individualized fashion. By developing an approach using induced Pluripotent Stem Cells (iPSCs) in combination with next-generation genetic engineering, this study seeks to determine the impact of specific genetic variants on CAD.

Comprehensive Molecular and Morphologic Characterization of Circulating Endothelial Cells

Chest pain is a leading reason for patients to seek medical evaluation. Currently available tests can diagnose a heart attack, however, a number of patients who present to an emergency room with chest pain do not test positive and are discharged, only for some of them to suffer from a heart attack or sudden cardiac death in subsequent days.

There is currently no biomarker for an impending cardiac event. Scientists at STSI have demonstrated that elevated numbers of Circulating Endothelial Cells (CECs) are indicative of the pathophysiology leading to heart attack and have built on this discovery to define a molecular signature predictive of heart attack. This was accomplished by defining a gene expression signature, first identified by us in CECs, but also present in the whole blood of heart attack patients. This signature forms the basis of a predictive test for impending heart attack that is currently being validated.

Genomic Risk Markers for Atrial Fibrillation Following Cardiac Rhythm Monitoring

Atrial fibrillation (AFib) is the most commonly encountered heart arrhythmia. About 20% of strokes are known to be caused by documented AFib. However, because AFib is often undocumented and difficult to detect, it is thought that the true proportion of strokes due to this type of heart arrhythmia may be much higher.

More effective screening strategies of AFib, a treatable condition, have the potential to significantly reduce the morbidity associated with stroke. The Genomic Risk Markers for Atrial Fibrillation Following Extended Cardiac Monitoring (GIRAFFE) study is designed to determine whether genetic risk scores for AFib can identify individuals at high risk of undiagnosed AFib.

During study enrollment, patients presenting to their outpatient doctor with symptoms leading to high clinical suspicion of AFib and at least one clinical risk factor of AFib were recruited to have genetic testing and to wear an ambulatory cardiac rhythm monitor called ZIO Patch for two weeks.

Over 900 participants successfully completed the study.

Publications

• Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction, Physical Biology 2014
• Characterization of circulating endothelial cells in acute myocardial infarction, Science Translational Medicine 2012