Driving Biomedical Projects

The software development phase of projects such as the CVRG must be closely linked with specific, underlying driving biomedical projects (DBPs) to assure that resource development is driven by real-world needs prior to software release to the general community. There are currently eight DBPs for the CVRG, listed below. These DBPs provide a rich set of use cases that drive CVRG technology development. The tools are fed back to the DBPs and an iterative process of technology development, feedback, and refinement is established.

CARDIA Study:

The original objectives of CARDIA were to document levels of risk factors for coronary artery disease and potential determinants of these risk factors in young adults; to study the interrelationships of risk factors and lifestyles and to document behavioral and environmental changes during the transition from adolescence to middle age; to compare cross-sectional and longitudinal data on age-related trends in cardiovascular disease risk factors; and to compare levels and evolution of risk factors between men and women, blacks and whites, and in groups of differing socioeconomic status.

CTRIP:

The principal aim of the Cardiac Translational Research Implementation Program (CTRIP) is to test the hypothesis that personalized risk assessment of patients for sudden cardiac death and heart failure development and progression is both feasible and efficient combining sequential electrocardiographic (ECG) and cardiac magnetic resonance imaging (MRI) diagnostic approaches.  CTRIP intends to detect prior myocardial infarct or fibrosis (scar) using an automated algorithm involving 12-lead ECG QRS scoring followed by detailed characterization of myocardial scar by contrast-enhanced MRI.

D. W. Reynolds Cardiovascular Clinical Research Center:

The Reynolds Project is a Driving Biomedical project for the CVRG. The CVRG is managing multi-scale data from this project that is being used to identify factors that predict risk of Sudden Cardiac Death and patients who should receive implantable cardioverter defibrillator placement.

Sudden Cardiac Death (SCD), subsequent to Coronary Artery Disease (CAD) accounts for approximately half of all heart disease-related deaths per year. Risk is sufficiently high in patients with prior myocardial infarction and left ventricular (LV) dysfunction that placement of implantable cardioverter-defibrillators (ICDs) produces a significant reduction of mortality. 3-4 million Americans may now be considered as candidates for prophylactic ICDs. However, wholesale deployment of ICDs in large populations of patients is economically impractical and ignores the fact that the majority of patients are likely never to require them. The challenge is to be able to predict reliably which patients with CAD are at highest risk for SCD so that they may receive ICDs. To address this problem, investigators of the D. W. Reynolds Cardiovascular Clinical Research Center at JHU are collecting SNP, transcriptional, proteomic, imaging and electrophysiological (ECG) data from a large (~1,200) patient population diagnosed with CAD and LV dysfunction and who have received ICD placement. Both prior and subsequent to ICD delivery (in follow up visits), patients undergo: a) clinical electrophysiological evaluation; b) multi-modal imaging including tagged MR, functional imaging of high-energy phosphate content, ATP production, myocardial regional sodium distribution and Gd-enhanced MRI and CT to assess cardiac structure, mechanical and metabolic function; c) gene and protein expression profiling from whole-blood extracts using DNA microarrays and proteomic assays; and d) sequencing of selected genomic regions to identify polymorphisms. Over time, this patient population will separate into two groups – those with appropriate ICD firings (the “high risk” group) and those without firings (the “low risk” group). All data collected at each time point will then be compared across the low- and high-risk populations to determine bio-markers that predict risk for SCD. The utility of these biomarkers will be tested in a separate validation cohort of approximately 520 patients collected during the final two years of the study. The Reynolds Project is funded from 2003 through 2008 and is renewable for an additional five years.

Emory-Morehouse Partnership (EMP) to reduce CV disparities:

The purpose of this study is to advance the scientific understanding of how to best help Metabolic Syndrome patients make healthy lifestyle changes. It is a community centered intervention study.

The Hypertrophic Cardiomyopathy Consortium:

The Hypertrophic Cardiomyopathy Consortium is a consortium of investigators from the Johns Hopkins University, Mayo Clinic, University of Texas, Harvard University, Duke University, University of Leiden, University of Athens, University of Copenhagen, Osaka City University, and the Hypertrophic Cardiomyopathy Association who are working to understand the basis and treatment of HCM in young adults. The CVRG is providing the underlying infrastructure supporting this project. The HCMC is now funded for 2 years through NHLBI’s PAR-07-426 grant.

Jackson Heart Study:

The purpose of this study is to investigate of cardiovascular disease among African Americans. It is a population-based prospective longitudinal study.

Multi-Ethnic Study of Artherosclerosis (MESA):

The MESA is a Driving Biomedical Project for the CVRG. MESA is investigating the prevalence, correlates, and progression of subclinical CVD and risk factors that predict progression to clinically overt CVD, and that predict progression of subclinical disease itself, in a population-based sample of 6,800 ethnically diverse men and women. The CVRG is working with the MESA MR and ECG Reading Centers in integrated data management supporting federated queries and data exploration.

Prose-ICD Study:

The overall hypothesis of this study is that subtle interactions between structural (substrate) and functional (trigger) abnormalities of the heart, some of which are genetically-determined, can be used to identify patients at high risk of sudden cardiac death (SCD). Such information may be used to better define patients most likely to benefit from implantation of an internal defibrillator (ICD). The prospective, observational study to enroll, categorize and follow patients who receive an ICD for primary prevention of SCD (PROSE-ICD) was established to:

1. To gain a better understanding of the biological mechanisms that predispose to SCD.
2. To develop readily determined clinical, electrocardiographic, genetic and blood protein markers identify patients with an increased risk of dying suddenly.

The Minority Health Grid:

The Minority Health Genomics and Translational Research BIo-Repository Database (MH-GRID) Network infrastructure will facilitate the ascertainment of biospecimens, the collection of multi-dimensional data elements and the tracking of patient outcomes in an electronic health records (EHRs)-linked data warehouse within a consortium of minority clinics.