McDevitt Cardiac Diagnostic Research: Implications and Purpose

Coronary heart disease (CHD) is caused by atherosclerosis, an inflammatory condition which results in plaque formation and narrowing of the coronary arteries. CHD is likely to produce angina pectoris (chest pain), heart attack or both. According to the American Heart Association, the following dire morbidity and mortality statistics are associated with this disease in the United States alone:

• CHD was responsible for 479,305 deaths in 2003
• CHD is the primary cause of death in America today
• 13,200,000 people (7,200,000 males and 6,000,000 females) living today have
  experienced a heart attack, angina or both
• 1.2 million Americans are expected to have a new or recurrent coronary event this year
• Approximately, 330,000 people a year will die of coronary attack inside or outside of the emergency room

In its initial, but crucial stages, CHD is indeed a silent disease whereby a series of molecular events occur within the vasculature, long before the obvious clinical manifestations of acute coronary syndrome (ACS), which includes acute myocardial infarction (AMI) and angina, begin to ensue. In spite of improved treatments for CHD, ACS often results in sudden death or permanent disability in a substantial percentage of patients, mostly because of a) the inability to efficiently test for all relevant cardiac biomarkers in a comprehensive manner and to establish an accurate assessment of the risk for having a heart attack and b) the lack of suitable point-of-care (POC) devices that would enable physicians and emergency care professionals to accurately and timely diagnose the actual event of a heart attack when it occurs.

In the McDevitt laboratory, we are now in the process of developing and testing the next generation of diagnostic tools that can aid in the assessment of cardiac risk factors. Here we address the need for multiplexed protein- and cellular-based assays for a more efficient screening of CHD and a more prompt diagnosis of cardiac events. The creation of an extensive cardiac panel on a dual-function highly customizable assay platform as developed in our laboratories promises to promote the inclusion of risk factors that have never been measured simultaneously on a single assay platform before. Furthermore, the development of ultra sensitive assays on our assay platform promise to help promote alternative and less-invasive diagnostic procedures that could reveal new patterns of association between cardiac disease and other systemic conditions. Likewise, we have begun to establish a bridge between lab-on-a-chip biosensor approaches and oral fluid diagnostics. The opportunities that are afforded through the marriage of the bead-based lab-on-a-chip system with salivary diagnostics are vast. The ability to monitor general health status, to evaluate both local and systemic diseases through their onset and progression, and the ability to influence treatment outcomes through non-invasive means are indeed attractive goals for this ongoing program.

The following significant contributions have been made by the McDevitt group in these areas:

1. First cardiac risk assessment chip developed and tested, 2002.
2. Multiplexed protein fingerprint method pioneered, 2002.
3. Exceeded the capacity of all FDA approved CRP detection kits, 2004.
4. Further reduced limit of detection by 10,000 for CRP using advanced bead-array testing methods, 2005.
5. Established method for CRP detection within saliva matrices, 2005.
6. Defined the physiological range for CRP in normal healthy, periodontitis and edentulous patients, 2005.
7. Developed first dual platform cellular analysis and protein detection method, 2005.