A Blood Test for Diastolic Dysfunction
Abstract
Portfolio Category: Cardiovascular Health Topic Area: Cardiomyopathy Strategic Goals: Develop strategies to enable detection of associated cardiovascular conditions before clinical symptoms are apparent. There are two types of heart failure (HF). One where the heart fails to contract sufficiently, known as systolic HF, and one where the heart fails to relax properly, known as diastolic HF. When the heart does not relax properly, it does not fill to the proper extent, so that even when contraction is adequate, there is insufficient blood in the chamber to eject. In both systolic and diastolic HF, the heart does not eject enough blood. When this happens, a patient experiences the symptoms of blood building up in the lungs and periphery that include shortness of breath and peripheral fluid accumulation. Systolic and diastolic HF are approximately equal in prevalence in the worldwide community, and they both have a similar mortality, which is roughly equivalent to locally invasive lung cancer (30% survival at 5 years). There are many medical and surgical options for systolic HF, but what has become clear is that these therapies do not work for diastolic HF. Therefore, it is important to distinguish these two types of HF. This can be done by imaging the heart, but it is expensive and time-consuming, usually only done after symptoms occur. Diastolic HF is preceded by a period of asymptomatic diastolic relaxation dysfunction. This period allows an ideal time to intervene in the disease process. Patients are at increased risk of HF but have not yet developed the disease. This application sets out to develop a simple, inexpensive blood test to identify diastolic dysfunction (DD), a prerequisite of diastolic HF. Through a decade of research, we have established that hypertension and diabetes mellitus induced DD is associated with a chemical modification of a cardiac-specific contractile protein, cardiac myosin binding protein C (cMyBP-C). This modified protein can also be found in blood, and we have preliminary evidence that its presence in blood is highly associated with cardiac DD. Hypothesis: This application sets out to validate a simple, inexpensive blood test to identify DD. Currently, diagnosis depends on costly, time-consuming imaging procedures that are only undertaken after symptoms develop. We have shown in animals (mice and monkeys) and humans that a modified contractile protein cMyBP-C in blood may serve as a marker of DD. We propose to do a non-interventional human clinical study to validate our animal and preliminary human data. Specific Aim: We will test if our proposed marker is increased in the blood of DD patients without HF when compared with age-matched control patients without DD or HF. Further, we will test if in plasma, the marker correlates with severity of DD as measured by cardiac imaging. Impact: A blood test for DD could revolutionize HF care by providing definitive diagnosis of DD patients in an expedient, cost-effective manner. It could allow for determining the prognosis and eligibility of novel therapies, and it could improve diagnostic accuracy and save time for correct treatment of HF patients. A blood test detecting asymptomatic DD could allow for therapy to prevent HF. While therapies are limited for DD or diastolic HF, the Principal Investigator is developing orally bioavailable compounds for use in DD, and there are other promising avenues, suggesting specific therapies will be available for this prevalent condition soon.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310042
Entities
People
- Samuel Dudley
Organizations
- United States Army
- University of Minnesota