Methods for diagnosing heart failure and other cardiac diseases
The invention relates to methods of diagnosing the severity of heart failure or a cardiac dysfunction in a subject. The invention further relates to monitoring the severity of heart failure in a subject and determining the prognosis of a subject that has suffered from heart failure. This invention also relates methods to identify patients at risk for cardiac dysfunction when exposed to cardiotoxic chemotherapy agents.
1. A method for providing a prognosis of heart failure severity in a subject having suffered from heart failure, said method comprising:
obtaining a biological sample from said subject;
contacting said sample with an antibody that specifically binds to Neuregulin-1β(NRG-1β) to form an antibody-NRG-1β complex;
measuring the amount of the antibody-NRG-1β complex to determine the level of expression of NRG-1β in the subject; and
comparing said level of expression of NRG-1β in the subject to that of a pre-determined standard to determine the level of NRG-1β over-expression or under-expression in said subject relative to the standard;
determining the heart failure severity in the subject, wherein the level of over-expression of NRG-1β in the subject indicates the heart failure severity in the subject.
2. The method of claim 1 , further comprising the steps of measuring the level of expression of BNP in the sample compared to a standard for BNP expression, and determining the heart failure severity in the subject based on the expression levels of both NRG-1β and BNP, thereby improving the indication of heart failure severity over either NRG-1β or BNP alone.
3. The method of claim 1 , wherein said heart failure is ischemic heart failure or nonischemic heartfailure, hypertensive heart disease, inflammatory heart disease, valvular heart disease, coronary heart disease, cardiomyopathy, cardiovascular disease, or chemotherapy-related disease.
4. The method of claim 1 , wherein the level of expression of NRG-1β is independently associated with transplant-free survival.
5. The method of claim 1 , wherein said subject is being monitored for the severity of heart failure.
6. The method of claim 1 , wherein said subject is undergoing chemotherapeutic therapy.
7. The method of claim 1 , wherein said biological sample is blood, sera, plasma, tissue biopsy, organ biopsy or a combination thereof.
8. The method of claim 1 , whereby the standard is taken from a subject or pool of subjects correctly diagnosed as being healthy.
9. The method of claim 1 , wherein sustained over-expression in circulating NRG-1β levels are associated with a subsequent increased risk of hospitalization for heart failure and cardiovascular death.
10. The method of claim 1 , wherein circulating NRG-1β levels are associated with progressive concentric cardiac remodeling and hypertrophy in a linear fashion in said subject.
11. The method of claim 1 , wherein said antibody that specifically binds to Neuregulin-1β is not cross-reactive with NRG-1α or epidermal growth factor.
12. The method of claim 1 , wherein the contacting and measuring steps comprise performing an immunoassay selected from the group consisting of enzyme immune assay (EIA), a radioimmune assay (RIA), a Western blot assay, and a slot blot assay.
13. The method of claim 12 , wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA).
14. The method of claim 13 , wherein the ELISA is an indirect sandwich ELISA.