Methods of identifying a subject as having heart failure

• US 9,568,481 B2
• Filed: 10/26/2011
• Issued: 02/14/2017
• Est. Priority Date: 04/24/2006
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Snider, James V., Jacobson, Sven
• Primary Examiner(s): Cheu, Jacob
• Application Number:
  US13/282,111
• Publication Number:
  US 20120040381A1
• Time in Patent Office: 1,938 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2333/54 Interleukins [IL]
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/12 Pulmonary diseases
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

Measurement of circulating ST2 and/or IL-33 concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, and the detection of severe disease.

Claims

1. A method of identifying, a subject having undiagnosed chest pain or undiagnosed chest discomfort as having heart failure, the method comprising:

(a) selecting a subject having undiagnosed chest pain or undiagnosed chest discomfort;

(b) performing an immunoassay to determine a level of soluble ST2 in a biological sample from the selected subject;

(c) performing an immunoassay to determine a level of one or more adjunct biomarkers selected from the group consisting of;

N-terminal (NT)-pro-brain natriuretic peptide (BNP), BNP, NT-pro-atrial natriuretic peptide (ANP), proANP, and ANP in a biological sample from the selected subject;

(d) comparing the level of soluble ST2 in the selected subject to a reference level of soluble ST2;

(e) comparing the level of the one or more adjunct biomarkers in the selected subject to a reference level of the one or more adjunct biomarkers; and

(f) identifying a selected subject having an elevation in the level of soluble ST2 compared to the reference level of soluble ST2 and an elevation in the level of the one or more adjunct biomarkers compared to the reference level of the one or more adjunct biomarkers as having heart failure by performing echocardiography.

2. The method of claim 1, wherein the reference level of soluble ST2 is a level of soluble ST2 in a subject that has no disease or has no acute disease.

3. The method of claim 1, wherein the reference level of soluble ST2 is a threshold level of soluble ST2.

4. The method of claim 1, wherein the subject in step (a) is previously undiagnosed.

5. The method of claim 1, wherein the biological sample in step (b) and step (c) comprises serum or plasma.

10. The method of claim 1, wherein the method is performed in an outpatient clinic.

12. The method of claim 1, wherein the immunoassay to determine the level of soluble ST2 is an enzyme-linked immunosorbant assay (ELISA).

14. The method of claim 1, wherein the immunoassay to determine the level of soluble ST2 utilizes a monoclonal antibody.

18. The method of claim 14, wherein the immunoassay to determine the level of soluble ST2 utilizes two different monoclonal antibodies that specifically bind to soluble ST2.

21. The method of claim 1, wherein the subject has undiagnosed chest pain.

22. The method of claim 1, wherein the subject has undiagnosed chest discomfort.

6. A method for identifying a subject having undiagnosed chest pain or undiagnosed chest discomfort as having heart failure, the method comprising:

(a) selecting a subject having undiagnosed chest pain or undiagnosed chest discomfort;

(b) performing an immunoassay to determine a level of soluble ST2 in a biological sample from the selected subject;

(c) performing an immunoassay to determine a level of one or more adjunct biomarkers selected from the group consisting of;

N-terminal (NT)-pro-brain natriuretic peptide (BNP), proBNP, BNP, NT-pro-atrial natriuretic peptide (ANT), proANP, and ANP in a biological sample from the selected subject;

(d) comparing the level of soluble ST2 in the selected subject to a reference level of soluble ST2;

(e) comparing the level of the one or more adjunct biomarkers in the selected subject to a reference level of the one or more adjunct biomarkers; and

(f) identifying a selected subject having an elevation in the level of soluble ST2 compared to the reference level of soluble ST2 and an elevation in the level of the one or more adjunct biomarkers compared to the reference level of the one or more adjunct biomarkers as having heart failure by performing cardiac catheterization.

7. The method of claim 6, wherein the reference level of soluble ST2 is a level of soluble ST2 in a subject that has no disease or has no acute disease.

8. The method of claim 6, wherein the reference level of soluble ST2 is a threshold level of soluble ST2.

9. The method of claim 6, wherein the subject is previously undiagnosed.

11. The method of claim 6, wherein the method is performed in an outpatient clinic.

13. The method of claim 11, wherein the ELISA is a sandwich ELISA.

15. The method of claim 6, wherein the immunoassay to determine the level of soluble ST2 is an enzyme-linked immunosorbant assay (ELISA).

16. The method of claim 15, wherein the ELISA is a sandwich ELISA.

17. The method of claim 6, wherein the immunoassay to determine the level of soluble ST2 utilizes a monoclonal antibody.

19. The method of claim 17, wherein the immunoassay to determine the level of soluble ST2 utilizes two monoclonal antibodies that specifically bind to soluble ST2.

20. The method of claim 6, wherein the biological sample in step (b) and step (c) comprises serum or plasma.

23. The method of claim 6, wherein the subject has undiagnosed chest pain.

24. The method of claim 6, wherein the subject has undiagnosed chest discomfort.