Identifying patients at risk for life threatening arrhythmias

• US 7,608,458 B2
• Filed: 06/21/2005
• Issued: 10/27/2009
• Est. Priority Date: 02/05/2004
• Status: Expired due to Fees

• Current Assignee: Yougene Corp.
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Soykan, Orhan, Sharma, Vinod, Olson, Walter H., Dearking, Amy C., Robinson, Timothy H.
• Primary Examiner(s): Marcheschi; Michael A
• Assistant Examiner(s): Hurst; Jonathan M
• Application Number:
  US11/157,549
• Publication Number:
  US 20050266576A1
• Time in Patent Office: 1,589 Days
• Field of Search: 436/86, 600/508, 600/515
• US Class Current: 436/86
• CPC Class Codes: G01N 2800/326 Arrhythmias, e.g. ventricular fibrillation, tachycardia, atrioventricular block, torsade de pointes
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The invention is a method for identifying proteins associated with sudden cardiac death (SCD) and for assessing a patient'"'"'s risk of SCD by determining the amount of one or more SCD-associated proteins in the patient. Typically, the patient submits a sample, such as a blood sample, which is tested for one or more SCD-associated proteins. Based upon the results of the tests, the patient'"'"'s risk of SCD may be assessed.

Claims

1. A method of assessing a patient for risk of sudden cardiac death (SCD), the method comprising:

determining an amount of at least one SCD-associated protein in the patient;

assessing the risk as a function of the determination;

determining occurrence of at least one class identifier that assesses the patient as having increased risk of SCD;

combining results of the occurrence of the class identifier and the amount of SCD-associated protein;

wherein assessing the patient is based on the combined results; and

wherein the SCD-associated protein is selected from a group of proteins having characteristics consisting of 10,146.5 Da and pI=9+;

15,006 Da and pI=9+;

166,582 Da and pI=5-7;

10,948 Da and pI=9+;

11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

2. The method of claim 1, wherein the at least one SCD-associated protein is identified by measuring a mass of the protein, measuring a mass-to-charge ratio of the protein with a mass spectrometer, and measuring an isoelectric pH (pI) of the protein.

3. The method of claim 1, wherein the amount of SCD-associated protein in the patient that indicates increased risk of SCD is one of higher and lower than an amount of SCD-associated protein in a patient having no increased risk of SCD.

4. The method of claim 1 wherein the SCD-associated protein is used as a therapeutic agent.

5. A method of identifying patients that would benefit from an implanted medical device, the method comprising:

identifying at least one SCD-associated protein;

determining an amount of SCD-associated protein from a protein-containing sample from a patient;

assessing whether the patient would benefit from an implanted medical device based on the amount of the SCD-associated protein

wherein the implanted medical device is an electronic stimulation device; and

wherein the SCD-associated protein is selected from a group of proteins having characteristics consisting of 10,146.5 Da and pI=9+;

15,006 Da and pI=9+;

166,582 Da and DI=5-7;

10,948 Da and pI=9+;

11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

6. The method of claim 5 wherein identifying at least one SCD-associated protein further comprises:

collecting protein-containing samples from patients having increased risk of SCD;

collecting protein-containing samples from patients having no increased risk of SCD;

identifying at least one protein from the protein-containing samples whose amount differs between patients having increased risk of SCD and patients having no increased risk of SCD; and

wherein the identified proteins are SCD-associated proteins.

7. The method of claim 5 wherein assessing is achieved with an algorithm comprising determination of at least one SCD-associated protein selected from a group of proteins having characteristics consisting of 11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

8. The method of claim 7 wherein the algorithm further comprises determination of a class identifier associated with SCD.

9. A method of identifying a SCD-associated protein comprising:

collecting first protein-containing samples from patients having increased risk of SCD;

collecting second protein-containing samples from patients having no increased risk of SCD;

determining amounts of proteins in the first and second protein-containing samples; and

identifying a protein having an amount that differs between the first and second protein-containing samples;

wherein the SCD-associated protein is selected from a group of proteins having characteristics consisting of 10,146.5 Da and pI=9+;

15,006 Da and pI=9+;

166,582 Da and pI=5-7;

10,948 Da and pI=9+;

11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

10. The method of claim 9, wherein the amount that differs between the first and second protein-containing samples comprises one of presence of the protein, absence of the protein, increased amount of the protein, decreased amount of the protein, and change of concentration of the protein over a time period.

11. The method of claim 9 wherein the identified protein is described by molecular weight and Isoelectric pH.

12. The method of claim 11 wherein the identified protein is further described by mass-to-charge ratio.

13. A method of assessing a patient for risk of sudden cardiac death (SCD), the method comprising:

determining an amount of at least one SCD-associated protein in the patient; and

assessing the risk based on the determined amount of SCD-associated protein wherein the SCD-associated protein is selected from a group of proteins having characteristics consisting of 10,146.5 Da and pI=9+;

15,006 Da and pI=9+;

166,582 Da and pI=5-7;

10,948 Da and pI=9+;

11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

14. The method of claim 13, wherein the at least one SCD-associated protein is identified by measuring a mass of the protein, measuring a mass-to-charge ratio of the protein with a mass spectrometer, and measuring an isoelectric pH (pI) of the protein.

15. The method of claim 13, wherein the amount of SCD-associated protein in the patient that indicates increased risk of SCD is one of higher and lower than an amount of SCD-associated protein in a patient having no increased risk of SCD.

16. The method of claim 13 wherein the SCD-associated protein is used as a therapeutic agent.

17. A method of identifying patients that would benefit from an implanted medical device, the method comprising:

identifying at least one SCD-associated protein;

determining an amount of SCD-associated protein from a protein-containing sample from a patient;

assessing whether the patient would benefit from an implanted medical device based on the amount of the SCD-associated protein, wherein the SCD-associated protein is selected from a group of proteins having characteristics consisting of 10,146.5 Da and pI=9+;

15,006 Da and pI=9+;

166,582 Da and pI=5-7;

10,948 Da and pI=9+;

11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

18. The method of claim 17 wherein identifying at least one SCD-associated protein further comprises:

collecting protein-containing samples from patients having increased risk of SCD;

collecting protein-containing samples from patients having no increased risk of SCD;

identifying at least one protein from the protein-containing samples whose amount differs between patients having increased risk of SCD and patients having no increased risk of SCD; and

wherein the identified proteins are SCD-associated proteins.

19. The method of claim 17 wherein the implanted medical device comprises at least one of an electronic stimulation device and a drug delivery device.

20. The method of claim 17 wherein assessing is achieved with an algorithm comprising determination of at least one SCD-associated protein selected from a group of proteins having characteristics consisting of 11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

21. The method of claim 20 wherein the algorithm further comprises determination of a class identifier associated with SCD.

22. A method of assessing a patient for risk of sudden cardiac death (SCD), the method comprising:

determining the presence or absence of at least one SCD-associated protein in the patient;

assessing the risk as a function of the determination;

determining occurrence of at least one class identifier that assesses the patient as having increased risk of SCD;

combining results of the occurrence of the class identifier;

wherein assessing the patient is based on the combined results; and

wherein the SCD-associated protein is selected from a group of proteins having characteristics consisting of 10,146.5 Da and pI=9+;

15,006 Da and pI=9+;

166,582 Da and pI=5-7;

10.948 Da and pI=9+;

11,991 Da and pI=5-7;

10,552.4 Da and pI=9;

43,529.4 Da and pI=9; and

13,806.8 Da and pI=9.

23. The method of claim 22, wherein the at least one SCD-associated protein is identified by measuring a mass of the protein, measuring a mass-to-charge ratio of the protein with a mass spectrometer, and measuring an isoelectric pH (pI) of the protein.

24. The method of claim 22, wherein the amount of SCD-associated protein in the patient that indicates increased risk of SCD is one of higher and lower than an amount of SCD-associated protein in a patient having no increased risk of SCD.

25. The method of claim 22 wherein the SCD-associated protein is used as a therapeutic agent.