Markers for differential diagnosis and methods of use thereof

• US 20040121343A1
• Filed: 12/27/2002
• Published: 06/24/2004
• Est. Priority Date: 12/24/2002
• Status: Active Grant

• Current Assignee: Quidel Cardiovascular, Inc. (Quidel Corporation)
• Original Assignee: BIOSITE INCORPORATED (Abbott Laboratories)
• Inventors: Maisel, Alan, Buechler, Kenneth F.
• Granted Patent: US 7,713,705 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2333/4737 C-reactive protein
• CPC Class Codes: G01N 2333/475 Assays involving growth factors
• CPC Class Codes: G01N 2333/52 Assays involving cytokines
• CPC Class Codes: G01N 2333/58 Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
• CPC Class Codes: G01N 2333/9123 with a nitrogenous group as acceptor (2.7.3), e.g. histidine kinases
• CPC Class Codes: G01N 2333/96486 Metalloendopeptidases (3.4.24)
• CPC Class Codes: G01N 2333/974 Thrombin
• CPC Class Codes: G01N 2800/326 Arrhythmias, e.g. ventricular fibrillation, tachycardia, atrioventricular block, torsade de pointes
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue
• CPC Class Codes: Y10S 436/804 Radioisotope, e.g. radioimmunoassay

Abstract

The present invention provides methods for the identification and use of diagnostic markers,for differential diagnosis of diseases. In a various aspects, the invention relates to methods and compositions able to determine the presence or absence of one, and preferably a plurality, of diseases that exhibit one or more similar or identical symptoms. Such methods and compositions can be used to provide assays and assay devices for use in determining the disease underlying one or more non-specific symptoms exhibited in a clinical setting.

Claims

1. A method of symptom-based diagnosis of a subject, comprising:

analyzing a test sample obtained from said subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to identify the presence or absence in said subject of a plurality of conditions within the differential diagnosis of a symptom exhibited by said subject; and

correlating the presence or amount of said markers in said test sample to the presence or absence of each of said plurality of conditions.

2. A method according to claim 1, wherein said symptom is selected from the group consisting of dyspnea, fever, chest pain, abdominal pain, disturbances in metabolic state, neurologic dysfunction, hypertension, dizzyness, and headache.

3. A method according to claim 2, wherein said symptom is dyspnea, and said plurality of conditions are selected from the group consisting of asthma, chronic obstructive pulmonary disease (“

COPD”

), tracheal stenosis, obstructive endobroncheal tumor, pulmonary fibrosis, pneumoconiosis, lymphangitic carcinomatosis, kyphoscoliosis, pleural effusion, amyotrophic lateral sclerosis, congestive heart failure, coronary artery disease, myocardial infarction, atrial fibrillation, cardiomyopathy, valvular dysfunction, left ventricle hypertrophy, pericarditis, arrhythmia, pulmonary embolism, metabolic acidosis, chronic bronchitis, pneumonia, anxiety, sepsis, and aneurismic dissection.

4. A method according to claim 3, wherein said plurality of conditions comprise myocardial infarction, pulmonary embolism, and congestive heart failure.

5. A method according to claim 2, wherein said symptom is dyspnea, and said plurality of markers comprise at least one subject-derived marker selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, pulmonary surfactant protein D, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, Atrial natriuretic peptide, a marker related to Atrial natriuretic peptide, and D-dimer.

6. A method according to claim 5, wherein said plurality of subject-derived markers comprise at least one cardiac troponin form, B-type natriuretic peptide or a marker related to B-type natriuretic peptide, and D-dimer.

7. A method according to claim 2, wherein said symptom is chest pain, and said plurality of conditions are selected from the group consisting of stable angina, unstable angina, myocardial ischemia, cardiac necrosis, atrial fibrillation, myocardial infarction, musculoskeletal injury, cholecystitis, gastroesophageal reflux, pulmonary embolism, pericarditis, aortic dissection, pneumonia, anxiety.

8. A method according to claim 7, wherein said plurality of conditions comprise aortic dissection, myocardial ischemia, cardiac necrosis, myocardial infarction, and atrial fibrillation.

9. A method according to claim 2, wherein said symptom is chest pain, and said plurality of markers comprise at least one subject-derived marker selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, creatine kinase MB, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, Atrial natriuretic peptide, a marker related to Atrial natriuretic peptide, smooth muscle myosin heavy chain, and myoglobin.

10. A method according to claim 9, wherein said plurality of subject-derived markers comprise at least one cardiac troponin form, B-type natriuretic peptide or a marker related to B-type natriuretic peptide, and smooth muscle myosin heavy chain.

11. A method according to claim 9, wherein said plurality of subject-derived markers comprise at least one cardiac troponin form and smooth muscle myosin heavy chain.

12. A method according to claim 9, wherein said plurality of subject-derived markers comprise at least one cardiac troponin form, B-type natriuretic peptide or a marker related to B-type natriuretic peptide, Atrial natriuretic peptide or a marker related to Atrial natriuretic peptide, creatine kinase MB, and smooth muscle myosin heavy chain.

13. A method according to claim 2, wherein said symptom is abdominal pain, and said plurality of conditions are selected from the group consisting of aortic dissection, mesenteric embolism, pancreatitis, appendicitis, myocardial ischemia, myocardial infarction, an infectious disease, influenza, esophageal carcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, pancreatic ductal adenocarcinoma, cystadenocarcinoma, and insulinoma.

14. A method according to claim 13, wherein said plurality of conditions comprise aortic dissection, myocardial ischemia, and myocardial infarction.

15. A method according to claim 2, wherein said symptom is abdominal pain, and said plurality of markers comprise at least one subject-derived marker selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, smooth muscle myosin heavy chain, and myoglobin.

16. A method according to claim 15, wherein said plurality of subject-derived markers comprise at least one cardiac troponin form, B-type natriuretic peptide or a marker related to B-type natriuretic peptide, and smooth muscle myosin heavy chain.

17. A method according to claim 15, wherein said plurality of subject-derived markers comprise at least one cardiac troponin form and smooth muscle myosin heavy chain.

18. A method according to claim 2, wherein said symptom is neurologic dysfunction, and said plurality of conditions are selected from the group consisting of stroke, ischemic stroke, subarachnoid hemorrhage, transient ischemic attack, intracerebral hemorrhage, hemorrhagic stroke, brain tumor, cerebral hypoxia, hypoglycemia, migraine, atrial fibrillation, myocardial infarction, cardiac ischemia, peripheral vascular disease, migraine, and seizure.

19. A method according to claim 18, wherein said plurality of conditions comprise ischemic stroke, hemorrhagic stroke, transient ischemic attack, atrial fibrillation, myocardial ischemia, and myocardial infarction.

20. A method according to claim 2, wherein said symptom is neurologic dysfunction, and said plurality of markers comprise at least one subject-derived marker selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, c-reactive protein, creatine kinase-BB, neurotrophin-3, vascular endothelial growth factor, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, Atrial natriuretic peptide, a marker related to Atrial natriuretic peptide, interleukin-6, matrix metalloproteinase-9, S-100β

, thrombin-antithrombin III complex, and a form of von Willebrand factor.

21. A method according to claim 1 wherein said test sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, a urine sample, a saliva sample, a sputum sample, and a pleural effusion sample.

22. A method according to claim 1, wherein said plurality of markers are selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, Atrial natriuretic peptide, a marker related to Atrial natriuretic peptide, pulmonary surfactant protein D, D-dimer, annexin V, enolase, creatine kinase, glycogen phosphorylase, heart-type fatty acid binding protein, phosphoglyceric acid mutase, S-100, S-100ao, plasmin-α

2-antiplasmin complex, β

-thromboglobulin, platelet factor 4, fibrinopeptide A, platelet-derived growth factor, prothrombin fragment 1+2, P-selectin, thrombin-antithrombin III complex, von Willebrand factor, tissue factor, thrombus precursor protein, human neutrophil elastase, inducible nitric oxide synthase, lysophosphatidic acid, malondialdehyde-modified low density lipoprotein, matrix metalloproteinase-1, matrix metalloproteinase-2, matrix metalloproteinase-3, matrix metalloproteinase-9, TIMP 1, TIMP2, TIMP3, C-reactive protein, interleukin-1β

, interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor α

, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule, monocyte chemotactic protein-1, caspase-3, human lipocalin-type prostaglandin D synthase, mast cell tryptase, eosinophil cationic protein, KL-6, procalcitonin, haptoglobin, s-CD40 ligand, S-FAS ligand, alpha 2 actin, basic calponin 1, CSRP2 elastin, LTBP4, smooth muscle myosin, smooth muscle myosin heavy chain, transgelin, aldosterone, angiotensin I, angiotensin II, angiotensin III, bradykinin, calcitonin calcitonin gene related peptide, endothelin 1, endotehlin 2, endothelin 3, renin, vasopressin, APO B48, pancreatic elastase 1, pancreatic lipase, sPLA2, trypsinogen activation peptide, alpha enolase, LAMP3, phospholipase D, PLA2G5, protein D, SFTPC, defensin HBD1, defensin HBD2, CXCL-1, CXCL-2, CXCL-3, CCL2, CCL3, CCL4, CCL8, procalcitonin, protein C, serum amyloid A, s-glutathione, s-TNF P55, s-TNF P75, TAFI, TGF beta, MMP-11, brain fatty acid binding protein, CA11, CABP1, CACNA1A, CBLN1, CHN2, cleaved Tau, CRHR1, DRPLA, EGF, GPM6B, GPR7, GPR8, GRIN2C, GRM7, HAPIP, HIF 1 alpha, HIP2 KCNK4, KCNK9, KCNQ5, MAPK10, n-acetyl aspartate, NEUROD2, NRG2, PACE4, phosphoglycerate mutase, PKC gamma, prostaglandin E2, PTEN, PTPRZ1, RGS9, SCA7, secretagogin, SLC1A3, SORL1, SREB3, STAC, STX1A, STXBP1, BDNF, cystatin C, neurokinin A, substance P, interleukin-1, interleukin-11, interleukin-13, interleukin-18, interleukin-4, and interleukin-10.

23. A method according to claim 1, wherein said analyzing step comprises contacting said test sample with a test surface comprising a plurality of discrete addressable locations each adapted to bind for detection one of said plurality of markers.

24. A method according to claim 23, wherein said plurality of markers are detected in a sandwich immunoassay.

25. A method according to claim 23, wherein said test surface is a porous membrane.

26. A method according to claim 23, wherein said test surface is a nonporous surface.

27. A method according to claim 23, wherein said test surface is within a capillary space.

28. A method according to claim 23, wherein said test surface comprises discrete particles immobilized at said plurality of discrete addressable locations, wherein said discrete particles comprise antibodies bound thereto.

29. A test device for performing a symptom-based diagnotic method, wherein said method comprises analyzing a test sample obtained from a subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to identify the presence or absence in said subject of a plurality of conditions within the differential diagnosis of a symptom exhibited by said subject;

and correlating the presence or amount of said markers in said test sample to the presence or absence of each of said plurality of conditions, said test device comprising;

a test surface comprising a plurality of discrete addressable locations, each said location comprising an antibody selected to bind for detection one of said plurality of markers immobilized at said location.

30. A test device according to claim 29, wherein said test surface comprises discrete particles immobilized at said plurality of discrete addressable locations, wherein said discrete particles comprise said antibody.

31. A test device according to claim 29, wherein said said symptom is selected from the group consisting of dyspnea, fever, chest pain, abdominal pain, disturbances in metabolic state, neurologic dysfunction, hypertension, dizzyness, and headache.

32. A test device according to claim 29, wherein said symptom is dyspnea, and said plurality of conditions are selected from the group consisting of asthma, chronic obstructive pulmonary disease (“

COPD”

), tracheal stenosis, obstructive endobroncheal tumor, pulmonary fibrosis, pneumoconiosis, lymphangitic carcinomatosis, kyphoscoliosis, pleural effusion, amyotrophic lateral sclerosis, congestive heart failure, coronary artery disease, myocardial infarction, atrial fibrillation, cardiomyopathy, valvular dysfunction, left ventricle hypertrophy, pericarditis, arrhythmia, pulmonary embolism, metabolic acidosis, chronic bronchitis, pneumonia, anxiety, sepsis, and aneurismic dissection.

33. A test device according to claim 32, wherein said plurality of conditions comprise myocardial infarction, pulmonary embolism, and congestive heart failure.

34. A test device according to claim 33, wherein said plurality of markers comprise at least one cardiac troponin form, B-type natriuretic peptide or a marker related to B-type natriuretic peptide, and D-dimer.

35. A test device according to claim 29 wherein said test sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, a urine sample, a saliva sample, a sputum sample, and a pleural effusion sample.

36. A test device according to claim 29, wherein said plurality of markers are selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, Atrial natriuretic peptide, a marker related to Atrial natriuretic peptide, pulmonary surfactant protein D, D-dimer, annexin V, enolase, creatine kinase, glycogen phosphorylase, heart-type fatty acid binding protein, phosphoglyceric acid mutase, S-100, S-100ao, plasmin-α

2-antiplasmin complex, β

-thromboglobulin, platelet factor 4, fibrinopeptide A, platelet-derived growth factor, prothrombin fragment 1+2, P-selectin, thrombin-antithrombin III complex, von Willebrand factor, tissue factor, thrombus precursor protein, human neutrophil elastase, inducible nitric oxide synthase, lysophosphatidic acid, malondialdehyde-modified low density lipoprotein, matrix metalloproteinase-1, matrix metalloproteinase-2, matrix metalloproteinase-3, matrix metalloproteinase-9, TIMP1, TIMP2, TIMP3, C-reactive protein, interleukin-1β

, interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor α

, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule, monocyte chemotactic protein-1, caspase-3, human lipocalin-type prostaglandin D synthase, mast cell tryptase, eosinophil cationic protein, KL-6, procalcitonin, haptoglobin, s-CD40 ligand, S-FAS ligand, alpha 2 actin, basic calponin 1, CSRP2 elastin, LTBP4, smooth muscle myosin, smooth muscle myosin heavy chain, transgelin, aldosterone, angiotensin I, angiotensin II, angiotensin III, bradykinin, calcitonin calcitonin gene related peptide, endothelin 1, endotehlin 2, endothelin 3, renin, vasopressin, APO B48, pancreatic elastase 1, pancreatic lipase, sPLA2, trypsinogen activation peptide, alpha enolase, LAMP3, phospholipase D, PLA2G5, protein D, SFTPC, defensin HBD1, defensin HBD2, CXCL-1, CXCL-2, CXCL-3, CCL2, CCL3, CCL4, CCL8, procalcitonin, protein C, serum amyloid A, s-glutathione, s-TNF P55, s-TNF P75, TAFI, TGF beta, MMP-11, brain fatty acid binding protein, CA11, CABP1, CACNA1A, CBLN1, CHN2, cleaved Tau, CRHR1, DRPLA, EGF, GPM6B, GPR7, GPR8, GRIN2C, GRM7, HAPIP, HIF 1 alpha, HIP2 KCNK4, KCNK9, KCNQ5, MAPK10, n-acetyl aspartate, NEUROD2, NRG2, PACE4, phosphoglycerate mutase, PKC gamma, prostaglandin E2, PTEN, PTPRZ1, RGS9, SCA7, secretagogin, SLC1A3, SORL1, SREB3, STAC, STX1A, STXBP1, BDNF, cystatin C, neurokinin A, substance P, interleukin-1, interleukin-11, interleukin-13, interleukin-18, interleukin-4, and interleukin-10.

37. A test device according to claim 29, wherein said test surface is within a capillary space.

38. A method of identifying a marker panel for performing a symptom-based diagnotic method, comprising:

determining the ability of one or more candidate panels comprising plurality of subject-derived markers to identify the presence or absence in a subject population of a plurality of conditions within the differential diagnosis of a symptom exhibited by individual subjects in said subject population, wherein a candidate panel that correctly identifies the presence or absence of said plurality of conditions is identified as a marker panel.

39. A method according to claim 38, wherein said symptom is selected from the group consisting of dyspnea, fever, chest pain, abdominal pain, disturbances in metabolic state, neurologic dysfunction, hypertension, dizzyness, and headache.

40. A method according to claim 39, wherein said symptom is dyspnea, and said plurality of conditions are selected from the group consisting of asthma, chronic obstructive pulmonary disease (“

COPD”

), tracheal stenosis, obstructive endobroncheal tumor, pulmonary fibrosis, pneumoconiosis, lymphangitic carcinomatosis, kyphoscoliosis, pleural effusion, amyotrophic lateral sclerosis, congestive heart failure, coronary artery disease, myocardial infarction, atrial fibrillation, cardiomyopathy, valvular dysfunction, left ventricle hypertrophy, pericarditis, arrhythmia, pulmonary embolism, metabolic acidosis, chronic bronchitis, pneumonia, anxiety, sepsis, and aneurismic dissection.

41. A method according to claim 40, wherein said plurality of conditions comprise myocardial infarction, pulmonary embolism, and congestive heart failure.

42. A method according to claim 41, wherein said plurality of markers comprise at least one cardiac troponin form, B-type natriuretic peptide or a marker related to B-type natriuretic peptide, and D-dimer.

43. A method according to claim 38 wherein said test sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, a urine sample, a saliva sample, a sputum sample, and a pleural effusion sample.

44. A method according to claim 38, wherein said plurality of markers are selected from the group consisting of free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, B-type natriuretic peptide, a marker related to B-type natriuretic peptide, Atrial natriuretic peptide, a marker related to Atrial natriuretic peptide, pulmonary surfactant protein D, D-dimer, annexin V, enolase, creatine kinase, glycogen phosphorylase, heart-type fatty acid binding protein, phosphoglyceric acid mutase, S-100, S-100ao, plasmin-α

2-antiplasmin complex, β

-thromboglobulin, platelet factor 4, fibrinopeptide A, platelet-derived growth factor, prothrombin fragment 1+2, P-selectin, thrombin-antithrombin III complex, von Willebrand factor, tissue factor, thrombus precursor protein, human neutrophil elastase, inducible nitric oxide synthase, lysophosphatidic acid, malondialdehyde-modified low density lipoprotein, matrix metalloproteinase-1, matrix metalloproteinase-2, matrix metalloproteinase-3, matrix metalloproteinase-9, TIMP1, TIMP2, TIMP3, C-reactive protein, interleukin-1β

, interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor α

, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule, monocyte chemotactic protein-1, caspase-3, human lipocalin-type prostaglandin D synthase, mast cell tryptase, eosinophil cationic protein, KL-6, procalcitonin, haptoglobin, s-CD40 ligand, S-FAS ligand, alpha 2 actin, basic calponin 1, CSRP2 elastin, LTBP4, smooth muscle myosin, smooth muscle myosin heavy chain, transgelin, aldosterone, angiotensin I, angiotensin II, angiotensin III, bradykinin, calcitonin calcitonin gene related peptide, endothelin 1, endotehlin 2, endothelin 3, renin, vasopressin, APO B48, pancreatic elastase 1, pancreatic lipase, sPLA2, trypsinogen activation peptide, alpha enolase, LAMP3, phospholipase D, PLA2G5, protein D, SFTPC, defensin HBD1, defensin HBD2, CXCL-1, CXCL-2, CXCL-3, CCL2, CCL3, CCL4, CCL8, procalcitonin, protein C, serum amyloid A, s-glutathione, s-TNF P55, s-TNF P75, TAFI, TGF beta, MMP-11, brain fatty acid binding protein, CA11, CABP1, CACNA1A, CBLN1, CHN2, cleaved Tau, CRHR1, DRPLA, EGF, GPM6B, GPR7, GPR8, GRIN2C, GRM7, HAPIP, HIF 1 alpha, HIP2 KCNK4, KCNK9, KCNQ5, MAPK10, n-acetyl aspartate, NEUROD2, NRG2, PACE4, phosphoglycerate mutase, PKC gamma, prostaglandin E2, PTEN, PTPRZ1, RGS9, SCA7, secretagogin, SLC1A3, SORL1, SREB3, STAC, STX1A, STXBP1, BDNF, cystatin C, neurokinin A, substance P, interleukin-1, interleukin-11, interleukin-13, interleukin-18, interleukin-4, and interleukin-10.

45. A method for distinguishing between systolic heart failure and diastolic heart failure in a subject, comprising:

analyzing a test sample obtained from said subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between systolic heart failure and diastolic heart failure; and

correlating the presence or amount of said markers in said test sample to the presence of systolic heart failure and diastolic heart failure in said subject.

46. A method according to claim 45, wherein said markers are selected from the group consisting of B-type natriuretic peptide, a marker related to B-type natriuretic peptide, atrial natriuretic peptide, a marker related to atrial natriuretic peptide, vasopressin, endothelin-2, calcitonin gene related peptide, calcitonin, urotensin 2, and angiotensin 2.

47. A method according to claim 45, wherein said markers are selected from the group consisting of B-type natriuretic peptide, a marker related to B-type natriuretic peptide, atrial natriuretic peptide, a marker related to atrial natriuretic peptide, and urotensin 2.

48. A test device for performing a diagnotic method, wherein said method comprises analyzing a test sample obtained from a subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between systolic heart failure and diastolic heart failure in a subject, comprising:

a test surface comprising a plurality of discrete addressable locations, each said location comprising an antibody selected to bind for detection one of said plurality of markers immobilized at said location.

49. A method for distinguishing between atrial fibrillation and congestive heart failure in a subject, comprising:

analyzing a test sample obtained from said subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between atrial fibrillation and congestive heart failure; and

correlating the presence or amount of said markers in said test sample to the presence of atrial fibrillation and congestive heart failure in said subject.

50. A method according to claim 49, wherein said markers are selected from the group consisting of atrial natriuretic peptide, a marker related to atrial natriuretic peptide, B-type natriuretic peptide, and a marker related to B-type natriuretic peptide.

51. A test device for performing a diagnotic method, wherein said method comprises analyzing a test sample obtained from a subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between atrial fibrillation and congestive heart failure in a subject, comprising:

a test surface comprising a plurality of discrete addressable locations, each said location comprising an antibody selected to bind for detection one of said plurality of markers immobilized at said location.

52. A method for distinguishing between atrial fibrillation and myocardial infarction in a subject, comprising:

analyzing a test sample obtained from said subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between atrial fibrillation and myocardial infarction; and

correlating the presence or amount of said markers in said test sample to the presence of atrial fibrillation and myocardial infarction in said subject.

53. A method according to claim 52, wherein said markers are selected from the group consisting of atrial natriuretic peptide, a marker related to atrial natriuretic peptide, free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, and myoglobin.

54. A test device for performing a diagnotic method, wherein said method comprises analyzing a test sample obtained from a subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between atrial fibrillation and myocardial infarction in a subject, comprising:

a test surface comprising a plurality of discrete addressable locations, each said location comprising an antibody selected to bind for detection one of said plurality of markers immobilized at said location.

55. A method for distinguishing between aortic dissection, myocardial ischemia, and myocardial infarction in a subject, comprising:

analyzing a test sample obtained from said subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between aortic dissection, myocardial ischemia, and myocardial infarction; and

correlating the presence or amount of said markers in said test sample to the presence of aortic dissection, myocardial ischemia, and myocardial infarction in said subject.

56. A method according to claim 55, wherein said markers are selected from the group consisting of B-type natriuretic peptide, a marker related to B-type natriuretic peptide, free cardiac troponin I, free cardiac troponin T, cardiac troponin I in a complex comprising one or both of troponin T and troponin C, cardiac troponin T in a complex comprising one or both of troponin I and troponin C, total cardiac troponin I, total cardiac troponin T, smooth muscle myosin heavy chain, and myoglobin.

57. A test device for performing a diagnotic method, wherein said method comprises analyzing a test sample obtained from a subject for the presence or amount of a plurality of subject-derived markers, wherein said markers are selected to distinguish between aortic dissection, myocardial ischemia, and myocardial infarction in a subject, comprising:

a test surface comprising a plurality of discrete addressable locations, each said location comprising an antibody selected to bind for detection one of said plurality of markers immobilized at said location.