TnT BASED DIAGNOSIS OF PAROXYSMAL ATRIAL FIBRILLATION

Abstract

The present invention relates to a method for diagnosing a recent paroxysmal atrial fibrillation. The method is based on the determination of the at least one marker selected from the group consisting of a cardiac Troponin, NT-proBNP (N-terminal prohormone of brain natriuretic peptide), hsCRP, IL-6 (Interleukin-6) and IGFBP7 (Insulin like growth factor binding protein 7) in a sample from the subject, and on the comparison of the, thus, determined amount(s) with a reference amount (reference amounts). Further, the present invention relates to a method for identifying a subject being treatable with anticoagulation therapy. Further envisaged are systems, reagents and kits used in performing the methods disclosed herein.

1 . A method for diagnosing a recent paroxysmal atrial fibrillation in a subject, comprising:
 (a) determining the amount of at least one marker selected from the group consisting of a cardiac Troponin, a BNP-type peptide, hsCRP (high sensitive CRP), IL-6 (Interleukin-6) and IGFBP7 (Insulin like growth factor binding protein 7) in a sample from the subject, and   (b) comparing the determined amount(s) of said at least one marker to a reference amount(s), whereby a recent paroxysmal atrial fibrillation is diagnosed,   
       wherein the subject does not suffer from atrial fibrillation at the time at which the sample is obtained. 
     
     
         2 . The method of  claim 1 , wherein the recent paroxysmal atrial fibrillation occurred up to twelve weeks before the sample has been obtained. 
     
     
         3 . The method of  claim 1 , wherein the recent paroxysmal atrial fibrillation occurred within 1 to 30 days before the sample has been obtained, in particular wherein the recent paroxysmal atrial fibrillation occurred within 1 to 7 days before the sample has been obtained. 
     
     
         4 . The method of  claim 1 , wherein the recent paroxysmal atrial fibrillation did not occur in connection with a stroke, in particular wherein the subject does not have a history of stroke. 
     
     
         5 . The method of  claim 1 , wherein the sample is a blood, serum or plasma sample. 
     
     
         6 . The method  claim 1 , wherein the subject is human. 
     
     
         7 . The method according to  claim 1 , wherein the reference amount is a calculated reference amount, and wherein an increased amount of the at least one marker(s) as compared to the reference amount(s) is indicative for the diagnosis of a recent paroxysmal atrial fibrillation, and/or wherein a decreased amount of the at least one at least one marker(s) as compared to the reference amount(s) indicates that the subject did not suffer from paroxysmal atrial fibrillation recently. 
     
     
         8 . The method of  claim 1 , wherein the reference amount(s) is (are) derived from (i) a subject or group of subjects known to have suffered from a recent paroxysmal atrial fibrillation, in particular, wherein essentially the same amount(s) or an increased amount of the at least one marker in the sample from the subject as compared to the reference amount(s) is (are) indicative for the diagnosis of a recent paroxysmal atrial fibrillation, and/or wherein the reference amount(s) is (are) derived from (ii) a subject or group of subjects known not to have suffered from a recent paroxysmal atrial fibrillation, in particular, wherein essentially the same amount(s) or an decreased amount of the at least one marker in the sample from the subject as compared to the reference amount(s) indicates that the subject did not suffer from paroxysmal atrial fibrillation recently. 
     
     
         9 . The method of  claim 1 , wherein i) the amounts of a cardiac Troponin and of hsCRP are determined, and wherein it is diagnosed whether the subject has suffered from paroxysmal atrial fibrillation within a period of 30 days before the sample has been obtained, or wherein ii) the amounts of a cardiac Troponin and of BNP-type peptide are determined, and wherein it is diagnosed whether the subject has suffered from paroxysmal atrial fibrillation within a period of one week before the sample has been obtained. 
     
     
         10 . The method according to  claim 1 , wherein the episode of atrial fibrillation terminated spontaneously. 
     
     
         11 . A method for identifying a subject who is treatable with anticoagulation therapy, comprising:
 (a) determining the amount of at least one marker selected from the group consisting of a cardiac Troponin, a BNP-type peptide, hsCRP, IL-6 (Interleukin-6) and IGFBP7 (Insulin like growth factor binding protein 7) in a sample from a subject who is suspected to have suffered from paroxysmal atrial fibrillation recently, and   (b) comparing the determined amount(s) of said at least one marker to a reference amount(s), whereby a subject is identified who is treatable with anticoagulation therapy,   
       wherein the subject does not suffer from atrial fibrillation at the time at which the sample is obtained. 
     
     
         12 . The method of  claim 11 , wherein the anticoagulation therapy is selected from heparin, a coumarin derivative, such as warfarin or dicumarol, tissue factor pathway inhibitor (TFPI), antithrombin III, factor IXa inhibitors, factor Xa inhibitors, inhibitors of factors Va and VIIIa, thrombin inhibitors 
     
     
         13 . The method of  claim 11 , wherein the reference amount is a calculated reference amount, and wherein an increased amount of the at least one marker (increased amounts of the markers) as compared to the reference amount(s) is indicative a subject treatable with anticoagulation therapy, and/or wherein a decreased amount of the at least one at least one marker (decreased amounts of the markers) as compared to the reference amount(s) indicates that the subject is not treatable with anticoagulation therapy. 
     
     
         14 . The method of  claim 11 , wherein the reference amount(s) is (are) derived from (i) a subject or group of subjects being treatable with anticoagulation therapy, in particular, wherein essentially the same amount(s) or an increased amount (increased amounts) of the at least one marker in the sample from the subject as compared to the reference amount(s) is (are) indicative a subject being treatable with anticoagulation therapy, and/or wherein the reference amount(s) is (are) derived from (i) a subject or group of subjects known not to be treatable with anticoagulation therapy, in particular, wherein essentially the same amount(s) or an decreased amount (decreased amounts) of the at least one marker in the sample from the subject as compared to the reference amount(s) indicates that the subject is not treatable with anticoagulation therapy. 
     
     
         15 . A method for diagnosing ongoing atrial fibrillation in a subject, comprising
 (a) determining the amount of the biomarker IGFBP7 in a sample from the subject, and   (b) comparing the amount of the biomarker IGFBP7 as determined in step (a) to a reference amount.   
     
     
         16 . The method of  claim 15 , wherein the sample is blood, serum or plasma sample. 
     
     
         17 . The method of  claim 15 , wherein the subject is human. 
     
     
         18 . The method according to  claim 15  wherein the subject suffers from heart failure classified as heart failure stage A or B according to ACC/AHA classification. 
     
     
         19 . The method according to  claim 15 , wherein an amount of the biomarker IGFBP7 in the sample from the subject above the reference amount indicates that the subject has atrial fibrillation and wherein an amount of the biomarker IGFBP7 in the sample from the subject below the reference amount indicates that the subject has not atrial fibrillation. 
     
     
         20 . A device adapted for diagnosing a recent paroxysmal atrial fibrillation in a subject comprising
 a) an analyzer unit comprising a detection agent (or agents) which specifically binds to a marker selected from the group consisting of a cardiac Troponin, a BNP-type peptide, hsCRP, IL-6 (Interleukin-6) and IGFBP7 (Insulin like growth factor binding protein 7), said unit being adapted for determining the amount(s) of the marker(s) in a sample; and   b) an analyzer unit for comparing the determined amount(s) with reference amount(s), whereby a recent paroxysmal atrial fibrillation is diagnosed, said unit comprising a database with a reference amount (or amounts) as set forth in  claim 7 , and a computer-implemented algorithm carrying out the comparison as set forth in  claim 7 .