Assessing susceptibility to cardiac intervention, susceptibility to therapy for heart failure, risk of mortality or further cardiovascular events, and risk of subsequent pulmonary embolism in relevant patients based on determinations of gdf-15, natriuretic peptide, cardiac troponin or combinations thereof

Abstract

The present invention relates to a method of identifying a subject being susceptible to a cardiac intervention based on the determination of GDF-15 in a sample of a subject in need of a cardiac intervention. Moreover, the present invention pertains to a method for predicting the risk of mortality or a further acute cardiovascular event for a subject suffering from a cardiovascular complication based on the determination of GDF-15 and a natriuretic peptide and/or a cardiac troponin in a sample the said subject. Also encompassed by the present invention, are devices and kits for carrying out the aforementioned methods.

1 . A device for identifying a subject at risk of mortality or a further acute cardiovascular complication comprising:
 a means for contacting a portion of a sample from the subject with an antibody having specific binding affinity for growth differentiation factor 15 (GDF-15), thereby forming a complex between the antibody and GDF-15, the antibody having a detectable label;   a means for separating the complex formed in said step of contacting from antibody not comprising the complex;   a means for quantifying a signal from the detectable label of the antibody comprising the complex formed in said step of contacting, the signal being proportional to an amount of GDF-15 in the sample, whereby an amount of GDF-15 in the sample is calculated, and   a means for comparing the amount of GDF-15 calculated in said step of quantifying to a reference amount for GDF-15, wherein the reference amount for GDF-15 is 1200 pg/ml.   
     
     
         2 . The device of  claim 1 , further comprising:
 a means for identifying the subject at risk of mortality or a further acute cardiovascular event if the amount of GDF-15 calculated in said step of quantifying is larger than the reference threshold amount for GDF-15.   
     
     
         3 . The device of  claim 1 , wherein said cardiovascular complication is an acute coronary syndrome or heart failure. 
     
     
         4 . The device of  claim 1 , further comprising:
 a means for determining an amount of a cardiac troponin in said sample; and a means for comparing the amount of the cardiac troponin to a reference amount for the cardiac troponin.   
     
     
         5 . The device of  claim 4 , wherein said reference amount of cardiac troponin is 0.01 ng/ml. 
     
     
         6 . The device of  claim 4 , further comprising:
 a means for identifying the subject at risk of mortality or a further acute cardiovascular event if the amount of the GDF-15 calculated in said step of quantifying is greater than the GDF-15 reference amount and the amount of the natriuretic peptide calculated in said step of quantifying is greater than the natriuretic peptide reference amount and the amount of the cardiac troponin calculated in said step of quantifying is greater than the cardiac troponin reference amount.   
     
     
         7 . The device of  claim 1 , further comprising:
 a means for determining an amount of a natriuretic peptide in said sample; and a means for comparing the amount of the natriuretic peptide to a reference amount for the natriuretic peptide.   
     
     
         8 . The device of  claim 7  wherein said natriuretic peptide is NT-proBNP. 
     
     
         9 . The device of  claim 7  wherein said reference amount of natriuretic peptide is 1000 pg/ml. 
     
     
         10 . The device of  claim 7 , further comprising:
 a means for identifying the subject at risk of mortality or a further acute cardiovascular event if the amount of the GDF-15 calculated in said step of quantifying is greater than the GDF-15 reference amount and the amount of the natriuretic peptide calculated in said step of quantifying is greater than the natriuretic peptide reference amount.   
     
     
         11 . A device for identifying a subject diagnosed with heart failure as sensitive to a cardiac intervention therapy, comprising:
 a means for contacting a portion of a sample from the subject with an antibody having specific binding affinity for growth differentiation factor 15 (GDF-15), thereby forming a complex between the antibody and GDF-15, the antibody having a detectable label;   a means for separating the complex formed in said step of contacting from antibody not comprising the complex;   a means for quantifying a signal from the detectable label of the antibody comprising the complex formed in said step of contacting, the signal being proportional to an amount of GDF-15 in the sample, whereby an amount of GDF-15 in the sample is calculated, and   a means for comparing the amount of GDF-15 calculated in said step of quantifying to a reference amount for GDF-15, wherein the reference amount for GDF-15 is 1200 pg/ml.   
     
     
         12 . The device of  claim 11 , further comprising:
 a means for identifying the subject as sensitive to a cardiac intervention therapy if the amount of GDF-15 calculated in said step of quantifying is larger than the reference threshold amount for GDF-15.   
     
     
         13 . The device of  claim 11 , wherein said cardiac intervention therapy is a drug-based therapy or an interventional therapy. 
     
     
         14 . The device of  claim 11 , further comprising:
 a means for determining an amount of a cardiac troponin in said sample; and a means for comparing the amount of the cardiac troponin to a reference amount for the cardiac troponin.   
     
     
         15 . The device of  claim 14 , wherein said reference amount of cardiac troponin is 0.01 ng/ml. 
     
     
         16 . The device of  claim 14 , further comprising:
 a means for identifying the subject as sensitive to a cardiac intervention therapy if the amount of the GDF-15 calculated in said step of quantifying is greater than the GDF-15 reference amount and the amount of the natriuretic peptide calculated in said step of quantifying is greater than the natriuretic peptide reference amount and the amount of the cardiac troponin calculated in said step of quantifying is greater than the cardiac troponin reference amount.   
     
     
         17 . The device of  claim 11 , further comprising:
 a means for determining an amount of a natriuretic peptide in said sample; and a means for comparing the amount of the natriuretic peptide to a reference amount for the natriuretic peptide.   
     
     
         18 . The device of  claim 17  wherein said natriuretic peptide is NT-proBNP. 
     
     
         19 . The device of  claim 17  wherein said reference amount of natriuretic peptide is 1000 pg/ml. 
     
     
         20 . The device of  claim 17 , further comprising:
 a means for identifying the subject as sensitive to a cardiac intervention therapy if the amount of the GDF-15 calculated in said step of quantifying is greater than the GDF-15 reference amount and the amount of the natriuretic peptide calculated in said step of quantifying is greater than the natriuretic peptide reference amount.   
     
     
         21 . A device for identifying a subject as suitably treated by a cardiac intervention comprising:
 a means for contacting a portion of a sample from the subject with an antibody having specific binding affinity for growth differentiation factor 15 (GDF-15), thereby forming a complex between the antibody and GDF-15, the antibody having a detectable label;   a means for separating the complex formed in said step of contacting from antibody not comprising the complex;   a means for quantifying a signal from the detectable label of the antibody comprising the complex formed in said step of contacting, the signal being proportional to an amount of GDF-15 in the sample, whereby an amount of GDF-15 in the sample is calculated, and   a means for comparing the amount of GDF-15 calculated in said step of quantifying to a reference amount for GDF-15, wherein the reference amount for GDF-15 is 1200 pg/ml.   
     
     
         22 . The device of  claim 21 , further comprising:
 a means for identifying the subject as suitably treated by a cardiac intervention if the amount of GDF-15 calculated in said step of quantifying is larger than the reference threshold amount for GDF-15.   
     
     
         23 . The device of  claim 22 , wherein said cardiac intervention is selected from the group consisting of percutaneous coronary angioplasty, percutaneous transluminal coronary balloon angioplasty, laser angioplasty, coronary stent implantation, bypass implantation, and intraluminal techniques to restore blood flow, vessel patency, stabilize plaque, and reduce intracoronary thrombus load. 
     
     
         24 . The device of  claim 21 , further comprising:
 a means for determining an amount of a cardiac troponin in said sample; and   a means for comparing the amount of the cardiac troponin to a reference amount for the cardiac troponin.   
     
     
         25 . The device of  claim 24 , wherein said reference amount of cardiac troponin is 0.01 ng/ml. 
     
     
         26 . The device of  claim 24 , further comprising:
 a means for identifying the subject as suitably treated by a cardiac intervention if the amount of the GDF-15 calculated in said step of quantifying is greater than the GDF-15 reference amount and the amount of the natriuretic peptide calculated in said step of quantifying is greater than the natriuretic peptide reference amount and the amount of the cardiac troponin calculated in said step of quantifying is greater than the cardiac troponin reference amount.   
     
     
         27 . The device of  claim 21 , further comprising:
 a means for determining an amount of a natriuretic peptide in said sample; and a means for comparing the amount of the natriuretic peptide to a reference amount for the natriuretic peptide.   
     
     
         28 . The device of  claim 27  wherein said natriuretic peptide is NT-proBNP. 
     
     
         29 . The device of  claim 27  wherein said reference amount of natriuretic peptide is 1000 pg/ml. 
     
     
         30 . The device of  claim 27 , further comprising:
 a means for identifying the subject as suitably treated by a cardiac intervention if the amount of the GDF-15 calculated in said step of quantifying is greater than the GDF-15 reference amount and the amount of the natriuretic peptide calculated in said step of quantifying is greater than the natriuretic peptide reference amount.   
     
     
         31 . The device of  claim 1 ,  11 , or  21 , wherein said steps of quantifying and comparing comprise use of a computing device executing a computer program. 
     
     
         32 . The device of  claim 31 , wherein said step of identifying comprises the computing device providing an output result.