Identification of patients with abnormal fractional shortening

Abstract

The present invention relates to a method for assessing whether a subject shall be subjected to an imaging based diagnostic assessment. The method is based on the determination of the amount(s) of a cardiac Troponin and/or Fibroblast Growth Factor 23 (FGF-23) in a sample from the subject, and on the comparison of the, thus, determined amount(s) with a reference amount (reference amounts). The present invention also relates to a system for performing an assessment whether a subject shall be subjected to an imaging based diagnostic assessment and to reagents and kits used in performing the methods disclosed herein. Moreover, the present invention is directed to a method for predicting the risk of mortality and/or of a cardiovascular event. Also encompassed is a method for diagnosing an early stage of LVH in a subject having a preserved left ventricular ejection.

1 . A method for assessing whether a subject shall be subjected to an imaging based diagnostic assessment comprising the steps of
 a) determining the amount(s) of a cardiac Troponin and/or Fibroblast Growth Factor 23 (FGF-23) in a sample from the subject, and   b) comparing the determined amount in step (a) to a reference amount, whereby it is assessed whether the subject shall be subjected to an imaging based diagnostic assessment.   
     
     
         2 . The method of  claim 1 , wherein the subject suffers from hypertension, and/or wherein the subject does not suffer from left ventricular hypertrophy. 
     
     
         3 . The method of  claim 1 , wherein the imaging based diagnostic assessment is echocardiography or magnetic resonance imaging for diagnosing abnormal midwall fractional shortening. 
     
     
         4 . The method of  claim 1 , wherein the reference amount is a calculated reference amount, wherein an increased amount in the sample from the subject as compared to the reference amount indicates that the subject shall be subjected to imaging based diagnostic assessment and/or wherein a decreased amount in the sample from the subject as compared to the reference amount indicates that the subject shall not be subjected to imaging based diagnostic assessment. 
     
     
         5 . The method of  claim 1 , wherein
 i) the reference amount is derived from a subject or group of subjects which is (are) known to be susceptible to an imaging based diagnostic assessment, wherein an amount of the cardiac Troponin and/or FGF-23 which is (are) essentially identical or which is (are) larger than the reference amount(s) indicate(s) that the subject shall be subjected to an imaging based diagnostic assessment (rule-in) and/or   ii) the reference amount is derived from a subject or group of subjects which is (are) known not to be susceptible to an imaging based diagnostic assessment, wherein an amount of the Troponin and/or FGF-23 which is (are) essentially identical or which is (are) lower than the reference amount(s) indicates that the subject to be tested shall not be subjected to an imaging based diagnostic assessment.   
     
     
         6 . The method of  claim 1 , wherein the reference amount is the amount of the cardiac Troponin and/or Fibroblast Growth Factor 23 (FGF-23) in a first sample that was obtained from the subject prior to the sample as set forth in step a) of  claim 1  (“second sample”). 
     
     
         7 . The method of  claim 6 , wherein the first sample has been obtained 6 to 18 months prior to the second sample. 
     
     
         8 . The method of  claim 6 , wherein an amount of a cardiac Troponin T in the second sample that is at least 10% larger than the amount in the first sample, and/or wherein an amount of FGF-23 in the second sample at least 10% larger than the amount in the first sample is indicative for a subject who shall be subjected to an imaging based diagnostic assessment and/or wherein an essentially unchanged amount of or a decreased amount of FGF-23 and/or of a cardiac Troponin in the second sample as compared to the first sample is indicative for a subject who shall not be subjected to an imaging based diagnostic assessment. 
     
     
         9 . The method of  claim 6 , wherein the subject did not suffer from abnormal MFS at the time at which the first sample has been obtained and wherein the subject suffered from hypertension at the time at which the first sample was obtained. 
     
     
         10 . The method of  claim 1  wherein the sample is a blood, serum or plasma sample. 
     
     
         11 . The method of any of  claim 1 , wherein the amounts of both a cardiac Troponin and FGF-23 are determined. 
     
     
         12 . The method of  claim 1 , wherein, if the amount of FGF-23 is determined, the method comprises the determination of the amount of vitamin D in step a) in addition to the determination of FGF-23, the calculation of a ratio between the amount of FGF-23 to the amount of vitamin D in a further step a1), and the comparison of the calculated ratio with a reference ratio. 
     
     
         13 . The method of  claim 1 , wherein the subject does not have increased NT-proBNP levels in a blood, serum or plasma sample. 
     
     
         14 . A device adapted for carrying out the method of  claim 1  comprising
 a) an analyzer unit comprising a detection agent which specifically binds to a cardiac troponin, a detection agent which specifically binds to FGF-23, a detection agent which specifically binds to IGFBP7, a detection agent which specifically binds to mimecan, and/or a detection agent which specifically binds to Endostatin, (and, optionally, if FGF-23 is determined, a detection agent which specifically binds to vitamin D), said unit being adapted for determining the amount(s) of the marker(s) in a sample of a subject; and 
 b) an analyzer unit for comparing the determined amount(s) with reference amount(s), whereby it is assessed whether the subject shall be subjected to an imaging based assessment, said unit comprising a database with a reference amount (or amounts) and a computer-implemented algorithm for carrying out the comparison. 
 
     
     
         15 . A method for predicting the risk of mortality and/or a cardiovascular event in a subject who does not suffer from heart failure and/or who does not show overt signs of heart failure said method comprising the steps of
 a) determining, in a sample from said subject the amount of IGFBP7 and/or the amount of FGF-23, and   b) comparing the amount (or the amounts) as determined in step a) to a reference amount (or to reference amounts), whereby the risk of mortality and/or a cardiovascular event in said subject is predicted.   
     
     
         16 . The method of  claim 15 , wherein the subject has a preserved LVEF (Left ventricular ejection fraction) wherein the LVEF is larger than 60%. 
     
     
         17 . The method of  claim 15 , wherein the method comprises the determination of the amount of FGF-23, and wherein the method further comprises the determination of the amount of vitamin D, the calculation of a ratio between the amounts of FGF-23 and vitamin D, and the comparison of the ratio to a reference ratio. 
     
     
         18 . The method of  claim 15 , wherein step a) further comprises determining the amount of a brain natriuretic peptide, in particular BNP or NT-proBNP, and/or the amount of a cardiac Troponin in the sample from the subject. 
     
     
         19 . The method of  claim 15 , wherein the subject who does not show overt signs of heart failure suffers from heart failure classified as stage A or stage B according to the ACC/AHA classification, or wherein the subject is healthy with respect to cardiac diseases and disorders. 
     
     
         20 . A method for diagnosing for diagnosing an early stage of left ventricular hypertrophy in a subject having a preserved left ventricular ejection fraction, said method comprising the steps of
 a) determining the amount of endostatin in a sample from the subject, and   b) determining the amount of a BNP-type peptide and/or of a cardiac Troponin in a sample from the subject, and   c) comparing the amounts as determined in step a) and b) to reference amounts, whereby an early stage of left ventricular hypertrophy is diagnosed.   
     
     
         21 . The method of  claim 20 , wherein the method comprises the determination of the amount of endostatin and a BNP-type peptide. 
     
     
         22 . The method of  claim 20 , wherein the method comprises the determination of the amount of endostatin and a cardiac Troponin. 
     
     
         23 . The method of  claim 20 , wherein the subject suffers from hypertension. 
     
     
         24 . The method of any  claim 20 , wherein the subject suffers from heart failure classified as stage B according to the ACC/AHA classification. 
     
     
         25 . The method of  claim 20 , wherein the early stage of LVH refers to a left ventricular mass index in a range between 116 g/m 2  to 149 g/m 2  if the subject is male. 
     
     
         26 . The method of  claim 20 , wherein the early stage of LVH refers to a left ventricular mass index in a range between 96 g/m 2  to 125 g/m 2  if the subject is female. 
     
     
         27 . The method of  claim 20 , wherein the subject having a preserved LVEF has a LVEF of larger than 55%. 
     
     
         28 . The method of  claim 20  wherein the test subject is determined to be in an early stage of LVH, if (i) the amount of one of the determined markers is larger than the reference amount, or if (ii) the amounts of both markers (or of all three markers) are larger than the reference amounts. 
     
     
         29 . The method of  claim 20  wherein the subject is determined not to be in an early stage of LVH if the amounts of both markers are lower than the reference amounts.