Biomarker for diagnosis, prediction and/or prognosis of acute heart failure and uses thereof

Abstract

The application discloses MCAM as a new biomarker for acute heart failure; methods for predicting, diagnosing, prognosticating and/or monitoring acute heart failure based on measuring said biomarker; and kits and devices for measuring said biomarker and/or performing said methods.

1 - 48 . (canceled) 
     
     
         49 . A method for treating acute heart failure (AHF) which involves systolic dysfunction, the method comprising the steps of:
 a) obtaining a plasma sample from a subject presenting with rapid onset of symptoms, wherein the symptoms comprise dyspnea;   b) having an assay conducted for measurement of melanoma cell adhesion molecule (MCAM), the assay comprising detecting the quantity of MCAM, thereby measuring the quantity of circulating MCAM in the sample from the subject;   (c) comparing the quantity of circulating MCAM measured in (b) with a reference value of the quantity of circulating MCAM, said reference value representing a known diagnosis, and/or prognosis of AHF which involves systolic dysfunction;   (d) finding a deviation or no deviation of the quantity of circulating MCAM measured in (b) from the reference value;   (e) attributing said finding of deviation or no deviation to a particular diagnosis, and/or prognosis of AHF in the subject, wherein elevated quantities of circulating MCAM in the sample from the subject compared to a reference value representing a diagnosis of no AHF or representing a good prognosis for AHF indicates that the subject has or is at risk of having AHF which involves systolic dysfunction or indicates a poor prognosis for AHF which involves systolic dysfunction in the subject;   (f) identifying subjects having AHF with systolic dysfunction in subjects presenting with rapid onset of symptoms comprising dyspnea;   (g) treating the subject having AHF with systolic dysfunction with one or more treatments selected from the group consisting of diuretics, beta blockers, ACE inhibitors, and inotropic drugs and avoiding treatment with calcium channel blockers.   
     
     
         50 . The method according to  claim 49 , wherein the subject has a medical history of heart failure. 
     
     
         51 . The method according to  claim 49 , wherein the subject is diagnosed with AHF with systolic dysfunction and wherein steps (b) to (f) of  claim 49  are repeated at a time point where a diagnosis of recovery of AHF has to be made. 
     
     
         52 . The method according to  claim 49  wherein the subject is diagnosed with AHF with systolic dysfunction and wherein steps (b) to (f) of  claim 49  are repeated for monitoring a change in the diagnosis, and/or prognosis of AHF in a subject, comprising:
 (i) applying the method of steps (b) to (f) of  claim 49  to the subject at one or more additional successive time points, whereby the diagnosis, and/or prognosis of AHF in the subject is determined at said successive time points; 
 (ii) comparing the diagnosis, and/or prognosis of AHF in the subject at said successive time points as determined in (i); and 
 (iii) finding the presence or absence of a change between the diagnosis, and/or prognosis of AHF in the subject at said successive time points as determined in (i), wherein the AHF in the subject involves systolic dysfunction. 
 
     
     
         53 . The method according to  claim 52 , wherein said change in the diagnosis, and/or prognosis of AHF in the subject is monitored in the course of a medical treatment of said subject. 
     
     
         54 . The method according to  claim 49  wherein, the presence or absence and/or quantity of one or more other biomarkers in the sample from the subject is measured and wherein said one or more other biomarker useful for diagnosing, and/or prognosticating AHF is selected from the group consisting of, B-type-natriuretic peptide (BNP), pro-B-type natriuretic peptide (proBNP), and amino terminal pro-B-type natriuretic peptide (NTproBNP). 
     
     
         55 . The method according to  claim 49 , wherein said systolic dysfunction is characterized by a decreased left ventricular ejection fraction (LVEF), preferably wherein said LVEF is less than 55% or less than 50% or less than 45%, and/or by increased cardiac filling pressure. 
     
     
         56 . The method according to  claim 49 , wherein the quantity of circulating MCAM and/or the presence or absence and/or quantity of the one or more other biomarkers is measured using, respectively, a binding agent capable of specifically binding to circulating MCAM and/or to fragments thereof, and a binding agent capable of specifically binding to said one or more other biomarkers. 
     
     
         57 . The method according to  claim 49 , wherein the quantity of circulating MCAM and/or the presence or absence and/or quantity of the one or more other biomarkers is measured using an immunoassay technology, such as direct ELISA, indirect ELISA, sandwich ELISA, competitive ELISA, multiplex ELISA, radioimmunoassay (RIA) or ELISPOT technologies, or using a mass spectrometry analysis method or using a chromatography method, or using a combination of said methods.