Bin1 as a Prognostic Marker in Cardiovascular Disease

Abstract

The present disclosure provides methods involving use of BIN1 expression levels, in heart tissue, in evaluating the risk of a poor outcome in a patient diagnosed with congestive heart failure. The methods finds use in evaluating patients who are heart transplant candidates as well as in assessing therapy options and efficacy of treatment in congestive heart failure patients.

1 . A method for determining a risk of a poor outcome in a congestive heart failure patient, the method comprising:
 assaying a BIN1 expression level in a heart tissue sample obtained from the patient; and   using the BIN1 expression level to determine the risk of a poor outcome in the patient, wherein a decreased BIN1 expression level is positively correlated to an increased risk of a poor outcome.   
     
     
         2 . The method of  claim 1 , wherein the congestive heart failure patient has received a heart transplant and the heart tissue sample is from the transplanted heart. 
     
     
         3 . The method of  claim 1 , wherein the heart of the congestive heart failure (CHF) patient is connected to a mechanical assist device. 
     
     
         4 . The method of  claim 1 , wherein the patient is undergoing treatment for CHF. 
     
     
         5 . The method of  claim 2 , wherein the patient is undergoing immunosuppression therapy. 
     
     
         6 . The method of  claim 1 , wherein the assaying comprises measuring the level of BIN1 mRNA. 
     
     
         7 . The method of  claim 1 , wherein the assaying comprises measuring the level of BIN1 protein. 
     
     
         8 . The method of  claim 1 , comprising assaying a CaV1.2 expression level and normalizing the BIN1 expression level using the assayed CaV1.2 expression level. 
     
     
         9 . The method of  claim 1 , wherein the poor outcome is cardiac mortality. 
     
     
         10 . A method for determining a risk of a poor outcome in a congestive heart failure patient, the method comprising:
 assaying expression levels of BIN1 and an internal control gene in a heart tissue sample obtained from the patient;   determining an Intrinsic Disease Factor (IDF) by calculating a ratio of the internal control gene expression level to the BIN1 expression level; and   using the IDF to determine the risk of a poor outcome in the patient, wherein an increased IDF is positively correlated to an increased risk of a poor outcome.   
     
     
         11 . The method of  claim 10 , wherein the internal control gene is a housekeeping gene. 
     
     
         12 . The method of  claim 10 , wherein the internal control gene is CaV1.2. 
     
     
         13 . The method of  claim 10 , wherein the assaying comprises measuring the levels of BIN1 and the internal control gene mRNA. 
     
     
         14 . The method of  claim 10 , wherein the congestive heart failure patient has received a heart transplant and the heart tissue sample is from the transplanted heart. 
     
     
         15 . The method of  claim 10 , wherein the heart of the congestive heart failure (CHF) patient is connected to a mechanical assist device. 
     
     
         16 . The method of  claim 10 , wherein the patient is undergoing treatment for CHF. 
     
     
         17 . The method of  claim 14 , wherein the patient is undergoing immunosuppression therapy. 
     
     
         18 . The method of  claim 10 , wherein the poor outcome is cardiac mortality.