Inhibition of Fibrosis and AF By TGF-Beta Inhibition in the Posterior Left Atrium (PLA)

Abstract

The disclosed methods pertain to diagnosing whether a non-ablative, gene therapy is needed for reducing AF fibrosis in a subject, and if so, methods of reducing AF fibrosis in a subject using gene therapy with a dominant negative TGF-β R2 cDNA expression vector. Kits and computer program products are also described, wherein the kits provide materials for diagnosing and treating AF fibrosis, and the computer program products include a computer readable medium having computer readable program code for monitoring the efficacy of therapeutic ablation of fibrosis in a subject using a gene therapy method.

1 . A method of diagnosing whether a non-ablative, gene therapy is needed for reducing AF fibrosis in a subject, comprising:
 (a) performing at least one EGM analysis of a plurality of recorded atrial EGMs for a tissue in a region suspected of having AF fibrosis;   (b) determining one or more correlations of at least one AF EGM characteristic to a region having AF fibrosis from the plurality of recorded atrial EGMs for the tissue; and   (c) determining a first outcome of executing step (b) and a second outcome of executing step (b) for the tissue based upon the one or more correlations of at least one AF EGM characteristic to a region having AF fibrosis;   
       wherein the first outcome triggers a first decision to forego therapy of the analysis region and the second outcome triggers a second decision to perform therapy of the analysis region of the tissue. 
     
     
         2 . The method of  claim 1 , wherein step (a) comprises at least one analytical subroutine selected from the group consisting of dominant frequency analysis (DF), organizational index analysis (OI), fractional interval analysis (FI) and Shannon Entropy analysis (ShEn). 
     
     
         3 . The method of  claim 1 , wherein the first outcome consists of evidence of fibrosis and the second outcome consists of no evidence of fibrosis. 
     
     
         4 . The method of  claim 1 , wherein the subject is a patient in need of preventative treatment for stroke or congestive heart failure as a result of atrial fibrillation. 
     
     
         5 . The method of  claim 1 , wherein the one or more correlations of at least one AF EGM characteristic to a region suspected of having fibrosis comprises at least one correlation selected from the group consisting of (i) mean DF negatively correlates with % fibrosis; heterogeneity of DF negatively correlates with heterogeneity of fibrosis; mean FI positively correlates with % fibrosis; heterogeneity of FI positively correlates with heterogeneity of fibrosis and combinations thereof. 
     
     
         6 . The method of  claim 1 , wherein the one or more correlations of at least one AF EGM characteristic to a region suspected of having fibrosis comprises two correlations selected from the group of (a) one correlation based upon % fibrosis and (b) one correlation based upon heterogeneity of fibrosis. 
     
     
         7 - 20 . (canceled)