Rate control during af using cellular intervention to modulate av node

Abstract

A biologic intervention method and apparatus generates a persistent modification to an AV node that is physiologically stable after the agent has matured but is alterable with subsequent application of an agent. Specifically, the generic agent is used to modulate a node in a cardiac conduction system including rate control using one and a combination of a family of K + channel or equivalent. Specifically, the channel is implemented to slow conduction by generating an outward current during optimization of action potential and repolarization phase thus decreasing the current that is available to excite downstream cells. A Kv 1.3 channel, for example, may be used as the biologic channel. The invention enables reversal of the modulation or adjustment for various heart rates (BPM) based on medical and patient-specific needs.

1 - 9 . (canceled) 
     
     
         10 . A method for manipulating cardiac conduction, the method comprising delivering a biological intervention agent in a cardiac conduction node; wherein the biological intervention agent imposes a greater voltage load in the conduction node to suppress charge transfer to an adjacent cell. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 10  further comprising performing effective refractory interval study to determine ERP and measuring Wenckebach rate prior to delivering the biological intervention agent in the cardiac conduction node. 
     
     
         13 . The method of  claim 10  further comprising titrating the dose of the biological intervention agent based on the patient's nodal modulation needs including heart rate (BPM) considerations to undertake various physical activities. 
     
     
         14 . The method of  claim 12  wherein the dosage of the biologic intervention agent is determined by the ERP and/or the lowest pacing rate that produces Wenckebach phenomenon. 
     
     
         15 - 20 . (canceled) 
     
     
         21 . The method of  claim 10 , wherein the cardiac conduction node is selected from the group consisting of atrio-ventricular (AV) node, His bundle and Purkinje fibers. 
     
     
         22 . The method of  claim 10 , wherein the biological intervention agent is selected from the group consisting of an unexcitable cell, an unexcitable cell transfected to express an exogenous gene encoding a voltage gated potassium channel ex vivo, and an exogenous gene encoding a voltage gated potassium channel. 
     
     
         23 . The method of  claim 22 , wherein the voltage gated potassium channel comprises I K1 , Kv2.1, or Kv1.3. 
     
     
         24 . The method of  claim 21 , wherein the electronic load on AV nodal cells is increased, cell-to-cell conduction is decreased, overall macroscopic conduction in the AV node is decreased, conduction velocity is slowed, overall activation time is delayed, and/or AV node conduction is slowed. 
     
     
         25 . The method of  claim 21 , wherein the biological intervention agent is delivered to cells of the AV node by a transvascular catheter, by injection into a nodal artery that perfuses the AV node, or endocardial injection into the AV node. 
     
     
         26 . The method of  claim 22 , wherein the unexcitable cell is transfected ex vivo to express an exogenous gene encoding a connexin (Cx) isoform. 
     
     
         27 . The method of  claim 22 , further comprising delivering an additional biological intervention agent comprising an exogenous gene encoding a connexin (Cx) isoform. 
     
     
         28 . The method of  claim 10 , further comprising delivering an additional biological intervention agent that modulates expression of connexin (C x ) molecules. 
     
     
         29 . A method for providing ventricular rate control in the treatment of a subject with atrial fibrillation (AF), the method comprising delivering an exogenous gene encoding a voltage gated potassium channel directly to atrio-ventricular (AV) nodal cells in the heart of the subject; wherein the encoded voltage gated potassium channel produces outward current and imposes a greater voltage load in the conduction node to suppress charge transfer to an adjacent cell. 
     
     
         30 . The method of  claim 29 , wherein the voltage gated potassium channel comprises I K1 , Kv2.1, or Kv1.3. 
     
     
         31 . The method of  claim 29 , wherein the exogenous gene encoding a voltage gated potassium channel is delivered directly to atrio-ventricular (AV) nodal cells by a catheter. 
     
     
         32 . The method of  claim 31 , wherein proximity of the catheter to AV nodal cells is determined by recording a His signal and/or by the delivery of a negative chronotropic agent. 
     
     
         33 . The method of  claim 29 , further comprising providing back up pacing of the heart rhythm of the subject. 
     
     
         34 . The method of  claim 29 , further comprising determining the dosage of the exogenous gene encoding a voltage gated potassium channel to be delivered based on an assessment of intrinsic AV node conduction. 
     
     
         35 . The method of  claim 34 , wherein an assessment of intrinsic AV node conduction comprises measuring effective refractory interval and/or the Wenckebach rate. 
     
     
         36 . The method of  claim 29 , further comprising delivering an exogenous gene encoding a regulatory subunit of a voltage gated potassium channel directly to AV nodal cells in the heart of the subject.