Methods and systems for providing therapies into the pericardial space

Abstract

Methods and systems for transvenously accessing the pericardial space via the vascular system and atrial wall, particularly through the superior vena cava and right atrial wall, to deliver a pharmacologic agent, particularly a NO-donor drug, to the heart are disclosed. A proximal connector of an infusion catheter is coupled to an infusion pump, and a distal catheter segment having a distal infusion catheter lumen end opening is disposed in the pericardial space. The implantable infusion pump is operable in conjunction with an implantable ischemia monitor to monitor the ischemic state and trigger delivery or regulate the periodic delivery of the pharmacologic agent to optimally treat ischemia. The patient may operate a patient activator that the patient when feeling ischemia symptoms to transmit a signal that is received by the implantable infusion pump and triggers delivery of a bolus and/or continuous infusion.

1 . A method of accessing the pericardial space between a heart and its pericardium to deliver a pharmacologic agent to the heart, the method comprising the steps of: 
 advancing an infusion catheter to dispose a distal catheter segment having a distal infusion catheter lumen end opening in the pericardial space;    attaching a proximal connector of the infusion catheter to an infusion pump having a reservoir containing the pharmacologic agent;    detecting an ischemic state of the heart; and    delivering the pharmacologic agent from the reservoir into the pericardial space to counter the detected ischemic state.    
   
   
       2 . The method of  claim 1 , further comprising: 
 detecting a remotely transmitted therapy delivery command; and    delivering a bolus of the pharmacologic agent.    
   
   
       3 . The method of  claim 2 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       4 . The method of  claim 1 , wherein the detecting step comprises: 
 sensing a feature of the EGM of the heart; and    detecting a characteristic of the sensed feature indicative of the ischemic state.    
   
   
       5 . The method of  claim 4 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       6 . The method of  claim 1 , wherein the detecting step comprises: 
 sensing blood pH; and    detecting a value of the sensed blood pH indicative of the ischemic state.    
   
   
       7 . The method of  claim 5 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       8 . The method of  claim 1 , wherein the detecting step comprises: 
 sensing blood oxygen saturation; and    detecting a value of the sensed oxygen saturation indicative of the ischemic state.    
   
   
       9 . The method of  claim 7 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       10 . The method of  claim 1 , wherein the detecting step comprises: 
 sensing one or both of blood pressure and flow in the heart; and    detecting a value of the sensed one or both of blood pressure and flow indicative of the ischemic state.    
   
   
       11 . The method of  claim 10 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       12 . A system for delivering a pharmacologic agent into the pericardial space surrounding the heart to treat an ischemic state: 
 an infusion pump having a reservoir adapted to receive a pharmacologic agent to be delivered into the pericardial space; and    an infusion catheter coupled a proximal catheter end to the infusion pump and adapted to be routed to dispose a distal catheter segment having a distal infusion catheter lumen end opening in the pericardial space; and    wherein the infusion pump further comprises: 
 means for detecting an ischemic state of the heart; and  
 means for delivering a bolus of the pharmacologic agent into the pericardial space to counter the detected ischemic state.  
   
   
   
       13 . The system of  claim 12 , wherein the infusion pump further comprises means responsive to a remotely transmitted therapy delivery command for delivering a bolus of the pharmacologic agent.  
   
   
       14 . The system of  claim 13 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       15 . The system of  claim 12 , wherein the detecting means comprises: 
 means for sensing a feature of the EGM of the heart; and    means for detecting a characteristic of the sensed feature indicative of the ischemic state.    
   
   
       16 . The system of  claim 15 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       17 . The system of  claim 12 , wherein the detecting means comprises: 
 means for sensing blood pH; and    means for detecting a value of the sensed blood pH indicative of the ischemic state.    
   
   
       18 . The system of  claim 17 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       19 . The system of  claim 12 , wherein the detecting means comprises: 
 means for sensing blood oxygen saturation; and    means for detecting a value of the sensed oxygen saturation indicative of the ischemic state.    
   
   
       20 . The system of  claim 19 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       21 . The system of  claim 12 , wherein the detecting means comprises: 
 means for sensing one or both of blood pressure and flow in the heart; and    means for detecting a value of the sensed one or both of blood pressure and flow indicative of the ischemic state.    
   
   
       22 . The system of  claim 21 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       23 . A method of transvenously accessing the pericardial space between a heart and its pericardium to deliver a pharmacologic agent to the heart to treat an ischemic state, the method comprising the steps of: 
 passing a fixation catheter having a fixation catheter lumen extending between proximal and distal fixation catheter lumen openings and a distal tissue fixation mechanism through a selected peripheral vein and one of the inferior vena cava and the superior vena cava to establish a transvenous route into the right atrium of the heart;    disposing the distal fixation mechanism and distal fixation catheter lumen opening proximate the right atrial wall;    affixing the distal fixation mechanism to the right atrial wall;    passing an infusion catheter through the fixation catheter lumen out of the distal fixation catheter lumen opening and through the stabilized atrial wall to dispose a distal catheter segment having a distal infusion catheter lumen end opening in the pericardial space; and    delivering a pharmacologic agent through the infusion catheter to treat an ischemic state.    
   
   
       24 . The method of  claim 23 , wherein the delivering step comprises: 
 attaching a proximal connector of the infusion catheter to an infusion pump;    subcutaneously implanting the infusion pump in the thoracic region; and    operating the infusion pump to deliver the pharmacologic agent into the pericardial space.    
   
   
       25 . The method of  claim 24 , wherein the operating step comprises: 
 detecting a remotely transmitted therapy delivery command; and    delivering a bolus of the pharmacologic agent.    
   
   
       26 . The method of  claim 25 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       27 . The method of  claim 24 , wherein the operating step comprises: 
 detecting an ischemic state of the heart; and    regulating the delivery of the pharmacologic agent to counter the detected ischemic state.    
   
   
       28 . The method of  claim 27 , wherein the detecting step comprises: 
 sensing a feature of the EGM of the heart; and    detecting a characteristic of the sensed feature indicative of the ischemic state.    
   
   
       29 . The method of  claim 28 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       30 . The method of  claim 27 , wherein the detecting step comprises: 
 sensing blood pH; and    detecting a value of the sensed blood pH indicative of the ischemic state.    
   
   
       31 . The method of  claim 30 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       32 . The method of  claim 27 , wherein the detecting step comprises: 
 sensing blood oxygen saturation; and    detecting a value of the sensed oxygen saturation indicative of the ischemic state.    
   
   
       33 . The method of  claim 32 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       34 . The method of  claim 27 , wherein the detecting step comprises: 
 sensing one or both of blood pressure and flow in the heart; and    detecting a value of the sensed one or both of blood pressure and flow indicative of the ischemic state.    
   
   
       35 . The method of  claim 34 , wherein the pharmacologic agent comprises NO-donor drugs selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       36 . A method of transvenously accessing the pericardial space between a heart and its pericardium to deliver a NO-donor drug to the heart, the method comprising the steps of: 
 advancing an infusion catheter to dispose a distal catheter segment having a distal infusion catheter lumen end opening in the pericardial space;    attaching a proximal connector of the infusion catheter to an infusion pump;    detecting a condition of the heart; and    delivering a bolus of NO-donor drug.    
   
   
       37 . The method of  claim 36 , further comprising: 
 detecting a remotely transmitted therapy delivery command; and    delivering a bolus of the NO-donor drug.    
   
   
       38 . The method of  claim 36 , wherein the detecting step comprises: 
 sensing a feature of the EGM of the heart; and    detecting a characteristic of the sensed feature indicative of an ischemic state.    
   
   
       39 . The method of  claim 36 , wherein the detecting step comprises: 
 sensing blood pH; and    detecting a value of the sensed blood pH indicative of an ischemic state.    
   
   
       40 . The method of  claim 36 , wherein the detecting step comprises: 
 sensing blood oxygen saturation; and    detecting a value of the sensed oxygen saturation indicative of an ischemic state.    
   
   
       41 . The method of  claim 36 , wherein the detecting step comprises: 
 sensing one or both of blood pressure and flow in the heart; and    detecting a value of the sensed one or both of blood pressure and flow indicative of an ischemic state.    
   
   
       42 . The method of  claim 36 , wherein the advancing step comprises: 
 passing a fixation catheter having a fixation catheter lumen extending between proximal and distal fixation catheter lumen openings and a distal tissue fixation mechanism through a selected peripheral vein and one of the inferior vena cava and the superior vena cava to establish a transvenous route into the right atrium of the heart    disposing the distal fixation mechanism and distal fixation catheter lumen opening proximate the right atrial wall;    affixing the distal fixation mechanism to the right atrial wall;    passing an infusion catheter through the fixation catheter lumen out of the distal fixation catheter lumen opening and through the stabilized atrial wall to dispose a distal catheter segment having a distal infusion catheter lumen end opening in the pericardial space.    
   
   
       43 . The method of  claim 36 , wherein the advancing step comprises advancing the distal catheter segment from the right atrium through the right atrial wall.  
   
   
       44 . The method of  claim 36 , wherein the NO-donor drug is selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).  
   
   
       45 . A system for delivering a NO-donor drug into the pericardial space surrounding the heart to treat an ischemic state: 
 an infusion pump having a reservoir adapted to receive a NO-donor drug;    an infusion catheter coupled a proximal catheter end to the infusion pump and adapted to be routed from the infusion pump to dispose a distal catheter segment having a distal infusion catheter lumen end opening in the pericardial space; and    wherein the infusion pump further comprises: 
 means for detecting a condition of the heart; and  
 means for delivering a bolus of the NO-donor drug from the reservoir into the pericardial space to counter the detected condition.  
   
   
   
       46 . The system of  claim 45 , wherein the infusion pump further comprises means for regulating the delivery of the NO-donor drug into the pericardial space to counter the detected condition.  
   
   
       47 . The system of  claim 45 , wherein the infusion pump further comprises means responsive to a remotely transmitted therapy delivery command for delivering a bolus of the NO-donor drug.  
   
   
       48 . The system of  claim 45 , wherein the detecting means comprises: 
 means for sensing a feature of the EGM of the heart; and    means for detecting a characteristic of the sensed feature indicative of an ischemic state.    
   
   
       49 . The system of  claim 45 , wherein the detecting means comprises: 
 means for sensing blood pH; and    means for detecting a value of the sensed blood pH indicative of an ischemic state.    
   
   
       50 . The system of  claim 45 , wherein the detecting means comprises: 
 means for sensing blood oxygen saturation; and    means for detecting a value of the sensed oxygen saturation indicative of an ischemic state.    
   
   
       51 . The system of  claim 45 , wherein the detecting means comprises: 
 means for sensing one or both of blood pressure and flow in the heart; and    means for detecting a value of the sensed one or both of blood pressure and flow indicative of an ischemic state.    
   
   
       52 . The system of  claim 45 , further comprising: 
 a fixation catheter having a fixation catheter lumen extending between proximal and distal fixation catheter lumen openings and a distal tissue fixation mechanism adapted to be advanced through a selected peripheral vein and one of the inferior vena cava and the superior vena cava to establish a transvenous route into the right atrium of the heart    means for disposing the distal fixation mechanism and distal fixation catheter lumen opening proximate the right atrial wall; and    means for affixing the distal fixation mechanism to the right atrial wall,    whereby the infusion catheter is adapted to be advanced through the fixation catheter lumen out of the distal fixation catheter lumen opening and through the stabilized atrial wall to dispose the distal catheter segment having the distal infusion catheter lumen end opening in the pericardial space.    
   
   
       53 . The system of  claim 45 , wherein the NO-donor drug is selected from the group consisting of nitroglycerin, isosorbide mononitrate, sodium nitroprusside, a diazenium diolate, an NO aspirin, an S-Nitrosothiol, and morpholinosydnonimime or any other NO-generating, NO-donor or NO-precursor drug (e.g. L-arginin).