Methods and apparatus to treat and prevent atrial tachyarrhythmias

• US 20090054943A1
• Filed: 08/22/2007
• Published: 02/26/2009
• Est. Priority Date: 08/22/2007
• Status: Active Grant

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Sinha, Prashant, Schwartz, Mark, Qu, Jihong, Sih, Haris J.
• Granted Patent: US 8,311,620 B2
• Time in Patent Office: Days
• US Class Current: 607/14
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61N 1/0568 with drug delivery
• CPC Class Codes: A61N 1/0587 Epicardial electrode systems; Endocardial electrodes piercing the pericardium
• CPC Class Codes: A61N 1/3621 for treating or preventing abnormally high heart rate
• CPC Class Codes: A61N 1/3962 in combination with another heart therapy
• CPC Class Codes: A61N 1/39622 Pacing therapy
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

The invention provides a cardiac rhythm management system which includes a tachyarrhythmia detection and classification circuit programmed to detect and classify a tachyarrhythmia, a biologic therapy delivery device configured to deliver or regulate an expression cassette suitable for terminating or preventing atrial fibrillation (AF), and a control circuit coupled to the tachyarrhythmia detection and classification circuit and the biologic therapy delivery device. Also provided is an implantable medical device for use in a body having a cardiovascular system, which includes an implantable device body including at least a cardiovascular portion configured to be in the cardiovascular system, and an expression cassette incorporated into the cardiovascular portion of the implantable device body, the expression cassette selected to express a gene product that terminates or prevents AF. Further provided are methods which employ particular expression cassettes to prevent, inhibit or treat AF.

Claims

1. A cardiac rhythm management system, comprising:

a tachyarrhythmia detection and classification circuit programmed to detect and classify a tachyarrhythmia;

a biologic therapy delivery device configured to deliver or regulate an expression cassette suitable for terminating or preventing AF; and

a control circuit coupled to the tachyarrhythmia detection and classification circuit and the biologic therapy delivery device, the control circuit programmed to trigger the delivery or regulation of the expression cassette in response to a detection of a tachyarrhythmia classified as AF.

2. The system of claim 1, wherein the biologic therapy delivery device comprises an agent delivery device configured to deliver one or more agents including the expression cassette.

3. The system of claim 1, wherein the biologic therapy delivery device comprises a gene regulatory signal delivery device configured to deliver a regulatory signal carrying a form of energy suitable for regulating the expression cassette.

4. An implantable medical device for use in a body having a cardiovascular system, the device comprising:

an implantable device body including at least a cardiovascular portion configured to be in the cardiovascular system; and

an expression cassette incorporated into the cardiovascular portion of the implantable device body, the expression cassette selected to terminate or prevent AF.

5. The implantable medical device of claim 4, comprising a layer of coating material coated on the cardiovascular portion, and wherein the expression cassette is embedded in the coating material.

6. The implantable medical device of claim 5, comprising an implantable lead having a distal end configured for endocardial or epicardial placement, the implantable lead including the cardiovascular portion.

7. The implantable medical device of claim 6, comprising an intravascular stent including the cardiovascular portion.

8. The implantable medical device of claim 4, comprising a patch configured to be placed on a wall of the cardiovascular system, and wherein the expression cassette is embedded in the patch.

9. The implantable medical device of claim 8, wherein the patch includes an isolated extracellular matrix support.

10. A method to prevent, inhibit or treat atrial fibrillation (AF), comprising:

delivering an effective amount of a regulatory signal to a mammal having or at risk of AF and having cells in the atria comprising an expression cassette comprising a regulatable transcriptional control element operably linked to a nucleic acid sequence for a gene product, wherein the gene product comprises sequences corresponding to those for an ion channel protein, a connexin, or a fragment thereof, and wherein the regulatory signal increases expression from the regulatable transcription control element.

12. The method of claim 10 or 11 wherein the expression from the expression cassette alters conduction velocity or effective refractory period (ERP).

13. The method of claim 10 further comprising delivering the regulatory signal in response to a physiological signal indicative of AF.

15. The method of claim 10 or 11 wherein the gene product sequences correspond to those for a protein which forms an ion channel associated with action potential duration, ERP, the Q-T interval, or a combination thereof.

16. The method of claim 10 or 11 wherein the gene product encodes a protein associated with I_Kur, I_K1 or I_f.

17. The method of claim 10 or 11 wherein the gene product encodes Cx40, Cx43, or Cx45.

18. The method of claim 10 or 11 wherein the gene product is a dominant negative protein, siRNA or an antisense oligonucleotide.

19. The method of claim 10 or 11 wherein the expression of the expression cassette prolongs action potential duration, ERP, or both.

20. The method of claim 10 or 11 wherein the expression of the gene product alters Kir2.1 expression, Kv1.5 expression or HCN expression in the atria of the mammal.

21. The method of claim 10 or 11 wherein the gene product is Kv1.5 siRNA, Kv1.5 antisense RNA or a dominant negative Kv1.5.

22. The method of claim 10 or 14 wherein the transcriptional control element is regulated by electromagnetic energy or selected wavelengths of light.

23. The method of claim 10 or 14 wherein the transcriptional control element is regulated by a drug.

24. The method of claim 10 or 14 wherein the transcriptional control element is regulated by a sensed rapid electrical rhythm.

25. The method of claim 10 or 11 wherein the expression cassette is systemically administered to the mammal.

26. The method of claim 25 wherein the expression cassette is infused into an artery.

27. The method of claim 10 or 11 wherein the expression cassette is injected into the atria of the mammal.

28. The method of claim 10 or 11 wherein a viral vector delivers the expression cassette to the mammal.

29. The method of claim 10 or 11 wherein the expression cassette is administered to the mammal via a biocompatible material placed on or near the atria of the mammal.

30. The method of claim 29 wherein electrophoresis or photolysis delivers the expression cassette from the biocompatible material to the atria.

11. A method to prevent, inhibit or treat AF, comprising:

administering to a mammal having or at risk of AF, an expression cassette comprising a transcriptional control element operably linked to a nucleic acid sequence for a gene product, wherein the gene product comprises sequences corresponding to those for an ion channel protein, a connexin, or a fragment thereof, wherein expression from the expression cassette in the atria of the mammal downregulates I_Kur, I_K1 or I_f or upregulates connexin expression or activity in an amount effective to prevent, inhibit or prevent AF.

14. The method of claim 11 wherein the transcriptional control element comprises a regulatable transcription control element.