Method and devices for heart treatment

• US 6,748,258 B1
• Filed: 11/03/2000
• Issued: 06/08/2004
• Est. Priority Date: 11/05/1999
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Mueller, Richard L., Chee, U. Hiram
• Primary Examiner(s): Ruhl, Dennis W.
• Assistant Examiner(s): Lin, Jeoyuh
• Application Number:
  US09/706,584
• Time in Patent Office: 1,313 Days
• Field of Search: 600/473, 600/476, 600/481, 600/508, 600/425, 600/407, 600/410, 600/411, 600/427, 600/456, 382/128, 382/130, 382/131, 382/133, 424/4.2, 324/307, 324/312, 128/899
• US Class Current: 600/425
• CPC Class Codes: A61B 17/32053 Punch like cutting instruments, e.g. using a cylindrical or oval knife A61B17/326 takes precedence; trepans A61B17/1695; for use on the cornea A61F9/007
• CPC Class Codes: A61B 17/3417 Details of tips or shafts, e.g. grooves, expandable, bendable; Multiple coaxial sliding cannulas, e.g. for dilating syringe needles A61M5/32; dilators A61M29/00
• CPC Class Codes: A61B 17/3478 Endoscopic needles, e.g. for infusion biopsy needles A61B10/0233; catheters with injection needles A61M25/0067
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 2017/00247 Making holes in the wall of the heart, e.g. laser Myocardial revascularization
• CPC Class Codes: A61B 2018/00392 Transmyocardial revascularisation
• CPC Class Codes: A61B 2090/036 abutting on tissue or skin

Abstract

Various methods and devices for treating a patient who has lost, or is at risk of losing cardiac function by cardiac ischemia are disclosed. Treatment includes first imaging a patient'"'"'s heart, or a portion thereof, to identify underperfused regions of cardiac muscle, and a source of oxygenated blood that is proximate to the underperfused region. Between the underperfused regions and the oxygenated blood source, a target area is selected where thermal or mechanical injury is introduced, and optionally reintroduced, to convert initial capillary blush, resulting from the injury.

Claims

1. A method of treating a patient at risk of loss of cardiac function by cardiac ischemia, comprising

(a) imaging the patient'"'"'s heart, or a portion thereof, to identify (i) an underperfused region of cardiac muscle, (ii) a source of oxygenated blood that is proximate a boundary of the underperfused region, and (iii) a target area that includes said underperfused-region boundary and a tissue expanse lying between said oxygenated blood supply and said boundary;

(b) at each of a plurality of sites throughout the target area, introducing a stimulus effective to stimulate angiogenesis in myocardial tissue and form a capillary network from the source of oxygenated blood to the underperfused region; and

(c) sustaining a demand for oxygen at the underperfused region for a period sufficient to covert the capillary network into an arterial network,

wherein said sustaining is accomplished by requiring the patient to undergo a regular exercise regime.

2. The method of claim 1, wherein step (a) includes monitoring blood flow in the heart by myocardial perfusion imaging by a method selected from (i) single-photon emission computed tomography (SPECT), (ii) positron-emission tomography (PET), (iii) echo-planar imaging, (iv) myocardial perfusion imaging by dynamic contrast MRI, or (v) angiography.

3. The method of claim 1, wherein said sustaining is further accomplished by producing a slow-healing or repeated injury at or near said target-area sites.

4. The method of claim 1, wherein the stimulus introduced in step (b) is a growth factor selected from fibroblast growth factor-I (FGF-1 or FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-1), or combinations of two or more of these growth factors.

5. The method of claim 4, wherein the growth factor is introduced in the form of a recombinant protein carried in a pharmaceutically acceptable medium, and the growth factor is introduced by a method selected from (i) injecting the protein directly into myocardial tissue at said site, (ii) drawing the protein into myocardial tissue at said site by iontophoresis from a reservoir placed against the site, (iii) forming a channel in the myocardium at said site, and placing the protein into the channel, or (iv) bombarding said site with a biolistic particle containing or coated with the protein.

6. The method of claim 4, wherein said growth factor is introduced by a vector containing the coding sequence for the growth factor and a control region effective to promote transcription of said coding region in patient myocardial cells, and the vector is introduced by a method selected from (i) injecting the vector directly into myocardial tissue at said site, (ii) drawing the vector into myocardial tissue at said site by iontophoresis from a reservoir placed against the site, (iii) forming a channel in the myocardium at said site, and placing the vector into the channel, or (iv) bombarding said site with a biolistic particle containing or coated with the vector.

7. The method of claim 4, wherein said growth factor is introduced in the form of a myocardial or cardiac myoblast cell which has been transformed with a gene encoding the growth factor, and the transformed cell is introduced by a method selected from (i) injecting the cell directly into myocardial tissue at said site, (ii) forming a channel in the myocardium at said site, and placing the cell into the channel, or (iii) bombarding said site with a biolistic particle containing or coated with the cell.

8. The method of claim 4, wherein step (b) is carried out so as to create a temporal gradient of growth factor availability in the target area, progressing from greater short-term availability near the source of oxygenated blood and more long-term availability near and in the boundary of the underperfused region.

11. The method of claim 1, wherein the stimulus introduced into the target area is a combination of mechanical injury and chemical injury.

9. A method of treating a patient at risk of loss of cardiac function by cardiac ischemia, comprising

(a) imaging the patient'"'"'s heart, or a portion thereof, to identify (i) an underperfused region of cardiac muscle, (ii) a source of oxygenated blood that is proximate a boundary of the underperfused region, and (iii) a target area that includes said underperfused-region boundary and a tissue expanse lying between said oxygenated blood supply and said boundary;

(b) at each of a plurality of sites throughout the target area, introducing a stimulus effective to stimulate angiogenesis in myocardial tissue and form a capillary network from the source of oxygenated blood to the underperfused region;

(c) equipping the patient with an exercise monitor that indicates the level and amount of heart exercise the patient achieves; and

(d) requiring the patient to achieve an amount and level of heart exercise effective to stimulate the conversion of capillary blush produced by said step (b) to arterioles in the target area.

10. The method of claim 9, wherein a pacemaker is used to exercise the patient'"'"'s heart.

12. A method of treating a patient at risk of loss of cardiac function by cardiac ischemia, comprising

(a) imaging the patient'"'"'s heart, or a portion thereof, to identify (i) an underperfused region of cardiac muscle, (ii) a source of oxygenated blood that is proximate a boundary of the underperfused region, and (iii) a target area that includes said underperfused-region boundary and a tissue expanse lying between said oxygenated blood supply and said boundary;

(b) at each of a plurality of sites throughout the target area, introducing a stimulus effective to stimulate angiogenesis in myocardial tissue and form a capillary network from the source of oxygenated blood to the underperfused region; and

(c) sustaining a demand for oxygen at the underperfused region for a period sufficient to covert the capillary network into an arterial network;

wherein;

the stimulus introduced in step (b) is a growth factor; and

the growth factor is introduced by a method selected from (i) drawing the growth factor into myocardial tissue at said site by iontophoresis from a reservoir placed against the site, (ii) forming a channel in the myocardium at said site, and placing the growth factor into the channel, or (iii) bombarding said site with a biolistic particle containing or coated with the growth factor.

13. The method of claim 12, wherein step (a) includes monitoring blood flow in the heart by myocardial perfusion imaging by a method selected from (i) single-photon emission computed tomography (SPECT), (ii) positron-emission tomography (PET), (iii) echo-planar imaging, (iv) myocardial perfusion imaging by dynamic contrast MRI, or (v) angiography.

14. The method of claim 12, wherein said sustaining is accomplished by producing a slow-healing or repeated injury at or near said target-area sites.

15. The method of claim 12, wherein the growth factor is introduced in the form of a recombinant protein carried in a pharmaceutically acceptable medium.

16. The method of claim 12, wherein said growth factor is introduced by a vector containing the coding sequence for the growth factor and a control region effective to promote transcription of said coding region in patient myocardial cells.

17. The method of claim 12, wherein said growth factor is introduced in the form of a myocardial or cardiac myoblast cell which has been transformed with a gene encoding the growth factor.

18. The method of claim 12, wherein the growth factor is selected from fibroblast growth factor-I (FGF-1 or FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-1), or combinations of two or more of these growth factors.

19. A method of treating a patient at risk of loss of cardiac function by cardiac ischemia, comprising

(a) imaging the patient'"'"'s heart, or a portion thereof, to identify (i) an underperfused region of cardiac muscle, (ii) a source of oxygenated blood that is proximate a boundary of the underperfused region, and (iii) a target area that includes said underperfused-region boundary and a tissue expanse lying between said oxygenated blood supply and said boundary;

(b) at each of a plurality of sites throughout the target area, introducing a stimulus effective to stimulate angiogenesis in myocardial tissue and form a capillary network from the source of oxygenated blood to the underperfused region; and

(c) sustaining a demand for oxygen at the underperfused region for a period sufficient to covert the capillary network into an arterial network;

wherein;

the stimulus introduced in step (b) is a growth factor selected from fibroblast growth factor-I (FGF-1 or FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-1), or combinations of two or more of these growth factors; and

wherein step (b) is carried out so as to create a temporal gradient of growth factor availability in the target area, progressing from greater short-term availability near the source of oxygenated blood and more long-term availability near and in the boundary of the underperfused region.