Systems and methods for treatment of coronary artery disease

• US 7,481,759 B2
• Filed: 08/02/2002
• Issued: 01/27/2009
• Est. Priority Date: 08/03/2001
• Status: Expired due to Fees

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Stultz, Mark R., Whitehurst, Todd K., McClure, Kelly H, McGivern, James P
• Primary Examiner(s): Bockelman; Mark W
• Assistant Examiner(s): Bertram; Eric D
• Application Number:
  US10/211,463
• Publication Number:
  US 20030036773A1
• Time in Patent Office: 2,370 Days
• Field of Search: 604/891.1, 607/120, 607/3
• US Class Current: 600/3
• CPC Class Codes: A61M 2205/3523 using telemetric means
• CPC Class Codes: A61M 2205/8206 battery-operated
• CPC Class Codes: A61M 2230/06 Heartbeat rate only
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362

Abstract

Methods and systems for treatment of coronary artery disease (CAD) include implantation of the discharge portion(s) of a catheter and, optionally, electrodes on a lead, near the tissue(s) to be stimulated. Stimulation pulses, i.e., drug infusion pulses and optional electrical pulses, are supplied by a stimulator implanted remotely, and through the catheter or lead, which is tunneled subcutaneously between the stimulator and stimulation site. Stimulation sites include the coronary arteries, the aorta, the left ventricle, the left atrium, and/or the pulmonary veins, among other locations. Disclosed treatments include drugs used for acute treatment of CAD, for chronic treatment of CAD, to promote angiogenesis, and/or as AGE Crosslink Breakers, among other drugs. For instance, the systems and methods reduce or eliminate the incidence of CAD and related morbidities, improve symptoms resulting from CAD, and/or improve cardiac blood flow, cardiac function, and patient quality of life.

Claims

1. A method for treating coronary artery disease (CAD), comprising:

implanting a fully implantable stimulator system for generating stimulating pulses;

acutely administering via the stimulator system stimulating pulses of at least one acute CAD drug;

chronically administering via the stimulator system stimulating pulses of at least one chronic CAD drug; and

administering via the stimulator system stimulating pulses of at least one drug that reverses CAD;

wherein acutely administering via the stimulator system stimulating pulses of at least one acute CAD drug, chronically administering via the stimulator system stimulating pulses of at least one chronic CAD drug, and administering via the stimulator system stimulating pulses of at least one drug that reverses CAD are performed in combination to simultaneously administer at least two of the drugs.

2. The method of claim 1 wherein the at least one drug that reverses CAD comprises at least one of VEGF, FGF, a gene that encodes a protein or other gene product that leads to angiogenesis, phVEGF, an AGE Crosslink breaker, ALT-711, and a gene that encodes a protein or other gene product that leads to removal of AGE Crosslinks.

3. The method of claim 1 further comprising administering electrical stimulation pulses via the stimulator system to treat CAD during the delivery of one or more drugs.

4. A method of treating coronary artery disease, comprising:

providing a stimulator that generates a pulse;

providing a catheter connected to the stimulator;

providing a lead connected to the stimulator;

delivering via the stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue;

delivering via the stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs;

providing at least one sensor and sensing a physical condition resulting from the delivered infusion and electrical stimulation pulses, and adjusting stimulation parameters based on the sensed condition; and

wherein sensing a physical condition includes sensing antibodies that bind to markers of ischemia.

5. The method of claim 4, wherein delivering via the stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue includes infusing a bolus of a vasodilator, and wherein delivering via the stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs includes producing a series of excitatory electrical stimulation pulses.

6. The method of claim 5, wherein producing a series of excitatory electrical stimulation pulses includes producing a series of excitatory electrical stimulation pulses at less than about 50-100 Hz.

7. The method of claim 4, wherein delivering via the stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs includes applying electrical stimulation to the vagus nerve, increasing parasympathetic stimulation to the heart, indirectly inhibiting sympathetic stimulation, and inhibiting sympathetic vasoconstriction of the coronary arteries.

8. The method of claim 7, wherein applying electrical stimulation to the vagus nerve includes delivering electrical stimulation pulses at about 10-50 pulses per second, wherein each pulse includes a pulse duration of about 100-500 microseconds and an amplitude of about 0.25- 10 milliamps.

9. The method of claim 4, wherein delivering via the stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue includes delivering magnesium sulfate.

10. The method of claim 4, wherein providing at least one sensor and sensing a physical condition includes providing a microstimulator and detecting abnormal cardiac electrocardiogram events.

11. The method of claim 10, wherein detecting abnormal cardiac electrocardiogram events includes predictively diagnosing the perfusion of the myocardium by finding the p, R, and T waves of the electrocardiogram.

12. The method of claim 10, wherein detecting abnormal cardiac electrocardiogram events includes predictively diagnosing the perfusion of the myocardium by analyzing the timing of the relationships and durations of the p-wave, QRS complex, and T-wave of the electrocardiogram.

13. The method of claim 4, wherein providing at least one sensor and sensing a physical condition includes providing a microstimulator containing at least one accelerometer, detecting motion of the myocardium with the at least one accelerometer, and inferring the contractility of the myocites of the myocardium by analyzing the acceleration of the myocardium.

14. A method of treating coronary artery disease, comprising:

providing a first stimulator that generates a pulse;

providing a catheter connected to the first stimulator;

providing a lead connected to the first stimulator;

providing a second stimulator dedicated to sensory processes, wherein the second stimulator communicates with the first stimulator;

delivering via the first stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue;

delivering via the first stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs;

sensing a physical condition with the second stimulator resulting from the delivered infusion and electrical stimulation pulses; and

adjusting stimulation parameters based on the sensed condition;

wherein delivering via the first stimulator and catheter includes;

acutely administering via the stimulator system stimulating pulses of at least one acute CAD drug;

chronically administering via the stimulator system stimulating pulses of at least one chronic CAD drug; and

administering via the stimulator system stimulating pulses of at least one drug that reverses CAD;

wherein acutely administering, chronically administering, and administering are performed in combination.

15. The method of claim 14, wherein providing a second stimulator and sensing a physical condition includes providing a micro stimulator and detecting abnormal cardiac electrocardiogram events.

16. The method of claim 15, wherein detecting abnormal cardiac electrocardiogram events includes predictively diagnosing the perfusion of the myocardium by finding the p, R, and T waves of the electrocardiogram.

17. The method of claim 15, wherein detecting abnormal cardiac electrocardiogram events includes predictively diagnosing the perfusion of the myocardium by analyzing the timing of the relationships and durations of the p-wave, QRS complex, and T-wave of the electrocardiogram.

18. The method of claim 14, wherein providing a second stimulator and sensing a physical condition includes providing a microstimulator containing at least one accelerometer, detecting motion of the myocardium with the at least one accelerometer, and inferring the contractility of the myocites of the myocardium by analyzing the acceleration of the myocardium.

19. The method of claim 18, wherein sensing a physical condition includes sensing antibodies that bind to markers of ischemia.

20. The method of claim 14, further comprising increasing the inotropic effect on the at least one cardiac tissue, wherein delivering via the first stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue includes delivering via the first stimulator and catheter infusion pulses of hypothalamic inhibitory factor.

21. A method of treating coronary artery disease, comprising:

providing a stimulator that generates a pulse;

providing a catheter connected to the stimulator;

providing a lead connected to the stimulator;

delivering via the stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue;

delivering via the stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs;

providing at least one sensor and sensing a physical condition resulting from the delivered infusion and electrical stimulation pulses, and adjusting stimulation parameters based on the sensed condition;

wherein providing at least one sensor and sensing a physical condition includes providing a microstimulator and detecting abnormal cardiac electrocardiogram events; and

wherein detecting abnormal cardiac electrocardiogram events includes predictively diagnosing the perfusion of the myocardium by finding the p, R, and T waves of the electrocardiogram.

22. A method of treating coronary artery disease, comprising:

providing a stimulator that generates a pulse;

providing a catheter connected to the stimulator;

providing a lead connected to the stimulator;

delivering via the stimulator and catheter infusion pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue;

delivering via the stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs;

providing at least one sensor and sensing a physical condition resulting from the delivered infusion and electrical stimulation pulses, and adjusting stimulation parameters based on the sensed condition;

wherein providing at least one sensor and sensing a physical condition includes providing a microstimulator and detecting abnormal cardiac electrocardiogram events; and

wherein detecting abnormal cardiac electrocardiogram events includes predictively diagnosing the perfusion of the myocardium by analyzing the timing of the relationships and durations of the p-wave, QRS complex, and T-wave of the electrocardiogram.

23. A method of treating coronary artery disease, comprising:

providing a stimulator that generates a pulse;

providing a catheter connected to the stimulator;

providing a lead connected to the stimulator;

delivering via the stimulator and catheter infrision pulses of at least one drug as at least one treatment for coronary artery disease to at least one cardiac tissue;

delivering via the stimulator and lead electrical stimulation pulses during the delivery of one or more stimulating drugs;

providing at least one sensor and sensing a physical condition resulting from the delivered infusion and electrical stimulation pulses, and adjusting stimulation parameters based on the sensed condition; and

wherein providing at least one sensor and sensing a physical condition includes providing a micro stimulator containing at least one accelerometer, detecting motion of the myocardium with the at least one accelerometer, and inferring the contractility of the myocites of the myocardium by analyzing the acceleration of the myocardium.