Surgery: light – thermal – and electrical application – Light – thermal – and electrical application – Electrical therapeutic systems
Reexamination Certificate
2001-08-21
2003-09-16
Schaetzle, Kennedy (Department: 3762)
Surgery: light, thermal, and electrical application
Light, thermal, and electrical application
Electrical therapeutic systems
C607S002000
Reexamination Certificate
active
06622041
ABSTRACT:
BACKGROUND OF THE INVENTION
It is currently estimated that some five million Americans suffer from congestive heart failure (CHF), a condition of abnormally low cardiac output. More than one million of these afflicted persons are under age 60. An increasing rate of CHF sufferers may be regarded as a sign of progress in the field of cardiology, since it stems in large measure from saving the lives of heart attack victims and patients with other heart problems. But many of the survivors are left with CHF, in which a markedly reduced cardiac output leads to an inability of the heart to maintain the body's need for oxygen-rich blood circulation. As many as 40 percent of CHF patients are at risk of sudden death.
Another fourteen million Americans are diabetic and forty million more exhibit hypertension (persistent elevated blood pressure). A considerable percentage of patients with diabetic neuropathy, hypertension and other pathologies affecting the nervous system are also at higher risk of sudden death.
Diseases such as CHF, hypertension and diabetes are characteristically associated with an increased autonomic cardiovascular drive (see, e.g., Blood Pressure 1998; Suppl 3:5-13). In addition, increased autonomic cardiovascular drive has been associated with myocardial infarction, cardiac transplantation, tetraplegia and anxiety disorders (Circulation 1996; 93:1043-1065, Bio Psychol March 1998; 47(3):243-63). “Tone” is the output that emanates from the central nervous system via sympathetic and parasympathetic efferent nerves. The overall “drive” depends on the balance between inhibitory (parasympathetic or vagal) and excitatory (sympathetic) tone and the responsiveness of the organ of interest to that tone. Responsiveness, in turn, depends on the receptor's properties as well as on the intrinsic functional or anatomic properties of the responding organ. An enhanced autonomic drive, independent of the underlying condition, greatly increases the risk of poor cardiovascular outcomes. It follows that targeting the underlying autonomic imbalance in congestive heart failure, hypertension and diabetes may not only be pathophysiologically sound but may also lead to better outcomes (Juilius, Blood Press 1998; Suppl 3:5-13).
As with any medical therapy, before a therapy is prescribed it is important to identify which patients are at increased risk. For CHF, research has established markers that identify patients at increased risk of sudden death from an imbalance between the sympathetic and parasympathetic systems. Results from a large multi-center trial established that baroreflex sensitivity and heart-rate variability are both predictors of mortality with CHF patients, and when combined, increase the predictive value (Lancet 1988:351:478-484). Similar studies have shown a predictive value of heart rate variability with diabetes (Circulation 1996;93:1043-1065).
The simplest measure of heart rate variability expresses the reciprocal of heart rate (R-R interval) and calculates a standard deviation of all normal beats (SDNN) over a period of time. The baroreflex sensitivity (BRS) is a marker of the capability to reflexly increase vagal activity and to decrease sympathetic activity in response to a sudden increase in blood pressure. It provides a more focused measure of autonomic control than heart rate variability. BRS is calculated from measurement of the rate-pressure response to intravenous phenylephrine.
Treatment strategies for CHF employ methods to decrease the excitatory or sympathetic drive, and/or to increase the inhibitory or parasympathetic drive. The results of clinical trials on two beta-blocker drugs demonstrate the efficacy of decreasing the sympathetic drive for such treatment. The clinical studies confirm earlier reports from dog study models of CHF treated with beta-blockers, that the drugs block the effects of adrenaline which is over-produced in CHF patients. Heart experts suspect that many symptoms of CHF occur as an overreaction of the body to some type of heart-muscle damage. The body misinterprets the situation and reacts as though severe dehydration or serious bleeding were the cause of the lowered blood flow. To stimulate the heart, the body produces more adrenaline, which makes the heart work harder. Deaths were reduced by 35% among patients given the beta-blockers Carvedilol or Metoprolol (Prog. cardiovascular Dis. January-February 1999; 41(4)301-312, which states that beta-blockers should be considered the standard of care for mild-to-moderate heart failure). Unfortunately, beta-blockers—the older versions of which are relatively inexpensive—have side effects that prevent many patients from tolerating this mode of therapy.
Mild exercise has also been demonstrated to improve the sympathetic-parasympathetic balance for CHF patients. In a recent randomized study of 99 patients, Belardinelli reported (Circulation Mar. 9, 1999; 99(9):1173-1182) an 18% mortality in the exercise group compared to a 41% mortality in the non-exercise patient group. This clinical study confirms protective benefits of exercise training in dogs with simulated CHF (Circulation February 1994; 89(2):548552). Heart rate variability (SDNN) also improved by 74% in the dog study, suggesting an improved sympathetic-parasympathetic balance. Although beneficial, exercise is initially risky for the CHF patient until an improved balance of the sympathetic-parasympathetic system can be obtained. Exercise can trigger a heart attack or other adverse cardiac events in patients with unstable CHF. It is essential to monitor the patient closely during the first four to eight weeks of exercise. Even aside from the risk, initiating and maintaining an exercise program is difficult for CHF patients, because of patient fatigue and shortness of breath associated with the disease.
A cardiac defibrillator may be implanted to protect the CHF patient against sudden death upon an event of cardiac fibrillation, but its effect on long term survival is limited (Circulation Dec. 1, 1995; 92(11):3273-3281). The device (as well as the implant procedure) is relatively expensive, and does nothing to correct the underlining imbalance between the sympathetic and parasympathetic systems.
It is a principal aim of the present invention to provide improved methods of treating patients who suffer disorders as a result of increased autonomic cardiovascular drive, including but not limited to CHF, diabetes and hypertension. These improved methods seek to relieve the underlying autonomic imbalance between inhibitory (parasympathetic) and excitatory (sympathetic) tone.
SUMMARY OF THE INVENTION
The methods of this invention involve increasing the inhibitory response of the parasympathetic or vagal system. The approach is to stimulate the cardiac branch of the vagus nerve. The protective role of vagal stimulation in the chronic dog CHF model has been reported (Circulation Research 1991;68:1471-1481). Prior to vagal stimulation, 100% of the dogs in the study were at risk of sudden death. After vagus nerve stimulation, only 10% remained at risk, versus 87% of a control group of dogs. The report states that the decrease in heart rate from vagal stimulation is an important but not always essential protective mechanism. The electrophysiological effects secondary to the vagally mediated antagonism of the sympathetic activity on the heart are likely to play a major role. In addition, vagal activity may have antagonized the vasoconstrictor effect of the sympathetic activity by acting on norepinephrine release and also by a direct vasodilatory effect.
Kamath reported on the neurocardiac responses to vagoafferent electrostimulation in eight patients with vagal stimulation for the control of epilepsy (Pace 1992, Vol 15, 1581-1587). These patients were chronically stimulated on the cervical branch below the cardiac branch; therefore, the effects are presumed to be central to the brain. The patients were randomized into High Level and Low Level stimulation groups. Those in the High Level stimulation group had a statistically significant improve
Adkins Robert A.
Barrett Burke T.
Terry, Jr. Reese S.
Blank Rome LLP
Cyberonics, Inc.
Droesch Kristen L
Schaetzle Kennedy
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