Apnea and hypopnea are forms of disordered breathing characterized by periods of significantly reduced respiration. With hypopnea, respiration is reduced but still present. With apnea, however, respiration may cease completely for a minute or longer. Apnea most commonly occurs while the patient is asleep. Indeed, individual episodes of sleep apnea can occur hundreds of times during a single night. Accordingly, patients with apnea often experience excessive fatigue during the day. In addition, apnea can exacerbate various medical conditions, particularly congestive heart failure (CHF) wherein the patient suffers from poor cardiac function. Other medical conditions that can be adversely affected by apnea include: high blood pressure, risk for heart attack and stroke, memory problems, impotency and sexual dysfunction, migraine headaches, depression and anxiety, polycythemia (increase in the number of red blood cells), cor pulmonale (an alteration in the structure and function of the right ventricle caused by a primary disorder of the respiratory system), bradycardia (excessively slow heart rate), tachycardia (excessively fast heart rate), pulmonary hypertension hypoxemia (chronic daytime low blood oxygen) and hypercapnia (increased blood carbon dioxide (CO2)).
Apnea is often associated with Cheyne-Stokes Respiration (CSR), which is an abnormal respiratory pattern occurring in some patients with congestive heart failure (CHF). CSR is characterized by alternating periods of hypopnea and hyperpnea (i.e. fast, deep breathing.) Briefly, respiration is regulated by groups of nerve cells in the brain in response to changing blood chemistry levels, particularly blood CO2 levels. When blood CO2 levels exceed a certain threshold, the groups of nerve cells generate a burst of nerve signals for triggering inspiration. The inspiration nerve signals are relayed via phrenic nerves to the diaphragm and via other nerves to chest wall muscles, which collectively contract to expand the lungs. CSR arises partly due to a time lag between blood CO2 levels sensed by the respiratory control nerve centers of the brain and the blood CO2 levels. With CHF, poor cardiac function results in poor blood flow to the brain such that the nerve centers respond to blood CO2 levels that are no longer properly representative of the overall blood CO2 levels in the body. Hence, the nerve centers trigger an increase in the depth and frequency of breathing in an attempt to compensate for perceived high blood CO2 levels—although the blood CO2 levels will have already dropped. By the time the respiratory control nerve centers detect the drop in blood CO2 levels and act to slow respiration, the blood CO2 levels will have already increased. This cycle becomes increasingly unbalanced until respiration alternates between hypopnea and hyperpnea. The periods of hypopnea often become sufficiently severe that no breathing occurs between the periods of hyperpnea, i.e. periods of frank apnea occur between the periods of hyperpnea. The fluctuating blood chemistry levels caused by alternating between hyperpnea and apnea/hypopnea can significantly exacerbate CHF and other medical conditions. When CHF is still mild, CSR occurs, if at all, only while the patient is sleeping. When it becomes more severe, CSR can occur while the patient is awake. Accordingly, CSR is one mechanism by which apnea can occur while a patient is awake. Hence, apnea is not limited to occurring only while a patient is asleep.
Herein, apnea arising due to CSR is referred to as “CSR-induced apnea.” Hypopnea arising due to CSR is referred to as “CSR-induced hypopnea.” For the sake of generality, the term “CSR-induced apnea/hypopnea” is used to encompass both conditions. Note that, in some of the medical literature, apnea arising due to CSR is referred to as “CSA-CSR,” where CSA stands for “Central Sleep Apnea.” However, as noted, CSR-induced apnea can potentially occur while the patient is awake and hence is not necessarily a form of sleep apnea. Moreover, the term CSA also refers to a fundamentally different type of apnea, which is believed to be the result of a neurological condition within the central nervous system. With CSA, phrenic nerve signals are simply not generated during extended periods of time while the patient is asleep or are of insufficient magnitude to trigger sufficient muscle contraction to achieve inhalation. This occurs regardless of the blood CO2 levels and hence appears to be unrelated to CSR-induced forms of apnea. Herein, to avoid any possible confusion, the term CSR-CSA is not used. As noted, the term CSR-induced apnea/hypopnea is instead used. Note, also, that there is yet another form of apnea—obstructive sleep apnea (OSA). OSA arises when the respiration airway is temporarily blocked. OSA is not particularly relevant to the techniques described herein but is mentioned for the sake of completeness.
In view of the adverse consequences of CSR-induced apnea/hypopnea, it is highly desirable to provide techniques for suppressing episodes of the condition. A variety of techniques have been proposed, particularly for use by pacemakers, ICDs or other implantable medical devices. With many such techniques, the implantable device first detects an episode of apnea/hypopnea and then delivers therapy to alleviate the episode. Examples of techniques for detecting episodes of apnea/hypopnea are discussed in U.S. patent application Ser. No. 10/883,857, of Koh et al., entitled “System and Method for Real-Time Apnea/Hypopnea Detection Using an Implantable Medical System,” filed Jun. 30, 2004. See, also, U.S. patent application Ser. No. 10/795,009, of Koh, entitled “System and Method for Distinguishing among Obstructive Sleep Apnea, Central Sleep Apnea and Normal Sleep Using an Implantable Medical System,” filed Mar. 4, 2004 and U.S. patent application Ser. No. 10/844,023, of Koh, filed May 11, 2004, entitled “System and Method for Providing Demand-Based Cheyne-Stokes Respiration Therapy Using an Implantable Medical Device”. Once an episode of apnea/hypopnea is detected, therapy is delivered to terminate the episode and restore respiration that is more normal. Exemplary techniques include applying electrical stimulation directly to the phrenic nerves via implantable nerve stimulators so as to cause the diaphragm to contract. These and other therapeutic techniques are discussed in the aforementioned patent applications as well. If therapy is ineffective, warning signals can be generated to awaken the patient, which is typically sufficient to restore normal respiration.
It would be preferable, however, to provide techniques for suppressing CSR-induced apnea/hypopnea that do not require detecting individual episodes of apnea or hypopnea, as reliable detection can sometimes be problematic. It would also be desirable to provide suppression therapies that do not require phrenic nerve stimulators or other potentially elaborate or intrusive therapeutic measures. One technique that has been proposed is simply to increase a cardiac pacing rate so as to increase cardiac output. So long as the stroke volume of the heart remains constant, an increase in the cardiac pacing rate produces an increase in cardiac output. The increase in cardiac output tends to suppress CSR by increasing the blood flow to the brain thus avoiding the blood CO2 imbalances described above. Suppression of CSR, in turn, suppresses CSR-induced episodes of apnea/hypopnea. However, it is believed by the inventor of the present invention that the increase in cardiac output resulting from an increase in pacing rate is only temporary. This is illustrated in FIG. 1. Briefly, a cardiac pacing rate 2 is increased at time 3 resulting in an increase in cardiac output 4. The increase in cardiac output suppresses CSR, which is illustrated in the figure by way of a respiratory pattern 5 having crescendo/decrescendo patterns alternating between hyperpnea 5 and apnea 6. The increase in cardiac output is sufficient to temporarily diminish the severity of CSR thus permitting more normal respiration 7 to resume. However, as illustrated in the figure, the increase in cardiac output does not last, even though the higher pacing rate is sustained for an extended period of time. The cardiac output soon begins to drop, apparently due to intrinsic hemodynamic compensatory mechanisms within the patient. In this regard, hemodynamic systems of the patient appear to operate to reduce the stroke volume to compensate for the artificially increased heart rate. As a result, CSR eventually resumes (or it again becomes more severe), thus triggering further episodes of apnea. Note that the graphs of FIG. 1 should not be construed as depicting actual clinically-obtained data. The graphs set forth hypothetical data provided to clearly illustrate the affect of the intrinsic compensatory mechanisms on cardiac output and respiration. Actual variations in cardiac output and respiration may differ. Also note that, during actual CSR, the intervals of apnea/hypopnea are often longer in duration than the intervening intervals of hyperpnea. FIG. 1 illustrates relatively short intervals of apnea/hypopnea so as to permit many complete cycles of CSR to be illustrated within the timeline of the figure. The vertical scales of the graphs are in arbitrary units and the features illustrated therein are not necessarily to scale.
It would be highly desirable to provide techniques for use by an implantable medical device for achieving a sustained increase in cardiac output sufficient to suppress apnea/hypopnea, particularly CSR-induced apnea/hypopnea. It is to this end that certain aspects of the invention are directed. Although a sustained increase in cardiac output is helpful in suppressing apnea/hypopnea, the increase is beneficial in and of itself, since increased cardiac output tends to mitigate CHF, pulmonary edema, and other conditions. Accordingly, other aspects of the invention are directed to the more general goal of improving cardiac output within a patient using an implantable medical device.