Treatment of cardiac decompensation, pulmonary congestion, and dyspnea

Abstract

A method for treating a cardiac problem, the method comprising performing a regulation of a patient's heart rhythm by increasing the number of heartbeats of the patient during time intervals with high pleural pressure relative to the number of heartbeats during periods of low (negative) pleural pressure, wherein the magnitude of the regulation of the heart rhythm between these segments is determined by the patient's respiratory effort and the severity of pulmonary congestion.

Description

Technical Field

[0001] The present invention relates to a novel method and apparatus for treating heart failure and pulmonary congestion and preventing atrial fibrillation. Without limitation, the present invention can be used to treat cardiac decompensation, improve dyspnea, and prevent worsening pulmonary congestion and pulmonary edema. The present invention is applicable to patients with acute or chronic heart failure of any etiology. Background Art

[0002] Heart failure is a major epidemic associated with poor quality of life, high morbidity and mortality. Various treatments for heart failure exist: various drugs, resynchronization of myocardial contraction by pacing the heart at different locations (CRT, cardiac resynchronization therapy), cardiac contractility regulation, neurohumoral stimulation, mechanical assist devices, attempts to use stem cell therapy for myocardial regeneration and various materials for tissue regeneration. Despite significant progress in all proposed technologies and therapies, mortality and morbidity remain high and quality of life is poor. In addition, it is expected that the prevalence of heart failure will increase in the near future as the population ages.

[0003] The main problem with all known solutions for treating heart failure is that their effectiveness is very limited. Current solutions have only limited success in changing the course of the disease, although they can improve the rate at which heart failure progresses. Thousands of assist devices are implanted in patients with end-stage heart failure each year. Although this technology significantly prolongs the survival of patients, these patients are only a small fraction of the population with severe heart failure, with a few thousand of the more than 1.5 million patients with stage III-IV heart failure in the United States alone. In addition, assist device technology is associated with high rates of complications such as gastrointestinal bleeding, stroke and right heart failure. In addition, it is a very expensive technology.

[0004] Cardiac resynchronization therapy (CRT) is another advanced technology, but it is effective only in a small group of patients with severe systolic heart failure (those with an ejection fraction of less than 35% and a significantly prolonged QRS). Interestingly, more than half of heart failure patients have diastolic heart failure, which is a problem with left ventricular filling. The underlying mechanisms of this type of heart failure are not well understood, and there is no effective treatment for this type of heart failure. This group of people with diastolic heart failure (or heart failure with preserved ejection fraction) is steadily growing as the population ages. Therefore, there is a critical unmet need for the development of new technologies for the treatment of heart failure.

[0005] Three major paradigms have been proposed to explain the development of heart failure: (1) cardiorenal and volume overload, (2) the integration of cardiocirculatory and cardiac function with peripheral impedance, and (3) activation of the neurohumoral and sympathetic nervous systems. Currently available pharmacotherapy and various technologies address these three paradigms. Summary of the Invention

[0006] The present invention provides novel methods and devices for treating heart failure and pulmonary congestion and preventing atrial fibrillation; without limitation, the present invention can be used to treat cardiac decompensation, improve dyspnea, and prevent worsening of pulmonary congestion and pulmonary edema.

[0007] The present invention can be used to treat worsening heart failure, which has been described as a "cardiopulmonary vicious cycle." The most common complaint and leading cause of rehospitalization in severe heart failure is severe dyspnea. The inventors have discovered that respiratory effort and the associated sensation of dyspnea are not only a hallmark of cardiac decompensation, but also that respiratory effort plays a key role in the "cardiopulmonary vicious cycle" that can lead to progressive worsening.

[0008] The new treatment is a breakthrough in the management of heart failure for the following main reasons:

[0009] 1. It is based on a novel paradigm for understanding heart failure progression.

[0010] 2. It counteracts the normal physiological control of cardiac pacing.

[0011] 3. It is independent of the various causes of heart failure and can treat all of them.

[0012] 4. It provides an assessment of the severity of cardiac decompensation and provides immediate treatment proportional to the severity of the decompensation.

[0013] 5. It can detect early deterioration and provide treatment before patients may become symptomatic – providing personalized medicine through early detection and prevention.

[0014] The advantages of the present invention include but are not limited to:

[0015] 1. It is applied to the huge heart failure market and can be used for all stage 3 and stage 4 heart failure patients.

[0016] 2. It is used in all forms of heart failure, regardless of the cause, whether it is heart failure with reduced ejection fraction or heart failure with preserved ejection fraction.

[0017] 3. It provides immediate treatment for the development of detected dyspnea or increased blood pressure in the lungs (hemodynamic congestion).

[0018] 4. It can detect the slow progression of the disease and treat it before the patient develops symptoms. Thus, it provides prevention and can reduce hospitalization rates.

[0019] 5. It represents a new type of autonomous control (diagnosis and treatment) of the human autonomic cardiac system. It enables strict continuous monitoring of patients with heart failure, while also closely monitoring changes in hemodynamic congestion and the effectiveness of treatment.

[0020] 6. Simple implementation. It is based on the integration of pacing technology with sensed respiratory effort and a novel algorithm.

[0021] 7. It requires low power because it uses the power of the "respiratory pump" and cardiac contraction to push blood out of the lungs and relieve hemodynamic congestion.

[0022] 8. Side effects are expected to be low. Side effects may involve the presence of the pacing electrodes within the heart and the regulation of heart rate, both of which have well-known low-rate side effects. Since patients with rate-controlled atrial fibrillation have the same prognosis as those with strict rhythm control, the regulation of heart rate is not expected to have any side effects.

[0023] According to a non-limiting embodiment of the present invention, a method for treating a cardiac condition is provided, the method comprising: regulating a patient's heart rhythm by increasing the number of heartbeats during periods of high pleural pressure relative to the number of heartbeats during other periods of relatively low pleural pressure. The magnitude of the regulation of the heart rhythm is determined by the patient's respiratory effort and the severity of pulmonary congestion. High pleural pressure is closer to zero than relatively low pleural pressure.

[0024] The method may also use modulation of cardiac pacing to remove fluid from the patient's lungs to reduce pressure within the patient's pulmonary vessels, thereby reducing breathing effort and the sensation of shortness of breath.

[0025] The method may also use modulation of cardiac pacing to reduce resistance to blood flow within the patient's pulmonary circulation and reduce respiratory effort, thereby reducing right and left ventricular workload.

[0026] Regulation of cardiac pacing may also include sensors in the patient's pleural cavity and / or intrathoracic vessels and / or ventricles and / or chest surface and upper abdomen, which record and measure respiratory waves, and wherein the severity of respiratory effort is defined as the peak-to-peak amplitude of the respiratory waves.

[0027] Regulation of cardiac pacing may also include the use of a long-term central control system with a memory and a communication unit that records the past history of heart rate, respiratory dynamics and hemodynamic indices.

[0028] Regulation of cardiac pacing may also include the use of a long-term central control system having a central processing unit that analyzes changes in hemodynamic congestion or hemodynamic pressure, respiratory effort and / or heart rate.

[0029] Regulation of cardiac pacing may also include use of a long-term central control system set to a threshold level for segmenting the respiratory cycle into intervals of relatively high and relatively low pleural pressures.

[0030] Regulation of cardiac pacing may also include inhibition of normal sinus node pacing.

[0031] Regulation of cardiac pacing may also include intentionally increasing the number of heartbeats during time intervals with high pleural pressure, which, in response to a transient increase in cardiac output during time intervals with high pleural pressure, inhibits sinus node pacing by the patient's autonomic nervous system during relatively low pressure time intervals.

[0032] Regulation of cardiac pacing may also include an adaptive control algorithm using feedback from a sensor assessing respiratory effort level within a long-term control system to control regulation of cardiac pacing, wherein controlling the regulation includes determining the number of pacing beats per minute (NpM) that should be added during high pleural pressure intervals, wherein the depth of the regulation (NpM) increases with the severity of the monitored respiratory effort.

[0033] The method may further include using a long-term central control system that determines the respiratory rate (RR) intervals of the induced pacing based on a past history of electrocardiogram (ECG) recordings.

[0034] The method may further include using a real-time control unit that accepts a threshold for segmenting respiratory waves, a desired number of additional pacings (NpM), and an induced RR interval of pacing, and identifies in real time the start of each high pleural pressure interval and calculates a pacing time based on identifying the last heartbeat, the most recently provided number of pacings, and the desired NpM.

[0035] The method may further include using a real-time control unit and an output power unit to perform real-time supplemental pacing.

[0036] Regulation of cardiac pacing may be performed via a pacing electrode placed within at least one of the cardiac chambers. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The present invention will be more fully understood and appreciated from the following detailed description taken in conjunction with the following drawings, in which:

[0038] Figure 1 is a simplified illustration of an embodiment of the novel cardiopulmonary reverse circulation therapy (CPRS) of the present invention. It is called "cardiopulmonary reverse circulation" because it breaks the "cardiopulmonary vicious cycle" and reverses the various interactions that cause progressive deterioration.

[0039] Figure 2is a simplified illustration of "Respiratory Sinus Arrhythmia," which is the normal physiological increase in heart rate during inspiration and decrease in heart rate during expiration (indicated by the arrows). The cardiopulmonary reverse circulation therapy of the present invention counteracts this normal physiology and increases heart rate only when intrathoracic pressure approaches zero, at the end and beginning of inspiration.

[0040] Figure 3 This is a simplified diagram illustrating the effects of physiological respiratory sinus arrhythmia on pulmonary congestion. During normal respiration, heart rate and lung inflow gradually increase during inspiration, which is compensated by an increase in outflow during expiration. Conversely, the proposed cardiopulmonary recirculation therapy results in a net reduction in hemodynamics and pulmonary congestion by increasing the absolute number of cardiac contractions during intervals with deep negative intrathoracic pressure, during intervals with near-zero intrathoracic pressure.

[0041] Figure 4 An example of a proposed method of synchronizing cardiac pacing with changes in intrathoracic pressure and sudden changes in the respiratory wave based on data from a heart failure patient is shown. The upper bar represents pacing (red bar) applied on top of the natural conventional sinus pacing (blue bar) on the recorded ECG. The lower trace represents the changes in measured intrathoracic pressure. Note that the patient suffers from severe dyspnea with a respiratory effort (peak-to-peak amplitude) of 15 mmHg, which is about 5 times the normal respiratory effort. The new algorithm sets a threshold (-5 mmHg in this example) and divides the respiratory cycle into two types of time intervals: (1) time intervals of deep negative intrathoracic pressure (red), late inspiration and early expiration. (2) time intervals of intrathoracic pressure approaching zero (green). When intrathoracic pressure approaches zero (green), the system adds excitation to provide cardiopulmonary recirculation and reduce hemodynamics and pulmonary congestion.

[0042] Figure 5A schematic diagram of an adaptive control of excitation is shown, which includes two subsystems; one system analyzes long time intervals and analyzes changes in the patient's condition and the severity of dyspnea and heart failure (long-term analysis). The second system works in real time, detects appropriate excitation windows in real time, and introduces appropriate pacing (real-time control). The input to both subsystems is the ECG, the direct measurement of intrathoracic pressure (Ppl, when directly measured) or the pressures measured by various pressure transducers (Pra, Rv) in other possible measurements described in this embodiment. The long-term analysis subsystem measures the average heart rate (HR) and the associated normal average RR interval (tRRorg), the respiratory rate (BR), and the average respiratory effort. Based on these measurements and the patient's recorded history, the system determines the following three parameters and determines the performance of the real-time control subsystem: (1) the RR interval of the pacing stimulus (tRRnew, tRRnew < tRRorg), i.e., the time interval between the last normal heartbeat and the paced heartbeat. (2) The threshold level (Pth), which divides the respiratory cycle into time intervals with deep negative pressure (where additional pacing should be avoided) and time intervals where the intrathoracic pressure is close to zero (allowing pacing). (3) The number of additional pacing times per minute (NpM). The latter determines the depth of regulation. When the patient breathes normally and the respiratory effort is normal (about 3 mmHg), no pacing will be performed (NpM = 0). As the respiratory effort increases, NpM should increase to provide cardiopulmonary counter circulation therapy. Detailed Description

[0043] The present invention provides a new cardiopulmonary counter circulation therapy for treating the "cardiopulmonary vicious cycle" described herein. The prior art does not address the key role of respiratory effort in the development of cardiac decompensation.

[0044] The goal of the new "cardiopulmonary counter circulation (CPRC)" is: 1. To disconnect all cardiopulmonary malignant feedback loops that lead to cardiac decompensation; 2. To prevent the development of hemodynamics and pulmonary congestion by using large changes in intrathoracic pressure (the work of the respiratory pump / machine) to pump blood and fluid from the lungs back to the peripheral circulation; 3. To reduce the transmural pressure across the pulmonary capillaries and the left atrium, thereby improving lung compliance; 4. To improve the problem of dyspnea; and 5. To reduce the workload of the right and left ventricles. The "cardiopulmonary vicious cycle" leads to a gradual increase in pulmonary capillary pressure and pulmonary congestion and increases the workload of both ventricles. The device provides cardiopulmonary counter circulation by reversing these side effects of the vicious cycle.

[0045] The device utilizes the work generated by the respiratory system ("respiratory pump") and cardiac contraction to remove fluid from the lungs, reduce pressure within the pulmonary vessels, and decrease resistance to blood flow within the pulmonary circulation. These actions reduce hemodynamics and pulmonary congestion. The pressure within the pulmonary circulation (hemodynamic congestion) and the amount of blood and fluid in the lungs (pulmonary congestion) are primarily determined by the inflow of blood into the lungs through the right ventricle and the outflow of blood from the lungs back into the peripheral circulation through the left ventricle. However, these inflows and outflows through the right and left ventricles are regulated by intrathoracic pressure. In the presence of deep negative intrathoracic pressure, the inflow into the lungs exceeds the outflow from the lungs. The opposite occurs when intrathoracic pressure is near zero and positive. Therefore, the inflow and outflow are regulated by the respiratory pump. The device utilizes the pressure generated by the respiratory pump to move blood out of the lungs and reduce pressure in the pulmonary circulation. This is achieved by pacing the heart and increasing the number of heartbeats when intrathoracic pressure is near zero relative to the number during periods of deep negative intrathoracic pressure.

[0046] The expected pacing rate is very low, about one pacing per 100 normal heartbeats. The average stroke volume for an adult is about 70 ml. Assuming that each pacing during an appropriate time interval (near zero intrathoracic pressure) only moves 0.2 ml of blood out of the lungs (0.3% of the stroke volume), that is, the stroke volume of the right ventricle and the left ventricle are 69.9 ml and 70.1 ml respectively. Therefore, in order to move a relatively large amount of 200 ml of blood out of the lungs, we must add 1000 heartbeats in the appropriate time window. However, in a day, we have an average of about 20,000 respiratory cycles and 100,000 heartbeats. Therefore, only moderate pacing is needed every 20 respiratory cycles or 100 heartbeats. In addition, it has been determined that cardiac decompensation in patients with chronic heart failure develops and progresses slowly over a period of 2 to 3 weeks. Therefore, there is a reverse circulation that can be extended over a few days.

[0047] It is important to note that, contrary to other patents that aim to alter heart rate based on breathing rate or phase (%%%%), this device does not significantly affect heart rate (less than 1%).

[0048] It is important to note that this device does not directly alter the respiratory rate, as suggested by various other patents (US8509902, US8483833, US9149642), but rather utilizes the respiratory pump to move blood out of the lungs. Furthermore, in contrast to these patents which suggest pacing the heart only when the patient is asleep, this device is intended to work around the clock and also reduce respiratory effort during physical activity.

[0049] Furthermore, in contrast to other patents, pacing is not aligned with a simple segmentation of the respiratory cycle into inspiration and expiration phases, but is based on intrathoracic pressure levels, e.g. Figure 4As shown. Inspiration is defined as the inspiratory time interval when the intrathoracic pressure drops from a pressure close to zero to the minimum intrathoracic negative pressure. Therefore, pacing during the inspiratory phase as suggested by other patents (US 8509902, US 8483833) will not provide the desired cardiopulmonary recirculation because pacing at low intrathoracic negative pressure only aggravates the vicious cycle and pulmonary congestion. Similarly, pacing during the expiratory phase is ineffective because the intrathoracic pressure is very low at the beginning of the expiratory phase. The appropriate pacing window spans the inspiratory phase and the expiratory phase and starts before the end of expiration and ends after the beginning of inspiration. This segmentation of the respiratory cycle is unique to this embodiment compared to all other proposed cardiac pacing (US8509902, US 8483833).

[0050] The present invention achieves this surprisingly by using a counter-intuitive mode of cardiac pacing that is contrary to the physiological autonomic regulation of cardiac pacing by respiration, which is denoted as "respiratory sinus arrhythmia." In physiological respiratory sinus arrhythmia, the heart rate increases during inspiration, as intrathoracic pressure drops to its deepest negative pressure. The CPRC performs the opposite pacing mode and increases the heart rate as intrathoracic pressure approaches zero, as in Figure 2 and Figure 4 Furthermore, the amplitude of cardiac pacing regulation is determined by respiratory effort and the severity of pulmonary congestion.

[0051] The new CPRC could include the following elements:

[0052] A. Means to inhibit normal sinus node pacing to reduce the normal pacing rate when intrathoracic pressure falls below a threshold. This may include at least one of the following:

[0053] a. Simply use drugs to lower the heart rate ( Figure 1 101), as beta-blockers or specific inhibitors of sinoatrial node rhythm, as ivabradine (inhibits vagal currents).

[0054] b. Any invasive or minimally invasive means of inhibiting sinus node activity ( Figure 1 102 in the ).

[0055] c. Selectively add cardiac pacing only during intervals when intrathoracic pressure is above a threshold and near zero. This mode itself induces cardiopulmonary recirculation as described above. In addition, the addition of cardiac pacing, the improvement of dyspnea symptoms, and the reduction of thermal workload downregulate the autonomic sympathetic nervous system and reduce the normal sinus node rate.

[0056] B. Sensors that monitor breathing and detect the inspiratory and expiratory phases and can quantify changes in intrathoracic pressure:

[0057] a. Pressure sensor inserted into the chest space ( Figure 1 201 in).

[0058] b. Sensors in any thoracic artery or vein ( Figure 1 202 in ), because pressure within blood vessels is regulated by changes in intrathoracic pressure. The heart and great vessels are located within the mediastinum and are surrounded by this intrathoracic pressure. The pulmonary vessels are connected to the great vessels in the mediastinum. Therefore, breathing changes intrathoracic pressure and affects right and left ventricular function and pressure, and it also regulates pressure throughout the pulmonary circulation.

[0059] c. Monitor chest wall motion and detect respiratory phase ( Figure 1 203) of any sensor, including for monitoring breathing ( Figure 1 Any strip (piezoelectric, impedance, inductive, optical) of 204).

[0060] d. Sensors in the heart (eg, right atrium and / or left atrium) Figure 1 205 in ), because the pressure within the ventricles (especially the pressure within the right and left atria) is regulated by changes in intrathoracic pressure.

[0061] e. Any intrathoracic or extrathoracic electrodes or devices used to quantify impedance changes during respiratory phases ( Figure 1 Any impedance technology between 206).

[0062] f. Any analysis of respiratory-induced changes in the electrocardiogram (ECG), such as monitoring chest impedance via ECG electrodes or monitoring changes in the cardiac axis during the respiratory cycle.

[0063] g. Any sensor that quantifies changes in airflow, such as a thermistor, microphone, vibration accelerometer, or stethoscope.

[0064] C. Sensors that quantify the severity of respiratory effort. All of the above sensors (201 to 206, a to g in the previous section) can be used to quantify respiratory effort and the severity of dyspnea. Intrapleural sensors can measure the peak-to-peak amplitude of intrathoracic pressure changes and can distinguish between the severity of inspiratory and expiratory effort. Similarly, all intravascular pressure sensors in the chest can quantify the amplitude of the modulation of intravascular pressure by respiratory effort.

[0065] D. Sensors to quantify cardiac function and severity of heart failure, including:

[0066] a. Pressure in the left atrium ( Figure 1 301 in

[0067] b. Pulmonary artery pressure ( Figure 1 302)

[0068] c. Pressure in the right ventricle ( Figure 1 303) in [the text] provides the pulmonary artery pressure and the right ventricular end-diastolic pressure during the ejection phase.

[0069] d. The pressure in the right atrium ( Figure 1 304) in [the text] is used to evaluate the severity of right heart failure.

[0070] e. The pressure in the left atrium, using a transseptal catheter or sensor located in the left atrium.

[0071] e. Evaluating changes in cardiac output. The catheter in the right ventricle ( Figure 1 305) in [the text] can be an impedance catheter for measuring right ventricular volume and stroke volume. This catheter can also be used to evaluate cardiac output using the thermodilution method.

[0072] f. Evaluating pulmonary congestion through, for example, impedance techniques. Impedance can be measured between any intrathoracic or extrathoracic electrode and the central unit ( Figure 1 306) in [the text] or between any other set of intrathoracic electrodes.

[0073] E. The new CPRC pacing can be adjusted according to the severity of the respiratory effort. If the patient feels well (low respiratory effort of about 3 mmHg), CPRC does not need to be applied. When a more severe deterioration of hemodynamic congestion is detected, due to the more urgent need to reverse the effects of the cardiopulmonary vicious cycle, the device enhances the pacing rate and increases the number of heartbeats at time intervals above the threshold (close to zero pleural pressure) and below the threshold (deep negative pleural pressure). The severity of the respiratory effort can be evaluated by all the above sensors (201 to 206).

[0074] F. Pacing electrodes in the right atrium or left atrium or / and in the ventricle. Pacing of the left atrium or left ventricle is less common.

[0075] a. Pacing the right atrium ( Figure 1 401) in [the text] is the simplest mode. CPRC pacing is initiated before a normal sinus beat (tRRew < tRRorg), and the sinoatrial node is reset. Atrial pacing is the preferred mode for pacing the heart when there is no atrial arrhythmia (such as atrial fibrillation or conduction abnormalities) because it maintains the normal activation of the ventricle with a narrow QRS complex.

[0076] b. Pacing the right ventricle ( Figure 1 402) in [the text]. In the presence of atrial fibrillation, direct pacing of the right ventricle is required. When there is atrioventricular block, the device can sense the right atrium and pace the right ventricle and set an appropriate AV delay.

[0077] c. The system can also use electrodes on the left side (left ventricle) to resynchronize left ventricular function, as in conventional cardiac resynchronization therapy (CRT).

[0078] d. If the patient has an implantable cardioverter device (ICD), the device can be integrated with the ICD and pace the heart using the ICD electrodes, or use additional electrodes within the ventricles.

[0079] G. Implantable main control unit that controls the system ( Figure 1 500 in the figure). The implantable unit collects data, executes novel algorithms, provides novel CPRC pacing, records patient status, and communicates with external devices. The unit can be implanted under the pectoral muscle as a conventional pacemaker. The implantable unit includes two subsystems, such as Figure 5 As shown in Figure 2, the long-term control system provides communication with external devices, records and stores data on the patient's electrical and various hemodynamic indicators, determines the severity of dyspnea, and sets the parameters required for the operation of the actual control subsystem. The actual control subsystem identifies the appropriate pacing window based on the respiratory wave and paces the patient at the appropriate time after the last heartbeat based on the designed RR interval. It is important to note that the pacing time cannot be predicted in advance, as in most pacemakers, because pacing is synchronized with the respiratory wave, and the respiratory wave is highly irregular, with large instantaneous variations in respiratory rate, amplitude, and shape.

[0080] H. In vitro unit ( Figure 1 600 in FIG). If necessary, the external unit communicates with the implanted main unit and the internet. It can set various parameters of the implanted device, check the proper function of various sensors, and check the thresholds of various pacing electrodes. It can also record past events for analysis of various cardiac and respiratory events. The system provides a user-friendly interface for medical personnel and enables remote monitoring by medical personnel and experts in the field.

[0081] There are two physiological advantages for having the heart inside the thoracic cavity: the thoracic cavity protects the heart and the major blood vessels from external interference, and the "respiratory pump" increases cardiac output by increasing venous return. Normal physiological control of heart rate is intended to increase cardiac output during exercise, and it is done effectively in healthy subjects. The increase in the work of breathing of the "respiratory pump" (the diaphragm and all respiratory and accessory muscles) reduces the intrathoracic pressure during inspiration and promotes venous return to the right atrium. In the steady state, the cardiac output of the left ventricle is equal to the venous return and is limited by the venous return. Under normal physiological conditions, the increase in venous return and the subsequent dilation of the right atrium accelerate the pacing rate of the sinus node. Especially during inspiration, the heart rate increases because venous return increases during inspiration. This phenomenon is denoted "respiratory sinus arrhythmia" and is described in the journal Circulatory System. Figure 2The increase in cardiac output during exercise is due to an increase in venous return to the heart and an increase in heart rate.

[0082] However, in addition to this positive effect of the "respiratory pump" on cardiac output under normal physiological conditions, increased respiratory effort has serious deleterious effects on the pulmonary circulation and cardiac workload. Increased respiratory effort increases: (1) pulmonary capillary pressure (PCWP); (2) pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), and right ventricular afterload; (3) pulmonary congestion by shifting blood into the lungs; (4) LV afterload; and (5) metabolic demand due to increased work of the respiratory muscles. All of these mechanisms are described in more detail in the attached supplement. In the case of heart or lung disease, these five side effects of increased respiratory effort lead to accelerated decompensation.

[0083] It is important to note that intrathoracic (pleural) pressure has a significant effect on pulmonary hemodynamics and pulmonary congestion. Negative pleural pressure increases the pulmonary blood pool and increases pulmonary bed pressure because it:

[0084] 1. Decrease in diameter of the vessels of the post-capillary pulmonary tree, resulting in increased resistance to inflow to the left atrium and decreased resistance to outflow from the lungs.

[0085] 2. Increases pulmonary vascular resistance throughout the pulmonary system and increases pulmonary capillary and pulmonary artery pressures (relative to instantaneous peripheral pleural pressure).

[0086] 3. Increases right atrial preload and venous return to the right ventricle, which increases right ventricular output.

[0087] 4. Increases left ventricular afterload and reduces left ventricular stroke volume. Thus, during inspiration, inflow through the right ventricle increases, while outflow through the left ventricle decreases. These effects worsen with increasing respiratory effort.

[0088] All of these effects are reversed when pleural pressure approaches or exceeds zero. During this phase, there are:

[0089] 1. Transvascular pressure in the postcapillary pulmonary tree increases, reducing resistance to flow from the lungs into the left atrium, which increases left atrial preload.

[0090] 2. Because the pulmonary vessels dilate at higher pressures, total transpulmonary resistance decreases.

[0091] 3. Decreased preload and venous return to the right atrium, as well as decreased blood inflow to the lungs through the right ventricle.

[0092] 4. LV afterload is reduced, which increases left ventricular stroke volume. Thus, when pleural pressure is negative, the movement of blood from the periphery through the right ventricle into the lungs increases. Conversely, near-zero pleural pressure is associated with an increase in the diameter of the pulmonary vasculature (lower resistance to flow through the pulmonary system) and blood movement out of the lungs through the left ventricle.

[0093] Under steady-state conditions, the average cardiac output per stroke is about 70 ml, about 70 ml of blood enters the lungs through the right ventricle, and the same amount of blood is expelled through the left ventricle, as shown in Figure 2. Figure 4 However, when pleural pressure decreases, inflow through the right ventricle increases, Figure 3 In the example, the pleural pressure increases from 70 to 70.5. At the same time, the outflow from the lungs through the left ventricle decreases from 70.0 ml to 69.5 ml. When the pleural pressure approaches zero, the image is reversed, as shown in Figure 4 As shown, and the amount of blood in the lungs reaches a steady state. Figure 3 A physiological "respiratory sinus arrhythmia" is also presented, in which the heart rate increases during inspiration. The main strategy behind the present invention is to use the "respiratory pump" (part of the work of inspiration and expiration) and cardiac contraction to pump blood out of the lungs and reduce hemodynamic congestion. It does this by regulating cardiac pacing according to changes in pleural pressure, but counterintuitively, it acts on normal physiology and increases heart rate during late expiration and early inspiration. During late inspiration and early expiration, when pleural pressure is negative and the "respiratory pump" increases right ventricular preload and left ventricular afterload, the novel device reduces the pacing rate to reduce the net inflow into the lungs. During late expiration and early inspiration, when the "respiratory pump" reduces right ventricular preload and increases left ventricular preload, the device increases the pacing rate to facilitate the removal of blood from the lungs.

[0094] exist Figure 3 In the example shown, in a normal situation with respiratory sinus arrhythmia and cardiopulmonary reverse circulation therapy (CPRC), the average heart rate is 72 bpm. However, the device applies a higher pacing rate during the late expiratory and early inspiratory phases compared to normal pacing. Therefore, during the two seconds of inspiration, there are only two heartbeats, while during the three seconds of expiration, there are four heartbeats. If the inflow to the lungs increases by 0.5 ml (+0.7% of the stroke volume) and the outflow through the left ventricle decreases by 0.5 ml (-0.7%), then for each heartbeat during the negative pleural pressure interval, each heartbeat during that interval increases the pulmonary blood volume by 1 ml of blood. In summary, during the negative pressure interval, the heart rate is reduced to two beats and the movement of blood during this time interval is reduced to only 2 ml (instead of 3 ml). As Figure 3As shown, during intervals of high pleural pressure, the image is reversed. With each heartbeat, inflow to the lungs decreases by 0.5 ml (-0.7% of stroke volume) and outflow through the left ventricle increases by 0.5 ml (+0.7%). During intervals of high pleural pressure, CPRC increases the heart rate to 4 beats (instead of 3 beats) and increases blood removal from the lungs to 4 ml (instead of 3 ml). Thus, CPRC produces a net removal of 2 ml during a single respiratory cycle (in 5 seconds). Although the effect is small within a single respiratory cycle, it is cumulative and over a 1 minute period, when the respiratory rate is Figure 3 At 12 bpm in the lungs, it produces a net outflow from the lungs of 24 ml, or 120 ml in just 10 minutes. It is important to note that under normal conditions, there is only about 500 ml of blood in the lungs, and the cumulative effect in 10 ml is enormous (theoretically a 24% reduction in pulmonary blood volume). The effect of the CPRC may diminish over time as the pulmonary blood pool may decrease. However, pulmonary congestion, increased respiratory effort, and deeper modulation of the CPRC (larger difference between inspiratory and expiratory heart rates) synergistically enhance the effect of the CPRC and synergistically help to reduce hemodynamics and pulmonary congestion.

[0095] Also, please note:

[0096] (1) A simple implementation of the proposed “cardiopulmonary reverse circulation therapy” includes:

[0097] A. Quantifies the severity of respiratory effort, a surrogate for dyspnea, by measuring the amplitude of respiratory waves within the chest cavity.

[0098] B. The long-term central control subsystem sets appropriate thresholds and divides the respiratory cycle into periods below the threshold (deep negative pressure phase) and periods above the threshold (near zero pleural pressure).

[0099] C. Place a single pacing lead in the right atrium (if the patient does not have atrial arrhythmias or any type of atrioventricular block).

[0100] D. The pacing rate increases as pleural pressure approaches zero (late expiration and early inspiration, e.g. Figure 4 (as shown), without artificial suppression of the normal sinus node. Pacing is controlled by a real-time central control subsystem.

[0101] E. Provide adaptive control of pacing rate. Adjust pacing based on the severity of respiratory effort. Long-term central subsystem determination provides such adaptive control of pacing based on acquired sensing.

[0102] A single cable can include both the required sensing (A) and pacing (C).

[0103] (2) Recent studies have shown that pulmonary congestion develops over an extended period of time in patients with heart failure. Pulmonary capillary wedge pressure and pulmonary artery pressure increase slowly and gradually over a period of 2 to 3 weeks before more aggressive treatment or hospitalization is required. Therefore, although the proposed method causes a small shift of fluid back from the lungs to the periphery, it can work slowly and continuously over long intervals of several days and thus prevent the gradual development of pulmonary congestion.

[0104] (3) Both the increase in the amplitude of respiratory effort and the extension of the inspiratory phase from 20-25% to 50% of the respiratory cycle promote pulmonary congestion. The former increases the movement of blood into the lungs with each heartbeat, while the latter increases the number of heartbeats during each inspiratory phase. Hemodynamic and pulmonary congestion increase respiratory effort. The proposed "cardiopulmonary reverse circulation therapy" breaks the "cardiopulmonary vicious cycle" and is expected to reduce hemodynamic congestion and the associated respiratory effort and inspiratory duration. Therefore, cardiopulmonary reverse circulation therapy can be regulated by respiratory effort.

[0105] (4) The device has no significant effect on cardiac output, but does have a significant effect on pulmonary congestion. Its effect on cardiac output is minimal because its effect on heart rate is minimal. Although this effect on cardiac output is negligible, there is a large cumulative effect on the pulmonary blood pool, and there is a large shift in blood from the lungs back to the periphery.

[0106] (5) Another advantage of the present invention is its protective effect on heart failure patients from atrial fibrillation. Hemodynamic and pulmonary congestion are associated with enormous respiratory effort. The enormous reduction in respiratory effort and the associated intrapleural pressure (to -20 mmHg and more, as observed in heart failure patients) significantly increases transmural atrial pressure and leads to atrial dilation. This mechanism can contribute to the deterioration of atrial function and lead to atrial dilation and the development of atrial fibrillation. Therefore, preventing hemodynamic congestion and the reduction in transmural atrial pressure can prevent the development of atrial fibrillation.

[0107] Applications of the present invention include, but are not limited to, treating patients with heart failure, including all types of heart failure. The present invention is intended to reduce the likelihood of progressive hemodynamic or pulmonary congestion. The present invention can provide an accurate diagnosis of the severity of decompensation based on an assessment of respiratory effort and the severity of hemodynamic congestion. In addition, it provides immediate and proportionate appropriate treatment to prevent further deterioration and restore normalcy. Dyspnea is the most common symptom of heart failure, and this technology directly targets this symptom.

[0108] It is important to note that:

[0109] (1) There is no effective treatment for heart failure with preserved ejection fraction, and this technology can alleviate symptoms in these patients.

[0110] (2) The present invention provides immediate diagnosis and real-time treatment, which are not available in the prior art.

[0111] (3) The present invention has a lesser effect on cardiac output and may even increase cardiac output, unlike diuretic therapy that can cause excessive dehydration and may reduce cardiac output. Unlike conventional prior art diuretic therapy, which has no control over the balance between the peripheral and pulmonary blood pools, the present invention can provide this important control over the movement of blood between the peripheral and pulmonary blood pools.

Claims

1. A device for treating heart problems, comprising: cardiac pacing units; Heart rate sensor; Pleural pressure sensor; as well as a control unit in communication with the cardiac pacing unit, the heart rate sensor, and the pleural pressure sensor, the control unit being configured to regulate the patient's heart rhythm by causing the cardiac pacing unit to increase the number of heart beats during time periods with high pleural pressure relative to the number of heart beats during other time periods with relatively low pleural pressure, the high pleural pressure and the relatively low pleural pressure being sensed by the pleural pressure sensor, wherein the magnitude of the regulation of the heart rhythm is determined by the patient's respiratory effort and the severity of pulmonary congestion, The period of high pleural pressure is a period of time when the intrathoracic pressure is close to zero.

2. The device according to claim 1, wherein The pacing of the cardiac pacing unit is controlled by the control unit to start before the end of exhalation of the patient and to end after the start of inspiration of the patient.

3. The device according to claim 1, wherein The pleural pressure sensor senses the intrathoracic pressure, and wherein pacing of the cardiac pacing unit is controlled by the control unit to increase the number of heartbeats when the intrathoracic pressure is close to zero relative to the number of heartbeats during deep intrathoracic negative pressure.

4. The device according to claim 1, wherein The pacing of the cardiac pacing unit is controlled by the control unit to remove fluid from the patient's lungs to reduce pressure within the patient's pulmonary vessels and thereby reduce the respiratory effort and feeling of dyspnea.

5. The device according to claim 1, wherein The pacing of the cardiac pacing unit is controlled by the control unit to reduce resistance to blood flow in the patient's pulmonary circulation and reduce the respiratory effort, thereby alleviating the workload of the right ventricle and the left ventricle.

6. The device according to claim 1, wherein The pleural pressure sensor includes: a sensor in the patient's pleural cavity, intrathoracic vessels, ventricle, chest surface or upper abdomen, the sensor records and measures respiratory waves, and wherein the severity of the respiratory effort is defined as the peak-to-peak amplitude of the respiratory wave.

7. The device according to claim 1, wherein The control unit comprises a long-term central control system having a memory and a communication unit, the long-term central control system being configured to record a past history of heart rate, respiratory dynamics and hemodynamic indices, and to analyze changes in hemodynamic congestion or hemodynamic pressure, respiratory effort and / or heart rate, and to set threshold levels for segmenting a respiratory cycle into intervals with high pleural pressure and relatively low pleural pressure.

8. The device according to claim 1, wherein The pacing of the cardiac pacing unit is controlled by the control unit to suppress normal sinoatrial node pacing.

9. The device according to claim 1, wherein The pacing of the cardiac pacing unit is controlled by the control unit to increase the number of heartbeats during time intervals with high pleural pressure in response to a transient increase in cardiac output during time intervals with high pleural pressure, which inhibits the patient's autonomic nervous system from performing sinoatrial node pacing during relatively low-pressure time intervals.

10. The device according to claim 1, further comprising an electrocardiogram (ECG) sensor, and wherein The control unit comprises a long-term central control system configured to determine the induced paced respiration rate RR intervals based on a past history of ECG recordings.

11. The device according to claim 6, wherein The control unit includes a real-time control unit configured to accept a threshold value for segmenting the respiratory wave, a desired number of additional pacing steps NpM, and an induced RR interval of pacing, and to identify in real time the start of each high pleural pressure interval and calculate a pacing time based on identifying the last heartbeat, the most recently provided number of pacing steps, and the desired NpM.

12. The device according to claim 1, wherein The high pleural pressure is closer to zero than the relatively low pleural pressure.

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