Intravascular catheter for adaptive control of cardiac pacing based on respiratory and hemodynamic indexes

Abstract

The endovascular catheter monitors respiratory and hemodynamic indices and simultaneously delivers cardiac stimulation, enabling cardiac rhythm regulation with respect to pleural pressure for adaptive treatment of heart failure, low cardiac output, or pulmonary congestion. The catheter is capable of measuring instantaneous pleural pressure based on measurement of intravascular volume and pressure of a large elastic blood vessel within the thoracic cavity.

Description

Technical Field

[0001] The present invention relates to a novel method for sensing respiratory and hemodynamic conditions and pacing the heart using a single or multiple catheters for treating heart failure, low cardiac output, or pulmonary congestion. The catheter is capable of measuring instantaneous pleural pressure based on the intravascular volume and pressure of large elastic vessels within the thoracic cavity. The present invention can be used to treat cardiac decompensation, improve dyspnea, and prevent worsening pulmonary congestion and edema. It 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 pharmacological therapies 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 most common presenting complaint in severe heart failure and the leading cause of hospital readmission is severe dyspnea. The present 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 a "cardiopulmonary vicious cycle" that can lead to progressive deterioration.

[0008] This new, small, implantable device provides continuous adaptive therapy based on real-time monitoring and diagnostics. The device monitors respiratory effort and exploits the opposing effects of respiratory effort on right and left ventricular outflow. Inspiration, or negative intrathoracic pressure, increases right-sided outflow to the lungs while simultaneously reducing left ventricular displacement and cardiac output. The reverse occurs during expiration. The development of cardiac decompensation exacerbates the effects of respiratory effort on left and right ventricular output, leading to the development of a "vicious cardiopulmonary cycle": increased respiratory effort accelerates pulmonary congestion, which further reduces lung compliance, which in turn increases respiratory effort, and the cycle repeats. The new device regulates heart rhythm and alters the distribution of heartbeats at varying pleural pressures. By pacing the heart when pleural pressure is near or above zero, the probability of a heartbeat at end-expiration is increased and the probability of a heartbeat at deep negative pleural pressure is reduced. This change in heart rhythm increases the number of heartbeats with high left ventricular stroke volume and low right ventricular stroke volume. This device disrupts the vicious cardiopulmonary circulation, shifting blood and fluid from the lungs to the periphery, relieving pulmonary congestion and dyspnea. It also reduces cardiac workload and improves cardiac output and cardiorespiratory endurance. Its feasibility has been demonstrated in healthy sheep and sheep with acute heart failure induced by acute infarction. The device shifts an average of 0.5 ml of blood from the lungs per respiratory cycle. Pacing only 400 respiratory cycles 2% of the time out of 20,000 daily cycles results in a daily transfer of 200 ml. Pacing is tailored to the patient's needs. As congestion develops slowly over several weeks, the device can provide early detection and prevent the progression of congestion and dyspnea.

[0009] The new treatment is a breakthrough in the management of heart failure for the following main reasons:

[0010] 1. It is based on a novel paradigm for understanding heart failure progression.

[0011] 2. It counteracts the normal physiological control of cardiac pacing.

[0012] 3. It is independent of the various causes of heart failure and can treat all of them.

[0013] 4. It provides an assessment of the severity of cardiac decompensation and provides immediate treatment proportional to the severity of the decompensation.

[0014] 5. It can detect early deterioration and provide treatment before patients may become symptomatic – providing personalized medicine through early detection and prevention.

[0015] The advantages of the present invention include but are not limited to:

[0016] 1. It is applied to the huge heart failure market and can be used for all patients with stage 3 and stage 4 heart failure.

[0017] 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.

[0018] 3. It provides immediate treatment for the development of detected dyspnea or increased blood pressure in the lungs (hemodynamic congestion).

[0019] 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.

[0020] 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.

[0021] 6. Simple implementation. It is based on the integration of pacing technology with sensed respiratory effort and a novel algorithm.

[0022] 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.

[0023] 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 a well-known low adverse effect rate. Since patients with rate-controlled atrial fibrillation have the same prognosis as those with tight rhythm control, the regulation of heart rate is not expected to have any adverse effects.

[0024] This invention describes a novel intravascular catheter that can be used to monitor respiratory and hemodynamic status and pace the heart. The catheter is connected to a device that regulates heart rhythm and synchronizes it with respiratory phase and pleural pressure. The catheter transmits the required inputs to the device and transmits the device's pacing output to the heart. It measures instantaneous pleural pressure based on measurements of the intravascular volume and pressure of the large elastic vessels within the chest cavity. The catheter is used to treat heart failure, low cardiac output, or pulmonary congestion, and is also used to prevent atrial fibrillation. Without limitation, the invention can be used to treat cardiac decompensation, improve dyspnea, and prevent worsening pulmonary congestion and pulmonary edema.

[0025] The present invention includes methods and systems for sensing, diagnosing and / or treating respiratory and hemodynamic conditions and pacing the heart using a single catheter including one or more sensors and one or more pacing electrodes.

[0026] The pacing electrode can be located at the tip of a catheter that is implanted in one of the heart chambers (atrium or ventricle, right or left). Sensors along the catheter can be located in the venous circulation or within the heart chambers.

[0027] Sensors along the catheter can provide two types of information: sensing cardiac and respiratory rhythms to control appropriate pacing timing in real time; and sensing long-term hemodynamic and respiratory indices to assess the severity of cardiac decompensation and respiratory effort.

[0028] The cardiac rhythm and cardiac decompensation index can be sensed by sensing the cardiac autonomous electrical activity through electrodes at the distal end of the catheter, which is used to (a) perform appropriate pacing according to the rhythm of the cardiac autonomous pacemaking, and (b) monitor the cardiac electrophysiological status by detecting arrhythmias and analyzing changes in heart rate variability as an index of the activity of the autonomous system and the severity of cardiac decompensation.

[0029] The severity of cardiac decompensation can be assessed by pressure transducers along the catheter, sensing the severity of hemodynamic congestion and increases in central venous pressure or cardiac camber pressure.

[0030] Respiratory rhythm and cardiac decompensation index can be sensed by pressure sensors placed along the catheter, which can be used to (a) provide appropriate pacing according to the rhythm of the respiratory cycle by detecting the instantaneous pressure changes caused by inspiration and expiration, and (b) monitor respiratory rate and respiratory pattern as an index of the severity of cardiac decompensation.

[0031] Indexes of cardiac decompensation can be sensed by pressure sensors placed along the catheter, which adjust for respiratory-induced intravascular pressure and assess peak-to-peak changes in intrathoracic pressure and the patient's respiratory effort.

[0032] Indices of cardiac decompensation can be detected by measuring changes in vessel diameter or volume within the vena cava segment or cardiac chambers as an indicator of the severity of blood congestion. Volume changes are monitored by measuring changes in electrical impedance. An increase in vessel diameter decreases impedance. For a well-defined segment, defined by the distance between the two sensing electrodes, impedance is a hyperbolic function of volume.

[0033] Measuring changes in vascular impedance can be done with four electrodes (and four wires) along the catheter, with two distal electrodes injecting alternating current and two central electrodes sensing the voltage. Alternatively, it can be done with just two electrodes (two wires), applying an alternating voltage and measuring the current. This current is proportional to the volume within the vessel.

[0034] Sensing indices of cardiac decompensation may include calculating respiratory-induced pleural pressure changes, an index of respiratory effort, and severity of cardiac decompensation based on measured intravascular pressure and concurrent intravascular blood volume changes.

[0035] Sensing indices of cardiac decompensation can be accomplished by measuring changes in pulmonary congestion by measuring impedance along the catheter, between electrodes deep in the chest, and on the pacemaker / controller.

[0036] Monitoring breathing may include monitoring changes in breathing pattern as the ratio between inhalation and exhalation intervals changes.

[0037] The pressure sensor can be (but is not limited to) an embedded solid-state strain gauge (with two wires) or half of a Wheatstone bridge (three wires), where only one gauge is exposed to pressure and the other is used for reference and temperature regulation, etc.

[0038] Each pressure sensor can be a flexible membrane with a small lumen that transmits pressure to a pressure sensor at the proximal end of the catheter, within the implanted pacemaker / controller connector, or even inside the pacemaker.

[0039] The catheter includes a thin lumen for a guide wire that is needed to position and implant the catheter in the ventricular wall.

[0040] The distal end of the catheter contains a control spring that allows for safe and secure implantation in the myocardium. This spring can also serve as a pacing electrode.

[0041] Some non-limiting features of the present invention include:

[0042] 1. Single catheter for sensing (10, 11, 12) and pacing (8, 9) Figure 3 ).

[0043] 2. The sensing signal includes a combination of the following signals:

[0044] a. ECG (8 in the figure) - monitors changes in heart rate, rhythm, and ECG axes

[0045] b. Pleural pressure (P PL )

[0046] c. Blood pressure in the chest blood vessels or heart (12 in the figure)

[0047] d. Volume changes of intrathoracic blood vessels, cardiac chambers, and vena cava (10 and 11 in the figure).

[0048] e. Measure the changes in lung impedance (13 in the figure)

[0049] 3. ECG is essential for accurately triggering cardiac pacing at the appropriate time after the last cardiac QRS signal.

[0050] 4. The peak-to-peak amplitude of pleural pressure was used as a surrogate for respiratory effort.

[0051] 5. Pleural pressure, intravascular volume and pressure, pulmonary impedance, and heart rate changes are used in combination or individually to define respiratory phase and severity of respiratory effort.

[0052] 6. From the intravascular volume (V V ) and pressure (P V ) to assess pleural pressure (P PL ), where C V is vascular compliance, and it is constant.

[0053] 7. Vascular compliance can be assessed non-invasively (C V ) by asking the patient to stop breathing at least twice and creating a different oral pressure each time. V1 、V V2 ), intravascular pressure (P V1 、P V2 ) and the pressure at the bracket (P M1 、P M2 ), vascular compliance can be calculated:

[0054] 8. Thoracic impedance can be measured from each catheter electrode and device (13 in the figure).

[0055] 9. The catheter can be implanted in any of the heart chambers (4, 5, 6, or 7). If the patient has normal sinus rhythm, the preferred site is the right atrium (4). If the patient has atrial fibrillation, the preferred site is the right ventricle (5).

[0056] 10. Multiple catheters can be used, some dedicated to sensing and some dedicated to pacing. Sensing can be performed simultaneously in the vena cava and some cardiac chambers (such as the right atrium and right ventricle). In the case of atrioventricular block, pacing can be performed in both the atria and ventricles.

[0057] Note that the term "catheter" includes any elongate member suitable for mounting a pressure sensor and electrodes thereon or therein.

[0058] BRIEF DESCRIPTION OF THE DRAWINGS

[0059] The present invention will be more fully understood and appreciated from the following detailed description taken in conjunction with the following drawings, in which:

[0060] Figure 1 The figure is a simplified illustration of "respiratory sinus arrhythmia," which is a normal physiological increase in heart rate during inspiration and a decrease in heart rate during expiration (indicated by the arrows). The cardiopulmonary reverse circulation therapy of the present invention counteracts normal physiology and increases heart rate only at the end and beginning of inspiration, when intrathoracic pressure approaches zero. During normal breathing, heart rate and inflow to the lungs gradually increase during inspiration, which is compensated by an increase in outflow during expiration. In contrast, the proposed cardiopulmonary reverse circulation 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 when intrathoracic pressure approaches zero.

[0061] Figure 2 Experimental validation of the effects of breathing on right and left ventricular stroke volume in sheep is presented. Changes in pleural pressure have distinctly opposite effects on the two ventricles. A decrease in pleural pressure during inspiration is associated with an increase in right ventricular stroke volume and a decrease in left ventricular stroke volume. Maximum right ventricular output and minimum left ventricular stroke volume are achieved at the end of inspiration, at the time of the most negative pleural pressure. The opposite occurs during expiration, with a decrease in right ventricular output and an increase in left ventricular output. Thus, pacing during mid-to-late expiration promotes blood flow out of the lungs via the left ventricle and reduces blood flow into the lungs via the right ventricle.

[0062] Figure 3An example of the present invention is shown of synchronizing cardiac pacing with changes in intrathoracic pressure and the amplitude of the respiratory wave based on data from a heart failure patient. The upper bar represents pacing (red bar) applied on top of natural conventional sinus pacing (blue bar) on top of the recorded ECG. The lower trace represents the changes in measured intrathoracic pressure. Note that the patient has severe dyspnea with a respiratory effort (peak-to-peak amplitude) of 15 mmHg, 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.

[0063] Figure 4 and 4A Different positions of the catheter are shown. The device (1) can be implanted under the pectoralis muscle in the upper left chest as a conventional pacemaker. In the embodiment described, the catheter (3) is inserted into the right atrium (4) via the subclavian vein and the superior vena cava (2). For patients with normal sinus rhythm, right atrial pacing is the preferred pacing mode. However, the catheter can be inserted into other chambers of the heart (5 - right ventricle, 6 - left atrium, 7 - left ventricle), and several similar catheters can be used. When the patient suffers from atrial fibrillation, the catheter is implanted in the right ventricle. When the patient suffers from atrioventricular conduction abnormalities, two catheters can be used, one implanted in the right atrium and the other implanted in the right ventricle.

[0064] Figure 5 、 5A 5B shows a more detailed structure of the catheter (3). The catheter can deliver cardiac stimulation via electrodes at the distal end of the catheter (8, 9). The distal end (9) can include a sharp spring that inserts into the myocardium during implantation and stabilizes the position of the catheter. Cardiac pacing can be provided by a single electrode (located between the distal end and a second reference electrode on the surface of the device) or by bipolar electrodes (8 and 9) at the distal end of the catheter. The spring can serve as the electrode.

[0065] The sensor is placed along the catheter to be able to measure the impedance between the intravascular pressure, intravascular volume and the electrode and the device. In order to measure the intravascular pressure and volume in the vena cava, the sensor (10, 11 and 12) is placed at a distance of at least 8-10 cm from the distal end. The intravascular volume is monitored by measuring the change in the impedance (14-potential wave) between the two closed electrodes (10, 11) in the vena cava. The intravascular pressure is measured by a miniature pressure sensor placed between the impedance electrodes to ensure that the pressure and volume are measured from the same vascular segment. Pleural pressure is calculated based on these simultaneously measured intravascular pressures and volumes. The change in pulmonary congestion can be sensed by measuring the change in the lung impedance between any catheter electrode and the device (13). DETAILED DESCRIPTION

[0066] The present invention enables a new method of adaptive therapy for heart failure, low cardiac output, or pulmonary congestion, easily implemented using only a single catheter for sensing and pacing. This new therapy, referred to herein as "cardiopulmonary recirculation" or "breaking the vicious cardiopulmonary cycle," works by altering the heart rhythm and slightly synchronizing cardiac contractions with different respiratory phases.

[0067] Normal physiological control of heart rate aims 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 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 increase the heart rate and stroke volume of the sinus node according to the Fran-Starling law of the heart. 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 1 The increase in cardiac output during exercise is due to increased venous return to the heart, increased heart rate, and increased bilateral ventricular stroke volume. Therefore, the "respiratory pump" has a significant impact on cardiac function.

[0068] However, while the respiratory effort of the "respiratory pump" increases cardiac output under normal physiological conditions, increased respiratory effort has several serious adverse effects on the pulmonary circulation and cardiac workload, especially in the setting of heart failure. 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 respiratory muscle work. All of these mechanisms are detrimental in the setting of heart failure. In the setting of heart disease or severe lung disease, these five side effects of increased respiratory effort lead to accelerated decompensation.

[0069] The main strategy behind this invention is to use the "respiratory pump" and cardiac contraction to pump blood out of the lungs and reduce hemodynamic congestion. It does this by adjusting cardiac pacing according to changes in pleural pressure, but counterintuitively, this works against normal physiology and increases heart rate during late expiration and early inspiration, as Figure 1 (Cardiopulmonary Reverse Circulation Therapy). During late expiration and early inspiration, when the "breathing pump" reduces right ventricular preload, reduces left ventricular afterload, and increases left ventricular preload, the device increases the pacing rate to facilitate removal of blood from the lungs. It is also desirable to reduce heart rate during late inspiration and early expiration when pleural pressure is negative and the "breathing pump" increases right ventricular preload and left ventricular afterload.

[0070] 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 the intrathoracic pressure. In the presence of a deep negative intrathoracic pressure, the inflow into the lungs is greater than the outflow from the lungs. The opposite situation occurs when the intrathoracic pressure is close to zero and positive. Therefore, the inflow and outflow are regulated by the respiratory pump.

[0071] The device uses the work generated by the respiratory system (the "respiratory pump") and cardiac contraction to remove fluid from the lungs. It uses the effect of the pleural pressure generated by the "respiratory pump" to "pump" blood out of the lungs and reduce the workload on the left ventricle. It does this by pacing the heart and increasing the number of heartbeats when the intrathoracic pressure is close to zero relative to the number during periods of deep negative intrathoracic pressure. Pacing the heart when the intrapleural pressure is close to or above zero also reduces the probability of cardiac contraction when the peripheral pleural pressure is negative due to a decrease in the sinus node rate, as we have observed in preclinical studies. The shift in cardiac contraction probability toward higher peripheral pleural pressure promotes left ventricular outflow and blood removal from the lungs, while reducing right ventricular outflow and blood flow into the lungs. The net effect is a reduction in pulmonary blood volume, intrapulmonary vascular pressure, pulmonary vascular resistance, and pulmonary congestion. It reduces cardiac workload by decreasing (1) LV afterload (when the LV contracts due to higher peripheral pressures), (2) LV preload (by gradually reducing pulmonary congestion and pulmonary venous pressure), and (3) RV afterload (by reducing pulmonary congestion and pulmonary vascular resistance).

[0072] The average stroke volume in an adult is approximately 70 ml. Our preclinical studies in sheep have revealed a significant effect of pleural pressure on the stroke volume of both ventricles, such as Figure 2 At end-inspiration, LV output is approximately 10% lower, whereas at mid-expiration it is 10% higher than average ( Figure 2 ). Based on our recent preclinical data, pacing when pleural pressure is high results in a net movement of 0.5 ml of blood out of the lungs per respiratory cycle. Therefore, to move 200 ml of blood out of the lungs, 400 respiratory cycles must be paced. However, in a single day, people have an average of about 20,000 respiratory cycles and 100,000 heartbeats. Therefore, only modest adjustments are needed in 2% of the respiratory cycles, that is, every 50 respiratory cycles or about every 3 minutes. It is well known that cardiac decompensation in patients with chronic heart failure can develop slowly over 2 to 3 weeks before more aggressive treatment or hospitalization is required. Therefore, modest pacing of only 2% of the respiratory cycles, once every 50, is sufficient. Therefore, although the proposed approach causes a small movement of fluid back from the lungs to the periphery, it can work slowly and continuously over long time intervals of several days and can therefore prevent the gradual development of pulmonary congestion.

[0073] The prior art does not address the suggested key role of respiratory effort in the development of cardiac decompensation. Some patents make the opposite suggestion, improving cardiac output by pacing the heart during inspiration. The present invention is based on a counter-intuitive mode of cardiac pacing that is opposite to the physiological autonomic regulation of cardiac pacing by respiration, which is denoted "respiratory sinus arrhythmia". In physiological respiratory sinus arrhythmia, the heart rate increases during inspiration, when the intrathoracic pressure drops to its deepest negative pressure, the mode suggested herein performs the opposite pacing mode and increases the heart rate as the intrathoracic pressure approaches zero, e.g. Figure 3 As shown in Figure 2, pacing during the inspiratory phase, as suggested by other patents (US 8509902, US 8483833), may only exacerbate the vicious cycle and pulmonary congestion because pacing at low negative intrathoracic pressure increases right ventricular output but increases the afterload of the failing left ventricle and reduces left ventricular filling. This pattern ultimately leads to progressive pulmonary congestion and cardiac decompensation.

[0074] The prior art does not involve an intravascular catheter for simultaneously monitoring respiratory and hemodynamic indices and pacing the heart. The use of a single catheter simplifies the implantation process and significantly reduces immediate and long-term complications.

[0075] U.S. patent application 2021 / 0068667 (“Quantification of the respiratory effort from hemodynamic measurements”) proposes a method for assessing respiratory effort by continuously measuring intravascular pressure. However, the temporal resolution of this method is low because it is based on decomposing the intravascular pressure signal into cardiac and respiratory signals. The current invention has two major advances: (1) simultaneous sensing and pacing, and (2) measurement of pleural pressure with high temporal resolution. The prior art measures the severity of cardiac decompensation and the severity of respiratory effort by measuring the average peak-to-peak swing of the respiratory signal over several respiratory cycles (i.e., more than 10 seconds). Unlike the prior art, the present invention is able to achieve precise synchronization of cardiac pacing and respiratory dynamics with a significantly improved resolution of less than 30 milliseconds. The present invention uses a different technique from the prior art, which is based on the simultaneous measurement of intravascular pressure and intravascular volume. After calibration of elastic vascular compliance, the instantaneous pleural pressure is calculated from these two measurements.

[0076] In contrast to existing techniques, the synchronization of cardiac pacing with respiratory dynamics does not correspond to a simple segmentation of the respiratory cycle into inspiration and expiration phases, but uses a more precise assessment of pleural pressure dynamics and defines thresholds related to pleural pressure levels, e.g. Figure 3As shown. Inspiration is defined as the inspiratory interval when intrathoracic pressure drops from near zero pressure to the lowest negative intrathoracic pressure. 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 and expiratory phases and begins 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, US8483833).

[0077] The catheter includes a combination of sensors that help diagnose and quantify the severity of heart failure and define when to pace the heart during the respiratory cycle. This includes:

[0078] 1. Intracardiac ECG and changes in intracardiac ECG caused by breathing ( Figure 5 8 and 9 in the figure).

[0079] ECG is essential for accurately triggering cardiac pacing at the appropriate time after the last cardiac QRS signal.

[0080] Monitor changes in the cardiac QRS axis and sinus node rate and rhythm during the respiratory cycle.

[0081] 2. In the intrathoracic artery or vein ( Figure 5 Any intravascular pressure measurement in 12) of the above is not recommended because intrathoracic intravascular pressure increases with cardiac decompensation, and intravascular pressure is regulated by changes in intrathoracic / intrapleural pressure. The heart and great vessels are located within the mediastinum and are surrounded by intrathoracic pressure. Therefore, breathing changes all intrathoracic, intravascular, and intracardiac pressures. In addition to affecting the peak-to-peak swing of intravascular pressure with breathing, respiratory effort also affects mean intravascular pressure. Increased respiratory effort is associated with an increase in mean intravascular pressure because it increases pulmonary vascular resistance.

[0082] 3. Using impedance technology ( Figure 5 10, 11) Intravascular volume is measured in either the intrathoracic artery or vein. Cardiac decompensation is associated with increases in both intravascular pressure and volume. However, the relationship between the two is not a simple linear one but an exponential one. At low intravascular pressures, vascular compliance is greater, and significant changes in volume are associated with relatively small changes in intravascular pressure. Therefore, intravascular volume is more sensitive to the severity of congestion.

[0083] 4. Evaluate the impedance of the catheter and device ( Figure 5 13) Pulmonary congestion between any electrodes.

[0084] 5. Measurement of intrathoracic (pleural) pressure. The peak-to-peak amplitude of pleural pressure is used as a surrogate for respiratory effort. In addition, pleural pressure defines when to pace the heart, based on its instantaneous absolute value (not just its peak-to-peak amplitude).

[0085] Assessment of pleural pressure (PPL) by measuring intravascular volume (VV) and pressure (PV):

[0086]

[0087] Where CV is vascular compliance, which is a constant.

[0088] Vascular compliance (CV) can be assessed non-invasively by asking the patient to stop breathing at least twice and to produce different oral pressures each time.

[0089] PV2) and the pressure at the stent (PM1, PM2), the vascular compliance can be calculated:

[0090]

[0091] However, more calibration data points will improve the accuracy of the calibration and will be able to account for non-linear compliance (decreased vessel compliance at large intravascular volumes).

[0092] The measurement of pleural pressure is based on the fact that the compliance of central blood vessels (such as the vena cava, pulmonary artery and aorta) is determined by passive elastic properties and is practically constant over a period of several months.

[0093]

[0094] Among them C V is vascular compliance, V V (t) is the vascular blood volume, P V (t) is the intravascular pressure, P PL (t) is the pleural pressure. v (t)) and pressure (P V (t)) Pleural pressure can be calculated:

[0095]

[0096] Vascular compliance can be assessed non-invasively by asking the patient to stop breathing at at least two pressures. Equal to the pressure measured at the mouth (PM). Under these conditions, the pleural pressure is also fixed and equal to:

[0097]

[0098] Among them C L and C W are the lung and chest wall compliances, respectively, and the coefficient C LW is a constant (C LW =C W / (C W +C L )).

[0099] Substituting Equation 3 into Equation 1 and rearranging, we obtain the vascular volume (V V ) formula:

[0100] V V (t) = C V (P V (t)-C LW P M ) (4)

[0101] Formula 4 includes two constants: C V and C LW Therefore, by simultaneously measuring the intravascular volume (V V1 、V V2 ), intravascular pressure (P V1 、P V2 ) and the pressure at the bracket (P M1 、P M2 ), vascular compliance can be calculated:

[0102]

[0103] These measurements (V V1 、V V2 、P V1 、P V2 、P M1 、P M2 ) can be an average measurement over one or several cardiac cycles.

[0104] Large elastic vascular compliance (C V ) changes slowly with age, so calibration is required every few months. In addition to checking pacing thresholds, recalibration of the vascular compliance factor will be part of routine pacemaker follow-up practice.

[0105] Additional notes:

[0106] ·The catheter can be placed in each heart chamber ( Figure 4 4, 5, 6, or 7 of 4. If the patient has normal sinus rhythm, the preferred site is the right atrium (4). If the patient has atrial fibrillation, the preferred site is the right ventricle ( Figure 4 5) in the above.

[0107] Multiple catheters can be used. Some can provide sensing and some can provide pacing. Sensing can be performed simultaneously in the vena cava and in cardiac chambers such as the right atrium and right ventricle. In the case of atrioventricular block, pacing can be performed in both the atria and ventricles.

[0108] Changes in intravascular volume, intravascular pressure, pulmonary impedance, and heart rate can be used in combination or alone to analyze the severity of cardiac decompensation.

[0109] • Changes in pleural pressure, intravascular volume, intravascular pressure, lung impedance, and heart rate can be used in combination or individually to define the inspiration and expiration phases and can help determine pacing periods within the respiratory cycle.

[0110] Applications of the present invention include, but are not limited to, treating patients with heart failure, including all types of heart failure, treating low cardiac output and pulmonary congestion. The present invention can be used for:

[0111] Early diagnosis of decompensation to prevent worsening. It can monitor for early signs of worsening, such as an increase in intravascular volume and an increase in respiratory effort (pleural pressure).

[0112] Adaptive (real-time) adjustment of cardiac pacing based on assessments of respiratory effort severity and cardiac decompensation severity.

[0113] Real-time diagnosis based on invasive respiratory and hemodynamic indices for telemedicine.

[0114] Precisely define the pacing cycle within the respiratory cycle

[0115] Simplify the implantation process by inserting a single catheter for sensing and pacing, and reduce short-term and long-term complications of catheter implantation by using a single catheter.

Claims

1. A device for treating heart problems, comprising: a cardiopulmonary reverse circulation therapy (CPRC) device for cardiac pacing, the CPRC device comprising at least one pacing electrode; at least one sensor for cardiac electrical activity; at least one intrathoracic sensor operable to sense parameters related to respiratory dynamics and effort, wherein the at least one pacing electrode and the at least one intrathoracic sensor are mounted within or on a common catheter; and A control unit is in communication with the CPRC device, the ECG sensor, and the intrathoracic sensor, the control unit being configured to regulate a patient's heart rhythm, wherein regulation of the heart rhythm is determined by the patient's respiratory effort and severity of pulmonary congestion.

2. The device according to claim 1, wherein The at least one pacing electrode is located at a distal end of the common catheter, and the at least one intrathoracic sensor is located proximal to the at least one pacing electrode.

3. The device according to claim 1, wherein The at least one intrathoracic sensor is located at least 8-10 cm from the distal end of the catheter.

4. The device according to claim 1, wherein The at least one intrathoracic sensor comprises an intravascular sensor.

5. The device according to claim 1, wherein The at least one intrathoracic sensor senses intrathoracic pressure, and wherein pacing of the CPRC device is controlled by the control unit to increase the number of heartbeats when the intrathoracic pressure approaches zero relative to the number of heartbeats during negative intrathoracic pressure.

6. The device according to claim 5, wherein The high pleural pressure is closer to zero than the relatively low pleural pressure.

7. The device according to claim 1, wherein Pacing of the CPRC device is controlled by the control unit to remove fluid from the patient's lungs, reducing pressure within the patient's pulmonary vessels, thereby reducing breathing effort and the sensation of dyspnea.

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

9. The apparatus of claim 1 , further comprising an electrocardiogram (ECG) sensor, and wherein the control unit comprises a long-term central control system configured to determine respiratory intervals at which pacing is induced based on a past history of ECG recordings, heart rate, and arrhythmias.

10. The device according to claim 1, wherein The intrathoracic sensor includes a pressure sensor in an intrathoracic blood vessel or a cardiac cavity, which 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.

11. The device according to claim 1, wherein The at least one intrathoracic sensor is configured to measure changes in diameter or volume of a blood vessel or heart chamber, which changes are used as an index of the severity of blood congestion.

12. The device according to claim 11, wherein The at least one intrathoracic sensor includes sensing changes in diameter or volume including changes in electrical impedance between the sensing electrodes, and wherein an increase in the diameter of the blood vessel reduces the electrical impedance.

13. The device according to claim 11, wherein The at least one intrathoracic sensor includes sensing electrodes, and the change includes a change in electrical impedance between the sensing electrodes, and wherein, for a vessel segment defined by a distance between the sensing electrodes, the impedance is a hyperbolic function of the volume.

14. The device according to claim 11, wherein The at least one intrathoracic sensor comprises four electrodes, wherein two of the electrodes are used to inject alternating current and the other two electrodes are used to sense voltage.

15. The device according to claim 11, wherein The at least one intrathoracic sensor includes two electrodes for applying an AC voltage and measuring a current that is proportional to the volume within the blood vessel, or it can apply a current and measure the resulting voltage to assess the impedance and associated volume.

16. The device according to claim 11, wherein The control unit is operable to sense an index of severity of cardiac decompensation, respiratory effort, and pulmonary congestion based on measurements of intrathoracic pressure from simultaneous changes in the intravascular pressure and intravascular blood volume.

17. The device according to claim 1, wherein The at least one intrathoracic sensor is configured to measure changes in lung congestion by measuring impedance between the at least one electrode along the catheter and electrodes on a surface of the CPRC device.

18. A device for treating heart problems, comprising: a cardiopulmonary reverse circulation therapy (CPRC) device for cardiac pacing, the CPRC device comprising at least one pacing electrode; At least one electrocardiogram electrode or sensor and at least one sensor of vascular congestion of an intrathoracic blood vessel, the at least one sensor being configured to measure a change in diameter of the intrathoracic blood vessel.

19. A device for treating heart problems, comprising: a cardiopulmonary reverse circulation therapy (CPRC) device for cardiac pacing, the CPRC device comprising at least one pacing electrode; At least one electrocardiogram electrode or sensor and at least one vascular congestion sensor, the at least one sensor comprising electrodes and configured to measure changes in pulmonary congestion by measuring impedance between the electrodes.

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