System for reducing blood pressure by reducing ventricular filling

Abstract

Systems and methods for reducing ventricular filling volume are disclosed.SOLUTION: The stimulation circuit is used to stimulate the patient's heart to reduce ventricular filling volume or blood pressure. When the heart is stimulated to a certain degree to reduce the blood pressure, the cardiovascular system may eventually adapt to the stimulation and return to a higher blood pressure. The stimulation pattern may be inconsistently configured such that an adaptive response of the heart is reduced or prevented, and the stimulation circuitry may be used to stimulate the patient's heart to cause at least a portion of the atrial contraction with the atrioventricular valve closed. Such atrial contraction causes less blood to enter the corresponding ventricle than when the atrioventricular valve is open throughout atrial contraction.SELECTED DRAWING: Figure 9

Description

[Technical Field]

[0001] The present invention relates to a method and system for lowering blood pressure through reduced ventricular filling. [Background technology]

[0002] Embodiments of the present invention treat hypertension by controlling cardiac filling. Certain embodiments relate to the field of cardiac focal electrical stimulation. Includes the application of

[0003] It is known that fluctuations in blood pressure usually occur due to, for example, increased activity (which usually increases blood pressure) or significant blood loss (which tends to cause a decrease in blood pressure). However, blood pressure is usually maintained within a limited range, for example, due to the body's baroreflex, whereby increased or decreased blood pressure affects cardiac function and cardiovascular characteristics through a feedback loop. Such feedback control is achieved by the nervous system and the endocrine system (e.g., natriuretic peptides). In people with hypertension, the baroreflex is functional, but blood pressure remains elevated.

[0004] High blood pressure (e.g., blood pressure above 140 / 90 mmHg) is a serious health problem that affects many people. For example, approximately 74.5 million people aged 20 years or older living in the United States have high blood pressure. High blood pressure can lead to life-threatening conditions such as stroke, heart attack, and / or congestive heart failure. Approximately 44.1% of people with high blood pressure and receiving modern treatment have their hypertension satisfactorily controlled. Correspondingly, 55.9% of these same people have poorly controlled hypertension. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] US Patent Application Publication No. 2012 / 0215272 [Patent Document 2] US Patent Application Publication No. 2011 / 0172731 [Patent Document 3] Pending U.S. Patent Application No. 13 / 688,978 [Patent Document 4] US Patent Application Publication No. 2012 / 0041502 Summary of the Invention [Problem to be solved by the invention]

[0006] Traditionally, treatment for high blood pressure has involved medication and lifestyle changes. Treatments for BP are not effective for all patients. Additionally, side effects may prevent certain patients from taking the medication. Therefore, there remains a need for additional techniques to lower blood pressure. [Means for solving the problem]

[0007] The present invention discloses methods and devices for reducing blood pressure. In some embodiments, instead of or in addition to treating high blood pressure pharmacologically, high blood pressure is treated mechanically. In some embodiments, an electrical stimulator, such as a pacemaker or other type of device with a pulse generator, may be used to stimulate the patient's heart to reduce blood pressure. If the heart is stimulated in a consistent manner to reduce blood pressure, the cardiovascular system may eventually adapt to the stimulation and return to a higher blood pressure. Thus, in some embodiments, pressure is reduced such that the adaptation response of the cardiovascular system is reduced or even prevented. Stimulation patterns may be configured to allow for reflex regulation.

[0008] In some embodiments, an electrical stimulator may be used to stimulate the patient's heart to cause at least some of the atrial contractions to occur with the atrioventricular valves closed, which may result in less blood entering the corresponding ventricle than if the atrioventricular valves were open during the atrial contraction.

[0009] In some embodiments, prosthetic valves may be used in treating hypertension. In some medical conditions in which the atrioventricular (AV) valves are dysfunctional, the valves may be replaced by the implantation of artificial (prosthetic) valves. These artificial valves may typically be configured to passively open and close in response to pressure differences between the atria and ventricles, similar to natural valves.

[0010] Passive prosthetic valves are usually classified based on their mechanical structure as caged ball valves, tilting disc valves, and bi-leaflet valves. Alternatively, in some embodiments, the valves are designed to be actively opened and closed. Alternatively, an active prosthetic valve configured as follows may be used.

[0011] In one aspect of the present invention, an embodiment of a system for reducing blood pressure in a patient having pre-treatment blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a heart of the patient with a stimulation pulse. The system may include a stimulation electrode for delivering a stimulation pulse to at least one chamber of the heart. The stimulation pattern may include at least one controller configured to apply the stimulation pattern. may include a first stimulation setting and a second stimulation setting different from the first stimulation setting. At least one of the first stimulation setting and the second stimulation setting is an atrial kick. The device may be configured to reduce or prevent

[0012] In one aspect of the present invention, an embodiment of a system for reducing blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a patient's heart. The system may include at least one controller configured to administer a stimulation pattern comprising a plurality of stimulation pulses. At least one of the plurality of stimulation pulses may be administered. At least one stimulation pulse may have a first stimulation setting configured to reduce atrial kick in at least one ventricle, and at least one stimulation pulse of the plurality of stimulation pulses may have a second stimulation setting configured to reduce a baroreflex response to the reduced atrial kick so as to limit an increase in blood pressure value occurring during the stimulation pulse to a predetermined value or range of values. Good too.

[0013] In another aspect of the present invention, an embodiment of a device for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricle filling volume is provided. The device includes a stimulation circuit configured to deliver stimulation pulses to at least one of an atrium and a ventricle. The device may include a processor circuit coupled to the stimulation circuit and preferably also to the sensing circuit.

[0014] In some embodiments, the device processor circuitry may be configured to operate in an operational mode in which the device controls an AV delay, which, as used herein, refers to the time between ventricular excitation and / or contraction and atrial excitation and / or contraction. Additionally, as used herein, an AV delay in a system or method may be understood to mean a delay that occurs within a single heartbeat between a contraction or a contraction of a small amount of blood to the ventricle. delivery of at least one excitatory stimulus, detection of the onset of atrial activation, timing of the expected onset of atrial activation, and delivery of at least one excitatory stimulus to the atrium. This may also be understood to mean the time delay between one of the transmissions of

[0015] The AV delay may be established by delivering at least one stimulation pulse to both at least one atrium and at least one ventricle. Such a measure may be implemented, for example, by using at least one sensing electrode for sensing natural activity in the heart (e.g., the right atrium) and The degree of stimulation pulse transmission may be adjusted and set according to the above.

[0016] Preferably, ventricular activation is timed to begin before delivery of one or more stimulation pulses to the atrium. When regulated, delivery of a stimulating pulse to the heart occurs when one or more excitatory pulses are delivered to the atria. It is timed to be delivered to the atrium earlier than the next expected natural onset of excitation.

[0017] In some embodiments, an AV delay may be established by delivering at least one stimulation pulse to one or more ventricles rather than to the atria. Natural cardiac activity may be sensed, and ventricular activation and / or contraction timing may be determined by the sensed The pulse may be set to precede its natural expected timing based on the degree of atrial activity.

[0018] In some embodiments, the processor circuitry determines atrial activation in at least one atrium. Approximately 0 milliseconds (ms) to approximately 50 ms before the start of ventricular activation, which leads to ventricular filling. The processor circuit may be configured to operate in a mode of operation that stimulates the ventricle such that the volume of atrial filling is reduced from a pre-treatment ventricular filling volume and the patient's blood pressure is reduced from a pre-treatment blood pressure. In such embodiments, atrial activation may be sensed to determine the onset of atrial activation. For example, the processor circuit may be configured to operate in a mode of operation that delivers one or more excitatory pulses to the ventricle from about 0 ms to about 50 ms before the next atrial activation is expected to occur. The time interval between the onset of atrial activation and the moment atrial activation is sensed may be known or estimated and may be used to calculate the timing of the onset of atrial activation. For example, it may be known or estimated that atrial activation will be sensed 5 ms after the onset of atrial activation, and the onset of atrial activation may be determined. If the ventricle is to be stimulated 20 ms before the next sensed expected atrial activation, then the ventricle will be stimulated 25 ms before the next sensed expected atrial activation.

[0019] In another embodiment, the processor circuitry is configured to stimulate the atrium and stimulate the at least one ventricle. Approximately 0 to 50 ms after the onset of ventricular excitation, atrial excitation begins, thereby accelerating ventricular filling. The processor circuit may be configured to operate in a mode of operation in which the filling volume is reduced from a pre-treatment ventricular filling volume and the patient's blood pressure is reduced from a pre-treatment blood pressure. The device may be configured to operate in a mode of operation in which one or more excitatory pulses are delivered to the atrium between about 0 ms and about 50 ms after delivery of the excitatory pulses to the patient's ventricle. In such an embodiment, pacing may be timed without relying on sensing atrial activation. Preferably, in such an embodiment, atrial activation is timed to ensure that one or more excitatory pulses are delivered to the atrium before natural activation occurs. is detected. Preferably, atrial activation is set to commence between about 0 ms and about 50 ms after the onset of ventricular activation when the intrinsic atrial activation rate is lower than the intrinsic ventricular activation rate.

[0020] In some embodiments, the timing of mechanical contractions relative to the electrical excitation of the chambers for a patient can be determined by, for example, sensing changes in atrial and ventricular pressure, measuring wall motion using ultrasound (e.g., echocardiography or echocardiography), implantation and / or imaging techniques known in the art. Alternatively, it may be determined using external sensors, such as pressure sensors, impedance sensors, ultrasound sensors, and / or one or more sound sensors and / or one or more blood flow sensors, to detect changes in impedance or the opening and closing of a heart valve.

[0021] The timing of one or more excitatory pulses to produce the desired pattern of contractions The timing of mechanical contractions relative to electrical excitation of the chamber for the patient may be taken into account, and the processor circuitry configured accordingly, so that the electrical excitation of the chamber for the patient is delivered to the heart via the ventricle. This may be done in a closed-loop mode using one or more implanted sensors, and / or may be done intermittently (e.g., at the time of device implantation and / or testing), for example, using an interface with an external measurement device.

[0022] The operating mode is to stimulate the ventricles to contract before the start of at least one atrium contraction. may include initiating

[0023] The operating mode is to stimulate the ventricles and cause the ventricles to contract before the end of at least one atrial contraction. and initiating contraction of the at least one atrium, thereby causing the AV valve to contract during at least a portion of the contraction of the atrium. may include causing the

[0024] The mode of operation may include stimulating the ventricle to initiate a contraction within less than 100 ms after the onset of contraction of at least one atrium.

[0025] Preferably, care is taken to ensure that atrial contraction begins before ventricular contraction reaches peak pressure, even though atrial contraction is usually faster than ventricular contraction, meaning that ventricular contraction will begin before atrial contraction begins. Thus, one of the following settings may be selected:

[0026] a. The mode of operation may include stimulating the ventricle to begin contracting at some point during atrial contraction but before the atrium reaches its maximum contractile force.

[0027] b. The operating mode is to stimulate the ventricles while the atria are contracting but have not reached their maximum contractile force. The method may include causing the ventricle to begin contracting at some point after the ventricle has contracted.

[0028] c. The mode of operation is such that contraction is essentially the same in both the atrium and ventricle (e.g., This includes stimulating the ventricles with contractions initiated no more than 5 ms apart from each other. It's okay to do that.

[0029] d. The operating mode stimulates the ventricles to achieve peak atrial contraction when the ventricles are maximally dilated. This may include initiating a contraction of the ventricles at a time such that contraction occurs, thereby causing increased atrial wall expansion.

[0030] The operating mode is to stimulate the ventricles to contract a small amount before the onset of at least one atrium contraction. at least partially contracting, thereby causing the AV valve to contract during the initiation of contraction of at least one atrium. may include causing the

[0031] Preferably, the processor circuitry detects whether one or more excitatory pulses are delivered to the patient's ventricle. The atrium may be configured to operate in an operating mode in which one or more excitatory pulses are delivered to the atrium between about 0 ms and about 50 ms from the atrium.

[0032] In another aspect, an embodiment of a method for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume is provided, the method including delivering stimulation pulses from a stimulation circuit to at least one of an atrium and a ventricle and inhibiting atrial activation in at least one atrium. The ventricles are stimulated so that ventricular excitation begins approximately 0 ms to 50 ms before the start of the cardiac cycle. Reducing ventricular filling volume from pre-treatment ventricular filling volume and reducing the patient's blood pressure from pre-treatment blood pressure. and operating a processor circuit coupled to the stimulation circuit to operate in an operating mode in which the stimulation circuit operates.

[0033] In such embodiments, atrial activation may be sensed to determine the onset of atrial activation. For example, the method may include delivering one or more excitatory pulses to the ventricle between about 0 ms and about 50 ms before the next atrial activation is expected to occur. The time interval between the onset of atrial activation and the moment at which atrial activation is sensed may be known and used to determine the timing of the onset of atrial activation. For example, if atrial activation is sensed 5 ms after the onset of atrial activation, the time interval may be known and used to determine the timing of the onset of atrial activation. If it is known or estimated that the ventricle will be stimulated 20 ms before the onset of atrial activation, then the ventricle will be stimulated 25 ms before the next expected sense of atrial activation.

[0034] In another embodiment, the method includes stimulating the atrium and ventricular stimulation in at least one ventricle. Atrial excitation is initiated between approximately 0 ms and 50 ms after the onset of excitation, thereby controlling ventricular filling. and operating a processor circuit coupled to the stimulation circuit to operate in an operating mode that reduces a pre-treatment ventricular filling volume and reduces the patient's blood pressure from a pre-treatment blood pressure. For example, the method may include delivering one or more excitatory pulses to the atrium between about 0 ms and about 50 ms after the one or more excitatory pulses are delivered to the patient's ventricle. In such embodiments, pacing may be timed without relying on sensing atrial activation. Preferably, such embodiments provide for one or more atrial activation events before spontaneous activation occurs. Atrial activation is sensed to ensure that the excitatory pulse is delivered to the atrium. Preferably, atrial activation is configured to commence between about 0 ms and about 50 ms after the onset of ventricular activation when the intrinsic atrial activation rate is lower than the intrinsic ventricular activation rate.

[0035] In some embodiments, the timing of the mechanical contractions relative to the electrical excitation of the chamber for the patient may be assessed using, for example, ultrasound (e.g., echocardiography or echocardiography) or other known means. The timing of the mechanical contractions relative to the electrical excitation of the chamber for the patient may be considered, and the timing at which one or more excitatory pulses are delivered to the heart may be selected to produce a desired pattern of contractions.

[0036] The operating mode is to stimulate the ventricles to contract before at least one atrium begins to contract. This may include shrinking.

[0037] The operating mode is to stimulate the ventricles to contract before at least one atrium begins to contract. contracting the atrium, thereby closing the AV valve during at least a portion of the contraction of at least one atrium. This may include enabling the user to

[0038] The operating mode is to stimulate the ventricles to contract before at least one atrium has finished contracting. contraction, thereby closing the AV valve during the onset of at least one atrial contraction. The method may include:

[0039] Preferably, the method may include delivering one or more excitatory pulses to the atrium between about 0 ms and about 50 ms after the one or more excitatory pulses are delivered to the patient's ventricle. .

[0040] In another aspect, an embodiment of a device for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume is provided. The device includes: a stimulation circuit configured to deliver stimulation pulses to the cardiac chamber. The device may include a processor circuit coupled to the stimulation circuit, the processor circuit configured to generate approximately 40% atrial contraction and approximately 100% ventricular contraction when an atrioventricular valve associated with the atrium is closed. and atrial contraction to induce a contraction of at least one cardiac chamber, thereby reducing ventricular filling volume from a pre-treatment ventricular filling volume and reducing the patient's blood pressure from a pre-treatment blood pressure. The cardiac stimulator may be configured to operate in a mode of operation that stimulates the atria to contract approximately 60 ms or less prior to the closure of the AV valve. This may be achieved, for example, by causing the atria to begin contracting approximately 60 ms or less prior to the closure of the AV valve. Preferably, this timing may be set periodically (e.g., at the time of implantation) based on data from an external sensor and / or as a closed loop using one or more implanted sensors.

[0041] In another aspect, an embodiment of a device for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume is provided. The device includes a stimulator for at least one cardiac chamber. The device may include a stimulation circuit configured to deliver pulses. The device may include a processor circuit coupled to the stimulation circuit, the processor circuit configured to cause between about 50% and about 95% of the atrial contraction during a ventricular systole, thereby reducing ventricular filling. and configured to operate in an operational mode that paces at least one heart chamber such that the volume of the cardiac chamber is reduced from a pre-treatment ventricular filling volume and the patient's blood pressure is reduced from a pre-treatment blood pressure. This may be done, for example, by inducing the atrium to contract approximately 50 ms to 5 ms before the onset of ventricular contraction. This can be achieved by initiating a ventricular contraction. Preferably, the timing of the onset of ventricular contraction may be set according to the timing of AV valve closure. Preferably, this timing may be set periodically (e.g., at the time of implantation) based on data from an external sensor and / or as a closed loop using one or more implanted sensors.

[0042] In another aspect, blood pressure disorders are diagnosed in patients with pretreatment blood pressure. An embodiment of a method performed by an implanted cardiac stimulator associated with a patient's heart for treatment is provided. The method may include stimulating the heart to contract an atrium while closing a heart valve associated with the atrium, such that the contraction expands the ventricle, and the ventricular expansion results in a reduction in the patient's blood pressure from a pre-treatment blood pressure. This may be achieved, for example, by contracting the atrium at a time when ventricular pressure is at a maximum, such that the active force of the atrial contraction increases atrial expansion beyond the maximum passive expansion caused by contraction of the associated ventricle. In such a case, the timing of the maximum atrial contraction should coincide with the end of an isovolumic period, or or during the rapid ejection period of the ventricle. , this timing may be set periodically (eg, at the time of implantation) based on data from external sensors and / or as a closed loop using one or more implanted sensors.

[0043] In another aspect, an embodiment of a system for reducing blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a patient's heart with a stimulation pattern comprising at least one stimulation pulse. The system may include at least one controller configured to receive input related to the patient's blood pressure and adjust the stimulation pattern based on the blood pressure. For example, the input may be receiving data sensed by one or more sensors (embedded or external); , and / or may include receiving user-supplied data. For example, during implantation and / or periodic checks, the user may Data may be provided.

[0044] Preferably, the system receives from the measurement sensor and / or the user interface: It includes an input port for receiving this input via wired and / or wireless communication. The input may comprise data related to blood pressure (BP), or changes in BP, which may be measured as systolic BP (SysBP), diastolic BP, mean arterial BP, and / or other related BP parameters. For example, at least one sensor may measure blood pressure in one or more cardiac chambers. The pressure or change in pressure may be sensed and the stimulation pattern adjusted based on the pressure or change in pressure. In another embodiment, the sensor may sense pressure in more than one chamber and adjust stimulation based on the relationship between the pressure waveforms of the two chambers.

[0045] The controller controls a parameter of at least one first stimulation setting of the at least one stimulation pulse. The stimulation pattern may be adjusted by performing an adjustment process including adjusting the

[0046] The first stimulation setting may be configured to reduce or prevent atrial kick in at least one ventricle.

[0047] The parameters may include adjustment of the AV delay, for example, the natural AV delay, whether it occurs naturally (i.e., without delivery of a stimulus to the heart) or as a result of a pulse delivered by one or more atria and the heart. By timing the delivery of the stimulus to the ventricles, the delay between the onset of atrial activation and the onset of ventricular activation may be in the range of 120-200 ms. Preferably, adjusting the AV delay allows it to be adjusted from a normal AV delay (e.g., 120 ms) to a shorter AV delay (e.g., 120 ms between the onset of atrial activation and the onset of ventricular activation). This means adjusting the delay from the start of the pulse to the start of ventricular activation (0 to 70 ms, or 0 to 50 ms AV delay, where ventricular activation occurs before atrial activation). Preferably, stimulation settings with an AV delay between -40ms and 60ms, more preferably between -50ms and 0 or 0-70ms, preferably >0-70ms, are chosen to reduce or prevent atrial kick.

[0048] The stimulation pattern is designed to increase blood pressure by at least the prescribed amount within approximately 3 seconds of application of electrical current to the heart. and to maintain the reduction in blood pressure for a time interval of at least 1 minute. For example, the stimulation pattern may be configured to respond to one or more sensed BP parameters. The parameters may be selected and / or adjusted based on feedback related to the

[0049] The time interval may be at least 5 minutes.

[0050] The predetermined amount of blood pressure reduction may be 8 mmHg or less.

[0051] The predetermined amount of blood pressure reduction may be at least 4% of the patient's pre-treatment blood pressure.

[0052] The patient's blood pressure must not exceed a predetermined average value by more than a predetermined amount during the time interval.

[0053] The predetermined degree may be a difference of about 8 mmHg or less.

[0054] The controller may be configured to administer a plurality of stimulation patterns and, during stimulation, receive corresponding input data for each stimulation pattern related to the patient's blood pressure. The controller may also receive, for each of the plurality of stimulation patterns, at least one blood pressure variability pattern related to the input data. The controller may be configured to calculate a blood pressure variability parameter. The controller may be configured to adjust the stimulation pattern in response to the blood pressure variability parameter.

[0055] The controller may be configured to adjust the stimulation pattern to have the best blood pressure variability parameters.

[0056] The best blood pressure variability parameter may be one that exhibits the lowest degree of baroreflex or the lowest degree or degree of adaptation as detailed herein.

[0057] The best blood pressure variability parameters are those that exhibit baroreflex or adaptive responses within predetermined ranges as detailed herein. It may also indicate the degree.

[0058] At least two stimulation patterns of the plurality of stimulation patterns each include at least one stimulation pattern having a stimulation setting configured to reduce or prevent atrial kick in at least one ventricle. The at least two stimulation patterns may differ from each other by the number or length of time that at least one stimulation pulse is delivered in succession.

[0059] The multiple stimulation patterns may differ by the number or length of time that the system is configured to sequentially elicit the predetermined AV delay.

[0060] At least two of the plurality of stimulation patterns may differ from the others by one or more stimulation settings included within each of the at least two stimulation patterns.

[0061] The plurality of stimulation patterns may include a first stimulation setting and a second stimulation setting administered after the first stimulation setting. The second stimulation setting may include at least one stimulation setting based on an algorithm that uses blood pressure variability parameters associated with input data of the first stimulation setting. It may have settings.

[0062] The system may include a blood pressure sensor for providing input data related to the patient's blood pressure.

[0063] The blood pressure sensor may be implantable.

[0064] The blood pressure sensor and controller may be configured to operate at least partially as a closed loop.

[0065] In another aspect, an embodiment of a system for reducing blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a patient's heart with a stimulation pulse. The system may include a controller. The controller may be configured to provide a first stimulation setting comprising at least one stimulation setting configured to reduce or prevent atrial kick in at least one ventricle during a first time interval and to receive first input data related to the patient's blood pressure during the first time interval. The controller may be configured to calculate at least one blood pressure variability parameter related to the first input data. The controller may be configured to provide a first stimulation setting comprising at least one stimulation setting configured to reduce or prevent atrial kick in at least one ventricle during the first time interval. at least one parameter of a second stimulation pattern having a second stimulation setting configured to stop The controller may be configured to adjust the meter. The second stimulation setting may be based on the at least one blood pressure variability parameter. The controller may be configured to deliver the second stimulation pattern for a second time interval.

[0066] In another aspect, an embodiment of a system for reducing blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a patient's heart with a stimulation pulse. The system may include an atrial kick in at least one ventricle. a stimulation pattern comprising at least one stimulation setting configured to reduce or prevent The stimulation pattern may include at least one controller configured to administer the stimulation pattern. and selected to cause an immediate reduction in blood pressure from the initial pressure value to a reduced pressure value and to maintain the patient's mean blood pressure at rest at least 8 mmHg below the initial pressure. Good too.

[0067] The reduced blood pressure value may be maintained for a time interval of at least 1 minute.

[0068] In another aspect, an embodiment of a kit for reducing blood pressure is provided, the kit including at least one device for setting a stimulation pattern for reducing blood pressure. The device may include at least one stimulation electrode. The device may include a controller for setting a stimulation pattern and a set of instructions for adjusting the stimulation pattern based on inputs related to the patient's blood pressure.

[0069] In another aspect, an embodiment of a system for reducing blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a patient's heart. The system may include at least one ventricle for reducing atrial kick or stimulating atrial fibrillation. The stimulation pattern may include at least one controller configured to administer a stimulation pattern comprising at least one stimulation pulse having at least one stimulation setting configured to prevent At least one stimulation setting must be selected so that maximum atrial stretch is achieved without stimulation. The atrial dilation may be configured to be approximately equal to or less than the maximum atrial dilation of the same heart when the heart is not in a ventricular chamber. Atrial dilation may be measured, calculated, and / or calculated in a manner known in the art. In some embodiments, the atrial dilation determination may be In some embodiments, the atrial diastole calculation may include measuring or estimating atrial dimensions (e.g., diameter, size, or circumference).

[0070] At least one stimulation setting is designed to maximize the atrium contraction when the AV valves are open. The configuration may be as follows.

[0071] The at least one stimulation setting is configured to alter the mechanics of at least one atrial contraction such that the mechanics of the at least one atrial contraction differs from the mechanics of a preceding natural atrial contraction. The mechanics of atrial contraction may be assessed using known techniques, including, for example, ultrasound (e.g., echocardiography or echocardiography).

[0072] At least one stimulation setting may be configured to reduce the force of at least one atrial contraction. The force of the atrial contraction may be reduced by, for example, temporarily generating an atrial spasm or an atrial flutter. One example is a rapid stimulation pulse. The purpose of the present invention is to transmit a burst of atrial contraction to the atrium for a short period of time. The force of the atrial contraction can be determined by sensing atrial pressure and / or its derivatives, such as wall motion or wall flow, using known means. Such sensing may be used as closed-loop feedback and / or occasionally (e.g., at the time of implantation and / or testing).

[0073] At least one stimulation setting may be configured to prevent at least one atrial contraction. The atrial contraction may be prevented, for example, by temporarily producing an atrial spasm or atrial flutter. One example is delivering a burst of rapid stimulation pulses to the atrium for a short period of time.

[0074] In another aspect, an embodiment of a system for reducing blood pressure is provided. The system may include at least one stimulation electrode for stimulating at least one chamber of a patient's heart. The at least one controller may deliver a stimulation pattern of stimulation pulses to the patient's heart. The at least one controller may be configured to administer a pacing control to the patient based on the state of the patient's AV valve. The device may be configured to receive relevant inputs, such as from implanted or external acoustic or blood flow sensors, via wired or wireless communication, and / or from a user. The at least one controller may be provided via a user interface. The device may be configured to adjust at least one stimulation pattern based on the state of the patient.

[0075] Inputs related to the state of the patient's AV valve may indicate the timing of AV valve closure.

[0076] Input related to the state of the patient's AV valve may be provided based on a heart sound sensor.

[0077] Input related to the state of the patient's AV valve may be provided based on a blood flow sensor.

[0078] The blood flow sensor may include an implanted sensor.

[0079] The blood flow sensor may include an ultrasound sensor for sensing blood flow through the AV valve.

[0080] The blood flow sensor and controller may be configured to operate at least partially as a closed loop.

[0081] The stimulation pattern is configured to reduce or prevent atrial kicks in at least one ventricle. The stimulation device may include at least one stimulation pulse.

[0082] The step of adjusting the at least one stimulation pattern may include adjusting an AV delay of the at least one stimulation pulse.

[0083] In another aspect, an embodiment of a system for reducing ventricular filling volume in a patient having a pre-treatment ventricular filling volume is provided. The system includes: delivering a stimulation pulse to at least one cardiac chamber; The system may include at least one controller configured to administer delivery of one or more stimulation patterns of stimulation pulses to at least one cardiac chamber. At least one of the stimulation pulses may be a first stimulation pulse. and at least one of the stimulation pulses has a second stimulation setting that is different from the first stimulation setting. At least one of the first stimulation setting and the second stimulation setting may be configured to reduce or prevent atrial kicks, thereby reducing ventricular filling volume from a pre-treatment ventricular filling volume.

[0084] The first stimulation setting and the second stimulation setting may be configured to reduce or prevent atrial kick.

[0085] The first stimulation setting may have an AV delay that is different from the AV delay of the second stimulation setting.

[0086] At least one of the one or more stimulation patterns may be repeated at least twice in a one hour period.

[0087] The at least one controller may be configured to apply one or more stimulation patterns continuously for a time interval lasting 10 minutes or more, the first stimulation setting being active for at least 50% of the time interval. configured to reduce or prevent atrial kicks in at least one ventricle during good.

[0088] The second stimulation setting may have a longer AV delay than the first stimulation setting.

[0089] The second stimulation setting has a longer AV delay than the first stimulation setting.

[0090] The one or more consecutive stimulation patterns may comprise at least one stimulation pulse having the first stimulation setting for at least about 85% of the time interval.

[0091] The time interval may be at least 30 minutes long.

[0092] The time interval may be at least one hour long.

[0093] The time interval may be at least 24 hours long.

[0094] The one or more sequential stimulation patterns have a third stimulation setting different from the first stimulation setting and the second stimulation setting and are configured to reduce or prevent atrial kick in at least one ventricle. The stimulation pulse may comprise at least one stimulation pulse generated.

[0095] The one or more consecutive stimulation patterns have a third stimulation setting different from the first stimulation setting and the second stimulation setting, and produce an atrial kick in at least one ventricle for less than about 50% of the time interval. At least one stimulation pulse may be configured to reduce or prevent stomach.

[0096] The one or more consecutive stimulation patterns may comprise a third stimulation configured to reduce or not prevent atrial kick in at least one ventricle for about 20% or less of the time interval.

[0097] The one or more sequential stimulation patterns may comprise a sequence of 10 to 60 stimulation pulses having a first stimulation setting, the first stimulation setting reducing or inhibiting an atrial kick in at least one ventricle and a sequence of 1 to 10 beats embedded within the 10 to 60 stimulation pulses. The sequence of 1 to 10 beats may have a longer AV delay than the first stimulation setting.

[0098] The sequence of 1 to 10 beats may include at least one stimulation pulse having a first stimulation setting configured to reduce or prevent an atrial kick in at least one ventricle.

[0099] A sequence of 1 to 10 beats delivers at least one stimulation pulse with the second stimulation setting. It may also contain.

[0100] The sequence of 1 to 10 beats may include a natural AV delay.

[0101] At least one beat of the sequence of 1 to 10 beats may occur without stimulation.

[0102] The first stimulation setting is set so that the increase in blood pressure occurring during the stimulation pulse is limited to a predetermined value. , may be configured to reduce atrial kick in at least one ventricle, and the second stimulation setting may be configured to reduce baroreflex response or adaptation to the reduced atrial kick.

[0103] The second stimulation setting is configured to allow the blood pressure to increase for approximately 1 to 5 heartbeats. It may be possible.

[0104] The stimulation pattern may include a plurality of stimulation pulses having a first stimulation setting.

[0105] The stimulation pattern may include a plurality of stimulation pulses having a second stimulation setting.

[0106] The stimulation pattern may have a second stimulation setting between about 1% of the plurality of stimulation pulses and about 40% of the plurality of stimulation pulses.

[0107] The stimulation pattern corresponds to the ratio of the time constants of the response to increases and decreases in blood pressure. The ratio of stimulation pulses having the first stimulation setting to stimulation pulses having the second stimulation setting. It's okay to be.

[0108] The first stimulation setting may include a first AV delay and the second stimulation setting may include a second AV delay, and the first AV delay may be shorter than the second AV delay.

[0109] The stimulation pattern may include a plurality of stimulation pulses having a first stimulation setting.

[0110] The stimulation pattern may include a plurality of stimulation pulses having a second stimulation setting.

[0111] The stimulation pattern may have a second stimulation setting between about 1% of the plurality of stimulation pulses and about 40% of the plurality of stimulation pulses.

[0112] The stimulation pattern corresponds to the ratio of the time constants of the response to increases and decreases in blood pressure. The ratio of stimulation pulses having the first stimulation setting to stimulation pulses having the second stimulation setting. It's okay to be.

[0113] The stimulation pattern may include a ratio of about 2 to about 5 stimulation pulses having the second stimulation setting to about 8 to about 13 stimulation pulses having the first stimulation setting.

[0114] One of the first stimulation setting and the second stimulation setting may be configured to elicit a hormonal response from the patient's body.

[0115] In another aspect, an embodiment of a system for reducing ventricular filling volume in a patient having a pre-treatment ventricular filling volume is provided. The system includes: a stimulation pulse delivered to at least one cardiac chamber; The system may include a stimulation circuit configured to deliver one or more stimulation patterns of stimulation pulses to at least one cardiac chamber. The system may include at least one controller configured to administer delivery of one or more stimulation patterns of stimulation pulses to at least one cardiac chamber, wherein at least one of the stimulation pulses initiates ventricular activation between about 0 ms and about 70 ms after onset of atrial activation, thereby increasing ventricular filling volume to a level lower than that of a pre-treatment cardiac chamber. For example, the processor circuit may include a setting configured to reduce the ventricular filling volume by about 0 ms to about 70 ms after the onset of ventricular activation occurs in at least one atrium or about 0 ms to about 70 ms after the delivery of one or more excitatory pulses to the atrium. It may be configured to operate in a mode of operation in which an excitatory pulse is delivered to the ventricle.

[0116] In some embodiments, the timing of sensed atrial activation may be determined by taking into account the delay between the actual onset of activation and its setting. For example, if the sensing delay is estimated to be 20-40 ms and the stimulation pulse is delivered 0-70 ms after the onset of atrial activation. In this case, the system may be configured to deliver a pulse between 40 ms before the next expected sensed event and 30 ms after the next expected sensed event, or 30 ms after the next sensed event. Similarly, a stimulation pulse may be delivered to the ventricle between 0 and 50 ms before the onset of atrial activation. For example, if the same 20-40 ms sensing delay is assumed, the system may be configured to deliver a pulse between 40 ms before the next expected sensing event and 90 ms before the next expected sensing event. The sensing delay may be due to one or more of the distance between the location of activation onset and the sensing electrode, the level of the electrical signal, the characteristics of the sensing circuitry, and the threshold set for the sensing event. For example, the duration of signal propagation from the origin of excitation to the electrode location, the duration related to the frequency response of the sensing circuitry, and / or the time it takes for the signal propagation energy to reach a level that is detectable by the sensing circuitry. The delay may be significant, for example, in the range of about 5 ms to about 100 ms. One approach to estimating the delay is to use a method in which both the atrium and ventricle are sensed. One approach is to use the time difference between the AV delay measured when the atrium is paced and the AV delay when the ventricle is sensed and the AV delay when the atrium is paced. Another approach may use a calculation of the amplifier response time based on a set threshold, signal strength, and frequency content. Another approach is to use the effect on blood pressure. This may involve modifying the delay used in conjunction with atrial sensing until the result is similar to that achieved by pacing both the atrium and ventricle with the desired AV delay.

[0117] In another aspect, an embodiment of a system for reducing ventricular filling volume in a patient having a pre-treatment ventricular filling volume is provided. The system includes: a stimulation pulse delivered to at least one cardiac chamber; The at least one controller may deliver one or more stimulation pulses to at least one cardiac chamber for a time interval lasting 10 minutes or more. At least one of the stimulation pulses may be configured to deliver a stimulation pattern of , may have a first stimulation setting configured to reduce or prevent atrial kicks in at least one ventricle for at least 5 minutes of the time interval, and at least one of the stimulation pulses has a second stimulation setting different from the first stimulation setting, thereby reducing the ventricular filling volume from the pre-treatment ventricular filling volume.

[0118] In another aspect, a method is provided for reducing ventricular filling in a patient having a pre-treatment ventricular filling volume, the method comprising: The method may include delivering one or more stimulation patterns of stimulation pulses to the At least one of the pulses is transmitted to at least one ventricle for at least 5 minutes of the time interval. and a first stimulation setting configured to reduce or prevent atrial kicks at At least one of the stimulation pulses has a second stimulation setting that is different from the first stimulation setting.

[0119] Other systems, methods, features, and advantages of the invention will be or become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description and this summary, be within the scope of the invention, and be protected by the following claims. [Brief explanation of the drawings]

[0120] [Figure 1] 1 is a graph showing the systolic blood pressure of a hypertensive patient receiving a stimulation signal plotted against time. [Figure 2] FIG. 2 is an enlarged view of the portion indicated by the dashed rectangle A in FIG. [Figure 3A] FIG. 3 is an enlarged view of the portion between points a and a′ in FIG. 2. [Figure 3B] FIG. 2 is an enlarged view of the portion indicated by the dashed rectangle A' in FIG. [Figure 4]FIG. 2 is an enlarged view of the portion indicated by the dashed rectangle B in FIG. [Figure 5A] FIG. 2 is an enlarged view of the portion indicated by the dashed rectangle C in FIG. [Figure 5B] FIG. 5B is an enlarged view of the portion between points c and c′ in FIG. 5A. [Figure 6] 1 is a graph showing the systolic blood pressure of a hypertensive patient receiving a stimulation signal plotted against time. [Figure 7] 1 is a graph showing the systolic blood pressure of a hypertensive patient receiving a stimulation signal plotted against time. [Figure 8] 10 is a flowchart illustrating a method for setting and / or selecting a stimulation pattern. [Figure 9] FIG. 1 is a schematic diagram illustrating a system for reducing blood pressure. [Figure 10A] 1 is a time plot of the electrocardiogram, aortic pressure, and left ventricular pressure of a healthy dog ​​heart. [Figure 10B] 1 is a time plot of the electrocardiogram, aortic pressure, and left ventricular pressure of a healthy dog ​​heart. [Figure 11A] 1 is a time plot of the heart of a hypertensive dog showing right atrial pressure, the enlarged diastolic portion of right ventricular pressure, right ventricular pressure and an electrocardiogram. [Figure 11B] 1 is a time plot of the heart of a hypertensive dog showing right atrial pressure, the enlarged diastolic portion of right ventricular pressure, right ventricular pressure and an electrocardiogram. [Figure 12] 1 is a graph showing right atrial pressure, enlarged diastolic portion of right ventricular pressure, right ventricular pressure, left ventricular pressure, as well as aortic pressure and electrocardiogram on the same graph in a hypertensive dog heart. [Figure 13] 1 is a flow chart illustrating a method 40 for reducing blood pressure. [Figure 14] 1 is a flow chart illustrating a method 40 for reducing blood pressure. [Figure 15] 1 is a schematic diagram showing an artificial valve according to one embodiment of the present invention. FIG. [Figure 16] 1 is a graph showing the systolic blood pressure of a hypertensive patient receiving a stimulation signal plotted against time. DETAILED DESCRIPTION OF THE INVENTION

[0121] The present invention may be better understood by reference to the following drawings and description. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. Moreover, in the figures, like reference numerals indicate corresponding parts throughout the different views.

[0122] The human heart has two atria and two ventricles. In a normal cardiac cycle, cardiac contraction begins with an atrial contraction, followed by a ventricular contraction.

[0123] The mechanical process of cardiac contraction is controlled by electrical conduction in the heart. During each heartbeat, a wave of depolarization is elicited by cells in the sinoatrial node. The depolarization propagates within the atria to the atrioventricular (AV) node and then to the ventricles. In a healthy heart, the atrioventricular delay (AV delay), i.e., the delay time between the onset of atrial and ventricular activation, is typically between 120 and 200 milliseconds (ms). The relative timing of atrial and ventricular contraction is influenced, among other things, by the relative timing of each chamber's activation and the time required for the chambers to generate a mechanical contraction as a result of electrical activation (which depends on size, propagation speed, differences in myocyte properties, etc.).

[0124] Before contraction, the heart muscle relaxes, allowing blood to flow freely from the atria to the ventricles through the valves between them. This period can be divided into the rapid filling phase and the slow filling phase. In the rapid filling phase, blood from the venous system and the atria rapidly fills into the ventricles. The rapid filling phase lasts for approximately 110 ms and begins immediately after the relaxation of the ventricles, filling the atria. This is followed by a slow filling phase that continues until the onset of contraction. The duration of the slow filling phase is dependent on the heart rate. As the atria then contract, pressure increases within the atria, causing blood to flow more rapidly into the ventricles. This contribution of atrial contraction to ventricular filling is known as the "atrial kick." The atrial kick is normally responsible for approximately 10% to 30% of ventricular filling.

[0125] The cardiac cycle begins with the onset of atrial activation. Then, 50-70 ms later, the atria begin to contract, lasting approximately 70-110 ms. Meanwhile, the electrical impulse propagates to the ventricles, and the onset of ventricular activation occurs with an AV delay of approximately 120-200 ms (the AV delay can be as long as 250 ms in unhealthy individuals).

[0126] As the ventricles contract, pressure builds up within them, passively closing the valves between each atrium and its respective ventricle (the AV valves), thus stopping the flow of blood from the atria to the ventricles and preventing backflow. During the next contraction, a period known as isovolumic contraction, which lasts approximately 50 ms, all ventricular valves close and the pressure within the ventricles rises rapidly without a significant change in volume. As ventricular pressure increases further, the valves between the ventricles and atria open, allowing blood to flow out of the ventricles and out of the heart. Contraction is further divided into a rapid ejection period and a decreased ejection period. The rapid ejection period lasts approximately 90-110 ms and is the time during which a single stroke is performed. At the end of the rapid ejection phase, the ventricular and atrial pressures reach their peaks. The rapid ejection phase is followed by a slow ejection phase lasting approximately 130-140 ms. All valves then close again, and the ventricles relax in an isovolumic state for approximately 60-80 ms, during which time the ventricular pressure decreases. At this time, the valves between the ventricles and atria reopen, allowing blood to flow freely into the ventricles, and a new excitation cycle begins.

[0127] In the present disclosure, cardiac stimulation is used to reduce ventricular filling volume and / or blood pressure (BP). BP or change in BP may be measured as systolic BP (SysBP), diastolic BP, mean arterial BP, BP in one or more chambers, and / or other relevant BP parameters. In some embodiments, an electrical stimulator, such as a pacemaker or other type of device having a pulse generator, may be used to stimulate the patient's heart and reduce blood pressure. Electrodes electrically connected to the electrical stimulator by a wired or wireless connection may be positioned adjacent to the heart chamber. The electrical stimulator may be activated to deliver pulses to the heart chamber via the electrodes.

[0128] In some embodiments, stimulating the heart to reduce or even prevent the contribution of atrial contraction to ventricular filling (atrial kick) reduces cardiac filling at the end of diastole, resulting in a reduction in blood pressure. For simplicity, the following description will refer to such stimulation as "BPR (blood pressure reducing) stimulation." BPR stimulation The present invention provides a method for treating at least one chamber of the heart such that atrial kicks are reduced or even prevented. The method may include delivering at least one stimulation pulse to the pulsed pulsed member. The pulse will be referred to herein as a "BPR stimulation pulse" or "BPR pulse."

[0129] As used herein, a "stimulation pulse" refers to a pulse that stimulates one or more of the heart's A sequence of one or more electrical pulses is delivered to the upper chamber. For example, in some embodiments, the stimulation pulses may be one or more electrical pulses delivered to one or more locations in the ventricles and / or one or more electrical pulses delivered to one or more locations in the atria. Thus, in some embodiments, the stimulation pulses may include a first electrical pulse delivered to an atrium and a second electrical pulse delivered to a corresponding ventricle. In some embodiments, the stimulation pulses may be delivered to one or more chambers of the heart. The pulse may include a single pulse being transmitted to multiple locations on the amplifier.

[0130] Stimulation settings refer to one or more parameters of one or more stimulation pulses delivered in a single cardiac cycle. For example, these parameters may include power, (power), the time interval between electrical pulses contained in a single stimulation pulse (e.g., AV delay ), the duration of the delivery relative to the natural rhythm of the heart, the length of the stimulation pulse or a portion thereof, and the location of the delivery between two or more chambers and / or within a single chamber. A BPR stimulation configuration or "BPR configuration" may include a configuration of one or more BPR pulses.

[0131] A stimulation pattern may include a series of pulses having the same stimulation setting, or a stimulation pattern may include multiple pulses, each having a different stimulation setting. For example, a stimulation pattern may include one or more pulses having a first setting and one or more pulses having a second setting that is different from the first setting. When a stimulation pattern is said to be active, this means that at least one stimulation pattern with this setting is active. It is understood to mean that in some embodiments, a stimulation pattern may include one or more cardiac cycles in which no stimulation pulses are delivered. In that case, the pulses can be considered to be delivered with zero power. A stimulation pattern can be a sequence of multiple identical pulses or pulses containing two or more different settings. Two stimulus sequences in one pattern may be used in one setting. The two or more stimulation sequences may differ in the order of pulses provided. Preferably, they may differ in length (in duration and / or number of beats) In some embodiments, the stimulation pattern includes pulses with BPR settings. In some embodiments, the stimulation pattern may include pulses with no BPR settings. It's fine.

[0132] Example of stimulation settings configured to reduce or prevent atrial kicks in at least one ventricle may include stimulation settings disclosed herein configured to cause a reduction in the patient's ventricular filling volume from the pre-treatment ventricular filling volume. This may be caused by causing at least some atrial contraction to occur against a closed AV valve. Some such examples may include:

[0133] a. Deliver one or more stimulation pulses to the patient between 0 and 50 ms before the onset of activation in the patient's atrium. and delivering one or more stimulation pulses to the ventricles. Preferably, this delay is set based on the atrial activation setting. Preferably, this includes delivering one or more stimulation pulses to the atria 0-50 ms after delivery of the stimulation pulse to the ventricles. Preferably, this is done at a rate slightly higher than the patient's natural heart rate.

[0134] b. Deliver one or more stimulation pulses to the patient between 0 and 70 ms after the onset of activation in the patient's atrium. and delivering one or more stimulation pulses to the atrium. Preferably, this delay is set based on the detection of atrial activation. Preferably, this includes delivering one or more stimulation pulses to the atrium 0-70 ms before delivering the stimulation pulse to the ventricle. Preferably, this is done at a rate slightly higher than the patient's natural heart rate.

[0135] Some embodiments may provide a system for reducing blood pressure configured to deliver stimulation at a rate higher than the natural heart rate based on a detected natural heart rate or natural activation. For example, the system may be configured to detect natural activation during delivery of stimulation pulses, and if natural activity is detected, the system may be configured to inhibit delivery of stimulation pulses to the chamber. If the amount of detected activation within a given time frame exceeds a threshold, the natural heart rate may be considered higher than the number of stimulation pulse deliveries, in which case the number of deliveries may be increased, for example, to accommodate the patient's increased heart rate. On the other hand, if the amount of detected activation within a given time frame exceeds a threshold, the natural heart rate may be considered higher than the number of stimulation pulse deliveries, in which case the number of deliveries may be increased, for example, to accommodate the patient's increased heart rate. If the amount of activation received is below a threshold (which may be 0), the natural heartbeat will be stimulated. The number of deliveries may be considered lower than the number of deliveries of a severe pulse, in which case the number of deliveries may be reduced to avoid, for example, over-excitation of the patient's heart.

[0136] To achieve this effect, according to one embodiment, a system for reducing blood pressure senses the excitation rate of at least one of the atria and ventricles of the patient's heart. The cardiac device may include a sensor for sensing an activation rate of at least one of the atria and ventricles, a stimulation circuit configured to deliver stimulation pulses to the atria and ventricles, and a processor circuit coupled to the stimulation circuit. Preferably, the sensor for sensing an activation rate of at least one of the atria and ventricles may include an electrode for detecting atrial activation. The processor circuit may be configured to detect a patient's heart rate based on the sensing and to operate in a mode of operation in which stimulation pulses are delivered to each of the atria and ventricles. The stimulation pulses may be delivered at a rate higher than the sensed activation rate and may be configured to stimulate the ventricles at a time between about 50 ms before and about 70 ms after stimulation of the atria.

[0137] Reducing atrial kick may have an immediate effect on blood pressure, while hormone-mediated mechanisms may take longer. Some devices may be configured to have both immediate and hormone-mediated effects, but preferably, some BPR settings and / or stimulation patterns may be configured to reduce or prevent atrial kick without significantly increasing atrial dilation. For example, if the AV valve closes at or after atrial contraction is at peak pressure, atrial dilation will not increase due to premature closure of the valve.

[0138] Thus, in some embodiments, the device may be configured to produce relative timing of atrial and ventricular activation comparable to an AV delay at least 40 ms long or at least 50 ms long. Atrial stretch may be measured, determined, and / or estimated in a manner known in the art. In some embodiments, atrial stretch determination may include measuring atrial pressure. In some embodiments, the atrial dilation calculation may include measuring or estimating atrial dimensions (e.g., diameter, size, or circumference).

[0139] In some embodiments, the atrial kick may be reduced because the BPR stimulation settings may be set such that the atrial contraction of the cardiac cycle is incomplete when the AV valve is open. In some embodiments, atrial contraction may occur completely or partially against a closed AV valve, and in some embodiments, atrial contraction may be effectively prevented or reduced.

[0140] In some embodiments, only one or more ventricles may be stimulated, and the stimulation pulses may be delivered to the different ventricles. Even if timed to have a normal AV delay (e.g., 50 ms before and 120 ms after atrial activation), In some embodiments, the BPR stimulation configuration may include at least one electrical pulse to one or more atria. In some embodiments, the at least one atrial stimulus may include delivery of an electrical pulse or stimulus. In some embodiments, the at least one atrial stimulus may cause an atrial contraction. At least one atrial stimulus may interfere with atrial contraction. At least one atrial pulse may cause an atrial spasm or other type of inefficient atrial contraction. There is a match.

[0141] The reduction in blood pressure resulting from BPR stimulation may be observed virtually immediately upon application of the stimulation signal (e.g., within 1 or 3 seconds or within 1, 3, or 5 beats), and may be observed within 5 beats from the onset of stimulation. A minimum blood pressure value may be reached within less than one minute.

[0142] By controlling the settings of the BPR stimulation, the degree to which BP is reduced may be controlled. The degree may in some cases be patient specific and / or related to the exact location of one or more stimulating and / or sensing electrodes in or on the heart.

[0143] Adaptation a. The inventors have discovered that while stimulation is maintained, blood pressure may exhibit an adaptive pattern in which, after a period of time (some of which often occurs within a short period of time, less than 5 minutes or even less than 1 minute), blood pressure increases, sometimes reaching near or even higher pre-stimulation blood pressure values ​​(at least due to baroreflexes). Adaptation is due, at least in part, to changes in cardiovascular properties, such as an increase in total peripheral resistance. The inventors further discovered that termination of stimulation results in a rapid return of blood pressure to pre-stimulation values ​​or even higher values, and that the heart then responds to blood pressure reducing stimulation signals to a degree similar to a heart that was not so stimulated. Additionally, different stimulation patterns comprising multiple BPR stimulation settings may result in different blood pressure reductions. It has been found to lead to adaptive patterns.

[0144] b. The stimulation pattern includes, for example, at least one first stimulation setting and a second stimulation setting that is different from the first stimulation setting. and a second stimulation setting, wherein the first stimulation setting and the second stimulation setting are The stimulation pattern is configured to reduce or prevent stimulation of more than two different The second setting in some embodiments may even have a longer AV delay than the first setting. In some embodiments, the second setting may have a longer AV delay than the first setting to reduce atrial kick. The configuration may not be as follows.

[0145] In Figure 1, the systolic blood pressure of a hypertensive patient receiving a stimulation signal is plotted against time. The crosses along the plotted line represent the peak systolic blood pressure for each beat. The plot shows the pressure. No stimulation signal was delivered during approximately the first 2 minutes of the plot. As can be seen, the initial blood pressure of the patients averaged over 150 mmHg. The blood pressure fluctuations (approximately ±10 mmHg) are due to the respiratory cycle, as is known in the art.

[0146] A first stimulation pattern is then applied during time interval a-a', and a second stimulation pattern is applied during time interval a-a'. A first stimulation pattern was applied during the time interval b-b', and a third stimulation pattern was applied during the time interval c-c'. After the middle and third stimulation patterns of the line, the heart was not stimulated.

[0147] Attention is now directed to FIG. 2, which shows an enlarged portion of the portion of FIG. 1 designated by dashed rectangle A. During the time designated by the dashed rectangle in FIG. 2, which corresponds to time interval a-a' in FIG. 1, stimulation began and was delivered to the patient's right atrium and right ventricle, resulting in the atrium receiving the BPR stimulation signal (pulse) 2 ms before the ventricle. Stimulation ended at the time designated a' in FIGS. 1 and 2. During time interval a-a', the patient's systolic pressure first decreased to a minimum of less than 110 mmHg, then increased to the initial blood pressure. The blood pressure gradually increased to a value intermediate between 170 mmHg and the minimum value achieved. At point a', the stimulation was stopped and an immediate overshoot of the blood pressure was observed to exceed 170 mmHg. Within about a dozen heartbeats, the blood pressure Back to that original range.

[0148] The changes in blood pressure shown in Figures 1 and 2 represent, at least in part, the cardiovascular system's response to changes in blood pressure, known as the baroreflex. The baroreflex modulates blood pressure to its corresponding stimulus by altering cardiovascular characteristics (e.g., peripheral resistance and / or myocardial contractility). It may be assumed that the reduction in blood pressure resulting from the reduction in ventricular filling elicits a baroreflex response directed toward restoring the pre-stimulus blood pressure. The effect of the baroreflex on the cardiovascular system is evident, for example, at point a' in Figure 2. At this point, the stimulus that affected ventricular filling has receded and the blood pressure immediately exceeds the pre-stimulus blood pressure. This may be taken to indicate a baroreflex change to the cardiovascular system (e.g., increased peripheral resistance and increased contractility). At point a', when the stimulus is stopped and the blood pressure peaks, The baroreflex acts on one or more features of the cardiovascular system to lower blood pressure to its pre-change level. The baroreflex responded to the increase in blood pressure by again changing its response to blood pressure. As can be clearly seen, the response of the baroreflex feedback to increases and decreases in blood pressure is asymmetric in that the response to increases in blood pressure is much faster than the response to decreases in blood pressure. In some embodiments, this asymmetry of the baroreflex may be exploited to reduce or even prevent adaptations of reduced blood pressure due to reduced filling, for example, by controlling stimulation patterns accordingly, as described further herein.

[0149] FIG. 3A shows an expanded view of the curve of FIG. 1 between time points a and a'. In FIG. 3A, the exponential function The data were fitted to a plotted curve showing the adaptation response. The number describes the relationship between time and SysBP and has the following formula:

[0150] P = Pi + DP(1-e -t / k ) where P (in mmHg) represents the systolic blood pressure, Pi (mmHg) is the first average reduced blood pressure at the start of BPR stimulation, and DP (mmHg) is the mean reduced blood pressure after the initial decline to a new steady-state level. is a constant that represents the amount of pressure increase, k (seconds) is the response time constant, e is a mathematical constant that is the base of the natural logarithm, and t (seconds) is time.

[0151] In Figure 3A, the matching function was:

[0152] P=115+23(1-e -t / 15.5 ) In the formula, Pi was found to be 115 mmHg. DP was 23 mmHg. K was 15.5 seconds. .

[0153] FIG. 3B shows an enlarged view of the portion of FIG. 1 indicated by the dashed rectangle A′. In FIG. 3B, the index Fit a function to the plotted curve showing the adaptation response to the end of delivery of the BPR stimulus. As can be seen, this response in blood pressure reduction was faster than the response to BPR stimulation. Ta.

[0154] In Figure 3B, the matching function was:

[0155] P = 190-35(1 - e -t / 4.946 ) where Pi was found to be 190 mmHg. DP was -35 mmHg. K was 4.946 seconds.

[0156] As noted above, the baroreflex response to a reduction in blood pressure is much slower than the baroreflex response to an increase in blood pressure. This is shown as the ratio of the time constant k (about 15 seconds to about 5 seconds) noted above to the much faster response to an increase in blood pressure. This asymmetry in the speed of the baroreflex response may provide a means to design stimulation patterns that produce mean blood pressure reductions and reduced or even prevented adaptation. For example, in a preferred embodiment, a weighted response may be provided such that the stimulation pattern alternates between two stimulation settings in a manner that favors the cardiovascular changes caused by an increase in blood pressure. In this embodiment, the stimulation pattern may be weighted to reduce ventricular filling and / or to reduce or even prevent ventricular filling. The first setting is designed to reduce blood pressure and the second setting is designed to allow normal ventricular filling or at least Two stimulations were performed, with the second setting designed to have a higher ventricular filling than the first setting. The heart may be stimulated using a stimulation pattern having a setting. The stimulation pattern may include pulses having a first setting (BPR) delivered for a duration shorter than the time constant of the baroreflex response to a decrease in blood pressure. In such a case, adaptation may begin to become apparent, and blood pressure may increase from a reduced level, but may not reach its pre-stimulation level.

[0157] The stimulation pattern may also comprise pulses having a second setting (e.g., natural AV delay) that are delivered for a period longer than the time constant of the baroreflex response to an increase in blood pressure. In some cases, the baroreflex-induced reduction in blood pressure may be fully utilized, and blood pressure may even return to its level before the stimulation pattern was switched to this second setting. The weighted response of the baroreflex in such a pattern may reduce or prevent adaptation, but the average pressure may be lower than pre-stimulation levels. The relationship between the time constant and duration assigned to the delivery of pulses with different settings may determine the level of baroreflex response that is in effect during the entire stimulation pattern. For a given stimulation setting, if the duration of delivery is selected to be shorter than the time constant of the response, the baroreflex may not be able to alter the cardiovascular system back to pre-stimulation levels; if the selected duration is greater than the time constant, the baroreflex effect may be more pronounced.

[0158] As can be seen in Figure 1, in the interval between points b and b', a second stimulation pattern was delivered. Figure 4 shows an enlarged version of this portion of Figure 1 (indicated by dashed rectangle B in Figure 1). In the second stimulation pattern, a sequence of 12 BPR pulses was delivered to the atrial and ventricular chambers with a 2 ms AV delay. During this period, the atrial impulse was delivered to both the corresponding ventricles, followed by three beats in which only the atrial impulse was artificially delivered and no ventricular impulse was delivered. During these last three beats, ventricular activation occurred via natural conductance through the AV node, resulting in an AV delay of ~180 ms. This second stimulation pattern was repeated for the duration of the time interval previously mentioned. In Figure 4, an exponential function fit to the curve was found to be:

[0159] P=112+30(1-e -t / 25.5 ) As can be seen, both Pi and DP were comparable to the corresponding values ​​for the first stimulation pattern (a-a' in Figure 3A). However, k for the second pattern was nearly twice the time constant of the first stimulation pattern. During this time interval, adaptation occurred at a slower rate than in Figure 3A, but blood pressure rose more rapidly when the patterns switched between stimulation pulses than in Figure 3A. This result demonstrates that using stimulation patterns with alternating stimulation settings reduces adaptation.

[0160] A third stimulation pattern was similarly delivered between points c and c', as seen in Figure 1. Figure 5A shows an enlarged view of the portion of Figure 1 indicated by the dashed rectangle C, which includes the portion of the curve between points c and c'. In the third stimulation pattern, a sequence of 12 BPR pulses was delivered with an AV delay of 2 ms, followed by three BPR pulses, each with an AV delay of 120 ms. This , repeated for the duration of the aforementioned time interval.

[0161] The portion of the curve in Figure 5A indicated by the dashed rectangle is plotted in Figure 5B. In Figure 5B, a BPR pulse delivered with a 2 ms AV delay is followed by three BPR pulses, each with an AV delay of 120 ms. Plotted curves showing the adaptive response to the delivery of a stimulation pattern of 12 BPR pulses. was fitted with an exponential function.

[0162] In Figure 5B, the exponential function was:

[0163] P = 109.7 + 22.3 (1 - e -t / 45.4 ) In the formula, Pi was found to be 109.7 mmHg. DP was 22.3 mmHg. K was 45.4 seconds. As can be seen, the initial reduction in blood pressure was comparable to that shown in Figure 3A (Pi = 115 or 109.5), but the adaptation time constant (k) was higher (45.4 seconds vs. 15.5 seconds). This means that low blood pressure was maintained for a period approximately three times longer than in the control group.

[0164] Attention is now directed to Figure 6, in which the heart of a hypertensive patient was stimulated with a stimulation pattern having a sequence of 12 BPR pulses delivered with an AV delay of 2 ms, followed by three BPR pulses each with an AV delay of 80 ms.

[0165] As can be seen, in this case the adaptation rate was very low and barely detectable in the allotted time interval. The exponential formula could not be fitted. This suggests that adaptation was extremely slow or non-existent.

[0166] In Figure 7, a stimulation pattern with a sequence of 12 BPR pulses delivered with an AV delay of 2 ms is shown. In this study, the heart of a hypertensive patient was stimulated with three BPR pulses, each with a 40 ms AV delay. The stimulation began at point t1 and ended at point t2. There was no measured adaptive response, and the fitted curve was indeed linear, with a fixed average reduced blood pressure of approximately 112 mmHg, approximately 31 mmHg lower than the blood pressure immediately before and after the time interval t1-t2.

[0167] As is evident from the different stimulation patterns described above, a stimulation pattern comprising at least one BPR stimulus can be configured to at least approximate one or more targets. For example, in some embodiments, the stimulation pattern may be configured to cause an initial reduction in blood pressure (systolic and / or diastolic) that exceeds a predetermined threshold or falls within a predetermined range. In more particular embodiments, the blood pressure may be adjusted by at least a given percentage or by at least a given measure (e.g., 10 or even 20 mmHg or 30 mmHg), or blood pressure may be reduced to within a given range (e.g., SysBP of 90-130 mmHg) or below a given target (e.g., SysBP of 130 mmHg or less). In some embodiments, the target is a sustained period of time. For example, the predetermined blood pressure may be reduced to a predetermined average blood pressure for a period of time or for a number of heartbeats.

[0168] In another embodiment, the goal is to keep a given percentage of beats within a reduced range / threshold. In some embodiments, the goal may include reducing blood pressure while also reducing the level of spikes between stimulation pulses. For example, a stimulation pattern may be used to reduce blood pressure to a constant blood pressure for a predetermined time interval. In some embodiments, a stimulation pattern may be used to reduce blood pressure without significantly affecting cardiac output. For example, intermittent BPR pulses may be used to reduce blood pressure to a constant blood pressure. By applying a higher (or even sufficient) atrial kick, a pulse with a higher (or even sufficient) atrial kick may occur between BPR pulses. Pulses with a buck can prevent BPR pulses from significantly reducing cardiac output. .

[0169] In another embodiment, cardiac output can be dynamically affected by affecting flow through the vasculature by reducing the adaptations associated with lowering total peripheral resistance, along with reducing blood pressure (afterload). In yet another embodiment, pacing at a higher rate than the patient's natural rhythm can avoid the negative effects on cardiac output that may be associated with a lower stroke volume.

[0170] In some embodiments, a time constant for blood pressure change for a given pattern may be calculated, and the stimulation pattern may be configured to have one or more BPR stimulation parameters for an amount of time or number of beats set as a particular percentage of the calculated time constant. For example, in FIGS. 3A and 3B, k was measured to be approximately 15 seconds for the rate of increase in blood pressure during delivery of a BPR pulse and approximately 4.9 seconds for the rate of adaptation to the end of delivery of the BPR pulse. In some embodiments, it may be desirable to prevent blood pressure from increasing beyond a given value, in which case the period of delivery of the BPR pulse may be selected to be significantly less than k (e.g., 30%-60% of k). In this embodiment, the interval is selected to be less than 15 seconds. Such intervals may be about 6 to 10 seconds or 8 seconds, which results in a heart rate of about 80 beats per minute. May contain ~14 beats.

[0171] Preferably, an adaptive response to the delay of the BPR pulse is utilized. In such cases, a larger fraction of k may be applied. For example, based on FIG. 3B, 3 to 5 drums A period of time may be selected (where k is approximately 4.9 seconds). Thus, for example, based on Figures 3A and 3B, the inventors applied the stimulation pattern of Figure 4.

[0172] The stimulation pattern may be set, for example, to be the best of multiple stimulation patterns (i.e., the one that is closest to the set target parameters) and / or to be the best of the set target parameters. may be selected as the first tested stimulation pattern that matches.

[0173] Methods for Setting and / or Selecting Stimulation Patterns A method 600 for setting and / or selecting a stimulation pattern is shown schematically in FIG. Method 600 may be used during implantation of a device for performing BPR stimulation and / or to control device operating parameters. This may be done periodically to adjust the temperature and / or continuously during operation. Method 600 may be performed by system 700, described below. Thus, system 700 The system 700 may be configured to perform the steps of the method 600. Similarly, the method 600 may include steps that the system 700 is configured to perform. For example, the method 600 may include the functionality described below for the system 700. Additionally, the method 600 may be performed by the device 50 described below. The method 600 may include steps that the device 50 is configured to perform. It's okay to do that.

[0174] Throughout this disclosure, the terms "first," "second," and "third" refer to the order of events. An ordering is not always meant to be implied. In some cases, these terms are used to distinguish individual events from one another without any reference to an order.

[0175] In some embodiments, step 601 may include setting a target blood pressure value. This goal may be an absolute blood pressure value (e.g., a target blood pressure range, a target spike threshold, and / or Alternatively, the target blood pressure value may be a number or fraction of spikes within a given time frame, a relative value (e.g., compared to the patient's pre-treatment blood pressure or as a comparison between multiple tested stimulation patterns), or both. The target blood pressure value may be associated with a blood pressure value (e.g., measured in mmHg) and / or a formula calculated to fit the stimulation pattern to the blood pressure measurement, etc. This target blood pressure value may be set before, during and / or after other method steps. It may be determined, for example, and corrected if not reached by the tested stimulation pattern.

[0176] Step 602 may include delivering one or more stimulation patterns, including a first stimulation pattern, to one or more chambers of the patient's heart. The first stimulation pattern may be a generic stimulation pattern, or the first stimulation pattern may be a stimulation pattern specific to a particular device (e.g., implanting a replacement device). The first stimulus may already be selected to suit a given patient (when implanted). The patterns may include at least one stimulation pattern configured to reduce or prevent atrial kick in at least one ventricle during a first time interval.

[0177] Step 603 may be performed before, during, and after each delivery of one or more stimulation patterns (step 602). In some embodiments, the method may include sensing one or more parameters during and / or after the initiation of ... It may also include information relating to the timing and / or extent of release. In some embodiments, the sensed parameters may comprise information related to the timing and / or degree of blood flow between the atria and ventricles of the heart. The sensed parameter senses pressure within the heart chambers (atria and / or ventricles). In some embodiments, sensing the state or position (i.e., closed or open) of the patient's AV valve may include sensing heart sounds, for example, using an audio sensor. In some embodiments, sensing the state of the patient's AV valve may include Doppler sensing and / or imaging of cardiac motion. In an embodiment, the state of the patient's AV valve may be sensed by a blood flow sensor.

[0178] In some embodiments, blood flow sensing may be performed by one or more implanted sensors in one or more cardiac chambers. For example, one or more pressure sensors may be placed in the right ventricle. In some embodiments, multiple pressure sensors may be located in multiple chambers. Preferably, measurements from multiple sensors may be combined. Preferably, pressure changes, trends in pressure changes, and / or patterns of pressure changes are used to provide information related to blood flow. In some embodiments, the relative position between two or more sensors in different chambers may be Comparing the changes may be used.

[0179] Once the stimulation pattern is delivered to the heart (step 602), at least One or more parameters may be measured at any one time, multiple times, or even continuously. Each stimulation pattern may be delivered more than once.

[0180] Step 604 may include analyzing the sensed parameters. In this embodiment, at least one stimulation pattern is delivered and a corresponding parameter is sensed. Once determined, an analysis may be performed 604. In embodiments where multiple parameters are sensed, comparing the sensed parameter value with a target; Comparison between stimulation patterns, calculated values ​​relating to two or more stimulation patterns (e.g. Step 604 may include comparing a constant (e.g., k) and comparing additional sensed parameters between two or more stimulation patterns. This last function may be performed to determine and select which stimulation pattern will produce a higher ejection fraction, stroke volume, cardiac output, and / or lower battery usage. .

[0181] Step 605 may include setting a pacing (stimulation) pattern. If more than one parameter is sensed, multiple parameters, multiple targets, and / or multiple pacing (stimulation) patterns may be set. Based on the target range of numbers, the stimulation pattern used in step 605 may be selected.

[0182] In some embodiments, the steps shown in FIG. 8 may be performed in the order indicated by the arrows in FIG. 8. In other embodiments, the steps may be performed in a different order. For example, step 602 may be performed before setting the target blood pressure value according to step 601. In some embodiments, the stimulation pattern may be configured to be performed indefinitely. In some embodiments, the stimulation pattern may be configured to be performed for a predetermined period of time. For example, in some embodiments, the stimulation pattern configured during step 605 may be performed for a predetermined period of time. Steps 602, 603 and 604 may then be repeated to generate another It may be determined how the stimulation pattern affects the patient's blood pressure. Based on the analysis performed in step 604, step 605 may then also be repeated.

[0183] In some embodiments, the method 600 may include adjusting the first stimulation pattern, thus forming the first stimulation pattern into a second stimulation pattern. In some embodiments, the step 605 of setting the stimulation pattern includes adjusting the stimulation pattern. For example, step 605 may include adjusting a parameter of the first stimulation setting (e.g., the time interval from step 602). Step 605 may include adjusting parameters of a first stimulation setting configured to reduce or prevent atrial kick in at least one ventricle. Alternatively, step 605 may include adjusting the first stimulation setting to a second stimulation setting configured to cause a reduction in blood pressure by at least a predetermined amount. In embodiments, the predetermined amount may include, for example, about 8 mmHg to about 30 mmHg. In some embodiments, the predetermined amount may be about 4% of the patient's pre-treatment blood pressure. This predetermined amount may range from about 4% of the patient's pre-treatment blood pressure to about 30% of the patient's pre-treatment blood pressure. Good too.

[0184] In some embodiments, step 605 modulates the stimulation pattern by at least a predetermined amount. This may include adjusting the stimulation pattern to be configured to cause an immediate reduction in blood pressure. For example, in some embodiments, step 605 may adjust the stimulation pattern to: It is designed to cause a reduction in blood pressure by at least the specified amount within approximately 3 seconds of application of electrical current to the heart. In some embodiments, step 605 may include adjusting the stimulation pattern to a stimulation pattern configured to cause a reduction in blood pressure by at least a predetermined amount within at least five beats of the applied current. In some embodiments, step 605 may include adjusting the stimulation pattern to a stimulation pattern configured to cause a reduction in blood pressure by at least a predetermined amount within at least five beats of the applied current. The reduction in blood pressure resulting from the selected stimulation pattern may occur within 1 to 3 seconds of application of the current to the heart, or within 1, 3, or 5 heartbeats of application of the current to the heart.

[0185] In some embodiments, the stimulation pattern set during step 605 results in The resulting reduction in blood pressure may be such that the patient's average blood pressure at rest is at least 8 mmHg lower than the patient's initial blood pressure at rest. In some embodiments, the reduction in blood pressure resulting from the stimulation pattern established during step 605 is maintained for at least one minute. In some embodiments, the results of the stimulation pattern set during step 605 The resulting reduction in blood pressure may be maintained for at least 5 minutes. In this case, the blood pressure may reach a minimum blood pressure value within less than five heartbeats from the start of stimulation. For example, step 605 may combine a first stimulation pattern with a second stimulation pattern configured to cause a reduction in blood pressure. In some embodiments, step 605 may include adjusting the first stimulation pattern to a second stimulation pattern configured to cause a reduction in blood pressure for a predetermined time interval. For example, The interval may comprise at least 1 minute or at least 5 minutes.

[0186] In some embodiments, the second stimulation pattern is greater than a predetermined degree for a predetermined interval. The blood pressure monitor may be configured to maintain the blood pressure so that it does not exceed a predetermined average value. For example, the predetermined amount may be a difference of about 20 mmHg or less. In some embodiments, the predetermined amount may be a difference of about 1 mmHg to about 8 mmHg.

[0187] In some embodiments, the second stimulation pattern may include second stimulation settings configured to reduce or prevent atrial kicks in at least one ventricle, and the second stimulation settings may be based on at least one blood pressure variability parameter calculated from input data sensed during application of the first stimulation pattern.

[0188] In some embodiments, the second stimulation pattern comprises a stimulation pattern for reducing blood pressure spikes during the stimulation pattern. In some embodiments, the second stimulation pattern may be configured to reduce or limit the magnitude of the blood pressure spike between stimulation pulses to a percentage of the basal blood pressure value. For example, the second stimulation pattern may be configured to prevent blood pressure from increasing by more than about 80% between pulses. That is, the second stimulation pattern may be configured to prevent blood pressure from spiking by more than about 80% between pulses. In the second stimulation pattern, the blood pressure is prevented from increasing by more than about 40% between pulses. In some embodiments, the second stimulation pattern may be configured to The device may be configured to prevent a sudden rise in blood pressure of more than about 10 mmHg to about 30 mmHg during this period. For example, in some embodiments, the second stimulation pattern may provide a pulse pressure of greater than about 20 mmHg between pulses. The device may be configured to prevent a sudden rise in blood pressure.

[0189] In some embodiments, the second stimulation pattern may comprise multiple stimulation pulses. At least one stimulation pulse of the plurality of stimulation pulses may have a first stimulation setting configured to reduce atrial kick in at least one ventricle. At least one stimulation pulse is delivered, limiting the increase in blood pressure between stimulation pulses to a predetermined value. a second stimulus configured to reduce a baroreflex response to the reduction in atrial kick so that the In some embodiments, the second stimulation pattern may be configured to increase blood pressure for approximately 1 to 5 heartbeats to elicit a baroreflex response. In some embodiments, the second stimulation pattern may include a plurality of stimulation pulses having the first stimulation setting and a plurality of stimulation pulses having the second stimulation setting. In an embodiment, between about 1% of the plurality of stimulation pulses and about 40% of the plurality of stimulation pulses of the stimulation pattern. In some embodiments, the second stimulation pattern may include a plurality of stimulation pulses having the first stimulation setting and a plurality of stimulation pulses having the second stimulation setting. In such embodiments, between about 1% of the plurality of stimulation pulses and about 40% of the plurality of stimulation pulses of the stimulation pattern may have the second stimulation setting.

[0190] In some embodiments, the stimulation pattern includes timing of responses to increases and decreases in blood pressure. The stimulation pulses may include a ratio of stimulation pulses having the first stimulation setting to stimulation pulses having the second stimulation setting based on a ratio of the number of stimulation pulses having the first stimulation setting to stimulation pulses having the second stimulation setting. The ratio of stimulation pulses having the first stimulation setting is In some embodiments, the second stimulation pattern may be based on a ratio of the time constants of the resulting blood pressure change. In some embodiments, the first stimulation setting may include a first AV delay and the second stimulation setting may include a second AV delay, the first AV delay being shorter than the second AV delay. In some embodiments, the second stimulation pattern may include a plurality of stimulation pulses with the first stimulation setting and a plurality of stimulation pulses with the second stimulation setting. In some embodiments, the stimulation may include one or more stimulation pulses having a stimulation setting. The second stimulation pattern comprises about 2 to about 5 stimulation pulses having a second setting, and a first setting. The stimulation pulses may include a ratio of about 8 to about 13 pulses with a constant frequency. In the second stimulation pattern, a stimulation pattern is configured to elicit a hormonal response from the patient's body. In some embodiments, the stimulation pulse may include at least one stimulation pulse having a high stimulation setting. The first stimulation pattern was configured to not elicit a hormonal response from the patient's body. The stimulation setting may include at least one stimulation pulse. In a given sequence of stimulation patterns, a second stimulation pattern may be applied before a first stimulation pattern.

[0191] In some embodiments, method 600 may include alternating between two or more stimulation patterns. For example, method 600 may include alternating between two to ten stimulation patterns.

[0192] In some embodiments, the blood pressure sensor and controller may be configured to operate at least partially as a closed loop.

[0193] In some embodiments, the method 600 applies multiple stimulation patterns and, during stimulation, The device may include a controller configured to receive, for each of the stimulation patterns, corresponding input data related to the patient's blood pressure. at least one stimulation setting configured to reduce or prevent atrial kicks in the chamber; The stimulation pattern may include at least two stimulation patterns each comprising a stimulation pulse. The two stimulation patterns may differ from each other by the number or length of time that at least one stimulation pulse is delivered in succession. In some embodiments, the stimulation settings may differ from each other by the number or length of time that a given AV delay occurs consecutively. In some embodiments, the stimulation settings may be the same for at least two stimulations. Each of the stimulation patterns may include the same AV delay. In some embodiments, the at least two stimulation patterns may differ from one another by one or more stimulation settings included within each of the at least two stimulation patterns.

[0194] In some embodiments, the method 600 includes, for each of a plurality of stimulation patterns, and a controller for calculating at least one blood pressure variability parameter associated with the data. The method 600 may include a controller that adjusts the stimulation pattern according to the blood pressure variability parameter. In some embodiments, the method 600 may include selecting the patient with the best blood pressure variability parameters. The stimulation pattern may include a controller that adjusts the stimulation pattern to result in a stimulation pattern. For example, the best blood pressure variability parameter may include a blood pressure variability parameter that indicates a lowest degree of baroreflex. The best blood pressure variability parameter may include a blood pressure variability parameter that indicates a baroreflex within a predetermined range.

[0195] In some embodiments, the second stimulation pattern elicits a hormonal response from the patient's body. The stimulation setting may include at least one stimulation pulse having a stimulation setting configured to stimulate the In some embodiments, the first stimulation pattern elicits a hormonal response from the patient's body. The stimulation device may include at least one stimulation pulse having a stimulation setting configured to prevent the stimulation device from vibrating. stomach.

[0196] In some embodiments, the plurality of stimulation patterns may include a first stimulation pattern and a second stimulation pattern administered after the first stimulation pattern, the second stimulation pattern being determined by an algorithm using blood pressure variability parameters associated with input data for the first stimulation setting. The device may have at least one stimulation setting set based on the stimulation setting.

[0197] <System for reducing blood pressure> FIG. 9 schematically illustrates a system 700 for reducing blood pressure, according to some embodiments. System 700 may be a single device or may include multiple devices, preferably associated by wired or wireless communication. The device may have multiple components disposed within a housing and / or connected to the housing electrically and / or by wires. As shown in FIG. 9, a heart 701 is connected to system 700 by one or more stimulation electrodes 702. The stimulation electrodes may be configured to stimulate at least one chamber of the patient's heart with stimulation pulses.

[0198] In some embodiments, each of the multiple electrodes 702 is positioned in a different chamber of the heart. For example, one electrode may be placed in the atrium and another in the ventricle. In some embodiments, multiple electrodes 702 may be arranged in a single chamber. For example, two electrodes may be placed in the atrium and / or two electrodes may be placed in the ventricle. In some embodiments, one electrode may be placed in the first chamber and multiple electrodes may be placed in the second chamber.

[0199] In this embodiment, the electrodes 702 may include common cardiac pacemaker leads, such as Medtronic Capsure® pacing leads. The pacing lead is used to connect the pacing device to the system 700. The pacing lead consists of an industry standard IS-1 B1 connector (reference standard ISO 5148-3:2013) on one end and an electrode on the other end with insulation between them. In some embodiments, the IS-1 B1 connector may be configured with a conductor system. The inverter uses stainless steel for the two electrode contacts and silicon as the insulating material. Some embodiments may use polyurethane as the insulating material.

[0200] Stimulation of one or more cardiac chambers may be achieved by placing a voltage between two electrodes of the atrial or ventricular cardiac pacing lead described above. The stimulation circuit uses a network of transistors (e.g., MOSFETs) to change a capacitor to a specific programmable voltage, such as 2.0 V, and then to change the voltage across the electrodes for a programmable time of fixed duration, such as 0.5 ms. The same network may also manage the discharge of residual charge that may accumulate in the electrodes after stimulation is completed. The type of stimulation applied, such as unipolar (between one electrode and the stimulator housing) or unipolar (between one electrode and the stimulator housing) The type of

[0201] As is known in the art, one or more electrodes may be placed in contact with one or both ventricles and / or one or both atria. Such electrodes are used to sense and / or deliver stimuli to the respective heart chambers. For example, one electrode may be implanted in the right ventricle and an additional electrode may be implanted in the left ventricle through the coronary sinus. and wherein the system 700 includes means for generating biventricular stimulation of both ventricles to reduce dyssynchrony caused by ventricular stimulation. Pacing electrodes can be introduced into both ventricles.

[0202] System 700 includes a controller 703. System 700 may be an electrical stimulator that includes a power source 704 (e.g., a battery as known in the art of electrical stimulators). and / or the electrodes 702 may draw power from a power source 704 .

[0203] Preferably, the electrical stimulator of system 700 is housed in a sealed housing and header. The housing may be made of titanium or other biocompatible material and may contain a power source 704, electronics, and a telemetry coil or communication module 707 for communication with external devices. The power source 704 may be implantable. The battery chemistry may be a graded sealed primary battery. The battery may be lithium-iodine. Other embodiments may use larger or smaller batteries. Other embodiments may use rechargeable batteries, such as Li-ion rechargeable batteries. The electronics of some embodiments may use standard off-the-shelf electronics (e.g., transistors and diodes) and / or custom-made electronics. It may be configured as a child device (for example, an ASIC).

[0204] To detect the onset of atrial and / or ventricular activation, one or more sensing electrodes may be implanted at or near a location of interest within the heart. These sensing electrodes may be the same electrodes used to deliver pulses to the heart or may be dedicated sensing electrodes. The electrical activity may be bandpass filtered to remove unwanted noise with a programmable cutoff frequency, and may comply with the international standard for cardiac pacemakers (reference EN45502-2-1:2003). Electrical circuitry may be used to amplify the electrical signal generated by the propagating activation of the cardiac chambers and to determine the onset of activation when the electrical signal meets certain criteria, such as crossing a predetermined threshold. The signal may be amplified, for example, by a programmable gain and then adjusted to a level below 0.2 mV (cardiac activation level). for threshold detection, with programmable detection thresholds in steps of 0.4 mV (atria) and 0.4 mV (ventricles) These means of detecting excitation may introduce a delay between the actual onset of activation in the chamber and its detection. This is because the detection electrode may be far from the origin of excitation, and the time it takes for the signal to meet the detection criteria may be significant, in the range of 5-50 ms, or even longer. In such cases, the timing of the onset of activation may be estimated based on the timing of sensed activation, and the delivery of the stimulation pulse may be timed to compensate for this delay.

[0205] Preferably, the controller 703 is linked to an accelerometer to measure the patient's activity level. This patient activity level is used to determine the degree of pacing and / or Alternatively, BPR settings and / or stimulation patterns may be adjusted. Activity level may also be used to control the desired level's effect on blood pressure. For example, blood pressure reduction may be reduced at high activity levels to allow for better performance when increased blood pressure is needed. Preferably, blood pressure may naturally decrease when the patient is inactive (e.g., sleeping), in which case pacing may be adjusted to avoid reducing blood pressure below a desired threshold. Activity level may also be used to adjust settings based on baroreflex, if needed, to allow for better response. The sensor may be, for example, a piezoelectric sensor. In other embodiments, a MEMS-based accelerometer sensor may be used. In other embodiments, a fine ventilation sensor may be used, preferably in combination with an accelerometer.

[0206] The controller 703 may be configured to deliver electrical current to the heart 701 via one or more electrodes 702. The controller 703 may also be configured to administer a stimulation pattern of stimulation pulses according to embodiments of the present disclosure. In some embodiments, the stimulation pulses may be delivered to at least a ventricle of the heart.

[0207] In some embodiments, the stimulation pattern may include a first stimulation setting and a second stimulation setting different from the first stimulation setting, the first stimulation setting and the second stimulation setting being associated with an atrial rhythm. In some embodiments, the first stimulation setting is configured to reduce or prevent blockage. The first stimulation setting has a different AV delay than the second stimulation setting. In some embodiments, the first stimulation setting and / or the second stimulation setting may be configured to provide a maximum atrial dilation that is approximately equal to or less than a maximum atrial dilation of the same heart without stimulation. In some embodiments, the first stimulation setting and / or the second stimulation setting may provide a maximum atrial dilation that is approximately equal to or less than a maximum atrial dilation of the same heart without stimulation. In some embodiments, the first stimulation setting and / or the second stimulation setting are configured to stimulate the atrium to a maximum force when the atrium is open, such that the mechanics of the at least one atrial contraction are different from the mechanics of a preceding natural atrial contraction. In some embodiments, the first stimulation setting and the the first and / or second stimulation setting is configured to reduce the force of at least one atrial contraction. In some embodiments, the first stimulation setting and / or the second stimulation setting include at least The valve is configured to prevent even one atrial contraction.

[0208] In some embodiments, the controller 703 is configured to deliver a variety of different AV delays. The controller 703 may be configured to determine whether an atrial contraction or excitation occurs (as described herein). The controller 703 may be configured to sense when an atrial activation or contraction occurs and then deliver a ventricular stimulus at a fixed interval thereafter or before a future anticipated atrial activation or contraction. This interval may be programmable. The controller 703 may also stimulate the atrium and then deliver a ventricular stimulus, also programmed. The programmable interval may be configured to deliver at fixed intervals thereafter, which may be programmable. The programmable interval may be, for example, a time interval to accommodate the desired therapeutic effect. , or may even be varied between 2ms and 50ms to give a negative AV delay of up to -50ms.

[0209] In some embodiments, the controller 703 is configured to repeat the stimulation pattern multiple times. For example, the controller 703 may repeat the stimulation pattern twice. In another embodiment, the controller 703 is configured to repeat the stimulation pattern at least twice during a one hour period. The stimulation pattern repeated by the controller 703 may be any kind of stimulation pattern. For example, the stimulation pattern may include at least one ventricular stimulation and an atrial stimulation. In another embodiment, the stimulation patterns may include stimulation settings configured to reduce or prevent atrial kicks in at least one ventricle. The stimulation configuration may include two different stimulation settings configured in the stimulation unit, which may differ by one or more parameters, for example, by AV delay.

[0210] In some embodiments, the controller 703 may be configured to administer one or more consecutive stimulation patterns for a predetermined time interval. For example, in some embodiments, the time interval may be 10 minutes or more. In other embodiments, the time interval may be 30 minutes or more, 1 hour or more, or 24 hours or more. In some embodiments, the time interval may be a period of time greater than or equal to one month, such as one month to one year. In some embodiments, the time interval may be one year or longer.

[0211] In some embodiments, the one or more successive stimulation patterns are, for a portion of the time interval: The stimulation pattern may include a first stimulation setting configured to reduce or prevent atrial kicks in at least one ventricle, for example, the one or more consecutive stimulation patterns may be configured to reduce or prevent atrial kicks in at least one ventricle, for example, about 50% to 100% of the time interval. In another embodiment, the one or more successive stimulation patterns may include a first stimulation setting configured to reduce or prevent atrial kicks in at least one ventricle for between about 50% of the time interval and about 85% of the time interval. Some stimulation settings may include a first stimulation setting configured to reduce or prevent pain. In embodiments, the one or more consecutive stimulation patterns may include a second stimulation setting having a longer AV delay than the first stimulation setting for at least one beat during the time interval.

[0212] In another embodiment, the one or more sequential stimulation patterns include a second stimulation setting and / or The stimulation setting may include a third stimulation setting. The second stimulation setting and / or the third stimulation setting may each be different from the first stimulation setting. In some embodiments, the second stimulation setting and / or the third stimulation setting each reduce or prevent atrial kick in at least one ventricle. In some embodiments, the second stimulation setting and / or the third stimulation setting may each be configured not to reduce or prevent atrial kicks in at least one ventricle. In some embodiments, the second stimulation setting and / or the third stimulation setting may each be configured not to reduce or prevent atrial kicks in at least one ventricle. The stimulation settings may include from about 0% of the time interval to about 50% of the time interval. In embodiments, the second stimulation setting and / or the third stimulation setting may comprise between about 0% of the time interval and about 30% of the time interval. In some embodiments, the second stimulation setting and / or the third stimulation setting may comprise between about 0% of the time interval and about 20% of the time interval. In some embodiments, the second stimulation setting and / or the third stimulation setting may comprise between about 5% of the time interval and about 20% of the time interval.

[0213] In some embodiments, the controller 703 controls the sequence of 10 to 60 stimulation pulses having a first stimulation setting configured to reduce or prevent atrial kick in at least one ventricle. The stimulation device may be configured to deliver one or more sequential stimulation patterns, including: In embodiments, the controller 703 may be configured to administer one or more sequential stimulation patterns including a sequence of 1 to 10 beats embedded within 10 to 60 stimulation pulses, and the sequence of 1 to 10 beats may have a longer AV delay than the first stimulation setting. For example, the 10 to 60 stimulation pulses may include five stimulation pulses with a first stimulation setting, followed by one beat with an AV delay longer than the first stimulation setting, followed by one beat with an AV delay longer than the first stimulation setting. The sequence of 1 to 10 beats may include 50 stimulation pulses having a minimum of 10 beats. The sequence of 1 to 10 beats may include at least one stimulation pulse having a first stimulation setting configured to reduce or prevent an atrial kick in at least one ventricle. The sequence of 1 to 10 beats may include a natural AV delay. The sequence of 1 to 10 beats may include a natural AV delay that occurs without stimulation. That's fine.

[0214] The system 700 may further include one or more sensors 705. Some embodiments In some embodiments, such a sensor 705 may include one or more sensing electrodes for sensing electrical activity of the heart. In some embodiments, the one or more sensing electrodes may include one or more stimulating electrodes 702. In some embodiments, the sensor 705 may include one or more sensors (e.g., implanted electrodes). In some embodiments, the sensor may include one or more sensors. The sensor 705 includes one or more pressure sensors implanted in the heart (e.g., in the atria and / or ventricles). In some embodiments, the sensor 705 may include one or more blood flow sensors (implanted or external). For example, the one or more sensors 705 may include ultrasound sensing of blood flow through the AV valve. In some embodiments, the sensor 705 may include one or more sensors (implanted or external) for sensing blood flow through the AV valve. The device may include one or more sensors configured to monitor the timing of the closure of the valve. One or more of these sensors are configured to operate in a closed loop with a controller. Good too.

[0215] Information from the sensors 705 may be provided to the controller 703 by some form of communication, including wired and / or wireless communication. Preferably, the system 700 may include one or more communication modules 707 for receiving and / or transmitting information between system components and / or to devices external to the system. In some embodiments, the controller 703 may be configured to receive input data related to the patient's blood pressure. For example, input data relating to a patient's blood pressure may represent BP measured at one or more time points. or BP variability (e.g., degree of change and / or rate of change or time course) data showing the function of the change in BP, and / or the BP or BP fluctuation, maximum and / or statistical data relating to the minimum BP value.

[0216] Preferably, the system 700 may include one or more user interfaces 708 for providing information and / or allowing input of information. Providing information may include, for example, displaying operational information related to the system and / or displaying information related to the system during operation. even if it includes a display of data recorded by and / or received by the system. This may be based on the sensed parameters and / or the sensed parameters and the operating Information (stimulation pattern settings and / or correlation between a given pace and sensed information) The relationship may include relationships between the time and the time (e.g., relative timing).

[0217] Preferably, the user interface 708 is a user interface for running software applications. A commercially available laptop computer (e.g., a Windows®-based computer) The software application may be connected to a handheld wand that contains a telemetry circuit for communication with the implantable stimulator. The wand may also function to generate commands that are transmitted to the associated interface. The commands sent to the wand may be used to set stimulation parameters and / or to generate diagnostic messages for the device. The wand may be used to retrieve diagnostics, device data, cardiac data, and real-time cardiac sensing. The interface also allows for connection of a 3-lead ECG, and this data is displayed on a laptop computer screen by a software application. In other embodiments, 3-lead ECG electronics may not be included, or 12-lead ECG electronics may be included. In other embodiments, the wand, interface, and and laptop computer functionality with specialized hardware that performs all three functions. In other embodiments, printing capabilities may also be added to the user interface 708.

[0218] In some embodiments, the interface 708 allows a user (e.g., a physician) to Preferably, the interface 708 allows a user to provide a set of control instructions (e.g., target values ​​and / or ranges, and / or other limits or instructions) for the system. Preferably, the interface 708 allows a user to receive data from one or more sensors 705 (e.g., manual blood pressure measurements) and / or other parameters. The device may allow the user to input the results of the ultrasound monitoring and / or the results of the ultrasound monitoring.

[0219] Preferably, one or more user interfaces 708 allow the user to select a stimulation pattern (e.g., from a set of stimulation patterns stored in the system 700) or to select a stimulation pattern. It may be possible to impose constraints on the setting and / or selection of patterns.

[0220] Preferably, the system 700 may include one or more processors 706. is based on sensed parameters from the sensor 705 and / or input from the interface 708. configured to process the force data to select a stimulation pattern for delivery by the system 700. Preferably, the processor 706 is configured to analyze the sensed parameters by: and may be configured to extract information and / or formula constants to be used in selecting and / or evaluating stimulation patterns.

[0221] One or more components of system 700, or portions of such components, may be implanted in a patient, while some components of system 700, or portions of such components, may be external to the patient. When some components (or portions thereof) are implanted and others are not, communication between the components may be by wired and / or wireless means known in the art. For example, some of both the controller 703 and / or the processor 706 may Some or all of the functions may be performed outside the body. By placing it outside the patient's body, the size and / or energy requirements of the implanted device can be reduced. This may help reduce and / or improve the computational power of the system.

[0222] The system 700 may provide additional functions related to cardiac function and the overall performance of the cardiovascular system. For example, system 700 may include one or more algorithms and / or electrodes that enable biventricular pacing or cardiac resynchronization therapy to reduce asynchrony that may be caused by ventricular stimulation. In some embodiments, system 700 may include one or more algorithms to offset possible reductions in cardiac output. Such algorithms may vary the heart rate to increase cardiac output or implement other methods known in the art for controlling cardiac output. In some embodiments ... Rate response algorithms affect changes in heart rate in response to conditions. For example, system 700 may include a rate response algorithm that affects changes in heart rate in response to changes in levels of exercise, ventilatory activity, and / or oxygen consumption.

[0223] In some embodiments, the system 700 may include a sensor that detects activity. In some embodiments, the system 700 may include a real-time clock (time Such a clock may be used to control the timing of stimulation. For example, system 700 may be configured to turn stimulation on and off depending on the time of day. Such algorithms may be used to prevent hypotension during the night while the patient is asleep.

[0224] In some embodiments, a kit may be provided that includes one or more components of the system 700 and a set of instructions for adjusting stimulation patterns based on inputs related to the patient's blood pressure.

[0225] In some embodiments, a system for reducing blood pressure may be provided that is configured to deliver stimulation at a rate higher than the natural heart rate based on a detected natural heart rate or natural activation. For example, the system may be configured to detect natural activation during delivery of the stimulation pulses, and if natural activity is detected, the system may be configured to inhibit delivery of the stimulation pulses to the chamber. If the amount of detected activation exceeds a threshold within a given time frame, the natural heart rate may be deemed higher than the transmission rate of the stimulation pulses, and the transmission rate may be increased, for example, to accommodate the patient's increased heart rate. On the other hand, if the amount of detected activation is lower than a threshold (which may be zero) within a given time frame, the natural heart rate may be deemed lower than the transmission rate of the stimulation pulses, and the transmission rate may be reduced, for example, to avoid excessive activation of the patient's heart.

[0226] To achieve this effect, according to one embodiment, a system for lowering blood pressure includes a sensor for detecting the activation rate of at least one of the atria and ventricles of a patient's heart; The cardiac device may include a stimulation circuit configured to deliver stimulation pulses to the atria and ventricles, and a processor circuit coupled to the stimulation circuit. The processor circuit may be configured to detect the patient's heart rate based on sensing and to operate in a mode of operation in which stimulation pulses are delivered to each of at least one of the atria and ventricles. The stimulation pulses may be delivered at a rate higher than the sensed activation rate and may be configured to stimulate the ventricles at a time between about 50 ms before and about 70 ms after stimulation of the atria.

[0227] In some embodiments, a system for reducing blood pressure based on a predicted upcoming atrial contraction may be provided, for example, the system for reducing blood pressure may include a sensor for sensing the activation rate of at least one of the atria and the ventricles, and a sensor for sensing the activation rate of at least one of the atria and the ventricles. The system may include a stimulation circuit configured to deliver stimulation pulses and a processor circuit coupled to the stimulation circuit, the processor circuit configured to predict timing of a next atrial activation based on a detected activation rate of a preceding atrial activation, and to trigger at least one ventricle to activate the predicted next atrial activation. The device may be configured to operate in a mode of operation where the device stimulates at a time between about 50 ms before and about 10 ms after an atrial activation. The predicted timing may be the time between two preceding sensed atrial activations. The atrial activation time may be based on the time interval between the atrial activations and a function that is based on the previously sensed time interval between the atrial activations, the change in the time interval, the rate of change of the time interval, and / or This may include detecting periodic variations in the time interval (eg, periodic variations due to breathing).

[0228] Preferably, the sensor for sensing atrium and / or ventricle activation rate may include an electrode for sensing atrial activation.

[0229] In a further aspect, prediction of the next atrial activation may be based on functions of the preceding sensed activation, including the interval and rate of change of the cyclic variation.

[0230] In a further aspect, the timing of the predicted next atrial activation may be adjusted to reflect the delay between atrial activation and sensed atrial activation.

[0231] In a further aspect, the system may further comprise an additional sensor for sensing a parameter related to cardiac activity and for adjusting the time at which the ventricle is stimulated accordingly. The parameter may be one of the group consisting of blood pressure, blood flow, the state of the AV valve, and data related to wall motion of the heart or a portion thereof. The additional sensor may be a pressure sensor. , an impedance sensor, an ultrasonic sensor, and / or one or more sound sensors, and / or or one or more blood flow sensors. It may be possible to include it.

[0232] <Reduced atrial kick> Some embodiments stem from the inventors' realization that blood pressure can be reduced by causing closure of at least one AV valve during at least a portion of atrial activation. This reduces or even prevents the contribution of atrial contraction to ventricular filling, resulting in reduced cardiac filling at the end of occlusion and therefore reduced blood pressure.

[0233] In some embodiments, at least a portion of the atrial contractions may occur against a closed AV valve. For example, in some embodiments, 40% or more of the atrial contractions may occur against a closed AV valve. In some embodiments, 80% or more of the atrial contractions may occur against a closed AV valve. For example, the contractions may begin within about 20 ms before the ventricular contraction, and atrial activation may occur within 20 ms before the ventricular contraction. In some embodiments, 100% of the atrial contractions may occur against a closed AV valve, in which case ventricular activation occurs at a time when the ventricular contraction is complete. The stimulation is timed to begin before the onset of atrial contraction. This may include ventricular activation before the onset of atrial activation. The higher the percentage of atrial activation that occurs with the AV valve closed, the greater the reduction in atrial kick. Stimulation of both the atrium and the ventricle may provide better control of the percentage of atrial contraction that occurs with the valve closed.

[0234] Various embodiments may be implemented to cause at least a portion of the atrial contraction to occur with the valve closed. For example, the AV valve may close within 70 ms after the onset of the atrial mechanical contraction, or within 40 ms after the onset of the atrial mechanical contraction, or within 5 or 6 ms after the onset of the atrial mechanical contraction. In some embodiments, the AV valve may be closed even within 10 ms. In some embodiments, the AV valve may be closed before the onset of mechanical contraction of the atria. For example, the AV valve may be closed within 5 ms before the onset of mechanical contraction of the atria. In some embodiments, the AV valve may be closed simultaneously with the onset of a mechanical contraction. In some embodiments, the AV valve may be closed after the onset of an atrium's mechanical contraction. For example, the AV valve may be closed within 5 ms after the onset of an atrium's mechanical contraction. Good too.

[0235] In some embodiments, the onset of contraction of the chamber may be detected, and the stimulation pulse may be timed relative to the detected onset of contraction. The onset of contraction in the chamber is the start of active generation of contractile force in the chamber. The onset of contraction can be detected by a sudden change in pressure that is not related to blood flow into the chamber. The onset of contraction may also be detected by measuring wall movement of the cardiac chamber using ultrasound, or by measuring a reduction in the volume of the chamber. These methods of detecting the onset of contraction may have a delay between the actual onset of contraction and the detection of the onset of contraction.

[0236] In some embodiments, the AV valve is closed after the onset of at least one atrial contraction. For example, the AV valve may be closed from about 0 ms to about 70 ms after the onset of contraction of at least one atrium. In some embodiments, the AV valve may be closed from about 0 ms to about 40 ms after the onset of contraction of at least one atrium. In some embodiments, the AV valve may be closed from about 0 ms to about 40 ms after the onset of contraction of at least one atrium. In some embodiments, the AV valve may be closed from about 0 ms to about 10 ms after the onset of contraction. The valve may be closed about 0 ms to about 5 ms after the onset of contraction of at least one atrium.

[0237] Typically, atrial contraction may begin about 40 ms to about 100 ms after the onset of atrial excitation. In some embodiments, the AV valve may be closed after the onset of atrial activation. For example, the AV valve may be closed from about 40 ms to about 170 ms after the onset of atrial activation. In another embodiment, the valve may be closed about 40 ms to about 110 ms after the onset of atrial activation. For example, the AV valve may be closed for about 40 ms to about 75 ms after the onset of atrial activation. For example, the AV valve may be closed for about 40 ms to about 50 ms after the onset of atrial activation.

[0238] In some embodiments, the onset of excitation in the chamber may be detected, and the stimulation pulse may be timed to the detected onset of excitation. The onset of excitation is the onset of an action potential propagating through the chamber. The onset of excitation may be detected by sensing local electrical activity in the chamber using sensing electrodes connected to an amplifier. The onset of excitation may also be detected by electrocardiography.

[0239] In some embodiments, the method for detecting the onset of activation may include a delay between the actual onset of activation and the detection of the onset of activation. The timing of sensed atrial activation may be determined by taking into account the delay between the actual onset of activation and its detection. For example, if the detection delay is estimated to be 20-40 ms and the stimulation pulse is delivered 0-70 ms after the onset of atrial activation, If the system is to transmit a pulse between 40 ms before the next expected detection event and 30 ms after the next expected detection event, or 30 ms after the next expected detection event, Similarly, a stimulation pulse may be set to initiate atrial activation 0-50 ms before the onset of atrial activation. If a pulse is to be delivered to the chamber and the same 20-40 ms sensing delay is assumed, the system may be configured to deliver a pulse between 40 ms before the next expected sensing event and 90 ms before the next expected sensing event. The sensing delay may be due to one or more of the distance between the location of activation onset and the sensing electrode, the level of the electrical signal, the characteristics of the sensing circuitry, and the threshold set for the sensing event. The delay may be, for example, a duration related to the duration of signal propagation from the origin of excitation to the electrode location, a duration related to the frequency response of the sensing circuitry, and / or a duration related to the time at which the signal propagation energy is detectable by the sensing circuitry. The delay may be significant and may vary, for example, between about 5 ms and about 100 ms.

[0240] One method for estimating delay is the AV delay measured when both the atrium and ventricle are sensed. One approach is to use the time difference between the delay and the AV delay when the atrium is paced and the ventricle is sensed. Another approach may use a calculation of amplifier response time based on a set threshold, signal strength, and frequency content. Another approach may involve varying the delay used with atrial sensing until the effect on blood pressure is the same as that achieved by pacing both the atrium and ventricle with the desired AV delay.

[0241] In some embodiments, the AV valve is actuated to contract the at least one atrium prior to the onset of activation or contraction of the atrium. For example, the AV valve may be closed within about 0 ms to about 5 ms before the onset of activation or contraction of at least one atrium. In some embodiments, the AV valve may be closed simultaneously with the onset of activation or contraction of at least one atrium.

[0242] In some embodiments, direct mechanical control of AV valve closure may be achieved. In such embodiments, a mechanical device, or portion thereof, may be implanted in a patient and actuated to cause closure of the valve between the atrium and ventricle. For example, a prosthetic valve may be implanted in a patient's heart and actuated to mechanically close according to some embodiments. In such embodiments, instead of or in addition to delivering a stimulation pattern, such closure of the AV valve may be achieved by controlling the function of the implanted valve.

[0243] In some embodiments, a shortened, or even negative, time interval between the onset of atrial activation and the onset of ventricular activation is used to reduce cardiac filling and thereby reduce blood pressure. As used herein, a negative time interval between the onset of atrial activation and the onset of ventricular activation means that in a single cardiac cycle, the onset of activation for at least one ventricle occurs before the onset of atrial activation. In this case, atrial contraction may occur, at least in part, against a closed AV valve. This is because the pressure generated in the ventricle may be greater than the pressure in the atrium. A short time after the onset of ventricular contraction, the ventricular pressure may exceed the atrial pressure, leading to passive closure of the valve. This valve closure may reduce or even eliminate the atrial kick, which may then reduce ventricular filling. As a result, the force of ventricular contraction may be reduced, and blood pressure may drop.

[0244] The time between the onset of excitation in each cardiac chamber and the onset of mechanical contraction is not fixed. Therefore, the timing of excitation does not guarantee the same effect on the timing between contractions. However, in some embodiments, the timing between excitations is used as a frame of reference for practical reasons. The ultimate goal of controlling the timing of excitation is to control the timing of contractions.

[0245] In some embodiments, a shortened, or even negative, time interval between the onset of atrial activation and ventricular activation may be used to reduce cardiac filling and thereby reduce blood pressure, thereby obtaining better control over atrial contribution, since the onset of ventricular contraction results in valve closure.

[0246] In some embodiments, 40% or more of atrial contractions may occur during ventricular contractions. For example, atrial contractions may begin about 60 ms or less before ventricular contractions, or atrial activation may occur about 60 ms or less before ventricular activation. In some embodiments, 80% or more of atrial contractions may occur during ventricular contractions. For example, contractions may begin about 20 ms or less before ventricular contractions, or atrial activation may occur about 20 ms or less before ventricular activation. In some embodiments, 100% of atrial contractions may occur during ventricular contractions, in which case ventricular activation may occur about 100 ms or less before ventricular activation. The contraction is timed to begin before the onset of atrial contraction, which may include ventricular excitation before the onset of atrial activation.

[0247] In some embodiments, at least one ventricle contracts during or before the corresponding atrium contracts. A method is provided for causing contraction of at least one ventricle of a heart to contract. One method to achieve this goal is to measure the pulse width between approximately 50 ms before and 70 ms after the onset of corresponding atrial activation. In some embodiments, at least one The time interval between the onset of activation of a ventricle and the onset of activation of the corresponding atrium may be zero, i.e., the onset of activation for at least one ventricle is greater than or equal to the onset of activation of the corresponding atrium. In some embodiments, the onset of ventricular activation may occur between about 0 ms and about 50 ms before the onset of atrial activation. In some embodiments, the onset of ventricular activation may occur between about 0 ms and about 50 ms before the onset of atrial activation. occurs at least about 2 ms before and at least about 2 ms after the onset of excitation of at least one atrium In some embodiments, the onset of ventricular activation may be preceded by at least one atrial activation. In some embodiments, the onset of ventricular activation may occur at least about 10 ms before to at least about 10 ms after the onset of at least one atrial activation. In some embodiments, the onset of ventricular activation may occur at least about 40 ms before to at least about 40 ms after the onset of at least one atrial activation. stomach.

[0248] In some embodiments, the method includes delivering a stimulation pulse from a stimulation circuit to at least one of an atrium and a ventricle, stimulating the ventricle to induce atrial activation in at least one atrium. Ventricular excitation is initiated between approximately 0 ms and approximately 50 ms before the start of treatment, thereby increasing the ventricular filling volume to the level before treatment. and operating a processor circuit coupled to the stimulation circuit in an operating mode that reduces ventricular filling volume from a pre-treatment volume and reduces the patient's blood pressure from a pre-treatment blood pressure. In such embodiments, atrial activation may be sensed to determine the onset of atrial activation. The time interval between the onset of atrial activation and the moment atrial activation is sensed may be known and used to calculate the timing of the onset of atrial activation. For example, if atrial activation is sensed 20 ms after the onset of atrial activation and it is known that the ventricle will be stimulated 40 ms before the onset of atrial activation, the ventricle will be stimulated 60 ms before the expected sensing of atrial activation.

[0249] In another embodiment, the method includes stimulating the atrium to induce ventricular activation in at least one ventricle. Atrial excitation is initiated between approximately 0 ms and approximately 50 ms before the start of treatment, thereby reducing the ventricular filling volume before treatment. The method may include operating a processor circuit coupled to the stimulation circuit in an operating mode that reduces ventricular filling volume from a pre-treatment volume and reduces the patient's blood pressure from a pre-treatment blood pressure. For example, the processor circuit may be configured to operate in an operating mode in which one or more excitatory pulses are delivered to the atrium between about 0 ms and about 50 ms before the one or more excitatory pulses are delivered to the patient's ventricle. In such embodiments, pacing may be timed without relying on sensing atrial activation. Preferably, in such embodiments, pacing is timed to ensure that one or more excitatory pulses are delivered to the atria before spontaneous activation occurs. Activation is detected. Preferably, atrial activation is configured to commence between about 0 ms and about 50 ms after the onset of ventricular activation when the intrinsic atrial activation rate is lower than the intrinsic ventricular activation rate.

[0250] In some embodiments, the device may include a stimulation circuit configured to deliver stimulation pulses to at least one of an atrium and a ventricle. The device may include a processor circuit coupled to the stimulation circuit. In some embodiments, the processor circuit may be configured to operate in an operating mode that stimulates the ventricles to initiate ventricular activation between about 0 ms and about 50 ms before the onset of atrial activation in at least one atrium, thereby reducing ventricular filling volume from a pre-treatment ventricular filling volume and reducing the patient's blood pressure from a pre-treatment blood pressure. In such embodiments, atrial activation may be sensed to determine the onset of atrial activation. The time interval between the onset of atrial activation and the moment the atrial activation is sensed may be known and may be used to calculate the timing of the onset of atrial activation. For example, if atrial activation is sensed 20 ms after the onset of atrial activation and it is known or estimated that the ventricle shall be stimulated 40 ms before the onset of atrial activation, the ventricle will be stimulated 60 ms before the expected sensing of atrial activation.

[0251] In another embodiment, the processor circuitry is configured to stimulate the atrium and stimulate the at least one ventricle. Atrial excitation is initiated between approximately 0 ms and 50 ms after the onset of ventricular excitation, thereby controlling the ventricular filling volume. The processor circuit may be configured to operate in an operating mode that reduces the ventricular filling volume from a pre-treatment ventricular filling volume and reduces the patient's blood pressure from a pre-treatment blood pressure. The pacing device may be configured to operate in a mode of operation in which one or more excitatory pulses are delivered to the atrium between about 0 ms and about 50 ms after an excitatory pulse is delivered to the patient's ventricle. In such an embodiment, pacing may be timed without relying on sensing atrial activation. Preferably, in such an embodiment, one or more excitatory pulses are delivered to the atrium before natural activation occurs. Atrial activation is sensed to ensure that the pulse is delivered to the atrium. Preferably, atrial activation is set to begin between about 0 ms and about 50 ms after the onset of ventricular activation when the intrinsic atrial activation rate is lower than the intrinsic ventricular activation rate.

[0252] Figures 10A and 10B represent the heart of a healthy anesthetized dog, showing the electrocardiogram (ECG), left ventricular pressure (LVP), and arterial (blood) pressure (AP) tracked over time. In Figure 10A, prior to point 101, the heart was allowed to beat naturally, and the ECG, LVP, and AP were tracked. At point 101, ventricular pacing was initiated. The ventricles were paced 2 ms after the onset of atrial activation. This pacing caused an immediate change in the ECG, accompanied by a reduction in both LVP and AP. Pacing continued with a 2 ms time interval between the onset of atrial contraction and the onset of ventricular pacing, until point 103 in Figure 10B, where pacing ceased. As can be seen, As soon as pacing was stopped, the ECG, LVP, and BP all returned to essentially the same values ​​as before pacing.

[0253] 11A and 11B show the cardiac rhythm during a natural beat (FIG. 11A) and during the onset of atrial contraction and ventricular pacemaker (FIG. 11B). The figures show the heart of a hypertensive dog when paced with a 2 ms time interval between the onset of pacing and the onset of pacing (Fig. 11B). These figures show the cardiac ECG, right ventricular pressure (RVP), and RVP diastolic pressure, respectively. Major and right atrial pressure (RAP) tracings are shown.

[0254] In Figure 11A, the P wave and QRS of a natural heartbeat are clearly visible. By following the P wave as a result of atrial contraction, the increase in atrial pressure is visible. In the RVP tracing, by following the QRS complex against the ECG, A sudden increase in RVP is observed, which indicates ventricular contraction. When the right ventricle is pacing, this sudden increase in RVP is preceded by an earlier, smaller increase in RVP that occurs simultaneously with atrial contraction and a reduction in blood pressure and results from blood shifting from the atrium to the chambers. This is the atrial kick. In Figure 11B, the pacing is at a 2 ms time interval, the P wave is essentially unnoticeable on the ECG, and electrical stimulator artifacts are discernible. The atrial kick in this case is not discernible on the enlarged tracing of right ventricular pressure. This is because the atrial contraction occurs simultaneously with, or even shortly after, the onset of ventricular contraction.

[0255] In Figure 12, the hypertensive dog heart exhibited a 60 ms time interval between atrial and ventricular pacing (trace points 105 and 107) or between atrial and ventricular pacing (trace point 109). The pacemaker was paced at a time interval of 120 ms. Tracking included cardiac ECG, left ventricular pressure (LVP), right heart rate (HR), and ventricular pressure (VPR). Left ventricular pressure (RVP), RVP magnification, and right atrial pressure (RAP) are shown for tracking points 105 and 107. As can be seen in the correspondingly enlarged trace of the RVP, the pacing time interval of 60 ms The atrial kick is very slight, and the ventricular contraction begins shortly after the peak of the atrial contraction. In this case, the contribution of the atrial kick to ventricular filling is significantly reduced, but not completely eliminated, while the peak of the atrial contraction does not occur against a closed valve, and atrial dilation is not increased. During pacing with a time interval of 120 ms, the atrial kick is clearly visible (enlarged). Although the onset of ventricular contraction and closure of the AV valves occurs before the completion of atrial contraction, the contribution of the atrial kick to ventricular filling is slightly reduced.

[0256] In Figure 16, the heart of a hypertensive patient was paced with different AV delays. This example shows the results obtained by pacing both the atrium and the corresponding ventricle, as opposed to pacing only the ventricle based on an atrial sensed pulse. During the interval d-d', the atrium A pulse was sensed and the ventricular pulse was paced with a 2 ms AV delay. During interval e-e', both the atrium and ventricle were paced with a 2 ms AV delay. During interval f-f', both the atrium and ventricle were paced with a 40 ms AV delay. During interval g-g', both the atrium and ventricle were paced with a 20 ms AV delay. During the interval h-h', both the atrium and ventricle were paced with an AV delay of 80 ms. As shown in this example, comparing the interval d-d' with the interval e-e', it is clear that blood pressure is lower when the atrium is paced during the interval e-e' than when atrial activity is just sensed. As further illustrated in this example, comparing intervals e-e', f-f', g-g', and h-h', shorter AV delays caused a greater reduction in blood pressure than longer ones. For example, interval g-g' (20 ms AV delay) caused a greater reduction in blood pressure than interval e-e' (2 ms AV delay). As can be seen from the results of this example, the changes in blood pressure may be caused at least in part by different AV delays, which lead to different percentages of atrial contraction relative to the closed valve.

[0257] Embodiments of a Method for Reducing Atrial Kick Method 40 for reducing blood pressure is shown schematically in FIG. 13. Method 40 may be performed by device 50 of FIG. 14, described below. Thus, device 50 may be configured to perform any or all of the steps of method 40. Similarly, method 40 may include any step that device 50 is configured to perform. For example, method 40 may include any of the functions described above with respect to device 50. Method 40 may also include any step from method 600. Similarly, method 600 may include any step from method 40. Method 40 may include any step that system 700 is configured to perform. System 700 may be configured to perform any or all of the steps of method 40. It may also be used.

[0258] In some embodiments, method 40 may include step 41 of atrial contraction. In some embodiments, step 41 includes sensing atrial activation. For example, step 41 may include sensing intrinsic atrial activation. In some embodiments, method 40 includes inducing atrial activation. Method 40 may include step 42, in which a time interval is applied. Method 40 may include step 43, inducing AV valve closure. In some embodiments, step 43 may include inducing an excitatory current to at least one ventricle. This may be accomplished by applying a current to both atria and / or actuating a prosthetic valve between at least one atrium and the corresponding ventricle to close. In some embodiments, steps 41, 42, and 43 may be repeated, as indicated by the reverse arrow from step 43 back to step 41. In some embodiments, excitatory current may be applied to both ventricles simultaneously or sequentially. In some embodiments where both ventricles are paced sequentially, the initiation of activation of at least one atrium (e.g., the right atrium) and the initiation of activation of the paced atrium are synchronized. A time interval may be measured between the onset of activation of the corresponding ventricle (e.g., the right ventricle) that will trigger the activation of the corresponding ventricle (e.g., the right ventricle). In some embodiments, step 43 may occur before or simultaneously with step 41, where the time interval is set to zero or negative. In some embodiments, the time interval may be measured in milliseconds.

[0259] Preferably, atrial and ventricular contractions may be caused by controlling the contraction of both (e.g., by controlling the activation leading to the contraction). Preferably, the onset of atrial activation is sensed, and this sensing triggers valve closure at a predetermined timing interval. Preferably, both atria are paced. In some embodiments where both AV valves are closed sequentially (e.g., when both ventricles are paced sequentially), the timing interval is determined by the onset of activation of the first atrium to be paced, and the onset of valve closure. Preferably, the timing of activation of one or more chambers (e.g., activation onset) is measured from the onset of activation of at least one ventricle, e.g., from the onset of activation of one or more preceding cardiac chambers. One or more excitatory stimuli are estimated based on the timing in the cycle, and The mixture may be delivered to the same and / or different chambers at desired time intervals before and / or after mixing.

[0260] In some embodiments, method 40 may be repeated for each heartbeat. In some embodiments, method 40 may be performed intermittently. For example, the method may be applied every few heartbeats. Alternatively, method 40 may be applied for every few heartbeats, with one or more heartbeats remaining. For example, method 40 may be applied for 5 to 15 heartbeats. In some embodiments, the application / avoidance pattern may be more complex, preferably based on a predetermined algorithm. The algorithm may be based on a stimulation parameter. For example, the algorithm may adjust the parameters of the stimulation rather than simply stopping and starting the stimulation. Application of method 40 in some embodiments reduces ventricular filling between beats, thereby potentially reducing the ejection profile. As used herein, cardiac ejection profile refers to the total volume of blood pumped by the heart in a given period of time. In some embodiments, intermittent application of method 40 may be applied to counteract the reduction in cardiac ejection profile.

[0261] In some embodiments, the time interval applied in step 42 may be selected based on feedback. In such cases, method 40 may include selecting one or more of the cardiac chambers, Detecting feedback parameters from the part and / or the patient's body, step 44 For example, one or more of atrial kick, blood pressure (e.g., in arteries), and ventricular pressure and / or atrial pressure, directly or indirectly, to provide feedback information. In some embodiments, the feedback information may additionally or alternatively include the time for the atria to contract and the AV valves to close and / or the time for the ventricles to contract. For example, an ultrasound sensor may be used to sense cardiac activity, for example, by ultrasound imaging of cardiac activity or by generating an echocardiogram (ECHO).

[0262] In some embodiments, step 44 uses pulsed wave or continuous wave Doppler ultrasound to sense blood flow (e.g., flow velocity) and / or cardiac tissue motion at any point. Preferably, step 44 uses an ultrasound sensor to detect A waves, which correspond to contractions of the left atrium and blood flow to the left ventricle. It may also include the following.

[0263] The method may include step 45, adjusting the time interval from step 42 based on feedback information from step 44. For example, step 45 may include adjusting the time interval based on sensed blood pressure. As shown in FIG. 13 by the arrow pointing from step 45 to step 41, steps 41, 42, 43, and / or 44 may be repeated after performing step 45. Some embodiments Then, the time interval may be initially set to a first value during step 41, and then during step 44 Based on the feedback detection performed, the time interval may be decreased or increased during step 45 until the feedback value is within a given range (or above or below a given value). For example, until the systolic blood pressure is above 100 mmHg and / or below 140 mmHg and / or the diastolic blood pressure is below 90 mmHg and / or above 60 mmHg. The spacing may be adjusted.

[0264] In some embodiments, steps 44 and 45 may be performed for each application of step 43 (e.g., application of a ventricular pacing stimulus) during operation of method 40. In this case, alternatively or additionally, a device may be administered to the patient (e.g., a device) in accordance with one or more embodiments. Steps 44 and 45 may be performed when the cardiac pacing device is provided (e.g., by implantation of a cardiac pacing device). The adjusting steps may be repeated periodically (e.g., by a caregiver during testing) and / or intermittently (e.g., once per hour or every two or three applications of ventricular pacing stimuli). In some embodiments, the adjusting steps may be performed based on one or more sensed parameters. Step 45 may be performed when feedback information indicates that the meter has exceeded a preset range for more than a predetermined period of time.

[0265] The steps of method 40 may be performed in any order, for example, in the order indicated by the arrows shown in Figure 13. In another embodiment, step 42 may be performed before step 41.

[0266] Timing of atrial contraction, atrial activation, ventricular contraction, AV valve closure and / or opening, and / or the flow or lack thereof of blood from one or more atria to the respective ventricles, and / or blood pressure, may be detected using methods known in the art, and the feed In some embodiments, the onset of excitation may be determined by one or more It may be used as a trigger for delivery of an excitatory pulse to the ventricle. The sensed information may additionally or alternatively be used in adjusting the timing intervals of the device.

[0267] Preferably, the feedback parameters may allow for conditions requiring additional throughput from the heart to be accommodated, and these may be used to automatically stop causing valve closure at shortened time intervals instead of adjusting the timing interval. For example, the feedback parameters may lead to adjustments during exercise. In this example, a heart rate sensor may be used to provide feedback information regarding the patient's heart rate. If the heart rate is above a given threshold, the feedback may be used to stop the device. The device may, for example, stop when the heart rate is below a given threshold and / or for a predetermined period of time. After a certain time has passed, it may be reactivated based on sensed feedback information.

[0268] Device for reducing blood pressure Reference is now made to Figure 14, which shows a schematic representation of a device 50 according to one embodiment. The device 50 may be constructed essentially in a manner known in the art, with certain modifications as described herein, and may have components similar to a cardiac pacemaker. Preferably, the device is implantable. Preferably, the device is adapted to provide additional and / or additional cardiac support. includes components capable of providing alternative electrical therapy (e.g., defibrillation). Device 50 may be configured for implantation in a patient's body in a manner essentially known in the art for implantable pacemakers, preferably with certain modifications as described herein. Device 50 may include components of system 700, and system 700 may include components of device 50.

[0269] The device 50 comprises a biocompatible body 51, one or more controllers 52, a power source 53, and a telemetry unit. The body 51 may include a controller 56. The body 51 may comprise a housing for housing multiple components of the device. The controller 52 may be configured to control operation of the device. For example, the controller 52 may be configured to control delivery of stimulation pulses. In some embodiments, the power source 53 may include a battery. For example, the power source 53 may include a rechargeable battery. In some embodiments, the power source 53 may include an inductively rechargeable battery. In some embodiments, the telemetry unit 56 may be connected to one or more other The device may be configured to communicate with the unit and / or component, e.g., a telemeter. The unit 56 may be programmed by an external programmer and / or by data recorded in the device 50 during operation. The signal may be configured to communicate with a receiving unit for receiving the signal.

[0270] In some embodiments, device 50 may be configured to be attached to one or more electrodes and / or sensors. The electrodes and / or sensors may be integrated within device 50. whether or not it is attached to and / or connectable to In some embodiments, the electrodes are configured to pace at least one ventricle. Additionally or alternatively, the device preferably includes a ventricular electrode 561. The device 50 may be connected, by wire or wirelessly, to at least one implanted prosthetic valve 562. Additionally, the device 50 may include one or more atrial electrodes 57 for pacing one or more atria, and / or one or more atrial sensors 58 for detecting the onset of atrial activation, and / or other The system may include one or more sensors 59 for providing feedback parameters of the system.

[0271] In some embodiments, sensors 59 may comprise one or more pressure sensors, electrical sensors (e.g., ECG monitoring), flow sensors, heart rate sensors, activity sensors, and / or volume sensors. Sensors 59 may be mechanical and / or electronic sensors (e.g., For example, ultrasonic sensors, electrodes and / or RF transceivers. In some embodiments, the sensor 59 may communicate with the device 50 via telemetry.

[0272] In some embodiments, the ventricular electrode 561 and / or the atrial electrode 57 may be standard pacing electrodes. The ventricular electrode 561 may be positioned in a manner known in the art for ventricular pacing. For example, a ventricular electrode may be positioned relative to the heart. In some embodiments, the atrial electrode 57 may be located near In some embodiments, the atrial electrode 57 may be positioned in and / or near one or more of the atria. In some embodiments, the atrial electrode 57 may be positioned in one or more of the atria selected to provide early detection of atrial activation or depolarization. For example, in some embodiments, the atrium may be attached to one or more atria at different positions. The atrial electrode 57 may be attached to the right atrium near the location of the sinoatrial (SA) node.

[0273] One location of the ventricular electrode 561 is such that when the heart is paced, the pacing reduces or minimizes QRS prolongation in order to reduce or even minimize asynchrony. In some embodiments, this location is in the ventricular septum near the His bundle. The ventricular electrode 561 may additionally or alternatively be located on the epicardial or coronary It may be placed in a coronary vein, preferably to reduce asynchrony. More than one electrode can be placed in the ventricle to provide biventricular pacing.

[0274] The device 50 includes a pulse generator configured to deliver stimulation pulses to at least one cardiac chamber. The pulse generator or stimulation circuitry may include a pulse generator or stimulation circuitry. The pulse generator or stimulation circuitry may include some or all of the standard capabilities of a conventional pacemaker. Controller 52 may be configured to control the pulse generator or stimulation circuitry. Atrial sensor 58 (and preferably other electrode sensors configured to sense other cardiac chambers) may be connected to device 50 via specific circuitry that amplifies the electrical activity of the heart and allows sampling and detection of activation of specific chambers. Other circuitry may be configured to deliver stimuli to specific electrodes to pace the heart and generate propagating electrical activation.

[0275] In some embodiments, one or more additional sensors 59 are located in or on one or more of the atria and / or in or on one or more of the ventricles and / or preferably adjacent to the heart. For example, one or more sensors may be located on and / or in a vena cava, and / or on and / or in one or more arteries, and / or on and / or in one or more cardiac chambers. These sensors may measure pressure, or may measure other indicators such as impedance and / or flow.

[0276] In some embodiments, controller 52 may include or be a microprocessor powered by power supply 53. In some embodiments, device 50 may include a clock 54, for example generated by a crystal. Device 50 may include internal memory 55 and / or may be connected to external memory, for example The device may be connected to an external memory via a telemetry unit 56. In some embodiments, the telemetry unit 56 may be configured to allow communication with an external device, such as a programmer and / or one or more of the sensors 59. Any or all feedback information and / or a log of the device's operation may be stored in an internal memory 55. and / or may be stored in an external memory unit by the telemetry unit 56. The information may be relayed to the

[0277] In some embodiments, the controller 52 may be configured to perform at least one of the methods described herein. It may operate according to the embodiment.

[0278] In some embodiments, the device 50 senses one or more feedback parameters. , may include one or more sensors for controlling the application and / or magnitude of the AV delay.

[0279] Artificial valves Additionally or alternatively, device 50 may be configured to directly control the operation of at least one implanted prosthetic valve 562. Attention is now directed to FIG. 15, which schematically illustrates a prosthetic valve 60 according to an embodiment of the present invention. Valve 60 shown in this example is bileaflet, as is known per se in the art for prosthetic valves. While the following example relates to a bileaflet valve, embodiments may also be implemented with other prosthetic valves, such as, for example, caged ball valves and disc valves.

[0280] As shown in Figure 15, valve 60 may include a ring 61 for suturing the valve in place when implanted in a patient's heart. Valve 60 may include two semicircular leaflets 62 that rotate about struts 63 attached to ring 61. In this schematic depiction, another device component is shown schematically as body 64, which corresponds to body 51 shown in Figure 14. Body 64 may receive feedback information from a heart 65 in which valve 60 is implanted.

[0281] Valve 60 differs from conventional prosthetic valves in that its closure may be controlled directly by device 50. Valve 60 may be opened (e.g., by rotating struts 63 or by opening one or more leaflets 62). The valve may include a mechanism (e.g., a coil or hydraulic mechanism) configured to dynamically cause closure of the valve (by inflating a portion of the valve). , and may later be returned to a relaxed position to allow the valve to open and, if desired, to be repeatedly closed. Relaxation may occur at a predetermined time after closure. Additionally or alternatively, relaxation may be affected in response to a sensor (e.g., a pressure sensor) reading ventricular activity. Control of valve 60 may be wireless (using a telemetry unit associated with the valve) or by wired communication with components in body 64. In some embodiments, valve 60 may be configured to open and close independently of fluid pressure acting on the valve. For example, valve 60 may be a ball valve.

[0282] Effect of the embodiment on reducing blood pressure Generally, some of the disclosed method and system embodiments include at least one Unlike previous mechanical methods for reducing blood pressure, some of the embodiments described herein achieve this goal without increasing pressure within at least one corresponding atrium. Atrial natriuretic hormone or atrial The disclosed embodiment can mechanically control the reduction of blood pressure without increasing atrial pressure, which induces the secretion of atrial natriuretic peptide. This can prevent undesirable effects on heart rate and can reduce the possibility of canonical atrial waves. This can reduce the risk of

[0283] Some of the disclosed embodiments may increase atrial dilation while reducing atrial kick, causing the release of atrial natriuretic peptide. For example, disclosed embodiments may include stimulating the heart to contract its atria while closing a heart valve associated with the atrium so that the contraction causes the atrium to expand. Reducing atrial kick while simultaneously causing the release of atrial natriuretic peptide may have a synergistic effect on lowering blood pressure. In some embodiments, the amount of dilation of one or more atria may be controlled by controlling the timing of valve closure relative to atrial contraction.

[0284] Unlike previous pharmaceutical or mechanical methods for reducing blood pressure, some of the disclosed embodiments achieve the goal of immediately reducing blood pressure. For example, reduction in blood pressure may occur within 1-3 seconds or within 1, 3, or 5 heartbeats of application of electrical current, and blood pressure may decrease immediately after stimulation. The lowest blood pressure value may be reached within less than 5 seconds of the start of the test.

[0285] The above example combines mechanical therapy with neuronal feedback and the natural release of hormones that induce adaptation. The mechanical therapy and the natural release of hormones may be additive or even synergistic mechanisms. While hormone release affects the cardiovascular system, the mechanical therapy affects the heart itself. Intermittent mechanical therapy to reduce blood pressure may affect both the neuronal and hormonal feedback that controls the cardiovascular system, reducing adaptation.

[0286] The headings used herein are intended as an editorial aid only and do not define terms.

[0287] This application claims priority to U.S. Provisional Application No. 61 / 740,977, filed December 21, 2012, the entire contents of which are incorporated herein by reference.

[0288] The present disclosure is related to the following applications: US Pat. Nos. 5,629,292; 5,729,316; 5,729,326; 5,729,336; 5,729,346; 5,729,35 ...

[0289] While various embodiments of the present invention have been described, this description is intended to be illustrative rather than limiting, and many more embodiments and implementations will be apparent to those skilled in the art. Accordingly, the present invention is limited only in light of the appended claims and equivalents thereof. Various modifications and variations can be made within the scope of the appended claims. The spirit and scope of the present invention lie in the appended claims, but are also embodied in the following [preliminary claims], which existed as claims at the time of filing this application and have been partially amended to eliminate them, the contents of which [preliminary claims] are incorporated herein by reference.

[0290] [Preliminary Claims] [Preliminary Claim 32] 1. A method of reducing ventricular filling in a patient having a pre-treatment ventricular filling volume, comprising: delivering one or more stimulation patterns of stimulation pulses to at least one cardiac chamber for a time interval lasting 10 minutes or more; At least one of the stimulation pulses is at least 1 minute during at least 5 minutes of the time interval. a first stimulation setting configured to reduce or prevent atrial kicks in one ventricle, At least one of the stimulation pulses has a second stimulation setting different from the first stimulation setting. The way it is done.

[0291] [Preliminary Claim 33] 1. An apparatus for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: a stimulation circuit configured to deliver stimulation pulses to at least one of the atrium and the ventricle; a processor circuit coupled to the stimulation circuit, the processor circuit comprising: a first stimulation circuit for detecting a first stimulation signal in at least one atrium; The ventricles are stimulated so that ventricular excitation begins approximately 0 ms to 50 ms before the onset of atrial excitation. and a processor circuit configured to operate in an operating mode in which the ventricular filling volume is reduced from the pre-treatment ventricular filling volume and the patient's blood pressure is reduced from the pre-treatment blood pressure.

[0292] [Preliminary Claim 34] The mode of operation stimulates the ventricle to initiate contraction of the at least one atrium prior to the onset of contraction. 34. The apparatus of claim 33, further comprising contracting the ventricle. [Preliminary Claim 35] The mode of operation stimulates the ventricle to initiate contraction of the at least one atrium. contracting the ventricle prior to contraction of the at least one atrium, thereby 35. The apparatus of claim 34, further comprising causing the AV valve to be closed during a portion.

[0293] [Auxiliary Claim 36] The operating mode stimulates the ventricle to synchronize it with the contraction of the at least one atrium. contracting before said initiation, thereby causing at least one of said atria to contract. 36. The apparatus of any one of preliminary claims 33 to 35, including causing the AV valve to close during the period. [Preliminary Claim 37] The device of any one of preliminary claims 33 to 36, wherein the operating mode includes delivering one or more excitatory pulses to the at least one atrium approximately 0 ms to 50 ms after the one or more excitatory pulses are delivered to the ventricle.

[0294] [Preliminary Claim 38] 1. A method for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: delivering stimulation pulses from the stimulation circuit to at least one of the atrium and the ventricle; and operating a processor coupled to the stimulation circuit to operate in an operating mode that stimulates a ventricle such that ventricular activation begins about 0 ms to about 50 ms before onset of atrial activation in at least one atrium, thereby reducing the ventricular filling volume from the pre-treatment ventricular filling volume and reducing the patient's blood pressure from the pre-treatment blood pressure. [Preliminary Claim 39] The mode of operation stimulates the ventricle to initiate contraction of the at least one atrium prior to the onset of contraction. 39. The method of claim 38, further comprising: contracting the ventricle.

[0295] [Auxiliary Claim 40] The mode of operation stimulates the ventricle to initiate contraction of the at least one atrium. contracting the ventricle prior to contraction of the at least one atrium, thereby The method of claim 39, further comprising causing the AV valve to close during a portion of the period. [Preliminary Claim 41] The mode of operation stimulates the ventricle to initiate contraction of the at least one atrium. contracting the ventricle prior to the initiation of contraction of at least one atrium, thereby 41. The method of claim 40, further comprising causing the AV valve to close.

[0296] [Preliminary Claim 42] The device of any one of preliminary claims 38 to 41, wherein the operating mode includes delivering one or more excitatory pulses to the at least one atrium approximately 0 ms to 50 ms after the one or more excitatory pulses are delivered to the ventricle.

[0297] [Preliminary Claim 43] 1. An apparatus for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: a stimulator configured to deliver stimulation pulses to at least one cardiac chamber of the patient's heart; With intense circuit, a processor circuit coupled to the stimulation circuit, the processor circuit causing between about 40% of an atrioventricular contraction and about 100% of an atrioventricular contraction when an atrioventricular valve associated with the atrium is closed, preferably by initiating the atrial contraction no more than 60 ms before the atrioventricular valve closure, thereby and operating in an operating mode to stimulate at least one heart chamber to reduce the ventricular filling volume from the pre-treatment ventricular filling volume and reduce the patient's blood pressure from the pre-treatment blood pressure. and a processor circuit configured to:

[0298] [Preliminary Claim 44] 1. An apparatus for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: a stimulation circuit configured to deliver stimulation pulses to at least one cardiac chamber; A processor circuit coupled to the stimulation circuit, preferably causing an atrial contraction to begin about 50 ms to 5 ms before the onset of a ventricular contraction, thereby achieving about 50% to 50% of the atrial contraction during the ventricular contraction. and a pressure sensor configured to operate in an operational mode that paces at least one heart chamber and a ventricle to induce approximately 95% of the pressure in the at least one heart chamber and the ventricle, thereby reducing the ventricular filling volume from the pre-treatment ventricular filling volume and reducing the patient's blood pressure from the pre-treatment blood pressure. and a processor circuit.

[0299] [Preliminary Claim 45] 1. An apparatus for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: a stimulation circuit configured to deliver stimulation pulses to at least one cardiac chamber; a processor circuit coupled to the stimulation circuit, the processor circuit configured to generate a pulse having a frequency of about 0 ms to about 70 ms before the onset of atrial activation; a processor circuit configured to operate in an operational mode to stimulate at least one of the heart chambers such that a subsequent ventricular activation is initiated, thereby reducing the ventricular filling volume from the pre-treatment ventricular filling volume and reducing the patient's blood pressure from the pre-treatment blood pressure; An apparatus comprising:

[0300] [Auxiliary Claim 46] 1. A method performed by an implanted myocardial stimulator associated with a patient's heart for treating a blood pressure disorder in a patient having a pre-treatment blood pressure, the method comprising: Preferably, the method includes stimulating the heart to contract the atrium while closing a heart valve associated with the atrium, such that the contraction expands the atrium by contracting it at a time when ventricular pressure is greatest, such that the active force of the atrial contraction increases atrial expansion beyond the maximum passive expansion caused by ventricular contraction, and the expanded atrium reduces the patient's blood pressure from the blood pressure before the treatment.

[0301] [Preliminary Claim 47] 1. A system for reducing blood pressure, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart with stimulation pulses; configured to administer one or more successive stimulation patterns for a time interval lasting 10 minutes or more; and at least one controller, The one or more consecutive stimulation patterns are at least a first stimulation setting configured to reduce or prevent atrial kicks in both ventricles, and a second stimulation setting having a longer AV delay than the first stimulation setting for at least one beat during the time interval.

[0302] [Auxiliary Claim 48] The one or more consecutive stimulation patterns are 48. The system of preliminary claim 47, comprising a first stimulation setting. [Preliminary Claim 49] 49. The system of preliminary claim 47 or preliminary claim 48, wherein the time interval is at least 30 minutes long. [Preliminary Claim 50] 50. The system of preliminary claim 49, wherein the time interval is at least one hour long.

[0303] [Preliminary Claim 51] 51. The system of preliminary claim 50, wherein the time interval is at least 24 hours long. [Preliminary Claim 52] A system as described in any one of preliminary claims 47 to 51, wherein the one or more consecutive stimulation patterns include a third stimulation setting that is different from the first stimulation setting and is configured to reduce or prevent atrial kick in at least one ventricle.

[0304] [Preliminary Claim 53] The one or more successive stimulation patterns are different from the first stimulation setting and reduce or eliminate atrial kick in at least one ventricle for at least about 50% of the time interval. and a third stimulation setting configured to prevent the stimulation from occurring. Item 51. A system according to any one of items 51. [Preliminary Claim 54] The one or more successive stimulation patterns are different from the first stimulation setting and reduce or eliminate atrial kick in at least one ventricle for at least about 20% or less of the time interval. and a third stimulation setting configured to prevent the stimulation from occurring. Item 51. A system according to any one of items 51.

[0305] [Preliminary Claim 55] 1. A system for reducing blood pressure, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart with stimulation pulses; The device is designed to deliver one or more continuous stimulation patterns comprising a sequence of 10 to 60 stimulation pulses. and at least one controller configured to generate the sequence of 10 to 60 stimulation pulses. delivers an atrial kick to at least one ventricle and 10 to 60 stimulation pulses. a first stimulation setting configured to reduce or prevent a sequence of 1 to 10 beats from being stimulated, the sequence of 1 to 10 beats having a longer AV delay than the first stimulation setting.

[0306] [Preliminary Claim 56] 56. The system of claim 55, wherein the sequence of 1 to 10 beats includes at least one stimulation pulse having a first stimulation setting configured to reduce or prevent atrial kick in at least one ventricle. [Preliminary Claim 57] Preliminary claim 55 or preliminary claim 56, wherein the sequence of 1 to 10 beats includes a natural AV delay. 57. The system of claim 56.

[0307] [Preliminary Claim 58] 58. The system of any one of preliminary claims 55 to 57, wherein the sequence of 1 to 10 beats occurs without stimulation. [Preliminary Claim 69] The controller administering a plurality of stimulation patterns and, during said stimulation, receiving, for each of said stimulation patterns, a corresponding input data set related to the patient's blood pressure; determining at least one blood pressure variability parameter associated with the input data set for each of the plurality of stimulation patterns; and 52. A system according to any one of claims 42 to 51, configured to adjust stimulation patterns in accordance with the blood pressure variability parameters.

[0308] [Preliminary Claim 70] 70. The system of auxiliary claim 69, wherein the controller is configured to adjust the stimulation pattern to be the one having the longest blood pressure variability parameter. [Preliminary Claim 71] 71. The system of preliminary claim 70, wherein the longest blood pressure variability parameter is indicative of the lowest degree of baroreflex or the lowest degree or degree of adaptation.

[0309] [Preliminary Claim 72] A system as described in preliminary claim 70 or preliminary claim 71, wherein the longest blood pressure variability parameter is indicative of a baroreflex within a predetermined range or a degree of adaptation within a predetermined range. [Preliminary Claim 73] At least one stimulation pattern, wherein at least two of the plurality of stimulation patterns each have a stimulation setting configured to reduce or prevent atrial kick in at least one ventricle. 73. The system of any one of preliminary claims 69 to 72, comprising stimulation pulses, wherein the at least two stimulation patterns differ from each other by the number or length of time that the at least one stimulation pulse is delivered in succession.

[0310] [Preliminary Claim 74] A system as described in any one of preliminary claims 69 to 73, wherein the multiple stimulation patterns differ by the number or length of time the system is configured to successively elicit a predetermined AV delay. [Preliminary Claim 75] At least two of the plurality of stimulation patterns differ from each other by one or more stimulation settings included within each of the at least two stimulation patterns. A system according to any one of claims 69 to 74.

[0311] [Preliminary Claim 76] The plurality of stimulation patterns include a first stimulation setting and a second stimulation setting that is applied after the first stimulation setting, and the second stimulation setting is a stimulation pattern that is applied after the first stimulation setting. Based on an algorithm that uses blood pressure variability parameters related to the data set, 76. The system of any one of preliminary claims 69 to 75, having at least one stimulation setting. [Preliminary Claim 77] 77. The system of any one of preliminary claims 69 to 76, comprising a blood pressure sensor for providing the input data set relating to the patient's blood pressure.

[0312] [Preliminary Claim 78] 78. The system of preliminary claim 77, wherein the blood pressure sensor is implantable. [Preliminary Claim 79] 79. The system of any one of preliminary claims 77 to 78, wherein the blood pressure sensor and the controller are configured to operate at least partially as a closed loop.

[0313] [Auxiliary Claim 80] 1. A system for reducing blood pressure, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart with stimulation pulses; a controller, the controller comprising: configured to provide a first stimulation pattern comprising at least one stimulation setting configured to reduce or prevent atrial kicks in at least one ventricle during a first time interval and to receive a first input data set related to a blood pressure of the patient during the first time interval; configured to determine at least one blood pressure variability parameter associated with the first input data set; adjusting at least one parameter of a second stimulation pattern comprising a second stimulation setting configured to reduce or prevent atrial kicks in at least one ventricle, the second stimulation setting being based on the at least one blood pressure variability parameter; and The system is configured to deliver the second stimulation pattern for a second time interval.

[0314] [Preliminary Claim 81] 1. A system for reducing blood pressure, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart with stimulation pulses; at least one controller configured to administer a stimulation pattern comprising at least one stimulation setting configured to reduce or prevent atrial kick in at least one ventricle; The stimulation pattern causes an immediate reduction in blood pressure from an initial pressure value to a reduced pressure value and reduces the patient's mean resting blood pressure to at least 8 mmHg below the initial pressure. The system is selected to maintain full capacity. [Preliminary Claim 82] Preliminary claim 81, wherein the reduced blood pressure value is maintained for a time interval of at least one minute. The system described in

[0315] [Preliminary Claim 83] 1. A kit for reducing blood pressure, comprising: at least one device for setting a stimulation pattern for reducing blood pressure; The at least one device at least one stimulation electrode; a controller for setting an adjustable stimulation pattern; and a set of instructions for adjusting the stimulation pattern based on input related to the patient's blood pressure.

[0316] [Preliminary Claim 84] 1. A system for reducing blood pressure, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart; configured to deliver a stimulation pattern comprising at least one stimulation pulse having at least one stimulation setting configured to reduce or prevent atrial kick in at least one ventricle; and at least one controller, The at least one stimulation setting may be configured such that maximum atrial expansion is greater than or equal to the maximum atrial expansion when not stimulated. The system is configured to provide a value that is approximately equal to or lower than the maximum atrial dilation of the same heart.

[0317] [Back-up Claim 85] The at least one stimulation setting is configured to maximize the contraction of the atrium when the AV valve is open. 85. The system of preliminary claim 84, configured to: [Back-up Claim 86] The at least one stimulation setting is preferably configured to stimulate the at least one atrial contraction so that the at least one atrial contraction contracts with less force than in a preceding natural atrial contraction. 85. The system of claim 84, wherein the force is reduced.

[0318] [Back-up Claim 87] The at least one stimulation setting is configured to temporarily produce an atrial spasm or atrial flutter. a preliminary claim configured to reduce the force of the at least one atrial contraction by Item 87. The system of item 86. [Back-up Claim 88] The at least one stimulation setting preferably temporarily produces an atrial spasm or atrial flutter. 86. The system of claim 84 or claim 85, wherein the system is configured to prevent at least one atrial contraction by:

[0319] [Back-up Claim 89] 1. A system for reducing blood pressure, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart; and at least one controller, wherein the at least one controller: applying a stimulation pattern of stimulation pulses to the patient's heart; receiving input related to the patient's AV valve status; and and configured to adjust the at least one stimulation pattern based on the state of the patient's AV valve. A system that is made up of: [Preliminary Claim 90] 90. The system of claim 89, wherein the input related to the state of the patient's AV valve indicates timing of closure of the AV valve.

[0320] [Preliminary Claim 91] The system of alternative claim 89 or alternative claim 90, wherein the input related to the state of the patient's AV valve is provided based on a heart sound sensor. [Preliminary Claim 92] The system of alternative claim 89 or alternative claim 90, wherein the input related to the state of the patient's AV valve is provided based on a blood flow sensor.

[0321] [Preliminary Claim 93] Preliminary claim 91 or the heart sound sensor or the blood flow sensor is an implanted sensor. 93. The system of preliminary claim 92. [Preliminary Claim 94] The system of any one of preliminary claims 92 and 93, wherein the blood flow sensor includes an ultrasonic sensor for detecting blood flow through the AV valve.

[0322] [Preliminary Claim 95] Preliminary claims 91 to 94 are as defined in any one of preliminary claims 91 to 94, wherein the controller and each blood flow or heart sound sensor are configured to operate at least partially in a closed loop. system. [Preliminary Claim 96] The stimulation pattern is configured to reduce or prevent the atrial kick in at least one ventricle. 96. The system of any one of preliminary claims 89 to 95, comprising at least one stimulation pulse configured to:

[0323] [Preliminary Claim 97] Preliminary claims 89 through 96, wherein adjusting the at least one stimulation pattern includes adjusting an AV delay of at least one stimulation pulse. The system described in [Preliminary Claim 108] 1. A system for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: a stimulation circuit configured to deliver stimulation pulses to at least one atrium; a processor circuit coupled to the stimulation circuit for controlling the force of at least one atrial contraction; and a processor circuit configured to operate in an operating mode to stimulate the atria to reduce a ventricular filling volume from a pre-treatment ventricular filling volume and to reduce the patient's blood pressure from a pre-treatment blood pressure.

[0324] [Preliminary Claim 109] The at least one stimulation setting is configured to temporarily produce an atrial spasm or atrial flutter. 109. The system of claim 108, wherein the system is configured to reduce the force of at least one atrial contraction or prevent said at least one atrial contraction. [Back-up Claim 110] 1. A system for reducing blood pressure, comprising: a sensor for sensing the activation rate of at least one of the atria and the ventricles; a stimulation circuit configured to deliver stimulation pulses to at least one of the atrium and the ventricle; a processor circuit coupled to the stimulation circuit, wherein a timing of next atrial activation is predicted based on the detected activation rate, and wherein at least one ventricle is activated based on the predicted activation rate; and a processor circuit configured to operate in an operating mode in which the atrial stimulation is stimulated at a time between about 50 ms before and about 10 ms after the next atrial excitation.

[0325] [Preliminary Claim 111] 111. The system of auxiliary claim 110, wherein the sensor for sensing the activation rate of at least one of the atria and ventricles comprises an electrode for sensing atrial activation. [Preliminary Claim 112] Prediction of the next atrial activation is based on a function of the preceding sensed activation, including the interval and rate of change of the cyclic variation. system.

[0326] [Preliminary Claim 113] The timing of the predicted next atrial activation is determined by the time interval between the atrial activation and the detection of the atrial activation. Any one of preliminary claims 110 through 112, adjusted to reflect the delay between The system described in [Preliminary Claim 114] Preliminary claims 110 to 114 further comprise an additional sensor for sensing a parameter related to cardiac activity and for adjusting the time at which the ventricle is stimulated accordingly. 114. The system of claim 113.

[0327] [Back-up Claim 115] 115. The system of claim 114, wherein the parameter is one of the group consisting of data related to blood pressure, blood flow, AV valve status, and wall motion of the heart or a portion thereof. [Preliminary Claim 116] The additional sensor may be a pressure sensor, an impedance sensor, an ultrasonic sensor, and / or or one or more audio sensors, and / or one or more blood flow sensors. A system as claimed in any one of preliminary claims 114 and 115,

[0328] [Back-up Claim 117] The system of any one of preliminary claims 114 to 116, wherein the additional sensor is implantable. [Preliminary Claim 118] 1. A system for reducing blood pressure, comprising: a sensor for sensing the activation rate of at least one of the atria and ventricles of a patient's heart; a stimulation circuit configured to deliver stimulation pulses to the atrium and the ventricle; a processor circuit coupled to the stimulation circuit, the processor circuit configured to detect a heart rate of the patient based on the sensing, and configured to operate in a mode of operation in which stimulation pulses are delivered to each of at least one of the atria and the ventricles; The system is configured such that the stimulation pulse is delivered at a rate greater than the detected excitation rate, and the stimulation pulse stimulates the ventricle at a time between about 50 ms before and about 70 ms after stimulation of the atrium.

[0329] [Preliminary Claim 119] The operating mode stimulates the ventricle to contract the at least one atrium before the end of the contraction. 34. The apparatus of claim 33, further comprising contracting the ventricle. [Preliminary Claim 120] The mode of operation stimulates the ventricle to terminate the contraction of the at least one atrium. contracting the ventricle prior to contraction of the at least one atrium, thereby 35. The apparatus of claim 34, further comprising causing the AV valve to be closed during a portion.

[0330] [Preliminary Claim 121] The operational mode involves delivering a stimulation pulse to the ventricle to stimulate the at least one contracting prior to said delivery of a stimulation pulse to said at least one atrium, thereby 36. The apparatus of any one of preliminary claims 33 to 35, comprising causing the AV valve to close during at least a portion of the deflation of the ventricle. [Preliminary Claim 122] The device of any one of preliminary claims 33 to 36, wherein the operating mode includes delivering one or more excitatory pulses to the at least one atrium approximately 0 ms to 50 ms after the one or more excitatory pulses are delivered to the ventricle.

[0331] [Preliminary Claim 123] The operating mode stimulates the ventricle to contract the at least one atrium before the end of the contraction. 39. The method of claim 38, further comprising: contracting the ventricle. [Preliminary Claim 124] The operating mode stimulates the ventricle to contract the at least one atrium before the end of the contraction. contracting the ventricle, thereby causing at least one of the contractions of the at least one atrium. 40. The method of claim 39, further comprising causing the AV valve to close during the period.

Claims

1. 1. A system for reducing blood pressure in a patient having a pre-treatment blood pressure and a pre-treatment ventricular filling volume, comprising: a stimulation circuit configured to deliver stimulation pulses to at least one atrium of the patient; a processor circuit coupled to the stimulation circuit, the processor circuit configured to operate in a first mode of operation to stimulate an atrium to reduce the force of or prevent at least one atrial contraction, thereby reducing ventricular filling volume from a pre-treatment ventricular filling volume and reducing the patient's blood pressure from a pre-treatment blood pressure.

2. 10. The system of claim 1, wherein the processor circuit is configured to operate in a second mode of operation in which the atrium is stimulated to reduce the force of or prevent at least one atrial contraction by temporarily producing an atrial spasm or atrial flutter.

3. 10. The system of claim 1, wherein the processor circuit is configured to deliver a burst of rapid stimulation pulses to the atrium for a predetermined time.

4. 2. The system of claim 1, wherein the atrial stimulation in the first operating mode is selected to cause a reduction in blood pressure from an initial blood pressure value to a reduced blood pressure value and to maintain the patient's average blood pressure value at rest at least 8 mmHg below the initial blood pressure value.

5. The system of claim 4 , wherein the reduced blood pressure value is maintained for at least one minute.

6. The system of claim 4 , wherein the reduced blood pressure value is maintained for at least 5 minutes.

7. 5. The system of claim 4, wherein the reduction in blood pressure is observed within 3 seconds of application of the stimulation pulse.

8. 5. The system of claim 4, wherein the blood pressure reaches a minimum blood pressure value within five or fewer heartbeats from the start of stimulation.

9. 1. A system for reducing blood pressure in a patient, comprising: at least one stimulation electrode for stimulating at least one chamber of the patient's heart with stimulation pulses; at least one controller configured to administer a stimulation pattern comprising at least one stimulation setting configured to reduce or prevent atrial kick in at least one ventricle; The system wherein the stimulation pattern of the stimulation pulses is selected to cause a reduction in blood pressure from an initial blood pressure value to a reduced blood pressure value and to maintain the patient's average resting blood pressure value at least 8 mmHg below the initial blood pressure value.

10. 10. The system of claim 9, wherein the reduced blood pressure value is maintained for at least 1 minute.

11. 10. The system of claim 9, wherein the reduced blood pressure value is maintained for at least 5 minutes.

12. 10. The system of claim 9, wherein the reduction in blood pressure is observed within 3 seconds of application of the stimulation pulse.

13. 10. The system of claim 9, wherein the blood pressure reaches a minimum blood pressure value within five or fewer heartbeats from the start of stimulation.

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