Stimulation of nerves to affect cardiac, cardiovascular and systemic vascular function

Abstract

A system including: one or more electrodes configured to be disposed at one or more target treatment sites within a blood vessel of a patient; and processing circuitry configured to: determine a first characteristic of a cardiac cycle based on cardiac, cardiovascular and / or and systemic vascular signals; determine, based at least in part on the first characteristic, one or more first stimulation parameters for a first stimulation signal; determine a second characteristic of the cardiac cycle determine, based at least in part on the second characteristic, one or more second stimulation parameters for a second stimulation signal; and cause the one or more electrodes to deliver one or more of: the first stimulation signal to one or more nerves of the patient to cause a parasympathetic stimulation of the heart; or the second stimulation signals to the one or more nerves to cause a sympathetic stimulation of the heart.

Description

STIMULATION OF NERVES TO AFFECT CARDIAC, CARDIOVASCULAR ANDSYSTEMIC VASCULAR FUNCTION

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 766,724, filed March 04, 2025, and to U.S. Provisional Patent Application No. 63 / 644,029, filed May 8, 2024, the entire contents of each of which are incorporated herein by reference.TECHNICAL FIELD

[0002] The disclosure relates generally to medical device systems and, more particularly, cardiac sensing and therapy delivery by medical device systems.BACKGROUND

[0003] Some types of implantable medical device (IMD) systems, such as cardiac pacemaker or implantable cardioverter defibrillator systems, may be used to sense signals from and deliver therapy to one or more locations within a body of a patient. The sensed signals may include cardiac signals, systemic hemodynamic signals or nerve signals. The therapy may include cardiac pacing signals and nerve stimulation signals. Some IMDs include an implantable housing that encloses a pulse generator and other electronic components, which may be configured to be implanted subcutaneously in the chest of the patient, as an example.SUMMARY

[0004] In some examples, this disclosure is directed to techniques for controlling the delivery of stimulation signals, by an implantable medical device (IMD), to nerve(s) of the patient to affect cardiac, cardiovascular and systemic vascular function of the patient. The IMD may control the delivery of the stimulation signals based at least in part on sensed cardiac and systemic hemodynamic parameters from the patient. The IMD may control the delivery of the stimulation signals based at least in part on the cardiac cycle, cardiovascular functions, and / or systemic hemodynamics of the patient. The stimulation signals may affect a sympathetic or parasympathetic response to the cardiac, cardiovascular and systemic vascular function of the patient, which may balance and / or improve the cardiac, cardiovascular and systemic vascular function of the patient over time and inhibit progression of cardiac, cardiovascular and systemic vascular disease.

[0005] Stimulation of autonomic nerves of the patient to cause a sympathetic responses may increase the heart rate and / or heart contractility, systemic hemodynamics of the patient.Stimulation of autonomic nerves of the patient to cause a parasympathetic responses may decrease the heart rate, heart contractility and / or systemic vascular resistance of the patient. The devices, systems, and techniques described herein deliver stimulation signals to autonomic nerve(s) to elicit sympathetic and / or parasympathetic responses to control the heart rate, heart contractility, and / or blood pressure, thereby improving hemodynamic function and / or cardiac output of the heart. In some examples, the devices, systems, and techniques described herein may involve delivery of stimulation signals to nerve(s) (e.g., autonomic nerve(s)) during specific time windows within the cardiac cycle of the patient, e.g., to elicit specific cardiac, cardiovascular and / or systemic vascular responses during the cardiac cycle of the patient.

[0006] When the body of the patient maintains cardiac output, e.g., when the patient is experiencing a cardiac, cardiovascular and systemic vascular condition, the maintenance of the cardiac output may lead to an imbalance in the autonomic nervous system. For example, the autonomic nervous system may experience an increase in sympathetic activity and a decrease in parasympathetic activity, or vice versa. The imbalance in the autonomic nervous system may lead to cardiac, cardiovascular and systemic vascular conditions such as, but is not limited to, acute decompensated heart failure. The devices, systems, and techniques described herein may stimulate nerve(s) (e.g., autonomic nerve(s)) to cause sympathetic and / or parasympathetic responses to balance the autonomic nervous system. Balancing the autonomic nervous system may improve and / or maintain cardiac, cardiovascular and systemic vascular functionality, reduce the effects of a cardiac, cardiovascular and systemic vascular condition experienced by the patient (e.g., acute decompensated heart failure), and / or reduce a progression of a cardiac, cardiovascular and systemic vascular condition experienced by the patient (e.g., heart failure).

[0007] In some examples, this disclosure describes a system comprising: one or more electrodes configured to be disposed at one or more target treatment sites within a blood vessel of a patient; and processing circuitry configured to: receive cardiac, cardiovascular and / or systemic vascular signals from a heart of the patient; determine a first characteristic of a cardiac cycle of the heart based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the first characteristic, one or more first stimulation parameters for a first stimulation signal; determine a second characteristic of the cardiac cycle based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the second characteristic, one or more second stimulation parameters for a second stimulation signal; and cause the one or more electrodes to deliver one or more of: the first stimulation signal to one or more nerves of the patient at or around the one or more target treatment sites to cause a parasympathetic stimulation of the heart; or the second stimulationsignal to the one or more nerves at or around the one or more target treatment sites to cause a sympathetic stimulation of the heart.

[0008] In some examples, this disclosure describes a system comprising: one or more electrodes configured to be disposed at one or more target treatment sites within a blood vessel of a patient; and processing circuitry configured to: receive cardiac, cardiovascular and / or systemic vascular signals from a heart of the patient; determine a characteristic of a cardiac cycle of the heart based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the characteristic, at least one of one or more first stimulation parameters for a first stimulation signal, or one or more second stimulation parameters for a second stimulation signal; compare the characteristic against a threshold condition; based on a determination that the characteristic satisfies the threshold condition, cause the one or more electrodes to deliver the first stimulation signal to one or more nerves of the patient at or around the one or more target treatment sites to cause a parasympathetic stimulation of the heart; and based on a determination that the characteristic does not satisfy the threshold condition, cause the one or more electrodes to deliver the second stimulation signals to the one or more nerves at or around the one or more target treatment sites to cause a sympathetic stimulation of the heart.

[0009] In some examples, this disclosure describes a method comprising: receiving, by processing circuitry of a medical device system, cardiac, cardiovascular and / or systemic vascular signals from a heart of a patient; determining, by the processing circuitry and based on the received cardiac, cardiovascular and / or systemic vascular signals, a first characteristic of a cardiac cycle of the heart; determining, by the processing circuitry and based at least in part on the first characteristic, one or more first stimulation parameters for a first stimulation signal; determining, by the processing circuitry and based on the received cardiac, cardiovascular and / or systemic vascular signals, a second characteristic of the cardiac cycle; determining, by the processing circuitry and based at least in part on the second characteristic, one or more second stimulation parameters for a second stimulation signal; causing, by the processing circuitry, one or more electrodes of the medical device system to deliver one or more of: the first stimulation signal to one or more first nerves of the patient to cause a parasympathetic stimulation of the heart; or the second stimulation signal to one or more second nerves of the patient to cause a sympathetic stimulation of the heart.

[0010] This summary is intended to provide an overview of the subject matter described in this disclosure. It is not intended to provide an exclusive or exhaustive explanation of the methods and systems described in detail within the accompanying drawings and description below. The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below.BRIEF DESCRIPTION OF DRAWINGS

[0011] The details of one or more examples of this disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of this disclosure will be apparent from the description and drawings, and from the claims.

[0012] FIG. 1 A is a conceptual diagram illustrating an example medical device system configured to deliver stimulation signals to nerves of the patient.

[0013] FIG. IB is a conceptual diagram illustrating an example medical device system configured to deliver stimulation signals to nerves adjacent to cardiac and cardiovascular tissue of the patient.

[0014] FIG. 1C is a conceptual diagram illustrating another example medical device system configured to deliver stimulation signals to nerves of the patient.

[0015] FIG. 2A is a conceptual diagram illustrating an example delivery of stimulation signals to the nerves of the patient within a cardiac cycle of the patient.

[0016] FIG. 2B is a conceptual diagram illustrating another example delivery of stimulation signals to the nerves of the patient within a cardiac cycle of the patient.

[0017] FIG. 2C is a conceptual diagram illustrating another example delivery of stimulation signals to the nerves of the patient within a cardiac cycle of the patient.

[0018] FIG. 2D is a conceptual diagram illustrating another example delivery of stimulation signals to the nerves of the patient within a cardiac cycle of the patient.

[0019] FIG. 3 is a conceptual diagram illustrating an example implantable lead of the medical device system of any of FIGS. 1A-1C.

[0020] FIG. 4 is a conceptual diagram illustrating another example of an implantable lead of the medical device system of any of FIGS. 1A-1C.

[0021] FIG. 5 is a conceptual diagram illustrating another example of an implantable lead of the medical device system of any of FIGS. 1A-1C.

[0022] FIG. 6 is a block diagram illustrating components of an example implantable medical device (IMD) of the medical device system of any of FIGS. 1A-1C.

[0023] FIG. 7 is a flowchart illustrating an example process of delivering stimulation signals to the nerves of the patient using the medical device system illustrated in any of FIGS. 1 A-6.

[0024] FIG. 8 is a flowchart illustrating another example process of delivering stimulation signals to the nerves of the patient using the medical device system illustrated in any of FIGS. 1A-6.

[0025] FIG. 9 is a flowchart illustrating another example process of delivering stimulation signals to the nerves of the patient using the medical device system illustrated in any of FIGS. 1A-6.

[0026] FIG. 10 is a flowchart illustrating another example process of delivering stimulation signals to the nerves of the patient using the medical device system illustrated in any of FIGS. 1A-6.

[0027] FIG. 11 A is a conceptual diagram illustrating an example of the implantable lead of FIG. 3 in an expanded configuration.

[0028] FIG. 1 IB is a conceptual diagram illustrating the example implantable lead of FIG.11 A in a collapsed configuration.

[0029] FIG. 12A is a conceptual diagram illustrating an example of the implantable lead of FIG. 3 in an expanded configuration.

[0030] FIG. 12B is a conceptual diagram illustrating the example implantable lead of FIG. 12A in a collapsed configuration.

[0031] FIG. 12C is a cross-sectional diagram illustrating a cross-section of the implantable lead of FIG. 12 A, the cross-section being take along line A-A in FIG. 12B.

[0032] FIG. 13 is a conceptual diagram illustrating an example implantable lead of the medical device system of any of FIGS. 1A-6.

[0033] FIG. 14 is a conceptual diagram illustrating another example implantable lead of the medical device system of any of FIGS. 1A-6.

[0034] FIG. 15A is a conceptual diagram illustrating another example implantable lead of the medical device system of any of FIGS. 1A-6.

[0035] FIG. 15B is a conceptual diagram illustrating another example implantable lead of the medical device system of any of FIGS. 1A-6.

[0036] FIG. 16 is a conceptual diagram illustrating an example implantation of the implantable lead of any of FIGS. 15A-15B within the heart of the patient.DETAILED DESCRIPTION

[0037] In some examples, this disclosure describes example techniques related to stimulation of nerve(s) of a patient to affect and / or moderate cardiac, cardiovascular and systemic vascular functions of the patient. While the devices, systems, and techniques described in this disclosure are primarily described with respect to stimulation of autonomic nerve(s), the devices, systems, and techniques described herein may be used to stimulate other nerves within the body of the patient. Efforts by the body of the patient to maintain cardiac, cardiovascular and systemic vascular function may lead to an imbalance of the autonomic nerve system of the patient. Forexample, there may be an increase in sympathetic nerve responses and a decrease in parasympathetic nerve responses. The imbalance in the autonomic nervous system may lead to an onset of a cardiac, cardiovascular and systemic vascular condition and / or a worsening of a status of an existing cardiac, cardiovascular and systemic vascular condition, cardiac, cardiovascular and systemic vascular conditions may include, but are not limited to, acute heart failure, ischemia, chronic heart failure, pulmonary artery hypertension and hypertension.

[0038] This disclosure describes devices, systems, and techniques for stimulation of nerve(s) of the patient to elicit a sympathetic or a parasympathetic response in the cardiovascular system of the patient. The elicited sympathetic and / or parasympathetic responses may improve the balance within the autonomic nervous system, improve cardiac, cardiovascular and systemic vascular function (e.g., improve the balancing of cardiac, cardiovascular and systemic vascular parameters such as heart rate, blood pressure, and / or contractility), reduce the likelihood and / or severity of cardiac, cardiovascular and systemic vascular conditions, and / or improve hemodynamic function of the heart.

[0039] Sympathetic nerve stimulation and parasympathetic nerve stimulation may have effects on the cardiac, cardiovascular and systemic vascular function of the patient. For example, stimulation of nerve(s) to elicit a sympathetic response may lead to an increase in heart rate, heart contractility, blood pressure, or the like. In some examples, stimulation of nerve(s) to elicit a parasympathetic response may lead to a decrease in heart rate, heart contractility, blood pressure, or the like. The medical device systems and techniques described herein may balance the delivery of sympathetic and parasympathetic nerve stimulations to nerve(s) of the patient, e.g., to improve cardiac and cardiovascular and systemic hemodynamic function of the patient, to reduce the likelihood of cardiac, cardiovascular and systemic vascular conditions (e.g., acute heart failure), and / or to improve the balance of the autonomic nervous system of the patient.

[0040] An example medical device system described herein may adjust stimulation parameters of one or more stimulation signals based on cardiac, cardiovascular and systemic vascular parameter values, e.g., to elicit an appropriate response (e.g., a sympathetic response and / or a parasympathetic response) based on the cardiac, cardiovascular and systemic vascular parameter values. For example, the medical device system may select stimulation parameters for a stimulation signal to elicit a sympathetic response in the heart in response to cardiac, cardiovascular and systemic vascular parameters indicating a reduced heart rate and / or contractility, or vice versa. The medical device system may transmit the one or more stimulation signals to the nerve(s) at one or more time intervals within a cardiac cycle of the patient, e.g., to improve cardiac, cardiovascular and systemic vascular function during one or more cardiac cycles of the patient. The medical device system may elicit a sympathetic or parasympatheticresponse by stimulating specific target sites near nerve(s) of the patient and / or during specific portions of the cardiac cycle of the patient.

[0041] FIG. 1 A is a conceptual diagram illustrating an example medical device system 100 (alternatively referred to herein as “system 100”) configured to deliver stimulation signals to nerves 106 A, 106B (collectively referred to herein as “nerves 106”) of a patient. As illustrated in FIG. 1 A, system 100 may include one or more IMDs 108 A configured to deliver electrical stimulation signals to nerves 106 via electrode(s) 120 disposed on implantable lead(s) 118 coupled to IMD 108 A. IMD 108 A may include one or more components including, but not limited to, processing circuitry 110, signal generation circuitry 112, memory 114, and communications circuitry 116.

[0042] Heart 102 may be connected to nerves 106 at or around a target region 104 at or around a base of heart 102. Target region 104 may include, but is not limited to, a cardiac and vascular plexus of the patient. A plurality of blood vessels may extend through target region 104, and nerves 106 (e.g., nerve(s) 106A, 106B) may be disposed around the blood vessels. Nerve(s) 106 A may include a right sympathetic trunk of the patient, a right vagus nerve of the patient, and / or one or more nerves connected to the right sympathetic trunk and / or the right vagus nerve, such as, but are not limited to, the right inferior cervical cardiac and vascular branch, the right thoracic cardiac and vascular nerves, the right thoracic cardiac and vascular branch, the dorsal cardiac and vascular plexus, or the right coronary nerve of the patient. Nerve(s) 106B may include a left sympathetic trunk of the patient, a left vague nerve of the patient, and / or one or more nerves connected to the left sympathetic trunk and / or the left vagus nerve, such as, but are not limited to, the left inferior cervical cardiac and vascular nerve, the ventral cardiac and vascular plexus, the left lateral cardiac and vascular nerve, or the left coronary nerve of the patient.

[0043] Stimulation of one or more of nerves 106 may elicit a sympathetic or parasympathetic response in heart 102 of the patient. Sympathetic stimulation of heart 102 (e.g., stimulation leading to a sympathetic response in heart 102) may lead to changes in one or more cardiac, cardiovascular and systemic vascular parameters such as, but is not limited to, an increase a heart rate of heart 102, increase the heterogeneity of refractory period of the heart 102, an increase in an abnormal direction of repolarization of heart 102, an increase in an action potential duration, an increase in a contraction force by heart 102, and / or an increase in a ventricular refractory period of heart 102. Parasympathetic stimulation of heart (e.g., stimulation leading to a parasympathetic response in heart 102) may lead to changes in one or more cardiac, cardiovascular and systemic vascular parameter such as, but is not limited to, a decrease in the heart rate of heart 102, a decrease in cardiac and vascular inflammatory cytokines duringischemia, an increase in Connexin 43 in heart 102, and increase in gap junctions, a decrease in atrioventricular (AV) node conduction, an increase in vagally derived nitric oxide, a decrease of vascular resistance, a change in blood flow rate (e.g., as determined by a blood pressure and a compliance of a blood vessel), and / or a decrease in the ventricular refractory period. An imbalance between the parasympathetic and sympathetic responses in heart 102 may lead to an onset and / or an increase in severity of one or more cardiac, cardiovascular and systemic vascular conditions, e.g., due at least in part to the effects of sympathetic or parasympathetic stimulation on cardiac, cardiovascular and systemic vascular parameters.

[0044] IMD 108 A may transmit stimulation signal(s) to nerves 106 within target location 104 to elicit a sympathetic and / or a parasympathetic response in heart 102. The stimulation signal(s) may elicit a sympathetic or parasympathetic response in heart 102 based on stimulation site(s) for the stimulation signal(s) within target location 104, the timing of delivery of the stimulation signal(s), and / or stimulation parameters for the stimulation signal(s). IMD 108 A may transmit stimulation signal(s) to nerves 106 to elicit a sympathetic and / or a parasympathetic response in heart 102 during specific portions of the cardiac cycle of heart 102, e.g., to assist in the cardiac, cardiovascular and systemic vascular function and / or hemodynamic output of heart 102.

[0045] Processing circuitry 110 of IMD 108 A may determine stimulation parameters of stimulation signal(s) based at least in part on sensed cardiac, cardiovascular and systemic vascular parameter values. Cardiac, cardiovascular and systemic vascular parameters may include, but are not limited to, heart rate, cardiac output, heart blood pressure (e.g., systolic blood pressure, diastolic blood pressure), blood pressure in a blood vessel of the patient, a nerve response to cardiac activity of heart 102 (e.g., an evoked compound action potential (ECAP) signal in response to cardiac activity of heart 102), a blood flow rate through heart 102 and / or a blood vessel of the patient, an R-R interval variability in cardiac activity of heart 102 (e.g., in a frequency or time domain and reflecting sympathetic and / or parasympathetic nerve activity of the patient), a heart rate variability (HRV) of heart 102, heart rate of heart 102 during a specific respiratory phase (e.g., inspiration phase) of patient, the P-R interval of heart 102, a Q-T interval of heart 102, parameter(s) derived from a T-wave of heart 102 (e.g., an interval between a peak of the T-wave and an end of the T-wave, an area of the T-wave, an amplitude of the T-wave), a frequency and / or magnitude of arrhythmic cardiac events experienced by heart 102 (e.g., arrhythmic atrial or ventricular cardiac events), parameter(s) indicating a Heart Rate Turbulence of heart 102 (e.g., a turbulence onset (TO) indicating an initial acceleration of the heart rate following a premature beat by heart 102, a turbulence slope(TS) indicating a deceleration of the heart rate), a deceleration capacity of heart 102 (e.g., indicating neural control of heart 102 to decelerate the heart rate), a presence of ectopic beats in the cardiac activity of heart 102, anejection fraction of heart 102, pulse wave velocity of one or more blood vessels of the patient, a rate of change in pressure (e.g., dp / dt) in a chamber of heart 102 (e.g., in left ventricle), and / or thoracic impedance. The cardiac, cardiovascular, and / or systemic vascular parameters may be indicative Cardiac, cardiovascular, and / or systemic vascular parameters described herein may be measured via electrodes coupled to IMD 108A (e.g., via electrode 120), via sensor(s) disposed on and / or within IMD 108 A, via other sensors and / or IMDs implanted within the body of patient, and / or via external sensors and / or computing devices coupled to the patient. Stimulation parameters may include, but are not limited to, a timing, a frequency, a duration, a number of stimulation pulses, a pulse width of a stimulation pulse, an amplitude, a duty cycle, a ramp up time, a ramp down time, a ratio of stimulation signal duration relative to a duration of another stimulation signal, and / or an electrode selection for each stimulation signal.

[0046] Processing circuitry 110 may sense (e.g., via sensors coupled to IMD 108A and / or via electrode 120) cardiac, cardiovascular and systemic vascular parameter values from the patient. In some examples, processing circuitry 110 receives, via communications circuitry 116, sensed cardiac, cardiovascular and systemic vascular parameter values (e.g., from sensor(s) coupled to the patient, from another IMD, from an external programmer). Based on the sensed cardiac, cardiovascular and systemic vascular parameter values, processing circuitry 110 may determine a type of response to be elicited from the patient and may adjust stimulation parameters for stimulation signal(s) to elicit the determine response from the patient. For example, processing circuitry 110 may adjust, based on receiving cardiac, cardiovascular and systemic vascular parameter values indicating a reduced heart rate, stimulation parameters to elicit a sympathetic response in the patient (e.g., to improve the heart rate of the patient).

[0047] Processing circuitry 110 may cause signal generation circuitry 112 to generate stimulation signal(s) based at least in part on the determined stimulation parameters. Signal generation circuitry 112 may be coupled to electrodes (e.g., electrode 120) via implantable lead(s) 118. Signal generation circuitry 112 may transmit the generated stimulation signal(s) to Electrode 120 along implantable lead(s) 118. Electrode 120 may transmit the stimulation signal(s) through a blood vessel wall and into nerves within target location 104 and adjacent the blood vessel, e.g., to elicit a sympathetic or parasympathetic response in heart 102.

[0048] Processing circuitry 110 may transmit sensed cardiac, cardiovascular and systemic vascular parameter values and / or determined stimulation parameter values to one or more other computing devices and / or systems (e.g., another IMD, an external programmer) via communications circuitry 116. In some examples, processing circuitry 110 may store sensed cardiac, cardiovascular and systemic vascular parameter values and / or stimulation parametervalues in memory 114. Values stored in memory 114 may be retrieved and / or transmitted to other computing devices and / or systems at a later time.

[0049] While electrode 120 is primarily illustrated and described herein as being disposed within a blood vessel within target location 104, in some examples electrode 120 may be disposed within another body lumen at or around target location 104. For example, electrode 120 may be disposed within a trachea of the patient (e.g., at or around a trachea bifurcation of the patient) or within an esophagus of the patient at or around target location 104. While FIG. 1 A illustrates one electrode 120 coupled to IMD 108 A, some examples of IMD 108 A may include two or more electrodes 120 coupled to IMD 108 A via one or more implantable leads 118.

[0050] FIG. IB is a conceptual diagram illustrating another example of system 100 configured to deliver stimulation signals to nerves 106 adjacent to cardiac and vascular tissue of the patient. As illustrated in FIG. IB, system 100 may include IMD 108B and electrodes 122, 124A, and / or 124B disposed on implantable lead(s) 118 coupled to IMD 108B. IMD 108B may be substantially identical to IMD 108 A aside from the elements discussed below.

[0051] In some examples, as illustrated in FIG. IB, IMD 108B is configured to deliver cardiac pacing signals to heart 102 of the patient in addition to nerve stimulation signal(s) to target region 104. IMD 108B may be coupled to one or more pacing electrodes (e.g., pacing electrode 122) and to one or more stimulation electrodes (e.g., electrode 124 A, electrode 124B) via implantable lead(s) 118. Each electrode may be disposed on a separate implantable lead (e.g., pacing electrode 122 is disposed on one implantable lead 118 and electrode 124A or electrode 124B is disposed on another implantable lead 118). In some examples, electrodes are disposed on a same implantable lead 118. For example, pacing electrode 122 may be disposed at a distal end of implantable lead 118 and electrode 124B may be disposed along implantable lead 118 and proximal to pacing electrode 122. IMD 108B may be connected to a single nerve stimulation electrode (e.g., either electrode 124A or electrode 124B) or to multiple nerve stimulation electrodes (e.g., to both of electrodes 124A, 124B).

[0052] Pacing electrode 122 may be affixed within a chamber of heart 102. In some examples, as illustrated in FIG. IB, pacing electrode 122 is affixed to cardiac and vascular tissue within a right ventricle (RV) of heart 102. In some examples, pacing electrode 122 may be affixed to one or more of cardiac and vascular tissue within a left ventricle (LV), left atrium (LA), or right atrium (RA) of heart 102. In some examples, pacing electrode 122 may be affixed at or around one or more cardiac and vascular features within heart 102 including, but are not limited to, a bundle of His or a triangle of Koch of heart 102). In some examples, IMD 108B is configured to monitor one or more biometric signals (e.g., impedance, blood vessel volume, electrocardiogram signals) via pacing electrode 122.

[0053] IMD 108B may be configured to sense cardiac, cardiovascular and / or systemic vascular signal from heart 102 via pacing electrode 122. In some examples, IMD 108B is configured to deliver, via pacing electrode 122, a pacing signal to heart 102, e.g., to alleviate a cardiac, cardiovascular and systemic vascular condition (e.g., arrhythmia or hypertension) and / or to maintain cardiac, cardiovascular and systemic vascular function of heart 102.

[0054] Electrodes 124A, 124B (collectively referred to herein as “electrodes 124”) may be disposed and / or affixed within blood vessels of the patient at or around target location 104. In some examples, as illustrated in FIG. IB, electrodes 124 may transition to a deployed configuration within the blood vessel to deliver stimulation signals to a vessel wall of the blood vessel and / or to interface with the vessel wall, e.g., to maintain the positions of electrodes 124 within the blood vessels.

[0055] IMD 108B may deliver stimulation signal(s) to nerves 106 (e.g., as illustrated in FIG.1 A) in addition to or instead of pacing signals to heart 102, e.g., to maintain cardiac, cardiovascular, and system vascular function of heart 102. IMD 108B may adjust timing of the stimulation signal(s) based on the timing of the pacing signals, e.g., to augment the effects of the pacing signals and / or to maintain autonomic nervous system balance as IMD 108B delivers pacing signals to heart 102. IMD 108B may determine stimulation signal(s) to nerves 106 based on the sensed cardiac, cardiovascular and systemic vascular parameters and / or pacing parameters (e.g., the timing of pacing signals) for pacing signals delivered to heart 102.

[0056] FIG. 1C is a conceptual diagram illustrating another example of system 100 configured to deliver stimulation signals to nerves 106 of the patient. As illustrated in FIG. 1C, system 100 may include IMD 108C and implantable leads 130A, 130B coupled to IMD 108B and disposed within blood vessels at target location 104. IMD 108C may be substantially identical to IMD 108 A aside from the elements discussed below.

[0057] Each of implantable leads 130A, 130B (collectively referred to herein as “implantable leads 130”) may include an electrode array arranged at or around distal ends of implantable leads 130. The electrode arrays may each include a plurality of electrodes, e.g., disposed along a stent disposed at or around a distal end of one of implantable leads 130.When implantable leads 130 are disposed within blood vessels at or around target location 104, the plurality of electrodes of each electrode array may contact a blood vessel wall at different locations and / or orientations. IMD 108C may select, e.g., based on the intended type of response to the stimulation signal(s) to be elicited from the patient, one or more electrodes from the electrode array for delivery of the stimulation signal(s).

[0058] Different selections of electrodes may transmit the stimulation signal(s) to different tissue and / or nerves 106 within target location 104, which may elicit a sympathetic responseand / or a parasympathetic response. In such examples, IMD 108C may select a first group of electrodes within the electrode array to deliver stimulations signal(s) to elicit a sympathetic response in heart 102 and may select a second group of electrodes within the electrode array to deliver stimulation signal(s) to elicit a parasympathetic response in heart 102. IMD 108C may sense cardiac, cardiovascular and systemic vascular parameters from the patient via one or more electrodes disposed within electrode arrays of implantable leads 130.

[0059] While FIGS. 1A-C illustrate IMDs 108A-C as different IMDs, Each of IMDs 108-C may be of the same or substantially similar IMD and may be coupled to any combination of the electrodes and / or implantable leads illustrated in FIGS. 1 A-C. The electrodes and / or implantable leads coupled to IMDs 108 may not be limited to the example implantation locations and / or configurations illustrated in FIGS. 1 A-C, and may be implanted at any of the locations described in this disclosure.

[0060] FIG. 2A is a conceptual diagram illustrating an example delivery of stimulation signals to the nerves of the patient within a cardiac cycle of the patient. As illustrated in FIG. 2A, an example cardiac cycle of heart 102 may be represented as an electrocardiogram (ECG) signal 202 of heart 102. While the example delivery of stimulation signals illustrated in FIG. 2A is primarily described with reference to a cardiac, cardiovascular and systemic vascular parameter being a sensed nerve response from the patient, the techniques described below may be applied to manage the delivery of stimulation signals based on other cardiac, cardiovascular and systemic vascular parameters described herein.

[0061] ECG signal 202 may represent a single cardiac cycle of heart 102 and may define a plurality of complexes or waves within the cardiac cycle. ECG signal 202 may include a P wave 204, a Q wave 206, an R wave 208, a S wave 210, and a T wave 212. In some examples, Q wave 206, R wave 208, and S wave 210 are collectively referred to as a “QRS complex” of heart 102 and may indicate depolarization of a ventricle of heart 102.

[0062] In some examples, as illustrated in FIG. 2 A, system 100 may deliver a stimulation signal 218 between P wave 204 and Q wave 206, sense cardiac, cardiovascular and systemic vascular parameter values (e.g., ECAP values, as illustrated in FIG. 2A) during a first time window 214 (e.g., covering the QRS complex of ECG signal 202), deliver a stimulation signal 220 between S wave 210 and T wave 212, and sense cardiac, cardiovascular and systemic vascular parameter values (e.g., ECAP values, as illustrated in FIG. 2A) during a second time window (e.g., between delivery of stimulation signal 220 and T wave 212).

[0063] Stimulation signal 218 may be a different type of stimulation (e.g., may elicit a different type of response by heart 102) than stimulation signal 220. For example, stimulation signal 218 may be a parasympathetic nerve stimulation signal (e.g., may be configured to elicit aparasympathetic response in heart 102) and stimulation signal 220 may be a sympathetic nerve stimulation signal (e.g., may be configured to elicit a sympathetic response in heart 102). System 100 may deliver stimulation signals 218, 220 to target location 104 with different stimulation parameters (e.g., different timing, amplitude, frequency, duration, electrode selection, and the like). System 100 may only deliver stimulation signal 218, only deliver stimulation signal 220, and / or deliver both stimulation signals 218, 220 (e.g., as illustrated in FIG. 2A) within a single cardiac cycle.

[0064] System 100 may deliver stimulation signal 218 (e.g., a parasympathetic nerve stimulation signal) to target location 104 between P wave 204 and Q wave 206, e.g., to reduce pulmonary vascular resistance (PVR) as blood enters heart 102. System 100 may deliver stimulation signal 220 (e.g., a sympathetic nerve stimulation signal) to target location following the QRS complex to increase contractility as heart 102 expels blood out of heart 102 and into the vasculature of the patient.

[0065] System 100 may determine stimulation parameter values for stimulation signal 220 based on cardiac, cardiovascular and systemic vascular parameter values sensed from a prior time window (e.g., first time window 214 within a same cycle, time windows 214, 216 within a prior cardiac cycle). Based on the sensed cardiac, cardiovascular and systemic vascular parameter values, system 100 may adjust one or more parameters of seconds stimulation signal 220, e g., to address potential imbalance in the autonomic nervous system, to increase contractility after QRS complex of signal 202.

[0066] System 100 may determine stimulation parameter values for stimulation signal 218 based on cardiac, cardiovascular and systemic vascular parameter values sensed from a prior time window (e.g., one or more of windows 214, 216 within a prior cardiac and cardiovascular cycle). Based on the sensed cardiac, cardiovascular and systemic vascular parameter values, system 100 may adjust one or more parameters of stimulation signal 218, e g., to address potential imbalance in the autonomic nervous system, to reduce PVR of the cardiac cycle.

[0067] In some examples, system 100 may determine stimulation parameters for stimulation signals 218, 220 based on cardiac, cardiovascular and systemic vascular parameter values across two or more different cardiac cycles. In such examples, system 100 may continue to monitor sensed cardiac, cardiovascular and systemic vascular parameter values and may adjust stimulation parameters for stimulation signals 218, 220 based on changes in the sensed cardiac, cardiovascular and systemic vascular parameter values over time.

[0068] FIG. 2B is a conceptual diagram illustrating another example delivery of stimulation signals to nerves 106 of the patient within a cardiac cycle of the patient. As illustrated in FIG. 2B, an example cardiac cycle of heart 102 may be represented as an electrocardiogram (ECG)signal 202 of heart 102. While the example delivery of stimulation signals illustrated in FIG. 2B is primarily described with reference to a cardiac, cardiovascular and systemic vascular parameter being a sensed nerve response from the patient, the techniques described below may be applied to manage the delivery of stimulation signals based on other cardiac, cardiovascular and systemic vascular parameters described herein.

[0069] In some examples, as illustrated in FIG. 2B, system 100 may deliver a stimulation signal 222 at or around R wave 208 (e.g., at or around an apex of R wave 208) of ECG signal 202 and may deliver a stimulation signal 224 at or around T wave 212 (e.g., at or around an apex of T wave 212). Stimulation signal 222 may be an SNS stimulation signal and stimulation signal 224 may be a parasympathetic nerve stimulation signal.

[0070] System 100 may deliver stimulation signal 222 at or around R wave 208 of ECG signal 202 to increase contractility of heart 102 during a systole phase of heart 102. The increased contractility of heart 102 may assist in ventricular contraction of heart 102 during the systole phase. System 100 may deliver stimulation signal 224 at or around T wave 212, e.g., to reduce PVR during the ejection phase of the stole phase of the cardiac cycle and / or during the diastole phase of the cardiac cycle. System 100 may adjust stimulation parameters for stimulation signals 222, 224, to account for changes in the cardiac cycle (e.g., changes in cardiac cycle duration over time) and to maintain the cardiac, cardiovascular and systemic vascular function (e.g., contractility, PVR, heart rate, heart blood pressure.) of heart 102 throughout the cardiac cycles.

[0071] FIG. 2C is a conceptual diagram illustrating another example delivery of stimulation signals to nerves 106 of the patient within a cardiac cycle of the patient. As illustrated in FIG. 2C, cardiac cycles of heart 102 may be represented as an electrocardiogram (ECG) signal 202 of heart 102. FIG. 2C outlines systole phases 230 and diastole phases 232 of each cardiac cycle within ECG signal 202. While the example delivery of stimulation signals illustrated in FIG. 2C is primarily described with reference to a cardiac, cardiovascular and systemic vascular parameter being a sensed nerve response from the patient, the techniques described below may be applied to manage the delivery of stimulation signals based on other cardiac, cardiovascular and systemic vascular parameters described herein.

[0072] FIG. 2C illustrates signal 202 corresponding in time with ventricular volume 234 within heart 102. As illustrated in FIG. 2C, system 100 may deliver a first stimulation signal 236 during the ejection phase of the cardiac cycle (e.g., within systole phase 230). First stimulation signal 236 may cause a parasympathetic response in heart 102 and cause a decrease in the PVR of heart 102, e.g., during the ejection phase. System 100 may deliver second stimulation signal 238 during the filing phase of the cardiac cycle (e.g., within diastole phase 232). Secondstimulation signal 238 may cause a parasympathetic response in heart 102 and cause an increase in ventricular compliance, e.g., during the filing phase. System 100 may deliver both first stimulation signal 236 and second stimulation signal 238 within a single cardiac cycle or within different cardiac cycles. Delivery of first and second stimulation signals 236, 238 to nerves 106 may reduce filling pressure on heart 102 and / or any increases in ventricular stiffness over time, thereby reducing the demand on heart 102.

[0073] FIG. 2D is a conceptual diagram illustrating another example delivery of stimulation signals to nerves 106 of the patient within a cardiac cycle of the patient. As illustrated in FIG. 2D, cardiac cycles of heart 102 may be represented as an electrocardiogram (ECG) signal 202 of heart 102. FIG. 2D outlines systole phases 230 and diastole phases 232 of each cardiac cycle within ECG signal 202. While the example delivery of stimulation signals illustrated in FIG. 2D is primarily described with reference to a cardiac, cardiovascular and systemic vascular parameter being a sensed nerve response from the patient, the techniques described below may be applied to manage the delivery of stimulation signals based on other cardiac, cardiovascular and systemic vascular parameters described herein.

[0074] FIG. 2D illustrates signal 202 corresponding in time with ventricular volume 234 within heart 102. As illustrated in FIG. 2D, system 100 may deliver a stimulation signal 240 during the ejection phase of the cardiac cycle (e.g., within systole phase 230). Stimulation signal 240 may cause a sympathetic response in heart 102 and cause an increase in contractility of heart 102, e.g., during the ejection phase. Delivery of stimulation signal 240 to nerves 106 may increase cardiac output of heart 102 without increasing the heart rate of heart 102. Delivery of stimulation signal 240 may assist in the return of heart 102 to a compensated state and facilitate continuous cardiac function of heart 102 in the compensated state.

[0075] FIG. 3 is a conceptual diagram illustrating an example implantable lead 300 of system 100 of any of FIGS. 1A-1C. Implantable lead 300 may be one example of implantable lead 118 connecting one or more of electrodes 124A, 124B to IMD 108B. While implantable lead 300 is primarily described herein as being coupled to IMD 108B illustrated in FIG. IB, implantable lead 300 may be used in conjunction with any other IMD described herein.

[0076] Implantable lead 300 may define an elongated body 302 extending from a proximal end 304 to a distal end 306. Elongated body 302 may be sized to be disposed within a blood vessel of the patient. Elongated body 302 may define a length sufficient place distal end 306 in a blood vessel at or around target location 104 when IMD 108B is implanted in another location within the body of the patient, e.g., in an extravascular, subcutaneous pocket within the body of the patient, in the torso of the patient.

[0077] Implantable lead 300 may define a distal portion 308 at or around distal end 306. Distal portion 308 may include electrodes 310 disposed on an outer portion of a portion of elongated body 302 defining distal portion 308. Electrodes 310 may be one example of electrodes 124A, 124B as illustrated in FIG. IB. Distal portion 308 may include one, two or three or more electrodes 310. Distal portion 308 may be configured to expand radially outwards into an expanded configuration within a blood vessel. In the expanded configuration distal portion 308 may define a helix (e.g., as illustrated in FIG. 3), an expanded basket, expanded prongs, or the like.

[0078] When expanded, distal portion 308 may place electrodes 310 in contact with a blood vessel wall, e.g., to enable transmission of stimulation signals from electrodes 310 into the tissue at or around blood vessel wall (e.g., nerves 106). IMD 108B may deliver stimulation signals via different selections of electrodes 310 to deliver stimulation signals to different tissue regions around the blood vessel (e.g., to stimulate different nerves 106 and / or elicit different responses in nerves 106). Each of electrodes 310 may be electrically coupled to IMD 108B via a corresponding electrical contact disposed at proximal end 304 of elongated body 302.

[0079] FIG. 4 is a conceptual diagram illustrating another example of an implantable lead 400 of system 100 of any of FIGS. 1A-1C. Implantable lead 400 may include pacing electrode(s) (e.g., pacing electrode 122, not pictured in FIG. 4) at or around a distal portion of implantable lead 400. While implantable lead 400 is primarily described herein as being coupled to IMD 108B illustrated in FIG. IB, implantable lead 400 may be used in conjunction with any other IMD described herein.

[0080] Implantable lead 400 may include an elongated body 402 extending from a proximal end to a distal end and a fixation feature 406 disposed at or around the distal end of elongated body 402. The proximal end of elongated body 402 may be coupled to IMD 108B. the pacing electrode(s) of implantable lead 400 may be electrically connected to IMD 108B via electrical contact(s) extending along the length of elongated body 402. IMD 108B may deliver cardiac pacing signals to cardiac tissue of heart 102 via implantable lead 400 and the pacing electrode(s) disposed on implantable lead 400.

[0081] Fixation feature 406 may be configured to puncture cardiac tissue of heart 102 and affix implantable lead 400 to a target site within heart 102 (e.g., within the RV of heart 102, at or around a triangle of Koch of heart 102). Fixation feature 406 may include, but is not limited to, a fixation helix, a fixation side helix, fixation tine(s), fixation barb(s), or the like. In some examples, at least a portion of fixation feature 406 defines pacing electrode(s). In some examples, pacing electrode(s) are disposed at or around the distal end of elongated body 402 (e.g., around or proximal to fixation feature 406).

[0082] FIG. 5 is a conceptual diagram illustrating another example of an implantable lead 130A of system 100 of any of FIGS. 1A-1C. While implantable lead 130A is primarily described herein as being coupled to IMD 108C illustrated in FIG. 1C, implantable lead 130A may be used in conjunction with any other IMD described herein. Implantable lead 130B illustrated in FIG. 1C may be substantially similar to implantable lead 130A.

[0083] Implantable lead 130A may define an elongated body 502 extending from proximal end 504 to distal end 506. Distal end 506 may define an expandable electrode array 508 including a plurality of electrodes 510. Each of electrodes 510 may be electrically connected to a corresponding electrical contact disposed at proximal end 504. IMD 108C may transmit electrical signals to electrodes 510 and / or sense electrical signals from electrodes 510 via the electrical contacts at proximal end 504.

[0084] Distal end 506 of elongated body 502 may assume a radially expanded configuration where electrodes 510 are placed in contact with a vessel wall of a blood vessel within target location 104. Distal end 506 may assume a basket configuration, e.g., as illustrated in FIG. 5, to place electrodes 510 in contact with the vessel wall without substantially restricting blood flow in the blood vessel. Electrodes 510 may be configured to transmit electrical signals into and / or sense electrical signals from tissue at or around the vessel wall. IMD 108C may select different combinations of electrodes 510 for sensing and / or stimulation. The sensed regions and / or stimulated regions around a blood vessel may be dependent on the select electrodes 510. IMD 108C may elicit a sympathetic or parasympathetic response in heart 102 by stimulating nerves 106 with different combinations of electrodes 510 on implantable lead 130A.

[0085] FIG. 6 is a block diagram illustrating components of an example implantable medical device (IMD) 108 of the medical device system of any of FIGS. 1A-1C. IMD 108 may be an example configuration of any of the IMDs described herein (e.g., IMD 108A, 108B, 108C). As shown in FIG. 2, IMD 12 includes processing circuitry 110, sensing circuitry 608, signal generation circuitry 112, switch circuitry 604, sensor(s) 610, communication circuitry 116, memory 114, and power source 612. IMD 108 may include one or more electrodes 606A-606N (collectively referred to as “electrodes 606”) coupled to IMD 108. Electrodes 606 may be disposed on implantable leads coupled to housing 602 of IMD 108 and may include, but are not limited to, electrodes 120, 122, 124, 510, or the like.

[0086] Memory 114 may include computer-readable instructions that, when executed by processing circuitry 110, cause IMD 108 and processing circuitry 110 to perform various functions attributed to IMD 108 and processing circuitry 110 herein. Memory 114 may include any volatile, non-volatile, magnetic, optical, or electrical media, such as a random-accessmemory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media.

[0087] Processing circuitry 110 may include fixed function circuitry and / or programmable processing circuitry. Processing circuitry 110 may include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or equivalent discrete or analog logic circuitry. In some examples, processing circuitry 110 may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry. The functions attributed to processing circuitry 102 herein may be embodied as software, firmware, hardware or any combination thereof.

[0088] Switch circuitry 604 may be configured to (e.g., in response to instructions from processing circuitry 110) switch the coupling of one or more of electrodes 606 between signal generation circuitry 112 and sensing circuitry 608. In some examples, such as when another IMD and / or sensor(s) are configured to sense signals (e.g., cardiac, cardiovascular and systemic vascular signals) from the patient. IMD 108 may not include sensing circuitry 608 and / or sensor(s) 610. In such examples, electrodes 6 may be directly coupled to signal generation circuitry 112. Switching circuitry 604 may include one or more transistors or other circuitry for selectively coupling electrodes 606 to other circuitry of IMD 108.

[0089] Processing circuitry 110 may monitor cardiac, cardiovascular and systemic vascular parameters (e.g., heart rate, heart blood pressure, signal(s) indicative of nerve response) via one or more of electrodes 606 and / or of sensor(s) 610. Signal generation circuitry 112 and / or sensing circuitry 608 may include circuitry to generate a signal, e.g., current or voltage source circuitry, having a known current or voltage amplitude, and switching circuitry 604 may couple the signal to selected electrodes of electrodes 606. Sensing circuitry 608 may include circuitry to sample the electrical signals from electrodes 606 and / or sensor(s) 610 to determine cardiac, cardiovascular and systemic vascular parameter values based on the electrical signals. In some examples, processing circuitry 110 may determine, based on the cardiac, cardiovascular and systemic vascular parameter values, whether to deliver sympathetic and / or parasympathetic nerve stimulation signals to the patient via one or more of electrodes 606. Processing circuitry 110 may determine stimulation parameter values and / or whether to deliver stimulation signals to the patient based on the cardiac, cardiovascular and systemic vascular parameter values. Processing circuitry 110 may determine whether to deliver a type of stimulation signal (e.g., sympathetic and / or parasympathetic nerve stimulation signals) and / or determine the stimulation parameter values for the stimulation signal based on whether one or more cardiac, cardiovascular andsystemic vascular parameter values satisfy a corresponding threshold condition (e.g., a threshold minimum heart rate, a threshold maximum heart rate, a threshold minimum blood pressure, a threshold maximum blood pressure, a threshold nerve response frequency, a threshold nerve response amplitude, etc.).

[0090] Sensor(s) 610 may include one or more sensing elements configured to sense one or more cardiac, cardiovascular and systemic vascular parameters from the patient. Sensor(s) 610 may include, but are not limited to, sensing electrodes, a heart rate sensor, a blood pressure sensor, impedance sensor, or the like. Each of sensor(s) 610 may produce a signal (e.g., an electrical signal) corresponding to one or more cardiac, cardiovascular systemic vascular parameters. Sensing circuitry 608 and / or processing circuitry 110 may analyze the signals from sensor(s) 610 to determine cardiac, cardiovascular and systemic vascular parameter values corresponding to the signals. Sensor(s) 610 may be disposed within housing 602 of IMD 108, disposed on an outer surface of housing 602, and / or separately disposed within the body of patient and / or in one or more other IMDs and communicatively coupled to processing circuitry 110 and / or to sensing circuitry 608 via communications circuitry 116. Sensing circuitry 608 may include filters, amplifiers, and / or analog-to-digital conversion circuitry, as examples, to condition any of these sensed signals for analysis by processing circuitry 110 and / or to detect cardiac, cardiovascular and systemic vascular parameter values based on the signals. Sensing circuitry 104 may include rectification circuitry, sample-and-hold circuitry, one or more comparators, and / or analog-to-digital conversion circuitry. The functionality provided by such circuitry may be applied to the signal in the analog or digital domain.

[0091] Processing circuitry 110 may modify one or more stimulation parameters for a stimulation signal based on sensed cardiac, cardiovascular and systemic vascular parameter value(s). Stimulation parameter values may be stored in memory 114. Processing circuitry 110 may determine, based on the cardiac, cardiovascular and systemic vascular parameter value(s), whether the autonomic nervous system of the patient is imbalanced and, if so, the type of imbalance (e.g., whether the autonomic nervous system has an excessive sympathetic or parasympathetic response). Processing circuitry 110 may adjust stimulation parameter values to elicit a response in the autonomic nervous system, e.g., to balance the autonomic nervous system and / or temporarily elicit a sympathetic or parasympathetic response in heart 102. In some examples, processing circuitry 110 determine to elicit a sympathetic or parasympathetic response in heart 102 based on a determination that one or more cardiac, cardiovascular and systemic vascular parameter values satisfy a threshold condition (e.g., is below a threshold minimum cardiac, cardiovascular and systemic vascular parameter value, is above a threshold maximum cardiac, cardiovascular and systemic vascular parameter value).

[0092] As IMD 108 continues to sense cardiac, cardiovascular and systemic vascular parameter values, processing circuitry 110 may continue to monitor and adjust stimulation parameter values, e.g., to maintain balance in the autonomic nervous system of the patient. Stimulation parameter values may include, but are not limited to, a timing of the stimulation signal, a frequency of the stimulation signal, a duration of the stimulation signal, a number of stimulation pulses within the stimulation signal, an amplitude of the stimulation signal, a ratio of the duration of the stimulation signal to a duration of another stimulation signal (e.g., a ratio of the duration of an sympathetic nerve stimulation signal to the duration of a parasympathetic nerve stimulation signal), a duty cycle of the stimulation signal, a pulse width of a pulse of the stimulation signal, a ramp up time for the pulse of the stimulation signal, a ramp down time for the pulse of the stimulation signal, or a selection of electrodes from electrodes 606 for delivery of the stimulation signal.

[0093] Signal generation circuitry 112 may include one or more regulated current sources or sinks. Each of electrodes 610 may be configured to be coupled to a corresponding current source or sink of signal generation circuitry 112. Signal generation circuitry 112 may include circuitry for generating a signal, such as one or more capacitors, charge pumps, and / or current sources, as well as circuitry for selectively coupling the signal to electrodes 606, e.g., transistors or other switching circuitry. Signal generation circuitry 112 may be configured to, in response to instructions from processing circuitry 110, generate one or more stimulation signals and / or pacing signals to be delivered to the patient. Signal generation circuitry 112 may generate stimulation signals based on stimulation parameters stored in memory 114 and / or based on stimulation parameter determined by processing circuitry 110.

[0094] Signal generation circuitry 112 may transmit stimulation signals to the patient electrodes 606 in one or more stimulation modes. Stimulation modes may include, but are not limited to, monopolar, unipolar or bipolar stimulation modes. Signal generation circuitry 112 may determine, for each stimulation signal, the stimulation mode based at least in part on the stimulation parameters for the stimulation signal (e.g., based on the electrode selection for the stimulation signal). Signal generation circuitry 12 may transmit stimulation signals in a cathodal mode to stimulation nerves 106 and / or transmit stimulation signals in an anodal mode, e.g., to block afferent conduction along nerves 106 and / or to stimulate nerves 106 at determined frequency.

[0095] Communication circuitry 116 may include any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as an external programmer, or another IMD or sensor. Communication circuitry 116 may include voltage regulators, current generators, oscillators, or circuitry for generating a signal, resistors,capacitors, inductors, and other filtering circuitry for processing received signal, as well as circuitry for modulating and / or demodulating a signal according to a communication protocol. Communication circuitry 116 may also include transistors or other switching circuitry for selectively coupling transmitted signal to or receiving signals from an antenna of IMD 108 (not shown) or electrodes 606 (e.g., in the case of tissue conductance communication (TCC)). Under the control of processing circuitry 110, communication circuitry 116 may receive signals from and / or transmit signals to another device. In some examples, communications circuitry 116 receives sensed cardiac, cardiovascular and systemic vascular parameter values from another IMD or sensor(s) coupled to the body of the patient. In some examples, communications circuitry 116 transmits determined stimulation parameter values to another computing device. In some examples, communication circuitry 116 communicates with a networked computing device via an external device and a computer network, such as the Medtronic CareLink® Network developed by Medtronic, pic, of Dublin, Ireland.

[0096] A clinician or another user may retrieve data from IMD 108 using an external programmer and / or another local or networked computing device (e.g., a remote computer located with the clinician) configured to communicate with processing circuitry 110 via communication circuitry 116. In some examples, the clinician may also program parameters of IMD 108 (e.g., stimulation parameters, threshold cardiac, cardiovascular and systemic vascular parameter values) using the external programmer or another local or networked computing device. For example, the clinician may update stimulation parameter values and / or threshold cardiac, cardiovascular and systemic vascular parameter values, e.g., based on changes in patient physiology and / or disease state.

[0097] Any steps described herein as being carried out by processing circuitry 110 of IMD 108 may carried out by processing circuitry of one or more other devices. For example, processing circuitry of an external programmer, a remote computer, or any other suitable implantable or external device or server, may be configured to carry out one or more of the steps of the techniques described herein, such as via communication circuitry 116 of IMD 108.

[0098] FIG. 7 is a flow chart illustrating an example process of delivering stimulation signals to the nerves of the patient using the medical device system illustrated in any of FIGS. 1 A-6. While the example process illustrated in FIG. 7 is primarily described below with reference to system 100 including IMD 108 A, the example process may be performed using any IMD and / or combination of components for system 100 as described herein. Additionally, the steps within the example process illustrated in FIG. 7 may be performed in other orders.

[0099] IMD 108A (e.g., processing circuitry 110 of IMD 108A) of system 100 may determine a first cardiac, cardiovascular and / or systemic vascular parameter of a patient based oncardiac, cardiovascular, and / or systemic vascular signals (702). Cardiac, cardiovascular and systemic vascular parameters of the patient may be indicative of cardiac, cardiovascular and systemic vascular function and / or hemodynamic output of heart 102 of the patient. Cardiac, cardiovascular and systemic vascular parameter may include, but are not limited to, a heart rate, a heart blood pressure, and / or nerve response (e.g., action potential signals) to the cardiac, cardiovascular and systemic vascular function of the patient. In some examples, IMD 108 A may sense electrical signals corresponding to cardiac, cardiovascular and systemic vascular parameters via electrodes coupled to IMD 108A (e.g., electrodes 120, 124, 130, 606) and / or sensor(s) 610 coupled to IMD 108 A. Processing circuitry 110 and / or sensing circuitry 608 may then analyze the electrical signals to determine cardiac, cardiovascular and systemic vascular parameter values corresponding to the electrical signals. In some examples, one or more other IMDs and / or sensor(s) separate from IMD 108 A and coupled to the patient may sense the electrical signals. IMD 108 A may receive the electrical signals for analysis via communications circuitry 116. In some examples, another computing device (e.g., an external programmer) may determine the cardiac, cardiovascular and systemic vascular parameter values based on the electrical signals. In such examples, processing circuitry 110 may receive the cardiac, cardiovascular and systemic vascular parameter values from the other computing device via communications circuitry 116.

[0100] IMD 108A may determine stimulation parameter(s) for a first stimulation signal (e.g., stimulation signal 218, stimulation signal 224) based on the first cardiac, cardiovascular and systemic vascular parameters (704). Stimulation parameters may include, but are not limited to, a timing of the stimulation signal, a frequency of the stimulation signal, a duration of the stimulation signal, a number of stimulation pulses within the stimulation signal, an amplitude of the stimulation signal, a ratio of the duration of the stimulation signal to a duration of another stimulation signal, a duty cycle of the stimulation signal, a pulse width of a pulse of the stimulation signal, a ramp up time for the pulse of the stimulation signal, a ramp down time for the pulse of the stimulation signal, or a selection of electrodes for delivery of the stimulation signal.

[0101] Processing circuitry 110 may determine values for one or more stimulation parameters based on the cardiac, cardiovascular and systemic vascular parameter values to elicit a response in the autonomic nervous system (e.g., a sympathetic response). Processing circuitry 110 may select stimulation parameter values to elicit a sympathetic response based on a determination that the cardiac, cardiovascular and systemic vascular parameter values indicate a reduced heart rate, reduced blood pressure in heart 102, and / or reduced contractility of heart 102, e.g., by comparing cardiac, cardiovascular and systemic vascular parameter values tocorresponding threshold cardiac, cardiovascular and systemic vascular parameter values. Processing circuitry 110 may select stimulation parameter values to elicit a sympathetic response in heart 102 during a specific portion of the cardiac cycle of heart 102, e.g., to improve cardiac, cardiovascular and systemic vascular function and / or hemodynamic output through the cardiac cycle. For example, processing circuitry 110 may select stimulation parameter values to elicit a sympathetic response in heart 102 between S wave 210 and T wave 212 of a cardiac cycle of heart 102 and / or at or around R wave 208 of the cardiac cycle.

[0102] In some examples, processing circuitry 110 determines, based on the cardiac, cardiovascular and systemic vascular parameter values, one or more autonomic reflexes (e.g., Baroreflex, chemical reflex) exhibited by the patient. For example, processing circuitry 110 may determine the presence of the Baroreflex based on a determination of whether the patient is experienced a decrease in heart rate alongside a decrease in blood pressure. In some examples, processing circuitry 110 determines the presence of a chemical reflex based on a determination of whether the patient is experiencing an increase in blood pressure alongside an increase in heart rate. Processing circuitry 110 may determine stimulation parameter values to address the autonomic reflexes and balance the autonomic nervous system.

[0103] IMD 108 A may deliver the first stimulation signal to the patient to cause a sympathetic effect (706). Processing circuitry 110 may select one or more electrodes within target location 104 (e.g., electrode 120) for delivery of the first stimulation signal to one or more of nerves 106 with target location 104 to cause a sympathetic effect (e.g., to elicit a sympathetic response in heart 102). Processing circuitry 110 may cause signal generation circuitry 112 to generate the first stimulation signal in accordance with the determines stimulation parameter values and to transmit the first stimulation signal along implantable lead 118, through electrode 120, and into nerves 106 at or around target location 104. Processing circuitry 110 may case signal generation circuitry 112 to generate and transmit one or more pulses of the first stimulation signal and / or in accordance with a timing determined by processing circuitry 110, e.g., to cause the sympathetic effect during specific time windows within each of one or more cardiac cycles of heart 102.

[0104] IMD 108 A may determine a second cardiac, cardiovascular and systemic vascular parameter of the patient based on cardiac, cardiovascular, and / or systemic vascular signals (708). Processing circuitry 110 may determine the second cardiac and cardiovascular parameter, e.g., in a manner similar to the determination of the first cardiac, cardiovascular and systemic vascular parameter previously described above. The second cardiac, cardiovascular and systemic vascular parameter may be the same as or different from the first cardiac and cardiovascular parameter. In some examples, where the first and second cardiac, cardiovascular and systemic vascularparameters are the same, the values for the first and second cardiac, cardiovascular and systemic vascular parameters may be the same or may be different (e.g., the values may be sensed during different time periods and / or with different sensor(s) 610 and / or electrodes).

[0105] IMD 108 A may determine stimulation param eter(s) for a second stimulation signal (e.g., stimulation signal 220, stimulation signal 222) based on the second cardiac, cardiovascular and systemic vascular parameter (710). Processing circuitry 110 may determine the stimulation parameter(s) for the second stimulation signal, e.g., in a manner similar to the determination of stimulation parameter(s) for the first stimulation signal previously described above.

[0106] The second stimulation signal may be configured to elicit a parasympathetic response in heart 102. Processing circuitry 110 may select, for the second stimulation values, the same or different stimulation parameters as the first stimulation signals. In some examples, where processing circuitry 110 selects values for at least one stimulation parameter for both the first simulation signal and the second stimulation signal, the values for the at least one stimulation parameter may be unique to each stimulation signal or maybe the same for both stimulation signals. Processing circuitry 110 may select, for the second stimulation signal, a same or different selection of electrodes for delivery of the second stimulation signal. In some examples, processing circuitry 110 selects the same electrodes for delivery of the first and second stimulation signals. In such examples, processing circuitry 110 may select different stimulation parameter values for each stimulation signal to cause each stimulation signal to elicit the corresponding effect on heart 102.

[0107] IMD 108 A may deliver the second stimulation signal to the patient to cause a parasympathetic effect (712). Processing circuitry 110 may deliver the second stimulation signal in accordance with the determined stimulation parameters and / or with different selections of electrodes to elicit the parasympathetic effect. IMD 108 A may deliver the second stimulation signal prior to or following the first stimulation signal. Processing circuitry 110 may cause signal generation circuitry 112 to generate and transmit the second stimulation signal based on the determined stimulation parameter, e.g., in a manner similar to the generation and transmission of the first stimulation signal previously described above.

[0108] FIG. 8 is a flow chart illustrating another example process of delivering stimulation signals to nerves 106 of the patient using system 100 illustrated in any of FIGS. 1 A-6. While the example process illustrated in FIG. 8 is primarily described below with reference to system 100 including IMD 108 A, the example process may be performed by any other medical device system described herein, with any combination of the components described herein. While the example process is primarily described with reference to a cardiac, cardiovascular and systemic vascular parameter being a heart rate of the patient, the example process may be performed withany other cardiac, cardiovascular and systemic vascular parameter described herein (e.g., heart blood pressure, nerve response to cardiac activity, etc.).

[0109] System 100 may sense cardiac, cardiovascular and / or systemic vascular signals from the patient (802). System 100 may sense the cardiac, cardiovascular and systemic vascular signals via one or more electrodes coupled to IMD 108 A, via sensor(s) 610 of IMD 108 A, and / or via one or more other IMDs and / or sensor(s) coupled to the body of the patient. System 100 may sense electrical signals from the patient corresponding to the cardiac, cardiovascular and systemic vascular signals. System 100 (e.g., processing circuitry 110 of IMD 108A) may analyze the electrical signals to determine the cardiac, cardiovascular and systemic vascular signals. IMD 108 A (e.g., processing circuitry 110) may determine a heart rate of the patient based on the sensed cardiac, cardiovascular and systemic vascular signals (804).

[0110] Processing circuitry 110 of IMD 108A may determine whether the determined heart rate satisfies a threshold heart rate (806). Threshold heart rate may be a threshold cardiac, cardiovascular and systemic vascular parameter value and may be a threshold maximum heart rate of a threshold minimum heart rate. The threshold maximum heart rate may correspond to a maximum heart rate within an acceptable heart rate range for the patient. The threshold minimum heart rate may correspond to a minimum heart rate within the acceptable heart range. The threshold heart rate may be inputted into system 100 by a clinician and / or may be adjusted over time based on trends in sensed patient heart rate values. Processing circuitry 110 may determine that the patient has satisfied the threshold heart rate based on a determination that the determined heart rate is less than or equal to the threshold heart rate, or vice versa.[OHl] Based on a determination that the determined heart rate satisfies the threshold heart rate (“YES” branch of 806), IMD 108 A may stimulate nerve(s) of the patient with a first stimulation signal (808). Based on a determination that the determined heart rate does not satisfy the threshold heart rate (“NO” branch of 806), IMD 108 A may stimulate the nerve(s) of the patient with a second stimulation signal. The first stimulation signal may elicit a sympathetic effect in the heart and the second stimulation signal may elicit a parasympathetic effect in the heart, or vice versa. The first stimulation signal may be at least one of, but is not limited to, stimulation signal 220 or stimulation signal 222 and the second stimulation signal may be at least one of, but is not limited to, stimulation signal 218 or stimulation signal 224, or vice versa. In some examples, IMD 108A may not deliver any stimulation signals in response to a determination that the determined heart rate satisfies the threshold heart rate and may deliver a stimulation signal in response to a determination that the determined heart rate does not satisfy the threshold heart rate, or vice versa.

[0112] After stimulation of nerve(s) of the patient with the first or the second stimulation signal, (808, 810), system 100 may continue to sense cardiac, cardiovascular and systemic vascular signals from the patient (802) and repeat the process illustrated in FIG. 8. System 100 may deliver the first and second stimulation signals to the patient in accordance with the process illustrated in FIG. 8, e.g., to maintain balance within the autonomic nervous system. Delivery of the first and second stimulation signals based on whether the threshold heart rate is satisfied may maintain cardiac, cardiovascular and systemic vascular function and hemodynamic output of heart 102.

[0113] FIG. 9 is a flow chart illustrating another example process of delivering stimulation signals to nerves 106 of the patient using system 100 illustrated in any of FIGS. 1 A-6. While the example process illustrated in FIG. 9 is primarily described below with reference to system 100 including IMD 108 A, the example process may be performed by any other medical device system described herein, with any combination of the components described herein.

[0114] System 100 may sense, by an IMD (e.g., IMD 108A), one or more cardiac, cardiovascular and / or systemic vascular parameter values from the patient (902). IMD 108 A may sense cardiac, cardiovascular and systemic vascular parameter values from the patient in accordance with one or more example techniques previously described herein (e.g., with reference to FIG. 7). System 100 may determine a type of nerve stimulation for each of one or more electrodes (e.g., electrode 120, electrodes 124, electrodes 130, electrodes 606) coupled to the IMD. Each electrode may be disposed at a separate location within target location 104 and may be adjacent to a different combinations of nerve fibers of nerves 106. Types of nerve stimulation may include, but are not limited to, sympathetic nerve stimulation or parasympathetic nerve stimulation. IMD 108 A may determine the types of stimulation for different electrodes to elicit sympathetic and / or parasympathetic responses in heart 102. For example, IMD 108A may o transmit sympathetic nerve stimulation through a first electrode to elicit a sympathetic response in a first set of nerve fibers around the first electrode and may transmit parasympathetic nerve stimulation through a second electrode to elicit a parasympathetic response in a second set of nerve fibers around the second electrode.

[0115] System 100 may select stimulation parameters to cause IMD 108 A to stimulate, via one or more electrodes, nerve(s) of a parasympathetic nervous system (PSNS) of the patient after a first feature in a cardiac cycle of the patient (906). Nerve(s) of the PSNS may be next to and / or intertwined with other nerves (e.g., as a part of a sympathetic trunk of the patient). System 100 may select stimulation parameters to active nerve(s) of the PSNS without activating other nerves around the target nerve(s) of the PSNS. Activation of the nerve(s) of the PSNS may elicit a parasympathetic response in heart 102. System 100 may select stimulation parameters tostimulate the nerves of the PSNS between P wave 204 and Q wave 206 and / or at or around T wave 212.

[0116] System 100 may select stimulation parameters to cause IMD 108 A to stimulate, via one or more electrodes, nerve(s) of a sympathetic nervous system (SNS) of the patient after a second feature in a cardiac cycle of the patient (908). Nerve(s) of the SNS may be next to and / or intertwined with other nerves (e.g., with nerve(s) of the PSNS, as a part of the sympathetic trunk of the patient). System 100 may select stimulation parameters to active nerve(s) of the SNS without activating other nerves around the target nerve(s) of the SNS. Activation of the nerve(s) of the SNS may elicit a sympathetic response in heart 102. System 100 may select stimulation parameters to stimulate the nerves of the SNS after S wave 210 and / or at or around R wave 208.

[0117] System 100 may adjust the stimulation parameters based on an intended effect on heart 102 of the patient (910). System 100 may adjust the stimulation parameters based at least in part on the cardiac, cardiovascular and systemic vascular parameter values. In some examples, system 100 may adjust the stimulation parameters based at least in part on patient response to previously transmitted stimulation signals (e.g., to nerve(s) of PSNS and / or SNS). System 100 may adjust the stimulation parameters based on a detected imbalance in the autonomic nervous system, a change in cardiac, cardiovascular and systemic vascular function, and / or a change in hemodynamic output (e.g., based on changes in cardiac, cardiovascular and systemic vascular parameter values and / or based on patient feedback). System 100 may adjust the stimulation parameters to increase or decrease one or more of the sympathetic or parasympathetic response of heart 102 to stimulation signals, thereby balancing the autonomic nervous system, improving cardiac, cardiovascular and systemic vascular function, and / or improve hemodynamic output.System 100 may deliver, via the one or more electrodes, stimulation signal(s) to the patient based on the adjusted stimulation parameters (912). System 100 may deliver stimulation signal(s) to the patient in accordance with the example techniques previously described herein.

[0118] FIG. 10 is a flow chart illustrating another example process of delivering stimulation signals to nerves 106 of the patient using system 100 illustrated in any of FIGS. 1 A-6. While the example process illustrated in FIG. 10 is primarily described below with reference to system 100 including IMD 108 A, the example process may be performed by any other medical device system described herein, with any combination of the components described herein. Additionally, steps of the example process illustrated in FIG. 10 may be performed alone or in conjunction with the example processes illustrated in any of FIGS. 7-9.

[0119] System 100 may determine a cardiac, cardiovascular and / or systemic vascular parameter of a patient (1002), determine stimulation parameter(s) for a stimulation signal based on the cardiac, cardiovascular and systemic vascular parameter (1004), and deliver thestimulation signal to the patient to elicit an autonomic response in the patient (1006). The autonomic response may be a sympathetic or a parasympathetic response. System 100 may perform steps 1002-1006 in accordance with the example techniques previously described herein.

[0120] System 100 may receive signals corresponding to autonomic markers (1008). Autonomic markers may indicate a type of autonomic activation (e.g., sympathetic activation, parasympathetic activation) within nerves 106. Values for autonomic markers may indicate whether nerves 106, and by extension heart 102, are experiencing a sympathetic or a parasympathetic response and / or a magnitude of the response. Autonomic markers may include, but are not limited to, cardiac, cardiovascular and systemic vascular parameter values, corresponding to autonomic reflexes, and / or parameters corresponding to cardiac and cardiovascular and systemic vascular function such as, but are not limited to, heart rate, a duration of a QRS complex of a cardiac cycle, a duration of an ST interval of a cardiac cycle, a size and / or volume of one or more chambers of heart 102, a pumping speed of heart 102, or the like.

[0121] In some examples, IMD 108 A is configured to sense, e.g., via electrodes 606 and / or sensor(s) 610, electrical signals corresponding to one or more autonomic markers. Processing circuitry 110 of IMD 108 A may analyze the electrical signals to determine autonomic marker values based on the received signals (1010). In some examples, processing circuitry 110 may receive the electrical signals from another IMD and / or sensor(s) coupled to the patient and determine the autonomic marker values based on the electrical signals. In some examples, processing circuitry 110 may directly receive the autonomic marker values, e.g., from another computing device of system 100.

[0122] System 100 may sense the electrical signals corresponding to the one or more autonomic markers after system 100 has delivered the stimulation signals. For example, system 100 may sense the electrical signals for a specified period of time (e.g., up to 10 seconds) after delivery of the stimulation signals. In some examples, system 100 senses the electrical signals while IMD 108 A delivers the stimulation signal to nerves 106 of the patient.

[0123] IMD 108 A may determine whether the autonomic marker values satisfy a threshold autonomic marker value (1012). The threshold autonomic marker value may correspond to one or more of an expected autonomic marker value in response to the delivery of the stimulation signal or an autonomic marker value indicating that the patient is not experiencing decreased cardiac, cardiovascular and systemic vascular function, decreased hemodynamic output, and / or a cardiac, cardiovascular and systemic vascular event associated with a cardiac and cardiovascular condition (e.g., ischemia, heart failure and hypertension). Processing circuitry 110 may determinethat the autonomic marker values satisfies the threshold autonomic marker value based on a determination that the determined autonomic marker values are less than or equal, greater than or equal to, or within a threshold range of the threshold autonomic marker value.

[0124] Based on a determination that the autonomic marker values do not satisfy the threshold autonomic marker value (“NO” branch of 1012), IMD 108A may adjust one or more stimulation parameters of the stimulation signal (1014) and deliver the stimulation signal to the patient to elicit an autonomic response in the patient (1006) based on the adjusted stimulation parameters. IMD 108 A may adjust the one or more stimulation parameters of the stimulation signal in accordance with any of the example techniques previously described herein. In some examples, IMD 108 A adjusts one or more stimulation parameters of the stimulation signal by adjusting a stimulation site (e.g., within target location 104) and / or a stimulation mode of the stimulation signal.

[0125] Based on a determination that the autonomic marker values satisfy the threshold autonomic marker value (“YES” branch of 1012), IMD 108 A may continue to transmit the stimulation signal to the patient (e.g., without adjust the stimulation parameter(s) of the stimulation signal). IMD 108 A may determine that a threshold period of time has elapsed since an adjustment of one or more stimulation parameters of the stimulation signal (1016), e.g., during steps 1004, 1014 of the example process of FIG. 10. The threshold period of time may be up to 1 hour, up to 24 hours, up to 48 hours, up to 1 week, etc. Based on a determination that the threshold period of time has elapsed, IMD 108 A may perform steps 1002-1016 of the example technique illustrated in FIG. 10, as described above.

[0126] In some examples, as illustrated in FIG. 10, system 100 may adjust stimulation parameters of stimulation signal(s), e.g., to maintain the balance of the autonomic nervous system, maintain cardiac, cardiovascular and systemic vascular function of the patient, and / or maintain the hemodynamic output of the patient over an extended period of time. The adjustments of the stimulation parameters may be based on the patient’s response to the stimulation signal(s) and / or may be time-based. In such examples, system 100 may continuously monitor and control stimulation parameters of stimulation signal(s) regardless of whether there are observable changes in patient response to receiving the stimulation signals.

[0127] FIG. 11 A is a conceptual diagram illustrating an example of implantable lead 1100, which is an example implanted lead 300 of FIG. 3 in an expanded configuration. FIG. 1 IB is a conceptual diagram illustrating implantable lead 1100 of FIG. 11 A in a collapsed configuration. Implantable lead 1100 may be an example of implantable lead 300 and may be substantially similar to implantable lead 300, aside from the elements described below.

[0128] Implantable lead 1100 may define an elongated body 302 extending from a proximal end 304 to distal end 306. Elongated body 302 may define a distal portion 308 at or around distal end 306. Elongated body 302 may extend along longitudinal axis 1101. Elongated body 302 may define an inner lumen 1114 extending along longitudinal axis 1101. Inner lumen 1114 may extend at least partially through elongated body 302. In some examples, inner lumen 1114 may extend through distal end 306 (e.g., through a header defining distal end 306 of elongated body 302). Inner lumen 1114 may be sized to receive a guide element 1112 (e.g., a stylet, a guidewire), a sensing element (e.g., a pressure sensor), or the like. Implantable lead 1100 may include a plurality of electrodes 310 disposed on elongated body 302 at or around distal portion 308. Each of electrodes 310 may extend partially or entirely around an outer perimeter of elongated body 302.

[0129] A tether 1104 may be at least partially disposed within implantable lead 1100. Tether 1104 may enter elongated body 302 through port 1106. When implantable lead 1100 is disposed within the patient body, port 1106 may be outside of the patient body. From port 1106, tether 1104 may extend through elongated body 302 to distal end 306. A distal end 1116 of tether 1104 may be coupled to distal end 306, e.g., to a header defining distal end 306. Tether 1104 may be disposed within inner lumen 1114 or between inner lumen 1114 and an outer surface of elongated body 302. Tether 1104 may be formed from one or more of a high-strength composite material and / or polymer (e.g., Dyneema® available from Avient Corporation of Minneapolis, Minnesota), a high-tensile strength metallic alloy (e.g., L605, MP35N), or high-tensile strength metallic alloy strands.

[0130] The clinician may advance implantable lead 1100 within the vasculature of the patient in the collapsed configuration (e.g., FIG. 1 IB). Once the clinician determines that implantable lead 1100 is at a target location within the vasculature (e.g., within heart 102, at target region 104), the clinician may expand implantable lead 1100 to the expanded configuration (e.g., FIG. 11 A) to place electrodes 310 in contact with patient tissue at or around the target location. For example, the clinician may expand implantable lead 1100 to form loops 1108 extending radially away from longitudinal axis 1101 near distal portion 308, as one example but other locations are possible. In such examples, electrodes 310 may be disposed on portions of elongated body 302 forming loops 1108.

[0131] The clinician may cause implantable lead 1100 to expand into the expanded configuration via retraction of tether 1104 along longitudinal axis 1101. As distal end 1116 of tether 1104 is coupled to distal end 306, retraction of tether 1104 may cause retraction of distal end 306, e.g., thereby causing elongated body 302 to form loops 1108 and assume the expanded configuration. The clinician may cause implantable lead 1100 to transition from the expandedconfiguration to the collapsed configuration via advancement of tether 1104 distally along longitudinal axis 1101. Advancement of tether 1104 may cause advancement of distal end 306, e.g., thereby causing elongated body 302 to extend distally and assume the collapsed configuration.

[0132] The clinician may adjustably secure tether 1104 to elongated body 302 to control a length of tether 1104 within elongated body 302, e.g., thereby locking implantable lead 1100 in either the collapsed configuration or the expanded configuration. The clinician may secure tether 1104 to elongated body 302 via an adjustable element (e.g., an adjustable set screw) disposed on elongated body 302 (not pictured in FIGS. 11 A-B). In some examples, one or more fixation elements 1102 are disposed on or around elongated body 302. Fixation element(s) 1102 may interface with (e.g., puncture, penetrate, contact) patient tissue to secure implantable lead 1100 within the patient vasculature at or around the target location. Fixation element(s) 1102 may include, but are not limited to, a fixation helix (e.g., a side helix), fixation tines, fixation barbs, expandable elements, or the like.

[0133] FIG. 12A is a conceptual diagram illustrating an example of implantable lead 1200, which is an example implanted lead 300 of FIG. 3 in an expanded configuration. FIG. 12B is a conceptual diagram illustrating implantable lead 1200 of FIG. 12B in a collapsed configuration. FIG. 12C is a cross-sectional diagram illustrating a cross-section of implantable lead 1200 of FIG. 12 A, the cross-section being take along line A-A in FIG. 12B. Implantable lead 1200 may be an example of implantable lead 300, and may be substantially similar to implantable leads 300 and 1100, aside from the elements described herein.

[0134] Implantable lead 1200 may include an expandable element 1208 and an inner jacket 1206 disposed within elongated body 302. Expandable element 1208 may be formed from one or more shape-memory materials. Expandable element 1208 may be configured to self-expand within the patient body, e.g., thereby causing implantable lead 1200 to expand from the collapsed configuration to the expanded configuration. A distal end of expandable element 1208 may be coupled to distal end 306 of implantable lead 1200, e.g., to a header defining distal end 306. The shape-memory material may include, but is not limited to, nitinol. In some examples, expandable element 1208 is formed from one or more strands and / or wires wound into a tube (e.g., in a helical shape) and defining inner lumen 1204. Inner lumen 1204 may be sized to retain guide element 1112.

[0135] Inner jacket 1206 may be disposed over expandable element 1208. Conductors 1210 may be disposed radially outside of inner jacket 1206. Conductors 1210 may electrically couple each of electrodes 310 to corresponding electrical contacts at or around proximal end 304 of implantable lead 1200. Inner jacket 1206 may electrically insulate expandable element 1208 fromconductors 1210. Inner jacket 1206 may be formed from a biocompatible polymer. Conductors 1210 may be wound helically around inner jacket 1206.

[0136] The clinician may advance implantable lead 1200 within the vasculature of the patient in the collapsed configuration. For example, the clinician may dispose implantable lead 1200 within a delivery sheath, e.g., to maintain implantable lead 1200 in the collapsed configuration. Once the clinician determines that implantable lead 1200 is at a target location within the vasculature (e.g., within heart 102, at target region 104), the clinician may retract the delivery sheath from around distal portion 308 of implantable lead 1200 to allow implantable lead 1200 to transition to the expanded configuration and place electrodes 310 in contact with patient tissue at or around the target location. When expanded, implantable lead 1100 may form loops 1202 extending radially away from longitudinal axis 1201 and define an expanded helical shape. In such examples, electrodes 310 may be disposed on portions of elongated body 302 forming loops 1202.

[0137] FIG. 13 is a conceptual diagram illustrating an example implantable lead 1300 of system 100 of any of FIGS. 1A-6. Implantable lead 1300 may be an example of implantable lead(s) 118. As illustrated in FIG. 13, implantable lead 1300 may include an expandable portion 1302 including a plurality of expandable arms 1306. A plurality of electrodes 1308 may be disposed on expandable arms 1306. Electrodes 1308 may be examples of stimulation electrodes (e.g., electrodes 124) as previously described herein.

[0138] Expandable portion 1302 may be retained within sheath 1304 of implantable lead 1300. The clinician may retract sheath 1304 proximally to expose expandable portion 1302 and allow expandable arms 1306 to expand radially outwards, e.g., to place electrodes 1308 in contact with patient tissue at or around target region 104. The clinician may advance sheath 1304 distally over expandable portion 1302 to cause expandable arms 1306 to transition into a collapsed configuration, e.g., for delivery and / or re-position of implantable lead 1300 within the vasculature of the patient. Implantable lead 1300 may be configured to retain a guide element (e.g., a guidewire) to facilitate navigation of implantable lead 1300 to target region 104 by the clinician. The guide element may be disposed radially inwards of expandable arms (e.g., along a central axis of implantable lead 1300), within an inner lumen defined by sheath 1304, and / or within one of expandable arms 1306 (e.g., within an inner lumen 1310 of expandable arms 1306).

[0139] Each of expandable arms 1306 may define an inner lumen extending along a length of expandable arm 1306 through a distal end of expandable arm 1306. Each of expandable arms 1306 may include one or more electrodes 1308 disposed on an outer surface of expandable arm 1306. Each electrode 1308 may extend partially or entirely around a circumference of expandable arm 1306. In some examples, where electrode 1308 extend partially around the circumference ofexpandable arm 1306, electrode 1308 may be oriented such that when expandable arms 1306 expand outwards in the expanded configuration, electrode 1308 is oriented to contact a surface of patient tissue (e.g., a blood vessel wall of a blood vessel of the patient). Implantable lead 1300 may include a plurality of expandable arms 1306 (e.g., two expandable arms 1306, three expandable arms 1306, four or more expandable arms 1306).

[0140] Each of expandable arms 1306 may define an expandable element 1314. Expandable element 1314 may, in response to clinician input or automatically, expand radially outwards away from the central axis of implantable lead 1300 into an expanded configuration. Together, the expanded configurations of expandable elements 1314 may define the expanded configuration for implantable lead 1300. Expandable element 1314 may be formed from a shapememory material. Expandable element 1314 may be pre-formed into the expanded shape and restricted into a collapsed configuration, e.g., by sheath 1304. The shape-memory material may include, but is not limited to, ni tinol.

[0141] An outer coating 1312 may be disposed around the expandable element 1314. In some examples, as illustrated in FIG. 13, outer coating 1312 extends around an entire circumference of expandable element 1314. Outer coating 1312 may reduce friction between expandable portion 1302 of implantable lead 1300 and an inner surface of sheath 1304. In some examples, outer coating 1312 electrically insulates expandable element 1314 and / or controls a surface area of each of electrodes 1308.

[0142] Each electrode 1308 may be electrically coupled to electrical contacts 1318 disposed at a proximal end of implantable lead 1300 via electrical connectors 1316. Electrical connectors 1316 may be disposed within an inner lumen of expandable element 1314 and / or may extend along an outer surface of expandable element 1314 (e.g., between expandable element 1314 and outer coating 1312). In some examples where multiple electrodes 1308 are disposed on each expandable arm 1306, the multiple electrodes 1308 may be wired in series or in parallel by electrical connectors 1316. Electrical connectors 1318 may exit from within expandable arm 1306 to electrically connect to electrodes 1308 via openings within outer coating 1312. The openings in outer coating 1312 may extend through to expandable elements 1314. In some examples, the openings in outer coating 1312 may align with openings in expandable elements 1314 to define openings extending from the outer surfaces of outer coatings 1312 to the inner lumens defined by expandable elements 1314. Electrical connectors 1316 may be flexible and may flex as expandable portion 1302 transitions between the collapsed configuration and the expanded configuration.

[0143] FIG. 14 is a conceptual diagram illustrating another example implantable lead 1400 of system 100 of any of FIGS. 1A-6. Implantable lead 1400 may be an example of implantablelead(s) 118. As illustrated in FIG. 14, implantable lead 1400 may include an expandable portion 1402 including a plurality of expandable arms 1406. A plurality of electrodes 1408 may be disposed on expandable arms 1406. Electrodes 1408 may be examples of stimulation electrodes (e.g., electrodes 124) as previously described herein.

[0144] Expandable portion 1402 may be retained within sheath 1404 of implantable lead 1400. The clinician may retract sheath 1404 proximally to expose expandable portion 1402 and allow expandable arms 1406 to expand radially outwards, e.g., to place electrodes 1408 in contact with patient tissue at or around target region 104. The clinician may advance sheath 1404 distally over expandable portion 1402 to cause expandable arms 1406 to transition into a collapsed configuration, e.g., for delivery and / or re-position of implantable lead 1400 within the vasculature of the patient. Implantable lead 1400 may be configured to retain a guide element (e.g., a guidewire) to facilitate navigation of implantable lead 1400 to target region 104 by the clinician.

[0145] Each of expandable arms 1406 may include an outer portion 1410 and an expandable element 1412 affixed to a radially-inward surface of outer portion 1410. Aside from a section affixed to outer portion 1410, a remaining surface area of each expandable element 1412 may be exposed. Each of expandable arms 1406 may include one or more electrodes 1408 disposed on an outer surface of expandable arm 1406, e.g., on an outer surface of outer jacket 1410. Electrodes 1408 may be coupled to corresponding electrical contacts via electrical connectors 1414. Electrical connectors 1414 may extend within expandable elements 1412, alongside expandable elements 1412, and / or between expandable elements 1412 and corresponding outer portions 1410. Electrodes 1408 may be oriented on outer portions 1410 such that when expandable arms 1406 expand outwards in the expanded configuration, electrodes 1408 are oriented to contact a surface of patient tissue (e.g., a blood vessel wall of a blood vessel of the patient). Outer portion 1410 may reduce friction between expandable portion 1402 of implantable lead 1400 and an inner surface of sheath 1404. In some examples, outer coating 1410 electrically insulates expandable element 1412 and / or controls a surface area of each of electrodes 1408.

[0146] Implantable lead 1400 may include a plurality of expandable arms 1406 (e.g., two expandable arms 1406, three expandable arms 1406, four or more expandable arms 1406). When implantable lead 1400 is in the collapsed configuration, outer portions 1410 of expandable arms 1406 may become aligned and define a continuous annular outer portion extending around the outer perimeter of expandable elements 1412. For example, in the example illustrated in FIG. 3, each outer portion 1410 of the three expandable arms 1406 may define an arc length of about one-third of an outer perimeter defined by the three expandable elements 1412. In such examples,when expandable portion 1402 is retained in the collapsed configuration by sheath 1404, outer portions 1410 may form a continuous outer surface against an inner surface of sheath 1404.

[0147] Expandable elements 1412 may, in response to clinician input or automatically, expand radially outwards away from the central axis of implantable lead 1400 into the expanded configuration. Together, the expanded configurations of expandable elements 1412 may define the expanded configuration for implantable lead 1400. Expandable element 1412 may be formed from a shape-memory material. Expandable element 1412 may be pre-formed into the expanded shape and restricted into a collapsed configuration, e.g., by sheath 1404. The shape-memory material may include, but is not limited to, nitinol.

[0148] FIG. 15A is a conceptual diagram illustrating another example implantable lead assembly 1500A of system 100 of any of FIGS. 1A-6. Implantable lead assembly 1500A may include an elongated body 1508 disposed within sheath 1502. Elongated body 1508 may extend terminate at distal end 1512. Elongated body 1508 may include two or more expandable portions 1510A, 1510B (collectively referred to herein as “expandable portions 1510”). Each of expandable portions 1510 may be substantially similar to expandable portion 1302 or expandable portion 1402 as previously described herein.

[0149] Implantable lead assembly 1500A may allow for the simultaneous stimulation of two different target regions within the patient. Sheath 1502 may define a plurality of windows 1504 at a first position along a length of sheath 1502. When one of expandable portions 1510 is aligned with windows 1504, the respective expandable portion 1510 may transition from a collapsed configuration to an expanded configuration. As illustrated in FIG. 15 A, both expandable portions 1510 may be simultaneously expanded the expanded configuration to stimulate both target regions. For example, a first expanded portion 1510A may be expanded through windows 1504 while a second expanded portion 1510B may be expanded when advanced out of distal opening 1506 of sheath 1504. Windows 1504 may allow for the deployment of one of expandable portions 1510, positioning of the other expandable portions 1510, and subsequent deployment of the other expandable portion 1510. While implantable lead assembly 1500A as illustrated in FIG. 15A includes two expandable portions 1510, other examples may include three or more expandable portions 1510. In such examples, sheath 1504 may include a corresponding number of sets of windows 1504 (e.g., two sets of windows 1504 for implantable lead assembly 1500A with three expandable portions 1510, etc.). The clinician may expand each expandable portion 1510 independent of any other expandable portions 1510.

[0150] FIG. 15B is a conceptual diagram illustrating another example implantable lead assembly 1500B of system 100 of any of FIGS. 1A-6. Implantable lead assembly 1500B may besubstantially similar to implantable lead assembly 1500A, aside from the elements described herein.

[0151] Implantable lead assembly 1500B may include an outer sheath 1522, a first lead 1526 disposed within an inner lumen of outer sheath 1522, with a first expandable portion 1528 disposed at or around a distal end of first lead 1526, an inner sheath 1530 disposed within an inner lumen of first lead 1526, and a second lead 1534 disposed within an inner lumen of inner sheath 1530 and including a second expandable portion 1538 disposed at or around a distal end of second lead 1534. Each of expandable portions 1528, 1538 may be identical to or substantially similar to expandable portion 1302 or expandable portion 1402.

[0152] Outer sheath 1522 may define a recess 1524 at or around the distal end of outer sheath 1522. Recess 1524 may be sized to retain first expandable portion 1528 in the collapsed configuration. First expandable portion 1528 may be collapsed when first expandable portion 1528 is disposed within outer sheath 1522. The clinician may advance first expandable portion 1528 out of outer sheath 1522 to expand first expandable portion 1528 and may retract first expandable portion 1528 into outer sheath 1522 to collapsed first expandable portion 1528. The clinician may advance or retract outer sheath 1522 independent of first lead 1526, or vice versa.

[0153] Inner sheath 1530 may define a recess 1532 at or around the distal end of inner sheath 1530. Recess 1532 may be sized to retain second expandable portion 1538 in the collapsed configuration. Second expandable portion 1538 may be collapsed when second expandable portion 1538 is disposed within inner sheath 1530. The clinician may advance second expandable portion 1538 out of inner sheath 1530 to expand second expandable portion 1538 and may retract second expandable portion 1538 into inner sheath 1530 to collapsed second expandable portion 1538. The clinician may independently advance or retract any of outer sheath 1522, first lead 1526, inner sheath 1530, or second lead 1534 to expand any combination of expandable portions 1528, 1538. In some examples, as illustrated in FIG. 15B, second lead 1534 may define an inner lumen 1536 configured to retain a guide element, a sensing element, or the like.

[0154] FIG. 16 is a conceptual diagram illustrating an example implantation of lead assembly 1600 of any of FIGS. 15A-15B within heart 102 of the patient. Lead assembly 1600 may include lead assembly 1500A, lead assembly 1500B, or any other lead assembly described herein.

[0155] The clinician may advance lead assembly 1600 into blood vessel 1602. Blood vessel 1602 may be a superior vena cava (SVC) of the patient. Lead assembly 1600 may be contained within an outer sheath 1604. Outer sheath 1604 may be, but is not limited to, outer sheath 1522.

[0156] In one example, the clinician may deploy a first expandable portion 1606 of lead assembly 1600 within blood vessel 1602 into an expanded configuration. First expandable portion 1606 may include, but is not limited to, first expandable portion 1510A or firstexpandable portion 1528. The clinician may deploy first expandable portion 1606 by proximally retracting outer sheath 1604 to expose first expandable portion 1606. Once exposed, expandable arms 1608 may expand (e.g., self-expand) radially outwards to contact a vessel wall of blood vessel 1602. When expandable arms 1608 contact the vessel wall, electrodes 1609 may contact the vessel wall and may be used to deliver stimulation signals to nerves surrounding blood vessel 1602, e.g., to elicit a parasympathetic or sympathetic stimulation of heart 102. Expandable arms 1608 may exert forces on the vessel wall and the reactive forces on expandable arms 1608 may affix first expandable portion 1606 within blood vessel 1602.

[0157] The clinician may then advance inner sheath 1612 through heart 102 (e.g., through one or more chambers of heart 102) into blood vessel 1610. In the example illustrated in FIG. 16, blood vessel 1610 may be a pulmonary artery of the patient. The clinician may advance inner sheath 1612 through one or more valves in heart 102 e.g., along a guide element extending through inner sheath 1612. In the example illustrated in FIG. 16, inner sheath 1612 may extend through a right atrium (RA) and a right ventricle (RV) of heart 102 and into blood vessel 1610.

[0158] The clinician may expand second expandable portion 1614 within blood vessel 1610. Second expandable portion 1614 may include, but is not limited to, second expandable portion 1510B or second expandable portion 1538. The clinician may retract inner sheath 1612 proximally to expose expandable arms 1616 of second expandable portion 1614. Once exposed, expandable arms 1616 may expand (e.g., self-expand) radially outwards to contact a vessel wall of blood vessel 1610. When expandable arms 1616 contact the vessel wall, electrodes 1617 may contact the vessel wall and may be used to deliver stimulation signals to nerves surrounding blood vessel 1610, e.g., to elicit a parasympathetic or sympathetic stimulation of heart 102. Expandable arms 1616 may exert forces on the vessel wall and the reactive forces on expandable arms 1616 may affix first expandable portion 1616 within blood vessel 1610.

[0159] In the example described above, the clinician deploys first expandable portion 1606 in blood vessel 1602, advances inner sheath 1612 into blood vessel 1610, and deploys second expandable portion 1614 within blood vessel 1610. In other examples, the clinician may first advance lead assembly 1600 into blood vessel 1610 and deploy second expandable portion 1614 within blood vessel 1610. The clinician may then retract outer sheath 1604 and position first expandable portion 1606 within blood vessel 1602. The clinician may then deploy first expandable portion 1606 into within blood vessel 1602.

[0160] Various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, embodied in programmers, such as physician or patient programmers, electrical stimulators, orother devices. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry or any other equivalent circuitry.

[0161] In one or more examples, the functions described in this disclosure may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored on, as one or more instructions or code, a computer- readable medium and executed by a hardware-based processing unit. Computer-readable media may include computer-readable storage media forming a tangible, non-transitory medium. Instructions may be executed by one or more processors, such as one or more DSPs, ASICs, FPGAs, general purpose microprocessors, or other equivalent integrated or discrete logic circuitry. Accordingly, the terms “processor” or “processing circuitry” as used herein may refer to one or more of any of the foregoing structures or any other structure suitable for implementation of the techniques described herein.

[0162] In addition, in some aspects, the functionality described herein may be provided within dedicated hardware and / or software modules. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components. Also, the techniques could be fully implemented in one or more circuits or logic elements. The techniques of this disclosure may be implemented in a wide variety of devices or apparatuses, including an IMD, an external programmer, a combination of an IMD and external programmer, an integrated circuit (IC) or a set of ICs, and / or discrete electrical circuitry, residing in an IMD and / or external programmer.

[0163] This disclosure describes one or more examples including the following examples:

[0164] Example 1 A: a system comprising: one or more electrodes configured to be disposed at one or more target treatment sites within a blood vessel of a patient; and processing circuitry configured to: receive cardiac, cardiovascular and / or systemic vascular signals from a heart of the patient; determine a first characteristic of a cardiac cycle of the heart based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the first characteristic, one or more first stimulation parameters for a first stimulation signal; determine a second characteristic of the cardiac cycle based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the second characteristic, one or more second stimulation parameters for a second stimulation signal; and cause the one or more electrodes to deliver one or more of: the first stimulation signal to one ormore nerves of the patient at or around the one or more target treatment sites to cause a parasympathetic stimulation of the heart; or the second stimulation signal to the one or more nerves at or around the one or more target treatment sites to cause a sympathetic stimulation of the heart.

[0165] Example 2A: the system of example 1 A, wherein the first characteristic is the same as the second characteristic.

[0166] Example 3A: the system of any of examples 1 A or 2A, wherein the one or more first stimulation parameters comprise a timing for the first stimulation signal, and wherein to determine, based at least in part on the first characteristic, the one or more first stimulation parameters for the first stimulation signal, the processing circuitry is configured to: determine, based at least in part on the first characteristic, the timing for delivery of the first stimulation signal after a first feature of the cardiac cycle of the heart.

[0167] Example 4A: the system of example 3 A, wherein the first feature comprises an Il- wave of the cardiac cycle.

[0168] Example 5A: the system of any of examples 1 A-4A, wherein the one or more second stimulation parameters comprise a timing for the second stimulation signal, and wherein to determine, based at least in part on the second characteristic, the one or more second stimulation parameters for the second stimulation signal, the processing circuitry is configured to: determine, based at least in part on the second characteristic, the timing for delivery of the second stimulation signal after a second feature of the cardiac cycle of the heart.

[0169] Example 6A: the system of example 5A, wherein the second feature comprises a P- wave of the cardiac cycle.

[0170] Example 7A: the system of any of examples 1 A-6A, wherein the first or second characteristic comprises at least one of: a heart rate of the heart, a pressure within a chamber of the heart, a nerve response to cardiac, cardiovascular and systemic vascular activity of the patient, a blood pressure within a blood vessel of the patient, a rate of change of blood pressure within one or more of the heart or the blood vessel, a flow rate of blood through the blood vessel, an RR variability of the heart, a frequency of arrhythmic cardiac events experienced by the heart, a presence of ectopic beats in cardiac activity of the heart, an ejection fraction of the heart, a pulse wave velocity through the blood vessel, or a thoracic impedance of the patient.

[0171] Example 8A: the system of any of examples 1 A-7A, wherein the one or more first stimulation parameters comprises one or more of: a timing of the first stimulation signal; a frequency of the first stimulation signal; a first duration of the first stimulation signal; a number of stimulation pulses within the first stimulation signal; an amplitude of the first stimulation signal; a ratio of the first duration of the first stimulation signal to a second duration of thesecond stimulation signal; a duty cycle of the first stimulation signal; a pulse width of a pulse of the first stimulation signal; a ramp up time for the pulse of the first stimulation signal; a ramp down time for the pulse of the first stimulation signal; or a selection of electrodes from the one or more electrodes for delivery of the first stimulation signal.

[0172] Example 9A: the system of any of examples 1 A-8A, wherein the one or more target treatment sites are located within one or more of: a left brachiocephalic vein of the patient, a jugular vein of the patient; a superior vena cava of the patient; a pulmonary artery of the patient; an aortic artery of the patient; an inferior vena cava of the patient; a trachea bifurcation of the patient; or an esophagus of the patient.

[0173] Example 10A: the system of any of examples 1 A-9A, further comprising one or more pacing electrodes coupled to cardiac tissue of the heart, and wherein the processing circuitry is configured to: determine, based at least in part on one or more of the first characteristic, the second characteristic, the one or more first stimulation parameters, or the one or more second stimulation parameters, one or more pacing parameters for a cardiac pacing signal; and cause the one or more pacing electrodes to deliver, based on the one or more pacing parameters, the cardiac pacing signal to the cardiac tissue.

[0174] Example 11 A: the system of any of examples 1 A-10A, wherein to cause the one or more electrodes to deliver one or more of the first stimulation signal or the second stimulation signal, the processing circuitry is configured to cause the one or more electrodes to deliver the first stimulation signal and the second stimulation signal within the same cardiac cycle.

[0175] Example 12A: a system comprising: one or more electrodes configured to be disposed at one or more target treatment sites within a blood vessel of a patient; and processing circuitry configured to: receive cardiac, cardiovascular and / or systemic vascular signals from a heart of the patient; determine a characteristic of a cardiac cycle of the heart based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the characteristic, at least one of one or more first stimulation parameters for a first stimulation signal, or one or more second stimulation parameters for a second stimulation signal; compare the characteristic against a threshold condition; based on a determination that the characteristic satisfies the threshold condition, cause the one or more electrodes to deliver the first stimulation signal to one or more nerves of the patient at or around the one or more target treatment sites to cause a parasympathetic stimulation of the heart; and based on a determination that the characteristic does not satisfy the threshold condition, cause the one or more electrodes to deliver the second stimulation signals to the one or more nerves at or around the one or more target treatment sites to cause a sympathetic stimulation of the heart.

[0176] Example 13A: the system of example 12A, wherein the one or more first stimulation parameters comprise a timing for the first stimulation signal, and wherein to determine, based at least in part on the characteristic, the one or more first stimulation parameters for the first stimulation signal, the processing circuitry is configured to: determine, based at least in part on the characteristic, the timing for delivery of the first stimulation signal after a first feature of the cardiac cycle of the heart.

[0177] Example 14A: the system of any of examples 12A-13A, wherein the one or more second stimulation parameters comprises a timing for the second stimulation signal, and wherein to determine, based at least in part on the characteristic, the one or more second stimulation parameters for the second stimulation signal, the processing circuitry is configured to: determine, based at least in part on the characteristic, the timing for delivery of the second stimulation signal after a second feature of the cardiac cycle of the heart.

[0178] Example 15 A: the system of any of examples 12A-14A, wherein the characteristic comprises one or more of: a heart rate of the heart, a pressure within a chamber of the heart, a nerve response to cardiac, cardiovascular and systemic vascular activity of the patient, a blood pressure within a blood vessel of the patient, a rate of change of blood pressure within one or more of the heart or the blood vessel, a flow rate of blood through the blood vessel, an RR variability of the heart, a frequency of arrhythmic cardiac events experienced by the heart, a presence of ectopic beats in cardiac activity of the heart, an ejection fraction of the heart, a pulse wave velocity through the blood vessel, or a thoracic impedance of the patient.

[0179] Example 16A: the system of any of examples 12A-15A, wherein the one or more first stimulation parameters comprises one or more of: a timing of the first stimulation signal; a frequency of the first stimulation signal; a first duration of the first stimulation signal; a number of stimulation pulses within the first stimulation signal; an amplitude of the first stimulation signal; a ratio of the first duration of the first stimulation signal to a second duration of the second stimulation signal; a duty cycle of the first stimulation signal; a pulse width of a pulse of the first stimulation signal; a ramp up time for the pulse of the first stimulation signal; a ramp down time for the pulse of the first stimulation signal; or a selection of electrodes from the one or more electrodes for delivery of the first stimulation signal.

[0180] Example 17A: the system of any of examples 12A-16A, further comprising one or more pacing electrodes coupled to cardiac and vascular tissue of the heart, and wherein the processing circuitry is configured to: determine, based at least in part on one or more of the characteristic, the one or more first stimulation parameters, or the one or more second stimulation parameters, one or more pacing parameters for a cardiac pacing signal; and cause the one or morepacing electrodes to deliver, based on the one or more pacing parameters, the cardiac pacing signal to the cardiac and vascular tissue.

[0181] Example 18 A: a method comprising: receiving, by processing circuitry of a medical device system, cardiac, cardiovascular and / or systemic vascular signals from a heart of a patient; determining, by the processing circuitry and based on the received cardiac, cardiovascular and / or systemic vascular signals, a first characteristic of a cardiac cycle of the heart; determining, by the processing circuitry and based at least in part on the first characteristic, one or more first stimulation parameters for a first stimulation signal; determining, by the processing circuitry and based on the received cardiac, cardiovascular and / or systemic vascular signals, a second characteristic of the cardiac cycle; determining, by the processing circuitry and based at least in part on the second characteristic, one or more second stimulation parameters for a second stimulation signal; causing, by the processing circuitry, one or more electrodes of the medical device system to deliver one or more of: the first stimulation signal to one or more first nerves of the patient to cause a parasympathetic stimulation of the heart; or the second stimulation signal to one or more second nerves of the patient to cause a sympathetic stimulation of the heart.

[0182] Example 19A: the method of example 18 A, wherein causing, by the processing circuitry, the one or more electrode of the medical device system to deliver one or more of the first stimulation signal or the second stimulation signal comprises: causing, by the processing circuitry, the one or more electrodes to deliver the first stimulation signal and the second stimulation signal within the same cardiac cycle.

[0183] Example 20A: the method of any of example 18A or 19A, further comprising: determining, by the processing circuitry, that a threshold period of time has elapse since one or more of the determining of the one or more first stimulation parameters or the determining of the one or more second stimulation parameters; and based on a determination that the threshold period of time has elapsed, adjusting, by the processing circuitry, at least one stimulation parameter within the one or more first stimulation parameters or the one or more second stimulation parameters based on the received cardiac, cardiovascular and / or systemic vascular signals.

[0184] Example IB: a medical device system comprising: an implantable lead configured to transition between a collapsed configuration and an expanded configuration; one or more electrodes disposed on the implantable lead, wherein the implantable lead is configured to transition to the expanded configuration within a blood vessel of a patient to place the one or more electrodes at one or more target treatment sites within the blood vessel, and wherein the one or more electrodes are configured to deliver one or more of: a first stimulation signal to one or more nerves at or around the one or more target treatment sites to cause a parasympatheticstimulation of the heart; or a second stimulation signal to the one or more nerves to cause a sympathetic stimulation of the heart.

[0185] Example 2B: the medical device system of example IB, wherein the first stimulation signal comprises one or more first stimulation parameters, the one or more first stimulation parameters being based on a first characteristic of a cardiac cycle of the heart, and wherein the second stimulation signal comprises one or more second stimulation parameters, the one or more second stimulation parameters being based on a second characteristic of the cardiac cycle of the heart.

[0186] Example 3B: the medical device system of example 2B, wherein the first or second characteristic comprises at least one of: a heart rate of the heart, a pressure within a chamber of the heart, a nerve response to cardiac, cardiovascular and systemic vascular activity of the patient, a blood pressure within a blood vessel of the patient, a rate of change of blood pressure within one or more of the heart or the blood vessel, a measure of contractility of the heart comprising one or more of: a maximum rise of left ventricular pressure in the heart, or a maximum slope of an end-systolic pressure volume curve of the heart, a flow rate of blood through the blood vessel, an RR variability of the heart reflecting one or more of sympathetic nerve activity of the patient or parasympathetic nerve activity of the patient in one or more of a frequency domain or a time domain, a PR interval of an electrocardiogram (ECG) signal of the heart, a QT interval of the ECG signal of the heart, a parameter derived from a T-wave of the ECG signal of the heart and indicating heterogeneity of repolarization of tissue of the heart, a presence of ectopic beats in cardiac activity of the heart, a parameter of Heart Rate Turbulence of the heart, the parameter comprising one or more of: a turbulence onset (TO) the heart rate, or a turbulence slope (TS) of the heart rate, a deceleration capacity, which expresses the property of the neural control of the heart extrinsically to decelerate its rate, a frequency of arrhythmic cardiac events experienced by the heart, an ejection fraction of the heart, a pulse wave velocity through the blood vessel, or a thoracic impedance of the patient indicating congestion by the patient.

[0187] Example 4B: the medical device system of any of examples 2B or 3B, wherein at least one stimulation parameter of the one or more first stimulation parameters or the one or more second stimulation parameters comprises one or more of: a timing of the first or the second stimulation signal; a frequency of the first or the second stimulation signal; a first duration of the first or the second stimulation signal; a number of stimulation pulses within the first or the second stimulation signal; an amplitude of the first or the second stimulation signal; a ratio of a first duration of the first stimulation signal to a second duration of the second stimulation signal; a duty cycle of the first or the second stimulation signal; a pulse width of a pulse of the first orthe second stimulation signal; a ramp up time for the pulse of the first or the second stimulation signal; a ramp down time for the pulse of the first or the second stimulation signal; or a selection of electrodes from the one or more electrodes for delivery of the first or the second stimulation signal.

[0188] Example 5B: the medical device system of any of examples 1B-4B, wherein the implantable lead assumes a helical shape in the expanded configuration.

[0189] Example 6B: the medical device system of example 5B, wherein the one or more electrodes are disposed around an outer perimeter of the helical shape when the implantable lead is in the expanded configuration.

[0190] Example 7B: the medical device system of any of examples 1B-6B, wherein the implantable lead comprises: an elongated body extending from a proximal end to a distal end along a longitudinal axis; and a tether extending along the longitudinal axis and disposed at least partially within the elongated body, wherein a distal end of the tether is coupled to the distal end of the elongated body, and wherein the implantable lead is configured to transition from the collapsed configuration to the expanded configuration in response to a retraction of the tether along the longitudinal axis.

[0191] Example 8B: the medical device system of any of examples 1B-6B, wherein the implantable lead is configured to be retained within a delivery catheter, and wherein the implantable lead further comprises: an elongated body; and a shape-memory material disposed within the elongated body, wherein when a distal portion of the implantable lead is advanced out of the delivery catheter, the shape-memory material may at least partially self-expand and cause the implantable lead to assume the expanded configuration.

[0192] Example 9B: the medical device system of example 8B, wherein the shape-memory material comprises nitinol.

[0193] Example 10B: the medical device system of any of examples 8B or 9B, wherein the shape-memory material defines a plurality of strands forming an elongated tube, and wherein the elongated tube is disposed within the elongated body.

[0194] Example 1 IB: the medical device system of any of examples 1B-10B, further comprising a fixation feature on an outer surface of the implantable lead, wherein the fixation feature is configured to interface with tissue of the patient to affix the implantable lead within vasculature of the patient.

[0195] Example 12B: the medical device system of example 1 IB, wherein the fixation feature comprises one or more of: a side helix; one or more fixation tines; one or more fixation barbs; or an expandable element.

[0196] Example 13B: the medical device system of any of examples 1B-12B, wherein the implantable lead defines an inner lumen extending through the implantable lead from a distal end of the implantable lead to a proximal end of the implantable lead.

[0197] Example 14B: the medical device system of example 13B, wherein the inner lumen is sized to retain one or more of: a guidewire; or a sensing element.

[0198] Example 15B: a medical device system comprising: an implantable lead comprising two or more expandable arms at or around a distal end of the implantable lead; one or more electrodes disposed on the implantable lead, the one or more electrodes being disposed on the two or more expandable arms; wherein the implantable lead is configured to transition from a collapsed configuration to an expanded configuration within a blood vessel of a patient to place the one or more electrodes at one or more target treatment sites within the blood vessel, and wherein the one or more electrodes are configured to deliver one or more of: a first stimulation signal to one or more nerves at or around the one or more target treatment sites to cause a parasympathetic stimulation of the heart; or a second stimulation signal to the one or more nerves to cause a sympathetic stimulation of the heart.

[0199] Example 16B: the medical device system of example 15B, wherein when the implantable lead transitions to the expanded configuration, the two or more expandable arms expand radially away from a longitudinal axis of the implantable lead.

[0200] Example 17B: the medical device system of any of examples 15B or 16B, wherein each expandable arm of the two or more expandable arms comprises: a self-expandable element; at least one electrode of the one or more electrodes; an insulating material disposed over at least a portion of the self-expandable element; and one or more electrical connectors electrically coupling the at least one electrode to at least one electrical contacts at or around a proximal end of the implantable lead.

[0201] Example 18B: the medical device system of example 17B, wherein the selfexpandable element comprises a shape-memory material, the shape-memory material comprising ni tinol.

[0202] Example 19B: the medical device system of any of examples 17B or 18B, wherein the one or more electrical connectors comprises one or more flex circuits.

[0203] Example 20B: the medical device system of any of examples 17B-19B, wherein the insulating material is disposed around an entire outer perimeter of the self-expandable element.

[0204] Example 21B: the medical device system of any of examples 17B-19B, wherein the insulating material is disposed over a portion of an outer surface of the self-expandable element oriented to contact tissue of the patient.

[0205] Example 22B: the medical device system of any of examples 17B-21B, wherein the one or more electrical connectors is configured to be: disposed radially inwards of the shapememory material; or disposed between the shape-memory material and the insulating material.

[0206] Example 23B: the medical device system of any of examples 15B-22B, wherein the implantable lead comprises a first implantable lead, and wherein the implantable lead is configured to retain an elongated element radially inwards of the two or more expandable arms, the elongated element comprising one or more of: a guidewire; a second implantable lead different from the first implantable lead; or an elongated sensing element.

[0207] Example 24B: a medical device system comprising: an implantable device extending along a longitudinal axis, the implantable device comprising a first plurality of expandable arms at a first location along the longitudinal axis and a second plurality of expandable arms at a second location along the longitudinal axis, the second location being longitudinally offset to the first location; a first plurality of electrodes disposed on the first plurality of expandable arms; and a second plurality of electrodes disposed on the second plurality of expandable arms, wherein each of the first plurality of expandable arms or the second plurality of expandable arms is configured to transition from a collapsed configuration to an expanded configuration within a vasculature of a patient to place a respective plurality of electrodes at a respective target treatment site, wherein the first plurality of electrodes is configured to deliver a first stimulation signal to one or more nerves at or around a first target treatment site to cause a parasympathetic stimulation of the heart, and wherein the second plurality of electrode is configured to deliver a second stimulation signal to one or more nerves at or around a second target treatment site to cause a sympathetic stimulation of the heart.

[0208] Example 25B: the medical device system of example 24B, wherein one of the first or the second target treatment site is within a superior vena cava (SVC) of the patient, and wherein the other of the first or second target treatment site is within a pulmonary artery of the patient.

[0209] Example 26B: the medical device system of any of examples 24B or 25B, wherein each of the first or the second plurality of expandable arms is configured to transition between the collapsed and expanded configurations independent of the other of the first or the second plurality of expandable arms.

[0210] Example 27B: the medical device system of any of examples 24B-26B, wherein the implantable device comprises an implantable lead, wherein the medical device system further comprises a sheath configured to be disposed over the implantable lead, the sheath being configured to retain the first and the second plurality of expandable arms in the collapsed configuration, wherein the sheath defines one or more windows, and wherein when the one or more windows are longitudinally aligned with one of the first or the second plurality ofexpandable arms, the respective plurality of expandable arms is configured to transition to the expanded configuration.

[0211] Example 28B: the medical device system of any of examples 24B-26B, further comprising a sheath, wherein the implantable device comprises: a first implantable lead disposed within the sheath, the first plurality of expandable arms being coupled to a distal end of the first implantable lead, wherein the first implantable lead defines an inner lumen; and a second implantable lead disposed within the inner lumen of the first implantable lead, the second plurality of expandable arms being coupled to a distal end of the second implantable lead.

[0212] Example 29B: the medical device system of example 28B, wherein the first plurality of expandable arms is configured to transition to the expanded configuration when the distal end of the first implantable lead is advanced out of the sheath, and wherein the second plurality of expandable arms is configured to transition to the expanded configuration when the distal end of the second implantable lead is advanced out of the inner lumen of the first implantable lead.

[0213] Example 30B: the medical device system of any of examples 24B-29B, wherein each expandable arm of the first plurality of expandable arms or the second plurality of expandable arms comprises elements of any of examples 17B-22B.

[0214] Example 3 IB: a method comprising: advancing an implantable lead of a medical device system through vasculature of a patient to a first target treatment site within a patient; expanding a first plurality of expandable arms coupled to the implantable lead at the first target treatment site to place a first plurality of electrodes on the first plurality of expandable arms in contact with tissue of the patient at or around the first target treatment site; positioning a second plurality of expandable arms coupled to the implantable lead at a second target treatment site within the patient; expanding the second plurality of expandable arms to place a second plurality of electrodes on the second plurality of expandable arms in contact with tissue of the patient at or around the second target treatment site; delivering, via the first plurality of electrodes, a first stimulation signal to one or more nerves at or around a first target treatment site to cause a parasympathetic stimulation of a heart of the patient; and delivering, via the second plurality of electrodes, a second stimulation signal to one or more nerves at or around a second target treatment site to cause a sympathetic stimulation of the heart.

[0215] Example 32B: the method of example 3 IB, wherein one of the first or the second target treatment site is within a superior vena cava (SVC) of the patient, and wherein the other of the first or second target treatment site is within a pulmonary artery of the patient.

[0216] Example 33B: the method of any of examples 3 IB or 32B, wherein the first plurality of expandable arms is distal to the second plurality of expandable arms along the implantable lead, and wherein positioning the second plurality of expandable arms at the second targettreatment site comprises: retracting the implantable lead once the first plurality of expandable arms is expanded until the second plurality of expandable arms are aligned with the second target treatment site.

[0217] Example 34B: the method of any of examples 3 IB or 32B, wherein the first plurality of expandable arms is proximal to the second plurality of expandable arms along the implantable lead, and wherein positioning the second plurality of expandable arms at the second target treatment site comprises: advancing a portion of the implantable lead distal to the first plurality of expandable arms once the first plurality of expandable arms is expanded until the second plurality of expandable arms are aligned with the second target treatment site.

[0218] Example 35B: the method of any of examples 31B-34B, wherein the medical device system includes one or more elements of any of examples 25B-30B.

[0219] Various aspects of the disclosure have been described. These and other aspects are within the scope of the following claims and clauses.

Claims

WHAT IS CLAIMED IS:

1. A system comprising: one or more electrodes configured to be disposed at one or more target treatment sites within a blood vessel of a patient; and processing circuitry configured to: receive cardiac, cardiovascular and / or systemic vascular signals from a heart of the patient determine a first characteristic of a cardiac cycle of the heart based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the first characteristic, one or more first stimulation parameters for a first stimulation signal; determine a second characteristic of the cardiac cycle based on the received cardiac, cardiovascular and / or systemic vascular signals; determine, based at least in part on the second characteristic, one or more second stimulation parameters for a second stimulation signal; and cause the one or more electrodes to deliver one or more of: the first stimulation signal to one or more nerves of the patient at or around the one or more target treatment sites to cause a parasympathetic stimulation of the heart; or the second stimulation signal to the one or more nerves at or around the one or more target treatment sites to cause a sympathetic stimulation of the heart.

2. The system of claim 1, wherein the first characteristic is the same as the second characteristic.

3. The system of any of claims 1 or 2, wherein the one or more first stimulation parameters comprise a timing for the first stimulation signal, and wherein to determine, based at least in part on the first characteristic, the one or more first stimulation parameters for the first stimulation signal, the processing circuitry is configured to: determine, based at least in part on the first characteristic, the timing for delivery of the first stimulation signal after a first feature of the cardiac cycle of the heart.

4. The system of claim 3, wherein the first feature comprises an R-wave of the cardiac cycle.

5. The system of any of claims 1-4, wherein the one or more second stimulation parameters comprise a timing for the second stimulation signal, and wherein to determine, based at least in part on the second characteristic, the one or more second stimulation parameters for the second stimulation signal, the processing circuitry is configured to: determine, based at least in part on the second characteristic, the timing for delivery of the second stimulation signal after a second feature of the cardiac cycle of the heart.

6. The system of claim 5, wherein the second feature comprises a P-wave of the cardiac cycle.

7. The system of any of claims 1-6, wherein the first or second characteristic comprises at least one of: a heart rate of the heart, a pressure within a chamber of the heart, a nerve response to cardiac, cardiovascular and systemic vascular activity of the patient, a blood pressure within a blood vessel of the patient, a rate of change of blood pressure within one or more of the heart or the blood vessel, a measure of contractility of the heart comprising one or more of: a maximum rise of left ventricular pressure in the heart, or a maximum slope of an end-systolic pressure volume curve of the heart, a flow rate of blood through the blood vessel, an RR variability of the heart reflecting one or more of sympathetic nerve activity of the patient or parasympathetic nerve activity of the patient in one or more of a frequency domain or a time domain, a PR interval of an electrocardiogram (ECG) signal of the heart, a QT interval of the ECG signal of the heart, a parameter derived from a T-wave of the ECG signal of the heart and indicating heterogeneity of repolarization of tissue of the heart, a presence of ectopic beats in cardiac activity of the heart,a parameter of Heart Rate Turbulence of the heart, the parameter of Heart Rate Turbulence comprising one or more of: a turbulence onset (TO) the heart rate, or a turbulence slope (TS) of the heart rate, a deceleration capacity, which expresses the property of the neural control of the heart extrinsically to decelerate its rate, a frequency of arrhythmic cardiac events experienced by the heart, an ejection fraction of the heart, a pulse wave velocity through the blood vessel, or a thoracic impedance of the patient indicating congestion by the patient.

8. The system of any of claims 1-7, wherein the one or more first stimulation parameters comprises one or more of: a timing of the first stimulation signal; a frequency of the first stimulation signal; a first duration of the first stimulation signal; a number of stimulation pulses within the first stimulation signal; an amplitude of the first stimulation signal; a ratio of the first duration of the first stimulation signal to a second duration of the second stimulation signal; a duty cycle of the first stimulation signal; a pulse width of a pulse of the first stimulation signal; a ramp up time for the pulse of the first stimulation signal; a ramp down time for the pulse of the first stimulation signal; or a selection of electrodes from the one or more electrodes for delivery of the first stimulation signal.

9. The system of any of claims 1-8, wherein the one or more target treatment sites are located within one or more of: a left brachiocephalic vein of the patient, a jugular vein of the patient; a superior vena cava of the patient; a pulmonary artery of the patient; an aortic artery of the patient; an inferior vena cava of the patient;a trachea bifurcation of the patient; or an esophagus of the patient.

10. The system of any of claims 1-9, further comprising one or more pacing electrodes coupled to cardiac tissue of the heart, and wherein the processing circuitry is configured to: determine, based at least in part on one or more of the first characteristic, the second characteristic, the one or more first stimulation parameters, or the one or more second stimulation parameters, one or more pacing parameters for a cardiac pacing signal; and cause the one or more pacing electrodes to deliver, based on the one or more pacing parameters, the cardiac pacing signal to the cardiac tissue.

11. The system of claim 10, wherein the one or more electrodes are disposed on a first implantable lead, and wherein the one or more pacing electrodes are disposed on a second implantable lead, the second implantable lead being different from the first implantable lead.

12. The system of claim 10, wherein the one or more electrodes and the one or more pacing electrodes are disposed on a same implantable lead.

13. The system of any of claims 1-12, wherein the processing circuitry comprises processing circuitry within an implantable medical device.

14. The system of any of claims 1-13, wherein the processing circuitry is further configured to: compare, one or more autonomic marker values from the patient against a threshold autonomic marker value; and based on a determination that the one or more autonomic marker values satisfy the threshold autonomic marker value, adjust one or more of: the one or more first stimulation parameters, or the one or more second stimulation parameters.

15. The system of any of claims 1-14, wherein to cause the one or more electrodes to deliver one or more of the first stimulation signal or the second stimulation signal, the processing circuitry is configured to cause the one or more electrodes to deliver the first stimulation signal and the second stimulation signal within the same cardiac cycle.

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