System for Selective Occlusion of Peripheral Venous Vessels for Heart Unloading

Abstract

A system and method are provided for increasing cardiac output and improving perfusion of a patient's heart by intermittently occluding the patient's venous vasculature to unload the heart. The system may include first and second balloon catheters, which are selectively actuated to intermittently occlude the first and second veins to increase venous vascular resistance in the patient's lower and upper extremities, thereby selectively reducing arterial blood flow to the lower and upper extremities while maintaining arterial vascular resistance in the patient's heart and central organs and increasing perfusion to the patient's heart and central organs.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims priority to U.S. Provisional Application No. 63 / 365,941, filed Jun. 6, 2022, the entire contents of which are incorporated herein by reference.

[0002] (Technical Field) The present disclosure is directed to unloading the heart to improve cardiac function in patients suffering from heart failure, including patients with a reduced ejection fraction, and to treat pulmonary hypertension.

Background Art

[0003] Heart failure is a leading cause of death worldwide. Heart failure often results in multiple long - term hospitalizations, especially in the later stages of the disease. Without a heart transplant, the long - term prognosis for such patients is poor, and pharmaceutical approaches are only palliative. As a result, there are few effective treatments to slow or reverse the progression of this disease.

[0004] Heart failure can result from any of a number of causative events. Heart failure can occur as a result of ischemic heart disease, hypertension, valvular disease, infections, genetic cardiomyopathy, pulmonary hypertension, or under metabolic stress conditions including pregnancy. Heart failure can occur without an identifiable cause, as is also known as idiopathic cardiomyopathy. The term heart failure encompasses left ventricular, right ventricular, or biventricular failure.

[0005] The heart can often initially respond successfully to increased workloads resulting from, for example, hypertension or loss of contractile tissue. Over time, however, this stress induces compensatory cardiomyocyte hypertrophy and remodeling of the ventricular wall. In particular, over the next several months following an initial cardiac injury, the damaged portion of the heart will typically begin to remodel as the heart struggles to continue pumping blood with a reduced muscle mass or lower contractility. This, in turn, often leads to myocardial overexertion, whereby the myocardium in the damaged area becomes progressively thinner, dilates, and becomes overloaded. At the same time, the ejection fraction of the damaged ventricle decreases, leading to lower cardiac output and higher mean pressures and volumes in the ventricle throughout the cardiac cycle, i.e., signs of heart failure. Not surprisingly, when a patient's heart falls into this progressive self-perpetuating vicious cycle, the patient's quality of life is severely affected and the risk of morbidity increases sharply. Depending on several factors, including the patient's pre-existing physical condition, age, gender, and lifestyle, the patient may experience one or more hospitalizations at significant cost to the patient and the social healthcare system until the patient dies of any one of several co-morbidities, including cardiac arrest or stroke, kidney failure, liver failure, or pulmonary hypertension.

[0006] Pharmacological approaches are available as a stopgap measure to reduce the symptoms of heart failure, but there is no pharmacological procedure that can prevent or reverse heart failure. Moreover, existing pharmacological approaches are essentially systemic and do not address the local effects of remodeling on heart structure. Accordingly, it would be desirable to provide a system and method for treating heart failure that can prevent, and more preferably reverse, cardiac remodeling that gives rise to the effects associated with this disease.

[0007] Pulmonary hypertension (PH) is also a major cause of morbidity and mortality worldwide. As mentioned above, heart failure is a common cause of pulmonary hypertension, but pulmonary hypertension can also be caused by primary lung diseases. Today, pharmacological treatment can reduce the pulmonary artery systolic pressure (PASP) and improve symptoms and ultimately survival in patients with pulmonary hypertension. However, there are drawbacks to pharmacological treatment such as cost and side effects. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEM

[0008] The present disclosure overcomes the drawbacks of previously known systems and methods by providing a system for unloading a patient's heart to improve cardiac performance. The system can include a first flow-limiting element selectively operable to occlude a first vein in fluid communication with a first limb of the patient, a second flow-limiting element selectively operable to occlude a second vein in fluid communication with a second limb of the patient, and a controller operably coupled to the first and second flow-limiting elements. The controller can be programmed to expand the first and / or second flow-limiting elements according to a predetermined actuation regimen to selectively occlude the first and / or second veins, reduce preload, increase mean arterial pressure, thereby selectively increasing the arterial vascular resistance of the patient's limbs while maintaining the arterial vascular resistance of the patient's heart and end organs and increasing perfusion to the patient's heart and end organs.

[0009] In some embodiments, the first vein can be the contralateral iliac vein and the second vein can be the ipsilateral iliac vein. The system can further include a third flow-limiting element operably coupled to the controller and selectively operable to occlude the patient's superior vena cava (SVC). Thus, the controller can be programmed to expand the third flow-limiting element according to a second predetermined actuation regimen to occlude the SVC and reduce preload. The system can further include a mechanical circulatory support (MCS) device.

[0010] The system may further include a third flow-limiting element operably coupled to the controller and selectively actuable to occlude the patient's contralateral subclavian vein, and a fourth flow-limiting element operably coupled to the controller and selectively actuable to occlude the patient's ipsilateral subclavian vein. Thus, the controller is programmed to expand the third and / or fourth flow-limiting elements according to a second predetermined actuation regimen to selectively occlude the contralateral and / or ipsilateral subclavian veins, reduce the preload, increase the mean arterial pressure, thereby selectively increasing the arterial vascular resistance of the patient's extremities while maintaining the arterial vascular resistance of the patient's heart and end organs and increasing the perfusion to the patient's heart and end organs.

[0011] The system may further include a fifth flow-limiting element operably coupled to the controller and selectively actuable to occlude the patient's superior vena cava (SVC). Thus, the controller is configured to expand the fifth flow-limiting element according to a third predetermined actuation regimen to occlude the SVC and reduce the preload. The system may further include a catheter operably coupled to the controller, and the first and second flow-limiting elements are disposed on the distal region of the catheter.

[0012] In some embodiments, the first vein may be the superior vena cava (SVC) and the second vein may be the inferior vena cava (IVC). Thus, the system may include a first catheter operably coupled to the controller and a second catheter operably coupled to the controller, the first flow-limiting element is disposed on the distal region of the first catheter, and the second flow-limiting element is disposed on the distal region of the second catheter. The system may further include a mechanical circulatory support (MCS) device.

[0013] Furthermore, a predetermined actuation regimen can be programmed to expand only to the first flow restriction element over a first period, expand to the first and second flow restriction elements over a second period after the first period, expand only to the second flow restriction element over a third period after the second period, and expand to the first and second flow restriction elements over a fourth period after the third period. Thus, the predetermined actuation regimen can be programmed to cause at least 70% occlusion of the first and second veins during the treatment period. The predetermined actuation regimen can be programmed in the controller such that the first flow restriction element or the second flow restriction element, or both, maintain occlusion throughout the treatment session. Each occlusion period during the treatment session can be at least 1 minute.

[0014] The system can further include one or more sensors capable of measuring one or more parameters and generating one or more signals indicative of the one or more measured parameters. For example, a first sensor of the one or more sensors can be disposed proximal to the first flow restriction element, and a second sensor of the one or more sensors can be disposed proximal to the second flow restriction element. Additionally, the controller can be programmed to adjust a predetermined actuation regimen to selectively occlude the first and / or second veins in response to one or more signals indicative of the one or more measured parameters.

[0015] According to another aspect of the present disclosure, a method of unloading a patient's heart to improve cardiac performance is provided. The method includes positioning a first flow-limiting element within a first vein in fluid communication with a first limb of the patient, positioning a second flow-limiting element within a second vein in fluid communication with a second limb of the patient, and expanding the first and / or second flow-limiting elements according to a predetermined actuation regimen to selectively occlude the first and / or second vein, reduce pre-cardiac load, increase mean arterial pressure, thereby maintaining the arterial vascular resistance of the patient's heart and end organs while selectively increasing the arterial vascular resistance of the patient's limbs and increasing perfusion to the patient's heart and end organs. For example, expanding the first and / or second flow-limiting elements according to a predetermined actuation regimen may involve maintaining occlusion of the first flow-limiting element or the second flow-limiting element or both throughout the treatment session.

[0016] In some embodiments, positioning a first flow-limiting element within a first vein of the patient may include positioning a first flow-limiting element within the patient's contralateral iliac vein, and positioning a second flow-limiting element within a second vein of the patient may include positioning a second flow-limiting element within the patient's ipsilateral iliac vein. The method may further include positioning a third flow-limiting element within the patient's contralateral subclavian vein, positioning a fourth flow-limiting element within the patient's ipsilateral subclavian vein, and expanding the third and / or fourth flow-limiting elements according to a second predetermined actuation regimen to selectively occlude the contralateral and / or ipsilateral subclavian vein, reduce pre-cardiac load, increase mean arterial pressure, thereby maintaining the arterial vascular resistance of the patient's heart and end organs while selectively increasing the arterial vascular resistance of the patient's limbs and increasing perfusion to the patient's heart and end organs.

[0017] Alternatively, the method can include positioning a third flow-limiting element within the patient's superior vena cava and intermittently actuating the third flow-limiting element according to a second predetermined actuation regimen to occlude the SVC and reduce preload on the heart. The method can further include positioning a mechanical circulatory support (MCS) device within the patient's heart and actuating the MCS device. In some embodiments, positioning a first flow-limiting element within a first vein of the patient includes positioning the first flow-limiting element within the patient's superior vena cava (SVC), and positioning a second flow-limiting element within a second vein of the patient includes positioning the second flow-limiting element within the patient's inferior vena cava (IVC).

Brief Description of the Drawings

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[0032] In human anatomical structure, deoxygenated blood returns to the heart through the vena cava, which comprises the superior vena cava and the inferior vena cava that are coupled to the right atrium of the heart. Blood moves from the right atrium, through the tricuspid valve, into the right ventricle, where the blood is pumped to the lungs via the pulmonary artery. Oxygenated blood returns from the lungs to the left atrium via the pulmonary veins. The oxygenated blood then enters the left ventricle, which pumps blood through the aorta to the rest of the body.

[0033] Attempts have been made to address heart failure by treating various aspects of heart failure, but there is nothing that is intended to, or is capable of, reducing left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic pressure (LVEDP), left ventricular end-diastolic diameter (LVEDD), right ventricular end-diastolic volume (RVEDV), or right ventricular end-diastolic pressure (RVEDP) without causing serious and potentially life-threatening side effects. In view of the foregoing drawbacks of the known systems and methods for regulating venous return for addressing heart failure, it would be desirable to provide systems and methods for treating acute and chronic heart failure that reduce the risk of exacerbating co-morbidities associated with the disease and prevent or reverse cardiac remodeling. Further, it would be desirable to provide systems and methods for increasing cardiac output and improving perfusion of a patient's heart while unloading the heart.

[0034] According to one aspect of the present disclosure, Applicants have determined that controlling the venous return to the right ventricle by intermittent venous occlusion is beneficial in reducing RVEDP, RVEDV, LVEDP, and LVEDV without detrimentally reducing left ventricular systolic pressure (LVSP). It is theorized that selective intermittent occlusion of the venous vasculature will further reduce the risk of exacerbating renal congestion. Renal congestion can impair renal function due to volume overload and neurohormonal activation in patients with heart failure. Volume overload can occur when a weakened heart is unable to pump an equivalent amount of blood, which leads to less blood flow through the kidneys. Less blood flow through the kidneys causes less blood to be filtered by the kidneys and less water to be excreted via urination, resulting in an excessive volume being retained in the body. With an excessive volume, the heart pumps increasingly inefficiently and the patient ultimately heads towards death as the body becomes increasingly congested.

[0035] By reducing the flow into the right atrium, the volume in the left ventricle is ultimately reduced, allowing the muscle fibers to stretch within the normal range, naturally enhancing contractility, and enabling the heart to pump more fluid into the kidneys. The kidneys can then extract water, which can be removed from the body through urination. For example, as described in U.S. Patent No. 10,842,974 to Kapur et al. (the entire content of which is incorporated herein by reference), it should be further understood that a negative pressure sink is generated within the right atrium due to a sudden reduction in right atrial pressure and volume during venous occlusion, for example, during SVC occlusion. As a result, the flow from the renal vein is accelerated, thereby increasing renal congestion removal, promoting blood flow across the kidneys, and increasing urine output. Thus, venous occlusion can benefit patients suffering from heart failure by reducing heart and pulmonary pressures and promoting congestion removal.

[0036] The Applicant understands that intermittent occlusion of the venous vasculature (i.e., cardiopulmonary unloading) over a period of time (e.g., minutes, hours, days, weeks, or months) will, beneficially, allow the patient's heart to interrupt or recover from myocardial remodeling. The system described herein allows the myocardium to transition from a pressure-stroke volume curve indicative of heart failure towards one more closely resembling that of a healthy heart.

[0037] Generally, the systems and methods of the present disclosure can be used to treat any disease and improve cardiac function by preventing or reversing myocardial remodeling, particularly those conditions in which a patient is suffering from heart failure. Such conditions include, but are not limited to, for example, systolic heart failure, diastolic (non-systolic) heart failure, decompensated heart failure patients in acute heart failure (ADHF), chronic heart failure, acute heart failure and pulmonary hypertension, heart attack, heart failure with preserved ejection fraction, right heart failure, restrictive and dilated cardiomyopathy, and cardiorenal syndrome (types 1-5). The systems and methods of the present invention can also be used as a prophylactic to reduce the aftermath of acute right or left ventricular myocardial infarction, pulmonary hypertension, RV failure, post-operative shock, or rejection after orthotopic heart transplantation (OHTx), or, alternatively, for cardiorenal applications and / or to treat renal dysfunction, liver dysfunction, or lymphatic congestion. The systems and methods of the present disclosure can also reduce hospitalizations caused by the various diseases described herein, including at least acute exacerbations.

[0038] The relationship between left ventricular pressure or left ventricular volume and stroke volume is often referred to as the Frank-Starling relationship or the "Starling curve". That relationship shows that cardiac stroke volume depends on preload, contractility, and afterload. Preload refers to the volume of blood returning to the heart, contractility is defined as the inherent ability of the myocardium to contract, and afterload is determined by vascular resistance and impedance. In heart failure due to diastolic or systolic dysfunction, a decreased stroke volume leads to increased volume and pressure in the left ventricle, which can result in pulmonary edema. The increased ventricular volume and pressure also result in increased workload and increased myocardial oxygen consumption. Such excessive exercise of the heart leads to worsening of cardiac function as the heart becomes increasingly deprived of oxygen due to a mismatch between supply and demand. Furthermore, as volume and pressure accumulate within the heart, systolic function deteriorates due to stretching of the myocardium. This condition is called "congestive heart failure".

[0039] In a typical Starling curve for a normal heart, stroke volume increases with increasing LVEDP or LVEDV, begins to flatten, i.e., the slope of the curve decreases only at very high pressures or volumes. A patient who has just had an acute myocardial infarction (AMI) will exhibit a decreased stroke volume at all values of LVEDV or LVEDP. However, since the heart has just begun to experience the overload caused by the local effects of the infarction, the myocardial contractility of the entire ventricle is still relatively good, and the stroke volume is still relatively high at low LVEDP or LVEDV. In contrast, patients with a history of heart injury can experience progressive deterioration of cardiac function as the myocardium remodels over time to compensate for increased workload and decreased oxygen availability. As described above, this can lead to a progressively lower stroke volume as the ventricles dilate due to progressively higher volumes and pressures throughout the cardiac cycle. Thus, the stroke volume will continue to decrease as LVEDP or LVEDV increases until the heart finally stops or the patient dies in a circulation-related stage of the disease.

[0040] For a normal heart, as the end-diastolic volume increases, the stroke volume increases. However, for a healthy heart, beyond a certain point, an increased end-diastolic volume no longer results in an increased stroke volume, and a continued increase in end-diastolic volume does not result in a further increase in stroke volume. In contrast, for patients with heart failure, a further increase in end-diastolic volume does not result in a substantially uniform stroke volume; instead, the stroke volume decreases. Thus, an increasing EDV in patients with HF leads to a further decrease in SV, a vicious cycle of cardiac function, and ultimately, death. A phenomenon termed "diastolic ventricular interaction" occurs, in part, due to the structural arrangement of the heart chambers. For example, as discussed in the paper "Diastolic ventricular interaction in chronic heart failure" by J. Atherton et al. (Lancet 1997; 349:1720-24), the pericardium restricts the extent to which the ventricles of a failing heart can expand. As a result, as the right ventricular end-diastolic volume increases, it necessarily causes a decrease in the left ventricular end-diastolic volume. As reported in that paper, a decrease in right ventricular diastolic filling caused by external lower body suction enables an increased left ventricular diastolic filling.

[0041] The Applicant understands that the aforementioned phenomenon can, advantageously, be utilized in the context of the present disclosure to improve cardiac performance. In particular, in the presence of heart failure and pulmonary hypertension, right ventricular congestion due to increased volume overload pushes the interventricular septum towards the left ventricular lumen, thereby reducing LV stroke volume and cardiac output. By occluding venous flow to the right atrium, right ventricular pressure and volume are reduced. This, in turn, will shift the interventricular septum away from the LV lumen, allowing for increased left ventricular stroke volume and increased cardiac output. For these reasons, venous occlusion according to the principles of the present disclosure can, advantageously, modify diastolic ventricular interaction and increase cardiac output. Specifically, with respect to diastolic heart failure, venous occlusion according to the principles of the present invention can provide a decrease in cardiac filling pressure, increased LV relaxation (tau), increased LV capacitance, increased myocardial relaxation, decreased LV stiffness, and decreased cardiac tension. To enter the right ventricle and then reduce the volume of blood that must be pumped by the left ventricle, and thus its pressure, in patients with HF, systems and methods that induce intermittent venous occlusion according to the present disclosure reduce the workload and wall stress of the myocardium throughout the cardiac cycle, reduce myocardial oxygen consumption, and improve systolic function. This improves cardiac function by moving the patient's cardiac contractility towards the Frank-Starling curve of a healthy patient.

[0042] Referring now to FIGS. 1A and 1B, an exemplary system 100 for venous occlusion is provided. System 100 includes a balloon catheter 101 that includes a catheter 106 having a proximal region 102 and a distal region 104 coupled to a controller 200, and one or more independently actuable flow limiting elements disposed on the distal region 104, such as a first flow limiting element 108 and a second flow limiting element 110. The first and second flow limiting elements 108, 110 are fluidly coupled to the controller 200, and the controller 200 is programmed to independently and intermittently actuate the first and second flow limiting elements 108, 110 according to a predetermined actuation regimen stored in the memory of the controller 200.

[0043] As shown in FIG. 1A, the second flow limiting element 110 is disposed on the catheter 106 proximal to the first flow limiting element 108. The first and second flow limiting elements 108, 110 may be sufficiently spaced along the catheter 106 such that the first flow limiting element 108 may be disposed in a first portion of the vein, e.g., on the opposite side of the vein, and the second flow limiting element 110 may be disposed in a second portion of the same vein, e.g., on the same side of the same vein. For example, the first flow limiting element 108 may be sized and shaped to be disposed within the contralateral iliac vein, while the second flow limiting element 110 may be sized and shaped to be disposed within the ipsilateral iliac vein. Further, as will be described in more detail below, the first flow limiting element 108 may be sized and shaped to be disposed within the contralateral subclavian vein, while the second flow limiting element 110 may be sized and shaped to be disposed within the ipsilateral subclavian vein.

[0044] In addition, the system 100 may include one or more sensors, such as sensors 103, 105, 107, for measuring one or more parameters (e.g., heart rate, blood flow rate, blood volume, and / or pressure including cardiac filling pressure) across the system 100 and generating a signal indicative of the measured parameter. For example, as shown in FIG. 1A, the sensor 103 may be disposed on the catheter 106 proximal to the second flow limiting element 110, the sensor 105 may be disposed on the catheter 106 between the first and second flow limiting elements 108, 110, and the sensor 107 may be disposed on the catheter 106 distal to the first flow limiting element 108. Alternatively, the one or more sensors may be one or more fluid columns within the catheter 106 such that pressure may be measured in the proximal region 102 of the catheter 106. The sensor 105 may be used, for example, to determine the extent of occlusion caused by the second flow limiting element 110 by monitoring the pressure drop across the second flow limiting element 110, and the sensor 107 may be used, for example, to determine the extent of occlusion caused by the first flow limiting element 108 by monitoring the pressure drop across the first flow limiting element 108.

[0045] The catheter 106 may include a flexible tube. The distal region 104 of the catheter 106 may be configured for placement within a patient's vein, such as the iliac vein, subclavian vein, SVC, or IVC, as will be described in more detail below. The distal end of the catheter 106 may include a tapered non-traumatic tip. As shown in FIG. 1A, the first and second flow limiting elements 108, 110 are, by way of example, expandable balloons that are capable of transitioning between a contracted state that enables transvascular placement and an expanded deployed state, thereby selectively obstructing blood flow into the patient's right atrium. The first and second flow limiting elements 108, 110 may be sized and shaped to completely occlude the target vein in the expanded state. Additionally, the catheter 106 may include an anchoring mechanism configured to anchor the flow distal region 104 to the target vein. For example, the anchoring mechanism may be contractible for delivery in the contracted state and expandable, for example, upon release from a delivery device, such as a sheath. The anchoring mechanism may be coupled to the catheter 106 proximal to the second flow limiting element 110, between the first and second flow limiting elements 108, 110, distal to the first flow limiting element 108, or combinations thereof.

[0046] Referring now to FIG. 2, an exemplary controller 200 is provided. The controller 200 includes a drive mechanism 220 (e.g., a motor, a pump) for actuating the first and second flow limiting elements 108, 110, a processor 202 programmed to control signals to the drive mechanism 210, and may store additional optional sensors for monitoring a patient's physiological parameters such as heart rate or blood pressure. The controller 200 may include or be fluidly coupled to a source of inflation medium (e.g., a gas or a fluid), such as a first inflation source 212 fluidly coupled to the first flow limiting element 108 and a second inflation source 214 fluidly coupled to the second flow limiting element 110. The drive mechanism 210 may be actuated to transfer the inflation medium between the first and second inflation sources 212, 214 and the respective first and second flow limiting elements 108, 110 in response to commands from the processor 202.

[0047] As shown in FIG. 1B, the catheter 106 may include a first inflation lumen 114 for fluidly coupling the first flow limiting element 108 to the first inflation source 212 and a second inflation lumen 116 for fluidly coupling the second flow limiting element 110 to the second inflation source 214. The proximal ends of the first inflation lumen 114 and the second inflation lumen 116 may each be connected to a side arm tube that terminates, for example, at a stopcock or a standard luer lock fitting. Each side arm tube may have a clamp configured to enable / disable flow through the respective lumen. Further, the proximal region 102 of the catheter 106 may include a hub that may be secured to the patient, for example, via a suture hole integrated within the hub or a through hole adapted to a stat lock. Additionally, the catheter 106 may include a guidewire lumen 112 sized and shaped to receive a guidewire to facilitate delivery of the distal region 104 of the catheter 106 to a target location within the patient's vasculature.

[0048] When either or both of the first and second flow limiting elements 108, 110 are inflated with an inflation medium, they occlude venous blood flow through each of the patient's veins, either partially or completely. When the inflation medium is withdrawn, the first and / or second flow limiting elements 108, 110 deflate, removing the occlusion and thereby allowing flow to resume within each vein. Each of the flow limiting elements may preferably be a balloon comprising a compliant or semi-compliant material, such as nylon, and the compliant or semi-compliant material allows the degree of balloon inflation to be adjusted to provide the desired partial or complete occlusion of the vein vessel. Additionally, the catheter 106 provides a fail-safe design in that when it is partially external, it can be inflated to provide occlusion only when the flow limiting element is such that the proximal end of the catheter 106 is coupled to the controller 200. Such quick-disconnect coupling in the proximal region 102 allows the catheter 106 to be quickly disconnected from the controller 200 for servicing and / or in the event of an emergency.

[0049] Referring again to FIG. 2, the controller 200 preferably also includes a power source 206 (e.g., a battery) that provides the power necessary to operate the processor 202, the data transfer circuit 208, and the drive mechanism 210. The power source 206 can be charged transcutaneously via an external power source, for example, via respective induction coils when the controller 200 is implanted. The controller 200 can be sized and of such a weight that it can be worn within an appliance under the patient's clothing, whereby the system can be used while the patient walks, or the controller 200 can be implanted within the patient. As discussed below in this specification, the processor 202 includes a memory 204 for storing computer software for operating the controller 200. The controller 200 can be configured for implantation at an appropriate location within the patient (e.g., subcutaneously under the collarbone). In such embodiments, the implantable controller is configured for bi-directional communication with an external controller, e.g., a computing device or a system-specific device. The external controller can be used, for example, to charge the battery of the implantable controller via respective induction coils (either within or coupled to each controller), and the external controller can receive data indicative of sensed parameters resulting from the patient's ambulatory activities, including pressure, including heart rate, blood flow, blood volume, and cardiac filling pressure.

[0050] The processor 202 can be programmed to maintain partial or complete venous occlusion over a preset number of cardiac cycles according to a predetermined actuation regimen determined at the initial implantation of the catheter. For example, the predetermined actuation regimen can be to expand only the first flow-limiting element 108 over a first period, then expand both the first and second flow-limiting elements 108, 110 over a second period after the first period, then contract the first flow-limiting element 108 to only the first flow-limiting element 110, whereby only the second flow-limiting element 110 is expanded over a third period after the second period, and then expand both the first and second flow-limiting elements 108, 110 over a fourth period after the third period. The predetermined actuation regimen can be repeated throughout the treatment session. Thus, during the treatment session according to the predetermined actuation regimen, at least one or both of the first flow-limiting element 108 and the second flow-limiting element 110 are expanded throughout the treatment session, thereby providing at least 70-90%, or preferably at least 80% overall occlusion throughout the treatment session, thereby effectively reducing the preload.

[0051] Each of the first, second, third, and fourth periods can be 1-15 minutes, or preferably 5-10 minutes. For example, the predetermined actuation regimen can be to expand only the first flow-limiting element 108 for 5 minutes, then expand both the first and second flow-limiting elements 108, 110 for 5 minutes, then expand only the second flow-limiting element 110 for 5 minutes, and then expand both the first and second flow-limiting elements 108, 110 for 5 minutes.

[0052] In one embodiment, the data transfer circuit 208 monitors inputs from external sensors, such as sensors 103, 105, 107 positioned on the catheter 200, and provides the signals to the processor 200. The processor 200 may be programmed to receive the inputs from the data transfer circuit 208 and adjust the interval during which the first and second flow limiting elements 108, 110 are maintained in the expanded state, or to adjust the degree of occlusion caused by the first and second flow limiting elements 108, 110. Thus, for example, sensors 103, 105, 107 disposed on the catheter 106 may measure parameters, such as pressures including heart rate, blood flow, blood volume, cardiac filling pressure, and central venous pressure. The outputs of sensors 103, 105, 107 are relayed to the data transfer circuit 208 of the controller 200, and the data transfer circuit 208 may preprocess the input signals, such as decimating and digitizing the outputs of the sensors, before the input signals are supplied to the processor 202. The signals provided to the processor 202 enable the assessment of the effectiveness of the flow limiting elements, for example, by indicating the reduced venous pressure during occlusion and during the open state, and the signals may be used by the patient or clinician to determine the amount of occlusion required to adjust the venous blood reflux based on the severity of congestion in the patient.

[0053] As another example, at least one of sensors 103, 105, 107 can be one or more electrodes for sensing a patient's heart rate. It may be desirable to adjust a predetermined actuation regimen, e.g., the intervals during which venous occlusion by each flow restriction element is maintained, in response to the patient's walking activity, which will typically be reflected in the patient's hemodynamic state by sensed physiological parameters such as heart rate, blood flow, blood volume, cardiac filling pressure and / or pressure including central venous pressure. Thus, the electrodes can provide signals to data transfer circuit 208, which then processes the signals for use by a programmed routine initiated by processor 202. For example, if the occlusion by the first flow restriction element 108 is maintained for a programmed time during initial system setup such that the flow restriction element is deployed for 15 minutes and then released for 5 minutes before being re-expanded, it may be desirable to reduce the occluded time interval by 10 minutes or more in response to a level of the patient's physical activity detected by a change in pressure including heart rate, blood flow, blood volume, cardiac filling pressure and / or central venous pressure that exceeds or falls below a predetermined threshold. Sensor inputs provided to data transfer circuit 208, such as hemodynamic state data, can also be used to adjust the duty cycle of the flow restriction element in response to the detected level of the patient's activity. Additionally, processor 202 can be programmed to maintain partial or complete occlusion within each vein for a preset number of cardiac cycles after a predetermined occlusion interval has been adjusted.

[0054] The data transfer circuit 208 may also be configured to provide bidirectional transfer of data, for example, by including a wireless network for transferring data from the controller 200 to an external unit for display, auditing, or adjustment. For example, the data transfer circuit 208 may include a Bluetooth® network, which enables the controller 200 to communicate with an external controller, such as a smartphone, laptop, smartwatch, or tablet, etc., of a patient on which a special-purpose application for controlling it and / or communicating with it is installed. In this way, the controller 200 may use a suitably configured mobile application to directly transmit information regarding the system's functions to a computing device for display of important physiological or system parameters. In addition, the patient may review the data displayed on the screen of the computing device and determine whether he or she needs to seek medical assistance to address a malfunction or to adjust system parameters. Further, the mobile application resident on the computing device may be configured to automatically initiate an alert to a clinician's monitoring service via a cellular phone network.

[0055] Referring now to FIG. 3, an exemplary method 300 is provided for delivering and operating the system 100 of FIG. 1A within a patient's common iliac vein to improve cardiac performance. Some of the steps of method 300 may be further detailed by referring to FIGS. 4A - 4D. At step 302, a guidewire may be inserted into the patient through the femoral vein, up the femoral vein, across the ipsilateral common iliac vein towards the common iliac vein, and into the contralateral side of the common iliac vein. At step 304, the catheter 106 may be inserted into the introducer sheath, with the first and second flow - limiting elements 108, 110 in their folded delivery state within the sheath. The introducer sheath and the balloon catheter 101 disposed therein may then be advanced over the guidewire, within the sheath, until the first flow - limiting element 108 is positioned within the contralateral iliac vein and the second flow - limiting element 110 is positioned within the ipsilateral iliac vein, for example, via the guidewire lumen 112 of the catheter 106. The guidewire may then be removed from the catheter 106. The guidewire lumen 112 may be flushed prior to closing the guidewire lumen 112 with a cap or clamp on a sidearm coupled to the guidewire lumen 112. The proximal end of the catheter 106 may then be coupled to the controller 200 such that the first inflation lumen 114 is coupled to the first inflation source 212 and the second inflation lumen 116 is coupled to the second inflation source 214.

[0056] At step 306, the sheath may be retracted relative to the catheter 106 such that the first flow - limiting element 108 is deployed within the contralateral iliac vein and the second flow - limiting element 110 is deployed within the ipsilateral iliac vein. At step 308, the first and second flow - limiting elements 108, 110 may be actuated via the controller 200 to expand within respective portions of the common iliac vein according to a predetermined actuation regimen, intermittently occluding blood flow through the contralateral and ipsilateral iliac veins, thereby reducing pre - cardiac load and selectively increasing the arterial vascular resistance of the patient's extremities in fluid communication with the occluded veins while increasing perfusion to the patient's heart and organs.

[0057] For example, during a first period, e.g., over 5 minutes, a predetermined actuation regimen may expand only the first flow limiting element 108 within the contralateral iliac vein, as shown in FIG. 4A. During a second period following the first period, e.g., over 5 minutes, a predetermined actuation regimen may expand both the first and second flow limiting elements 108, 110 within the contralateral and ipsilateral iliac veins, respectively, as shown in FIG. 4B. During a third period following the second period, e.g., over 5 minutes, a predetermined actuation regimen may contract the first flow limiting element 108 such that only the second flow limiting element 110 remains expanded within the ipsilateral iliac vein, as shown in FIG. 4C. During a fourth period following the third period, e.g., over 5 minutes, a predetermined actuation regimen may expand both the first and second flow limiting elements 108, 110 within the contralateral and ipsilateral iliac veins, respectively, as shown in FIG. 4D. This actuation pattern may be repeated throughout the treatment session. Thus, during a fifth period following the fourth period, e.g., over 5 minutes, a predetermined actuation regimen may contract the second flow limiting element 110 such that only the first flow limiting element 108 remains expanded within the contralateral iliac vein, and so on.

[0058] Referring now to FIG. 5, an exemplary method 500 is provided for delivering and operating the system 100 of FIG. 1A within a patient's subclavian vein to improve cardiac performance. Some of the steps of method 500 may be further detailed by referring to FIGS. 6A-6D. At step 502, a guide wire may be inserted into the patient, through the jugular vein, down the jugular vein, across the ipsilateral superior subclavian vein, and to the contralateral side of the subclavian vein. At step 504, the catheter 106 may be inserted into the introducer sheath such that the first and second flow limiting elements 108, 110 are in their folded delivery state within the sheath. The introducer sheath and the balloon catheter 101 disposed therein may then be advanced over the guide wire, for example, through the guide wire lumen 112 of the catheter 106, until the first flow limiting element 108 is positioned within the contralateral subclavian vein and the second flow limiting element 110 is positioned within the ipsilateral subclavian vein. The guide wire may then be removed from the catheter 106. As described above, the guide wire lumen 112 may be flushed prior to closing the guide wire lumen 112 with a cap or clamp on a side arm coupled to the guide wire lumen 112, and the proximal end of the catheter 106 may then be coupled to the controller 106 such that the first inflation lumen 114 is coupled to the first inflation source 212 and the second inflation lumen 116 is coupled to the second inflation source 214.

[0059] At step 506, the sheath may be retracted relative to the catheter 106 such that the first flow limiting element 108 is deployed within the contralateral subclavian vein and the second flow limiting element 110 is deployed within the ipsilateral subclavian vein. At step 508, the first and second flow limiting elements 108, 110 may be expanded within respective portions of the subclavian vein according to a predetermined actuation regimen to intermittently occlude blood flow through the contralateral and ipsilateral subclavian veins, thereby reducing preload on the heart and selectively increasing the arterial vascular resistance of the patient's extremities that are in fluid communication with the occluded veins while increasing perfusion to the patient's heart and organs, and may be actuated via the controller 200.

[0060] For example, during a first period, for example, over 5 minutes, a predetermined actuation regimen may expand only the first flow limiting element 108 within the contralateral subclavian vein, as shown in FIG. 6A. During a second period following the first period, for example, over 5 minutes, a predetermined actuation regimen may expand both the first and second flow limiting elements 108, 110 within the contralateral and ipsilateral subclavian veins, respectively, as shown in FIG. 6B. During a third period following the second period, for example, over 5 minutes, a predetermined actuation regimen may reduce the first flow limiting element 108 such that only the second flow limiting element 110 remains expanded within the ipsilateral subclavian vein, as shown in FIG. 6C. During a fourth period following the third period, for example, over 5 minutes, a predetermined actuation regimen may expand both the first and second flow limiting elements 108, 110 within the contralateral and ipsilateral subclavian veins, respectively, as shown in FIG. 6D. This actuation pattern may be repeated throughout the treatment session. Thus, during a fifth period following the fourth period, for example, over 5 minutes, a predetermined actuation regimen may reduce the second flow limiting element 110 such that only the first flow limiting element 108 remains expanded within the contralateral subclavian vein, and so on.

[0061] Referring now to FIG. 7, an exemplary system 700 for vein occlusion is provided. System 700 may be constructed similarly to system 100, except that system 700 includes two balloon catheters, e.g., a first balloon catheter 101 and a second balloon catheter 101'. The first balloon catheter 101 of system 700 may be constructed similarly to the balloon catheter of system 100, and the second balloon catheter 101' may be constructed similarly to the first balloon catheter 101, with similar components having similar prime reference numbers. However, the second balloon catheter 101' differs from the first balloon catheter 101 in that the third and fourth flow-limiting elements 108', 110' may be sized and shaped to completely occlude the contralateral and ipsilateral subclavian veins, respectively, while the first and second flow-limiting elements 108, 110 may be sized and shaped to completely occlude the contralateral and ipsilateral iliac veins, respectively (or vice versa).

[0062] Therefore, as shown in FIG. 8, the first balloon catheter 101 can be inserted into a patient via the femoral vein using the method 300 described above such that the first flow limiting element 108 is deployed within the contralateral iliac vein and the second flow limiting element 110 is deployed within the ipsilateral iliac vein, and the second balloon catheter 101' can be inserted into a patient via the jugular vein using the method 500 described above such that the third flow limiting element 108' is deployed within the contralateral subclavian vein and the fourth flow limiting element 110' is deployed within the ipsilateral subclavian vein. The first and second flow limiting elements 108, 110 can be actuated via the controller 200 to expand within respective portions of the common iliac vein according to a predetermined actuation regimen and intermittently occlude blood flow through the contralateral and ipsilateral iliac veins, and the third and fourth flow limiting elements 108', 110' can be actuated via the controller 200' to expand within respective portions of the subclavian vein according to a predetermined actuation regimen and intermittently occlude blood flow through the contralateral and ipsilateral subclavian veins, thereby reducing the preload on the heart and selectively increasing the arterial vascular resistance of the patient's extremities in fluid communication with the occluded veins while increasing perfusion to the patient's heart and organs. Two controllers are illustrated in FIGS. 7 and 8, but as will be understood by those skilled in the art, the system 700 can include a single controller with a number of flow limiting elements of the system 700 and a corresponding number of inflation sources such that both the first and second balloon catheters 101, 101' can be coupled to the controller.

[0063] The selective actuation of the first and second balloon catheters 101, 101' provides corresponding selective occlusion of the respective veins, e.g., the common iliac vein and the subclavian vein, thereby selectively increasing the vascular resistance within each vein, which can then selectively reduce the arterial blood flow to the limb in fluid communication with the occluded vein. For example, FIG. 9 is a schematic diagram illustrating the selective modulation of vascular resistance according to the principles of the present disclosure. In FIG. 9, Q1 represents the arterial blood flow from the heart to the upper limb of the patient, e.g., the head and arm, Q2 represents the arterial blood flow from the patient's lungs to the heart H and the central organs, and Q3 represents the arterial blood flow from the heart to the lower limb of the patient, e.g., the leg. Further, R1 represents the arterial vascular resistance to the upper limb of the patient, R2 represents the arterial vascular resistance to the patient's heart and central organs, and R4 represents the arterial vascular resistance to the lower limb of the patient.

[0064] In addition, R3 represents the venous vascular resistance as a result of occlusion by the second balloon catheter 101' of the venous vessel in fluid communication with the upper limb of the patient, e.g., the subclavian vein, and R5 represents the venous vascular resistance as a result of occlusion by the first balloon catheter 101 of the venous vessel in fluid communication with the lower limb of the patient, e.g., the common iliac vein. R6 represents the venous vascular resistance of the collateral reflux of the blood flow from the lower limb of the patient, and R7 represents the venous vascular resistance of the collateral reflux of the blood flow from the upper limb of the patient. Thus, when the first balloon catheter 101 is actuated to occlude the common iliac vein, e.g., via the intermittent expansion of the first and second flow-limiting elements 108, 110, R5, and correspondingly, R6, increase, which causes a corresponding increase in R4 and a corresponding decrease in Q3. Similarly, when the second balloon catheter 101' is actuated to occlude the subclavian vein, e.g., via the intermittent expansion of the first and second flow-limiting elements 108', 110', R3, and correspondingly, R7, increase, which causes a corresponding increase in R1 and a corresponding decrease in Q1.

[0065] As a result, the patient's mean arterial pressure (MAP) increases, similar to the result of "pressing" the patient with a vasopressor. However, since there is no increase in R2 (arterial vascular resistance to the patient's heart and central organs), as the MAP increases, Q2 increases (i.e., perfusion to the patient's heart and organs increases), but the overall fluid flow in the body decreases. This is because the changes in Q1 and Q3 are greater than the change in Q2. Therefore, the patient's heart is unloaded in a manner equivalent to the reduction in the overall fluid flow reduction in the system while maintaining the state where the patient's heart and central organs are perfused. Thus, assuming that 30% of the blood flow goes to the patient's upper extremities and 20% of the blood flow goes to the patient's lower extremities, the patient's heart can be unloaded by up to 50%.

[0066] Therefore, the system 700 can selectively and intermittently occlude the venous vessels to the patient's lower and upper extremities, for example, by increasing R5 and / or R3, which reduces the arterial blood flow to the patient's lower and / or upper extremities, for example, by decreasing Q3 and / or Q1, and can improve the perfusion to the patient's heart and central organs. Thus, the arterial blood flow to the patient's extremities, such as the lower extremities like the legs, can be selectively reduced to maintain or improve the perfusion to the patient's heart and central organs. This can be important for patients (e.g., patients who require less oxygen to the legs) who are in a situation that requires at least a minimum / optimal perfusion to the heart and can tolerate a temporarily reduced arterial blood flow to the legs. As will be understood by those skilled in the art, the selective modulation of vascular resistance can be achieved by using the system 100 in either the common iliac vein by the method 300 or the subclavian vein by the method 500, or by using the system 700 in both the common iliac vein and the subclavian vein. Further, according to another aspect of the present disclosure, the selective modulation of vascular resistance can be achieved by selectively and intermittently occluding the patient's superior vena cava (SVC) and inferior vena cava (IVC).

[0067] Referring now to FIG. 10, an exemplary system 1000 for venous occlusion is provided. System 1000 includes a first balloon catheter 1001 and a second balloon catheter 1001'. The first balloon catheter 1001 includes a catheter 1006 having a proximal region 1002 and a distal region 1004 coupled to a controller 200'', and an independently operable first flow limiting element 1008 disposed on the distal region 1004. As shown in FIG. 10, the first flow limiting element 1008 can be an expandable balloon, and the expandable balloon can transition between a collapsed state that enables transvascular placement and an expanded deployed state that selectively impedes blood flow into the patient's right atrium. The first flow limiting element 1008 can be sized and shaped to completely occlude a target vein, e.g., the SVC, in the expanded state. Additionally, the first balloon catheter 1001 can include one or more sensors, e.g., a sensor 1003 disposed on the catheter 1006 proximal to the first flow limiting element 1008 and a sensor 1005 disposed on the catheter 1006 distal to the first flow limiting element 1008, to measure one or more parameters across the system 1000 and generate a signal indicative of the measured parameters. Further, the first flow limiting element 1008 is fluidly coupled to a controller 200'', which can be constructed similarly to controller 200 except that the controller 200'' can have only a single inflation source. Thus, the controller 200'' is programmed to independently and intermittently operate the first flow limiting element 1008 according to a predetermined operating regimen stored in the memory of the controller 200''.

[0068] The second balloon catheter 1001' can be constructed similarly to the first balloon catheter 1001, and similar components have similar prime reference numbers. However, the second flow limiting element 1008' of the second balloon catheter 1001' can be sized and shaped to completely occlude the IVC in the expanded state. Additionally, the catheter 1006' of the second balloon catheter 1001' can be coupled to a controller 200''' that can be constructed similarly to the controller 200''. Thus, the controller 200''' is programmed to independently and intermittently operate the second flow limiting element 1008' according to a predetermined actuation regimen stored in the memory of the controller 200'''.

[0069] Referring now to FIG. 11, an exemplary method 1100 is provided for delivering and operating the system 1000 of FIG. 10 within a patient's SVC and IVC to improve cardiac performance. Some of the steps of method 1100 may be described in further detail by referring to FIGS. 12A-12D. At step 1102, a guidewire may be inserted into the patient through the jugular vein, down the jugular vein, across the subclavian vein, and toward the SVC. At step 1104, the catheter 1006 may be inserted into the introducer sheath, and the first flow-limiting element 1008 is in its folded delivery state within the sheath. The introducer sheath and the first balloon catheter 1001 disposed therein may then be advanced over the guidewire through the guidewire lumen of the catheter 1006 within the sheath until the first flow-limiting element 1008 is positioned within the SVC. The guidewire may then be removed from the catheter 1006, and the guidewire lumen of the catheter 1006 may be flushed prior to closing the guidewire lumen with a cap or clamp on a side arm coupled to the guidewire lumen. The proximal end of the catheter 1006 may then be coupled to the controller 200'' such that the inflation lumen of the catheter 1006 fluidly coupled to the first flow-limiting element 1008 may be coupled to an inflation source within (or fluidly coupled to) the controller 200''. At step 1106, the sheath may be retracted relative to the catheter 1006 such that the first flow-limiting element 1008 is deployed within the SVC.

[0070] In step 1108, the guide wire can be inserted into the patient through the femoral vein, up the femoral vein, towards the common iliac vein, across the common iliac vein, and towards the IVC. In step 1110, the catheter 1006' can be inserted into the introducer sheath, and the second flow limiting element 1008' is in its folded delivery state within the sheath. The introducer sheath and the second balloon catheter 1001' disposed therein can then be advanced over the guide wire through the guide wire lumen of the catheter 1006' within the sheath until the second flow limiting element 1008' is positioned within the IVC. The guide wire can then be removed from the catheter 1006', and the guide wire lumen of the catheter 1006' can be flushed prior to closing the guide wire lumen with a cap or clamp on a side arm coupled to the guide wire lumen. The proximal end of the catheter 1006' can then be coupled to the controller 200''' such that the inflation lumen of the catheter 1006' fluidly coupled to the second flow limiting element 1008' can be coupled to an inflation source within (or fluidly coupled to) the controller 200'''. In step 1112, the sheath can be retracted relative to the catheter 1006' such that the second flow limiting element 1008' is deployed within the IVC.

[0071] In step 1114, the first and second flow-limiting elements 1008, 1008' expand within the SVC and IVC respectively according to a predetermined actuation regime, intermittently occluding blood flow through the SVC and IVC, thereby reducing the preload of the heart and selectively increasing the arterial vascular resistance of the patient's limbs that are in fluid communication with the occluded vein while increasing perfusion to the patient's heart and organs, and can be actuated via controllers 200'', 200'''. For example, for a first period, for example, over 5 minutes, the predetermined actuation regime can expand only the second flow-limiting element 1008' within the IVC, as shown in FIG. 12A. For a second period following the first period, for example, over 5 minutes, the predetermined actuation regime can expand both the first and second flow-limiting elements 1008, 1008' within the SVC and IVC respectively, as shown in FIG. 12B. For a third period following the second period, for example, over 5 minutes, the predetermined actuation regime can contract the second flow-limiting element 1008' such that only the first flow-limiting element 1008 remains expanded within the SVC, as shown in FIG. 12C. For a fourth period following the third period, for example, over 5 minutes, the predetermined actuation regime can expand both the first and second flow-limiting elements 1008, 1008' within the SVC and IVC respectively, as shown in FIG. 12D. This actuation pattern can be repeated throughout the treatment session. Thus, for a fifth period following the fourth period, for example, over 5 minutes, the predetermined actuation regime can contract the first flow-limiting element 1008 such that only the second flow-limiting element 1008' remains expanded within the IVC, and so on.

[0072] As described above with respect to FIG. 9, the selective intermittent modulation of the SVC and IVC by the system 1000 can selectively modulate vascular resistance. For example, the intermittent occlusion of the SVC by the first flow limiting element 1008 of the system 1000 can achieve results equivalent to the intermittent occlusion of the contralateral and ipsilateral subclavian veins by the third and fourth flow limiting elements 108', 110' of the system 700, e.g., increased R3 and R7, and correspondingly, increased R1 and decreased Q1. In addition, the intermittent occlusion of the IVC by the second flow limiting element 1008' of the system 1000 can achieve results equivalent to the intermittent occlusion of the contralateral and ipsilateral common iliac veins by the first and second flow limiting elements 108, 110 of the system 700, e.g., increased R5 and R6, and correspondingly, increased R3 and decreased Q3. Thus, with a higher MAP and no increase in R2, Q2 increases (i.e., perfusion to the patient's heart and organs increases), but the overall flow of the body decreases. Therefore, the patient's heart is unloaded in a manner equivalent to the reduction in the overall flow of the system while maintaining the state in which the patient's heart and central organs are perfused.

[0073] Referring now to FIG. 13, an additional system for improving cardiac performance can be used in conjunction with any one of the systems of FIGS. 1A, 7, and 10 according to the principles of the present disclosure. For example, as shown in FIG. 13, a system 1000 having a first balloon catheter 1001 positioned within the SVC and a second balloon catheter 1001' positioned within the IVC can be used in conjunction with a mechanical circulatory support (MCS) device such as an Impella® heart pump (available from Abiomed® (Danvers, Massachusetts)). The MCS device includes a pump disposed on the distal region of the catheter, for example, an Impella pump, which can be selectively actuated to pump blood from the left ventricle through an inflow end and discharge the blood into the aorta through an outflow end, and an MCS device controller 200'''' operably coupled to the MCS device, the MCS device controller 200'''' actuating the pump to pump blood from the left ventricle to the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. The MCS device controller 200'''' can coordinate the activation and deactivation of a first flow limiting element 1008 for at least partially occluding the SVC and a second flow limiting element 1008' for at least partially occluding the IVC while the MCS device controller 200'''' actuates the pump to pump blood from the left ventricle to the aorta. Alternatively, the first balloon catheter 1001 positioned within the SVC can be used in conjunction with the MCS device without the second balloon catheter 1001' positioned within the IVC to improve cardiac performance. Alternatively, the second balloon catheter 1001' positioned within the IVC can be used in conjunction with the MCS device without the first balloon catheter 1001 positioned within the SVC to improve cardiac performance.When using any of the systems described herein with an MCS device, the size of the MCS is reduced because the pump of the MCS device will be required to provide less flow to provide complete unloading of the heart, thereby reducing the arterial access size. Thus, the size of the delivery sheath can also be reduced without increasing vascular recoil and can reduce insertions related to vascular complications, ischemia risk, and compatibility with small-bore closures. Further, a vasodilator can be administered to the patient while the vascular resistance of the arm, head, and legs will continue to be limited, and the vasodilator will further increase perfusion to the heart and organs even in patients with low MAP.

[0074] Alternatively, or in addition, system 1000 can further include an MCS device configured to be selectively actuated to pump blood from the SVC through the inflow end of the MCS device and discharge the blood into the pulmonary artery through the outflow end of the MCS device. The controller can also be operably coupled to the MCS device to actuate the pump to pump blood from the SVC to the pulmonary artery, thereby unloading the right ventricle. For example, the controller can intermittently actuate the first flow limiting element 1008 to at least partially occlude the SVC and intermittently actuate the second flow limiting element 1008' to at least partially occlude the IVC while actuating the MCS device pump to pump blood from the SVC to the pulmonary artery.

[0075] Similarly, either of systems 100 and 700 can be used in combination with any or both of the MCS devices described above to improve cardiac performance in accordance with the principles of the present disclosure described herein. Further, either of systems 100 and 700 can also be used with a first balloon catheter 1001 positioned within the SVC and / or a second balloon catheter 1001' disposed within the IVC to improve cardiac performance. For example, the balloon catheter 101 of system 100 can be positioned within the subclavian vein such that a first flow-limiting element 108 is positioned within the contralateral subclavian vein and a second flow-limiting element 110 is positioned within the ipsilateral subclavian vein, and the first flow-limiting element 1008 of the second balloon catheter 1001 can be positioned within the SVC. The balloon catheter 101 and the first balloon catheter 1001 can be intermittently actuated according to a predetermined actuation regimen to selectively modulate vascular resistance as described above to improve cardiac performance.

[0076] Although various illustrative embodiments of the present invention have been described above, it will be apparent to those skilled in the art that various changes and modifications can be made therein without departing from the invention. The appended claims are intended to cover all such changes and modifications that fall within the true scope of the invention.

Claims

**Claim 1** A system for unloading a patient's heart to improve cardiac performance, the system comprising: a first flow-limiting element configured to be selectively actuated to occlude a first vein in fluid communication with a first limb of the patient; a second flow-limiting element configured to be selectively actuated to occlude a second vein in fluid communication with a second limb of the patient; a controller operably coupled to the first and second flow-limiting elements; wherein the controller is configured to expand the first and / or second flow-limiting elements according to a predetermined actuation regimen to selectively occlude the first and / or second vein, reduce pre-cardiac load, increase mean arterial pressure, thereby selectively increasing the arterial vascular resistance of the patient's limbs while maintaining the arterial vascular resistance of the patient's heart and end organs, and increasing perfusion to the patient's heart and end organs. **Claim 2** The system of claim 1, wherein the first vein is the contralateral iliac vein and the second vein is the ipsilateral iliac vein. **Claim 3** The system of claim 2, further comprising a mechanical circulatory support (MCS) device. **Claim 4** The system of claim 2, further comprising a third flow-limiting element operably coupled to the controller and configured to be selectively actuated to occlude the patient's superior vena cava (SVC); wherein the controller is configured to expand the third flow-limiting element according to a second predetermined actuation regimen to occlude the SVC and reduce pre-cardiac load. **Claim 5** The system of claim 4, further comprising a mechanical circulatory support (MCS) device. **Claim 6** The system further comprising a third flow-limiting element operably coupled to the controller and configured to be selectively actuated to occlude the patient's contralateral subclavian vein; and a fourth flow-limiting element operably coupled to the controller and configured to be selectively actuated to occlude the patient's ipsilateral subclavian vein. wherein The controller is configured to expand the third and / or fourth flow limiting elements according to a second predetermined actuation regimen, selectively occlude the contralateral and / or ipsilateral subclavian veins, reduce the pre-cardiac load, increase the mean arterial pressure, thereby maintaining the arterial vascular resistance of the heart and end organs of the patient while selectively increasing the arterial vascular resistance of the limbs of the patient and increasing the perfusion of the heart and end organs of the patient, the system according to claim 2.

7. The system according to claim 6, further comprising a mechanical circulatory support (MCS) device.

8. Further comprising a fifth flow limiting element operably coupled to the controller and configured to be selectively actuated to occlude the superior vena cava (SVC) of the patient, The controller is configured to expand the fifth flow limiting element according to a third predetermined actuation regimen to occlude the SVC and reduce the pre-cardiac load, the system according to claim 6.

9. The system according to claim 8, further comprising a mechanical circulatory support (MCS) device.

10. Further comprising a catheter operably coupled to the controller, The first and second flow limiting elements are disposed on a distal region of the catheter, the system according to claim 2.

11. The first vein is the superior vena cava (SVC) and the second vein is the inferior vena cava (IVC), the system according to claim 1.

12. The system according to claim 11, further comprising a mechanical circulatory support (MCS) device.

13. A first catheter operably coupled to the controller, A second catheter operably coupled to the controller and further comprising, The first flow limiting element is disposed on a distal region of the first catheter, and the second flow limiting element is disposed on a distal region of the second catheter, the system according to claim 11.

14. The predetermined actuation regimen is expanding only the first flow limiting element over a first period, expanding the first and second flow limiting elements over a second period after the first period, expanding only the second flow limiting element over a third period after the second period, expanding the first and second flow restriction elements over a fourth period after the third period The system of claim 1, programmed to perform the above. **Claim 15** The system of claim 1, wherein the predetermined operating regimen is programmed to cause at least 70% occlusion of the first and second veins during a treatment period. **Claim 16** The system of claim 1, wherein the predetermined operating regimen is programmed in the controller such that the first flow restriction element or the second flow restriction element, or both, maintain occlusion throughout a treatment session. **Claim 17** The system of claim 1, wherein each occlusion period during a treatment session is at least 1 minute. **Claim 18** The system of claim 1, further comprising one or more sensors configured to measure one or more parameters and generate one or more signals indicative of the one or more measured parameters. **Claim 19** The system of claim 18, wherein a first sensor of the one or more sensors is disposed proximal to the first flow restriction element, and a second sensor of the one or more sensors is disposed proximal to the second flow restriction element. **Claim 20** The system of claim 18, wherein the controller is configured to adjust the predetermined operating regimen to selectively occlude the first and / or second veins in response to the one or more signals indicative of the one or more measured parameters. **Claim 21** A method of unloading a patient's heart to improve cardiac performance, the method comprising: positioning a first flow restriction element within a first vein in fluid communication with a first limb of the patient; positioning a second flow restriction element within a second vein in fluid communication with a second limb of the patient; expanding the first and / or second flow restriction elements according to a predetermined operating regimen to selectively occlude the first and / or second veins, reduce pre-cardiac load, increase mean arterial pressure, thereby selectively increasing the arterial vascular resistance of the patient's limbs while maintaining the arterial vascular resistance of the patient's heart and end organs and increasing perfusion to the patient's heart and end organs including the method. **Claim 22** Positioning the first flow-limiting element within the first vein of the patient includes positioning the first flow-limiting element within the contralateral iliac vein of the patient, The method of claim 21, wherein positioning the second flow-limiting element within the second vein of the patient includes positioning the second flow-limiting element within the ipsilateral iliac vein of the patient.

23. Positioning a third flow-limiting element within the contralateral subclavian vein of the patient, Positioning a fourth flow-limiting element within the ipsilateral subclavian vein of the patient, Expanding the third and / or fourth flow-limiting elements according to a second predetermined actuation regimen to selectively occlude the contralateral and / or ipsilateral subclavian veins, reduce pre-cardiac load, increase mean arterial pressure, thereby selectively increasing the arterial vascular resistance of the patient's extremities while maintaining the arterial vascular resistance of the patient's heart and end organs and increasing perfusion to the patient's heart and end organs The method of claim 22, further comprising:

24. Positioning a third flow-limiting element within the superior vena cava of the patient, Intermittently actuating the third flow-limiting element according to a second predetermined actuation regimen to occlude the SVC and reduce pre-cardiac load The method of claim 21, further comprising:

25. Positioning a mechanical circulatory support (MCS) device within the patient's heart, Actuating the MCS device The method of claim 21, further comprising:

26. Expanding the first and / or second flow-limiting elements according to the predetermined actuation regimen includes maintaining occlusion of the first flow-limiting element or the second flow-limiting element, or both, throughout the treatment session. The method of claim 21.

27. Expanding the first and / or second flow-limiting elements according to the predetermined actuation regimen includes: Expanding only the first flow-limiting element over a first period, Expanding the first and second flow-limiting elements over a second period after the first period, Expanding only the second flow-limiting element over a third period after the second period, Expanding the first and second flow-limiting elements over a fourth period after the third period The method of claim 21, comprising:

28. Positioning the first flow-limiting element within the first vein of the patient includes positioning the first flow-limiting element within the superior vena cava (SVC) of the patient, The method of claim 21, wherein positioning the second flow-limiting element within the second vein of the patient includes positioning the second flow-limiting element within the inferior vena cava (IVC) of the patient.

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