System and method for selectively occluding superior vena cava for treating cardiac disease

Abstract

To provide a method and a system for improving cardiac function in patients suffering from heart failure, including patients with reduced ejection fraction, and for treating pulmonary hypertension and / or cardiorenal syndrome.SOLUTION: Systems and methods and devices are provided for treating conditions such as heart failure and / or pulmonary hypertension by at least partially occluding blood flow through the superior vena cava for an interval spanning multiple cardiac cycles. A catheter 31 with an occlusion device 32 is provided along with a controller that actuates a drive mechanism to provide at least partial occlusion of the patient's superior vena cava (SVC), which reduces cardiac filling pressures, and induces a favorable shift in the patient's Frank-Starling curve towards healthy heart functionality and improved cardiac performance. The occlusion device may include a lumen obstructed by a relief valve that may permit fluid flow through the occlusion device to release an excessive build-up of pressure.SELECTED DRAWING: Figure 43

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 62 / 576,529, filed October 24, 2017, and U.S. Provisional Application No. 62 / 642,569, filed March 13, 2018, the entire contents of each of which are incorporated herein by reference. This application is also related to U.S. Patent Application No. 15 / 753,300, filed February 17, 2018, which is a national stage application of PCT / US2016 / 047055, filed August 15, 2016, which is a continuation-in-part of U.S. Patent Application No. 15 / 203,437, filed July 6, 2016, which is a continuation-in-part of U.S. Patent Application No. 14 / 828,429, filed August 17, 2015, now U.S. Patent No. 9,393,384, the entire contents of each of which are incorporated herein by reference.

[0002] The present disclosure relates to methods and systems for improving cardiac function and treating pulmonary hypertension and / or cardiorenal syndrome in patients suffering from heart failure, including patients with reduced ejection fraction. [Background technology]

[0003] Heart failure is the leading cause of death worldwide. It often necessitates repeated long-term hospitalizations, especially in the later stages of the disease. Without heart transplantation, the long-term prognosis for such patients is poor, and pharmaceutical approaches provide only palliative care. Thus, there are few effective treatments to slow or reverse the progression of the disease.

[0004] Heart failure can result from any of several initiating events. It can occur as a result of ischemic heart disease, hypertension, valvular disease, infection, inherited cardiomyopathies, pulmonary hypertension, or conditions of metabolic stress, including pregnancy. Heart failure can also develop without a clear cause - also known as idiopathic cardiomyopathies. The term heart failure includes left ventricular failure, right ventricular failure, or biventricular failure.

[0005] Although the heart can often initially respond successfully to increased workload due to hypertension or contractile tissue damage, this stress over time induces compensatory cardiomyocyte hypertrophy and ventricular wall remodeling. In particular, over the next few months after the initial cardiac injury, the damaged portion of the heart will usually begin to remodel as the heart struggles to continue pumping blood with reduced muscle mass or reduced contractility. This in turn leads to overwork of the myocardium, which gradually thins, expands, and becomes more overloaded in the damaged area. At the same time, the ejection fraction of the damaged ventricle decreases, reducing cardiac output, and the mean ventricular pressure and volume become larger throughout the cardiac cycle, a sign of heart failure. Not surprisingly, once a patient's heart is caught in this progressive, never-ending downward spiral, the patient's quality of life is severely affected and the risk of morbidity soars. Depending on many factors, including the patient's previous physical condition, age, sex, and lifestyle, patients may experience one or several hospitalizations, at considerable cost to the patient and to the healthcare system as a whole, until they die from cardiac arrest or from one of many comorbidities, including stroke, kidney failure, liver failure, or pulmonary hypertension.

[0006] Currently, there are no solutions that utilize devices specifically aimed at reducing preload to slow the progression of heart failure. Although pharmaceutical approaches are available as a palliative to alleviate the symptoms of heart failure, there are no pharmaceutical procedures that can halt or reverse the progression of heart failure. Furthermore, existing pharmaceutical approaches are systemic in nature and do not address the local effects that remodeling has on cardiac structures. Therefore, it would be desirable to provide a system and method for treating heart failure that can halt and, more preferably, reverse the progression of cardiac remodeling, which in turn has consequences associated with this disease.

[0007] Applicant has noted that there have been several attempts in the prior art to resolve heart failure. Prior to Applicant's invention described herein, there have been no commercially available and effective devices to treat this disease. Below, several known examples of known systems and methods for treating various symptoms of heart failure are described, but none of them appear to attempt or be able to reduce left ventricular end-diastolic volume ("LVEDV"), left ventricular end-diastolic pressure ("LVEDP"), right ventricular end-diastolic volume ("RVEDV"), or right ventricular end-diastolic pressure ("RVEDP") without causing severe side effects.

[0008] For example, US Patent No. 4,546,759 to Solar describes a triple balloon catheter designed to be deployed, with a distal balloon intermittently occluding the superior vena cava, a proximal balloon intermittently occluding the inferior vena cava, and a middle balloon expanding in synchrony with the onset of right ventricular systole, thereby increasing the ejection of blood from the right ventricle. The patent describes the system as being designed to expand and contract in synchrony with normal cardiac rhythm, reducing the load on the right ventricle and allowing right ventricular damage or defects to heal. The patent does not describe or suggest that the proposed adjustments to blood flow into or out of the right ventricle affect either the LVEDV or LVEDP, or that such adjustments can be used to halt or reverse the progression of acute / chronic heart failure.

[0009] US Patent Application Publication No. 2006 / 0064059 by Gelfand describes a system and method that seeks to reduce myocardial infarction size and / or myocardial remodeling after acute myocardial infarction by reducing stress on the heart wall. The system described in this patent includes a catheter having a proximal portion with an occlusion balloon configured to be placed in the inferior vena cava and a distal portion configured to be placed through the tricuspid valve and pulmonary valve into the pulmonary artery. The patent application describes that by partially occluding the inferior vena cava, the system regulates the amount of blood entering the ventricle, thereby reducing the load on the ventricle and allowing for faster healing, thus limiting the expansion of the myocardial infarction. The system described in the US Patent Application by Gelfand includes sensors attached to the catheter that are read by a controller to regulate the amount of blood flow entering the heart and other measured parameters within predetermined limits. This patent application does not state or suggest that the system can be used to treat congestive heart failure, arrest or reverse the progression of congestive heart failure, thereby resolving the symptoms of congestive heart failure once the heart has already shown the extensive remodeling that is typically observed during patient readmission.

[0010] Cedeno, US Patent Application Publication No. 2010 / 0331876, describes a system and method for treating congestive heart failure by regulating venous blood return through the inferior vena cava, similar to the structure described in the Gelfand US Patent Application. The system described in the Cedeno US Patent Application describes a fixed volume balloon placed in the inferior vena cava that restricts blood flow into the IVC. The degree of occlusion changes as the blood vessel expands and contracts during inspiration and expiration, allowing normal venous blood return. The patent application further describes that the symptoms of heart failure improve within three months of use of the claimed system. Although the system and method described in the Cedeno US Patent Application appear promising, the applicant has found a number of potential drawbacks of such a system during his own research. The applicant has found during his own research that total occlusion of the inferior vena cava not only reduces the left ventricular volume, but also significantly reduces the left ventricular systolic pressure, reducing systemic blood pressure and cardiac output. Furthermore, complete occlusion of the inferior vena cava can promote venous congestion in the kidneys, liver, and mesenteric veins, which is a major cause of renal failure in patients with congestive heart failure.

[0011] The approach of partial or total occlusion of the inferior vena cava to alter blood filling pressure to the heart and improve cardiac function has several major limitations. First, the IVC must be accessed via the femoral or internal jugular vein. When approached via the femoral vein, the patient must remain supine, rendering them non-ambulatory. When approached via the jugular or subclavian vein, the device must traverse the superior vena cava and right atrium, thus penetrating the heart, which predisposes to potential risks, including right atrial injury and inducing arrhythmias resulting in supraventricular tachycardia or bradycardia due to heart block. Second, the IVC approach described by Cedeno et al. relies on several highly variable indicators, especially in congestive heart failure care centers: 1) IVC diameter, which is often dilated in patients with heart failure; b) IVC intermittent occlusion (total or partial occlusion) causes injury by increasing renal venous pressure, which reduces glomerular filtration rate and exacerbates renal dysfunction; c) dependency on the patient's ability to breathe, which is often severely compromised in HF. The traditional breathing pattern with HF is known as Cheynes Stokes breathing, defined by intermittent apneic periods, which may collapse the IVC and cause the balloon to completely occlude, resulting in a drop in systemic blood pressure and high renal vein pressure; d) When sustained unloading of the heart is required to see clinical improvement or beneficial changes in cardiac structure or function, IVC occlusion is not effective because sustained IVC occlusion reduces blood pressure and renal function. Third, the approach defined by Cedeno requires customization of the balloon according to the size of the IVC, which may vary widely. Fourth, many heart failure patients carry IVC filters due to their increased propensity for deep vein thrombosis, which hampers the widespread application of IVC therapy.

[0012] Pulmonary hypertension (PH) also accounts for a major proportion 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 disease. Today, pharmacological treatments can reduce pulmonary artery systolic pressure (PASP), improve symptoms, and ultimately improve survival rates of patients with pulmonary hypertension. However, there are drawbacks to pharmacological treatments, such as cost and side effects.

[0013] In view of the above-mentioned shortcomings of known systems and methods for regulating venous return to cure heart failure, it would be desirable to provide a system and method for treating acute and chronic heart failure that reduces the risk of exacerbating comorbidities associated with the disease.

[0014] It would further be desirable to provide systems and methods for treating acute and chronic heart failure, preventing or reversing the progression of cardiac remodeling, and that are practical for chronic and / or ambulatory use.

[0015] It would further be desirable to provide systems and methods for treating heart failure and improving the quality of life for patients suffering from this disease, reducing the need for hospitalization, the length of hospital stays, and the associated burden on the social healthcare network.

[0016] It would also be desirable to provide a system and method that allows for the treatment of pulmonary hypertension and cardiorenal syndrome. [Prior art documents] [Patent documents]

[0017] [Patent Document 1] U.S. Pat. No. 4,546,759 [Patent Document 2] US Patent Application Publication No. 2006 / 0064059 Summary of the Invention [Means for solving the problem]

[0018] In view of the shortcomings of known systems and methods for treating heart failure, it would be desirable to provide systems and methods for treating acute and / or chronic heart failure that can halt, and more preferably reverse, the progression of cardiac remodeling that in turn results in the consequences associated with the disease.

[0019] It would further be desirable to provide systems and methods for preventing or reversing the progression of cardiac remodeling in patients suffering from heart failure that are practical for ambulatory and / or chronic use.

[0020] It would further be desirable to provide a system and method for treating heart failure that reduces the risk of exacerbating co-morbidities associated with the disease, such as venous congestion that leads to renal and hepatic complications.

[0021] It would also be desirable to provide a system and method for treating heart failure that can improve the quality of life for patients suffering from this disease, thereby reducing the need for re-hospitalization and the associated burden on the social healthcare network.

[0022] It would further be desirable to provide a system and method for treating pulmonary hypertension and improving the quality of life for patients suffering from this disease, and to provide a system and method for treating heart attack, acute heart failure, chronic heart failure, heart failure with preserved ejection fraction, right ventricular failure, restrictive and constrictive cardiomyopathies, and cardiorenal syndromes (Types 1-5).

[0023] These and other advantages are provided by the present disclosure, which provides a system and method for modulating venous blood return to the heart via the superior vena cava ("SVC") over a time interval that includes several cardiac cycles, reducing ventricular overload, and reducing cardiac preload and pulmonary artery pressure without increasing renal venous pressure. In accordance with the principles of the present disclosure, venous modulation via the SVC can be used to reduce LVEDP, LVEDV, RVEDP, and / or RVEDV, and prevent or reverse ventricular myocardial remodeling. In a counterintuitive manner, applicants have found in preliminary animal studies that intermittent partial occlusion of the SVC does not lead to cerebral blood flow stagnation or observable adverse side effects. More importantly, applicants' preliminary animal studies have revealed that occlusion of the SVC results in a significant reduction in both RVEDP and LVEDP, while improving total cardiac output and without a significant reduction in left ventricular systolic pressure ("LVSP"). Thus, unlike the approach described in the aforementioned published Cedeno patent application, the present disclosure provides beneficial reductions in LVEDP, LVEDV, RVEDP, and / or RVEDV with negligible impact on LVSP, but with improved stroke volume (cardiac output) and reduced risk of venous congestion resulting in increased comorbidities. The systems and methods described herein provide acute improvements in blood filling pressures to the heart and cardiac function, benefiting patients at risk for acute decompensated heart failure.

[0024] Targeting SVC blood flow (rather than IVC blood flow) has several major advantages. First, by placing the device within the SVC, the use of the femoral vein can be avoided, and penetration of the heart can be avoided. This allows the development of a fully implantable, yet portable, system to treat acute or chronic diseases. Second, SVC occlusion can be intermittent or continuous, depending on the amount of unloading required. Unlike IVC occlusion, continuous occlusion of the SVC can preserve systemic blood pressure and improve cardiac output. This maintains both right and left ventricular unloading, which can acutely improve hemodynamics and have long-term beneficial effects on cardiac structure or function. Third, unlike IVC occlusion, SVC occlusion does not vary with patient respiration. Fourth, by deploying an internal regulator of SVC occlusion driven by mean right atrial pressure or pressure difference across the occlusion balloon, the SVC device can be programmed and personalized to each patient's condition. Fifth, by placing the device within the SVC, the device can be used in patients with existing IVC filters.

[0025] According to another aspect of the present disclosure, intermittent occlusion of the SVC, either partial or total, over multiple cardiac cycles is predicted to allow the myocardium to heal and reduce myocardial wall stress, thereby preventing or reversing the progression of remodeling, which is indicative of the progression of heart failure. Without wishing to be bound by theory, applicant believes that intermittent occlusion of the SVC can transition the heart from a Starling curve indicative of heart failure with reduced ejection fraction to a Starling curve with LVEDP and LVEDP more indicative of normal cardiac function, when the occlusion is achieved over a period of hours, days, weeks, or months, for example 3-6 months. Thus, applicant's preliminary animal studies suggest that use of the present system over a period of hours, days, weeks, or months, for example 3-6 months, not only prevents the progression of the downward spiral typical of the disease, but also restores cardiac function sufficiently to allow the patient to discontinue use of the present system, pharmaceutical treatments, or both.

[0026] According to another aspect of the present disclosure, a system is provided that includes a catheter having a flow restricting member configured to be placed in or on the SVC, and a controller that controls activation of the flow restricting member. The controller is preferably programmed to receive inputs indicative of variations in the patient's hemodynamics and adjust activation / deactivation of the flow restricting member in response to the inputs. The variations in the patient's hemodynamics may be caused by the patient's ambulatory movements. The controller may be programmed at the time of implantation of the catheter to maintain full or partial occlusion of the SVC for a predetermined number of cardiac cycles or a predetermined time interval based on the patient's resting heart rate, and the preset number of cardiac cycles or time interval may be continuously adjusted by the controller in response to the patient's heart rate input. The controller may further receive signals from the sensors and / or electrodes indicative of sensed parameters indicative of hemodynamics, such as blood flow velocity, blood volume, pressures including blood filling pressure to the heart, and the like, and the controller may continuously adjust the preset number of cardiac cycles or time interval in response to the sensed parameter(s).

[0027] In one preferred embodiment, the catheter is configured to be implanted intravascularly (e.g., via the patient's left subclavian vein) and the flow restricting member is placed in the SVC just proximal to the right atrium. The proximal end of the catheter can be coated or impregnated with an antimicrobial agent to allow for sustained use of the catheter with reduced risk of infection at the site where the catheter is passed percutaneously. The controller is preferably battery powered and preferably includes a quick connect coupling that can operably couple the controller's actuation mechanism to the flow restricting member. In a preferred embodiment, the controller is small enough to allow the patient to wear the controller in a brace around the shoulder. Unlike known systems that restrain the patient to a bed or an emergency care facility, the disclosed system allows the patient to ambulate and perform most of their daily activities, thus improving the quality of life of the patient and increasing the patient's compliance with the treatment regimen using the system of the present invention. In one embodiment, the controller is configured to be implanted in a suitable location in the patient's body, for example subcutaneously under the clavicle. In such an embodiment, the implantable controllers are configured to communicate bidirectionally with an external controller, e.g., a mobile device or a system-specific device. The external controllers can be configured to charge the batteries of the implantable controllers, e.g., via respective inductive coils in each controller, and can receive data representative of sensed parameters, which can include heart rate, blood flow rate, blood volume, and pressure, including blood filling pressure to the heart. The one or more external power sources can be in electrical communication with the implantable controllers and further configured to provide power to the controllers to charge the batteries of the implantable controllers. The one or more external power sources can generate an alert when the power of the one or more external power sources falls below a threshold power amount.

[0028] In a preferred embodiment, the flow-restricting member comprises a non-compliant or semi-compliant balloon or balloons attached to a distal region of the catheter, and the controller actuates the balloons by periodically inflating and deflating the balloons to selectively fully or partially occlude the SVC and / or the azygos vein. For example, the controller can be programmed to intermittently actuate the flow-restricting member to at least partially occlude the SVC for a first predetermined time interval and to deflate for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval can be at least five times greater than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes, while the second predetermined time interval is 1-30 seconds. In another embodiment, the flow-restricting member can comprise a membrane-covered umbrella, basket, or other mechanical arrangement that can be rapidly transitioned between deployed and deflated positions, for example, by a drive system connected to the controller. In still further embodiments, the flow restricting member may take the form of a butterfly valve or a ball valve, provided that the flow restricting member does not create stagnant flow areas within the SVC when in a contracted or open position. In still further embodiments, the flow restricting member comprises a cuff configured to be applied to the exterior of the SVC and operates by narrowing or occluding the SVC when inflated.

[0029] The system of the present invention may include a sensor disposed in a catheter placed in the venous or arterial vasculature to measure the patient's heart rate or blood pressure. The sensor preferably generates an output signal that is used as an input to the controller to adjust the degree or timing of the occlusion caused by the flow restricting member. In another embodiment, the controller may be configured to connect to a third-party heart rate or blood pressure sensor, such as a sensor commonly used by sports enthusiasts, e.g., Fitbit, via the patient's smartphone using available wireless standards such as Bluetooth. In this embodiment, the cost, size, and complexity of the controller may be reduced by integrating the controller with commercially available third-party components.

[0030] According to another aspect of the present disclosure, a method of controlling blood flow in a patient includes inserting and guiding a venous occlusion device into a patient's vena cava, coupling the occlusion device to a controller that is worn externally by the patient or implanted within the patient, and intermittently activating the venous occlusion device over a time period comprising multiple cardiac cycles to arrest or reverse the progression of myocardial remodeling over a period of minutes, hours, days, weeks, or months.

[0031] According to another aspect of the present disclosure, a system is provided for use in conjunction with a ventricular assist device (VAD) to improve the efficiency and functionality of the VAD and reduce the risk of adverse side effects of the VAD. The system includes a catheter having a proximal end and a distal region, the catheter sized and shaped for placement (e.g., intravascular placement, such as via a patient's subclavian or jugular vein) such that the distal region is positioned within the patient's superior vena cava (SVC). The system also includes a flow-restricting member, such as an SVC occlusion balloon, disposed on the distal region of the catheter, that is selectively actuated to at least partially occlude the SVC, and a controller operably coupled to the catheter for intermittently actuating the flow-restricting member to at least partially occlude the SVC for a time period that includes a single or multiple cardiac cycles, thereby reducing cardiac preload and pulmonary artery pressure and improving cardiac performance. For example, the controller may reduce cardiac preload sufficiently during the time interval to improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac tension.

[0032] The system may further include a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal, and a second pressure sensor disposed on the catheter and distal to the flow restricting member, the second pressure sensor outputting a second pressure signal, and the controller generates a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicating a degree of occlusion of the flow restricting member. The controller may use the first signal to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. The controller may also be programmed to activate an alarm as a safety signal for an operator based on the first signal. In one embodiment, the controller is configured to be implanted in a suitable site within the patient, for example subcutaneously below the clavicle.

[0033] The controller can also be programmed to intermittently activate the flow restricting member to at least partially occlude the SVC for a first predetermined time interval and contract for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval can be at least 10 times greater than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes, while the second predetermined time interval is 1-10 seconds.

[0034] In one preferred embodiment, the flow restricting member is an inflatable cylindrical balloon having a relief valve coupled thereto, the relief valve having an open position and a closed position. The relief valve can be opened at a predetermined pressure of 30-60 mmHg to allow fluid to flow through the SVC to the right atrium of the patient. The system can further include an azygos vein occlusion balloon disposed on the catheter proximal to the flow restricting member. The azygos vein occlusion balloon can be selectively actuated to at least partially occlude the azygos vein of the patient, and the azygos vein occlusion balloon and the SVC occlusion balloon can be independently actuated. The system also allows operation of the VAD at slower speeds to achieve a hemodynamic response equal to or greater than the hemodynamic response of the VAD alone at higher speeds.

[0035] The system may also include a left ventricular assist device (LVAD), the LVAD including a catheter having a proximal end and a distal region, the distal region having an inflow end and an outflow end, the catheter sized and shaped for placement via a patient's femoral artery, with the inflow end disposed within the patient's left ventricle and the outflow end disposed within the patient's aorta, the LVAD also including a pump, e.g., an impeller pump, disposed on the distal region of the catheter, the pump capable of being selectively activated to pump blood from the left ventricle through the inflow end and eject blood into the aorta through the outflow end, and an LVAD controller operably coupled to the LVAD to activate the pump to pump blood from the left ventricle into the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. An LVAD controller operably connected to the catheter of the system can regulate the activation and deactivation of the flow restricting member to at least partially occlude the SVC while the LVAD controller operates the pump to pump blood from the left ventricle to the aorta.

[0036] Alternatively, or in addition, the system may further include a right ventricular assist device (RVAD) including a pump, e.g., an impeller pump, that may be selectively activated to pump blood from the SVC through an inflow end of the RVAD and to eject blood into the pulmonary artery through an outflow end of the RVAD. The controller may also be operably coupled to the RVAD and may actuate the pump to pump blood from the SVC into the pulmonary artery, thereby unloading the right ventricle. For example, the controller may actuate a flow restricting member to at least partially occlude the SVC at the same time the controller actuates the pump to pump blood from the SVC into the pulmonary artery.

[0037] In another preferred embodiment, the RVAD includes a catheter having a proximal end and a distal region, the distal region having an inflow end and an outflow end, the catheter sized and shaped for placement via a patient's femoral artery, with the outflow end disposed in the patient's pulmonary artery and the inflow end disposed in the patient's IVC. The RVAD also includes a pump, e.g., an impeller pump, disposed on the distal region of the catheter, the pump capable of being selectively activated to pump blood from the IVC through the inflow end and to eject blood into the pulmonary artery through the outflow end, and an RVAD controller operably coupled to the RVAD to actuate the pump to pump blood from the IVC into the pulmonary artery, thereby unloading the right ventricle. The RVAD controller operably coupled to the catheter of the system can regulate activation and deactivation of the flow restricting member to at least partially occlude the SVC while the RVAD controller actuates the pump to pump blood from the IVC into the pulmonary artery. The present invention provides, for example, the following items. (Item 1) 1. A system for providing improved cardiac performance in a patient with heart failure, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a period spanning multiple cardiac cycles; Equipped with The system, wherein the controller is configured to sufficiently reduce cardiac preload during the interval to improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain. (Item 2) a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal; a second pressure sensor disposed on the catheter and distal to the flow restricting member, the second pressure sensor outputting a second pressure signal; Further comprising: 2. The system of claim 1, wherein the controller is configured to generate a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicating a degree of obstruction of the flow restricting member. (Item 3) 2. The system of claim 1, further comprising an azygos vein occlusion balloon disposed on the catheter proximal to the flow restricting member, the flow restricting member being an SVC occlusion balloon. (Item 4) 4. The system of claim 3, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein. (Item 5) 5. The system of claim 4, wherein the azygos vein occlusion balloon and the SVC occlusion balloon are independently actuated. (Item 6) 3. The system of claim 2, wherein the second pressure sensor is disposed between the azygos vein occlusion balloon and the SVC occlusion balloon, the system further comprising a third pressure sensor disposed on the catheter distal to the azygos vein occlusion balloon, the third pressure sensor configured to output a third pressure signal, and the controller configured to generate a second signal corresponding to a difference between the second pressure signal and the third pressure signal, the second signal indicating a degree of occlusion of the azygos vein. (Item 7) 2. The system of claim 1, wherein the controller is configured for implantation. (Item 8) 2. The system of claim 1, wherein the controller is configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a first predetermined time interval and to contract for a second predetermined time interval over a plurality of cardiac cycles. (Item 9) 9. The system of claim 8, wherein the first predetermined time interval is at least five times greater than the second predetermined time interval. (Item 10) 9. The system according to item 8, wherein the first predetermined time interval is 4 to 6 minutes, and the second predetermined time interval is 1 to 30 seconds. (Item 11) 3. The system of claim 2, wherein the controller is configured to use the first signal to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. (Item 12) Item 1, wherein the flow restricting member comprises an inflatable cylindrical balloon having a relief valve coupled to the inflatable cylindrical balloon, the relief valve having an open position and a closed position. (Item 13) Item 13. The system of item 12, wherein the relief valve is configured to open at a pressure of 30 to 60 mmHg to allow fluid to flow through the SVC to the patient's right atrium. (Item 14) Item 13. The system of item 12, wherein the relief valve is a binary valve configured to rapidly deform to an open position in response to application of pressure above a certain threshold. (Item 15) Item 13. The system of item 12, wherein the relief valve is a progressive valve configured to gradually deform to an open position as pressure applied to the relief valve increases. (Item 16) 2. The system of claim 1, wherein the controller is further configured to intermittently actuate the flow restricting member to create a negative pressure sink within the patient's right atrium and accelerate blood flow from the renal veins to enhance renal decongestion and facilitate blood flow across the patient's kidneys. (Item 17) 1. A system for treating heart failure in a patient, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC during a time interval spanning multiple cardiac cycles; a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a signal; Equipped with The controller is configured to receive the signal and generate an output signal indicative of jugular venous pressure (JVP). (Item 18) 20. The system of claim 17, wherein the signal corresponds to a pressure waveform that varies in response to actuation of the flow restricting member, and the first signal is used to determine whether the SVC is occluded. (Item 19) 20. The system of claim 17, further comprising an azygos vein occlusion balloon disposed on the catheter and proximal to the flow restricting member, the flow restricting member being an SVC occlusion balloon. (Item 20) Item 18. The system of item 17, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein, and the azygos vein occlusion balloon and the SVC occlusion balloon are independently actuated. (Item 21) 20. The system of claim 17, wherein the first signal is used to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. (Item 22) Item 18. The system of item 17, wherein the flow restricting member comprises an inflatable cylindrical balloon. (Item 23) Item 23. The system of item 22, wherein the inflatable cylindrical balloon has a relief valve coupled to the inflatable cylindrical balloon having an open position and a closed position. (Item 24) Item 24. The system of item 23, wherein the relief valve is configured to open at a predetermined pressure of 30 to 60 mmHg to allow fluid to flow through the SVC to the patient's right atrium. (Item 25) Item 24. The system of item 23, wherein the relief valve is a binary valve configured to rapidly deform to an open position in response to application of pressure above a certain threshold. (Item 26) Item 24. The system of item 23, wherein the relief valve is a progressive valve configured to gradually deform to an open position as pressure applied to the relief valve increases. (Item 27) 1. A system for improving cardiac function by moving a patient's cardiac contractility towards a healthy range of a Frank-Starling curve, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC over a plurality of cardiac cycles to reduce the patient's diastolic volume and improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain; and A system comprising: (Item 28) 1. A system for providing improved cardiac and renal function in a patient, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a period spanning multiple cardiac cycles; Equipped with The system, wherein the controller is configured to intermittently actuate the flow restricting member to create a negative pressure sink within the patient's right atrium and accelerate flow from the renal veins to enhance renal decongestion and encourage blood flow across the patient's kidneys. (Item 29) 1. A system for treating hypertension, comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC over a number of cardiac cycles, thereby reducing cardiac preload and pulmonary artery pressure without increasing renal vein pressure; Equipped with The controller is operably coupled to the flow restricting member to enable sustained use of the system with reduced risk of percutaneous infection. (Item 30) a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal; a second pressure sensor disposed on the catheter and distal to the flow restricting member, the second pressure sensor outputting a second pressure signal; Further comprising: 30. The system of claim 29, wherein the controller is configured to generate a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicating a degree of obstruction of the flow restricting member. (Item 31) 30. The system of claim 29, further comprising an azygos vein occlusion balloon disposed on the catheter proximal to the flow restricting member, the flow restricting member being an SVC occlusion balloon. (Item 32) 32. The system of claim 31, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein. (Item 33) Item 33. The system of item 32, wherein the azygos vein occlusion balloon and the SVC occlusion balloon are independently actuated. (Item 34) 31. The system of claim 30, wherein the second pressure sensor is disposed between the azygos vein occlusion balloon and the flow restricting member, the system further comprising a third pressure sensor disposed on the catheter distal to the azygos vein occlusion balloon, the third pressure sensor configured to output a third pressure signal, and the controller configured to generate a second signal corresponding to a difference between the second pressure signal and the third pressure signal, the second signal indicating a degree of occlusion of the azygos vein. (Item 35) 30. The system of claim 29, wherein the controller is configured for implantation. (Item 36) 30. The system of claim 29, wherein the controller is configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a first predetermined time interval and to contract for a second predetermined time interval over a plurality of cardiac cycles. (Item 37) Item 37. The system of item 36, wherein the first predetermined time interval is at least 10 times greater than the second predetermined time interval. (Item 38) Item 37. The system of item 36, wherein the first predetermined time interval is 4 to 6 minutes, and the second predetermined time interval is 1 to 10 seconds. (Item 39) 31. The system of claim 30, wherein the controller is configured to use the first signal to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. (Item 40) 30. The system of claim 29, wherein the flow restricting member comprises an inflatable cylindrical balloon having a relief valve coupled to the inflatable cylindrical balloon, the relief valve having an open position and a closed position. (Item 41) Item 41. The system of item 40, wherein the relief valve is configured to open at a pressure of 30 to 60 mmHg to allow fluid to flow through the SVC to the patient's right atrium. (Item 42) Item 41. The system of item 40, wherein the relief valve is a binary valve configured to rapidly deform to an open position in response to application of pressure above a certain threshold. (Item 43) Item 41. The system of item 40, wherein the relief valve is a progressive valve configured to gradually deform to an open position as pressure applied to the relief valve increases. (Item 44) 1. A system for treating hypertension, comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC over a number of cardiac cycles, thereby reducing preload and pulmonary artery pressure without increasing renal venous pressure; a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a signal; Equipped with The controller is configured to receive the signal and generate an output signal indicative of jugular venous pressure (JVP). (Item 45) Item 45. The system of item 44, wherein the signal corresponds to a pressure waveform that varies in response to actuation of the flow restricting member, and the first signal is used to determine whether the SVC is occluded. (Item 46) Item 45. The system of item 44, further comprising an azygos vein occlusion balloon disposed on the catheter and proximal to the flow restricting member, the flow restricting member being an SVC occlusion balloon. (Item 47) Item 45. The system of item 44, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein, and the azygos vein occlusion balloon and the SVC occlusion balloon are independently actuated. (Item 48) Item 45. The system of item 44, wherein the first signal is used to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. (Item 49) Item 50. The system of item 44, wherein the flow restricting member comprises an inflatable cylindrical balloon. 50. The system of claim 49, wherein the inflatable cylindrical balloon has a relief valve coupled to the inflatable cylindrical balloon having an open position and a closed position. (Item 51) Item 51. The system of item 50, wherein the relief valve is configured to open at a predetermined pressure of 30 to 60 mmHg to allow fluid to flow through the SVC to the patient's right atrium. (Item 52) Item 51. The system of item 50, wherein the relief valve is a binary valve configured to rapidly deform to an open position in response to application of pressure above a certain threshold. (Item 53) Item 51. The system of item 50, wherein the relief valve is a progressive valve configured to gradually deform to an open position as pressure applied to the relief valve increases. (Item 54) 1. A system for use with a ventricular assist device (VAD) to improve the efficiency and functionality of the VAD, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively activated to at least partially occlude the SVC; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a segment spanning multiple cardiac cycles to reduce cardiac preload and pulmonary artery pressure and improve cardiac performance; A system comprising: (Item 55) 55. The system of claim 54, wherein the flow restricting member is an SVC occlusion balloon. (Item 56) Item 55. The system of item 54, wherein the flow restricting member is an inflatable cylindrical balloon, the inflatable cylindrical balloon comprising a relief valve coupled to the inflatable cylindrical balloon having an open position and a closed position. (Item 57) Item 57. The system of item 56, wherein the relief valve is configured to open at a predetermined pressure of 30 to 60 mmHg to allow fluid to flow through the SVC to the patient's right atrium. (Item 58) 55. The system of claim 54, wherein the controller is configured to reduce cardiac preload sufficiently during the interval to improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain. (Item 59) a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal; a second pressure sensor disposed on the catheter and distal to the flow restricting member, the second pressure sensor outputting a second pressure signal; Further comprising: 55. The system of claim 54, wherein the controller is configured to generate a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicating a degree of obstruction of the flow restricting member. (Item 60) 60. The system of claim 59, wherein the controller is configured to use a first signal to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. (Item 61) Item 55. The system of item 54, wherein the controller is configured for implantation. (Item 62) Item 55. The system of item 54, wherein the controller is configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a first predetermined time interval and to contract for a second predetermined time interval over a plurality of cardiac cycles. (Item 63) Item 63. The system of item 62, wherein the first predetermined time interval is at least 10 times greater than the second predetermined time interval. (Item 64) Item 63. The system of item 62, wherein the first predetermined time interval is 4 to 6 minutes, and the second predetermined time interval is 1 to 10 seconds. (Item 65) 55. The system of claim 54, further comprising an azygos vein occlusion balloon disposed on the catheter proximal to the flow restricting member, the flow restricting member being an SVC occlusion balloon. (Item 66) Item 66. The system of item 65, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein. (Item 67) Item 66. The system of item 65, wherein the azygos vein occlusion balloon and the SVC occlusion balloon are independently actuated. (Item 68) Item 55. The system of item 54, wherein the controller is configured to control delivery by the VAD. (Item 69) 55. The system of claim 54, wherein the system enables operation of the VAD at slower speeds to achieve a hemodynamic response equal to or greater than the hemodynamic response of the VAD alone at higher speeds. (Item 70) 55. The system of claim 54, wherein the VAD is a left ventricular assist device (LVAD), and the system further comprises the LVAD. (Item 71) Item 71. The system of item 70, wherein the LVAD comprises a pump configured to pump blood from the left ventricle through an inflow end of the LVAD and eject blood into the aorta through an outflow end of the LVAD. (Item 72) Item 72. The system of item 71, wherein the pump is an impeller pump. (Item 73) Item 71. The system of item 70, further comprising an LVAD controller operably coupled to the LVAD and configured to operate the pump to pump blood from the left ventricle into the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. (Item 74) The system of item 73, wherein the controller operably connected to a catheter of the system actuates the flow restricting member to at least partially occlude the SVC at the same time that the LVAD controller actuates the pump to pump blood from the left ventricle to the aorta. (Item 75) 55. The system of claim 54, wherein the VAD is a right ventricular assist device (RVAD), and the system further comprises the RVAD. (Item 76) Item 76. The system of item 75, wherein the RVAD comprises a pump configured to pump blood from the SVC through an inflow end of the RVAD and to expel blood through an outflow end of the RVAD into a pulmonary artery. (Item 77) Item 77. The system of item 76, wherein the pump is an impeller pump. (Item 78) 77. The system of claim 76, wherein the controller is further operably coupled to the RVAD and configured to actuate the pump to unload the right ventricle by pumping blood from the SVC to the pulmonary artery. (Item 79) 80. The system of claim 78, wherein the controller actuates the flow restricting member to at least partially occlude the SVC at the same time the controller actuates the pump to pump blood from the SVC to the pulmonary artery. (Item 80) Item 76. The system of item 75, wherein the RVAD comprises a pump configured to pump blood from the inferior vena cava (IVC) through an inflow end of the RVAD and discharge blood into the pulmonary artery through an outflow end of the RVAD. (Item 81) Item 81. The system of item 80, wherein the pump is an impeller pump. (Item 82) Item 83. The system of item 80, further comprising a RVAD controller operably coupled to the RVAD and configured to actuate the pump to unload the right ventricle by pumping blood from the IVC to the pulmonary artery. The system of claim 82, wherein the controller operably coupled to a catheter of the system actuates the flow restricting member to at least partially occlude the SVC at the same time that the RVAD controller actuates the pump to pump blood from the IVC to the pulmonary artery. [Brief description of the drawings]

[0038] Features and advantages of the present disclosure will become apparent from the detailed description of the embodiments of the present disclosure presented below when taken in conjunction with the accompanying drawings.

[0039] [Figure 1A] FIG. 1A is a frontal, partially cut-away view of the major arteries and veins of the heart.

[0040] [Figure 1B] FIG. 1B shows the vena cava including the main vein that leads to the vena cava.

[0041] [Figure 2A] 2A and 2B are graphs illustrating Frank-Starling curves corresponding to normal and diseased cardiac conditions. [Figure 2B] 2A and 2B are graphs illustrating Frank-Starling curves corresponding to normal and diseased cardiac conditions.

[0042] [Diagram 3] FIG. 3 is a graph of an exemplary pressure-volume loop curve illustrating the relationship between left ventricular pressure and left ventricular volume throughout the cardiac cycle in a patient with normal cardiac function and in a patient suffering from congestive heart failure.

[0043] [Figure 4A]FIG. 4A is a schematic diagram of a system constructed in accordance with the principles of the present disclosure.

[0044] [Figure 4B] FIG. 4B is a schematic diagram of an implantable system constructed in accordance with the principles of the present disclosure.

[0045] [Figure 4C] FIG. 4C is a diagram of the power supply and charging base.

[0046] [Figure 5A] FIG. 5A is a schematic diagram of the catheter of FIGS. 4A and 4B, in which the flow restricting member includes a cylindrical balloon with an altered anchoring member, showing the flow restricting member in an expanded and contracted state, respectively. [Figure 5B] FIG. 5B is a schematic diagram of the catheter of FIGS. 4A and 4B, in which the flow restricting member includes a cylindrical balloon with an altered anchoring member, showing the flow restricting member in an expanded and contracted state, respectively.

[0047] [Figure 6] FIG. 6 is a schematic diagram of the catheter of FIGS. 4A and 4B, in which the flow restricting member includes a mechanically actuated, membrane-covered basket.

[0048] [Figure 7] FIG. 7 is a cross-sectional view of the catheter of FIGS. 4A and 4B.

[0049] [Figure 8] 8A and 8B are schematic diagrams of a flow restricting member including a spherical balloon shown in an expanded and deflated state, respectively.

[0050] [Figure 9]9A and 9B are schematic diagrams of a flow restricting member including a spring-loaded plug shown in an expanded and contracted state, respectively.

[0051] [Figure 10] 10A and 10B are schematic diagrams of a flow restricting member including another embodiment of a spring-loaded plug shown in an expanded and contracted state, respectively.

[0052] [Figure 11] FIG. 11 shows graphs and tables depicting left ventricular (LV) pressures and LV volumes over several consecutive heart rates in a porcine model following complete occlusion of the inferior vena cava (IVC).

[0053] [Figure 12] FIG. 12 shows graphs and tables depicting LV pressures and LV volumes over several consecutive heart rates in a porcine model following partial occlusion of the superior vena cava (SVC).

[0054] [Figure 13] FIG. 13 is a graph showing pressure change with left ventricular volume upon occlusion and release of the superior vena cava (SVC) in a pig suffering from heart failure in accordance with the principles of the present disclosure. [Figure 14] FIG. 14 is a graph showing pressure change with right ventricular volume upon occlusion and release of the superior vena cava (SVC) in a pig suffering from heart failure in accordance with the principles of the present disclosure.

[0055] [Figure 15] 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 16] 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 17]15-22 show the results of the study on test pigs suffering from heart failure. [Figure 18] 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 19] 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 20] 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 21] 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 22] 15-22 show the results of the study on test pigs suffering from heart failure.

[0056] [Diagram 23] FIG 23A illustrates the clinical pressure change in left ventricular end diastolic pressure during the deflation time of a one minute episode of continuous SVC occlusion in accordance with the principles of the present disclosure. FIG 23B illustrates the clinical pressure change in left ventricular end systolic pressure during the deflation time of a one minute episode of continuous SVC occlusion in accordance with the principles of the present disclosure. FIG 23C illustrates the clinical pressure change in left ventricular volume during the deflation time of a one minute episode of continuous SVC occlusion in accordance with the principles of the present disclosure. FIG 23D illustrates the clinical pressure change in ventricular stroke work during the deflation time of a one minute episode of continuous SVC occlusion in accordance with the principles of the present disclosure.

[0057] [Figure 24] FIG 24A illustrates the clinical pressure change in left ventricular end diastolic pressure during the deflation time of a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 24B illustrates the clinical pressure change in left ventricular end systolic pressure during the deflation time of a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 24C illustrates the clinical pressure change in left ventricular volume during the deflation time of a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 24D illustrates the clinical pressure change in ventricular stroke work during the deflation time of a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0058] [Diagram 25] FIG 25A illustrates the clinical pressure change in left ventricular end diastolic pressure during the deflation time of a 10 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 25B illustrates the clinical pressure change in left ventricular end systolic pressure during the deflation time of a 10 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 25C illustrates the clinical pressure change in left ventricular volume during the deflation time of a 10 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 25D illustrates the clinical pressure change in ventricular stroke work during the deflation time of a 10 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0059] [Figure 26] 26A-26C show clinical pressure changes in pulmonary capillary wedge pressure observed during a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 26B shows clinical pressure changes in pulmonary artery pressure observed during a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. FIG 26C shows clinical pressure changes in right atrial pressure observed during a 5 minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0060] [Figure 27-1] Figure 27A illustrates the clinical pressure change of systolic pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure, Figure 27B illustrates the clinical pressure change of diastolic pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure, and Figure 27C illustrates the clinical pressure change of mean arterial pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure. [Figure 27-2] Figure 27D illustrates the clinical pressure change of mean pulmonary artery pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure. Figure 27E illustrates the clinical pressure change of mean pulmonary capillary wedge pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure.

[0061] [Figure 28]28A and 28B show clinical pressure changes in mean pulmonary artery pressure during 10 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure.

[0062] [Figure 29] FIG. 29 illustrates cardiac output before and during occlusion of the SVC in accordance with the principles of the present disclosure.

[0063] [Diagram 30] FIG. 30 illustrates pulmonary artery systolic pressure with and without SVC obstruction in accordance with the principles of the present disclosure.

[0064] [Diagram 31] FIG. 31 is a prophetic example of how SVC obstruction according to the principles of the present disclosure is expected to alter the spectrum of diseases.

[0065] [Diagram 32] FIG. 32 is a perspective view of a cylindrical flow restrictor member.

[0066] [Diagram 33] FIG. 33 is a cross-sectional view of a cylindrical flow restriction member illustrating a relief valve.

[0067] [Diagram 34] 34A-B are cross-sectional views of cylindrical flow restriction members having binary and progressive relief valves.

[0068] [Diagram 35] FIG. 35 is a top view of a cylindrical flow restricting member having a relief valve in a closed position.

[0069] [Diagram 36] 36A-B are top views of a cylindrical flow restricting member having a binary relief valve and a progressive relief valve in an open position.

[0070] [Figure 37]37A-B are perspective and cutaway views of a cylindrical flow restricting member engaged with a stent.

[0071] [Figure 38] 38A-B are top views of a cylindrical flow restricting member with a balloon occluder in inflated and deflated positions.

[0072] [Figure 39] 39A-B are top views of a cylindrical flow restricting member with a cylindrical balloon occluder in inflated and deflated positions.

[0073] [Diagram 40] 40A-B are perspective and cutaway views of a stent coupled to a relief valve.

[0074] [Diagram 41] FIG. 41 is a cutaway view of a cylindrical flow restrictor connected to a filter.

[0075] [Figure 42A] FIG. 42A is a cutaway perspective view of a cylindrical flow restricting member coupled to a catheter with a sensor, and FIG. 42B is an exemplary phase curve. [Figure 42B] FIG. 42A is a cutaway perspective view of a cylindrical flow restricting member coupled to a catheter with a sensor, and FIG. 42B is an exemplary phase curve.

[0076] [Diagram 43] FIG. 43 is a diagram of the introducer sheath entering the SVC, the flow restricting member within the SVC, and the catheter positioned within the heart.

[0077] [Diagram 44] FIG. 44 is a diagram of an introducer sheath placed in the SVC, a flow restricting member incorporated within the introducer sheath, and a catheter placed within the heart.

[0078] [Diagram 45]FIG. 45 is a diagram of an occlusion system having an azygos vein occlusion balloon and a second occlusion balloon placed in the SVC.

[0079] [Figure 46] FIG. 46 is a diagram of an occlusion cuff wrapped around the SVC.

[0080] [Figure 47] 47A-B show outside and inside views of the occlusion cuff, and FIGS. 47C-D show perspective views of the occlusion cuff.

[0081] [Figure 48] FIG. 48 is another exemplary system constructed in accordance with the principles of the present disclosure.

[0082] [Figure 49] FIG. 49 shows an SVC occlusion system in combination with a transvalvular LVAD.

[0083] [Figure 50] FIG. 50 is a graph showing enhanced unloading capacity of SVC obstruction when used in combination with a transvalvular LVAD.

[0084] [Figure 51] FIG. 51 shows an SVC occlusion system in combination with a transvalvular RVAD.

[0085] [Figure 52] FIG. 52 shows an SVC occlusion system in combination with another transvalvular RVAD.

[0086] [Figure 53] FIG. 53 shows an SVC occlusion system in combination with an LVAD.

[0087] [Figure 54] FIG. 54 shows an SVC occlusion system in combination with an intra-aortic balloon pump (IABP). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0088] With reference to Figures 1A and 1B, the human anatomy in which the present disclosure is designed to deploy and operate will be described in conjunction with the systems and methods of the present disclosure.

[0089] 1A, deoxygenated blood returns to the heart 10 via the vena cava 11, which includes the superior vena cava 12 and the inferior vena cava 13, which connect to the right atrium 14 of the heart. From the right atrium 14, blood travels through the tricuspid valve 15 to the right ventricle 16, which pumps the blood to the lungs via the pulmonary artery 17. Oxygenated blood returns from the lungs via the pulmonary veins to the left atrium 18. The oxygenated blood then flows into the left ventricle 19, which pumps the blood to the rest of the body via the aorta 20.

[0090] As shown in Figure 1B, the superior vena cava 12 is located at the top of the vena cava 11, while the inferior vena cava 13 is located at the bottom of the vena cava. Figure 1B also shows the azygos vein 16 and some of the major veins that connect to the vena cava. As described herein, obstruction of the inferior vena cava 13 can pose a risk of venous congestion and, in particular, potential blockage or enlargement of the hepatic and / or adrenal veins, which can worsen rather than improve the patient's cardiovascular status and overall health.

[0091] In accordance with one aspect of the present disclosure, Applicant has determined that selective intermittent occlusion of the superior vena cava ("SVC") poses fewer potential harmful risks than occlusion of the inferior vena cava ("IVC"). Moreover, Applicant's animal and human studies have demonstrated that controlling venous blood return to the right ventricle by partially or completely occluding the SVC beneficially reduces RVEDP, RVEDV, LVEDP, and LVEDV without adversely reducing left ventricular systolic pressure (LVSP).

[0092] Applicant understands that selective intermittent occlusion of the SVC, compared to IVC occlusion, will reduce the risk of worsening renal congestion, which is the primary cause of the "cardiorenal" syndrome. Cardiorenal syndrome is impaired renal function due to volume overload and neurohormonal activation in patients with heart failure. Volume overload can occur where the weakened heart cannot pump as much blood, leading to less blood flow through the kidneys. With less blood flow through the kidneys, less blood is filtered by the kidneys and less water is released through urination, causing excess volume to be retained in the body. With excess volume, the heart pumps more and more inefficiently, and the patient ultimately dies as the body becomes progressively more congested.

[0093] Applicant understands that IVC occlusion generally reduces the kidney's ability to filter and remove fluids by reducing blood flow through the kidney because the occluded IVC increases pressure in the renal veins. IVC occlusion further stagnates blood, preventing otherwise deoxygenated blood from returning to the heart. As a result, renal function may be excessively reduced, exacerbating congestion. However, SVC occlusion ultimately improves renal function by increasing blood flow to the kidney. In particular, by reducing blood flow into the right atrium via SVC occlusion, the volume within the left ventricle is ultimately reduced, allowing muscle fibers to stretch within normal ranges, naturally increasing contractility and allowing the heart to pump more fluid to the kidney. The kidney can then extract water, which can be removed from the body via urination. It should further be understood that during SVC occlusion, a negative pressure sink is created within the right atrium, caused by the sudden reduction in right atrial pressure and volume. As a result, blood flow from the renal vein can be accelerated, enhancing renal decongestion, aiding blood flow across the kidney, and increasing urine volume. Thus, SVC occlusion can benefit patients with heart failure and / or cardiorenal syndrome by reducing cardiac and pulmonary pressures and aiding decongestion.

[0094] Also, implantation in the SVC allows for device implantation in the superior phrenic artery, whereas device implantation in the superior phrenic artery devices cannot be used in the IVC without penetrating the heart and crossing the right atrium. Furthermore, implantation of an occluder in the SVC avoids the need for groin access required for IVC implantation, which limits mobility making portable devices impractical for short- or long-term use. Also, whereas small changes in IVC occlusion (time or degree) can cause more dramatic changes in preload reduction and therefore more dramatic changes in total cardiac output / systemic blood pressure, the disclosed system and method can predictably finely tune the reduction in venous return (preload reduction).

[0095] Applicant understands that intermittent occlusion of the SVC (i.e., cardiopulmonary unloading) for a period of time (e.g., minutes, hours, days, weeks, or months) will beneficially allow the patient's heart to halt or recover from myocardial remodeling. Applicant's animal and human studies have shown that the system allows the myocardium to shift away from a pressure-stroke volume curve indicative of heart failure toward a pressure-stroke volume curve that more closely resembles that of a healthy heart.

[0096] In general, the disclosed system and method can be used to treat any disease and improve cardiac function by preventing or reversing myocardial remodeling, particularly those conditions in which the patient suffers from heart failure. Such conditions include, but are not limited to, systolic heart failure, diastolic (non-systolic) heart failure, decompensated heart failure patients in (ADHF), chronic heart failure, acute heart failure and pulmonary hypertension, heart attack, heart failure with preserved ejection fraction, right heart failure, restrictive and constrictive cardiomyopathy, and cardiorenal syndrome (types 1-5). The disclosed system and method can also be used as a prophylactic to reduce the aftereffects of acute right or left ventricular myocardial infarction, pulmonary hypertension, RV failure, post-open heart surgery shock, or post-orthotopic heart transplant (OHTx) rejection, or otherwise for cardiorenal applications and / or to treat renal dysfunction, hepatic dysfunction, or lymphatic congestion. Additionally, the systems and methods of the present disclosure may reduce hospitalizations caused by various illnesses described herein, including at least acute exacerbations.

[0097] The relationship between left ventricular pressure or volume and stroke volume is often referred to as the Frank-Starling relationship or "Starling curve" and is shown in Figures 2A-2B. The 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 intrinsic ability of the myocardium to contract, and afterload is determined by vascular resistance and impedance. In heart failure due to diastolic or systolic dysfunction, reduced stroke volume leads to increased volume and pressure in the left ventricle, which can result in pulmonary edema. Increased ventricular volume and pressure also leads to increased workload and increased myocardial oxygen consumption. Such overwork of the heart leads to deterioration of cardiac function as the heart becomes increasingly oxygen-deprived due to a mismatch between supply and demand. Furthermore, as volume and pressure build up in the heart, contractile function deteriorates due to myocardial stretching. This condition is called "congestive heart failure."

[0098] Referring to FIG. 2, a series of Starling curves are shown, with the top curve (curve 1) representing normal cardiac function. As can be seen, stroke volume increases with increasing LVEDP or LVEDV and begins to plateau, i.e., the slope of the curve decreases only at very high pressures or very large volumes. A patient who has just suffered an acute myocardial infarction ("AMI"), as shown in the middle curve (curve 2), has a low stroke volume at each value of LVEDV or LVEDP. However, because the heart is just beginning to experience overload caused by the local effects of the infarction, the overall myocardial contractility of the ventricle is still relatively good, and stroke volume is still relatively large at low LVEDP or low LVEDV. In contrast, patients with previous cardiac damage, as myocardial remodeling progresses over time, will experience a gradual decline in cardiac function to compensate for the increased workload and reduced oxygen intake, as shown in the bottom curve (curve 3) of FIG. 2A. As discussed above, this results in a progressive decrease in stroke volume as the ventricles expand due to the generally greater volume and pressure at each stage of the cardiac cycle. As can be seen by comparing curves 1 and 3, stroke volume continues to decrease as LVEDP or LVEDV increases until the heart eventually fails or the patient dies from cardiovascular disease.

[0099] FIG. 2B provides another formulation of the Frank-Starling curve, i.e., curve 6, showing the difference between the function of a healthy heart and one with heart failure. Line 7 shows the Frank-Starling curve for a normal healthy heart up to point 8. As explained with respect to FIG. 2A, for a normal heart, as the end-diastolic volume increases, the stroke volume increases. However, for a healthy heart, beyond point 8, an increase in the end-diastolic volume no longer results in an increase in the stroke volume, and continued increases in the end-diastolic volume do not result in a further increase in the stroke volume. This phenomenon is shown by the flat solid line extending substantially horizontally beyond point 8. The decreasing dashed line 9 extending beyond point 8 in FIG. 2B represents the Frank-Starling curve for a patient with heart failure. The dashed line 9 shows that for a patient with heart failure, a further increase in the end-diastolic volume does not result in a nearly flat stroke volume, but instead, a decrease in the stroke volume. Thus, an increase in EDV in HF patients leads to a further reduction in SV, leading to a downward spiral in cardiac function and, ultimately, to death. Figure 2B reflects a phenomenon called "diastolic ventricular interaction", which is caused in part by the structural arrangement of the cardiac chambers. As explained, for example, in an article entitled "Diastolic ventricular interaction in chronic heart failure" (Lancet 1997; 349:1720-24) by J. Atherton et al., the pericardium constrains the extent to which the ventricles of a failing heart can expand. Thus, as right ventricular end-diastolic volume increases, this inevitably causes a reduction in left ventricular end-diastolic volume. As reported in that article, the reduction in right ventricular diastolic filling caused by external lower body suction allows for an increase in left ventricular diastolic filling.

[0100] Applicant has realized that the aforementioned phenomenon may be advantageously 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 may reduce LV stroke volume and cardiac output by pushing the interventricular septum towards the left ventricular cavity. By occluding blood flow through the SVC, right ventricular pressure and volume are reduced. This in turn will shift the interventricular septum away from the LV cavity, allowing for increased left ventricular stroke volume and enhanced cardiac output. For these reasons, SVC occlusion according to the principles of the present disclosure can preferably alter diastolic ventricular interactions and enhance cardiac output. In particular, with respect to diastolic heart failure, SVC occlusion according to the principles of the present disclosure can provide reduced blood filling pressure to the heart, increased LV relaxation (tau), increased LV capacitance, increased myocardial relaxation, reduced LV stiffness, and reduced cardiac tension. The effect of the present disclosure's SVC occlusion can thus be visualized as a shift in dashed line 9 of the Frank-Starling curve 6 in FIG. 2B for a heart failure patient toward a lower EDV, which in effect moves cardiac performance upward and closer to the flat portion of the curve extending beyond point 8 for a healthy patient. The systems and methods of inducing at least partial intermittent SVC occlusion of the present invention in HF patients thus improve cardiac function by moving the patient's cardiac contractility toward the healthy range of the Frank-Starling curve for patients with HF.

[0101] FIG. 3 exemplarily shows pressure-volume loops for a normal heart, labeled "normal," corresponding to curve 1 of FIG. 2B, and exemplarily shows pressure-volume loops for a heart suffering from congestive heart failure, labeled "CHF" (curve 3 of FIG. 2B). For each loop, the ventricular volume and pressure at end diastole correspond to the right-most lower corner of the loop (point A), while the left-most upper corner of each loop corresponds to the beginning of systole (point B). The stroke volume of each pressure-volume loop corresponds to the area enclosed within the loop. Thus, the most beneficial venoregulatory therapy is one that maximizes the stroke volume by reducing the volume and pressure at point A without causing a negligible reduction at point B.

[0102] According to one aspect of the present disclosure, the systems and methods of the present disclosure are designed to change or shift the Starling curve of a patient's heart toward the left on the diagram of FIG. 2B (or move the pressure-volume loop of FIG. 3 toward the left and downward) over the course of treatment over hours, days, weeks, or months. This is done by intermittently totally or partially occluding the SVC (superior vena cava) to reduce the amount of blood entering the right ventricle, and therefore the pressure, that must then be pumped out of the left ventricle. Preliminary animal studies by the applicant have shown that such intermittent occlusion maintained over several cardiac cycles reduces myocardial workload and wall stress throughout the cardiac cycle, reduces myocardial oxygen consumption, and improves contractile function.

[0103] A preferred system 30 of the present disclosure will now be described with reference to Figure 4A. System 30 includes a catheter 31 having a flow restricting member 32 connected to a controller 33 programmed to intermittently activate the flow restricting member 32. As described below, system 30 may optionally be configured to transfer information to and from a conventional computing device 45, such as a smart phone, laptop, smart watch, or tablet, e.g., an Apple iPhone® 5 or iPad®, available from Apple Inc. of Cupertino, Calif., having special purpose applications installed on it for communicating with and / or controlling controller 33.

[0104] Preferably, the catheter 31 comprises a flexible tube having a distal portion 34 configured to be placed in the SVC (superior vena cava). The distal portion 34 includes a flow restricting member 32 that, in use, is placed in the patient's superior vena cava 12 (see FIG. 1B) to selectively impede blood flow into the right atrium 14. In this embodiment, the flow restricting member 32 comprises a balloon that can transition between a deflated state, e.g., to allow for intravascular placement, and an expanded, deployed state. The flow restricting member 32 is preferably sized and shaped such that the flow restricting member 32 partially occludes or completely occludes flow in the SVC in the expanded state. The catheter 31 is coupled at a proximal end 35 to a controller 33 that houses a drive mechanism 36 (e.g., motor, pump) to operate the flow restricting member 32, a processor 37 that is programmed to control signals to drive the mechanism 36, and any sensors 42 that monitor physiological parameters of the patient, such as heart rate or blood pressure.

[0105] The controller 33 may include a source of inflation medium 48 (e.g., gas or fluid), and the drive mechanism 36 may transfer the inflation medium between the source and the flow restricting member 32 in response to commands from the processor 37. When the flow restricting member 32 is inflated with the inflation medium, it partially or completely occludes venous blood flow through the SVC; when the inflation medium is withdrawn, the flow restricting member 32 contracts to relieve the occlusion, thereby allowing blood to flow through the SVC again. The flow restricting member 32 may be a balloon, preferably comprising an elastic or semi-elastic material, such as nylon, which allows the degree of inflation of the balloon to be adjusted to provide the desired degree of partial or complete occlusion of the SVC. Additionally, the catheter 31 has a fail-safe design when partially external in that only the flow restricting member 32 may be inflated to provide the occlusion when the proximal end of the catheter 31 is connected to the controller 33. Such a quick release coupling 40 at the proximal end 35 allows for quick unclamping of the catheter from the controller 33 for flushing and / or emergency procedures.

[0106] The controller 33 preferably further includes a power source 39 (e.g., a battery) that provides the necessary power to operate the processor 37, the drive mechanism 36, and the data transfer circuit sensor 38. The controller 33 is sized and weighted to allow the controller 33 to be worn in a brace under the patient's clothing so that the system can be used while the patient is ambulatory, or the controller 33 can be implanted within the patient. As described herein below, the processor 37 includes a memory 41 that stores computer software that operates the controller 33. The controller 33 can be configured to be implanted in a suitable location within the patient's body, for example subcutaneously under the clavicle. In such an embodiment, the implantable controller is configured to bidirectionally communicate with an external controller, for example a computing device 45 or a system specific device. The external controller can be used to charge the batteries of the implantable controllers, for example via respective induction coils within or coupled to each controller, and can receive data representative of sensed parameters derived from the patient's ambulatory movements, which can include heart rate, blood flow velocity, blood volume, and pressure, including blood filling pressure to the heart.

[0107] In one embodiment, the data transfer circuit 38 monitors inputs, for example from external sensors located on the catheter 31, and provides the signals to the processor 37. The processor 37 is programmed to receive inputs from the data transfer circuit 38 and adjust the time period that the flow restricting member 32 is maintained in an expanded state or to adjust the degree of occlusion caused by the flow restricting member 32. Thus, for example, the catheter 31 may have optional sensors 42 located in the distal region 34 of the catheter to measure parameters such as heart rate, blood flow velocity, blood volume, blood filling pressure to the heart, and pressures including central venous pressure. The outputs of the sensors 42 are relayed to the data transfer circuit 38 of the controller 33, which pre-processes the input signals, for example decimating and digitizing the outputs of the sensors 42, before the outputs are provided to the processor 37. The signals provided to the processor 37 allow for an assessment of the effectiveness of the flow restricting member, for example by indicating the drop in venous pressure during occlusion and patency, which can be used by the patient or clinician to determine what degree of occlusion is needed to adjust venous return based on the severity of the patient's congestion. Sensors 43 can also be incorporated into the catheter 31 proximal to the flow restricting member 32 to measure parameters such as heart rate, blood flow velocity, blood volume, blood filling pressure to the heart, and pressure including central venous pressure. The sensors 43 can be used to determine the degree of occlusion caused by the member 32, for example by monitoring the pressure drop across the flow restricting member.

[0108] As another example, the catheter 31 may include electrodes 44 for detecting the patient's heart rate. It is anticipated that it may be desirable to adjust the time interval during which the SVC occlusion is maintained in response to the patient's ambulation, with this adjusted time interval typically reflecting the patient's hemodynamics in terms of the detected physiological parameter(s), such as heart rate, blood flow velocity, blood volume, blood filling pressure to the heart, and / or pressure including central venous pressure. Accordingly, the electrodes 44 provide signals to the data transfer circuitry 38, which in turn processes the signals for use by the program routines executed by the processor 37. For example, if the occlusion is maintained for a time programmed during initial system set-up, reflecting the patient being stationary, e.g., the flow restricting member is deployed for 5 seconds and then released for 2 seconds before expanding again, it may be desirable to shorten the occlusion time interval to a time of 4 seconds or more, depending on the degree of physical activity of the patient as detected by changes in heart rate, blood flow velocity, blood volume, pressure including blood filling pressure to the heart, and / or central venous pressure above or below a predetermined threshold. Alternatively, the processor 37 may be programmed to maintain partial or total occlusion of the SVC for a preset number of cardiac cycles determined at the time of initial implantation of the catheter. Sensor inputs provided to the data transfer circuitry 38, such as hemodynamics, may be used to adjust the duty cycle of the flow restricting member in response to the degree of motion detected in the patient. After adjustments are made to the predetermined occlusion time interval, the processor 37 may be programmed to maintain partial or total occlusion of the SVC for a preset number of cardiac cycles.

[0109] The data transfer circuitry 38 may also be configured for bidirectional transfer of data, for example by incorporating wireless circuitry to transfer data from the controller 33 to an external unit for display, review, or adjustment. For example, the data transfer circuitry may include Bluetooth circuitry by which the controller 33 may communicate with the patient's computing device 45. In this manner, the controller may transmit information regarding the functioning of the system directly to the computing device 45, thereby allowing vital physiological or system parameters to be displayed using a suitably configured mobile application. The patient may also review the data displayed on the screen of the computing device 45 to determine whether he or she needs to obtain medical assistance to correct a malfunction or adjust a system parameter. Furthermore, the mobile application resident on the computing device 45 may be configured to automatically initiate an alert to a clinician monitoring service via a cellular network.

[0110] Optionally, the data transfer circuitry 38 can be configured to synchronize receiving data from other mobile applications on the computing device 45, thus reducing the cost and complexity of the system of the present invention. For example, there are many third party vendors, such as Fitbit, Inc., San Francisco, California, that market monitors that measure physiological parameters in real time, and Charge HR wristband monitors that measure physical activity and heart rate. According to one aspect of the present disclosure, the data transfer circuitry 38 can be programmed to receive inputs from such third party monitors via wireless communication to the computing device 45, and the processor 37 can be programmed to control the operation of the drive mechanism 36 in response to the inputs. In this embodiment, the catheter does not need to include any sensors 42, 43, or electrodes 44, which can greatly simplify the construction of the catheter 31 and the fitting 40.

[0111] The catheter 31 can include an anchor member 46 configured to anchor the flow restricting member 32 within the SVC. The anchor member 46 can be collapsible such that it can be delivered in a contracted state and can be expanded upon release from a delivery device, e.g., a sheath. The anchor member 46 can be coupled to the catheter proximally or distally to the flow restricting member 32 and / or can be coupled to the flow restricting member 32. The system shown in FIG. 4A can effectively change the patient's cardiac contractility to the healthy range of the Frank-Starling curve shown in FIG. 2A.

[0112] Referring now to FIG. 4B, the controller 33 is illustrated as being implanted in a suitable location within the patient's body. As shown in FIG. 4B, an external power source 47 can be configured to charge the power source 39 (e.g., a battery) of the implantable controller. For example, the external power source 47 can transcutaneously charge the power source 39 via a respective induction coil. The external power source 47 can be integrated with a garment or appliance worn by the patient. In particular, the external power source 47 can be stored in a pocket or in a carrier configured to receive the external power source 47. When the garment or appliance is worn by the patient, the pocket or carrier is designed to store the external power source 47 in close proximity to the battery 39 for efficient transcutaneous charging. More than one external power source 47 can be integrated with the garment to provide extra power. The one or more external power sources can be permanently integrated with the garment or appliance, or can be removably engaged with the garment or appliance such that each external power source can be individually removed and individually attached. For example, as shown in Figure 4B, two external power sources 47 can be integrated into specially designed pockets in a vest 64. The vest 64 includes wires 66 attached to the vest 64 to allow electrical communication between the two external power sources.

[0113] The power source 47 can provide an alert when the available power voltage reaches or falls below a certain power threshold. For example, the power source 47 can have visual and / or audible indicators to provide a warning to the patient or caregiver. The visual indicator can be an LED lighting system or display embedded in the surface of the power source 47 that visually displays information regarding the available power voltage. The audible indicator can be a speaker embedded in the power source 47 that sounds an alert when the available power voltage reaches a predetermined threshold. A signal indicating that the available power voltage of the power source 47 has reached a predetermined threshold can also or alternatively be sent to an external device, such as the computing device 45, and / or directly to the controller 33, and then sent from the controller 33 to an external device, such as the computing device 45, which can be programmed to initiate a visual or audible alert. A further power source 47 provides power to the power source 39 when the primary power source runs out of power to ensure that power is continuously provided to the power source 39. The power source 47 may include a processor with memory for transcutaneously transmitting and transcutaneously receiving data from the processor 37. The processor of the power source 47 may be used to reprogram the processor 37 and / or to store information regarding operating parameters that may later be downloaded by an external device, such as the computing device 45.

[0114] Each external power source 47 can be housed in electrical connection to a wall power outlet or charging base 65 shown in FIG. 4C to charge the external power sources. The charging base 65 can be electrically connected to a wall power outlet and can be configured to charge one or more external power sources 47 simultaneously. To allow the power sources 39 to be continuously connected to a given power source, the external power sources 47 are periodically removed from the vest and charged such that at least one external power source 47 is electrically connected to the power source 39 while the other external power sources 47 are being charged by the charging base 65. The system also provides both reduced cost and reduced complexity by allowing the system to interface with commercially available heart rate monitors and smartphones and / or tablets.

[0115] A preferred embodiment of a catheter 31' will now be described with reference to Figures 5A and 5B, which is configured similarly to the catheter 31 of Figures 4A and 4B, except for a modified anchoring member. As shown in Figure 5A, where the flow restricting member 32' is in an expanded, totally occluded state, and as shown in Figure 5B, where the flow restricting member 32' is in a contracted state, the catheter 31' can include radially expanding anchoring arms 49. The anchoring arms 49 are configured, for example, upon emergence from a delivery sheath, to expand radially to contact an inner wall of the superior vena cava 12 and secure the flow restricting member 32' within the superior vena cava 12.

[0116] Referring now to FIG. 6, another embodiment in which the occlusion can include a wire basket is described. The flow restricting member 50 can be made of a biocompatible material such as nickel-titanium or stainless steel and includes a plurality of axially or helically extending wires 51 that, when compressed, are biased to expand radially outward. The flow restricting member 50 preferably includes a biocompatible coating such that, in the expanded state, the biocompatible coating partially or completely occludes flow into the SVC. The wires 51 can be coupled at their distal ends 52 to the distal ends 53 of the steering wires 54 and can be attached at their proximal ends 56 to rings 55. The rings 55 are positioned to slide over the steering wires 54 such that the wires 51 expand radially outward when the steering wires 54 are pulled proximally relative to the sheaths 57 (see FIGS. 5A and 5B). As shown in FIG. 5B, when a predetermined force is applied to the proximal end of the control wire 54 by the drive mechanism 36, the control wire 54 retracts proximally relative to the catheter sheath 57; transitioning the flow restricting member 50 to its expanded, deployed state. Alternatively, when the drive mechanism 36 is deactivated, the spring force applied by the wire 51 pulls the control wire 54 proximally, allowing the wire 51 to return to its uncompressed, deformed state, lying substantially flat against the control wire 54. As mentioned above, the flow restricting member 50 incorporates a "fail-safe" design, such that the flow restricting member reverts to the collapsed, contracted state shown in FIG. 5A when the catheter 31 is decoupled from the drive mechanism 36. In this embodiment, the drive mechanism 36 can be a motor, which can be a linear motor, a rotary motor, a solenoid piston, or a wire motor.

[0117] The flow restricting member 50 can be configured to bias the flow restricting member to a contracted position when the catheter 31 is disconnected from the controller 33, and to transition the flow restricting member 50 to an expanded, deployed state only when the catheter is connected to the controller 33 and the processor outputs a signal to the drive mechanism 36 to expand the flow restricting member.

[0118] 7, the catheter 31 preferably includes at least three lumens 60, 61, 62. Lumen 60 may be used as an inflation lumen and / or may be used to deliver a steering wire 54 that extends between the flow restricting member 32 / 50 and the drive mechanism 36 of the controller 33. Lumen 61 may allow any sensors 42, 43 or electrodes to communicate with the data transfer circuitry 38 and any lumen 62 to allow for the delivery of medication (e.g., a drug) to the heart.

[0119] In operation, the catheter 31 with the flow restricting member 32 / 50 is inserted into the patient's subclavian vein and guided to the patient's SVC, for example, to a location proximal to the inlet of the right atrium (see FIG. 1A). Using surgical techniques known in the art, the flow restricting member 32 / 50 can be inserted and secured to the patient's desired venous site. Proper positioning of the device can be confirmed, for example, using vascular ultrasound. Alternatively, the flow restricting member 32 / 50 can be inserted into a jugular vein or even a peripheral vein under fluoroscopic or ultrasound guidance and guided to the SVC.

[0120] Once the catheter 31 and flow restricting member 32 / 50 are positioned at the desired location, the controller 33 initiates a process in which the occlusion member expands and contracts to intermittently occlude and re-open blood flow into the SVC. The degree to which the flow restricting member obstructs blood flow can be adjusted by adjusting the degree to which the flow restricting member expands radially and over the time period of occlusion, e.g., over the number of heart beats. For example, in some embodiments, the flow restricting member can obstruct blood flow into the SVC by as little as 50% to as much as 100% at any one location. Blood flow impedance can be determined by methods known in the art, e.g., by measuring pressure drop, pressure fluctuation drop, or visually using ultrasound.

[0121] According to one aspect of the disclosure, the controller 33 includes software stored in the memory 41 that controls the timing and duration of the successive expansion and contraction of the flow restriction member 32 / 50. As described above, the program routine executed by the processor 37 can use the patient's cardiac cycle as an input. For example, in some embodiments, the software can be configured to activate the flow restriction member 32 / 50 to maintain partial or complete occlusion of the SVC over multiple cardiac cycles, such as four or more consecutive heartbeats of the subject. The controller 33 can accept as an input the output of the electrodes 44 representative of the patient's electrocardiogram (ECG) via the data transfer circuitry 38, or alternatively, the controller 33 can receive such input wirelessly from a third-party heart rate application running on the patient's smartphone, so that the software executing on the processor 37 can adjust the time interval and / or degree of occlusion provided by the system 30 depending on the patient's heart rate. Thus, for example, if the patient is physically exercising, the duration or degree of obstruction caused by the flow restrictor may be decreased to allow more rapid replenishment of oxygenated blood to the patient's upper extremities. Alternatively, if the heart rate indicates that the patient is not exercising, the degree of obstruction of the SVC may be increased to reduce the resting workload on the heart. Alternatively, or in addition, system 30 may accept inputs via data transfer circuitry 38 from optional sensors 42 and 43 or values ​​measured by third party applications and devices, such as a blood pressure cuff, indicative of the patient's blood pressure, such that controller 33 may adjust flow through the SVC in response to the patient's blood pressure.

[0122] Controller 33 may be programmed to instruct the flow restriction member to open when a sensed parameter falls outside a predetermined range and / or exceeds or falls below a predetermined threshold. For example, controller 33 may instruct the flow restriction member to open when right atrial ("RA") pressure is sensed by any of sensors 42 and / or 43 to be within a predetermined range, e.g., 15-30 mmHg, 18-30 mmHg, 20-30 mmHg, 20-25 mmHg, or exceeds a predetermined threshold, e.g., 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. As another example, controller 33 may direct the flow restriction member to open when the mean pulmonary artery ("PA") pressure is detected by any of sensors 42 and / or 43 to be within a predetermined range, e.g., 15-30 mmHg, 18-30 mmHg, 20-30 mmHg, 20-25 mmHg, or above a predetermined threshold, e.g., 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. The predetermined ranges and / or predetermined thresholds may be patient specific, and controller 33 may be programmed and reprogrammed for individual patients.

[0123] Next, with reference to Figures 8-10, another form of intravenous flow restricting member suitable for use in occluding the SVC will be described. As will be apparent to one skilled in the art, although Figures 4-6 show a cylindrical flow restricting member, other shapes may be used. Also, anchoring members may be incorporated, although not illustrated in the case of Figures 8-10. In each pair of Figures 8A, 8B, 9A, 9B, and 10A, 10B, the paired figures show each flow restricting member having a collapsed contracted state (Figures 8A, 9A, and 10A) in which the flow restricting member does not significantly impede blood flow, and an expanded deployed state (Figures 8B, 9B, and 10B) in which the flow restricting member partially or completely occludes blood flow through the SVC.

[0124] Specifically, with reference to Figures 8A and 8B, a catheter 70 includes a balloon 71 attached to a distal end 72. Balloon 71 is shown as having a circular ball shape.

[0125] 9A and 9B, a catheter 80 includes a flow restricting member 81 that includes a spring-loaded plug 82 formed of a biocompatible material (e.g., beryllium) and having a tapered conical shape. The spring-loaded plug 82 is captured in a sheath 83 disposed at a distal end 84 of the catheter 80 in a collapsed, contracted state of the spring-loaded plug. More specifically, the apex of the conical plug 82 is positioned adjacent a proximal end 85 of the sheath 83. During delivery of the catheter 80, the spring-loaded plug 82 is captured in the sheath 83 in a low-profile state of the spring-loaded plug, allowing blood flow into the SVC. To open the spring-loaded plug 82, a force is applied via a steering wire 86 to pull the plug 82 out of the sheath 83. In the previous embodiment, removal of the proximal force from the proximal end of the operating wire 86 urges the plug 81 back into the sheath 83, retaining the flow restricting member 82 in its collapsed contracted state when disconnected from the controller 33.

[0126] 10A and 10B, a catheter 90 illustrates yet another embodiment of an occlusion device 91 in the form of a spring-loaded plug 92. The spring-loaded plug 92 is similar to the plug 82 of FIGS. 9A and 9B, has a tapered conical shape, and is mounted within a sheath 93 that is disposed at the distal end 94 of the catheter 90. When a distal force is applied to the proximal end of the catheter 90 from the drive mechanism 36, the spring-loaded plug 92 is pushed out of the distal end of the sheath 94 and expands to occlude the SVC. When the distal force is removed, the spring-loaded plug 92 retracts to its collapsed, contracted state within the sheath 94, allowing blood to flow substantially unimpeded through the SVC.

[0127] Applicant has found that animal studies have demonstrated that a system constructed and operated in accordance with the methods of the present SVC occlusion system provides significant advantages over known IVC systems for treating heart failure. Preliminary animal studies performed on a porcine model one week after myocardial infarction are described below.

[0128] Referring to FIG. 11, the changes in LV pressure and LV volume over several consecutive heart rates in a porcine model after total occlusion of the inferior vena cava (IVC) are shown, as suggested in the aforementioned published Cedeno patent application. In particular, the IVC was totally occluded for about 30 seconds, during which the left ventricular end-diastolic pressure (corresponding to the lower right corner of the hysteresis loop) and the left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) decreased during each consecutive heart rate. The LV pressure rapidly increased to pre-occlusion levels once the IVC occlusion was released (i.e., similar to the first half of the pressure and volume traces). Because the IVC occlusion therapy proposed by Cedeno reduces systolic pressure, the therapy may lead to a reduction in the ejection fraction during systole, with potentially dangerous consequences for the patient. In addition, occlusion of the IVC may result in congestion of the renal and hepatic veins, which may lead to complications that are often associated with congestive heart failure, exacerbating rather than improving them.

[0129] Referring to FIG. 12, the changes in LV pressure and LV volume over several consecutive heart rates in a porcine model after partial occlusion of the superior vena cava (SVC) as described in accordance with the principles of the present disclosure are shown. In particular, the SVC was partially occluded for approximately 30 seconds, during which the left ventricular end-diastolic pressure (corresponding to the lower right corner of the hysteresis loop) decreased, while the left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) remained substantially unchanged during each consecutive heart rate. The LV pressure rapidly increased to pre-occlusion levels once the SVC occlusion was released (i.e., similar to the first half of the pressure and volume traces). Advantageously, the presently disclosed method of partially occluding the SVC appears to have little or no effect on the ejection fraction during systole, but reduces wall stress within the ventricle during diastole. Furthermore, as described in more detail below, occlusion of the SVC will be well tolerated by patients, will not contribute to renal or hepatic venous congestion, and will not exacerbate complications that often accompany congestive heart failure, including liver failure and renal failure.

[0130] 13-14 are graphs showing how pressure changes with left and right ventricular volumes during superior vena cava (SVC) occlusion and release of the superior vena cava in a pig being treated for heart failure in accordance with the principles of the present disclosure. As shown in these graphs, SVC occlusion significantly reduced left ventricular (LV) volume (240 mL to 220 mL) and reduced LV diastolic pressure (25 mmHg to 10 mmHg). SVC occlusion was also associated with reduced LV systolic pressure (94 mmHg to 90 mmHg). SVC occlusion was also associated with reduced right ventricular (RV) volume (230 mL to 210 mL), reduced diastolic pressure (12 mmHg to 4 mmHg), and reduced RV systolic pressure (27 mmHg to 16 mmHg). Advantageously, SVC occlusion by the systems and methods described herein reduces the volume of both ventricles, lowering diastolic (blood filling) pressures, without adversely affecting systemic blood pressure (LV systolic pressure). These findings suggest that SVC occlusion may have a profound beneficial effect on the interaction of both ventricles, thereby improving ventricular compliance by reducing diastolic blood filling pressures to both ventricles, thus improving blood filling pressures to the ventricles, resulting in increased stroke volume and cardiac output, which are primary goals in treating patients with heart failure.

[0131] 15 includes graphs showing that superior vena cava (SVC) occlusion according to the principles of the present disclosure improves cardiac function in a porcine study. Each of these graphs shows the results of a partial inferior vena cava (IVC) occlusion (left side of each graph) compared to a complete SVC occlusion (right side of each graph). The graphs show the measured left ventricular (LV) stroke volume, cardiac output, LV contractility, LV diastolic pressure, LV systolic pressure, and end systolic volume.

[0132] 16 is a graph showing that SVC occlusion according to the principles of the present disclosure in three test pigs does not adversely affect systolic blood pressure. These graphs show a comparison of LV end-systolic pressure (mmHg) with complete vena cava occlusion (1 min) in the case of complete IVC occlusion (left side of each study) and LV end-systolic pressure (mmHg) with complete vena cava occlusion (1 min) in the case of complete SVC occlusion (right column of each study). There is a smaller drop in LV end-systolic pressure with SVC occlusion compared to IVC occlusion.

[0133] 17 is a graph showing that SVC occlusion according to the principles of the present disclosure does not adversely affect LV diastolic filling pressure in three test pigs. The graphs show a comparison of LV end-diastolic pressure (mmHg) with complete vena cava occlusion (for 1 min) in the case of complete IVC occlusion (left side of each study) and LV end-diastolic pressure (mmHg) with complete vena cava occlusion (for 1 min) in the case of complete SVC occlusion (right side of each study). There is a smaller drop in LV end-diastolic pressure with SVC occlusion compared to IVC occlusion.

[0134] 18 is a graph showing that SVC occlusion according to the principles of the present disclosure improves LV stroke volume in three test pigs. The graphs show a comparison of LV stroke volume (mL / beats) with complete vena cava occlusion (1 min) in the case of complete IVC occlusion (left side of each study) and LV stroke volume (mL / beats) with complete vena cava occlusion (1 min) in the case of complete SVC occlusion (right side of each study). LV stroke volume increases with SVC occlusion compared to the decrease in LV stroke volume during IVC occlusion.

[0135] 19 is a graph showing how SVC occlusion according to the principles of the present disclosure improves LV contractility in three test pigs. The graphs show a comparison of LV contractility (mmHg / sec) with complete vena cava occlusion (1 min) in the case of complete IVC occlusion (left side of each study) and LV contractility (mmHg / sec) with complete vena cava occlusion (1 min) in the case of complete SVC occlusion (right side of each study). Compared to the reduced LV contractility during IVC occlusion, the increased LV contractility occurs during SVC occlusion.

[0136] Figure 20 is four graphs showing LV total volume and LV pressure with IVC occlusion (top left), RV total volume and RV (right ventricular) pressure with IVC occlusion (top right), LV total volume and LV pressure with SVC occlusion (bottom left), and RV total volume and RV pressure with SVC occlusion (bottom right). Figure 20 shows that compared to IVC occlusion, SVC occlusion can significantly reduce LV diastolic and RV diastolic pressures without significantly reducing LV systolic pressure.

[0137] FIG. 21 shows two graphs showing the pulmonary artery pressure and renal vein pressure measured for a test pig with IVC occlusion (graph on the left) and with SVC occlusion (graph on the right). Line 100 shows the pulmonary artery pressure after measurement for IVC occlusion, while line 102 shows the renal vein pressure after measurement for IVC occlusion. Line 104 shows the pulmonary artery pressure after measurement for SVC occlusion, while line 106 shows the renal vein pressure after measurement for SVC occlusion. The maximum renal vein pressure is measured as 22 mmHg for IVC occlusion, while the maximum renal vein pressure is measured as 7 mmHg for SVC occlusion. FIG. 21 shows that SVC occlusion can reduce the pulmonary artery pressure without increasing the renal vein pressure, compared to IVC occlusion.

[0138] FIG. 22 is a graph showing left subclavian venous pressure and renal venous pressure measured in a pig subjected to SVC occlusion according to the principles of the present disclosure. Line 108 shows the left subclavian venous pressure after measurement with SVC occlusion, while line 110 shows the renal venous pressure after measurement with SVC occlusion. The measured change in left subclavian venous pressure is 5 mmHg to 12 mmHg upon SVC occlusion. FIG. 22 shows that the proximal left subclavian venous pressure is nominally higher upon SVC occlusion.

[0139] The results of further animal experiments carried out on a porcine model over various occlusion periods are shown in Figures 23A-26C. Referring now to Figures 23A-23D, the clinical pressure changes of left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume, and ventricular one-stroke work, respectively, during the deflation time of a one-minute episode of continuous SVC occlusion in a porcine model are shown. In particular, the controller was programmed to cause the flow-restricting member to at least partially occlude the SVC for one minute, and then contract, e.g., deflate, for one second. As shown in Figures 23A-23D, one minute of SVC occlusion may not be sufficient to result in a steady-state reduction in ventricular volume after the deflation time.

[0140] 24A-24D, the clinical pressure changes of left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume, and ventricular rotational work, respectively, during the deflation time of a 5-minute episode of continuous SVC occlusion in a porcine model are shown. In particular, the controller was programmed to cause the flow restricting member to at least partially occlude the SVC for 5 minutes and then contract, e.g., deflate, for 1 second. As shown in FIGs. 24A-24D, the ventricular volume reached a clear steady-state reduction after the deflation time as a result of the 5-minute SVC occlusion.

[0141] Referring now to Figures 25A-25D, the clinical pressure changes of left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume, and ventricular rotational work, respectively, during the deflation time of a 10-minute episode of continuous SVC occlusion in a porcine model are shown. In particular, the controller was programmed to cause the flow restricting member to at least partially occlude the SVC for 10 minutes and then contract, e.g., deflate, for 1 second. By comparing Figures 25A-25D with Figures 24A-24D, the advantage of 10-minute SVC occlusion over 5-minute SVC occlusion is not significant in this model. Therefore, with consideration of patient safety, a 5-minute SVC occlusion was used during the initial clinical study, such as the Tufts IRB-approved protocol described below with reference to Figures 26A-26C, while a 10-minute occlusion in a human subject is described in more detail below with reference to Figures 28A-B.

[0142] Prompted by the animal studies, Applicant performed preliminary human trials and observed that a system constructed and operated according to the methods of the present SVC occlusion system provides significant benefits. Figures 26A-26C show the clinical pressure changes observed during a 5-minute episode of continuous SVC occlusion in three human patients enrolled in a Tufts IRB approved protocol. In particular, the three patients underwent 5-minute continuous SVC occlusion with acute neurological and cardiac monitoring and a 30-day neurological evaluation (Table 1). [Table 1]

[0143] As can be seen from Figures 26A-26C and in Table 1, pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, and right atrial pressure changed significantly during the 5-minute episode of SVC occlusion and had residual effects after the release of the balloon. As a result of the study, all patients benefited hemodynamically since there was a decrease in all blood filling pressures, e.g., capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure. It was observed that more congested patients experienced an increase in mean arterial pressure (MAP). The net effect of these hemodynamic changes is a reduction in cardiopulmonary pressure and an increase in systemic pressure perfusing vital organs, including the kidneys.

[0144] Prompted by the above preliminary porcine and human results, the applicant conducted further testing on three patients who were subjects of the testing described above with respect to Figs. 26A-26C, in addition to two new patients. Five human patients, each with heart failure, were subjected to the SVC occlusion system described above. In particular, the five patients underwent five minutes of continuous SVC occlusion. The baseline parameters of the five patients are shown in Table 2 below. The third patient had the lowest New York Heart Association (NYHA) functional class of 2. The results of the third patient suggest that application of the SVC occlusion system may preferably be used for patients with NYHA functional class of heart failure level 3 and above. [Table 2]

[0145] Figures 27A-27E show the change in systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), mean pulmonary artery (MPA) pressure, and pulmonary capillary wedge pressure (PCWP) from baseline measurements for each of the five patients during and after occlusion. In Figures 27A-27D, the change in systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), and mean pulmonary artery (MPA) pressure is shown minute by minute during a five minute occlusion. In Figure 27E, the change in pulmonary capillary wedge pressure (PCWP) is shown during and after the five minute occlusion.

[0146] The changes in systolic pressure are shown in Figure 27A. As shown in Figure 27A, patients 1, 2, and 5 generally experienced an increase in SP during occlusion, while patients 3 and 4 generally experienced a decrease in systolic pressure. The changes in diastolic pressure are shown in Figure 27B. As shown in Figure 27B, diastolic pressure during SVC occlusion generally increased for patients 1, 2, and 5, and generally decreased for patients 3 and 4.

[0147] The change in mean atrial pressure is shown in FIG. 27C. As shown in FIG. 27C, mean arterial pressure generally increased during SVC occlusion for patients 1, 2, and 5, and generally decreased for patients 3 and 4. The change in mean pulmonary artery pressure is shown in FIG. 27D. As shown in FIG. 27D, mean pulmonary artery pressure decreased during SVC occlusion for each patient, but note that there is no data point for the fourth patient at the fourth minute. The change in pulmonary capillary wedge pressure (PCWP) is shown at 5 minutes and after release in FIG. 27E. As shown in FIG. 27E, pulmonary capillary wedge pressure decreased for all patients at 5 minutes of SVC occlusion, indicating a decrease in blood filling pressure for each patient during occlusion.

[0148] As observed in the study described with respect to Figures 26A-26C, the study shown in Figures 27A-27E showed that all five patients benefited hemodynamically, as there was a reduction in blood filling pressures, e.g., capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure, and furthermore, as in the study described above with respect to Figures 26A-26C, the more congested patients generally experienced an increase in mean arterial pressure (MAP), and in many cases, at least some of the patients had residual effects following release of the occluder.

[0149] Next, with reference to Figures 28A-28B, similar to the study described above with respect to Figures 25A-25D, the applicant also studied the effect of extended SVC occlusion on human subjects. In particular, the controller was programmed to cause the SVC flow restricting member to at least partially occlude the SVC for 10 minutes. Prior to the 10 minute occlusion, the SVC was occluded for a period of 5 minutes and then allowed to rest for a period of 5 minutes. The change in mean pulmonary artery pressure and the change in mean atrial artery pressure from baseline measurements before occlusion (i.e., after 5 minutes of rest) were measured at each minute from 1 to 10 minutes of occlusion and after release. As shown in Figures 28A-B, the effects observed during the 5 minute occlusion were sustained throughout the entire 10 minute occlusion period without any reduction in the effect of "cardiopulmonary unloading".

[0150] Figure 28A shows the change in mean pulmonary artery pressure. As shown in Figure 28A, the mean pulmonary artery pressure decreased throughout the occlusion, reaching its lowest level during the last 2 minutes of occlusion. Figure 28B shows the change in mean arterial pressure change during occlusion. As shown in Figure 28B, the mean arterial pressure generally decreased during occlusion, but it fluctuated, rising above the baseline measurement at the 1st minute, and then rising again at the 4th and 5th minutes.

[0151] Next, with reference to FIG. 29, the applicant also conducted more extensive testing involving the use of the disclosed system and method over successive occlusion periods resulting in the prevention or reversal of further myocardial remodeling and degeneration. In particular, adult male pigs were subjected to a heart attack by occluding the left anterior descending artery (LAD) for 120 minutes, followed by reopening of the occluded artery. Repeated cycles of SVC occlusion were then performed, occluding the SVC for 5 minutes and deflating the occlusion device for 30 minutes. Repeated cycles were performed over a period of 18 hours. After each cycle of SVC occlusion, cardiac output was measured. FIG. 29 shows the results of repeated cycles of SVC occlusion.

[0152] As shown in FIG. 29, cardiac output was at its nadir after LAD infarction but before SVC occlusion treatment. After 1 hour of treatment, cardiac output returned to baseline levels. Cardiac output continued to increase gradually from 1 hour to 18 hours of treatment, reaching maximum cardiac output at 18 hours. These findings suggest for the first time that mechanically reducing cardiac pressure and volume (i.e., unloading) by intermittently occluding the SVC and then ceasing occlusion (i.e., recovery) after acute cardiac injury may condition the myocardium and allow periods of exercise and rest. In this way, the repeated cycle resembles an interval training high intensity workout (e.g., sprinting) followed by rest. The repeated cycle strengthens the heart and improves cardiac output and function. It should be understood that although the ratio of occlusion to rest is 10:1 (5 minutes on, 30 seconds off), other ratios will also produce beneficial results. For example, a range of ratios of 5-20 minutes of occlusion to 10-100 seconds of rest may be beneficial. It should further be appreciated that it may be beneficial to occlude the SVC for up to 95% of the hour. Thus, the SVC occlusion systems described herein can alternatively or additionally be used post-infarction to treat damage to the heart from infarction and enhance recovery through myocardial unloading.

[0153] As mentioned above, the SVC occlusion system described herein may alternatively or additionally be used to treat pulmonary hypertension, since occlusion of the SVC may result in a reduction in pulmonary artery pressure. Although heart failure is a common cause of pulmonary hypertension, pulmonary hypertension may be caused by primary lung disease. It should be understood that the SVC occlusion system may be used to treat pulmonary hypertension, regardless of whether the cause of pulmonary hypertension is heart failure.

[0154] Next, referring to FIG. 30, the applicant observed that implantation of an SVC occlusion system in five patients with pulmonary hypertension due to heart failure resulted in a significant reduction in pulmonary artery systolic pressure (PASP). The patients were subjected to a 5-minute SVC occlusion to mechanically reduce (i.e., unload) the cardiac pressure and volume. As shown in FIG. 30, SVC occlusion significantly reduced PASP below the level of moderate pulmonary hypertension, defined as a high PASP of more than 50 mmHg. Thus, the SVC occlusion system described herein can be implanted to treat pulmonary hypertension. As described above with respect to FIG. 26B as well as FIG. 27D, the applicant also observed that implantation of an SVC occlusion system resulted in a reduction in the mean pulmonary artery pressure in each patient.

[0155] The benefits observed in the aforementioned animal and human studies suggest that continuous SVC occlusion may be used to treat any cardiac injury, including, but not limited to, acute heart failure due to heart attack, myocarditis, valvular insufficiency, volume overload, or congestive heart failure, and many other acute or chronic cardiac injuries. In one example, the SVC occlusion system described herein may be used to shift the Frank-Starling curve shown in FIG. 2A toward line 7, which represents a healthy patient, by arresting or reversing the system of heart failure acutely, e.g., in an acute treatment setting. In this way, the patient will see an immediate improvement in increased cardiac performance, and further continued improvement in myocardial function throughout the entire course of treatment. To prolong the effect of the system, the SVC occlusion system may be implanted within the patient for long-term use. Because the SVC occlusion system described herein may be implanted or worn by the patient continuously and in an ambulatory setting rather than being confined to a bed, the patient may receive the benefits of the system for a much longer period of time compared to acute treatment.

[0156] 31 is a prophetic example of how SVC obstruction according to the principles of the present disclosure is expected to change across the disease spectrum. For example, major benefits include better patient hemodynamics, faster recovery, and reduced patient length of stay (LOS). Over time, SVC obstruction can significantly slow disease progression.

[0157] Referring now to FIG. 32, another flow restricting member is shown. One undesirable effect of occlusion of the SVC is an increase in venous blood pressure upstream of the occlusion device. It is well known that high cephalic venous pressure can lead to a variety of unwanted effects. To reduce this risk of excessive pressure build-up upstream of the flow restricting member, a relief valve can be integrally provided with the flow restricting member, as shown in FIG. 33, to allow fluid flow from the SVC to the right atrium. The relief valve can be unidirectional, allowing blood flow only in the direction of the right atrium. The relief valve is preferably configured to open at pressures in the SVC of 30-60 mmHg. However, it should be understood that the relief valve can be designed and configured to open at other pressures in the SVC.

[0158] The flow restricting member shown in FIG. 32 can be used with a system similar to that shown in FIG. 4A-4B. As shown in FIG. 32, the flow restricting member can be a cylindrical flow restricting member 112. The cylindrical flow restricting member 112 can include a cylindrical balloon 113 that can be inflated and deflated by pumping fluid from a catheter into the cylindrical balloon 113. The flow restricting member 112 can be sized and configured to fit within the SVC and can conform to the contours of the inner wall of the SVC. The flow restricting member 112 can be delivered to the SVC on a catheter. The cylindrical balloon 113 can be introduced into the SVC in a deflated configuration. In response to arriving at the SVC, the cylindrical balloon 113 can be inflated to block or restrict blood flow within the SVC.

[0159] The cylindrical balloon 113 can define an internal lumen 114 when the cylindrical balloon 113 is inflated. When the relief valve 115 is open and the cylindrical balloon 113 is inflated, blood can pass through the cylindrical balloon 113. The internal lumen 114 can extend from one end of the cylindrical balloon 113 to the other. The internal lumen 114 can have a consistent cylindrical shape throughout, although it should be understood that the size and shape of both the cylindrical balloon 113 and the internal lumen 114 can vary. Additionally, the internal lumen 114 need not be aligned with the center of the balloon, and can even adopt a non-circular shape.

[0160] Referring now to FIG. 33, a cutaway view of the cylindrical flow restriction member 112 is shown. As shown in FIG. 33, a relief valve 115 can be coupled to the inner wall of the cylindrical balloon 113 within the central lumen 114. The relief valve 115 can include a single flow blocking member or multiple flow blocking members (e.g., multiple flexible leaflets) that cooperate to block blood flow through the central lumen 114. The relief valve 115 can be coupled to the center of the cylindrical flow restriction member 112, or alternatively, can be located adjacent to or at the upstream or downstream end of the cylindrical flow restriction member 112. For example, the relief valve 115 can be located at the upstream end of the cylindrical flow restriction member 112 that is furthest from the patient's right atrium. This configuration can avoid pooling of blood or a stagnant column of blood within the central lumen 114 that can occur if the relief valve 115 is located in the center or downstream region of the central lumen 114.

[0161] The relief valve 115, shown in FIG. 33 in a closed position, can be designed to open at a certain pressure. For example, the relief valve 115 can be designed to open at a pressure of 30-40 mmHg. However, it should be understood that other pressures may also be desirable. Below the pressure at which the relief valve 115 is designed to open, the relief valve 115 can block fluid flow through the central lumen 114. Above the pressure at which the relief valve 115 is designed to open, the relief valve 115 can reduce cephalic venous pressure by allowing blood to pass through the inner lumen 114.

[0162] The relief valve 115 may be constructed from any suitable biocompatible material, including, but not limited to, elastomers, rigid or flexible polymers, metals, and any combination thereof. The functionality of the relief valve 115 may depend solely on the valve material and design (i.e., elasticity, stiffness, thickness) and / or may be dictated by mechanical, electrical, and / or magnetic characteristics. The threshold at which the valve allows fluid to flow may be predetermined by the valve design and / or may be mechanically adjustable.

[0163] 34A and 34B, two different relief valve designs are shown within the inner lumen 114 of the cylindrical flow restricting member 112. The binary relief valve 116 shown in FIG. 34A maintains a substantially closed position until a given force is applied to transition quickly to a substantially open position. The force at which the relief valve 116 transitions from a closed position to an open position is preferably 30-60 mmHg, although it should be understood that this pressure can be any pressure. To achieve binary (i.e., on / off) functionality, the binary relief valve can include a cutout section that is designed to transition in response to a given force. In response to releasing the pressure by opening and allowing fluid to pass, the elasticity or other mechanical characteristics of the material can cause the binary relief valve 116 to recoil to a closed position. It should be understood that this binary functionality can be achieved using various other designs and / or by incorporating other materials. For example, the relief valve 132 of FIG. 38A-B can also achieve binary functionality.

[0164] A progressive relief valve 117, as shown in Fig. 34B, is designed to gradually open with increasing pressure. This functionality can be achieved, for example, by leaflets having a constant thickness or a progressively thinner cross-section as the leaflets move from the inner wall of the cylindrical balloon 113 toward the center of the inner lumen 114. However, it should be understood that any valve design that allows for progressively increased fluid flow in response to increasing pressure may be used as a progressive relief valve.

[0165] 35, a top view of the cylindrical flow restricting member 112 is shown. The relief valve 115, shown here in a closed position, prevents blood flow through the inner lumen of the cylindrical balloon 113 as long as the pressure remains below a certain threshold. Although a relief valve design having four flexible leaflets or flaps is shown, any relief valve design that can be coupled within the inner lumen 114 of the cylindrical balloon 113 can be used, including valves with fewer / more leaflets.

[0166] 36A and 36B, top views of the cylindrical flow restricting member 112 are shown. Figure 36A shows the binary relief valve 116 in its open position, also shown in Figure 34A. Figure 36B shows the progressive relief valve 117 in a partially open position, also shown in Figure 34B. As discussed above, the binary relief valve 116 is designed to open to a generally open position in response to reaching its set pressure. On the other hand, the progressive relief valve 117 is designed to open gradually as pressure increases above a certain threshold.

[0167] 37A and 37B, it may be desirable to place a stent 118 around the cylindrical balloon 113. The stent 118 can, for example, act as both a receiver and a transmitter of electrical signals. Such uses include, but are not limited to, acting as an ECG lead, emitting signals related to autonomic activity, and receiving neuromodulation signals. The stent 118 can be self-expanding and made of a conductive material. The stent 118 can be integral to the cylindrical flow restricting member 112 and / or can be removably coupled to the cylindrical flow restricting member 112.

[0168] 38A and 38B, a cylindrical flow restricting member 130 is shown. As shown in these figures, the cylindrical flow restricting member 130 includes a balloon occluder 131 and a relief valve 132, both of which are integral with the stent 118. The relief valve 132 and the balloon occluder 131 are located adjacent to one another within the stent 118. FIG. 38A shows the cylindrical flow restricting member 130 in its expanded position, which occludes blood flow within the SVC. FIG. 38B shows the occlusion device in its deflated position, which allows blood flow through the SVC. As shown in FIG. 38B, the balloon occluder 131 can be coupled to the relief valve 132 and can contract towards the relief valve 132 when deflated. The relief valve 132 can be hinged to the stent 118 and can open to allow blood flow when a certain pressure is achieved within the SVC. The relief valve 132 may be constructed using any of the techniques, designs, and materials described above for the relief valve.

[0169] 39A and 39B, a cylindrical flow restriction member 133 is shown. As shown in these figures, the cylindrical flow restriction member 133 includes a cylindrical balloon occluder 134 and a relief valve 135, both of which are integral with the stent 118. The cylindrical balloon occluder 134 can be inflated to conform to the shape of the stent 118. As shown in FIG. 39B, the cylindrical balloon occluder 134 can have an outer surface that is coupled to the stent 118 along a portion of the outer surface. The relief valve 135 can be coupled to the cylindrical balloon occluder 134. When inflated, the cylindrical balloon occluder 134 can define an inner lumen 136 through which blood can pass when the relief valve 135 is open.

[0170] FIG. 39A shows the cylindrical flow restriction member 133 with the cylindrical balloon occluder 134 in an expanded configuration. When inflated, the cylindrical balloon occluder 134 restricts blood flow in the SVC. When the cylindrical balloon occluder 134 is inflated, the relief valve 135 can open on demand to relieve any excess pressure in the SVC. FIG. 39B shows the cylindrical flow restriction member 133 in a deflated configuration. When deflated, the cylindrical flow restriction member 133 allows blood flow through the SVC. In the deflated configuration, the cylindrical balloon occluder 134 reduces in size and moves toward the portion of the stent wall to which the cylindrical balloon occluder 134 is coupled. Similarly, the relief valve 135 moves toward the stent 118 when the cylindrical flow restriction member 133 is in the deflated configuration. The cylindrical balloon occluder 134 , which has a reduced size when deflated, allows blood to flow around the inflated balloon occluder 134 and through the stent 118 .

[0171] 40A and 40B, a cylindrical flow restriction member 137 is shown. The cylindrical flow restriction member 137 includes a stent 118 and a relief valve 138. Unlike the occlusion device shown in FIGS. 32-39, the cylindrical flow restriction member 137 does not include a balloon. Instead, the relief valve 138 can be directly coupled to the stent 118, as shown in FIG. 40B. The stent 118 can be an expandable stent and can be anchored to the inner wall of the SVC. The relief valve 138 can take a similar form and have similar features as any of the relief valves described above with respect to FIGS. 32-39. The cylindrical flow restriction member 137 can totally exclude blood flow in the SVC until a certain threshold pressure is achieved in the SVC, at which point the relief valve 138 can open to allow blood flow from the SVC to the right atrium.

[0172] 41, the cylindrical flow restriction member 112 of FIG. 32 is shown coupled to a filter 126. The filter 126 can be placed downstream of the cylindrical flow restriction member 112. When the relief valve 115 is closed, blood can pool in the central lumen 114 of the cylindrical balloon 113, resulting in a stagnant blood column, which can lead to thrombosis. When the relief valve 115 is opened, blood clots can be released into the right atrium, which can cause serious problems and even death. The filter 126 can be supported either directly by the catheter or by structural features of the cylindrical flow restriction member 112, such as the cylindrical balloon 113, the relief valve 115, or the stent 118, if applicable, and can serve to capture blood clots. For example, the filter 126 can be coupled to the cylindrical balloon 113 at the downstream end of the cylindrical flow restriction member 112, as shown in FIG. 41. It should be understood that the filter 126 may be integral with any of the flow restricting members described herein.

[0173] To determine whether the SVC is totally occluded or the degree to which it is occluded, a traditional method can be employed which involves injecting contrast into the patient and observing the movement of the contrast under fluoroscopy. Alternatively, a pressure sensor can be placed against the occlusion balloon as described herein and the pressure waveform can be analyzed to determine whether the SVC is occluded. For example, CardioMEMS TM HF System pressure sensors are now available at Abbott (St. Paul, Minnesota. The pressure sensor can, for example, wirelessly communicate with an implanted controller. The pressure waveform can also be analyzed to determine the patient's blood filling pressure, diastolic status, and / or other cardiac conditions or indications. For example, the waveform can be analyzed to detect prominent "CV" waves, indicative of tricuspid regurgitation due to volume overload. In another example, the waveform can detect "A" waves, suggestive of complete heart block, ventricular tachycardia (VT), or pulmonary hypertension. The systems described herein can be used as diagnostic monitoring tools by analyzing the waveform and can respond accordingly using the SVC occlusion techniques described herein.

[0174] FIG. 42A shows a pressure sensor 140 that can generate a pressure waveform. The pressure sensor 140 can be incorporated into the catheter 31 and placed at a site proximal to the occlusion balloon to provide a pressure measurement indicative of the jugular venous pressure (JVP). A pressure sensor 156 can be optionally incorporated into the catheter 31 distal to the occlusion balloon. A user of the system shown in FIG. 42A can monitor the waveform readings from the pressure sensor 140 and determine when the waveform changes from phasic to non-phasic. When the occlusion balloon is deflated, the pressure waveform will fluctuate in phase with the heart rate, as shown by curve 141 in FIG. 42B. When the occlusion balloon is inflated, the pressure waveform becomes flat. In this manner, it can be determined whether the SVC is occluded without the need to inject contrast and without the patient entering a catheterization lab or being exposed to an x-ray. The pressure waveform can also be used to determine when to activate and deactivate the flow restricting member.

[0175] Another configuration to using x-ray / fluoroscopy to determine SVC occlusion employs two pressure sensors on opposite sides of the occlusion device. For example, FIG. 4A, discussed above, shows a system having a catheter 31 including a flow restricting member 32, a sensor 42, and a sensor 43. As shown in FIG. 4A, the sensor 42 is disposed distal to the flow restricting member 32, and the sensor 43 is disposed proximal to the flow restricting member 32. The sensors 42 and 43 can be pressure sensors and can be used to determine the degree of occlusion caused by the flow restricting member 32, as discussed above, for example, by monitoring the pressure difference across the flow restricting member 32. The pressure difference value can indicate the amount or degree of occlusion. The pressure difference can also be used to determine when to activate the flow restricting member and when to deactivate the flow restricting member.

[0176] 4A shows one arrangement of sensors, it should be understood that other arrangements of sensors may be used to obtain relevant information. As shown in FIG. 43, another sensor arrangement includes a catheter 31 that may be introduced into the patient's vascular system via a delivery device such as an introducer sheath 144. The catheter 31 preferably extends into the SVC, enters the heart via the right atrium, extends into the right ventricle, and enters the pulmonary artery via the pulmonary valve. Sensors 145, 146, and 147 may be positioned along the catheter 31, with sensor 145 positioned within the flow restricting member 32 to measure pressure within the flow restricting member 32 (i.e., balloon pressure), sensor 146 positioned along the catheter 31 distal to the flow restricting member 32 and in the SVC to measure SVC or right atrial pressure, and sensor 147 positioned along the catheter 31 distal to sensor 146 to measure the pulmonary artery to measure pulmonary artery pressure. To measure the pressure above or proximal to the flow restricting member 32, a sensor 148 can be placed directly on or otherwise incorporated into the distal end of the introducer sheath 144 where it enters the SVC. The pressure measured by the sensor 148 is indicative of the JVP. The catheter 31 can include multiple lumens used as inflation lumens, working lumens, and / or for electrical communication between a controller and the flow restricting member 32 and / or sensors 145, 146, and 147. The introducer sheath 144 can also include a lumen for electrical communication between the sensor 148 and the controller.

[0177] Referring now to FIG. 44, yet another embodiment including an introducer sheath 144 is described. The embodiment shown in FIG. 44 is similar to that of FIG. 43, except that the flow restricting member 32 and sensors 145 and 146 are also incorporated into the introducer sheath 144. Similar to the device shown in FIG. 43, the sensor 148 can be positioned above or proximal to the flow restricting member 32 and can measure the pressure above or proximal to the flow restricting member 32, which is indicative of the JVP. The sensor 145 is positioned within the flow restricting member 32 and measures the pressure within the flow restricting member 32 (i.e., the balloon pressure). The sensor 146 is positioned near the distal end of the introducer sheath 144, distal to the flow restricting member 32 and positioned within the SVC, to measure the SVC or right atrial pressure. Also similar to the device shown in FIG. 43, the catheter 31 can be introduced through the introducer sheath 144 and extended through the right atrium and into the pulmonary artery. Sensor 147 is preferably located at the distal end of catheter 31, which is positioned in the pulmonary artery to measure pulmonary artery pressure. Introducer sheath 144 may include multiple lumens used as inflation lumens, working lumens, and / or for electrical communication between the controller and flow restricting member 32 and / or sensors 145, 146, and 148. Catheter 31 may also include lumens for electrical communication between sensor 147 and the controller.

[0178] 44, the flow restricting member 32 can be selectively inflated and deflated independent of the presence of the catheter 31. When the flow restricting member 32 and sensors 145, 146, and 148 are disposed on the introducer sheath 144, therapeutic treatment involving the inflation and deflation of the flow restricting member 32 to selectively occlude the SVC can be accomplished without the introduction of the catheter 31. Additionally, the pressure differential across the flow restricting member 32 can be determined using sensors 148 and 146 regardless of whether the catheter 31 is deployed.

[0179] 45, yet another embodiment of an SVC occlusion system constructed in accordance with the principles of the present disclosure is described. Catheter 31 preferably includes two occlusion balloons, an azygos vein occlusion balloon 142 and an SVC occlusion balloon 143. Sensors 129, 139, and 149 may also be disposed on catheter 31, with sensor 129 disposed proximal to azygos vein occlusion balloon 142 to measure pressure distal to the azygos vein occlusion balloon 142, sensor 139 disposed between azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 to measure pressure between the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143, and sensor 149 disposed distal to the SVC occlusion balloon 143 to measure pressure distal to the SVC occlusion balloon. Additionally, sensor 145 is disposed within SVC occlusion balloon 143 to measure the pressure within SVC occlusion balloon 143 (i.e., the SVC occlusion balloon pressure), and sensor 155 is disposed within azygos vein occlusion balloon 142 to measure the pressure within azygos vein occlusion balloon 142 (i.e., the azygos vein occlusion balloon pressure). Additionally, the pressure differential across azygos vein occlusion balloon 142 and SVC occlusion balloon 143 can be determined using sensors 129 and 139, and 139 and 149, respectively. The pressure differential value can indicate the amount or degree of occlusion.

[0180] The azygos vein 16 drains the posterior part of the chest into the SVC. When the SVC is blocked, the azygos vein can naturally shunt the occluded SVC blood flow back to the right atrium by providing an alternative route to the right atrium. In particular, if the SVC is occluded below the origin of the azygos vein, pressure built up above the occluded portion of the SVC can cause a percentage of venous blood to back up into the chest via the azygos vein. An azygos vein occlusion balloon 142 can be placed within the SVC adjacent to the azygos vein, such that inflation of the azygos vein occlusion balloon 142 restricts or prevents blood flow from the SVC into the azygos vein. An SVC occlusion balloon 143 can be placed below the azygos vein distal to the azygos vein occlusion balloon 142, such that inflation of the SVC occlusion balloon 143 occludes the SVC but allows blood flow into the azygos vein. The catheter 31 may include multiple lumens that are used as inflation lumens and / or working lumens between the controller and the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 .

[0181] The azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 can be selectively and independently inflated and deflated. For example, the azygos vein occlusion balloon 142 can be deflated while the SVC occlusion balloon 143 can be inflated, the azygos vein occlusion balloon 142 can be inflated while the SVC occlusion balloon 143 is deflated, or both balloons can be inflated or deflated simultaneously. The azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 can also be fully or partially inflated depending on the amount of backflow into the right atrium that is desired.

[0182] When SVC occlusion balloon 143 is inflated and azygos vein occlusion balloon 142 is deflated, the SVC opens above SVC occlusion balloon 143 and blood is allowed to proceed through the azygos vein into the right atrium. If it is desired to further reduce backflow into the right atrium (further reduce preload), azygos vein occlusion balloon 142 can be inflated to occlude the azygos vein and prevent it from acting as a natural shunt.

[0183] The systems and methods of the present disclosure can be used alone, as described in the examples above, or in combination with other devices configured to assist cardiac function. For example, SVC occlusion according to the principles of the present disclosure can be used in combination with pumps such as an intra-aortic balloon pump ("IABP") or a percutaneous or surgical left ventricular assist device ("LVAD"), right ventricular assist device ("RVAD"), or any other cardiovascular (i.e., cardiac, venous, arterial) pump, whether used for total cardiac support or temporary support, to allow synchronous or asynchronous (venous and arterial) unloading of cardiac preload and afterload, respectively. For example, SVC occlusion according to the principles of the present disclosure can be used in combination with an Impella® heart pump available from Abiomed® (Danvers, Massachusetts), as described in more detail below with reference to FIG. 49. FIGS. 49 and 51-54 show an SVC occlusion system in combination with exemplary RVAD, LVAD, and IABP systems.

[0184] The disclosed system may also be coupled to other devices such as biventricular pacemakers and neuromodulation devices. For example, biventricular pacemakers are designed to resynchronize cardiac function, and SVC occlusion preferably modifies RV and LV interactions, thereby making biventricular pacing more efficient. Similarly, SVC occlusion therapy may be used in conjunction with neuromodulation devices, and the present system enhances the effectiveness of the neuromodulation devices by having a greater combined effect in stimulating the efferent vagus nerve. A further potential application may be in manifesting right ventricular failure after a patient is fitted with an LVAD. By adjusting the amount of venous return to the right ventricle, it may be possible to "tune" the right ventricular myocardium to withstand the enhanced venous return being pumped by the LVAD by reducing overload.

[0185] Although the flow restricting member 32 is described above as being disposed within the SVC and inflated and deflated therein, therapeutic occlusion of the SVC as described herein can alternatively be achieved using a cuff wrapped around the exterior of the SVC to selectively restrain the SVC. Referring now to FIG. 46, a cuff 150 is shown wrapped around the SVC. As further shown in FIGS. 47A-D, the cuff 150 can include a strap 151, an occlusion member 152, and a locking member 153. The occlusion member 152 can be incorporated into the strap 151 such that the occlusion member 152 extends outwardly from both the outer surface of the strap 151 shown in FIG. 47A and the inner surface of the strap 151 shown in FIG. 47B. The inner or inner surface of the strap 151 is the side that faces the SVC, and the outer or outer surface of the strap 151 is the side that faces away from the SVC.

[0186] The strap 151 may be generally rectangular in shape. The locking member 153 may be any known system for removably attaching one side of the strap 151 to another side of the strap 151. For example, the strap 151 may have a magnetic locking member that securely attaches the cuff 150 to the SVC. An air line 154 may connect to the occlusion member 152 on one end and to a controller on the other end. The occlusion member preferably has elastic properties that expand when the air line 154 pumps air or other fluid into the occlusion member 152. When inflated, the occlusion member 152 may expand outward from the inside of the strap 151.

[0187] Referring again to FIG. 46, strap 151 of cuff 150 can be wrapped around the SVC and locked firmly onto the SVC using locking member 153. In response to locking cuff 150 in place on the SVC, occlusion member 152 can be selectively inflated by pumping fluid through air line 154, and thus expanded towards the SVC. Because strap 151 is substantially inelastic, expansion of occlusion member 152 will restrict blood flow through the SVC by causing expansion of occlusion member 152 and compression of the SVC. Thus, occlusion of the SVC can be achieved when occlusion member 152 expands and penetrates into the SVC, causing the SVC to collapse inward. Thus, by selectively deflating and expanding occlusion member 152, therapeutic occlusion of the SVC as described herein can be achieved.

[0188] The controller 33 is programmed to cause the flow restriction member 32 to at least partially occlude the SVC for a first predetermined time interval, and then to contract, e.g., deflate, for a second predetermined time interval, e.g., at least 1 second, less than 1 minute, or 1-30 seconds. Preferably, the first predetermined time interval is greater than 1 minute, 2-8 minutes, or 4-6 minutes. For example, the first predetermined time interval can be 5 minutes ±1 minute. Also, the first predetermined time interval is preferably significantly longer than the second predetermined time interval. For example, the first predetermined time interval can be at least 5 times longer, at least 10 times longer, at least 20 times longer, or at least 30 times longer than the second predetermined time interval. In some data described herein, for example, the occlusion time interval is 5 minutes, while the deflation time interval is 10 seconds. In some embodiments, the controller 33 is programmed to cause the flow restriction member 32 to completely occlude the SVC during the first predetermined time interval. The controller 33 can be programmed to transition the flow restricting member 32 from an occluded state for a first predetermined time interval to a deflated state for a second predetermined time interval over many cycles throughout the course of treatment. As described further herein, the controller 33 can be programmed to automatically (e.g., in response to parameters detected by the sensor(s)) and / or in response to user input, cause the flow restricting member 32 to adjust the timing of the first predetermined time interval (e.g., to a third predetermined time interval) and / or adjust the timing of the second predetermined time interval (e.g., to a fourth predetermined time interval). As will be appreciated by one of ordinary skill in the art, further adjustments of the time intervals can be made throughout the course of treatment.

[0189] 48, another exemplary system 30' of the present disclosure is described. System 30' is similar to system 30 and includes a catheter 31 having a flow restricting member 32 disposed on a distal portion 34. System 30' differs from system 30 in that catheter 31 is removably coupled at a proximal end 35 to an external controller system 200. For example, catheter 31 can be disconnected from controller 33 and coupled to external controller system 200 during a clinic visit, allowing a clinician to directly monitor and adjust operation of flow restricting member 32. Catheter 31 can include an optional distal floatation balloon 201 disposed on distal portion 34, distal to flow restricting member 32. As shown in FIG. 48, distal floatation balloon 201 can be positioned within a patient's pulmonary artery.

[0190] The external controller system 200 includes a display 202, e.g., a graphical user interface, electrically coupled to an inflation source 203 and an external controller 204. The display 202 communicates with the inflation source 203 and the external controller 204 and displays information regarding the functioning of the system 30', e.g., key physiological or system parameters, or alerts generated by the external controller 204, for review or adjustment by a clinician. The clinician can review the data displayed on the display 202 and resolve malfunctions or adjust system parameters via the graphical user interface.

[0191] The inflation source 203 includes a drive mechanism, e.g., a motor, pump, that actuates the flow restricting member 32. The inflation source 203 further includes a source of inflation medium, e.g., gas or fluid, and the drive mechanism can transfer the inflation medium between the inflation source 203 and the flow restricting member 32 via the flow restricting member connector 209 in response to commands from the external controller 204. The catheter 31 also provides a fail-safe design in that when partially external, the flow restricting member 32 can be inflated to provide an occlusion only when the proximal end of the catheter 31 is coupled to the external controller 204. Such a quick-release connection at the proximal end 35 allows the catheter to be quickly unclasped from the external controller 204 for cleaning and / or emergency situations.

[0192] The external controller 204 includes a processor that is programmed to control signals to a drive mechanism of the inflation source 203, and a memory that stores instructions thereon. The external controller 204 also includes a power source, such as a battery, that provides the power needed to operate the processor, the inflation source 203, and the display 202. Alternatively, the external controller 204 can receive power via a source of electrical energy, such as an electrical cord that plugs into an electrical outlet.

[0193] The catheter 31 can be coupled at the proximal end 35 to a distal flotation balloon connector 205 for fluid communication with a source of inflation media, e.g., gas or fluid, which can be transferred between the source of inflation media and the distal flotation balloon 201 in response to commands from an external controller 204 to anchor the distal flotation balloon 201 within the patient's pulmonary artery. The catheter 31 can also be coupled at the proximal end 35 to a thermistor connector 206 for communicating with a cardiac output (CO) monitor to measure and monitor temperature, and to a pulmonary artery pressure connector 207 for communicating with a CO monitor to measure and monitor pulmonary artery pressure.

[0194] The external controller 204 can be coupled to the catheter 31 at the proximal end 35 via a right atrial pressure connector 208 to measure and monitor right atrial pressure. The external controller 204 can also be coupled to the catheter 31 at the proximal end 35 via a flow restricting member connector 209 to measure and monitor the amount of inflation medium transferred between the inflation source 203 and the flow restricting member 32, such as the pressure within the flow restricting member 32. The external controller 204 can also be coupled to a jugular venous pressure connector 210 to measure and monitor the jugular venous pressure coming from the sheath side port.

[0195] The processor of the external controller 204 may include a data transfer circuit as described above that monitors inputs from, for example, external sensors located on the catheter 31 and provides the signals to the processor. The processor is programmed to receive inputs from the data transfer circuit and adjust the time interval during which the flow restricting member 32 is maintained in the expanded state or adjust the degree of occlusion caused by the flow restricting member 32. Thus, for example, the catheter 31 may have one or more optional sensors located in the distal portion 34 of the catheter to measure parameters such as heart rate, blood flow rate, blood volume, blood filling pressure to the heart, and pressure including central venous pressure. The output of the sensors is relayed to the data transfer circuit of the external controller 204, which may pre-process the input signals, for example decimating and digitizing the output of the sensors, before being provided to the processor. The signals provided to the processor allow for evaluation of the effectiveness of the flow restricting member 32, for example by indicating reduced venous pressure during occlusion and patency, and may be used by the clinician to determine the amount of occlusion required to adjust venous return based on the severity of the patient's congestion. As will be appreciated by one of ordinary skill in the art, the system 30' may employ any combination of flow restrictors and sensors as described above.

[0196] 49, an SVC occlusion system in combination with a transvalvular LVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be placed in the SVC to at least partially intermittently occlude the SVC as described above, and an LVAD system 211 can be placed on the left side of the heart to provide full hemodynamic support. In one example, the LVAD system 211 is an Impella CP® heart pump available from Abiomed® (Danvers, Massachusetts). The LVAD system 211 includes an inflow end 212, an outflow end 213, an impeller pump 214, and an anchor 215, for example, located on a distal portion of a catheter 216. For example, the anchor 215 can be a pigtail anchor. In operation, the inflow end 212 is located in the left ventricle and the outflow end 213 is located in the ascending aorta. When the impeller pump 214 is activated, blood in the left ventricle is pumped out through the inflow end 212 and out through the outflow end 213 into the aorta, thereby mimicking the natural path of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion. For example, the impeller pump 214 can pump up to 5.0 L / min of forward blood flow from the left ventricle to the aorta. As will be appreciated by one of ordinary skill in the art, any suitable pump can be used.

[0197] LVAD system 211 also includes a controller 217 operably coupled to catheter 216 and configured to actuate pump 214 to pump blood from the left ventricle into the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. Controller 217 and controller 33 can be the same and / or incorporated into the same housing unit, with a single controller operably coupled to flow restriction member 32 and pump 214. Controller 33 can actuate flow restriction member 32 to at least partially occlude the SVC at the same time that controller 217 actuates pump 214 to pump blood from the left ventricle into the aorta.

[0198] FIG. 50 presents results obtained in animal models demonstrating left ventricular ("LV") total volume, i.e., LV pressure, for (1) a baseline model, (2) an LVAD model, and (3) an LVAD+SVC occlusion system model. As is evident from comparing model (3) with models (1) and (2), reductions in cardiac preload ("CP") and left ventricular wall tension ("LVWT") result from the use of an SVC occlusion system as described herein in combination with a transvalvular LVAD (Impella CP® heart pump available from Abiomed®, Danvers, Massachusetts), demonstrating improved functionality and efficiency in preload reduction caused by the LVAD. Additionally, the transvalvular LVAD can be operated at a lower pumping rate while achieving sufficient systemic cardiovascular support, thus reducing the potential for adverse events associated with the LVAD.

[0199] 51, an SVC occlusion system in combination with a transvalvular RVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be positioned within the SVC to at least partially intermittently occlude the SVC as described above, and an RVAD system 218 can be positioned distal to the flow restricting member 32 on the catheter 31 to provide full hemodynamic support. In one example, the RVAD system 218 is an Impella RP® heart pump available from Abiomed® (Danvers, Massachusetts). The RVAD system 218 includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222, for example, positioned on a distal portion of a catheter 223. For example, the anchor 222 can be a pigtail anchor. In operation, the outflow end 220 is positioned within the pulmonary artery and the inflow end 219 is positioned within the SVC distal to the flow restricting member 32. When the impeller pump 221 is activated, blood in the SVC is pumped out through the inflow end 219 and out through the outflow end 220 into the pulmonary artery, thereby mimicking the natural path of blood flow and relieving the load on the right ventricle. For example, the impeller pump 221 can pump up to 5.0 L / min of forward blood flow from the SVC to the pulmonary artery. As will be appreciated by one of ordinary skill in the art, any suitable pump can be used.

[0200] The controller 33 may also be operably coupled to the RVAD system 218 and configured to unload the right ventricle by actuating the pump 221 to pump blood from the SVC to the pulmonary artery. Thus, the controller 33 may simultaneously actuate the flow restricting member 32 to at least partially occlude the SVC and actuate the pump 221 to pump blood from the SVC to the pulmonary artery.

[0201] 52, an SVC occlusion system in combination with another transvalvular RVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be positioned within the SVC to at least partially occlude the SVC intermittently, as described above, and an RVAD system 218 can be positioned on the right side of the heart to provide full hemodynamic support. In one example, the RVAD system 218 is an Impella CP® heart pump available from Abiomed® (Danvers, Massachusetts). The RVAD system 218 includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222, for example, positioned on a distal portion of a catheter 223. For example, the anchor 222 can be a pigtail anchor. In operation, the inflow end 219 is positioned within the inferior vena cava (IVC) and the outflow end 220 is positioned within the pulmonary artery. When the impeller pump 221 is activated, blood in the IVC is pumped out through the inflow end 219 and out through the outflow end 220 into the pulmonary artery, thereby mimicking the natural path of blood flow and relieving the load on the right ventricle. For example, the impeller pump 221 can pump up to 5.0 L / min of forward blood flow from the IVC to the pulmonary artery. As will be appreciated by one of ordinary skill in the art, any suitable pump can be used.

[0202] RVAD system 218 also includes a controller 224 operably coupled to catheter 223 and configured to actuate pump 221 to pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle. Controller 224 and controller 33 can be the same and / or incorporated into the same housing unit, with a single controller operably coupled to flow restriction member 32 and pump 221. Controller 33 can actuate flow restriction member 32 to at least partially occlude the SVC at the same time that controller 224 actuates pump 221 to pump blood from the IVC to the pulmonary artery.

[0203] 53, an SVC occlusion system in combination with a transapical LVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be placed in the SVC to at least partially occlude the SVC intermittently, as described above, and an LVAD system 225 can be placed transapically on the left side of the heart to provide full hemodynamic support. In one example, the LVAD system 225 is a HeartWare LVAD occlusion system available from HeartWare, Inc. (Miami Lakes, Florida). TM HVAD TM LVAD system 225 includes an inflow end 226, an outflow end 227, and a pump 228, for example, implanted near the apex of the left ventricle. In operation, inflow end 226 is located in the left ventricle and outflow end 227 is located in the ascending aorta. When pump 228 is activated, blood in the left ventricle is pumped through inflow end 226 and ejected into the aorta through outflow end 227, thereby mimicking the natural path of blood flow, relieving the left ventricle of load, and increasing coronary and systemic perfusion. As will be appreciated by one of ordinary skill in the art, any suitable pump may be used.

[0204] LVAD system 225 also includes a controller 229 operably coupled to pump 228 and configured to operate pump 228 to pump blood from the left ventricle into the aorta. Controller 229 and controller 33 can be the same and / or incorporated into the same housing unit, with a single controller operably coupled to flow restricting member 32 and pump 228. Controller 33 can operate flow restricting member 32 to at least partially occlude the SVC at the same time that controller 229 operates pump 228 to pump blood from the left ventricle into the aorta.

[0205] 54, an SVC occlusion system in combination with an intra-aortic balloon pump (IABP) is described. For example, an SVC occlusion system 30 having a flow restricting member 32 at a distal portion 34 of a catheter 31 can be placed in the SVC to at least partially intermittently occlude the SVC as described above, and an IABP 230 can be placed in the descending aorta. The IABP can include a flow restricting member 231 and a catheter 232 coupled to the flow restricting member 231. The flow restricting member 231 comprises a balloon that can transition between a contracted state, for example allowing for intravenous placement, and an expanded deployed state. The flow restricting member 231 is preferably sized and shaped such that in the expanded state it partially or completely occludes blood flow in the aorta. The catheter 232 can be coupled to a controller 33 at a proximal end. The controller 33 houses a drive mechanism 36 for independently actuating the flow restricting member 32 and the flow restricting member 231. As shown in FIG. 54, the flow restricting member 231 and the flow restricting member 32 can be connected to the same controller, with a single controller operably connected to the flow restricting member 32, the flow restricting member 231, and the pump 221. However, it should be understood that the flow restricting member 32 and the flow restricting member 231 can be connected to different controllers and / or different pumps. In operation, the flow restricting member 231 is positioned within the descending aorta and will intermittently expand and deflate. The expansion can be timed to coincide with diastole, and the deflation can be timed to coincide with systole. As the flow restricting member 231 deflates, a suction effect is created within the aorta, facilitating the transfer of blood from the left ventricle to the aorta during systole.

[0206] Combining an SVC occlusion system with a VAD, RVAD, or LVAD can reduce the required flow rate of the VAD and achieve the same hemodynamic response in the patient. This would reduce the required pump speed and thus reduce potential complications associated with the higher pump speed required to generate the higher flow rates. Additionally, intermittent occlusion of the SVC following pump implantation can help unload the right ventricle while the LVAD is brought up to operating speed.

[0207] It should be understood that the foregoing description is illustrative, but not limiting, of the scope of the invention, which is defined by the appended claims. Other embodiments are within the scope of the following claims.

Claims

1. A system for providing improved cardiac performance in a patient with heart failure, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively actuated to completely occlude the SVC, the flow restricting member being an SVC occlusion balloon; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to completely occlude the SVC for a period spanning multiple cardiac cycles; Equipped with the controller is programmed to intermittently actuate the flow restricting member to completely occlude the SVC for a first predetermined time interval greater than one minute and to contract for a second predetermined time interval over a plurality of cardiac cycles, thereby reducing cardiac preload during the intervals sufficiently to improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain; The controller is programmed such that the first predetermined time interval exceeds the second predetermined time interval by at least five times.

2. A first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal; a second pressure sensor disposed on the catheter and distal to the flow restricting member, the second pressure sensor outputting a second pressure signal; Further comprising:

2. The system of claim 1, wherein the controller is configured to generate a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicating a degree of obstruction of the flow restricting member.

3. The system described in claim 1, further comprising an azygos vein occlusion balloon positioned on the catheter proximal to the flow restricting member.

4. The system of claim 3, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein.

5. The system described in claim 4, wherein the azygos vein occlusion balloon and the SVC occlusion balloon are operated independently.

6. The system described in claim 4, wherein the second pressure sensor is positioned between the azygos vein occlusion balloon and the SVC occlusion balloon, the system further comprising a third pressure sensor positioned on the catheter distal to the azygos vein occlusion balloon, the third pressure sensor configured to output a third pressure signal, and the controller configured to generate a second signal corresponding to a difference between the second pressure signal and the third pressure signal, the second signal indicating a degree of occlusion of the azygos vein.

7. The system of claim 1, wherein the controller is configured for embedding.

8. The system of claim 1, wherein the first predetermined time interval is 4 to 6 minutes and the second predetermined time interval is 1 to 30 seconds.

9. The system of claim 2, wherein the controller is configured to use the first signal to determine when to activate the flow restricting member to completely block the SVC and when to cease activation of the flow restricting member.

10. The system described in claim 1, wherein the flow restricting member comprises an inflatable cylindrical balloon having a relief valve coupled to the inflatable cylindrical balloon, the relief valve having an open position and a closed position.

11. The system of claim 10, wherein the relief valve is configured to open at a pressure of 30 to 60 mmHg and allow fluid to flow through the SVC to the patient's right atrium.

12. The system of claim 10, wherein the relief valve is a binary valve configured to deform to an open position in response to the application of pressure above a certain threshold.

13. The system of claim 10, wherein the relief valve is a progressive valve configured to deform to an open position as pressure applied to the relief valve increases.

14. The system of claim 1, wherein the controller is further configured to intermittently actuate the flow restricting member to create a negative pressure sink within the patient's right atrium and accelerate flow from the renal veins to enhance renal decongestion and encourage blood flow across the patient's kidneys.

15. A system for improving cardiac function by moving a patient's cardiac contractility toward a healthy range of the Frank-Starling curve, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively actuated to completely occlude the SVC, the flow restricting member being an SVC occlusion balloon; a controller configured to be operably coupled to the catheter, the controller being programmed to intermittently actuate the flow restricting member to completely occlude the SVC for a first predetermined time interval greater than one minute and to contract for a second predetermined time interval over a plurality of cardiac cycles to reduce the patient's diastolic volume and improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain; Equipped with The controller is programmed such that the first predetermined time interval exceeds the second predetermined time interval by at least five times.

16. A system for improving cardiac and renal function in a patient, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of the patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively actuated to completely occlude the SVC, the flow restricting member being an SVC occlusion balloon; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to completely occlude the SVC for a period spanning multiple cardiac cycles; Equipped with the controller is programmed to intermittently activate the flow restricting member to completely occlude the SVC for a first predetermined time interval greater than one minute and to contract for a second predetermined time interval over a plurality of cardiac cycles to create a negative pressure sink within the patient's right atrium and accelerate flow from the renal vein to enhance renal decongestion and facilitate blood flow across the patient's kidneys; The controller is programmed such that the first predetermined time interval exceeds the second predetermined time interval by at least five times.

17. A system for use with a ventricular assist device (VAD) to improve the efficiency and functionality of the VAD, the system comprising: a catheter having a proximal end and a distal region, the catheter configured for intravascular placement such that the distal region is disposed within a superior vena cava (SVC) of a patient; a flow restricting member disposed on a distal region of the catheter, the flow restricting member configured to be selectively actuated to completely occlude the SVC, the flow restricting member being an SVC occlusion balloon; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to completely occlude the SVC for a segment spanning multiple cardiac cycles, thereby reducing cardiac preload and pulmonary artery pressure to improve cardiac performance; the controller is programmed to intermittently activate the flow restricting member to fully occlude the SVC for a first predetermined time interval greater than one minute and to deflate the SVC for a second predetermined time interval over a plurality of cardiac cycles; The controller is programmed such that the first predetermined time interval exceeds the second predetermined time interval by at least five times.

18. The system described in claim 17, wherein the flow restricting member is an inflatable cylindrical balloon, the inflatable cylindrical balloon comprising a relief valve coupled to the inflatable cylindrical balloon having an open position and a closed position.

19. The system of claim 18, wherein the relief valve is configured to open at a predetermined pressure of 30 to 60 mmHg and allow fluid to flow through the SVC to the patient's right atrium.

20. The system of claim 17, wherein the controller is configured to reduce cardiac preload during the interval sufficiently to improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac tension.

21. The method of claim 1, further comprising: a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal; and a second pressure sensor disposed on the catheter and distal to the flow restricting member, the second pressure sensor outputting a second pressure signal; Further comprising:

20. The system of claim 17, wherein the controller is configured to generate a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicating a degree of obstruction of the flow restricting member.

22. The system described in claim 21, wherein the controller is configured to use a first signal to determine when to activate the flow restricting member to completely block the SVC and when to cease activation of the flow restricting member.

23. The system of claim 17, wherein the controller is configured for embedding.

24. The system of claim 17, wherein the first predetermined time interval is at least 10 times longer than the second predetermined time interval.

25. The system of claim 17, wherein the first predetermined time interval is 4 to 6 minutes and the second predetermined time interval is 1 to 10 seconds.

26. The system described in claim 17, further comprising an azygos vein occlusion balloon positioned on the catheter proximal to the flow restricting member.

27. ​​The system of claim 26, wherein the azygos vein occlusion balloon is configured to be selectively actuated to at least partially occlude the patient's azygos vein.

28. The system of claim 26, wherein the azygos vein occlusion balloon and the SVC occlusion balloon are independently actuated.

29. The system of claim 17, wherein the controller is configured to control delivery by the VAD.

30. The system of claim 17, wherein the system enables operation of the VAD at slower speeds to achieve a hemodynamic response equal to or greater than the hemodynamic response of the VAD alone at higher speeds.

31. The system described in claim 17, wherein the VAD is a left ventricular assist device (LVAD), and the system further comprises the LVAD.

32. The system of claim 31, wherein the LVAD comprises a pump configured to pump blood from the left ventricle through an inflow end of the LVAD and discharge blood into the aorta through an outflow end of the LVAD.

33. The system described in claim 32, wherein the pump is an impeller pump.

34. The system of claim 32, further comprising an LVAD controller operably connected to the LVAD and configured to operate the pump and pump blood from the left ventricle to the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion.

35. The system of claim 34, wherein the controller operably connected to a catheter of the system actuates the flow restricting member to completely occlude the SVC at the same time that the LVAD controller actuates the pump to pump blood from the left ventricle to the aorta.

36. The system described in claim 17, wherein the VAD is a right ventricular assist device (RVAD), and the system further comprises the RVAD.

37. The system of claim 36, wherein the RVAD comprises a pump configured to pump blood from the SVC through an inflow end of the RVAD and discharge blood into a pulmonary artery through an outflow end of the RVAD.

38. The system described in claim 37, wherein the pump is an impeller pump.

39. The system of claim 37, wherein the controller is further operably connected to the RVAD and configured to actuate the pump to pump blood from the SVC to the pulmonary artery, thereby relieving load on the right ventricle.

40. The system of claim 39, wherein the controller actuates the flow restricting member to completely occlude the SVC at the same time that the controller actuates the pump to pump blood from the SVC to the pulmonary artery.

41. The system of claim 36, wherein the RVAD comprises a pump configured to pump blood from the inferior vena cava (IVC) through an inflow end of the RVAD and discharge blood into a pulmonary artery through an outflow end of the RVAD.

42. The system described in claim 41, wherein the pump is an impeller pump.

43. The system of claim 41, further comprising an RVAD controller operably coupled to the RVAD and configured to actuate the pump and pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle.

44. The system of claim 43, wherein the controller operably connected to a catheter of the system actuates the flow restricting member to completely occlude the SVC at the same time that the RVAD controller actuates the pump to pump blood from the IVC to the pulmonary artery.

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