Patent Publication Number: US-2021177425-A1

Title: Systems and methods for selectively occluding the superior vena cava for treating heart conditions

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Application Ser. No. 62/576,529, filed Oct. 24, 2017, and U.S. Provisional Application Ser. No. 62/642,569, filed Mar. 13, 2018, the entire contents of each of which are incorporated herein by reference. This application is also related to U.S. patent application Ser. No. 15/753,300, filed Feb. 17, 2018, which is a national stage application of PCT/US2016/047055, filed Aug. 15, 2016, which is a continuation-in-part of U.S. patent application Ser. No. 15/203,437, filed Jul. 6, 2016, which is a continuation of U.S. patent application Ser. No. 14/828,429, filed Aug. 17, 2015, now U.S. Pat. No. 9,393,384, the entire contents of each of which are incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     The disclosure relates to methods and systems 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. 
     BACKGROUND OF THE INVENTION 
     Heart failure is a major cause of global mortality. Heart failure often results in multiple long-term hospital admissions, especially in the later phases of the disease. Absent heart transplantation, the long-term prognosis for such patients is bleak, and pharmaceutical approaches are palliative only. Consequently, there are few effective treatments to slow or reverse the progression of this disease. 
     Heart failure can result from any of multiple initiating events. Heart failure may occur as a consequence of ischemic heart disease, hypertension, valvular heart disease, infection, inherited cardiomyopathy, pulmonary hypertension, or under conditions of metabolic stress including pregnancy. Heart failure also may occur without a clear cause—also known as idiopathic cardiomyopathy. The term heart failure encompasses left ventricular, right ventricular, or biventricular failure. 
     While the heart can often initially respond successfully to the increased workload that results from high blood pressure or loss of contractile tissue, over time this stress induces compensatory cardiomyocyte hypertrophy and remodeling of the ventricular wall. In particular, over the next several months after the initial cardiac injury, the damaged portion of the heart typically will begin to remodel as the heart struggles to continue to pump blood with reduced muscle mass or less contractility. This in turn often leads to overworking of the myocardium, such that the cardiac muscle in the compromised region becomes progressively thinner, enlarged and further overloaded. Simultaneously, the ejection fraction of the damaged ventricle drops, leading to lower cardiac output and higher average pressures and volumes in the chamber throughout the cardiac cycle, the hallmarks of heart failure. Not surprisingly, once a patient&#39;s heart enters this progressively self-perpetuating downward spiral, the patient&#39;s quality of life is severely affected and the risk of morbidity skyrockets. Depending upon a number of factors, including the patient&#39;s prior physical condition, age, sex and lifestyle, the patient may experience one or several hospital admissions, at considerable cost to the patient and social healthcare systems, until the patient dies either of cardiac arrest or any of a number of co-morbidities including stroke, kidney failure, liver failure, or pulmonary hypertension. 
     Currently, there are no device-based solutions that specifically target a reduction in preload to limit the progression of heart failure. Pharmaceutical approaches are available as palliatives to reduce the symptoms of heart failure, but there exists no pharmaceutical path to arresting or reversing heart failure. Moreover, the existing pharmaceutical approaches are systemic in nature and do not address the localized effects of remodeling on the cardiac structure. It therefore would be desirable to provide systems and methods for treating heart failure that can arrest, and more preferably, reverse cardiac remodeling that result in the cascade of effects associated with this disease. 
     Applicants note that the prior art includes several attempts to address heart failure. Prior to applicants&#39; invention as described herein, there are no effective commercial devices available to treat this disease. Described below are several known examples of previously known systems and methods for treating various aspects of heart failure, but none appear either intended to, or capable of, reducing 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 possibly severe side-effects. 
     For example, U.S. Pat. No. 4,546,759 to Solar describes a triple balloon catheter designed for placement such that a distal balloon intermittently occludes the superior vena cava, a proximal balloon intermittently occludes the inferior vena cava, and an intermediate balloon expands synchronously with occurrence of systole of the right ventricle, thereby enhancing ejection of blood from the right ventricle. The patent describes that the system is inflated and deflated in synchrony with the normal heart rhythm, and is designed to reduce the load on the right ventricle to permit healing of injury or defect of the right ventricle. It does not describe or suggest that the proposed regulation of flow into and out of the right ventricle will have an effect on either LVEDV or LVEDP, nor that it could be used to arrest or reverse acute/chronic heart failure. 
     U. S. Patent Publication No. US 2006/0064059 to Gelfand describes a system and method intended to reduce cardiac infarct size and/or myocardial remodeling after an acute myocardial infarction by reducing the stress in the cardiac walls. The system described in the patent includes a catheter having a proximal portion with an occlusion balloon configured for placement in the inferior vena cava and a distal portion configured for placement through the tricuspid and pulmonary valves 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 ventricles, and consequently, reduces the load on the ventricles, permitting faster healing and reducing the expansion of the myocardial infarct. The system described in Gelfand includes sensors mounted on the catheter that are read by a controller to adjust regulation of the blood flow entering the heart, and other measured parameters, to within predetermined limits. The patent application does not describe or suggest that the system could be used to treat, arrest or reverse congestive heart failure once the heart has already undergone the extensive remodeling typically observed during patient re-admissions to address the symptoms of congestive heart failure. 
     U.S. Patent Publication No. US 2010/0331876 to Cedeno describes a system and method intended to treat congestive heart failure, similar in design to described in Gelfand, by regulating the return of venous blood through the inferior vena cava. The system described in Cedeno describes that a fixed volume balloon disposed in the inferior vena cava will limit blood flow in the inferior vena cava (IVC). The degree of occlusion varies as the vessel expands and contracts during inspiration and expiration, to normalize 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 methods described in Cedeno appear promising, there are a number of potential drawbacks to such a system that applicants&#39; have discovered during their own research. Applicants have observed during their own research that fully occluding the inferior vena cava not only reduces left ventricular volume, but significantly reduces left ventricular systolic pressure, leading to reduced systemic blood pressure and cardiac output. Moreover, full inferior vena cava occlusion may increase venous congestion within the renal, hepatic, and mesenteric veins; venous congestion is a major cause of renal failure in congestive heart failure patients. 
     There are several major limitations to approaches that involve partial or full occlusion of the IVC to modulate cardiac filling pressures and improve cardiac function. First, the IVC has to be reached via the femoral vein or via the internal jugular vein. If approached via the femoral vein, then the patient will be required to remain supine and will be unable to ambulate. If approached via the jugular or subclavian veins, the apparatus would have to traverse the superior vena cava and right atrium, thereby requiring cardiac penetration, which predisposes to potential risk involving right atrial injury, induction of arrhythmias including supraventricular tachycardia or bradycardia due to heart block. Second, the IVC approach described by Cedeno and colleagues depends on several highly variable indices (especially in the setting of congestive heart failure): 1) IVC diameter, which is often dilated in patients with heart failure; b) intermittent (full or partial) IVC occlusion may cause harm by increasing renal vein pressure, which reduces glomerular filtration rates and worsens kidney dysfunction; c) dependence on the patient&#39;s ability to breathe, which is often severely impaired in HF (A classic breathing pattern in HF is known as Cheynes Stokes respiration, which is defined by intermittent periods of apnea where the IVC may collapse and the balloon will cause complete occlusion resulting in lower systemic blood pressure and higher renal vein pressure); d) if prolonged cardiac unloading is required to see a clinical improvement or beneficial changes in cardiac structure or function, then IVC occlusion will not be effective since sustained IVC occlusion will compromise blood pressure and kidney function. Third, the approach defined by Cedeno will require balloon customization depending on IVC size, which may be highly variable. Fourth, many patients with heart failure have IVC filters due to an increased propensity for deep venous thrombosis, which would preclude broad application of IVC therapy. 
     Pulmonary hypertension (PH) is also a major cause of morbidity and mortality worldwide. While heart failure is a common cause of pulmonary hypertension, as mentioned above, pulmonary hypertension may also be caused by primary lung disease. Today, pharmacologic treatments may reduce pulmonary artery systolic pressure (PASP) and improve symptoms and ultimately survival for patients with pulmonary hypertension. However, there are drawbacks to pharmacologic treatments such as costs and side effects. 
     In view of the foregoing drawbacks of the previously known systems and methods for regulating venous return to address heart failure, it would be desirable to provide systems and methods for treating acute and chronic heart failure that reduce the risk of exacerbating co-morbidities associated with the disease. 
     It further would be desirable to provide systems and methods for treating acute and chronic heart failure that arrest or reverse cardiac remodeling, and are practical for chronic and/or ambulatory use. 
     It still further would be desirable to provide systems and methods for treating heart failure that permit patients suffering from this disease to have improved quality of life, reducing the need for hospital admissions and the length of hospital stays, and the associated burden on societal healthcare networks. 
     It also would be desirable to provide systems and methods that permit treatment of pulmonary hypertension and cardiorenal syndrome. 
     SUMMARY OF THE INVENTION 
     In view of the drawbacks of the previously 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 arrest, and more preferably, reverse cardiac remodeling that result in the cascade of effects associated with this disease. 
     It further would be desirable to provide systems and methods for arresting or reversing cardiac remodeling in patients suffering from heart failure that are practical for ambulatory and/or chronic use. 
     It still further would be desirable to provide systems and methods for treating heart failure that reduce the risk of exacerbating co-morbidities associated with the disease, such as venous congestion resulting in renal and hepatic complications. 
     It also would be desirable to provide systems and methods for treating heart failure that permit patients suffering from this disease to have improved quality of life, while reducing the need for hospital re-admissions and the associated burden on societal healthcare networks. 
     It further would be desirable to provide systems and methods for treating pulmonary hypertension that permit patients suffering from this disease to have improved quality of life. In addition, it would be desirable to provide systems and methods for treating heart attacks, acute heart failure, chronic heart failure, heart failure with preserved ejection fraction, right heart failure, constrictive and restrictive cardiomyopathies, and cardio-renal syndromes (Types 1-5). 
     These and other advantages are provided by the present invention, which provides systems and methods for regulating venous blood return to the heart through the superior vena cava (“SVC”), over intervals spanning several cardiac cycles, to reduce ventricular overload, and to reduce cardiac preload and pulmonary artery pressure without increasing renal vein pressure. In accordance with the principles of the present invention, venous regulation via the SVC can be used to reduce LVEDP, LVEDV, RVEDP, and/or RVEDV, and to arrest or reverse ventricular myocardial remodeling. Counter-intuitively, applicants have observed in preliminary animal testing that intermittent partial occlusion of the SVC does not lead to stagnation of cerebral flow or observable adverse side effects. More importantly, applicants&#39; preliminary animal testing reveals that occlusion of the SVC results in significant reduction in both RVEDP and LVEDP, while improving total cardiac output and without a significant reduction on left ventricular systolic pressure (“LVSP”). Accordingly, unlike the approach discussed in the foregoing published Cedeno patent application, the present invention provides a beneficial reduction in LVEDP, LVEDV, RVEDP, and/or RVEDV, with negligible impact on LVSP, but improved stroke volume (cardiac output), and reduced risk for venous congestion resulting in increased co-morbidities. The systems and methods described herein provide acute improvement in cardiac filling pressures and function to benefit patients at risk for acutely decompensated heart failure. 
     There are several major advantages to targeting SVC flow (instead of IVC flow). First, device placement in the SVC avoids use of the femoral veins and avoids cardiac penetration. This allows for development of a fully implantable, and even ambulatory, system for acute or chronic therapy. Second, SVC occlusion can be intermittent or prolonged depending on the magnitude of unloading required. Unlike IVC occlusion, prolonged SVC occlusion maintains systemic blood pressure and improves cardiac output. This allows for sustained unloading of both the right and left ventricle, which allows for both acute hemodynamic benefit and the potential for long term beneficial effects on cardiac structure or function. Third, unlike IVC occlusion, SVC occlusion does not depend on patient respiration. Fourth, by developing an internal regulator of SVC occlusion driven by mean right atrial pressure or the pressure differential across the occlusion balloon, the SVC device can be programmed and personalized for each patient&#39;s conditions. Fifth, by placing the device in the SVC, the device can be used in patients with existing IVC filters. 
     In accordance with another aspect of the present invention, partial or total intermittent occlusion of the SVC over multiple cardiac cycles is expected to permit the myocardium to heal, such that the reduced wall stress in the heart muscle arrests or reverses the remodeling that is symptomatic of the progression of heart failure. Without wishing to be bound by theory, applicants believe that intermittent occlusion of the SVC permits the heart, when implemented over a period of hours, days, weeks, or months, to transition from a Starling curve indicative of heart failure with reduced ejection fraction towards a Starling curve having LVEDP and LVEDP more indicative of normal cardiac function. Consequently, applicant&#39;s preliminary animal testing suggests that use of the inventive system over a period of hours, days, weeks, or months, e.g., 3-6 months, may not only arrest the downward spiral typical of the disease, but also may enable the heart to recover function sufficiently for the patient to terminate use of either the system of the present invention, pharmaceutical treatments, or both. 
     In accordance with another aspect of the disclosure, a system is provided that comprises a catheter having a flow limiting element configured for placement in or on the SVC, and a controller for controlling actuation of the flow limiting element. The controller is preferably programmed to receive an input indicative of fluctuations in the patient&#39;s hemodynamic state and to regulate actuation/deactivation of the flow limiting element responsive to that input. The fluctuations in the patient&#39;s hemodynamic state may result from the patient&#39;s ambulatory activity. The controller may be programmed at the time of implantation of the catheter to retain full or partial occlusion of the SVC over a predetermined number of heart cycles or predetermined time interval based on the patient&#39;s resting heart rate, and this preset number of cycles or time interval may be continually adjusted by the controller responsive to the patient&#39;s heart rate input. The controller may further receive signals from sensors and/or electrodes indicative of sensed parameters reflecting the hemodynamic state, e.g., blood flow rate, blood volume, pressure including cardiac filling pressure, and the controller may continually adjust the preset number of cycles or time interval responsive to the sensed parameter(s). 
     In one preferred embodiment, the catheter is configured to be implanted intravascularly (e.g., via the patient&#39;s left subclavian vein), so that the flow limiting element is disposed within the SVC just proximal of the right atrium. A proximal end of the catheter may be coated or impregnated with an antibacterial agent to enable prolonged use of the catheter with reduced risk of infection at the site where the catheter passes percutaneously. The controller preferably is battery-powered, and includes a quick-connect coupling that permits the actuation mechanism of the controller to operatively couple to the flow limiting element. In a preferred embodiment, the controller is sufficiently small such that it may be worn by the patient in a harness around the shoulder. In contrast to previously-known systems, which tether the patient to a bed or acute-care setting, the system of the present invention is configured so that the patient can be ambulatory and go about most daily activities, thereby enhancing the patient&#39;s quality-of-life and improving patient compliance with the course of treatment using the inventive system. In one embodiment, the controller is configured for implantation at a suitable location within the patient, e.g., subcutaneously under the clavicle. In such an embodiment, the implantable controller is configured for bidirectional communication with an external controller, e.g., mobile device or system-specific device. The external controller may be configured to charge the battery of the implantable controller, e.g., via respective inductive coils in each controller, and may receive data indicative of the sensed parameters including heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure. One or more external power sources may be in electrical communication with the implantable controller and also may be configured to provide power to the controller to charge the battery of the implantable controller. The one or more external power sources may generate an alert when a power level of the one or more external power sources is below a threshold power level. 
     In a preferred embodiment, the flow limiting element comprises a non-compliant or semi-compliant balloon or balloons affixed to a distal region of the catheter, such that the controller actuates the balloon by periodically inflating and deflating the balloon to selectively fully or partially occlude the SVC and/or the azygos vein. For example, the controller may be programmed to intermittently actuate the flow limiting element to at least partially occlude the SVC for a first predetermined time interval and to contract for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval may be at least five times greater than the second predetermined time interval. For example, the first predetermined time interval may be 4-6 minutes, while the second predetermined time interval is 1-30 seconds. In alternative embodiments, the flow limiting element may comprise membrane covered umbrellas, baskets or other mechanical arrangement capable of being rapidly transitioned between deployed and contracted positions, e.g., by a driveline connected to the controller. In still further embodiments, the flow limiting element may take the form of a butterfly valve or ball valve, provided the flow limiting element does not create stagnant flow zones in the SVC when in the contracted or open position. In yet further embodiments, the flow limiting element comprises a cuff configured to be applied to the exterior of the SVC and operates by narrowing or occluding the SVC when inflated. 
     The inventive system may include a sensor disposed on the catheter for placement within the venous or arterial vasculature to measure the patient&#39;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 created by the flow limiting element. In another embodiment, the controller may be configured to couple to a third-party heart rate or blood pressure sensor, such as those typically used by sporting enthusiasts, e.g., the Fitbit, via available wireless standards, such as Bluetooth, via the patient&#39;s smartphone. In this embodiment, the cost, size and complexity of the controller may be reduced by integrating it with commercially available third-party components. 
     In accordance with another aspect of the disclosure, a method for controlling blood flow in a patient comprises inserting and guiding to the vena cava of a patient a venous occlusion device, coupling the occlusion device to a controller worn externally by, or implanted in, the patient; and activating the venous occlusion device intermittently, for intervals spanning multiple cardiac cycles, so that over a period of several minutes, hours, days, weeks, or months, remodeling of the myocardium is arrested or reversed. 
     In accordance with another aspect of the disclosure, a system for use in combination with a ventricular assist device (VAD) for improving efficiency and functionality of the VAD, and for reducing the risk of adverse effects of the VAD, is provided. 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 through a subclavian or jugular vein of the patient) so that the distal region is disposed in a superior vena cava (SVC) of the patient. The system also includes a flow limiting element, e.g., an SVC occlusion balloon, disposed on the distal region of the catheter, the flow limiting element selectively actuated to at least partially occlude the SVC, and a controller operatively coupled to the catheter to intermittently actuate the flow limiting element to at least partially occlude the SVC for an interval spanning a single or multiple cardiac cycles, thereby reducing cardiac preload and pulmonary artery pressure to improve cardiac performance. For example, the controller may reduce cardiac preload during the interval sufficiently to improve cardiac performance as measured by at least one of: reduced cardiac filling pressures, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased lusitropy, reduced left ventricular stiffness or reduced cardiac strain. 
     The system further may include a first pressure sensor disposed on the catheter proximal to the flow limiting element, the first pressure sensor outputting a first pressure signal, and a second pressure sensor disposed on the catheter and distal to the flow limiting element, the second pressure sensor outputting a second pressure signal, wherein the controller generates a first signal corresponding to a difference between the first pressure signal and the second pressure signal, the first signal indicative of a degree of occlusion of the flow limiting element. The controller may use the first signal to determine when to actuate the flow limiting element to at least partially occlude the SVC and when to cease actuation of the flow limiting element. The controller also may be programmed to activate an alarm as a safety signal for the operator based on the first signal. In one embodiment, the controller is configured for implantation at a suitable location within the patient, e.g., subcutaneously under the clavicle. 
     In addition, the controller may be programmed to intermittently actuate the flow limiting element to at least partially occlude the SVC for a first predetermined time interval and to contract for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval may be at least ten times greater than the second predetermined time interval. For example, the first predetermined time interval may be 4-6 minutes, while the second predetermined time interval is 1-10 seconds. 
     In one preferred embodiment, the flow limiting element is an inflatable cylindrical balloon, the inflatable cylindrical balloon having a relief valve coupled to the inflatable cylindrical balloon having an open and closed position. The relief valve may be opened at a predetermined pressure between 30-60 mmHg to permit fluid to flow through the SVC to a right atrium of the patient. The system further may include an azygos vein occlusion balloon disposed on the catheter proximal to the flow limiting element. The azygos vein occlusion balloon may be selectively actuated to at least partially occlude an azygos vein of the patient, and the azygos vein occlusion balloon and the SVC occlusion balloon may be independently actuated. In addition, the system permits operation of the VAD at slower speeds to achieve a hemodynamic response equivalent to or greater than a VAD-only hemodynamic response at higher speeds 
     In addition, the system may 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 through a femoral artery of the patient so that the inflow end is disposed in a left ventricle of the patient and the outflow end is disposed in an aorta of the patient. The LVAD also includes a pump, e.g., an impeller pump, disposed on the distal region of the catheter, wherein the pump may be selectively actuated to pump blood from the left ventricle through the inflow end and expel blood into the aorta via the outflow end, and an LVAD controller operatively coupled to the LVAD to actuate the pump to pump blood from the left ventricle to the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. The LVAD controller operatively coupled to the catheter of the system may regulate the activation and deactivation of the flow limiting element to at least partially occlude the SVC simultaneously as the LVAD controller actuates the pump to pump blood from the left ventricle to the aorta. 
     Alternatively or in addition to, the system may further include a right ventricular assist device (RVAD), the RVAD including a pump, e.g., an impeller pump, that may be selectively actuated to pump blood from the SVC through an inflow end of the RVAD and expel blood into a pulmonary artery via an outflow end of the RVAD. The controller also may be operatively coupled to the RVAD to actuate the pump to pump blood from the SVC to the pulmonary artery, thereby unloading the right ventricle. For example, the controller may actuate the flow limiting element to at least partially occlude the SVC simultaneously as the controller actuates the pump to pump blood from the SVC to the pulmonary artery. 
     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 through a femoral vein of the patient so that the outflow end is disposed in a pulmonary artery of the patient and the inflow end is disposed in an IVC of the patient. The RVAD also includes a pump, e.g., an impeller pump, disposed on the distal region of the catheter, wherein the pump may be selectively actuated to pump blood from the IVC through the inflow end and expel blood into the pulmonary artery via the outflow end, and an RVAD controller operatively coupled to the RVAD to actuate the pump to pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle. The RVAD controller operatively coupled to the catheter of the system may regulate the activation and deactivation of the flow limiting element to at least partially occlude the SVC simultaneously as the RVAD controller actuates the pump to pump blood from the IVC to the pulmonary artery. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The characteristics and advantages of the present invention will become apparent from the detailed description of the embodiment of the disclosure presented below in conjunction with the attached drawings, in which: 
         FIG. 1A  is a frontal, partially broken-away view of the major arteries and veins of the heart. 
         FIG. 1B  illustrates the vena cava including major veins associated with the vena cava. 
         FIGS. 2A and 2B  illustrate Frank-Starling curves for normal and afflicted cardiac conditions. 
         FIG. 3  is a graph of exemplary pressure-volume loop curves of left ventricular pressure versus left ventricular volume throughout a cardiac cycle for a patient having normal cardiac function and a patient suffering from congestive heart failure. 
         FIG. 4A  is a schematic drawing of a system constructed in accordance with the principles of the present invention. 
         FIG. 4B  is a schematic drawing of an implantable system constructed in accordance with the principles of the present invention. 
         FIG. 4C  is a drawing of a power source and a charging base. 
         FIGS. 5A-5B  are schematic drawings of the catheter of  FIG. 4A  and  FIG. 4B  wherein the flow limiting element comprises a cylindrical balloon with modified anchoring members shown in its expanded and contracted states, respectively. 
         FIG. 6  is a schematic drawing of the catheter of  FIG. 4A  and  FIG. 4B  wherein the flow limiting element comprises a mechanically actuated membrane covered basket. 
         FIG. 7  is a cross-sectional view of the catheter of  FIG. 4A  and  FIG. 4B . 
         FIGS. 8A and 8B  are schematic drawings of a flow limiting element comprising a ball-shaped balloon shown in its expanded and contracted states, respectively. 
         FIGS. 9A and 9B  are schematic drawings of a flow limiting element comprising a spring-loaded plug shown in its expanded and contracted states, respectively. 
         FIGS. 10A and 10B  are schematic drawings of a flow limiting element comprising an alternative embodiment of a spring-loaded plug shown in its expanded and contracted states, respectively. 
         FIG. 11  shows graphs and a table showing left ventricle (LV) pressure and LV volume for a number of successive heart beats in a swine model following full occlusion of the inferior vena cava (IVC). 
         FIG. 12  shows graphs and a table showing LV pressure and LV volume for a number of successive heart beats in a swine model following partial occlusion of the superior vena cava (SVC). 
         FIGS. 13-14  are graphs showing the changes in pressure as a function of left and right ventricular volume, respectively, during occlusion of the superior vena cava (SVC) and release in a swine subjected to heart failure in accordance with the principles of the present invention. 
         FIGS. 15-22  show test results for swine subjects subjected to heart failure. 
         FIGS. 23A to 23D  illustrate, respectively, clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume and ventricular stroke work during the deflation time of a one minute episode of continuous SVC occlusion in accordance with the principles of the present invention. 
         FIGS. 24A to 24D  illustrate, respectively, clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume and ventricular stroke work during the deflation time of a five minute episode of continuous SVC occlusion in accordance with the principles of the present invention. 
         FIGS. 25A to 25D  illustrate, respectively, clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume and ventricular stroke work during the deflation time of a ten minute episode of continuous SVC occlusion in accordance with the principles of the present invention. 
         FIGS. 26A to 26C  illustrate, respectively, clinical pressure changes in pulmonary capillary wedge pressure, pulmonary artery pressure and right atrial pressure observed during a five minute episode of continuous SVC occlusion in accordance with the principles of the present invention. 
         FIGS. 27A to 27E  illustrate, respectively, clinical pressure changes in systolic pressure, diastolic pressure, mean arterial pressure, mean pulmonary artery pressure, and mean pulmonary capillary wedge pressure during five minutes of continuous SVC occlusion in accordance with the principles of the present invention. 
         FIGS. 28A to 28B  illustrate, respectively, clinical pressure changes in mean pulmonary artery pressure and mean arterial pressure, during ten minutes of continuous SVC occlusion in accordance with the principles of the present invention. 
         FIG. 29  illustrates the cardiac output before occlusion and during occlusion of the SVC in accordance with the principles of the present invention. 
         FIG. 30  illustrates the pulmonary artery systolic pressure during with occlusion and without occlusion of the SVC in accordance with the principles of the present invention. 
         FIG. 31  is a prophetic example of how SVC occlusion in accordance with the principles of the present invention is expected to change the course of the disease. 
         FIG. 32  is a perspective view of the cylindrical flow limiting element. 
         FIG. 33  is a cross-sectional view of the cylindrical flow limiting element showing the relief valve. 
         FIGS. 34A-B  are cross-sectional views of the cylindrical flow limiting element having binary and gradual relief valves. 
         FIG. 35  is a top view of the cylindrical flow limiting element having a relief valve in a closed position. 
         FIGS. 36A-B  are top views of the cylindrical flow limiting element having a binary relief valve and a gradual relief valve in an open position. 
         FIGS. 37A-B  are perspective and cutaway views of the cylindrical flow limiting element engaged with a stent. 
         FIGS. 38A-B  are top views of the cylindrical flow limiting element having a balloon occluder in an inflated and deflated position. 
         FIGS. 39A-B  are top views of the cylindrical flow limiting element having a cylindrical balloon occluder in an inflated and deflated position. 
         FIGS. 40A-B  are perspective and cutaway views of a stent coupled to a relief valve. 
         FIG. 41  is a cutaway view of a cylindrical flow limiting element coupled to a filter. 
         FIG. 42A  is a cutaway perspective view of a cylindrical flow limiting element coupled to a catheter with a sensor and  FIG. 42B  is an exemplary phasic curve. 
         FIG. 43  is a view of an introducer sheath entering an SVC, a flow limiting element within the SVC, and a catheter positioned within the heart. 
         FIG. 44  is a view of an introducer sheath positioned within an SVC, a flow limiting element incorporated in the introducer sheath, and a catheter positioned within the heart. 
         FIG. 45  is a view of an occlusion system having an azygos vein occlusion balloon and a second occlusion balloon positioned within the SVC. 
         FIG. 46  is a view of an occlusion cuff wrapped around the SVC. 
         FIGS. 47A-B  are views of an exterior side and an interior side of an occlusion cuff, and  FIGS. 47C-D  are perspective views of an occlusion cuff. 
         FIG. 48  is an alternative exemplary system constructed in accordance with the principles of the present invention. 
         FIG. 49  illustrates an SVC occlusion system in combination with a trans-valvular LVAD. 
         FIG. 50  is a graph illustrating enhancement of the unloading capacity of SVC occlusion when used in combination with a trans-valvular LVAD. 
         FIG. 51  illustrates an SVC occlusion system in combination with a trans-valvular RVAD. 
         FIG. 52  illustrates an SVC occlusion system in combination with an alternative trans-valvular RVAD. 
         FIG. 53  illustrates an SVC occlusion system in combination with an LVAD. 
         FIG. 54  illustrates an SVC occlusion system in combination with an intra-aortic balloon pump (IABP). 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring to  FIGS. 1A and 1B , the human anatomy in which the present invention is designed for placement and operation is described as context for the system and methods of the present invention. 
     More particularly, referring to  FIG. 1A , deoxygenated blood returns to heart  10  through vena cava  11 , which comprises superior vena cava  12  and inferior vena cava  13  coupled to right atrium  14  of the heart. Blood moves from right atrium  14  through tricuspid valve  15  to right ventricle  16 , where it is pumped via pulmonary artery  17  to the lungs. Oxygenated blood returns from the lungs to left atrium  18  via the pulmonary vein. The oxygenated blood then enters left ventricle  19 , which pumps the blood through aorta  20  to the rest of the body. 
     As shown in  FIG. 1B , superior vena cava  12  is positioned at the top of vena cava  11 , while inferior vena cava  13  is located at the bottom of the vena cava.  FIG. 1B  also shows azygos vein  16  and some of the major veins connecting to the vena cava. As noted herein, occlusion of the inferior vena cava  13  may pose risks of venous congestion, and in particular, potential blockage or enlargement of the hepatic veins and/or suprarenal vein that may worsen, rather than improve, the patient&#39;s cardiovascular condition and overall health. 
     In accordance with one aspect of the present invention, applicants have determined that selective intermittent occlusion of the superior vena cava (“SVC”) poses fewer potential adverse risks than occlusion of the inferior vena cava (“IVC”). Moreover, applicants&#39; animal and human testing reveals that controlling the return of venous blood to the right ventricle by partially or fully occluding the SVC beneficially lowers RVEDP, RVEDV, LVEDP and LVEDV without adversely reducing left ventricular systolic pressure (LVSP). 
     Applicants understand that selective intermittent occlusion of the SVC will reduce the risk of worsening congestion of the kidneys, which is a major cause of ‘cardio-renal’ syndrome, as compared to IVC occlusion. Cardio-renal syndrome is impaired renal function due to volume overload and neurohormonal activation in patients with heart failure. Volume overload may occur where the weakened heart cannot pump as much blood, which leads 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 via urination causing excess volume to be retained in the body. With the excess volume, the heart pumps with increasingly less efficiency and the patient ultimately spirals toward death as the body becomes progressively more congested. 
     Applicants understand that IVC occlusion generally reduces the blood flow through the kidneys as the occluded IVC increases pressure in the renal vein, thereby reducing the kidneys ability to filter out fluid. IVC occlusion further causes blood to back-up and otherwise prevents deoxygenated blood from returning to the heart. As a result, renal function may too be reduced, worsening congestion. However, SVC occlusion ultimately increases flow to the kidneys thereby improving renal function. Specifically, by reducing flow into the right atrium via SVC occlusion, volume within the left ventricle is ultimately reduced, permitting the muscle fibers to stretch within a normal range, naturally increasing contractility and allowing the heart to drive more fluid to the kidneys. The kidneys may then extract water, which may be removed from the body through urination. It is further understood that during SVC occlusion, a negative pressure sink is created in the right atrium caused by an abrupt reduction in right atrial pressure and volume. As a result, flow from the renal vein may be accelerated thereby enhancing renal decongestion and promoting blood flow across the kidney, increasing urine output. Accordingly, SVC occlusion may benefit patients with heart failure and/or cardiorenal syndrome by reducing cardiac and pulmonary pressures and promoting decongestion. 
     In addition, implantation in the SVC permits a supra-diaphragmatic device implant that could not be used in the IVC without cardiac penetration and crossing the right atrium. Further, implantation of the occluder in the SVC avoids the need for groin access as required by IVC implantation, which would limit mobility making an ambulatory device impractical for short term or long term use. In addition, minor changes in IVC occlusion (time or degree) may cause more dramatic shifts in preload reduction and hence total cardiac output/systemic blood pressure whereas the systems and methods of the present invention as expected to permit finely tuned decrease in venous return (preload reduction). 
     Applicants understand that intermittent occlusion of the SVC (i.e., cardio-pulmonary unloading) over a period of time (e.g., minutes, hours, days, weeks, or months) will beneficially permit a patients&#39; heart to discontinue or recover from remodeling of the myocardium. Applicants&#39; animal and human testing indicates that the system enables the myocardium to transition from pressure-stroke volume curve indicative of heart failure towards a pressure-stroke volume curve more closely resembling that of a healthy heart. 
     In general, the system and methods of the present invention may be used to treat any disease to improve cardiac function by arresting or reversing myocardial remodeling, and particularly those conditions in which a patient suffers from heart failure. Such conditions include but are not limited to, e.g., systolic heart failure, diastolic (non-systolic) heart failure, decompensated heart failure patients in (ADHF), chronic heart failure, acute heart failure and pulmonary hypertension, heart attacks, heart failure with preserved ejection fraction, right heart failure, constrictive and restrictive cardiomyopathies, and cardio-renal syndromes (Types 1-5). The system and methods of the present invention also may be used as a prophylactic to mitigate the aftermath of acute right or left ventricle myocardial infarction, pulmonary hypertension, RV failure, post-cardiotomy shock, or post-orthotopic heart transplantation (OHTx) rejection, or otherwise may be used for cardiorenal applications and/or to treat renal dysfunction, hepatic dysfunction, or lymphatic congestion. Also, the system and methods of the present invention may reduce hospital stays caused by various ailments described herein, including at least acute exacerbation. 
     The relationship between left ventricular pressure or left ventricular volume and stroke volume is often referred to as the Frank-Starling relationship, or “Starling curve” and is illustrated in  FIGS. 2A-2B . That relationship states that cardiac stroke volume is dependent on preload, contractility, and afterload. Preload refers to the volume of blood returning to the heart; contractility is defined as the inherent ability of heart muscle 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 increase in the left ventricle, which can result in pulmonary edema. Increased ventricular volume and pressure also results in increased workload and increased myocardial oxygen consumption. Such over-exertion of the heart results in worsening cardiac function as the heart becomes increasingly deprived of oxygen due to supply and demand mismatch. Furthermore, as volume and pressure build inside the heart, contractile function worsens due to stretching of cardiac muscle. This condition is termed “congestive heart failure.” 
     Referring to  FIG. 2A , a series of Starling curves are illustrated, in which topmost curve (curve  1 ) depicts functioning of a normal heart. As shown in the curve, stroke volume increases with increasing LVEDP or LVEDV, and begins to flatten out, i.e., the slope of the curve decreases, only at very high pressures or volumes. A patient who has just experienced an acute myocardial infarction (“AMI”), as indicated by the middle curve (curve  2 ), will exhibit reduced stroke volume at every value of LVEDV or LVEDP. However, because the heart has just begun to experience the overload caused by the localized effect of the infarct, myocardial contractility of the entire ventricle is still relatively good, and stroke volume is still relatively high at low LVEDP or LVEDV. By contrast, a patient who has suffered from cardiac injury in the past may experience progressive deterioration of cardiac function as the myocardium remodels over time to compensate for the increased workload and reduced oxygen availability, as depicted by the lowermost curve (curve  3 ) in  FIG. 2A . As noted above, this can lead to progressively lower stroke volume as the ventricle expands due to generally higher volume and pressure during every phase of the cardiac cycle. As will be observed from comparison of curves  1  and  3 , the stroke volume continues to decline as the LVEDP or LVEDV climb, until eventually the heart gives out or the patient dies of circulatory-related illness. 
       FIG. 2B  provides an alternative formulation of a Frank-Starling curve, curve  6 , illustrating the differences between functioning of a healthy heart and one in heart failure. Line  7 , up to point  8 , illustrates a Frank-Starling curve for a normal healthy heart As discussed with respect to  FIG. 2A , for a normal heart, as the end-diastolic volume increases, the stroke volume increases. For a healthy heart, however, beyond point  8 , increased end-diastolic volume no longer results in increased stroke volume, and continued increases in end-diastolic volume do not result in further increases in stroke volume. This phenomenon is shown that the solid flat line that extends substantially horizontally beyond point  8 . Decreasing dotted line  9 , which extends beyond  8 , in  FIG. 2B , represents a Frank-Starling curve for a patient in heart failure. Dotted line  9  indicates that for patients with heart failure, further increases in end-diastolic volume do not result in a substantially flat stroke volume, but instead stroke volume decreases. Accordingly, increasing EDV for patients with HF results in further reduction in SV, leading to a downward spiral in heart function, and ultimately death.  FIG. 2B  reflects a phenomenon referred to as “diastolic ventricular interaction,” which arises in part due to the structural arrangement of the cardiac chambers. As discussed, 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. Consequently, as right ventricular end diastolic volume increases, it necessarily causes a reduction in the end diastolic volume of the left ventricle. As reported in that article, reduction in right ventricular diastolic filling caused by external lower body suction allows augmented left ventricular diastolic filling. 
     Applicants understand that the foregoing phenomenon can advantageously be utilized in the context of the present invention to improve cardiac performance. In particular, in heart failure and the presence of pulmonary hypertension, right ventricular congestion due to increased volume overload can push the interventricular septum towards the left ventricular cavity, thereby reducing LV stroke volume and cardiac output. By occluding 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 in accordance with the principles of the present invention may favorably alter diastolic ventricular interaction and enhance cardiac output. Specifically, with respect to diastolic heart failure, SVC occlusion in accordance with the principles of the present invention may provide a reduction in cardiac filling pressures, increased LV relaxation (tau), increased LV capacitance, increased lusitropy, reduced LV stiffness, and reduced cardiac strain. The effect of the SVC occlusion of the present invention can thus be visualized as shifting dotted line  9  of Frank-Starling curve  6  in  FIG. 2B  for a patient in heart failure towards lower EDV, which in effect moves the cardiac performance upwards and closer towards the flat portion of the curve that extends beyond point  8  for a healthy patient. The system and methods of inducing at least partial intermittent SVC occlusion of the present invention for patients in HF therefore improves heart function by moving a patient&#39;s heart contractility toward a healthy range of the patient&#39;s Frank-Starling curve. 
       FIG. 3  illustratively shows pressure-volume loops for a normal heart, labeled “normal”, corresponding to curve  1  in  FIG. 2B , and a heart suffering from congestive heart failure, labeled “CHF” (curve  3  in  FIG. 2B ). For each loop, the ventricular volume and pressure at the end of diastole correspond to the lower-most, right-most corner of the loop (point A), while the upper-most, left-most corner of each loop corresponds to the beginning systole (point B). The stroke volume for each pressure-volume loop corresponds to the area enclosed within the loop. Accordingly, the most beneficial venous regulation regime is one that reduces the volume and pressure at point A while not also causing negligible reduction in point B, thereby maximizing the stroke volume. 
     In accordance with one aspect of the present invention, the system and methods are designed, over the course of hours, days, weeks, or months, to shift or transition the Starling curve of the patient&#39;s heart leftwards on the diagram of  FIG. 2B  (or to move the pressure-volume loop in  FIG. 3  leftwards and downwards). This may be accomplished by intermittently fully or partially occluding the SVC to reduce the volume and hence pressure of blood entering the right ventricle, and which must then be pumped by the left ventricle. Applicants&#39; preliminary animal testing indicates that such intermittent occlusion, maintained over several cardiac cycles, reduces the workload and wall stress in the myocardium throughout the cardiac cycle, reduces myocardial oxygen consumption, and improves contractile function. 
     Referring now to  FIG. 4A , exemplary system  30  of the present invention is described. System  30  includes catheter  31  having flow limiting element  32  coupled to controller  33  programmed to intermittently actuate flow limiting element  32 . As discussed below, system  30  optionally may be configured to transfer information bi-directionally with conventional computing device  45  such as a smartphone, laptop, smartwatch, or tablet, illustratively an Apple iPhone 5 or iPad, available from Apple Inc., Cupertino, Calif., on which a special-purpose application has been installed to communicate and/or control controller  33 . 
     Preferably, catheter  31  comprises a flexible tube having distal portion  34  configured for placement in the SVC. Distal portion  34  includes flow limiting element  32  that, in use, is disposed in superior vena cava  12  (see  FIG. 1B ) of a patient to selectively impede blood flow into right atrium  14 . In this embodiment, flow limiting element  32  illustratively comprises a balloon capable of transitioning between a contracted state, allowing transluminal placement and an expanded, deployed state. Flow limiting element  32  preferably is sized and shaped so that it partially or fully occludes flow in the SVC in the expanded state. Catheter  31  is coupled at proximal end  35  to controller  33 , which houses drive mechanism  36  (e.g., motor, pump) for actuating flow limiting element  32 , processor  37  programmed to control signals to drive mechanism  36 , and optional sensor  42  for monitoring a physiologic parameter of the patient, such as heart rate or blood pressure. 
     Controller  33  may include source of inflation medium  48  (e.g., gas or fluid) and drive mechanism  36  may transfer the inflation medium between the source and flow limiting element  32  responsive to commands from processor  37 . When flow limiting element  32  is inflated with inflation medium, it partially or fully occludes venous blood flow through the SVC; when the inflation medium is withdrawn, flow limiting element  32  deflates to remove the occlusion, thereby permitting flow to resume in the SVC. Flow limiting element  32  may be a balloon that preferably comprises a compliant or semi-compliant material, e.g., nylon, which permits the degree of expansion of the balloon to be adjusted to effectuate the desired degree of partial or complete occlusion of the SVC. In addition, catheter  31 , when partially external, provides a fail-safe design, in that flow limiting element  32  only can be inflated to provide occlusion when the proximal end of catheter  31  is coupled to controller  33 . Such a quick-disconnect coupling  40  at proximal end  35  permits the catheter to be rapidly disconnected from controller  33  for cleaning and/or emergency. 
     Controller  33  preferably also includes power supply  39  (e.g., battery) that provides the power needed to operate processor  37 , drive mechanism  36  and data transfer circuit  38 . Controller  33  may be sized and of such a weight that it can be worn in a harness under the patient&#39;s clothing, so that the system can be used while the patient is ambulatory or such that controller  33  may be implanted within the patient. As discussed herein below, processor  37  includes memory  41  for storing computer software for operating the controller  33 . Controller  33  may be configured for implantation at a suitable location within the patient, e.g., subcutaneously under the clavicle. In such an embodiment, the implantable controller is configured for bidirectional communication with an external controller, e.g., computing device  45  or system-specific device. An external controller may be used to charge the battery of the implantable controller, e.g., via respective inductive coils in or coupled to each controller, and may receive data indicative of the sensed parameters resulting from the patient&#39;s ambulatory activity including heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure. 
     In one embodiment, data transfer circuit  38  monitors an input from an external sensor, e.g., positioned on catheter  31 , and provides that signal to processor  37 . Processor  37  is programmed to receive the input from data transfer circuit  38  and adjust the interval during which flow limiting element  32  is maintained in the expanded state, or to adjust the degree of occlusion caused by flow limiting element  32 . Thus, for example, catheter  31  may have optional sensor  42  positioned within distal portion  34  of the catheter to measure parameters, e.g., heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and central venous pressure. The output of sensor  42  is relayed to data transfer circuit  38  of controller  33 , which may pre-process the input signal, e.g., decimate and digitize the output of sensor  42 , before it is supplied to processor  37 . The signal provided to processor  37  allows for assessment of the effectiveness of the flow limiting element, e.g., by showing reduced venous pressure during occlusion and during patency, and may be used for patient or clinician to determine how much occlusion is required to regulate venous blood return based on the severity of congestion in the patient. Additionally, sensor  43  may be included on catheter  31  proximal to flow limiting element  32 , to measure parameters, e.g., heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and central venous pressure. Sensor  43  may be used to determine the extent of occlusion caused by element  32 , for example, by monitoring the pressure drop across the flow limiting element. 
     As another example, catheter  31  may include electrodes  44  for sensing the patient&#39;s heart rate. Applicants understand that it may be desirable to adjust the interval during which occlusion of the SVC is maintained responsive to the patient&#39;s ambulatory activities, which typically will be reflected in the patient&#39;s hemodynamic state by a sensed physiological parameter(s), e.g., heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and/or central venous pressure. Accordingly, electrodes  44  may provide a signal to data transfer circuit  38 , which in turn processes that signal for use by the programmed routines run by processor  37 . For example, if the occlusion is maintained for a time programmed during initial system setup to reflect that the patient is resting, e.g., so that flow limiting element is deployed for 5 seconds and then released for two seconds before being re-expanded, it may be desirable to reduce the occluded time interval to 4 seconds or more depending upon the level of physical activity of the patient, as detected by a change in heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and/or central venous pressure above or below predetermined thresholds. Alternatively, processor  37  may be programmed to maintain partial or full occlusion in the SVC for a preset number of cardiac cycles determined at the time of initial implantation of the catheter. Sensor inputs provided to data transfer circuit  38 , such as hemodynamic state, also may be used to adjust the duty cycle of the flow limiting element responsive to the patient&#39;s detected level of activity. In addition, processor  37  may be programmed to maintain partial or full occlusion in the SVC for a preset number of cardiac cycles after adjustment to the predetermined occlusion interval is made. 
     Data transfer circuit  38  also may be configured to provide bi-directional transfer of data, for example, by including wireless circuitry to transfer data from controller  33  to an external unit for display, review or adjustment. For example, data transfer circuit may include Bluetooth circuitry that enables controller  33  to communicate with patient&#39;s computing device  45 . In this manner, controller may send information regarding functioning of the system directly to computing device  45  for display of vital physiologic or system parameters using a suitably configured mobile application. In addition, the patient may review the data displayed on the screen of computing device  45  and determine whether he or she needs to seek medical assistance to address a malfunction or to adjust the system parameters. Further, the mobile application resident on computing device  45  may be configured to automatically initiate an alert to the clinician&#39;s monitoring service via the cellular telephone network. 
     Optionally, data transfer circuit  38  may be configured to synchronize to receive data from other mobile applications on computing device  45 , and thus reduce the cost and complexity of the inventive system. For example, a number of third party vendors, such as Fitbit, Inc., San Francisco, Calif., market monitors that measure physiologic parameters in real time, such as the Charge HR wristband monitor, that measures physical activity and heart rate. In accordance with one aspect of the disclosure, data transfer circuit  38  can be programmed to receive an input from such a third-party monitor via wireless communication with computing device  45 , and that processor  37  may be programmed to control activation of drive mechanism  36  responsive to that input. In this embodiment, the catheter need not include optional sensor  42 , sensor  43  or electrodes  44 , thereby greatly simplifying the construction of catheter  31  and coupling  40 . 
     Catheter  31  may include anchor member  46  configured to anchor flow limiting element  32  within the SVC. Anchor member  46  may be contractible for delivery in a contracted state and expandable upon release from a delivery device, e.g., a sheath. Anchor member  46  may be coupled to catheter proximal or distal to flow limiting element  32  and/or may be coupled to flow limiting element  32 . The system shown in  FIG. 4A  may effectively shift a patient&#39;s heart contractility into a healthy range of the Frank-Starling curve illustrated in  FIG. 2A . 
     Referring now to  FIG. 4B , controller  33  is shown implanted at a suitable location within the patient. As is illustrated in  FIG. 4B , external power source  47  may be configured to charge power supply  39  (e.g., battery) of the implantable controller. For example, external power source  47  may transcutaneously charge power supply  39  via respective inductive coils. External power source  47  may be integrated into clothing or a harness worn by the patient. Specifically, external power source  47  may be placed in a pocket or holder configured to receive external power source  47 . When the garment or harness is worn by the patient, the pocket or holder may be designed to place external power source  47  in close proximity to battery  39  for efficient transcutaneous charging. More than one external power source  47  may be integrated into the garment to provide additional power. The one or more external power sources may be permanently integrated into the garment or harness or may be removably engaged with the garment or harness such that each may be individually removed and attached. For example, two external power sources  47  may be integrated into specially designed pockets of vest  64  as is illustrated in  FIG. 4B . Vest  64  may include wire  66  incorporated into vest  64  to permit electrical communication between the two external power sources. 
     Power source  47  may generate an alert when an available power supply reaches or falls below a certain threshold power level. For example, power source  47  may have a visual indicator and/or an auditory indicator for providing a warning to the patient or caregiver. The visual indicator may be an LED light system or a display embedded into a surface of power source  47  that visually provides information regarding the available power supply. The auditory indicator may be a speaker embedded into power source  47  that sounds an alarm when the available power supply reaches a certain threshold. A signal indicating that the available power supply of power source  47  has reached a certain threshold also may or alternatively be communicated directly to an external device, e.g. computing device  45 , and/or to controller  33  and then from controller  33  to an external device, e.g. computing device  45 , which may be programmed to initiate a visual or audio alert. An additional power source  47  may supply power to power supply  39  when the primary power source runs out of power to ensure power can be continuously provided to power supply  39 . Power source  47  may include a processor with memory for transcutaneously transmitting and receiving data from processor  37 . The processor of power source  47  may be used to reprogram processor  37  and/or store information about operating parameters to be later downloaded by an external device, e.g. computing device  45 . 
     Each external power source  47  may be placed in electrical communication with a wall power outlet or base charger  65  shown in  FIG. 4C  to charge the external power source. Base charger  65  may be in electrical communication with a wall power outlet and may be configured to charge one or more external power sources  47  at the same time. To permit power supply  39  continuous access to a power source, external power sources  47  may be periodically disengaged from the vest and charged such that at least one external power source  47  is in electrical communication with power supply  39  while the other external power source  47  is being charged in base charger  65 . Also, by enabling the system to interface with commercially available heart rate monitors and smartphones and/or tablets, the system provides both reduced cost and reduced complexity. 
     Referring now to  FIGS. 5A and 5B , an exemplary embodiment of catheter  31 ′ is described, wherein catheter  31 ′ is constructed similarly to catheter  31  of  FIG. 4A  and  FIG. 4B  except with a modified anchor. As shown in  FIG. 5A  when flow limiting element  32 ′ is in an expanded, fully occluding state, and shown in  FIG. 5B , when flow limiting element  32 ′ is in a contracted state, catheter  31 ′ may include radially expanding anchoring arms  49 . Anchoring arms  49  are configured to radially expand, e.g., when exposed from a delivery sheath, to contact the inner wall of superior vena cava  12  and anchor flow limiting element  32 ′ therein. 
     Referring now to  FIG. 6 , an alternative embodiment is described wherein the occlusion may comprise a wire basket. Flow limiting element  50  may be formed of a biocompatible material, such as nickel-titanium or stainless steel, and comprises plurality of axially or spirally extending wires  51  that are biased to expand radially outward when compressed. Flow limiting element  50  preferably includes a biocompatible membrane covering, so that it partially or fully occludes flow in the SVC in the expanded state. Wires  51  may be coupled at distal end  52  to distal end  53  of actuation wire  54 , and affixed to ring  55  at their proximal ends  56 . Ring  55  is disposed to slide on actuation wire  54  so that when actuation wire  54  is pulled in the proximal direction against sheath  57  (see  FIGS. 5A and 5B ), wires  51  expand radially outward. As shown in  FIG. 5B , in response to a force applied to the proximal end of actuation wire  54  by drive mechanism  36 , actuation wire  54  is retracted proximally against sheath  57  of the catheter; transitioning flow limiting element  50  to its expanded deployed state. Conversely, when drive mechanism  36  is deactivated, spring force applied by wires  51  pulls actuation wire  54  in the proximal direction, thereby enabling wires  51  to return to their uncompressed state, lying substantially flat against actuation wire  54 . As noted above, flow limiting element  50  has a “fail safe” design, so that the flow limiting element resumes the collapsed, contracted state shown in  FIG. 5A  when catheter  31  is uncoupled from drive mechanism  36 . In this embodiment, drive mechanism  36  may be a motor, which may be a linear motor, rotary motor, solenoid-piston, or wire motor. 
     Flow limiting element  50  may be constructed so that it is biased to the contracted position when catheter  31  is disconnected from controller  33 , so that flow limiting element  50  can only be transitioned to the expanded, deployed state when the catheter is coupled to controller  33  and the processor has signaled drive mechanism  36  to expand the flow limiting element. 
     Referring now to  FIG. 7 , catheter  31  preferably includes at least three lumens  60 ,  61 ,  62 . Lumen  60  may be used as an inflation lumen and/or for carrying actuation wire  54  that extends between flow limiting element  32 / 50  and the drive mechanism  36  of controller  33 . Lumen  61  permits optional sensors  42 ,  43  or electrodes to communicate with data transfer circuit  38 , and optional lumen  62  for delivering a pharmacological agent (e.g., a drug) to the heart. 
     In operation, catheter  31  with flow limiting element  32 / 50  is inserted into the patient&#39;s subclavian vein and guided to the SVC of the patient, e.g., to a position proximal of the entrance to the right atrium (see  FIG. 1A ). Techniques known in the art can be used to insert and fix flow limiting element  32 / 50  at the desired venous location in the patient. Proper localization of the device may be confirmed using, for example, vascular ultrasound. Alternatively, flow limiting element  32 / 50  may be inserted through the jugular vein or even a peripheral vein and guided to the SVC under fluoroscopic or ultrasound guidance. 
     Once catheter  31  and flow limiting element  32 / 50  are positioned at the desired locations, controller  33  initiates a process in which the occlusion element is expanded and contracted such that blood flow in the SVC is intermittently occludes and resumed. The extent to which the flow limiting element impedes blood flow can be regulated by adjusting the degree to which the flow limiting element expands radially, and also for time interval for the occlusion, e.g., over how many heart beats. For example, in some embodiments the flow limiting element may impede blood flow in the SVC by anywhere from at least 50% up to 100%. Impedance of blood flow may be confirmed using methods known in the art, e.g., by measuring reductions in pressure, reductions in pressure fluctuations, or visually using ultrasound. 
     In accordance with one aspect of the disclosure, controller  33  includes software stored in memory  41  that controls the timing and duration of the successive expansions and contractions of flow limiting element  32 / 50 . As described above, the programmed routines run by processor  37  may use as an input the patient&#39;s cardiac cycle. For example, in some embodiments, the software may be configured to actuate flow limiting element  32 / 50  to maintain partial or complete occlusion of the SVC over multiple cardiac cycles, for example, four or more successive heart beats in the subject. Controller  33  may accept as input via data transfer circuit  38  an output of electrodes  44  representative of the patient&#39;s electrocardiogram (ECG), or alternatively may receive such an input wirelessly from a third-party heart rate application running on the patient&#39;s smartphone, such that the software running on processor  37  can adjust the interval and/or degree of the occlusion provided by system  30  responsive to the patient&#39;s heart rate. Thus, for example, if the patient is physically active, the timing or degree of occlusion caused by the flow limiting element may be reduced to permit faster replenishment of oxygenated blood to the patient&#39;s upper extremities. Conversely, if the heart rate indicates that the patient is inactive, the degree of occlusion of the SVC may be increased to reduce the resting workload on the heart. Alternatively, or in addition, system  30  may accept an input via data transfer circuit  38  a value, measured by optional sensors  42  and  43 , or a third party application and device, such as a blood pressure cuff, representative of the patient&#39;s blood pressure, such that controller  33  regulates flow through the SVC responsive to the patient&#39;s blood pressure. 
     Controller  33  may be programmed to cause the flow limiting element to expand when a sensed parameter is outside a predetermined range and/or above or below a predetermined threshold. For example, controller  33  may cause the flow limiting element to expand when right atrium (“RA”) pressure is sensed by optional sensors  42  and/or  43  to be within a predetermined range, e.g., 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg, 20 to 25 mmHg, or above a predetermined threshold, e.g., 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. As another example, controller  33  may cause the flow limiting element to expand when the mean pulmonary artery (“PA”) pressure is sensed by optional sensors  42  and/or  43  to be within a predetermined range, e.g., 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg, 20 to 25 mmHg, or above a predetermined threshold e.g., 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. The predetermined range and/or the predetermined threshold may be patient specific and controller  33  may be programmed and reprogrammed for individual patients. 
     Referring now to  FIGS. 8-10 , alternative forms of intravenous flow limiting elements suitable for use to occlude the SVC are described. As will be apparent to one skilled in the art, while  FIGS. 4-6  depict a cylindrical flow limiting element, other shapes may be used. In addition, while not illustrated with anchoring members in  FIGS. 8-10 , anchoring members may be included. In each pair of drawings,  8 A,  8 B,  9 A,  9 B and  10 A,  10 B, the pair-wise drawings depict that each flow limiting element has a collapsed contracted state ( FIGS. 8A, 9A and 10A ), where the flow limiting element does not significantly impede blood flow, and an expanded deployed state ( FIGS. 8B, 9B and 10B ), in which the flow limiting element partially of fully occludes blood flow through the SVC. 
     In particular, referring to  FIGS. 8A and 8B , catheter  70  includes balloon  71  attached to distal end  72 . Balloon  71  is illustrated as having a rounded ball shape. 
     Referring now to  FIGS. 9A and 9B , catheter  80  includes flow limiting element  81  comprising spring-loaded plug  82  formed of a biocompatible material (e.g., beryllium) and having a tapered conical shape. Spring-loaded plug  82  is captured in its collapsed contracted state within sheath  83  disposed at distal end  84  of catheter  80 . More particularly, a vertex of conically-shaped plug  82  is positioned adjacent the proximal end  85  of sheath  83 . During delivery of catheter  80 , spring-loaded plug  82  is captured within sheath  83  in its low-profile state to allow blood flow in the SVC. To expand spring-loaded plug  82 , force is applied via actuation wire  86  to withdraw plug  82  from sheath  83 . As for the previous embodiments, plug  82  is biased to return within sheath  83  when the proximal force is removed from the proximal end of actuation wire  86 , so that the flow limiting element  81  remains in its collapsed contracted state if disconnected from controller  33 . 
     Referring to  FIGS. 10A and 10B , catheter  90  depicts a further alternative embodiment of occlusive device  91 , which takes the form of spring-loaded plug  92 . Spring-loaded plug  92  is similar to plug  82  of  FIGS. 9A and 9B , and has a tapered conical shape and is loaded within sheath  93  disposed at distal end of catheter  90 . In response to a distally-directed force applied by drive mechanism  36  to the proximal end of catheter  90 , spring-loaded plug  92  is pushed out of distal end of sheath  94  and expands to occlude the SVC. When the distally-directed force is removed, spring-loaded plug  92  retracts to its collapsed contracted state within sheath  94 , thereby permitting blood to flow substantially unimpeded through the SVC. 
     Applicants have observed that animal testing indicates that a system constructed and operated in accordance with the methods of the present SVC occlusion system provides significant benefits over previously-known IVC systems for treating heart failure. Preliminary animal testing conducted on swine models one week post myocardial infarction is described below. 
     Referring to  FIG. 11 , changes in the LV pressure and LV volume are shown for a number of successive heart beats in a swine model following full occlusion of the inferior vena cava (IVC), as suggested in the foregoing published Cedeno patent application. In particular, the IVC was fully occluded for approximately 30 seconds during which the both left ventricular end diastolic pressure (corresponding to lower right-hand corner of the hysteresis loop) and left ventricular systolic pressure (corresponding to upper left-hand corner of the hysteresis loop) decreased during each successive heartbeat. LV pressure rapidly increased to pre-occlusion levels once the IVC occlusion was removed (i.e., similar to first half of the pressure and volume trace). Because IVC occlusion therapy proposed by Cedeno reduces systolic pressure, the therapy can lead to reduced ejection fraction during systole, with potentially dangerous consequences to the patient. In addition, occlusion of the IVC may result in congestion of the renal and hepatic veins, which could give rise to and exacerbate, rather than ameliorate, complications often associated with congestive heart failure. 
     Referring to  FIG. 12 , changes in the LV pressure and LV volume are shown for a number of successive heart beats in a swine model following partial occlusion of the superior vena cava (SVC), as described in accordance with the principles of the present invention. In particular, the SVC was partially occluded for approximately 30 seconds during which the left ventricular end diastolic pressure (corresponding to lower right-hand corner of the hysteresis loop) decreased while the left ventricular systolic pressure (corresponding to upper left-hand corner of the hysteresis loop) remained substantially unchanged during each successive heartbeat. LV pressure rapidly increased to pre-occlusion levels once the SVC occlusion was removed (i.e., similar to first half of the pressure and volume trace). Advantageously, the method of the present invention of partially occluding the SVC appears to have little or no impact on ejection fraction during systole, but reduces wall stress in the ventricles during diastole. Moreover, as discussed in more detail below, occlusion of the SVC will be tolerated well by the patient, will not contribute to congestion of the renal or hepatic veins, and will not exacerbate complications often associated with congestive heart failure including liver and kidney failure. 
       FIGS. 13-14  are graphs showing the changes in pressure as a function of left and right ventricular volume, respectively, during occlusion of the superior vena cava (SVC) and release in a swine treated for heart failure in accordance with the principles of the present invention. As shown in the graphs, SVC occlusion led to a significant reduction in left ventricular (LV) volume (240 to 220 mL) and a reduction in LV diastolic pressure (25 to 10 mmHg). SVC occlusion also was associated with reduction in LV systolic pressure (94 to 90 mmHg). SVC occlusion also decreased right ventricular (RV) volume (230 to 210 mL), diastolic pressure (12 to 4 mmHg), and RV systolic pressure (27 to 16 mmHg). Advantageously, SVC occlusion in accordance with the systems and methods described herein reduces biventricular volume and diastolic (filling) pressures without negatively impacting systemic blood pressure (LV systolic pressure). These findings suggest that SVC occlusion has a potentially important beneficial effect on biventricular interaction such that reducing diastolic filling pressures in both ventricles allows for increased ventricular compliance, thereby improving ventricular filling and resulting in increased stroke volume and cardiac output, which is the primary objective when treating a patient with heart failure. 
       FIG. 15  includes graphs showing that superior vena cava (SVC) occlusion in accordance with the principles of the present invention on a swine subject improves cardiac function. The graphs each show the results for partial inferior vena cava (IVC) occlusion (left side of each graph) versus full SVC occlusion (right side of each graph). The graphs show measured left ventricle (LV) stroke volume, cardiac output, LV contractility, LV diastolic pressure, LV systolic pressure, and end-systolic volume. 
       FIG. 16  is graph showing that SVC occlusion in accordance with the principles of the present invention on three swine subjects does not harm systolic blood pressure. The graph shows the full caval occlusion (1 minute) LV end systolic pressure (mmHg) for full IVC occlusion (left side of each study) versus full SVC occlusion (right column of each study). Less reduction in LV-end-systolic pressure with SVC occlusion compared to IVC occlusion. 
       FIG. 17  is graph showing that SVC occlusion in accordance with the principles of the present invention on three swine subjects does not harm LV diastolic filling. The graph shows the full caval occlusion (1 minute) LV end diastolic pressure (mmHg) for full IVC occlusion (left side of each study) versus full SVC occlusion (right side of each study). Less reduction in LV-end-diastolic pressure with SVC occlusion compared to IVC occlusion. 
       FIG. 18  is graph showing that SVC occlusion in accordance with the principles of the present invention on three swine subjects improves LV stroke volume. The graph shows the full caval occlusion (1 minute) LV stroke volume (mL/beat) for full IVC occlusion (left side of each study) versus full SVC occlusion (right side of each study). Increased LV stroke volume with SVC occlusion compared to reduced LV stroke volume IVC occlusion. 
       FIG. 19  is graph showing that SVC occlusion in accordance with the principles of the present invention on three swine subjects improves LV contractility. The graph shows the full caval occlusion (1 minute) LV contractility (mmHg/sec) for full IVC occlusion (left side of each study) versus full SVC occlusion (right side of each study). Increased LV contractility with SVC occlusion compared to reduced LV contractility with IVC occlusion. 
       FIG. 20  is four graphs depicting LV total volume and LV pressure for IVC occlusion (upper left), RV total volume and RV pressure for IVC occlusion (upper right), LV total volume and LV pressure for SVC occlusion (lower left), and RV total volume and RV pressure for SVC occlusion (lower right).  FIG. 20  illustrates that SVC occlusion provides a significant reduction in LV and RV diastolic pressures without a major reduction in LV systolic pressure as compared to IVC occlusion. 
       FIG. 21  includes two graphs depicting measured pulmonary artery pressure and renal vein pressure in a swine subject for IVC occlusion (left graph) and SVC occlusion (right graph). Line  100  shows the measured pulmonary artery pressure while line  102  shows the measured renal vein pressure for IVC occlusion. Line  104  shows the measured pulmonary artery pressure while line  106  shows the measured renal vein pressure for SVC occlusion. The max renal vein pressure is measured to be 22 mmHg for IVC occlusion whereas the max renal vein pressure is measured to be 7 mmHg for SVC occlusion.  FIG. 21  demonstrates that SVC occlusion reduces pulmonary artery pressures without increasing renal vein pressure as compared to IVC occlusion. 
       FIG. 22  is a graph depicting measured left subclavian vein pressure and renal vein pressure in a swine subjected to SVC occlusion in accordance with the principles of the present invention. Line  108  shows the measured left subclavian vein pressure while line  110  shows the measured renal vein pressure for SVC occlusion. The measured change in left subclavian vein pressure is 5 to 12 mmHg during SVC occlusion.  FIG. 22  demonstrates that proximal left subclavian vein pressure increases nominally during SVC occlusion. 
     Results of additional animal testing conducted on swine models over various occlusion periods are shown in  FIGS. 23A-26C . Referring now to  FIGS. 23A to 23D , clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume and ventricular stroke work, respectively, during the deflation time of a one-minute episode of continuous SVC occlusion in a pig model are depicted. Specifically, the controller was programmed to cause the flow limiting element to at least partially occlude the SVC for one minute, and then contract, e.g., deflate, for one second. As shown in  FIGS. 23A to 23D , one-minute SVC occlusion may not be sufficient to result in a steady-state reduction in ventricular volumes after the deflation time. 
     Referring now to  FIGS. 24A to 24D , clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume and ventricular stroke work, respectively, during the deflation time of a five minute episode of continuous SVC occlusion in a pig model are depicted. Specifically, the controller was programmed to cause the flow limiting element to at least partially occlude the SVC for five minutes, and then contract, e.g., deflate, for one second. As shown in  FIGS. 24A to 24D , ventricular volumes reached a clear steady-state reduction after the deflation time as a result of five-minute SVC occlusion. 
     Referring now to  FIGS. 25A to 25D , clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume and ventricular stroke work, respectively, during the deflation time of a ten minute episode of continuous SVC occlusion in a pig model are depicted. Specifically, the controller was programmed to cause the flow limiting element to at least partially occlude the SVC for ten minutes, and then contract, e.g., deflate, for one second. By a comparison of  FIGS. 25A to 25D  with  FIGS. 24A to 24D , the advantage of ten-minute SVC occlusion over five-minute SVC occlusion is not significant in this model. Accordingly, in consideration of patient safety, five-minute SVC occlusion was used during initial clinical studies such as the Tufts IRB-approved protocol described below with reference to  FIGS. 26A to 26C , though ten-minute occlusion in a human subject is described in more detail below with respect to  FIGS. 28A-B . 
     Encouraged by animal testing, Applicants conducted preliminary human testing and observed that a system constructed and operated in accordance with the methods of the present SVC occlusion system provides significant benefits.  FIGS. 26A to 26C  depict clinical pressure changes observed during a five-minute episode of continuous SVC occlusion for three human patients enrolled in a Tufts IRB-approved protocol. Specifically, the three patients underwent five minutes of continuous SVC occlusion with acute neuro and cardiac monitoring and thirty-day neuro assessment (Table 1). 
     
       
         
           
               
               
             
               
                   
                 TABLE 1 
               
             
            
               
                   
                   
               
               
                   
                 Baseline Parameters 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Baseline Parameters 
                 Patient # 1 
                 Patient # 2 
                 Patient # 3 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Mean Right Atrial 
                 30 
                 21 
                 18 
               
               
                   
                 Pressure 
               
               
                   
                 Mean Pulmonary 
                 52 
                 44 
                 28 
               
               
                   
                 Artery Pressure 
               
               
                   
                 Pulmonary Capillary 
                 50 
                 20 
                 23 
               
               
                   
                 Wedge Pressure 
               
               
                   
                 PCPW − RAP 
                 20 
                 −1 
                 5 
               
               
                   
                 Pressure Difference 
               
               
                   
                 LV Ejection Fraction 
                 10-15% 
                 35% 
                 25% 
               
               
                   
                 Systolic Pressure 
                 130 
                 128 
                 135 
               
               
                   
                 Diastolic Pressure 
                 97 
                 72 
                 84 
               
               
                   
                 Mean Arterial 
                 108 
                 90 
                 100 
               
               
                   
                 Pressure 
               
               
                   
                 Cardiac Output 
                 2.6 
                 4.4 
                 3.9 
               
               
                   
                 Heart Rate 
                 73 
                 83 
                 60 
               
               
                   
                 NYHA Class 
                 4 
                 4 
                 2 
               
               
                   
                 Overload Status 
                 severe 
                 severe 
                 moderate 
               
               
                   
                   
               
            
           
         
       
     
     As may be observed from  FIGS. 26A to 26C  and in Table 1, pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, and right atrial pressure changed significantly during the five minute episode of SVC occlusion, and had residual effect after release of the balloon. As a result of the study, all patients benefitted hemodynamically as there was a drop in all filling pressures, e.g., capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure. It was observed that the more congested patients experienced an increase in mean arterial pressure (MAP). The net effect of these hemodynamic changes is a reduction in cardio-pulmonary pressures and an increase in systemic pressures perfusing vital organs including the kidneys. 
     Encouraged by the foregoing preliminary swine and human results, Applicants performed additional testing on the three patients that were the subject of the testing discussed above with respect to  FIGS. 26A-26C  in addition to two new patients. The five human patients, each with heart failure, were subjected to the SVC occlusion system described above. Specifically, 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&#39;s New York Heart Association (NYHA) functional classification of 2 was the lowest. The results of the third patient suggest that application of the SVC occlusion system may preferably be used in patients with a NYHA functional classification of heart failure at level  3  and above. 
     
       
         
           
               
               
             
               
                   
                 TABLE 2 
               
             
            
               
                   
                   
               
               
                   
                 Baseline Parameters 
               
            
           
           
               
               
               
               
               
               
            
               
                 Baseline Parameters 
                 Pt #1 
                 Pt #2 
                 Pt #3 
                 Pt#4 
                 Pt#5 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Mean Right Atrial 
                 30 
                 21 
                 18 
                 12 
                   
               
               
                 Pressure 
               
               
                 Mean Pulmonary 
                 52 
                 44 
                 28 
                 52 
                 35 
               
               
                 Artery Pressure 
               
               
                 Pulmonary Capillary 
                 50 
                 20 
                 23 
                 29 
                 29 
               
               
                 Wedge Pressure 
               
               
                 PCWP − RAP 
                 20 
                 −1 
                  5 
                 17 
                 7 
               
               
                 Pressure Differential 
               
               
                 LV Ejection Fraction 
                 10-15% 
                 35% 
                     25% 
                 20-25% 
                 20% 
               
               
                 Systolic Pressure 
                 130 
                 128 
                 135  
                 124 
                 164 
               
               
                 Diastolic Pressure 
                 97 
                 72 
                 84 
                 79 
                 111 
               
               
                 Mean Arterial 
                 108 
                 90 
                 100  
                 94 
                 128 
               
               
                 Pressure 
               
               
                 Cardiac Output 
                 2.6 
                 4.4 
                   3.9 
                 4.2 
                 6.4 
               
               
                 Heart Rate 
                 73 
                 83 
                 60 
                 92 
                 89 
               
               
                 NYHA Class 
                 4 
                 4 
                   2 * 
                 3 
                 3 
               
               
                 Overload status 
                 severe 
                 severe 
                 moderate 
                 not 
                 not 
               
               
                   
                   
                   
                   
                 known 
                 known 
               
               
                   
               
            
           
         
       
     
       FIGS. 27A-27E  illustrates 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 a baseline measurement for each of the five patients during and after occlusion. In  FIGS. 27A-27D , the change in systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), and mean pulmonary artery (MPA) pressure is shown every minute during the five minutes of occlusion. In  FIG. 27E , the change in pulmonary capillary wedge pressure (PCWP) is shown at five minutes of occlusion and after occlusion. 
     The change in systolic pressure is illustrated in  FIG. 27A . As is shown in  FIG. 27A , the first, second and fifth patients generally experienced an increase in SP during occlusion, while the third and fourth patients generally experienced a decrease in systolic pressure. The change in diastolic pressure is illustrated in  FIG. 27B . As is shown in  FIG. 27B , the diastolic pressures during SVC occlusion generally increased for patients one, two and five and generally decreased for patients three and four. 
     The change in mean arterial pressure is illustrated in  FIG. 27C . As is shown in  FIG. 27C , the mean arterial pressure generally increased during SVC occlusion for patients one, two and five, and generally decreased for patients three and four. The change in mean pulmonary artery pressure is illustrated in  FIG. 27D . As is shown in  FIG. 27D , the mean pulmonary artery pressure decreased during SVC occlusion for each patient, though it should be noted that the there is no data point for the fourth patient at the fourth minute. The change in pulmonary capillary wedge pressure (PCWP) is illustrated in  FIG. 27E  at five minutes and after release. As is shown in  FIG. 27E , the pulmonary capillary wedge pressure decreased for all patients at five minutes of SVC occlusion, indicating a drop-in filling pressures for each patient during occlusion. 
     As was observed in the study discussed with respect to  FIGS. 26A-26C , the study illustrated in  FIGS. 27A-27E  indicated that all five patients benefitted hemodynamically as there was a drop in filling pressures, e.g., capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure and further, like the study discussed above with respect to  FIGS. 26A-26C , the more congested patients generally experienced an increase in mean arterial pressure (MAP). Also, in many cases, at least some of the patients had residual effects after release of the occluder. 
     Referring now to  FIGS. 28A-28B , similar to the study discussed above with respect to  FIGS. 25A-25D , Applicants also studied the effect of prolonged SVC occlusion on a human subject. Specifically, the controller was programmed to cause the SVC flow limiting element to at least partially occlude the SVC for ten minutes. Prior to the ten-minute occlusion, the SVC was occluded for a period of five minutes and then permitted to rest for a period of five minutes. The change in mean pulmonary artery pressure, and the change in mean arterial artery pressure, from a baseline measurement before occlusion (i.e., after five minutes of rest), was measured at each minute from 1-10 minutes of occlusion, and after release. As is shown in  FIGS. 28A-B , the effects observed during five minutes of occlusion persisted throughout the ten-minute occlusion period without any attrition of the ‘cardio-pulmonary unloading’ effect. 
       FIG. 28A  illustrates the change in mean pulmonary artery pressure. As is shown in  FIG. 28A , the mean pulmonary artery pressure decreased throughout the entirety of the occlusion and even reached its lowest level during the final two minutes of occlusion.  FIG. 28B  illustrates the change in mean arterial pressure change during occlusion. As is shown in  FIG. 28B , the mean arterial pressure generally decreased during occlusion though it fluctuated, rising above the baseline measurement at the first minute and then again at the fourth and fifth minutes. 
     Referring now to  FIG. 29 , Applicants also performed more extensive testing involving use of the system and methods of the present invention over successive periods of occlusion resulting in arresting or reversing further myocardial remodeling and degeneration. Specifically, adult male swine were subjected to a heart attack by occluding the left anterior descending artery (LAD) for 120 minutes, followed by a re-opening of the blocked artery. Repetitive cycles of SVC occlusion were then performed, occluding the SVC for 5 minutes and deflating the occlusion device for 30 minutes. The repetitive cycles were repeated and performed for 18 hours. After each cycle of SVC occlusion, cardiac output was measured.  FIG. 29  illustrates the results of the repetitive cycles of SVC occlusion. 
     As is shown in  FIG. 29 , cardiac output was at its lowest point post-LAD infarct but before SVC occlusion treatment. After one hour of treatment, cardiac output had returned to baseline levels. Cardiac output continued to gradually increase from one hour of treatment to eighteen hours of treatment, reaching a maximum cardiac output at eighteen hours. These findings suggest for the first time that after acute heart injury, mechanically reducing cardiac pressure and volume (i.e., unloading) by intermittently occluding the SVC and thereafter ceasing occlusion (i.e., recovery) may condition the heart muscle, allowing for periods of exercise and rest. In this manner, the repetitive cycles are akin to interval-training high-intensity workouts (e.g., sprinting) followed by rest. The repetitive cycles strengthen the heart and improve cardiac output and function. While the ratio of occlusion-to-rest was 10:1 (5 minutes on, 30 seconds off), it is understood that other ratios would produce beneficial results. For example, a ratio range of 5-20 minutes of occlusion to 10-100 seconds of rest may be beneficial. It is further understood that occluding the SVC for up to 95% of an hour may be beneficial. Accordingly, the SVC occlusion system described herein may alternatively or additionally be used post-infarction to treat injuries to the heart from the infarction to enhance recovery through myocardial unloading. 
     As referenced above, the SVC occlusion system described herein may alternatively or additionally be used to treat pulmonary hypertension as occlusion of the SVC may result in reduced pressure in the pulmonary arteries. While heart failure is a common cause of pulmonary hypertension, pulmonary hypertension may be caused by primary lung disease. It is understood that the SVC occlusion system may be used to treat pulmonary hypertension, whether or not the cause of pulmonary hypertension is heart failure. 
     Referring now to  FIG. 30 , Applicants have observed that implantation of the SVC occlusion system in five patients with pulmonary hypertension due to heart failure results in significant reduction in the pulmonary artery systolic pressure (PASP). The patients were subject to five minutes of SVC occlusion, mechanically reducing cardiac pressure and volume (i.e., unloading). As is shown in  FIG. 30 , SVC occlusion significantly reduced the PASP below the level of moderate pulmonary hypertension, defined as elevated PASP above 50 mmHg. Accordingly, the SVC occlusion system described herein may implanted to treat pulmonary hypertension. As discussed above with respect to  FIG. 26B  as well as  FIG. 27D , Applicants also observed that implantation of the SVC occlusion system resulted in a decrease in the mean pulmonary artery pressure for each patient. 
     The benefits observed in the foregoing animal and human testing suggests that successive SVC occlusion could be used to treat any heart injury including, but not limited to, acute heart injury due to a heart attack, myocarditis, valvular insufficiency, volume overload or congestive heart failure, and many other acute or chronic heart injury. In one example, the SVC occlusion system described herein may be used acutely, e.g., in an acute-care setting, to arrest or reverse the systems of heart failure, thereby shifting the Frank-Starling curve illustrated in FIG.  2 A, toward line  7  representing a healthy patient. In this manner, the patient will see immediate improvement in increased cardiac performance, with further continuous improvement in myocardial function throughout the course of treatment. To prolong the effects of the system, the SVC occlusion system may be implanted within the patient for long term use. As 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 over a much longer period as compared to acute care. 
       FIG. 31  is a prophetic example of how SVC occlusion in accordance with the principles of the present invention is expected to change over the course of the disease. For example, primary benefits include better patient hemodynamics, faster recovery, and decreased length of stay (LOS) of patients in the hospital. Over time, SVC occlusion may significantly slow disease progression. 
     Referring now to  FIG. 32  an alternative flow limiting element is illustrated. One undesired effect of occlusion of the SVC is increased venous blood pressure upstream of the occlusion device. It is well known that high cephalic venous pressure may lead to various unwanted effects. To reduce this risk of excessive pressure buildup upstream of the flow limiting element, a relief valve may be integrated into a flow limiting element, as illustrated in  FIG. 33 , to permit fluid flow from the SVC to the right atrium. The relief valve may be unidirectional, permitting blood flow only in the direction of the right atrium. The relief valve is preferably configured to open at a pressure in the SVC between 30-60 mmHg. However, it is understood that the relief valve may be designed and configured to open at other pressures in the SVC. 
     The flow limiting element illustrated in  FIG. 32  may be used with a system similar to the system illustrated in  FIGS. 4A-4B . As is shown in  FIG. 32 , the flow limiting element may be cylindrical flow limiting element  112 . Cylindrical flow limiting element  112  may include cylindrical balloon  113  which may be inflated and deflated by delivering fluid to cylindrical balloon  113  from a catheter. Flow limiting element  112  may be sized and configured to fit within the SVC and may conform to the contours of the inner wall of the SVC. Flow limiting element  112  may be delivered to the SVC on a catheter. Cylindrical balloon  113  may be introduced to the SVC in a deflated configuration. Upon arriving at the SVC, cylindrical balloon  113  may be inflated to obstruct or limit blood flow in the SVC. 
     Cylindrical balloon  113  may define internal lumen  114  when cylindrical balloon  113  is inflated. When relief valve  115  is open and cylindrical balloon  113  is inflated, blood may pass through cylindrical balloon  113 . Internal lumen  114  may extend from one end of cylindrical balloon  113  to the other. While internal lumen  114  may have a consistent cylindrical shape throughout, it is understood that the size and shape of both cylindrical balloon  113  and internal lumen  114  may vary. Additionally, internal lumen  114  need not be aligned with the center of the balloon and may even adopt a non-cylindrical shape. 
     Referring now to  FIG. 33 , a cutaway view of cylindrical flow limiting element  112  is shown. As is shown in  FIG. 33 , relief valve  115  may be coupled to the internal wall of cylindrical balloon  113  within central lumen  114 . Relief valve  115  may include a single flow obstructing element or a plurality of flow obstructing elements (e.g., a plurality of flexible leaflets) that work in concert to obstruct blood flow through central lumen  114 . Relief valve  115  may be coupled to the center of cylindrical flow limiting element  112  or alternatively may be positioned closer to or at an upstream or downstream end of cylindrical flow limiting element  112 . For example, relief valve  115  may be positioned at an upstream end of cylindrical flow limiting element  112  furthest from the right atrium of the patient. This configuration may avoid pooling of blood or a standing column of blood within central lumen  114  which may occur where relief valve  115  is positioned in a central or downstream region of central lumen  114 . 
     Relief valve  115 , illustrated in  FIG. 33  in a closed position, may be designed to open at a certain pressure. For example, relief valve  115  may be designed to open at a pressure between 30-40 mmHg. However, it is understood that other pressures may also be desirable. Below the pressure at which relief valve  15  is designed to open, relief valve  115  may obstruct fluid flow through central lumen  114 . Above the pressure at which relief valve  115  is designed to open, relief valve  115  may permit the passage of blood through internal lumen  114 , thereby reducing cephalic venous pressure. 
     Relief valve  115  may be constructed of 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 materials and design (i.e., elasticity, rigidity, thickness) of the valve, and/or may be dictated by mechanical, electrical, and/or magnetic features. The threshold for which the valve permits fluid to flow may be predetermined by valve design and/or may be mechanically adjustable. 
     Referring now to  FIGS. 34A and 34B , two different relief valve designs are shown within internal lumen  114  of cylindrical flow limiting element  112 . Binary relief valve  116 , shown in  FIG. 34A , maintains a substantially closed position until rapidly transitioning to a substantially open position when a given force is applied. The force at which relief valve  116  transitions from a closed to an open position is preferably between 30-60 mmHg though it is understood that this pressure could be any pressure. To achieve the binary (i.e., on/off) functionality, binary relief valve may include a cutout section designed to give-way in response to a given force. Upon opening and permitting fluid to pass, thereby releasing pressure, elasticity in the material or other mechanical features may cause binary relief valve  116  to spring back into a closed position. It is understood that this binary functionality may be achieved using a variety of other designs and/or by incorporating other materials. For example, relief valve  132  in  FIG. 38A-B  may also achieve the binary functionality. 
     Gradual relief valve  117 , as shown in  FIG. 34B , is designed to open gradually with increasing pressure. This functionality may be achieved, for example, with valve leaflets that have a constant thickness or a progressively thinner cross-section as the leaflets move from the internal wall of cylindrical balloon  113  towards the center of internal lumen  114 . However it is understood that any valve design that gradually permits increased fluid flow in response to increased pressure may be used as a gradual relief valve. 
     Referring now to  FIG. 35 , a top view of cylindrical flow limiting element  112  is shown. Relief valve  115 , shown here in a closed position, prevents flow through the internal lumen of cylindrical balloon  113  as long as pressure remains below a certain threshold. Although a relief valve design having four flexible leaflets or flaps is depicted, any relief valve design that may be coupled within internal lumen  114  of cylindrical balloon  113  may be used including valves with fewer/more leaflets. 
     Referring now to  FIGS. 36A and 36B , a top view of cylindrical flow limiting element  112  is shown.  FIG. 36A  illustrates binary relief valve  116 , also shown in  FIG. 34A , in its open position.  FIG. 36B  illustrates gradual relief valve  117 , also shown in  FIG. 34B , in a partially open position. As discussed above, binary relief valve  116  is designed to open to a substantially open position upon reaching its set pressure. On the other hand, gradual relief valve  117  is designed to open gradually as pressure increases above a certain threshold. 
     Referring now to  FIGS. 37A and 37B , it may be desirable to place a stent  118  around cylindrical balloon  113 . Stent  118  may, for example, serve as both a receiver and emitter of electrical signals. Such uses include, but are not limited to, serving as an ECG lead, emitting signals related to autonomic activity, and receiving neuromodulation signals. Stent  118  may be self-expanding and may be made of an electrically conductive material. Stent  118  may be integrated into to cylindrical flow limiting element  112  and/or may be removably coupled to cylindrical flow limiting element  112 . 
     Referring now to  FIGS. 38A and 38B , cylindrical flow limiting element  130  is illustrated. As is shown in these figures, cylindrical flow limiting element  130  includes balloon occluder  131  and relief valve  132  which are both integrated into stent  118 . Relief valve  132  and balloon occluder  131  are located adjacent to each other within stent  118 .  FIG. 38A  depicts the cylindrical flow limiting element  130  in its inflated position, occluding flow within the SVC.  FIG. 38B  depicts the occlusion device in its deflated position, permitting flow through the SVC. As is illustrated in  FIG. 38B , balloon occluder  131  may be coupled to relief valve  132  and when deflated may contract toward relief valve  132 . Relief valve  132  may be hinged to stent  118  and may open to permit blood flow when a certain pressure is achieved within the SVC. Relief valve  132  may be constructed using any of the techniques, designs, and materials disclosed above with respect to relief valves. 
     Referring now to  FIGS. 39A and 39B , cylindrical flow limiting element  133  is illustrated. As is shown in these figures, cylindrical flow limiting element  133  includes cylindrical balloon occluder  134  and relief valve  135  which are both integrated into stent  118 . Cylindrical balloon occluder  134  may be inflated to conform to the shape of stent  118 . As is shown in  FIG. 39B , cylindrical balloon occluder  134  may have an outer surface that is coupled to stent  118  along a portion of the outer surface. Relief valve  135  may be coupled to cylindrical balloon occluder  134 . Cylindrical balloon occluder  134  may define internal lumen  136  when inflated through which blood may pass if relief valve  135  is open. 
       FIG. 39A  depicts cylindrical flow limiting element  133  with cylindrical balloon occluder  134  in an inflated configuration. When inflated, cylindrical balloon occluder  134  limits flow within the SVC. With cylindrical balloon occluder  134  inflated, relief valve  135  may open as required to relieve any overpressure in the SVC.  FIG. 39B  depicts cylindrical flow limiting element  133  in a deflated configuration. When deflated, cylindrical flow limiting element  133  permits flow through the SVC. In the deflated configuration, cylindrical balloon occluder  134  reduces in size and moves toward the portion of the stent wall that cylindrical balloon occluder  134  is coupled to. Similarly, relief valve  135  moves toward stent  118  when cylindrical flow limiting element  133  is in a deflated configuration. Cylindrical balloon occluder  134  having a reduced size when deflated, permits blood to flow through stent  118 , around deflated balloon occluder  134 . 
     Referring now to  FIGS. 40A and 40B , cylindrical flow limiting element  137  is illustrated. Cylindrical flow limiting element  137  includes stent  118  and relief valve  138 . Unlike the occlusion devices illustrated in  FIGS. 32-39 , cylindrical flow limiting element  137  does not include a balloon. Instead, relief valve  138  may be coupled directly to stent  118  as is shown in  FIG. 40B . Stent  118  may be an expandable stent and may be anchored to the inner wall of the SVC. Relief valve  138  may take the form and have characteristics similar to any of the relief valves discussed above with respect to  FIGS. 32-39 . Cylindrical flow limiting element  137  may entirely eliminate flow in the SVC until a certain threshold pressure his achieved in the SVC, at which point relief valve  138  may open to permit flow from the SVC to the right atrium. 
     Referring now to  FIG. 41 , cylindrical flow limiting element  112  of  FIG. 32  is illustrated coupled to filter  126 . Filter  126  may be placed downstream of cylindrical flow limiting element  112 . When relief valve  115  is closed, blood may pool in central lumen  114  of cylindrical balloon  113  resulting in a stagnant blood column, leading to thrombosis. When relief valve  115  is opened, thrombus may be released into the right atrium, which may cause severe problems and even death. Filter  126 , may be supported either directly by a catheter or by a structural feature of cylindrical flow limiting element  112  such as cylindrical balloon  113 , relief valve  115 , or stent  118  if applicable, and may serve to catch thrombus. For example, filter  126  may be coupled to cylindrical balloon  113  at the downstream end of cylindrical flow limiting element  112 , as is shown in  FIG. 41 . It is understood that filter  126  may be integrated into any of the flow limiting elements described herein. 
     To determine whether the SVC is fully occluded or to what degree the SVC is occluded, traditional methods involving injecting contrast agent into the patient and observing movement of the contrast agent under fluoroscopy may be employed. Alternatively, pressure sensors may be positioned relative to the occlusion balloon as discussed herein, and pressure waveforms may be analyzed to determine whether the SVC is occluded. For example, CardioMEMS™ HF System pressure sensors are available from Abbott, St. Paul, Minn. The pressure sensors may communicate wirelessly with, e.g., the implanted controller. Pressure waveforms may also be analyzed to determine a patient&#39;s filling pressures, diastolic conditions and/or other cardiac conditions or indications. For example, waveforms may be analyzed to detect a prominent ‘C-V’ wave indicative of tricuspid regurgitation due to volume overload. In another example, waveforms may detect an ‘A’ wave suggestive of complete heart block, Ventricular Tachycardia (VT), or pulmonary hypertension. The systems described herein may be used as a diagnostic monitoring tool by analyzing waveforms and may respond accordingly using the SVC occlusion techniques described herein. 
       FIG. 42A  illustrates pressure sensor  140  which may generate pressure waveforms. Pressure sensor  140  may be incorporated into catheter  31  and may be disposed at a location proximal to the occlusion balloon to provide pressure measurements indicative of the Jugular Vein Pressure (JVP). Pressure sensor  156  optionally may be incorporated into catheter  31  distal to the occlusion balloon. A user of the system illustrated in  FIG. 42A  may monitor the waveform readings from pressure sensor  140  and determine when the wave form changes from phasic to non-phasic. When the occlusion balloon is deflated, the pressure waveform will vary in phase with the heartbeat, as is illustrated in curve  141  of  FIG. 42B . When the occlusion balloon is inflated, the pressure waveform then flatlines. In this manner it may be determined whether the SVC is occluded, without the need to inject contrast and without the patient being in a cathlab or under x-ray. Also, the pressure waveform may be used to determine when to actuate the flow limiting element and when to cease actuation of the flow limiting element. 
     Another alternative to using x-ray/fluoroscopy for determining occlusion of the SVC employs two pressure sensors on opposite sides of the occluding device. For example,  FIG. 4A  discussed above illustrates a system having catheter  31  including flow limiting element  32 , sensor  42  and sensor  43 . As is shown in  FIG. 4A , sensor  42  is positioned distal to flow limiting element  32  and sensor  43  is positioned proximal to flow limiting element  32 . Sensors  42  and  43  may be pressure sensors and, as explained above, may be used to determine the extent of occlusion caused by flow limiting element  32 , for example, by monitoring the pressure differential across flow limiting element  32 . The pressure differential value may be indicative of the amount or degree of occlusion. Also, the pressure differential may be used to determine when to actuate the flow limiting element and when to cease actuation of the flow limiting element. 
     While  FIG. 4A  illustrates one arrangement of sensors, it is understood other arrangements of sensors may be used to obtain relevant information. As shown in  FIG. 43 , an alternative sensor arrangement includes catheter  31 , which may be introduced into the vasculature of the patient via a delivery device, such as introducer sheath  144 . Catheter  31  preferably extends into the SVC, enters the heart through the right atrium, extends into the right ventricle, and enters the pulmonary artery through the pulmonary valve. Sensors  145 ,  146  and  147  may be positioned along catheter  31  so that sensor  145  is positioned within flow limiting element  32  to measure the pressure within flow limiting element  32  (i.e., balloon pressure), sensor  146  is positioned along catheter  31  distal to flow limiting element  32  and within the SVC to measure SVC or right atrium pressure, and sensor  147  is positioned along catheter  31 , distal to sensor  146 , such that sensor  147  is positioned within the pulmonary artery and measures pulmonary artery pressure. To measure the pressure above or proximal to flow limiting element  32 , sensor  148  may be placed directly on or otherwise incorporated into the distal end of sheath  144 , where introducer sheath  144  enters the SVC. The pressure measured by sensor  148  is indicative of the JVP. Catheter  31  may include a plurality of lumens, which are used as inflation lumens, actuation lumens and/or for electrical communication between the controller and flow limiting element  32  and/or sensors  145 ,  146  and  147 . Introducer sheath  144  also may include lumens for electrical communication between sensor  148  and the controller. 
     Referring now to  FIG. 44 , yet another alternative embodiment is described that includes introducer sheath  144 . The embodiment illustrated in  FIG. 44  is similar to that of  FIG. 43  except that flow limiting element  32  and sensor  145  and  146  are also incorporated into introducer sheath  144 . Similar to the device illustrated in  FIG. 43 , sensor  148  may be positioned above or proximal to flow limiting element  32  and may measure pressure above or proximal to flow limiting element  32 , which is indicative of JVP. Sensor  145  is positioned within flow limiting element  32  to measure the pressure within flow limiting element  32  (i.e., balloon pressure). Sensor  146  is positioned near a distal end of introducer sheath  144 , which is distal to flow limiting element  32  and positioned within the SVC to measure SVC or right atrium pressure. Also, similar to the device illustrated in  FIG. 43 , catheter  31  may be introduced via introducer sheath  144  and extend through the right atrium and into the pulmonary artery. Sensor  147  preferably is disposed at a distal end of catheter  31  so that it is positioned within the pulmonary artery and measures pulmonary artery pressure. Introducer sheath  144  may include a plurality of lumens used as inflation lumens, actuation lumens and/or for electrical communication between the controller and flow limiting element  32  and/or sensors  145 ,  146  and  148 . Catheter  31  may also include lumens for electrical communication between sensor  147  and the controller. 
     In the embodiment of  FIG. 44 , flow limiting element  32  may be selectively inflated and deflated independent of the presence of catheter  31 . As flow limiting element  32  and sensors  145 ,  146  and  148  are disposed on introducer sheath  144 , therapeutic treatment involving the inflation and deflation of flow limiting element  32  to selectively occlude the SVC may be achieved without the introduction of catheter  31 . Further, pressure differentials across flow limiting element  32  may be determined using sensors  148  and  146  whether or not catheter  31  is deployed. 
     Referring now to  FIG. 45 , yet another embodiment of the SVC occlusion system constructed in accordance with the principles of the present invention is described. Catheter  31  preferably includes two occlusion balloons, azygos vein occlusion balloon  142  and SVC occlusion balloon  143 . Sensors,  129 ,  139  and  149  may also be disposed on catheter  31  such that sensor  129  is disposed proximal to azygos vein occlusion balloon  142  to measure pressure distal to azygos vein occlusion balloon  142 , sensor  139  is disposed between azygos vein occlusion balloon  142  and SVC occlusion balloon  143  to measure the pressure between azygos vein occlusion balloon  142  and SVC occlusion balloon  143 , and sensor  149  is disposed distal to SVC occlusion balloon  143  to measure the pressure distal to SVC occlusion balloon. Also, sensor  145  is positioned within SVC occlusion balloon  143  to measure the pressure within SVC occlusion balloon  143  (i.e., SVC occlusion balloon pressure) and sensor  155  is positioned within azygos vein occlusion balloon  142  to measure the pressure within azygos vein occlusion balloon  142  (i.e., azygos vein occlusion balloon pressure). Further, pressure differentials across azygos vein occlusion balloon  142  and SVC occlusion balloon  143  may be determined using sensors  129  and  139 , and  139  and  149 , respectively. The pressure differential value may be indicative of the amount or degree of occlusion. 
     Azygos vein  16  drains the posterior part of the thorax into the SVC. When the SVC is blocked, the azygos vein may provide an alternative path to the right atrium, thereby naturally shunting occluded SVC blood flow back to the right atrium. Specifically, if the SVC is occluded below the origin of the azygous vein, pressure built up above the occluded portion of the SVC may cause a percentage of venous blood to move retrograde through the azygous vein into the thorax. Azygos vein occlusion balloon  142  may be positioned in the SVC adjacent the azygos vein such that inflation of azygos vein occlusion balloon  142  restricts or prevents blood flow from entering the azygos vein from the SVC. SVC occlusion balloon  143  may be positioned below the azygos vein, distal to azygos vein occlusion balloon  142 , such that inflation of SVC occlusion balloon  143  occludes the SVC but permits blood flow into the azygos vein. Catheter  31  may include a plurality of lumens used as inflation lumens and/or actuation lumens between the controller and azygos vein occlusion balloon  142  and SVC occlusion balloon  143 . 
     Azygos vein occlusion balloon  142  and SVC occlusion balloon  143  may be selectively and independently be inflated and deflated. For example, Azygos vein occlusion balloon  142  may be deflated while SVC occlusion balloon  143  may be inflated, Azygos vein occlusion balloon  142  may be inflated while SVC occlusion balloon  143  is deflated, or both balloons may be inflated or deflated at the same time. Azygos vein occlusion balloon  142  and SVC occlusion balloon  143  may also be fully or partially inflated depending upon how much flow back to the right atrium is desirable. 
     When SVC occlusion balloon  143  is inflated and the azygos vein occlusion balloon  142  is deflated, the SVC is open above SVC occlusion balloon  143  and blood is permitted to travel through the azygos vein to the right atrium. Should it be desirable to further reduce flow back to the right atrium (further reducing preload), azygos vein occlusion balloon  142  may be inflated, thereby occluding the azygos vein and preventing it from acting as a natural shunt. 
     The systems and methods of the present invention may be used alone, as described in the examples above, or in combination with other devices configured to assist cardiac function. For example, SVC occlusion in accordance with the principles of the present invention may be used in combination with a pump 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., heart, venous, arterial) pump, whether used for full cardiac support or for temporary assistance, thereby allowing for synchronous or asynchronous (venous and arterial) unloading of cardiac preload and afterload, respectively. For example, SVC occlusion in accordance with the principles of the present invention may be used in combination with the Impella® heart pump available from Abiomed®, Danvers, Mass., as described in further detail below with reference to  FIG. 49 .  FIGS. 49 and 51-54  illustrate the SVC occlusion system combined with exemplary RVAD, LVAD, and IABP systems. 
     A system of the present invention also could be coupled to other devices such as biventricular pacemakers and neuromodulatory devices. For example, biventricular pacemakers are designed to resynchronize cardiac function; if SVC occlusion favorably alters RV and LV interaction, then it may render biventricular pacing more efficient. Similarly, SVC occlusion therapy may be used in conjunction with neuromodulatory devices such that the systems have significant combined action in stimulating vagal efferents, thereby enhancing the efficacy of the neuromodulatory device. A further potential application may be in unmasking right ventricular failure after a patient is outfitted with an LVAD. By modulating the amount of venous return to the right ventricle, it may be possible to reduce overload and thereby “condition” the right ventricular myocardium to tolerate enhanced venous return being driven by the LVAD. 
     While flow limiting element  32  is described above as being positioned within the SVC and inflated and deflated within the SVC, therapeutic occlusion of the SVC as described herein alternatively may be achieved using a cuff wrapped around the exterior of the SVC to selectively constrict the SVC. Referring now to  FIG. 46 , cuff  150  is illustrated wrapped around the SVC. As further depicted in  FIGS. 47A-D , cuff  150  may include strap  151 , occlusion element  152  and locking element  153 . Occlusion element  152  may be incorporated into strap  151  such that occlusion element  152  extends outward from both an exterior surface of strap  151  illustrated in  FIG. 47A  and an interior surface of strap  151 , illustrated in  FIG. 47B . The interior side or surface of strap  151  is the side facing the SVC and the exterior side or surface of strap  151  is the side facing away from the SVC. 
     Strap  151  may be generally rectangular in shape. Locking element  153  may be any well-known system for removably affixing one side of strap  151  to another side of strap  151 . For example, strap  151  may have a magnetic locking element for tightly securing cuff  150  to the SVC. Air line  154  may connect to occlusion element  152  on one end and a controller on the other end. Occlusion element preferably has elastic properties such that it inflates when air line  154  delivers air or other fluid to occlusion element  152 . Occlusion element  152  may expand outwardly from the interior side of strap  151  when inflated. 
     Referring again to  FIG. 46 , strap  151  of cuff  150  may be wrapped around the SVC and locked tightly onto the SVC using locking element  153 . Upon locking cuff  150  into place on the SVC, occlusion element  152  may be selectively inflated and thus expanded toward the SVC by delivering fluid through air line  154 . As strap  151  is substantially non-elastic, the inflation of occlusion element  152  will result in expansion of occlusion element  152  and compression of the SVC, thereby restricting flow through the SVC. Accordingly, occlusion of the SVC may be achieved when occlusion element  152  expands and encroaches into the SVC, causing the SVC to collapse inward. Thus, by selectively deflecting and inflating occlusion element  152 , therapeutic occlusion of the SVC described herein may be achieved. 
     Controller  33  is programmed to cause flow limiting element  32  to at least partially occlude the SVC for a first predetermined time interval, and then contract, e.g., deflate, for a second predetermined time interval, e.g., at least one second, less than one minute, or one to thirty seconds. Preferably, the first predetermined time interval is more than a minute, between two and eight minutes, or between four and six minutes. For example, the first predetermined time interval may be five minutes, plus or minus a minute. In addition, the first predetermined time interval is preferably significantly longer than the second predetermined time interval. For example, the first predetermined time interval may 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 contracted time interval is 10 seconds. In some embodiments, controller  33  is programmed to cause flow limiting element  32  to fully occlude the SVC during the first predetermined time intervals. Controller  33  may be programmed to cause flow limiting element  32  to transition from the occlusion state for the first predetermined time interval to the contracted state for the second predetermined time interval for many cycles throughout the course of a treatment. As further described herein, controller  33  may be programmed to cause flow limiting element  32  to adjust the timing of the first predetermined time interval (e.g., to a third predetermined time interval) and/or to adjust timing of the second predetermined time interval (e.g., to a fourth predetermined time interval) automatically (e.g., responsive to parameters sensed by a sensor(s)) and/or responsive to user input. As will be understood by one skilled in the art, further adjustments to the time intervals may be made throughout the course of the treatment. 
     Referring now to  FIG. 48 , an alternative exemplary system  30 ′ of the present invention is described. System  30 ′ is similar to system  30  and includes catheter  31  having flow limiting element  32  disposed on distal portion  34 . System  30 ′ differs from system  30  in that catheter  31  is removably coupled at proximal end  35  to external controller system  200 . For example, catheter  31  may be decoupled from controller  33  and coupled to external controller system  200  during a hospital visit so the clinician may monitor and adjust operation of flow limiting element  32  directly. Catheter  31  may include optional distal flotation balloon  201  disposed on distal portion  34 , distal to flow limiting element  32 . As shown in  FIG. 48 , distal flotation balloon  201  may be positioned within the pulmonary artery of the patient. 
     External controller system  200  includes display  202 , e.g., graphical user interface, electrically coupled to inflation source  203  and external controller  204 . Display  202  communicates with inflation source  203  and external controller  204  to display information, e.g. vital physiologic or system parameters, regarding functioning of system  30 ′ for review or adjustment by the clinician, or an alert generated by external controller  204 . The clinician may review the data displayed on display  202  to address a malfunction or to adjust the system parameters via the graphical user interface. 
     Inflation source  203  includes a drive mechanism, e.g., motor, pump, for actuating flow limiting element  32 . Inflation source  203  further includes a source of inflation medium, e.g., gas or fluid, such that the drive mechanism may transfer the inflation medium between inflation source  203  and flow limiting element  32  via flow limiting element connector  209  responsive to commands from external controller  204 . In addition, catheter  31 , when partially external, provides a fail-safe design, in that flow limiting element  32  only can be inflated to provide occlusion when the proximal end of catheter  31  is coupled to external controller  204 . Such a quick-disconnect coupling at proximal end  35  permits the catheter to be rapidly disconnected from external controller  204  for cleaning and/or emergency. 
     External controller  204  includes a processor programmed to control signals to the drive mechanism of inflation source  203 , and memory for storing instructions thereon. External controller  204  also includes a power supply, e.g., battery that provides the power needed to operate the processor, inflation source  203 , and display  202 . Alternatively, external controller  204  may receive power via an electric cord plugged into a source of electric energy, e.g., an electric outlet. 
     Catheter  31  may be coupled at proximal end  35  to distal flotation balloon connector  205  for fluid communication with a source of inflation medium, e.g., gas or fluid, such that an inflation medium may be transferred between the source of inflation medium and distal flotation balloon  201  responsive to commands from external controller  204 , to thereby anchor distal flotation balloon  201  within the pulmonary artery of the patient. Catheter  31  also may be coupled at proximal end  35  to thermistor connector  206  for communication with a cardiac output (CO) monitor for measuring and monitoring temperature, and to pulmonary artery pressure connector  207  for communication with the CO monitor for measuring and monitoring pulmonary artery pressure. 
     External controller  204  may be coupled to catheter  31  at proximal end  35  via right atrial pressure connector  208  for measuring and monitoring right atrial pressure. External controller  204  also may be coupled to catheter  31  at proximal end  35  via flow limiting element connector  209  for measuring and monitoring the amount of inflation medium transferred between inflation source  203  and flow limiting element  32 , e.g., the pressure within flow limiting element  32 . External controller  204  also may be coupled to jugular vein pressure connector  210  for measuring and monitoring jugular vein pressure coming from a sheath sideport. 
     The processor of external controller  204  may include a data transfer circuit as described above that monitors an input from an external sensor, e.g., positioned on catheter  31 , and provides that signal to the processor. The processor is programmed to receive the input from the data transfer circuit and adjust the interval during which flow limiting element  32  is maintained in the expanded state, or to adjust the degree of occlusion caused by flow limiting element  32 . Thus, for example, catheter  31  may have one or more optional sensors positioned within distal portion  34  of the catheter to measure parameters, e.g., heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and central venous pressure. The output of the sensors is relayed to the data transfer circuit of external controller  204 , which may pre-process the input signal, e.g., decimate and digitize the output of the sensors, before it is supplied to the processor. The signal provided to the processor allows for assessment of the effectiveness of flow limiting element  32 , e.g., by showing reduced venous pressure during occlusion and during patency, and may be used by the clinician to determine how much occlusion is required to regulate venous blood return based on the severity of congestion in the patient. As will be understood by one or ordinary skill in the art, system  30 ′ may employ any combination of flow limiting elements and sensors as described above. 
     Referring now to  FIG. 49  an SVC occlusion system in combination with a trans-valvular LVAD is described. For example, SVC occlusion system  30  having flow limiting element  32  at distal portion  34  of catheter  31  may be positioned within the SVC, as described above, to at least partially occlude the SVC intermittently, and LVAD system  211  may be positioned in the left side of the heart, offering full hemodynamic support. In one example, LVAD system  211  is an Impella CP® heart pump available from Abiomed® of Danvers, Mass. LVAD system  211  illustratively includes inflow end  212 , outflow end  213 , impeller pump  214 , and anchor  215 , disposed on a distal portion of catheter  216 . For example, anchor  215  may be a pigtail anchor. During operation, inflow end  212  is positioned in the left ventricle and outflow end  213  is positioned in the ascending aorta. As impeller pump  214  is actuated, blood within the left ventricle is pumped through inflow end  212  and expelled into the aorta via outflow end  213 , thereby mimicking the natural pathway of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion. For example, impeller pump  214  may deliver up to 5.0 L/min of forward blood flow from the left ventricle to the aorta. As will be understood by one having ordinary skill in the art, any suitable pump may be used. 
     In addition, LVAD system  211  includes controller  217  configured to be operatively coupled to catheter  216  to actuate pump  214  to pump blood from the left ventricle to the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. Controller  217  and controller  33  may be the same and/or incorporated into the same housing unit, such that a single controller is operatively coupled to flow limiting element  32  and pump  214 . Controller  33  may actuate flow limiting element  32  to at least partially occlude the SVC simultaneously as controller  217  actuates pump  214  to pump blood from the left ventricle to the aorta. 
       FIG. 50  presents results obtained in an animal model, which demonstrates left ventricular (“LV”) total volume—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) to models (1) and (2), a reduction in cardiac preload (“CP”) and left ventricular wall tension (“LVWT”) results from use of a SVC occlusion system as described herein in combination with a trans-valvular LVAD (Impella CP® heart pump available from Abiomed® of Danvers, Mass.), showing improved functionality and efficiency in pre-load reduction caused by the LVAD. In addition, the trans-valvular LVAD may be operated at a lower rate of pumping while achieving sufficient systemic cardiovascular support, thus reducing the potential for adverse events related to the LVAD. 
     Referring now to  FIG. 51  an SVC occlusion system in combination with a trans-valvular RVAD is described. For example, SVC occlusion system  30  having flow limiting element  32  at distal portion  34  of catheter  31  may be positioned within the SVC, as described above, to at least partially occlude the SVC intermittently, and RVAD system  218  may be positioned distal to flow limiting element  32  on catheter  31 , offering full hemodynamic support. In one example, RVAD system  218  is an Impella RP® heart pump available from Abiomed® of Danvers, Mass. RVAD system  218  illustratively includes inflow end  219 , outflow end  220 , impeller pump  221 , and anchor  222 , disposed on a distal portion of catheter  223 . For example, anchor  222  may be a pigtail anchor. During operation, outflow end  220  is positioned in the pulmonary artery and inflow end  219  is positioned in the SVC, distal to flow limiting element  32 . As impeller pump  221  is actuated, blood within the SVC is pumped through inflow end  219  and expelled into the pulmonary artery via outflow end  220 , thereby mimicking the natural pathway of blood flow and unloading the right ventricle. For example, impeller pump  221  may deliver up to 5.0 L/min of forward blood flow from the SVC to the pulmonary artery. As will be understood by one having ordinary skill in the art, any suitable pump may be used. 
     In addition, controller  33  may be configured to be operatively coupled to RVAD system  218  to actuate pump  221  to pump blood from the SVC to the pulmonary artery, thereby unloading the right ventricle. Thus, controller  33  may simultaneously actuate flow limiting element  32  to at least partially occlude the SVC and pump  221  to pump blood from the SVC to the pulmonary artery. 
     Referring now to  FIG. 52  an SVC occlusion system in combination with an alternative trans-valvular RVAD is described. For example, SVC occlusion system  30  having flow limiting element  32  at distal portion  34  of catheter  31  may be positioned within the SVC, as described above, to at least partially occlude the SVC intermittently, and RVAD system  218  may be positioned in the right side of the heart, offering full hemodynamic support. In one example, RVAD system  218  is an Impella CP® heart pump available from Abiomed® of Danvers, Mass. RVAD system  218  illustratively includes inflow end  219 , outflow end  220 , impeller pump  221 , and anchor  222 , disposed on a distal portion of catheter  223 . For example, anchor  222  may be a pigtail anchor. During operation, inflow end  219  is positioned in the inferior vena cava (IVC) and outflow end  220  is positioned in the pulmonary artery. As impeller pump  221  is actuated, blood within the IVC is pumped through inflow end  219  and expelled into the pulmonary artery via outflow end  220 , thereby mimicking the natural pathway of blood flow, unloading the right ventricle. For example, impeller pump  221  may deliver up to 5.0 L/min of forward blood flow from the IVC to the pulmonary artery. As will be understood by one having ordinary skill in the art, any suitable pump may be used. 
     In addition, RVAD system  218  includes controller  224  configured to be operatively coupled to catheter  223  to actuate pump  221  to pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle. Controller  224  and controller  33  may be the same and/or incorporated into the same housing unit, such that a single controller is operatively coupled to flow limiting element  32  and pump  221 . Controller  33  may actuate flow limiting element  32  to at least partially occlude the SVC simultaneously as controller  224  actuates pump  221  to pump blood from the IVC to the pulmonary artery. 
     Referring now to  FIG. 53  an SVC occlusion system in combination with a transapical LVAD is described. For example, SVC occlusion system  30  having flow limiting element  32  at distal portion  34  of catheter  31  may be positioned within the SVC, as described above, to at least partially occlude the SVC intermittently, and LVAD system  225  may be positioned transapically in the left side of the heart, offering full hemodynamic support. In one example, LVAD system  225  is an HeartWare™ HVAD™ System available from HeartWare, Inc. of Miami Lakes, Fla. LVAD system  225  illustratively includes inflow end  226 , outflow end  227 , and pump  228 , implanted near the apex of the left ventricle. During operation, inflow end  226  is positioned in the left ventricle and outflow end  227  is positioned in the ascending aorta. As pump  228  is actuated, blood within the left ventricle is pumped through inflow end  226  and expelled into the aorta via outflow end  227 , thereby mimicking the natural pathway of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion. As will be understood by one having ordinary skill in the art, any suitable pump may be used. 
     In addition, LVAD system  225  includes controller  229  configured to be operatively coupled to pump  228  to actuate pump  228  to pump blood from the left ventricle to the aorta. Controller  229  and controller  33  may be the same and/or incorporated into the same housing unit, such that a single controller is operatively coupled to flow limiting element  32  and pump  228 . Controller  33  may actuate flow limiting element  32  to at least partially occlude the SVC as controller  229  simultaneously actuates pump  228  to pump blood from the left ventricle to the aorta. 
     Referring now to  FIG. 54  an SVC occlusion system in combination with an intra-aortic balloon pump (IABP) is described. For example, SVC occlusion system  30  having flow limiting element  32  at distal portion  34  of catheter  31  may be positioned within the SVC, as described above, to at least partially occlude the SVC intermittently, and IABP  230  may be positioned the descending aorta. IABP may include flow limiting element  231  and catheter  232  coupled to flow limiting element  231 . Flow limiting element  231  illustratively comprises a balloon capable of transitioning between a contracted state, allowing transluminal placement, and an expanded, deployed state. Flow limiting element  231  is preferably sized and shaped so that it partially or fully occludes flow in the aorta in the expanded state. Catheter  232  may be coupled to controller  33  at a proximal end. Controller  33 , houses drive mechanism  36  for independently actuating flow limiting element  32  and flow limiting element  231 . As shown in  FIG. 54 , flow limiting element  231  and flow limiting element  32  may be coupled to the same controller such that a single controller is operatively coupled to flow limiting element  32 , flow limiting element  231 , and pump  221 . However, it is understood that flow limiting element  32  and flow limiting element  231  may be coupled to different controllers and/or different pumps. During operation, flow limiting element  231  will be positioned within the descending aorta and will intermittently inflate and deflate. Inflation may be timed to coincide with diastole and deflation timed to coincide with systole. As flow limiting element  231  deflates, a suction effect is created in the aorta, facilitating the transfer of blood from the left ventricle to the aorta during systole. 
     The combination of the SVC occlusion system with a VAD, RVAD or LVAD may reduce the required flow rate of the VAD to achieve the same hemodynamic response in the patient. This would lower the required speed of the pump, thereby reducing the potential complications associated with the higher speed of the pump required to generate higher flow rates. Further, intermittent occlusion of the SVC following implantation of the pump may help unload the right ventricle while the LVAD is being brought up to operational speed. 
     It is to be understood that the foregoing description is intended to illustrate and not to limit the scope of the invention, which is defined by the scope of the appended claims. Other embodiments are within the scope of the following claims.