Systems and methods for selectively occluding the superior vena cava to treat heart conditions

Abstract

Systems and methods are provided for treating conditions such as heart failure and / or pulmonary hypertension by at least partially occluding flow through the superior vena cava for a duration spanning multiple cardiac cycles. Catheters with occlusion devices are provided, as well as controllers that actuate a drive mechanism to provide at least partial occlusion of a patient's superior vena cava, which reduces cardiac filling pressures and induces a favorable shift in the patient's Frank-Starling curve toward healthy cardiac functionality and improved cardiac performance. The system can include sensors to determine the degree of occlusion of the superior vena cava. The occlusion system can be used to reduce cardiac volume and facilitate cardiac surgery. The occlusion system can be used to relieve overburdened chambers during and / or after deployment of a VAD.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Application Serial No. 62 / 939,524, filed November 22, 2019, the entire contents of which are incorporated herein by reference. This application also relates to U.S. Patent Application Serial No. 16 / 402,194 (now U.S. Patent No. 10,842,975), filed May 2, 2019, which is a continuation to U.S. Patent Application Serial No. 15 / 203,437 (now U.S. Patent No. 10,279,152), filed July 6, 2016, which is a continuation to U.S. Patent Application Serial No. 14 / 828,429 (now U.S. Patent No. 9,393,384), filed August 17, 2015, the entire contents of each of which are incorporated herein by reference. This application also relates to U.S. Patent Application Serial No. 16 / 168,357 (now U.S. Patent No. 10,842,974), filed October 23, 2018, which claims priority to U.S. Provisional Application Serial No. 62 / 642,569, filed March 13, 2018, and U.S. Provisional Application Serial No. 62 / 576,529, filed October 24, 2017, and is a successor in part to U.S. Patent Application Serial No. 15 / 753,300 (now U.S. Patent No. 10,758,715), filed February 17, 2018. This continuation application is a continuation of the national phase of PCT / US2016 / 047055, filed August 15, 2016; a continuation of U.S. Patent Application Serial No. 15 / 203,437 (now U.S. Patent No. 10,279,152), filed July 6, 2016; and a continuation of U.S. Patent Application Serial No. 14 / 828,429 (now U.S. Patent No. 9,393,384), filed August 17, 2015. The entire contents of each of these applications are incorporated herein by reference. Technical Field

[0003] This disclosure relates to methods and systems for improving cardiac function in patients with heart failure, including those with decreased ejection fraction, and for treating pulmonary hypertension and / or cardiorenal syndrome. Background Technology

[0004] Heart failure is a leading cause of death worldwide. It often leads to multiple, prolonged hospital stays, especially in the later stages of the disease. Without a heart transplant, the long-term prognosis for these patients is poor, and medical treatments only provide temporary relief. Therefore, there are few effective therapies to slow or reverse the progression of the disease.

[0005] Heart failure can be caused by any of a variety of precipitating events. Heart failure can occur as a result of ischemic heart disease, hypertension, valvular heart disease, infection, genetic cardiomyopathy, pulmonary hypertension, or can occur under conditions of metabolic stress including pregnancy. Heart failure can also occur without an identifiable cause, also known as idiopathic cardiomyopathy. The term heart failure encompasses left ventricular failure, right ventricular failure, or biventricular failure.

[0006] While the heart can initially respond successfully to the increased workload caused by hypertension or loss of contractile tissue, over time this stress triggers compensatory cardiac hypertrophy and remodeling of the ventricular wall. Specifically, in the months following the initial cardiac insult, the damaged portion of the heart typically begins to remodel as the heart struggles to continue pumping blood with a reduced muscle mass or lower contractility. This in turn typically leads to overworking of the myocardium, such that the myocardium of the damaged region becomes increasingly thin, dilated, and further overburdened. At the same time, the ejection fraction of the damaged ventricle decreases, resulting in reduced cardiac output over the cardiac cycle and elevated intraventricular mean pressure and volume, which are hallmarks of heart failure. Not surprisingly, once a patient's heart enters this progressively self-perpetuating spiral of deterioration, the patient's quality of life is severely impacted and the risk of morbidity skyrockets. Depending on a number of factors, including the patient's prior physical condition, age, sex, and lifestyle, the patient can experience one or more hospitalizations, the patient and the healthcare system expend significant resources, and ultimately the patient dies from cardiac arrest or any of a number of secondary morbidities, including stroke, renal failure, liver failure, or pulmonary hypertension.

[0007] Currently, there are no device-based solutions that specifically target the reduction of preload to limit the progression of heart failure. Pharmacological approaches are available as palliative means to alleviate the symptoms of heart failure, but there are no pharmacological routes to arrest or reverse heart failure. Moreover, existing pharmacological approaches are systemic in nature and do not address the local effects of remodeling on the structure of the heart. Thus, it would be desirable to provide systems and methods for treating heart failure that arrest and more preferably reverse the remodeling of the heart that generates the cascade of effects associated with this disease.

[0008] Applicants note that the prior art contains several attempts to address heart failure. Prior to the Applicants' invention as described herein, there was no effective commercial device available to treat this disease. Several known examples of previously known systems and methods for treating various aspects of heart failure are described below, but none appear to be directed to or capable of reducing left ventricular end diastolic volume ("LVEDV"), left ventricular end diastolic pressure ("LVEDP"), left ventricular end diastolic diameter ("LVEDD"), right ventricular end diastolic volume ("RVEDV"), or right ventricular end diastolic pressure ("RVEDP") without causing potentially serious side effects.

[0009] For example, U.S. Patent No. 4,546,759 to Solar describes a triple balloon catheter designed to be placed so that the distal balloon intermittently occludes the superior vena cava, the proximal balloon intermittently occludes the inferior vena cava, and the middle balloon expands in synchrony with the occurrence of right ventricular contraction, thereby enhancing the ejection of blood from the right ventricle. The patent describes the system to be synchronous with normal heart rhythm to distend and deflate, and is designed to reduce the load on the right ventricle to permit healing of right ventricular damage or defects. The patent does not describe or suggest that the proposed modulation of flow into and out of the right ventricle would have an effect on LVEDV, LVEDD, or LVEDP, nor does it describe or suggest that it could be used to arrest or reverse acute / chronic heart failure.

[0010] U.S. Patent Publication No. US 2006 / 0064059 to Gelfand describes a system and method intended to reduce myocardial infarct size and / or myocardial remodeling after acute myocardial infarction by reducing stress in the heart wall. 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 into the pulmonary artery through the tricuspid and pulmonary valve. The patent application describes that by partially occluding the inferior vena cava, the system modulates the amount of blood entering the ventricle and thus reduces the load on the ventricle, permitting faster healing and reducing the expansion of the myocardial infarct. The system described by Gelfand includes sensors mounted on the catheter that are read by a controller to adjust the modulation of blood flow into the heart as well as other measured parameters to be 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 when the heart has undergone the large area remodeling typically observed during repeated hospitalization of patients to address symptoms of congestive heart failure.

[0011] US Patent Publication No. US 2010 / 0331876 to Cedeno describes a system and method similar to the design described by Gilfan, intended to treat congestive heart failure by modulating venous return through the inferior vena cava. The system described by Cedeno describes a fixed volume balloon placed in the inferior vena cava that will restrict blood flow in the inferior vena cava (IVC). The degree of occlusion varies with the expansion and contraction of the vessel during inspiration and expiration, thereby correcting venous return. The patent application additionally describes that heart failure symptoms are improved within three months of using the claimed system. While the system and method described by Cedeno appears promising, the applicants have discovered several potential shortcomings with such a system during their own research. The applicants have observed during their own research that completely occluding the inferior vena cava not only reduces left ventricular volume, but also significantly reduces left ventricular systolic pressure, thereby reducing systemic blood pressure and cardiac output. Furthermore, complete inferior vena cava occlusion can increase venous congestion within the renal veins, hepatic veins, and mesenteric veins; venous congestion is a major cause of renal failure in patients with congestive heart failure.

[0012] There are several major limitations to the approach of partially or totally occluding the IVC to modulate cardiac filling pressures and improve cardiac function. First, access to the IVC must be through the femoral vein or through the internal jugular vein. If access is through the femoral vein, the patient will be required to remain supine and unable to move. If access is through the jugular or subclavian vein, the device will have to traverse the superior vena cava and right atrium, thereby requiring cardiac puncture, which is prone to potential risks involving injury to the right atrium, including induction of cardiac arrhythmias such as supraventricular tachycardia or bradycardia due to heart block. Second, the IVC approach described by Seldinger and colleagues relies on several highly variable indices, especially in the setting of congestive heart failure: 1) IVC diameter, which is often dilated in heart failure patients; b) intermittent (total or partial) IVC occlusion can cause harm due to increased renal vein pressure, which decreases glomerular filtration rate and worsens renal insufficiency; c) dependence on the patient's respiratory capacity, which is often severely compromised in heart failure (the typical respiratory pattern in HF is known as Cheynes Stokes respiration, which is defined by intermittent periods of apnea, where the IVC can collapse and the balloon will form a total occlusion, resulting in lower systemic blood pressure and higher renal vein pressure); d) IVC occlusion will be ineffective if long-term cardiac unloading is required for clinical improvement or beneficial changes in cardiac structure or function, as continued IVC occlusion will compromise blood pressure and renal function. Third, the approach defined by Seldinger will require balloon customization depending on the IVC size, which can have great variability. Fourth, many patients with heart failure have IVC filters due to increased propensity for deep vein thrombosis, which will hinder widespread application of the IVC therapy.

[0013] Pulmonary hypertension (PH) is also a major cause of morbidity and mortality worldwide. As mentioned above, while heart failure is a common cause of pulmonary hypertension, pulmonary hypertension can also be caused by primary pulmonary disease. Today, medical therapy can reduce pulmonary artery systolic pressure (PASP) and improve symptoms and ultimate survival in patients with pulmonary hypertension. However, medical therapy has drawbacks, such as cost and side effects.

[0014] In view of the foregoing disadvantages of previously known systems and methods for modulating 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 exacerbation of the comorbidities associated with the disease.

[0015] Furthermore, it would be desirable to provide systems and methods for treating acute and chronic heart failure that arrest or reverse the effects of cardiac remodeling and are practical for chronic and / or ambulatory use.

[0016] Furthermore, it is desirable to provide systems and methods for treating heart failure that permit patients suffering from this disease to have an improved quality of life, thereby reducing the need for hospital admissions and length of hospital stays and the associated burden on the social healthcare network.

[0017] It is also desirable to provide systems and methods that allow for the treatment of pulmonary arterial hypertension and cardiorenal syndrome.

[0018] Another concern is that an overburdened heart can experience a remodeling and deformed wall and eventually reduced valve coaptation. Without proper valve coaptation, the valve will not seal properly and blood can flow back through the valve, causing regurgitation. Regurgitation can cause shortness of breath, fatigue, and an increased heart rate and / or palpitations. It is desirable to provide systems and methods that treat regurgitation.

[0019] Another problem with overburdening is that it complicates heart surgery, such as corrective surgery for regurgitation. For example, clips can be used to couple valve leaflets that no longer seal. However, if the volume of the heart chamber is too large, it can be impossible to deploy the clip because the leaflets are too far apart. It is also desirable to provide systems that reduce the volume of the heart to perform heart surgery.

[0020] It is known that overburdening also occurs during and / or after the installation of a ventricular assist device (VAD). For example, during and / or after the installation of a left ventricular assist device (LVAD), the right ventricle can become overburdened. A right ventricular assist device (RVAD) can be used to address this problem. However, this involves the installation and / or deployment of a second heart pump, leading to an increased risk of complications and infection. It is also desirable to provide systems that reduce the volume of the heart chamber and install a VAD. SUMMARY

[0021] In view of the disadvantages of previously known systems and methods for treating heart failure, it is desirable to provide systems and methods for treating acute and / or chronic heart failure that can arrest and, more preferably, reverse the remodeling of the heart that produces the cascade of effects associated with this disease.

[0022] Furthermore, it is desirable to provide systems and methods that are practical for ambulatory and / or chronic use for arresting or reversing the remodeling of the heart of a patient suffering from heart failure.

[0023] Furthermore, it is desirable to provide systems and methods for treating heart failure that reduce the risk of exacerbation of the side effects associated with the disease, such as venous congestion, which leads to renal hepatic complications.

[0024] It is also desirable to provide systems and methods for treating heart failure that permit patients suffering from this disease to have an improved quality of life, while reducing the need for repeated hospital admissions and the associated burden on the social healthcare network.

[0025] It is further 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 is 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, systolic and restrictive cardiomyopathy, and cardio-renal syndrome (types 1-5).

[0026] The present disclosure provides systems and methods for modulating venous return to the heart through the superior vena cava ("SVC") over an interval spanning several heartbeats, thereby reducing ventricular overload without increasing renal venous pressure, and reducing cardiac preload and pulmonary artery pressure. In accordance with the principles of the present invention, venous modulation through the SVC can be used to reduce LVEDP, LVEDV, LVEDD, RVEDP, and / or RVEDV, and to arrest or reverse ventricular myocardial remodeling. Contrary to intuition, Applicants have observed in preliminary animal testing that intermittent partial occlusion of the SVC does not result in cerebral blood flow stasis or observable adverse side effects. More importantly, Applicants' preliminary animal testing has revealed that occlusion of the SVC results in a significant reduction in RVEDP and LVEDP, while increasing total cardiac output and without a significant reduction in left ventricular systolic pressure ("LVSP"). Thus, unlike the methods discussed in the previously published Sedano patent applications, the present invention provides a beneficial reduction in LVEDP, LVEDV, LVEDD, RVEDP, and / or RVEDV, with negligible impact on LVSP, but with an increase in stroke volume (cardiac output) and a reduction in the risk of venous congestion leading to increased secondary morbidity. The systems and methods described herein provide acute improvements in cardiac filling pressures and function to benefit patients at risk of acute decompensated heart failure.

[0027] There are several major advantages to targeting SVC blood flow (optionally IVC blood flow). First, device placement in the SVC avoids the use of femoral veins and avoids cardiac puncture. This allows the development of a completely implantable system for acute or chronic therapy that does not even require bed rest. Second, SVC occlusion can be intermittent or long-term, depending on the amount of unloading required. Unlike IVC occlusion, long-term SVC occlusion maintains systemic blood pressure and increases cardiac output. This allows for sustained unloading of both the right and left ventricles, allowing for the possibility of acute hemodynamic benefits and long-term beneficial effects on cardiac structure or function. Third, unlike IVC occlusion, SVC occlusion is not dependent on patient respiration. Fourth, by developing an internal regulator for the SVC occlusion driven by right atrial mean pressure or pressure differential across the occlusion balloon, the SVC device can be programmed and individualized for each patient condition. Fifth, by placing the device in the SVC, the device can be used with existing IVC filters in patients.

[0028] According to another aspect of the present disclosure, it is contemplated that intermittent occlusion of the SVC over a plurality of cardiac cycles permits myocardial healing such that reduced myocardial wall stress arrests or reverses remodeling that is a symptom of heart failure progression. Without wishing to be bound by theory, Applicants believe that intermittent occlusion of the SVC permits the heart to shift from a Starling curve indicative of heart failure with declining ejection fraction toward a Starling curve with LVEDP and LVEDP indicative of normal heart function after implementation of a period of hours, days, weeks, or months. Thus, preliminary animal testing by Applicants suggests that the present system can not only arrest the spiral of worsening that is typical of the disease, but can enable the heart to recover function sufficient to allow the patient to cease use of the system of the present invention, medical therapy, or both, after a period of hours, days, weeks, or months of 3 to 6 months.

[0029] According to another aspect of the present disclosure, a system is provided that includes a catheter having a flow restriction element configured for placement in or on the SVC, and a controller for controlling actuation of the flow restriction element. Preferably, the controller is programmed to receive an input indicative of fluctuations in the patient's hemodynamic state and to adjust actuation / deactivation of the flow restriction element in response to the input. Fluctuations in the patient's hemodynamic state can be caused by ambulatory activity of the patient. The controller can be programmed at the time of implantation of the catheter to maintain full or partial occlusion of the SVC for a predetermined number of cardiac cycles or a predetermined time interval based on the patient's resting heart rate, and this preset number of cycles or time interval can be continuously adjusted by the controller in response to a patient's heart rate input. The controller can additionally receive signals from sensors and / or electrodes indicative of sensed parameters that reflect the hemodynamic state, such as blood flow rate, blood volume, pressure including cardiac filling pressure, and the controller can continuously adjust the preset number of cycles or time interval in response to the sensed parameter(s).

[0030] In a preferred embodiment, the catheter is configured for intravascular implantation (e.g., via the patient's left subclavian vein) such that the flow restriction element is disposed in the SVC just proximal to the right atrium. The proximal end of the catheter can be coated or impregnated with an antibacterial agent to enable prolonged use of the catheter and reduce the risk of infection at the site through which the catheter is percutaneously passed. Preferably, the controller is powered by a battery and includes a quick connect coupling that permits the actuation mechanism of the controller to be operatively coupled to the flow restriction element. In preferred embodiments, the controller is small enough such that it can be worn by the patient in a clothing harness near the shoulder. In contrast to previously known systems that constrain the patient to a bed or acute care facility, the system of the present invention is configured so that the patient can not have to be bedridden and can carry out most daily activities, thereby enhancing the patient's quality of life and improving patient compliance with the course of treatment using the system of the present invention. In one embodiment, the controller is configured for implantation in the patient at a suitable location, such as a subcutaneous implantation under the collarbone. In such embodiments, the implantable controller is configured for two-way communication with an external controller, such as a mobile device or system-specific device. The external controller can be configured to charge the battery of the implantable controller, for example, by a respective inductive coil in each controller, and can receive data indicative of sensed parameters, including heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure. One or more external power sources can be in electrical communication with the implantable controller and can also be configured to provide power to the controller to charge the battery of the implantable controller. One or more external power sources can generate an alert when the level of the one or more external power sources is below a threshold level.

[0031] In preferred embodiments, the flow restriction element comprises one or more non- compatible or semi-compatible balloons attached 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 azygos vein. For example, the controller can be programmed to intermittently actuate the flow restriction element to at least partially occlude the SVC for a first predetermined time interval and to deflate for a second predetermined time interval over a plurality of heartbeats. The first predetermined time interval can be at least five times greater than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes and the second predetermined time interval is 1-30 seconds. In alternative embodiments, the flow restriction element can comprise a membrane-covered stent, a basket or other mechanical arrangement that can be rapidly transitioned between an expanded position and a collapsed position, for example, by a transmission system connected to the controller. In yet further embodiments, the flow restriction element can be in the form of a butterfly valve or a ball valve, provided that the flow restriction element does not create a stagnant flow region in the SVC when in the collapsed or open position. In yet further embodiments, the flow restriction element comprises a cuff configured to be applied to the exterior of the SVC and, when inflated, operates by constricting or occluding the SVC.

[0032] The system of the present invention can include a sensor disposed on the catheter for disposition within a venous or arterial vessel to measure the patient's heart rate or blood pressure. Preferably, the sensor generates an output signal that is used as an input to the controller to adjust the degree or timing of occlusion created by the flow restriction element. In another embodiment, the controller can be configured to couple to a third party heart rate sensor or blood pressure sensor, such as those commonly used by sports enthusiasts, e.g., Fitbit, through the patient's smartphone through a wireless standard available such as Bluetooth. In this embodiment, the cost, size and complexity of the controller can be reduced by integrating the controller with a commercially available third party component.

[0033] According to another aspect of the present disclosure, a method for controlling blood flow in a patient includes inserting and guiding a venous occlusion device into the patient's superior vena cava; coupling the occlusion device to a controller worn extracorporeally or implanted intracorporeally in the patient; and intermittently activating the venous occlusion device for intervals spanning a plurality of heartbeats, such that over a period of minutes, hours, days, weeks or months, remodeling of the myocardial layer is arrested or reversed.

[0034] According to another aspect of the present disclosure, a system for use in conjunction with a ventricular assist device (VAD) is provided to improve the efficiency and functionality of the VAD and reduce the risk of adverse effects of the VAD. The system includes a catheter having a proximal end and a distal region, the catheter being sized and shaped for disposition, e.g., intravascularly through the patient's subclavian or jugular vein, so as to dispose the distal region in the patient's superior vena cava (SVC). The system further includes a flow restriction element, e.g., an SVC occlusion balloon, disposed on the distal region of the catheter that is selectively actuated to at least partially occlude the SVC, and a controller operably coupled to the catheter to intermittently actuate the flow restriction element to at least partially occlude the SVC for intervals spanning a single or multiple heartbeats, thereby reducing the cardiac preload and pulmonary artery pressure to improve cardiac performance. For example, the controller can reduce the cardiac preload during the interval sufficient to improve cardiac performance as measured by at least one of: reduced cardiac filling pressure, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased lusitropy, reduced left ventricular stiffness, or reduced cardiac strain.

[0035] The system can further include a first pressure sensor disposed proximal to the flow restriction element on the catheter, the first pressure sensor outputting a first pressure signal, and a second pressure sensor disposed on the catheter and distal to the flow restriction 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 indicating a degree of occlusion of the flow restriction element. Optionally, the system can include a pressure switch disposed on the catheter having a first lumen with a first open end disposed proximal to the flow restriction element and a second lumen with a second open end disposed distal to the flow restriction element. The pressure switch can be configured to generate a signal indicative of a pressure differential between the first lumen and the second lumen. The controller can include a data transmission circuit configured to receive the signal and communicate the signal to a computing device of the patient for display to the patient.

[0036] The controller can use the first signal to determine when to actuate the flow restriction element to at least partially occlude the SVC and when to stop actuation of the flow restriction element. The controller can also be programmed to activate an alarm as a safety signal to an operator based on the first signal. Further, the controller can be programmed to send an alarm condition to a clinician monitoring the patient via a cellular communication capability of the computing device. In one embodiment, the controller is configured for implantation within the patient at a suitable location, for example, subcutaneously under the clavicle.

[0037] Further, the controller can be programmed to intermittently actuate the flow restriction element to at least partially occlude the SVC for a first predetermined time interval and to relax for a second predetermined time interval over a plurality of cardiac cycles. The first predetermined time interval can be at least ten times greater than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes and the second predetermined time interval is 1-10 seconds. The controller can be programmed to modify the first predetermined time interval based on the signal or based on a heart rate of the patient.

[0038] In a preferred embodiment, the flow restriction element is an inflatable cylindrical balloon having a relief valve coupled to the inflatable cylindrical balloon, the relief valve having an open position and a closed position. The relief valve can open at a predetermined pressure between 30-60 mmHg to allow fluid flow through the SVC to the right atrium of the patient. The system can further include an azygos vein occlusion balloon disposed proximal to the flow restriction element on the catheter. The azygos vein occlusion balloon can be selectively actuated to at least partially occlude the azygos vein of the patient, and the azygos vein occlusion balloon and the SVC occlusion balloon can be independently actuated. Additionally, the system allows the VAD to operate at a lower speed to achieve a hemodynamic response equal to or greater than the hemodynamic response of the VAD alone at a higher speed.

[0039] Additionally, the system can include a left ventricular assist device (LVAD) including a catheter having a proximal end and a distal region having an inflow end and an outflow end, the catheter sized and shaped for placement through a femoral artery of the patient such that the inflow end is disposed in the left ventricle of the patient and the outflow end is disposed in the aorta of the patient. The LVAD further includes a pump, such as an impeller pump, disposed on the distal region of the catheter, where the pump can be selectively actuated to pump blood from the left ventricle through the inflow end and out into the aorta via the outflow end; and an LVAD controller operably coupled to the LVAD to actuate the pump to pump blood from the left ventricle to the aorta to offload the left ventricle and increase coronary and systemic perfusion. Concurrently with the LVAD controller actuating the pump to pump blood from the left ventricle to the aorta, the LVAD controller operably coupled to the catheter of the system can modulate activation and deactivation of the flow restriction element to at least partially occlude the SVC.

[0040] Optionally or additionally, the system can further include a right ventricular assist device (RVAD) including a pump, such as an impeller pump, that can be selectively actuated to pump blood from the SVC through an inflow end of the RVAD and out into the pulmonary artery via an outflow end of the RVAD. A controller can also be operably coupled to the RVAD to actuate the pump to pump blood from the SVC to the pulmonary artery to offload the right ventricle. For example, concurrently with the controller actuating the pump to pump blood from the SVC to the pulmonary artery, the controller can actuate the flow restriction element to at least partially occlude the SVC.

[0041] In another preferred embodiment, the RVAD includes a catheter having a proximal end and a distal region having an inflow end and an outflow end, the catheter sized and shaped for placement through a femoral vein of the patient such that the outflow end is disposed in the pulmonary artery of the patient and the inflow end is disposed in the IVC of the patient. The RVAD further includes a pump, such as an impeller pump, disposed on the distal region of the catheter, where the pump can be selectively actuated to pump blood from the IVC through the inflow end and out into the pulmonary artery via the outflow end; and an RVAD controller operably coupled to the RVAD to actuate the pump to pump blood from the IVC to the pulmonary artery to offload the right ventricle. Concurrently with the RVAD controller actuating the pump to pump blood from the IVC to the pulmonary artery, the RVAD controller operably coupled to the catheter of the system can modulate activation and deactivation of the flow restriction element to at least partially occlude the SVC.

[0042] The system can also be used to regulate a patient's heart and perform a cardiac procedure. The method can involve inserting a first catheter including a flow limiting element into a superior vena cava (SVC) of a patient such that the flow limiting element is disposed within the SVC, and actuating the flow limiting element within the SVC, thereby at least partially occluding the SVC. The cardiac procedure can be performed at the patient's heart before, during, and / or after at least partially occluding the SVC. The flow limiting element can be stopped and re-actuated within the SVC before or during the cardiac procedure. Actuation of the flow limiting element can stimulate the vagus nerve and increase the patient's urine output.

[0043] A parameter related to the patient's heart can be measured to generate a first measured parameter and can be used to determine whether the measured parameter satisfies a predetermined threshold. Determining the measured parameter can include receiving a first signal from a first sensor disposed within the SVC and receiving a second signal from a second sensor disposed within the SVC. The first sensor can be an electrode and can be disposed proximal to the flow limiting element on the catheter. The second sensor can also be an electrode and can be disposed distal to the flow limiting element on the catheter. If it is determined that the measured parameter satisfies the predetermined threshold, the cardiac procedure can be performed. Partial and / or complete SVC occlusion can facilitate making the heart more susceptible to a successful cardiac procedure. The cardiac procedure can be a different procedure than the SVC partial / occlusion, such as implantation of a cardiac prosthesis (e.g., a prosthetic valve, a reflux reducing device, a clip, a ring, a ventricular assist device (VAD), etc.) using a commercially available system and / or coronary revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

[0044] If the first measured parameter is determined not to satisfy the predetermined threshold, an actuation parameter can be changed and a second parameter can be further measured. The second parameter can be measured to generate a second measured parameter and can be used to determine whether the second measured parameter satisfies the predetermined threshold. If it is determined that the second measured parameter satisfies the predetermined threshold, the cardiac procedure can be performed.

[0045] The system can also include inserting a second catheter through an inferior vena cava (IVC) to the heart, which can be adapted to perform the cardiac procedure. The second catheter can be disposed within the first catheter along at least a portion of the first catheter.

[0046] Further, the system can be used to reduce volume overload of a patient's heart. For example, a catheter including a flow limiting element (e.g., a balloon) can be inserted into a superior vena cava (SVC) of a patient such that the flow limiting element is disposed within the SVC. A left ventricular assist device (LVAD) can also be implanted at a left ventricle of the patient. The flow limiting element can be actuated within the SVC, thereby at least partially occluding the SVC during or after implantation of the LVAD. The flow limiting element can subsequently be deflated for a set period of time after implantation of the LVAD. Actuation of the flow limiting element can reduce pressure in the heart and / or fluid volume in the right ventricle.

[0047] The method for reducing volume overload can include receiving a signal from one or more sensors. The method can include receiving a first signal from an accelerometer disposed on the catheter indicating that the flow limiting element at least partially occludes the SVC. The flow limiting element can be stopped based on the first signal. Alternatively, the method can include receiving a first signal from a sensor disposed on the flow limiting element indicating contact between the SVC and the flow limiting element. In another embodiment, the method can include generating light from a light disposed proximal to the flow limiting element on the catheter, determining a first signal from a light sensor disposed distal to the flow limiting element on the catheter, and determining the degree of occlusion of the flow limiting element based on the first signal. In another embodiment, the method can include receiving a signal from a stretch gauge disposed on a portion of the catheter, the flow limiting element, or both the catheter and the flow limiting element. The flow limiting element can be stopped based on the received signal.

[0048] The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments and features described above, additional aspects, embodiments, and features will become apparent in connection with the drawings and the following detailed description. BRIEF DESCRIPTION OF DRAWINGS

[0049] The characteristics and advantages of the application will become apparent with reference to the drawings and accompanying description, in which:

[0050] FIG. 1A is a front view of a portion of the heart showing the major arteries and veins.

[0051] FIG. 1B illustrates the vena cava including the major veins associated with the vena cava.

[0052] FIG. 2A and 2B illustrates the Frank-Starling curve for normal and diseased heart conditions.

[0053] FIG. 3 is an exemplary pressure-volume loop plot of left ventricular pressure versus left ventricular volume throughout the cardiac cycle for a patient with normal heart function versus a patient suffering from congestive heart failure.

[0054] FIG. 4A is a schematic diagram of a system constructed in accordance with the principles of the present invention.

[0055] FIG. 4B is a schematic diagram of an implantable system constructed in accordance with the principles of the present invention.

[0056] FIG. 4C is a diagram of a power source and charging base.

[0057] FIG. 5A to 5B is FIG. 4A and FIG. 4B schematic view of a catheter, wherein the flow restriction element comprises a cylindrical balloon with a modified anchoring member shown in expanded and collapsed states, respectively.

[0058] FIG. 6 is FIG. 4A and FIG. 4B schematic view of a catheter, wherein the flow restriction element comprises a mechanically actuated membrane-covered basket.

[0059] FIG. 7 is FIG. 4A and FIG. 4B cross-sectional view of a catheter.

[0060] FIG. 8A and 8B schematic view of a flow restriction element comprising a spherical balloon shown in its expanded and collapsed states, respectively.

[0061] FIG. 9A and 9B schematic view of a flow restriction element comprising a spring-loaded plug shown in its expanded and collapsed states, respectively.

[0062] FIG. 10A and 10B schematic view of a flow restriction element comprising an alternative embodiment of a spring-loaded plug shown in its expanded and collapsed states, respectively.

[0063] FIG. 11 Graphs and tables showing left ventricular (LV) pressure and LV volume over multiple consecutive heartbeats in a pig model after complete occlusion of the inferior vena cava (IVC) are shown.

[0064] FIG. 12 Graphs and tables showing LV pressure and LV volume over multiple consecutive heartbeats in a pig model after partial occlusion of the superior vena cava (SVC) are shown.

[0065] FIG. 13-14 is a graph showing pressure change as a function of left ventricular volume and right ventricular volume, respectively, during superior vena cava (SVC) occlusion and release in a pig with heart failure, in accordance with the principles of the present invention.

[0066] FIG. 15 to 22 Test results for a subject pig with heart failure are shown.

[0067] FIG. 23A to 23DClinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume, and ventricular stroke work during the downsize time of a one minute segment of continuous SVC occlusion are illustrated, respectively, according to the principles of the present application.

[0068] FIG. 24A to 24D Clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume, and ventricular stroke work during the downsize time of a five minute segment of continuous SVC occlusion are illustrated, respectively, according to the principles of the present application.

[0069] FIG. 25A to 25D Clinical pressure changes in left ventricular end diastolic pressure, left ventricular end systolic pressure, left ventricular volume, and ventricular stroke work during the downsize time of a ten minute segment of continuous SVC occlusion are illustrated, respectively, according to the principles of the present application.

[0070] FIG. 26A to 26C Clinical pressure changes in pulmonary capillary wedge pressure, pulmonary artery pressure, and right atrial pressure observed during a five minute segment of continuous SVC occlusion are illustrated, respectively, according to the principles of the present application.

[0071] FIG. 27A to 27E Clinical pressure changes in systolic pressure, diastolic pressure, mean arterial pressure, mean pulmonary artery pressure, and mean pulmonary capillary wedge pressure during a five minute segment of continuous SVC occlusion are illustrated, respectively, according to the principles of the present application.

[0072] FIG. 28A to 28B Clinical pressure changes in mean pulmonary artery pressure and mean arterial pressure during a ten minute segment of continuous SVC occlusion are illustrated, respectively, according to the principles of the present application.

[0073] FIG. 29 Cardiac output before and during SVC occlusion is illustrated, according to the principles of the present application.

[0074] FIG. 30 Pulmonary artery systolic pressure during SVC occlusion and non-occlusion is illustrated, according to the principles of the present application.

[0075] FIG. 31 Is a predictive example of how SVC occlusion according to the principles of the present application changes disease progression.

[0076] FIG. 32 Is a perspective view of a cylindrical flow restricting element.

[0077] FIG. 33 Is a cross-sectional view showing a cylindrical flow restricting element releasing a valve.

[0078] FIG. 34A -B is a cross-sectional view of a cylindrical flow restricting element with a binary release valve and a progressive release valve.

[0079] FIG. 35 is a top view of a cylindrical flow restriction element with a release valve in a closed position.

[0080] FIG. 36A is a top view of a cylindrical flow restriction element with a binary release valve and a progressive release valve in an open position.

[0081] FIG. 37A is a perspective view and a cross-sectional view of a cylindrical flow restriction element engaged with a stent.

[0082] FIG. 38A is a top view of a cylindrical flow restriction element with a balloon occluder in an expanded and deflated position.

[0083] FIG. 39A is a top view of a cylindrical flow restriction element with a cylindrical balloon occluder in an expanded and deflated position.

[0084] FIG. 40A is a perspective view and a cross-sectional view of a stent coupled to a release valve.

[0085] FIG. 41 is a cross-sectional view of a cylindrical flow restriction element coupled to a filter.

[0086] FIG. 42A is a cutaway perspective view of a cylindrical flow restriction element coupled to a catheter with a sensor, and FIG. 42B is an exemplary phasic curve.

[0087] FIG. 43A is a view of an introducer sheath into the SVC, a flow restriction element within the SVC, a catheter, and one or more sensors.

[0088] FIG. 44 is a view of an introducer sheath within the SVC, a flow restriction element incorporated into the introducer sheath, and a catheter within the heart.

[0089] FIG. 45 is a view of an occlusion system with an azygos vein occlusion balloon and a second occlusion balloon within the SVC.

[0090] FIG. 46 is a view of an occlusion cuff wrapped around the SVC.

[0091] FIG. 47A is a view of the outside and inside of an occlusion cuff, and FIG. 47C is a perspective view of an occlusion cuff.

[0092] FIG. 48is an alternative exemplary system configured according to the principles of the present application.

[0093] FIG. 49 illustrates an SVC occlusion system in combination with a transvalvular LVAD.

[0094] FIG. 50 is a graph illustrating the enhanced unloading capacity of SVC occlusion when used in combination with a transvalvular LVAD.

[0095] FIG. 51 illustrates an SVC occlusion system in combination with a transvalvular RVAD.

[0096] FIG. 52 illustrates an SVC occlusion system in combination with an alternative transvalvular RVAD.

[0097] FIG. 53 illustrates an SVC occlusion system in combination with an LVAD.

[0098] FIG. 54 illustrates an SVC occlusion system in combination with an LVAD, including a flow restriction element disposed on an introducer sheath.

[0099] FIG. 55 is a flowchart of an exemplary method for deploying an SVC occlusion system in the SVC and implanting an LVAD at the left ventricle.

[0100] FIG. 56 illustrates an SVC occlusion system in combination with an intra-aortic balloon pump (IABP).

[0101] FIG. 57A - C illustrates a normal heart, a chronically compensated heart, and a decompensated heart, respectively.

[0102] FIG. 58 illustrates an SVC occlusion system, including a flow restriction element disposed on an introducer sheath positioned within the SVC.

[0103] FIG. 59 illustrates an SVC occlusion system, including a flow restriction element disposed on an introducer sheath positioned within the SVC and a delivery catheter for deploying a valve clip via the IVC.

[0104] FIG. 60 is a flowchart of an exemplary method for deploying an SVC occlusion system in the SVC and performing a heart surgery.

[0105] FIG. 61 illustrates an SVC occlusion system, including a flow restriction element disposed on an introducer sheath positioned within the SVC and a delivery catheter for deploying an annuloplasty ring via the IVC.

[0106] FIG. 62An SVC occlusion system is illustrated that includes a flow restriction element disposed on an introducer sheath positioned within the SVC and a delivery catheter for deploying a transcatheter prosthesis via the IVC.

[0107] FIG. 63 An SVC occlusion system is illustrated that includes a flow restriction element disposed on an introducer sheath positioned within the SVC and a delivery catheter positioned within the introducer sheath. DETAILED DESCRIPTION

[0108] REFERENCE FIG. 1A AND 1B The present invention is designed to be placed and operate within the human anatomy as context for the systems and methods of the present invention.

[0109] More specifically, with reference to FIG. 1A Deoxygenated blood returns to the heart 10 through the vena cava 11, which includes the superior vena cava 12 and the inferior vena cava 13, which connect to the right atrium 14 of the heart. Blood moves from the right atrium 14 through the tricuspid valve 15 to the right ventricle 16, where it is pumped through the pulmonary artery 17 to the lungs. Oxygenated blood returns to the left atrium 18 from the lungs through the pulmonary veins. The oxygenated blood then enters the left ventricle 19, which pumps blood through the aorta 20 to the rest of the body.

[0110] As shown in FIG. 1B The superior vena cava 12 is located at the top of the vena cava 11, while the inferior vena cava 13 is located at the bottom of the vena cava. FIG. 1B Also shown are some of the azygos vein 16 and major veins that connect to the vena cava. As noted herein, occlusion of the inferior vena cava 13 can pose a risk of venous congestion, and in particular, occlusion or dilation of the hepatic veins and / or adrenal veins can worsen rather than improve the cardiovascular condition and overall health of the patient.

[0111] According to one aspect of the present invention, the applicant has determined that selective intermittent occlusion of the superior vena cava ("SVC") poses fewer potential adverse risks than inferior vena cava ("IVC") occlusion. Moreover, the applicant's animal and human trials have revealed that controlling venous return to the right ventricle by partially or completely occluding the SVC advantageously reduces RVEDP, RVEDV, LVEDP, and LVEDV without adversely reducing left ventricular systolic pressure (LVSP).

[0112] Applicants understand that selective intermittent occlusion of the SVC location, as compared to IVC occlusion, will reduce the risk of worsening congestion of the kidneys, which is a major contributor to the 'cardiorenal' syndrome. Cardiorenal syndrome is impaired kidney function due to volume overload and neurohormonal activation in patients with heart failure. Volume overload can occur when a weakened heart is unable to pump enough blood, which results in less blood flowing through the kidneys. With less blood flowing through the kidneys, less blood is filtered by the kidneys and less water is expelled via urination, which results in excess volume being retained in the body. Along with the excess volume, the heart pumps with less and less efficiency and as the body becomes increasingly congested, the patient spirals towards death.

[0113] Applicants understand that IVC occlusion generally reduces the blood flow through the kidneys by increasing the pressure in the renal veins with the occluded IVC, thereby reducing the ability of the kidneys to filter fluid. IVC occlusion further causes blood to back up and otherwise prevent deoxygenated blood from returning to the heart. As a result, kidney function can also be reduced and congestion worsened. However, SVC occlusion ultimately increases the flow to the kidneys, thereby improving kidney function. Specifically, by reducing the flow into the right atrium via the SVC occlusion, the volume in the left ventricle is ultimately reduced, which allows the muscle fibers to stretch within a normal range, which naturally increases the rate of contraction and allows the heart to drive more fluid to the kidneys. The kidneys can then extract water, which can be removed from the body through urination. It is further understood that the sudden reduction in right atrial pressure and volume during SVC occlusion causes a negative pressure sink in the right atrium. As a result, flow from the renal veins can be accelerated, thereby enhancing renal decongestion and promoting blood flow across the kidneys, increasing urine output. Thus, SVC occlusion can benefit heart failure and / or cardiorenal syndrome patients by reducing cardiac and pulmonary pressures and promoting decongestion.

[0114] Additionally, implantation in the SVC permits supravalvular device implantation, which is not possible in the IVC without cardiac puncture and traversal of the right atrium. Moreover, implantation of the occluder in the SVC avoids the need for a groin access as required for IVC implantation, which would limit mobility, making ambulatory devices unavailable for short or long term use. Additionally, small changes (in time or degree) in IVC occlusion can result in more dramatic changes in preload reduction and thus total cardiac output / systemic blood pressure, whereas the system and method of the present invention as desired permits fine-tuned reduction of venous return blood (preload reduction).

[0115] Applicants understand that intermittent occlusion of the SVC (i.e., cardiopulmonary unloading) over a period of time (e.g., minutes, hours, days, weeks, or months) will advantageously permit the patient's heart to cease or recover from myocardial remodeling. Applicant's animal and human testing indicates that the system enables the myocardial layer to shift from a pressure- stroke volume curve indicative of heart failure toward a pressure-stroke volume curve more approximating a healthy heart.

[0116] In general, the system and method of the present invention can be used to treat any disease to improve cardiac function by arresting or reversing myocardial remodeling, and in particular, those conditions in which a patient suffers from heart failure. Such conditions include, but are not limited to, for example, systolic heart failure, diastolic (non-systolic) heart failure, decompensated heart failure patients (ADHF), chronic heart failure, acute heart failure and pulmonary hypertension, heart attack, heart failure with preserved ejection fraction, right heart failure, systolic and restrictive cardiomyopathy, and cardiorenal syndrome (types 1-5). The system and method of the present invention can also be used as prophylaxis to mitigate the consequences of acute right or left ventricular myocardial infarction, pulmonary hypertension, RV failure, post-cardiotomy shock, or rejection following orthotopic heart transplantation (OHTx), or otherwise can be used in cardiorenal applications and / or to treat renal insufficiency, hepatic insufficiency, or lymphedema. Moreover, the system and method of the present invention can reduce hospitalization time resulting from the various diseases described herein, including at least the acute exacerbation phase.

[0117] The relationship between left ventricular pressure or left ventricular volume and stroke volume is commonly referred to as the Frank-Starling relationship or "Starling curve" and is graphically illustrated in FIG. 2A-2B The relationship indicates that the stroke volume of the heart depends on the preload, contractility, and afterload. Preload refers to the volume of blood returning to the heart; contractility is defined as the inherent ability of the myocardium to contract; and afterload is determined by vascular resistance and impedance. In heart failure due to diastolic or systolic dysfunction, a decrease in stroke volume leads to an increase in volume and pressure in the left ventricle, which can result in pulmonary edema. The increase in ventricular volume and pressure also results in an increase in the work load and myocardial oxygen consumption. This overwork of the heart leads to worsening cardiac function as the heart becomes more and more oxygen starved due to the mismatch between supply and demand. Moreover, as the internal volume and pressure of the heart increase, the contractile function worsens due to the stretching of the myocardium. This condition is referred to as "congestive heart failure."

[0118] Reference is made to FIG. 2A, showing a series of Starling curves, with the topmost curve (Curve 1) depicting the operation of a normal heart. As shown in the curves, cardiac output increases with increasing LVEDP or LVEDV, and only begins to plateau at very high pressures or volumes, i.e., the slope of the curve decreases. A patient who has just experienced an acute myocardial infarction ("AMI"), as indicated by the middle curve (Curve 2), will exhibit decreased cardiac output at each LVEDV or LVEDP value. However, because the heart has just begun to experience the effects of overload due to the infarction, the myocardial contractility of the entire ventricle is still relatively good, and the cardiac output is still relatively high at low LVEDP or LVEDV. In contrast, a patient who has suffered a heart injury in the past can experience a progressive worsening of cardiac function, as the myocardial layer remodels over time to compensate for increased workload and decreased oxygen availability, as depicted by the lowermost curve (Curve 3) in FIG. 2A As noted above, as the ventricle dilates due to generally higher volumes and pressures during each phase of the cardiac cycle, this can result in progressively decreasing cardiac output. As will be observed from a comparison of Curves 1 and 3, the cardiac output continues to fall as the LVEDP or LVEDV climbs, until eventually the heart fails or the patient dies from a circulation-related illness.

[0119] FIG. 2B A Frank-Starling curve, an alternative formulation of Curve 6, is provided that illustrates the difference between the function of a healthy heart and a heart that is failing. Line 7 up to point 8 illustrates the 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 cardiac output increases. However, for a healthy heart, beyond point 8, an increase in end diastolic volume no longer results in an increase in cardiac output, and continued increases in end diastolic volume will not result in further increases in cardiac output. This phenomenon is shown by the solid, flat line extending beyond point 8. In FIG. 2B The dashed line 9, which extends beyond 8, represents the Frank-Starling curve for a heart failure patient. Dashed line 9 indicates that for a patient with heart failure, further increases in end diastolic volume will not result in a substantially flat cardiac output, but rather a decrease in cardiac output. Thus, increasing the EDV of an HF patient results in a further decrease in SV, which results in a spiral downward in cardiac function, and ultimately death. FIG. 2Breflects a phenomenon known as "diastolic ventricular interaction," which occurs in part due to the structural arrangement of the heart chambers. As discussed, for example, in the article by J. Atherton et al., entitled "Diastolic ventricular interaction in chronic heart failure," Lancet 1997; 349: 1720-24, the pericardium limits the extent to which the ventricles of a failing heart can dilate. Thus, as the right ventricular end-diastolic volume increases, there is necessarily a decrease in the left ventricular end-diastolic volume. As reported in that article, a decrease in right ventricular diastolic filling caused by external lower body suction allows for an increase in left ventricular diastolic filling.

[0120] Applicants understand that the foregoing phenomenon can be advantageously utilized in the context of the present application to improve heart performance. In particular, in the case of heart failure and the presence of pulmonary arterial hypertension, right ventricular congestion due to increased volume overload can push the interventricular septum membrane toward the left ventricular chamber, thereby reducing LV stroke volume and cardiac output. By occluding flow through the SVC, right ventricular pressure and volume can be reduced. This, in turn, will displace the interventricular septum away from the LV chamber, allowing for increased left ventricular stroke volume and enhanced cardiac output. For these reasons, SVC occlusion according to the principles of the present application can advantageously alter diastolic ventricular interaction and enhance cardiac output. In particular, with respect to diastolic heart failure, SVC occlusion according to the principles of the present application can provide a reduction in cardiac filling pressure, increased LV relaxation (tau), increased LV volume, increased unloading effect, reduced LV stiffness, and reduced cardiac strain. Thus, the effect of SVC occlusion of the present application can be visualized as moving the heart toward a more normal state, as shown in the following figure. FIG. 2B The dashed line 9 of the Frank-Starling curve 6 of a heart failure patient shifts toward lower EDV, which effectively moves the heart performance upward and closer to the flat portion of the curve that extends beyond the point 8 of a healthy patient. Thus, the system and method of at least partially intermittent SVC occlusion of the present application for a HF patient improves heart function by moving the patient's heart contractility toward the healthy range of the patient's Frank-Starling curve.

[0121] FIG. 3 A pressure-volume loop of a normal heart is schematically shown, labeled "normal," corresponding to curve 1 in FIG. 2B and a pressure-volume loop of a heart suffering from congestive heart failure, labeled "CHF" ( FIG. 2BThe pressure-volume loop for each beat corresponds to the area enclosed within the curve 3) in FIG. 1. For each loop, the ventricular volume and pressure at the end of diastole correspond to the lower right corner of the loop (point A), while the upper left corner of each loop corresponds to the beginning of systole (point B). The stroke volume for each pressure-volume loop corresponds to the area enclosed within the loop. Thus, the most beneficial range of venous regulation is to decrease the volume and pressure at point A while not causing a negligible decrease in point B, thereby maximizing stroke volume.

[0122] According to one aspect of the present application, the system and method are designed to shift or transform the Starling curve of the patient's heart to the left on the graph of FIG. 2B (or to move the pressure-volume loop in FIG. 3 to the left and downward) after hours, days, weeks, or months. This can be accomplished by intermittently fully or partially occluding the SVC to decrease the volume of blood entering the right ventricle and then having to be pumped through the left ventricle and thus the pressure. Applicant's preliminary animal trials indicate that such intermittent occlusion for several heartbeats decreases the workload and wall stress in the myocardium throughout the heart cycle, decreases myocardial oxygen consumption, and improves contractile function.

[0123] Referring now to FIG. 4A , an exemplary system 30 of the present application is described. The system 30 includes a catheter 31 having a flow restriction element 32 coupled to a controller 33 programmed to intermittently actuate the flow restriction element 32. As discussed below, the system 30 can be configured to bidirectionally transfer information with a conventional computing device 45, such as a smartphone, laptop, smartwatch, or tablet, such as an Apple iPhone 5 or iPad available from Apple Inc., Cupertino, California, on which a dedicated application has been installed to communicate and / or control the controller 33, as desired.

[0124] Preferably, the catheter 31 includes a flexible tube with a distal portion 34 configured for placement in the SVC. The distal portion 34 includes the flow restriction element 32, which, in use, is placed in the superior vena cava 12 of a patient (see FIG. 1) to selectively block blood flow into the right atrium 14. In this embodiment, the flow restriction element 32 illustratively includes a balloon capable of transitioning between a contracted state allowing trans-catheter placement and an expanded deployed state. The flow restriction element 32 is preferably sized and shaped so that it partially or completely occludes blood flow in the SVC in the expanded state. The catheter 31 is coupled at a proximal end 35 to the controller 33, which houses a drive mechanism 36 (e.g., motor, pump) for actuating the flow restriction element 32, a processor 37 programmed to control signals to the drive mechanism 36, and optionally a sensor 42 for monitoring a physiological parameter of the patient, such as heart rate or blood pressure. FIG. 1B ​

[0125] The controller 33 can include an expansive media source 48 (e.g., gas or fluid), and the drive mechanism 36 can transfer the expansive media between the source and the flow restriction element 32 in response to commands from the processor 37. When the flow restriction element 32 is filled with the expansive media, the flow restriction element partially or completely occludes venous blood flow through the SVC; when the expansive media is withdrawn, the flow restriction element 32 deflates to unocclude, thereby permitting blood flow to resume in the SVC. The flow restriction element 32 can be a balloon, preferably including a compliant or semi-compliant material, such as nylon, that permits the degree of inflation of the balloon to be adjusted to achieve a desired degree of partial or complete occlusion of the SVC. Additionally, the catheter 31 provides a failsafe design with the portion external, such that the flow restriction element 32 can only inflate to provide occlusion when the proximal end of the catheter 31 is coupled to the controller 33. Such quick disconnect coupling 40 at the proximal end 35 permits the catheter to be quickly disconnected from the controller 33 for cleaning and / or emergencies.

[0126] The controller 33 preferably also includes a power supply 39 (e.g., a battery) that provides the power needed to operate the processor 37, the drive mechanism 36, and the data transmission circuit 38. The controller 33 can be sized and weighted so that it can be worn in clothing gear under the clothing of the patient, so that the system can be used while the patient is ambulatory or so that the controller 33 can be implanted in the patient. As discussed below, the processor 37 includes a memory 41 for storing computer software to operate the controller 33. The controller 33 can be configured for implantation in the patient at a suitable location, such as subcutaneously in the clavicle. In such an implementation, the implantable controller is configured for bidirectional communication with an external controller, such as a computing device 45 or system-specific device. The external controller can be used to, for example, charge the battery of the implantable controller through a respective inductive coil in or coupled to each controller, and can receive data indicative of sensed parameters resulting from ambulatory activity of the patient, including heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure.

[0127] In one embodiment, the data transmission circuit 38 monitors input from external sensors positioned, for example, on the catheter 31, and provides the signals to the processor 37. The processor 37 is programmed to receive input from the data transmission circuit 38 and adjust the interval that the flow restriction element 32 is maintained in the expanded state, or adjust the degree of occlusion created by the flow restriction element 32. Thus, for example, the catheter 31 can have an optional sensor 42 positioned within the distal portion 34 of the catheter to measure parameters such as heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and central venous pressure. The output of the sensor 42 is relayed to the data transmission circuit 38 of the controller 33, which can pre-process the input signal, such as by sampling and digitizing the output of the sensor 42, before it is supplied to the processor 37. Providing the signal to the processor 37 allows for assessment of the efficacy of the flow restriction element, for example, by displaying the reduced venous pressure during occlusion and during the open period, and can be used by the patient or clinician to determine what degree of occlusion is needed to regulate venous return based on the severity of the congestion in the patient. Additionally, a sensor 43 can be included on the catheter 31 proximate the flow restriction element 32 to measure parameters such as heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and central venous pressure. The sensor 43 can be used to determine the degree of occlusion created by the element 32, for example, by monitoring the pressure drop across the flow restriction element.

[0128] As another example, the catheter 31 can include an electrode 44 for sensing the patient's heart rate. Applicants understand that it can be desirable to adjust the interval of occlusion maintenance of the SVC in response to the patient's ambulatory activity, which would typically be reflected in the patient's hemodynamic status through sensed physiological parameters such as heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and / or central venous pressure. Thus, the electrode 44 can provide a signal to the data transmission circuit 38, which in turn processes the signal for use by the programmed routines executed by the processor 37. For example, if the occlusion maintenance is programmed for a certain time during the initial system setup to reflect the patient at rest, such that the flow restriction element is deployed for 5 seconds and then deflated for two seconds before re-expansion, it can be desirable to reduce the occlusion time interval to 4 seconds or more depending on the patient's level of physical activity, which is detected by changes in heart rate, blood flow rate, blood volume, pressure including cardiac filling pressure and / or central venous pressure above or below a predetermined threshold. Alternatively, the processor 37 can be programmed to maintain partial or complete occlusion in the SVC for a preset number of heartbeats determined at the time of initial implantation of the catheter. Sensor input provided to the data transmission circuit 38 of hemodynamic status, etc., can also be used to adjust the duty cycle of the flow restriction element in response to detected patient activity level. Additionally, the processor 37 can be programmed to maintain partial or complete occlusion in the SVC for a preset number of heartbeats after adjustment of the predetermined occlusion interval.

[0129] Data transmission circuit 38 can also be configured to provide two-way data transmission, for example, by including wireless circuitry to transmit data from controller 33 to an external unit for display, review, or adjustment. For example, the data transmission circuit can include Bluetooth circuitry that enables controller 33 to communicate with a patient's computing device 45. In this way, the controller can send information about the system's operation directly to computing device 45 to display important physiological or system parameters using a suitably configured mobile application. In addition, the patient can review the data displayed on the screen of computing device 45 and determine if it needs to seek medical help to address a malfunction or adjust system parameters. Furthermore, the mobile application resident on computing device 45 can be configured to automatically initiate an alert to a clinician's monitoring service over a cellular telephone network.

[0130] Optionally, data transmission circuit 38 can be configured to synchronize to receive data from other mobile applications on computing device 45 and thus reduce the cost and complexity of the system of the present disclosure. For example, a number of third party vendors, such as Fitbit, Inc. of San Francisco, California, market monitors that measure real-time physiological parameters, such as the Charge HR wristband monitor, which measures physical activity and heart rate. According to one aspect of the present disclosure, data transmission circuit 38 can be programmed to receive input from such third party monitors through wireless communication with computing device 45, and processor 37 can be programmed to control activation of drive mechanism 36 in response to the input. In this implementation, catheter need not include optional sensor 42, sensor 43, or electrodes 44, thereby greatly simplifying the construction of catheter 31 and coupling 40.

[0131] Catheter 31 can include an anchoring member 46 configured to anchor flow restriction element 32 within the SVC. Anchoring member 46 can be collapsible for delivery in a collapsed state and expandable upon release from a delivery device, such as a sheath. Anchoring member 46 can be coupled to catheter proximal or distal to flow restriction element 32 and / or can be coupled to flow restriction element 32. FIG. 4A The system shown in FIG. 1 can effectively shift the patient's heart contraction rate to FIG. 2A within the healthy range of the Frank-Starling curve illustrated in FIG. 2.

[0132] Referring now to FIG. 3, FIG. 4B controller 33 is implanted in the patient at a suitable location. As FIG. 4BAs shown in FIG. 6, external power sources 47 can be configured to charge the power supply 39 (e.g., battery) of the implantable controller. For example, external power sources 47 can charge the power supply 39 transdermally through respective induction coils. The external power sources 47 can be integrated into clothing or a patient-worn clothing apparatus. In particular, the external power sources 47 can be placed in pockets or holders configured to house the external power sources 47. The pockets or holders can be designed to place the external power sources 47 in close proximity to the battery 39 for efficient transdermal charging when the patient wears the clothing or clothing apparatus. More than one external power source 47 can be integrated into the clothing to provide additional power. The one or more external power sources can be permanently integrated into the clothing or clothing apparatus or can be removably engaged with the clothing or clothing apparatus such that each external power source can be individually removed and attached. For example, two external power sources 47 can be integrated into specially designed pockets of a vest 64 as shown in FIG. 6. The vest 64 can include wires 66 incorporated into the vest 64 to permit electrical communication between the two external power sources. FIG. 4B

[0133] The power sources 47 can generate an alert when the available power supply reaches or falls below a certain threshold level. For example, the power sources 47 can have a visual indicator and / or an audible indicator to provide a warning to the patient or caregiver. The visual indicator can be an LED light system or a display embedded in the surface of the power source 47 that visually provides information about the available power supply. The audible indicator can be a speaker embedded in the power source 47 that emits an alert sound when the available power supply reaches a certain threshold. The signal indicating that the available power supply of the power source 47 has reached a certain threshold can also or alternatively be communicated directly to an external device such as the computing device 45 and / or to the controller 33 and then from the controller 33 to an external device such as the computing device 45, which can be programmed to initiate a visual or audio alert. The additional power sources 47 can power the power supply 39 when the main power source is dead to ensure that power can continue to be provided to the power supply 39. The power sources 47 can include a processor with memory for transmitting data transdermally and receiving data from the processor 37. The processor of the power sources 47 can be used to reprogram the processor 37 and / or store information about operating parameters that can later be downloaded by an external device such as the computing device 45.

[0134] Each external power source 47 can be placed in close proximity to a wall outlet or FIG. 4C ​The base charger 65 is in electrical communication with the external power sources 47 to charge the external power sources. The base charger 65 can be in electrical communication with a wall outlet and can be configured to simultaneously charge one or more external power sources 47. To permit the power supply 39 continuous access to power, the external power sources 47 can be periodically disconnected from the vest and charged such that at least one external power source 47 is in electrical communication with the power supply 39 while the other external power sources 47 are being charged in the base charger 65. Also, by enabling the system to interface with commercially available heart rate monitors as well as smart phones and / or tablets, the system provides both reduced cost and reduced complexity.

[0135] Referring now to FIG. 5A and 5B , an exemplary embodiment of a catheter 31'is described, wherein the catheter 31'is configured similar to the catheter 31 of FIG. 4A and FIG. 4B , except that the anchors are modified. As shown in FIG. 5A , when the flow restricting element 32' is in the expanded, fully occluding state, and as shown in FIG. 5B , when the flow restricting element 32' is in the contracted state, the catheter 31'can include radially expanding anchor arms 49. The anchor arms 49 are configured to radially expand, for example upon exposure from a delivery sheath, to contact the inner wall of the superior vena cava 12 and anchor the flow restricting element 32' therein.

[0136] Referring now to FIG. 6 , an optional embodiment is described, wherein the occlusion can comprise a wire basket. The flow restricting element 50 can be formed of a biocompatible material such as nickel titanium or stainless steel, and comprises a plurality of axially or helically extending wires 51 that are biased to expand radially outward when compressed. The flow restricting element 50 preferably includes a biocompatible membrane covering such that it partially or fully occludes blood flow in the SVC in the expanded state. The wires 51 can be coupled at a distal end 52 to a distal end 53 of an actuation wire 54, and attached at a wire proximal end 56 to a ring 55. The ring 55 is disposed to slide over the actuation wire 54 such that the wires 51 expand radially outward when the actuation wire 54 is pulled in the proximal direction against a sheath 57 (see FIG. 5A and 5B ). As shown in FIG. 5B , in response to a force applied to the proximal end of the actuation wire 54 by the drive mechanism 36, the actuation wire 54 is retracted proximally against the sheath 57 of the catheter; thereby causing the flow restricting element 50 to transition to its expanded deployed state. Conversely, when the drive mechanism 36 is deactivated, the spring force exerted by the wires 51 pulls the actuation wire 54 in the proximal direction, thereby enabling the wires 51 to return to their uncompressed state, substantially flat against the actuation wire 54. As noted above, the flow restricting element 50 has a "fail-safe" design such that the flow restricting element reverts to its expanded state when the catheter 31 is decoupled from the drive mechanism 36. FIG. 5AThe image shows a converged / contracted state. In this embodiment, the drive mechanism 36 can be a motor, which can be a linear motor, a rotary motor, an electromagnetic piston, or a wire motor.

[0137] The current limiting element 50 may be configured such that it is biased to a constricted position when the conduit 31 is disconnected from the controller 33, such that the current limiting element 50 can only transition to an expanded state when the conduit is coupled to the controller 33, and the processor signals the drive mechanism 36 to expand the current limiting element.

[0138] Now for reference FIG. 7 The catheter 31 preferably includes at least three lumens 60, 61, and 62. Lumen 60 may serve as an expansion lumen and / or for carrying an actuation line 54 extending between the flow-limiting elements 32 / 50 and the drive mechanism 36 of the controller 33. Lumen 61 allows optional sensors 42, 43, or electrodes to communicate with the data transmission circuitry 38, and optional lumen 62 is used for delivering pharmacological agents (e.g., drugs) to the heart.

[0139] During the procedure, catheter 31, equipped with flow-limiting elements 32 / 50, is inserted into the patient's subclavian vein and guided to the patient's SVC, for example, at a location proximal to the right atrial inlet (see [reference]). FIG. 1A Techniques known in the art can be used to insert and fix the flow-limiting element 32 / 50 at the desired venous location within the patient. Proper positioning of the device can be confirmed using, for example, vascular ultrasound. Alternatively, the flow-limiting element 32 / 50 can be inserted and guided to the SVC via the jugular vein or even a peripheral vein under fluoroscopic or ultrasound guidance.

[0140] Once catheter 31 and flow-limiting elements 32 / 50 are positioned as desired, controller 33 immediately initiates the process of expanding and contracting the occlusion element to intermittently block and restore blood flow in the SVC. The degree to which the flow-limiting element impedes blood flow can be adjusted by regulating the radial expansion of the flow-limiting element, as well as the time interval of occlusion, such as the number of heartbeats. For example, in some embodiments, the flow-limiting element can impede blood flow in the SVC at any point from at least 50% to 100%. The impedance of the blood flow can be confirmed using methods known in the art, such as by measuring a decrease in pressure, a decrease in pressure fluctuations, or visually using ultrasound.

[0141] According to one aspect of the disclosure, the controller 33 includes software stored in the memory 41 that controls the timing and duration of successive expansions and contractions of the flow restriction element 32 / 50. As described above, the programmed routines executed by the processor 37 can be used as an input of the patient's cardiac cycle. For example, in some embodiments, the software can be configured to actuate the flow restriction element 32 / 50 to maintain partial or complete occlusion of the SVC over a number of cardiac cycles, e.g., four or more successive heartbeats of the subject. The controller 33 can accept as an input the output of the electrode 44, which represents the electrocardiogram (ECG) of the patient, through the data transmission circuit 38, or alternatively, can receive such input wirelessly from a third-party heart rate application running on the patient's smartphone, so that the software running on the processor 37 can adjust the occlusion interval and / or degree provided by the system 30 in response to the patient's heart rate. Thus, for example, if the patient is physically active, the occlusion timing or degree created by the flow restriction element can be decreased to permit faster replenishment of oxygenated blood to the patient's upper extremities. Conversely, if the heart rate indicates that the patient is not active, the degree of occlusion of the SVC can be increased to reduce the resting workload on the heart. Alternatively or additionally, the system 30 can accept as an input, through the data transmission circuit 38, values representing the blood pressure of the patient, measured by the optional sensors 42 and 43 or third-party applications and devices such as blood pressure cuffs, so that the controller 33 adjusts the blood flow through the SVC in response to the blood pressure of the patient.

[0142] The controller 33 can be programmed to cause the flow restriction element to expand when a sensed parameter is outside a predetermined range and / or above or below a predetermined threshold. For example, the controller 33 can cause the flow restriction element to expand when the optional sensor 42 and / or 43 senses that the right atrial ("RA") pressure is within a predetermined range of 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg, 20 to 25 mmHg, etc., or above a predetermined threshold of 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg, etc. As another example, the controller 33 can cause the flow restriction element to expand when the optional sensor 42 and / or 43 senses that the mean pulmonary arterial ("PA") pressure is within a predetermined range of 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg, 20 to 25 mmHg, etc., or above a predetermined threshold of 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg, etc. The predetermined ranges and / or predetermined thresholds can be patient-specific, and the controller 33 can be programmed and reprogrammed for individual patients.

[0143] Referring now to Figures 8 to 10, alternative forms of endovenous flow-limiting elements suitable for occluding SVCs are described. As will be apparent to those skilled in the art, although Figures 4 to 6 depict cylindrical flow-limiting elements, other shapes may be used. Additionally, although not illustrated in conjunction with anchoring members in Figures 8 to 10, anchoring members may be included. In each pair of attachments... FIG. 8A , 8B In figures 9A, 9B and 10A, 10B, paired figures depict each current-limiting element in a convergent-contraction state. FIG. 8B , 9A and 10A) and extended deployment state ( FIG. 8A , 9B (and 10B), in the converging contraction state, the flow-limiting element does not significantly impede blood flow, and in the expanding state, the flow-limiting element partially or completely blocks blood flow through the SVC.

[0144] Specifically, reference FIG. 9A and 8B The catheter 70 includes a balloon 71 attached to the distal end 72. The balloon 71 is shown as having a spherical shape.

[0145] Now for reference FIG. 10A and 9B The catheter 80 includes a flow-limiting element 81 comprising a spring-loaded plug 82 formed of a biocompatible material (e.g., beryllium) and having a tapered conical shape. The spring-loaded plug 82 is retracted in a convergent, contracted state within a sheath 83 located at the distal end 84 of the catheter 80. More specifically, the apex of the conical plug 82 is positioned adjacent to the proximal end 85 of the sheath 83. During catheter delivery, the spring-loaded plug 82 is retracted within the sheath 83 in its low-profile state to allow blood flow. To expand the spring-loaded plug 82, a force is applied via an actuation line 86 to withdraw the plug 82 from the sheath 83. As in the previous embodiment, when the proximal force is removed from the proximal end of the actuation line 86, the plug 82 is biased back to the sheath 83, such that the flow-limiting element 81 remains in its convergent, contracted state when disconnected from the controller 33.

[0146] refer to FIG. 9A and 10B The conduit 90 depicts a further alternative embodiment of the sealing device 91, which takes the form of a spring-loaded plug 92. The spring-loaded plug 92 is similar to... FIG. 11 and 9BA spring-loaded plug 82 is disposed within a sheath 93 disposed at the distal end of the catheter 90, and has a tapered conical shape and is loaded within the sheath 93. In response to a distally directed force applied to the proximal end of the catheter 90 by the drive mechanism 36, the spring-loaded plug 92 is pushed out of the distal end of the sheath 94 and expands to occlude the SVC. When the distally directed force is removed, the spring-loaded plug 92 collapses to its collapsed state within the sheath 94, thereby permitting blood to flow through the SVC substantially unimpeded.

[0147] Applicants have observed animal testing that indicates that a method of constructing and operating a system according to the present application provides significant advantages over previously known IVC systems for treating heart failure. A preliminary animal trial is described below on a pig model one week after myocardial infarction.

[0148] Reference is made to FIG. 12 , shows changes in LV pressure and LV volume over multiple consecutive heartbeats in a pig model after complete occlusion of the inferior vena cava (IVC), as proposed in the previously published Sedano patent application. Specifically, the IVC was completely occluded for about 30 seconds, during which the left ventricular end diastolic pressure (corresponding to the lower right corner of the hysteresis loop) and the left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) decreased during each consecutive heartbeat. Upon removal of the IVC occlusion, the LV pressure quickly rose to pre-occlusion levels (i.e., similar to the first half of the pressure and volume traces). Because the IVC occlusion therapy proposed by Sedano reduces systolic pressure, this therapy can result in a decrease in ejection fraction during systole, with potentially dangerous consequences for the patient. In addition, occlusion of the IVC can cause congestion of the renal and hepatic veins, which can cause and exacerbate complications commonly associated with congestive heart failure.

[0149] Reference is made to FIG. 13 to 14 , shows changes in LV pressure and LV volume over multiple consecutive heartbeats in a pig model after partial occlusion of the superior vena cava (SVC), as described according to the principles of the present application. Specifically, the SVC was partially occluded for about 30 seconds, during which the left ventricular end diastolic pressure (corresponding to the lower right corner of the hysteresis loop) decreased, while the left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) remained essentially unchanged during each consecutive heartbeat. Upon removal of the SVC occlusion, the LV pressure quickly rose to pre-occlusion levels (i.e., similar to the first half of the pressure and volume traces). Advantageously, the method of partially occluding the SVC of the present application appears to have little or no effect on ejection fraction during systole of the heart, but reduces wall stress in the ventricle during diastole of the heart. In addition, as discussed in more detail below, occlusion of the SVC will be well tolerated by the patient, will not promote congestion of the renal or hepatic veins, and will not exacerbate complications commonly associated with congestive heart failure, including liver and kidney failure.

[0150] FIG. 15 is a graph showing changes in pressure as a function of left and right ventricular volume, respectively, during superior vena cava (SVC) occlusion and release in a pig treated for heart failure according to the principles of the present application. As shown in the graph, SVC occlusion caused a significant decrease in left ventricular (LV) volume (240 to 220 mL) and LV diastolic pressure (25 to 10 mmHg). SVC occlusion was also associated with a decrease 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 according to the systems and methods described herein decreased biventricular volume and diastolic (filling) pressures without negatively affecting systemic blood pressure (LV systolic pressure). These findings suggest that SVC occlusion has potentially important beneficial effects on biventricular interaction, such that decreasing diastolic filling pressures in both ventricles allows for increased ventricular compliance, thereby improving ventricular filling and causing an increase in stroke volume and cardiac output, which are primary goals in treating heart failure patients.

[0151] FIG. 16 includes graphs showing that superior vena cava (SVC) occlusion according to the principles of the present application improves cardiac function in a subject pig. Each of the graphs shows results for partial inferior vena cava (IVC) occlusion (left side of each graph) versus complete SVC occlusion (right side of each graph). The graphs show measured left ventricular (LV) stroke volume, cardiac output, LV contractility, LV diastolic pressure, LV systolic pressure, and end-systolic volume.

[0152] FIG. 17 is a graph showing that SVC occlusion according to the principles of the present application does not impair systolic blood pressure in three subject pigs. The graph shows complete vena cava occlusion (1 minute) LV end-systolic pressure (mmHg) for complete IVC occlusion (left column of each study) versus complete SVC occlusion (right column of each study). LV end-systolic pressure is less reduced with SVC occlusion compared to IVC occlusion.

[0153] FIG. 18 is a graph showing that SVC occlusion according to the principles of the present application does not impair LV diastolic filling in three subject pigs. The graph shows complete vena cava occlusion (1 minute) LV end-diastolic pressure (mmHg) for complete IVC occlusion (left column of each study) versus complete SVC occlusion (right column of each study). LV end-diastolic pressure is less reduced with SVC occlusion compared to IVC occlusion.

[0154] FIG. 19is a graph showing SVC occlusion improves LV stroke volume according to the principles of the present application in three test pigs. The graph shows complete IVC occlusion (left side of each study) versus complete SVC occlusion (right side of each study) complete vena cava occlusion (1 minute) LV stroke volume (mL / beat). LV stroke volume is increased with SVC occlusion compared to decreased LV stroke volume with IVC occlusion.

[0155] FIG. 20 is a graph showing SVC occlusion improves LV contractility according to the principles of the present application in three test pigs. The graph shows complete IVC occlusion (left side of each study) versus complete SVC occlusion (right side of each study) complete vena cava occlusion (1 minute) LV contractility (mmHg / sec). LV contractility is increased with SVC occlusion compared to decreased LV contractility with IVC occlusion.

[0156] FIG. 20 is four graphs depicting LV total volume and LV pressure with IVC occlusion (upper left), RV total volume and RV pressure with IVC occlusion (upper right), LV total volume and LV pressure with SVC occlusion (lower left), and RV total volume and RV pressure with SVC occlusion (lower right). FIG. 21 illustrates that SVC occlusion provides significant LV and RV diastolic pressure reduction without significant LV systolic pressure reduction compared to IVC occlusion.

[0157] FIG. 21 includes two graphs depicting pulmonary artery pressure and renal vein pressure in a test pig measured for IVC occlusion (left graph) and SVC occlusion (right graph). Line 100 shows pulmonary artery pressure measured for IVC occlusion, while line 102 shows measured renal vein pressure. Line 104 shows pulmonary artery pressure measured for SVC occlusion, while line 106 shows measured renal vein pressure. The maximum renal vein pressure measured for IVC occlusion was 22 mmHg, while the maximum renal vein pressure measured for SVC occlusion was 7 mmHg. FIG. 22 illustrates that SVC occlusion reduces pulmonary artery pressure without increasing renal vein pressure compared to IVC occlusion.

[0158] FIG. 22 is a graph depicting left subclavian vein pressure and renal vein pressure measured in a pig undergoing SVC occlusion according to the principles of the present application. Line 108 shows left subclavian vein pressure measured for SVC occlusion, while line 110 shows measured renal vein pressure. The left subclavian vein pressure change measured during SVC occlusion was 5 to 12 mmHg. FIG. 23A-26C illustrates that proximal left subclavian vein pressure nominally increases during SVC occlusion.

[0159] In FIG. 23A to 23DThe results of additional animal tests conducted on the pig model at various closure phases are shown. Now refer to... FIG. 23A to 23D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the contraction time of a one-minute segment of continuous SVC occlusion in a porcine model were depicted. Specifically, the controller was programmed to cause the current-limiting element to at least partially occlude the SVC for one minute, and then contract, for example, contract for one second. FIG. 24A to 24D The study showed that a one-minute SVC occlusion may not be sufficient to cause a steady-state decrease in ventricular volume after the reduction in time.

[0160] Now for reference FIG. 24A to 24D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the contraction time of a five-minute segment of continuous SVC occlusion in a porcine model were depicted. Specifically, the controller was programmed to cause the current-limiting element to at least partially occlude the SVC for five minutes, and then contract, for example, to contract for one second. FIG. 25A to 25D As shown in the study, due to the five-minute SVC occlusion, the ventricular volume reached a significant steady-state decrease after the time was reduced.

[0161] Now for reference FIG. 25A to 25D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the contraction time of a ten-minute segment of continuous SVC occlusion in a porcine model were depicted. Specifically, the controller was programmed to cause the current-limiting element to at least partially occlude the SVC for ten minutes, and then contract, for example, contract for one second. By comparison... FIG. 24A to 24D and FIG. 26A to 26C In this model, the advantage of 10-minute SVC occlusion over 5-minute SVC occlusion was not significant. Therefore, considering patient safety, 5-minute SVC occlusion was used during the initial clinical study, as shown in the reference below. FIG. 28A The description refers to the Tufts IRB-approved protocol, but the following is about... FIG. 26A to 26C -B describes the ten-minute occlusion in human subjects in more detail.

[0162] Encouraged by animal testing, the applicant conducted preliminary human tests and observed that the method of constructing and operating the SVC occlusion system according to the present invention provides significant benefits. FIG. 26A to 26C Clinical stress changes observed during consecutive five-minute segments of SVC occlusion in three patients enrolled in a Tufts IRB-approved protocol are depicted. Specifically, the three patients underwent five-minute consecutive SVC occlusions, along with acute neurological and cardiac monitoring and a 30-day neurological assessment (Table 1).

[0163] Table 1

[0164]

[0165] If possible FIG. 26A-26C As observed in Table 1, significant changes were observed in pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, and right atrial pressure during the five-minute segment of SVC occlusion, with residual effects after balloon deflation. As a result of this study, all patients experienced hemodynamic benefits due to a decrease in all filling pressures, such as CWP and mean pulmonary artery (PA) pressure. Patients with greater congestion were observed to experience an increase in mean arterial pressure (MAP). The net effect of these hemodynamic changes was a decrease in cardiopulmonary pressure and an increase in systemic pressure perfused with vital organs, including the kidneys.

[0166] Encouraged by the aforementioned preliminary results in pigs and humans, in addition to the two new patients, the applicant conducted further tests on three other patients, who were mentioned above... FIG. 27A-27E The test subjects discussed. Five patients, each with heart failure, underwent the SVC closure system described above. Specifically, the five patients experienced five minutes of continuous SVC closure. The baseline parameters of the five patients are shown in Table 2 below. The third patient had the lowest New York Heart Association (NYHA) functional class of 2. The results from the third patient indicate that the application of the SVC closure system is preferably used for patients with heart failure and an NYHA functional class of 3 or higher.

[0167] Table 2

[0168]

[0169]

[0170] FIG. 27A-27D The graph illustrates the changes in systolic blood pressure (SP), diastolic blood pressure (DP), mean arterial pressure (MAP), mean pulmonary artery (MPA) pressure, and pulmonary capillary wedge pressure (PCWP) for each of the five patients measured from baseline during and after occlusion. FIG. 27E The figure shows the minute-by-minute changes in systolic (SP), diastolic (DP), mean arterial pressure (MAP), and mean pulmonary artery (MPA) pressure during the five-minute occlusion period. FIG. 27A The results show the changes in pulmonary capillary wedge pressure (PCWP) at five minutes after occlusion and after occlusion.

[0171] exist FIG. 27A The diagram illustrates the changes in systolic blood pressure. For example... FIG. 27BThe data shows that patients 1, 2, and 5 generally experienced an increase in SP during the occlusion period, while patients 3 and 4 generally experienced a decrease in systolic blood pressure. FIG. 27B The diagram illustrates the changes in diastolic blood pressure. For example... FIG. 27C The results showed that diastolic blood pressure generally increased in patients 1, 2, and 5 during SVC occlusion, and generally decreased in patients 3 and 4.

[0172] exist FIG. 27C The diagram illustrates the changes in mean arterial pressure. (For example...) FIG. 27D The results showed that mean arterial pressure generally increased in patients 1, 2, and 5 during SVC occlusion, and generally decreased in patients 3 and 4. FIG. 27D The diagram illustrates the changes in mean pulmonary artery pressure. (For example...) FIG. 27E As shown, it should be noted that although there was no data point for a fourth patient at the fourth minute, the mean pulmonary artery pressure decreased for each patient during SVC closure. FIG. 27E The graph illustrates the changes in pulmonary capillary wedge pressure (PCWP) at five minutes and after release. FIG. 26A-26C The study showed that the pulmonary capillary wedge pressure decreased in all patients five minutes after SVC occlusion, indicating a decrease in filling pressure for each patient during occlusion.

[0173] For example, regarding FIG. 27A-27E The observations made in the study discussed FIG. 26A-26C The study, illustrated in the diagram, showed that all five patients benefited hemodynamically due to a decrease in filling pressures such as capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure, and further as described above regarding... FIG. 28A-28B In the studies discussed, patients with more congestion generally experienced an increase in mean arterial pressure (MAP). Furthermore, in many cases, at least some patients experienced residual effects after occluder release.

[0174] Now for reference FIG. 25A-25D , and the above about FIG. 28A Similar to the studies discussed, the applicant also investigated the effects of prolonged SVC occlusion on human subjects. Specifically, the controller was programmed to at least partially occlude the SVC with the SVC flow-limiting element for ten minutes. Prior to the ten-minute occlusion, the SVC was occluded for a five-minute period, followed by a five-minute rest period. Changes in mean pulmonary artery pressure and mean arterial pressure were measured every minute from the baseline before occlusion (i.e., after the five-minute rest period) and after venting. FIG. 28AAs shown in FIG. B, the effect observed during the five minute occlusion persisted throughout the ten minute occlusion, with no attrition of the "cardiopulmonary unloading" effect.

[0175] FIG. 28A Changes in mean pulmonary arterial pressure are illustrated in FIG. C. As shown in FIG. 28B , mean pulmonary arterial pressure decreased throughout the occlusion, and reached its lowest level even during the last two minutes of occlusion. FIG. 28B Changes in mean arterial pressure during occlusion are illustrated in FIG. D. As shown in FIG. 29 , mean arterial pressure generally decreased during the occlusion, although it fluctuated, rising above baseline measurements in the first minute and then again in the fourth and fifth minutes.

[0176] Referring now to FIG. 29 , Applicants also conducted broader testing involving the use of the system and method of the present application during successive occlusions, which resulted in the containment or reversal of further myocardial remodeling and deterioration. Specifically, adult male pigs underwent a heart attack by occluding the left anterior descending artery (LAD) for 120 minutes, and then the occluded artery was reopened. A repetitive cycle of SVC occlusion was then performed, occluding the SVC for 5 minutes, and then allowing the occlusion device to deflate for 30 minutes. This repetitive cycle was repeated and performed for 18 hours. Cardiac output was measured after each cycle of SVC occlusion. FIG. 29 Results of the repetitive cycle of SVC occlusion are illustrated in FIG. E.

[0177] As shown in FIG. 30 , cardiac output was at its lowest point after the LAD infarction, but before the treatment of the SVC occlusion. One hour after treatment, cardiac output had returned to baseline levels. Cardiac output gradually increased from one hour of treatment to eighteen hours of treatment, reaching a maximum cardiac output at the eighteenth hour. These findings demonstrate for the first time that, after acute cardiac injury, mechanically reducing cardiac pressure and volume (i.e., unloading) by intermittently occluding the SVC and then stopping the occlusion (i.e., unloading) can condition the myocardium, allowing periods of exercise and rest. In this way, the repetitive cycle is analogous to interval training high intensity exercise (e.g., sprinting), followed by rest. The repetitive cycle can strengthen the heart, and improve cardiac output and function. Although the ratio of occlusion to rest was 10:1 (open 5 minutes, closed 30 seconds), it should be understood that other ratios would yield beneficial results. For example, a ratio of occlusion 5-20 minutes to rest 10-100 seconds can be beneficial. It should also be understood that occluding the SVC for up to 95% of an hour can be beneficial. Thus, the SVC occlusion system described herein can optionally or additionally be used post-infarction to treat cardiac injury from the infarction to enhance recovery through myocardial unloading.

[0178] As mentioned above, the SVC occlusion systems described herein can optionally or additionally be used to treat pulmonary hypertension, as occlusion of the SVC can result in a decrease in pulmonary artery pressure. While heart failure is a common cause of pulmonary hypertension, pulmonary hypertension can be caused by primary lung disease. It is to be understood that the SVC occlusion systems can be used to treat pulmonary hypertension regardless of whether the cause of the pulmonary hypertension is heart failure.

[0179] Referring now to FIG. 30 , the Applicant observed that implantation of the SVC occlusion system in five patients with pulmonary hypertension due to heart failure resulted in a significant decrease in pulmonary artery systolic pressure (PASP). The patients received five minutes of SVC occlusion to mechanically decrease cardiac pressure and volume (i.e., unloading). As shown in FIG. 26B , the SVC occlusion resulted in a significant decrease in PASP to below moderate pulmonary hypertension levels, which is defined as an increase in PASP to above 50 mmHg. Thus, the SVC occlusion systems described herein can be implanted to treat pulmonary hypertension. As discussed above with respect to FIG. 27D and FIG. 2A , the Applicant also observed that implantation of the SVC occlusion system resulted in a decrease in mean pulmonary artery pressure for each patient.

[0180] The benefits observed in the foregoing animal and human testing suggest that continuous SVC occlusion can be used to treat any cardiac injury, including but not limited to acute cardiac injury due to heart attack, myocarditis, valvular dysfunction, volume overload, or congestive heart failure, as well as many other acute or chronic cardiac injuries. In one example, the SVC occlusion systems described herein can be used emergently, for example in an emergency room setting, to arrest or reverse the heart failure system, thereby shifting the Frank-Starling curve illustrated in FIG. 31 toward line 7, which represents a healthy patient. In this manner, the patient will see an immediate improvement in cardiac performance, with further sustained improvement in myocardial function throughout the course of treatment. To extend the effects of the system, the SVC occlusion system can be implanted within the patient for long-term use. Since the SVC occlusion systems described herein can be implanted or worn continuously by the patient and in an ambulatory state, rather than being confined to a bed, the patient can receive the benefits of the system for a much longer period of time compared to acute care.

[0181] FIG. 32 is a predictive example of how SVC occlusion according to the principles of the present invention is expected to change the disease progression. For example, primary benefits include better patient hemodynamics, faster recovery, and a reduction in length of stay (LOS) for in-patients. Over time, SVC occlusion can significantly slow disease progression.

[0182] Now for reference FIG. 33 The diagram illustrates the optional flow-limiting elements. One undesirable effect of SVC occlusion is increased venous blood pressure upstream of the occlusion device. High cephalic venous pressure is well-known to cause various undesirable effects. To reduce the risk of excessive pressure buildup upstream of the flow-limiting element, a release valve can be integrated into the flow-limiting element, such as... FIG. 32 As shown, this allows fluid to flow from the SVC to the right atrium. The release valve can be unidirectional, allowing blood to flow only in the direction of the right atrium. The release valve is preferably configured to open when the pressure in the SVC is between 30 and 60 mmHg. However, it should be understood that the release valve can be designed and configured to open at other pressures in the SVC.

[0183] FIG. 4A-4B The current-limiting element shown in the diagram can be used with FIG. 32 Similar systems illustrated in the diagram are used together. For example... FIG. 33 As shown, the flow-limiting element can be a cylindrical flow-limiting element 112. The cylindrical flow-limiting element 112 may include a cylindrical balloon 113, which can be inflated and deflated by delivering fluid from a catheter to the cylindrical balloon 113. The size of the flow-limiting element 112 can be set and configured to fit within the SVC and conform to the contours of the inner wall of the SVC. The flow-limiting element 112 can be delivered to the SVC via a catheter. The cylindrical balloon 113 can be introduced into the SVC in a deflated configuration. Upon reaching the SVC, the cylindrical balloon 113 can inflate to impede or restrict blood flow within the SVC.

[0184] When the cylindrical balloon 113 inflates, it defines an inner lumen 114. When the release valve 115 opens and the cylindrical balloon 113 inflates, blood can flow through it. The inner lumen 114 can extend from one end of the cylindrical balloon 113 to the other. Although the inner lumen 114 can always have a consistent cylindrical shape, it should be understood that both the size and shape of the cylindrical balloon 113 and the inner lumen 114 can vary. Furthermore, the inner lumen 114 does not need to be aligned with the center of the balloon and can even be non-cylindrical.

[0185] Now for reference FIG. 33 This shows a cross-sectional view of the cylindrical current-limiting element 112. (See image.) FIG. 33As shown in the center, the release valve 115 can be coupled to the inner wall of the cylindrical balloon 113 within the central lumen 114. The release valve 115 can include a single flow obstruction element or multiple flow obstruction elements (e.g., multiple flexible leaflets) that work in concert to obstruct blood flow through the central lumen 114. The release valve 115 can be coupled to the center of the cylindrical flow restriction element 112, or can optionally be positioned closer to or at the upstream or downstream end of the cylindrical flow restriction element 112. For example, the release valve 115 can be positioned at the upstream end of the cylindrical flow restriction element 112 that is furthest from the patient's right atrium. This configuration can avoid blood pooling or blood column within the central lumen 114, which can occur when the release valve 115 is positioned in the center or downstream region of the central lumen 114.

[0186] FIG. 34A The release valve 115 in the closed position, illustrated in the center, can be designed to open at a certain pressure. For example, the release valve 115 can be designed to open at a pressure between 30-40 mmHg. However, it should be understood that other pressures can be desirable. Below the pressure at which the release valve 115 is designed to open, the release valve 115 can obstruct fluid flow through the central lumen 114. Above the pressure at which the release valve 115 is designed to open, the release valve 115 can allow blood to pass through the inner lumen 114, thereby reducing the jugular venous pressure.

[0187] The release valve 115 can 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 release valve 115 can depend solely on the material and design of the valve (i.e., elasticity, rigidity, thickness), and / or can be dictated by mechanical, electrical, and / or magnetic features. The threshold at which the valve allows fluid flow can be predetermined by the valve design and / or can be mechanically adjusted.

[0188] Referring now to FIG. 34A and 34B two different release valve designs are shown within the inner lumen 114 of the cylindrical flow restriction element 112. FIG. 38AThe binary relief valve 116 shown remains substantially closed until it rapidly transitions to a substantially open position when a given force is applied. The force required to transition the relief valve 116 from the closed to the open position is preferably between 30-60 mmHg, but it should be understood that this pressure can be any pressure. To achieve the binary (i.e., on / off) function, the binary relief valve may include a cutout portion designed to open (give-way) in response to a given force. Upon opening and allowing fluid to pass through to release pressure, the elasticity or other mechanical properties of the material may cause the binary relief valve 116 to spring back to the closed position. It should be understood that this binary function can be achieved by using a variety of other designs and / or by incorporating other materials. For example, FIG. 34B The release valve 132 in -B can also achieve binary functionality.

[0189] like FIG. 35 As shown, the progressive release valve 117 is designed to open gradually with increasing pressure. This function can be achieved, for example, using valve leaflets with a constant thickness or a gradually thinning cross-section as the leaflets move from the inner wall of the cylindrical balloon 113 toward the center of the lumen 114. However, it should be understood that any valve design that gradually allows increased fluid flow in response to increasing pressure can be used as a progressive release valve.

[0190] Now for reference FIG. 36A The image shows a top view of the cylindrical flow-limiting element 112. As long as the pressure remains below a certain threshold, the release valve 115, shown here in the closed position, prevents flow through the lumen of the cylindrical balloon 113. Although a release valve design with four flexible leaflets or flaps is depicted, any release valve design that can be coupled within the lumen 114 of the cylindrical balloon 113, including valves with fewer / more leaflets, can be used.

[0191] Now for reference FIG. 36A and 36B The image shows a top view of the cylindrical current-limiting element 112. FIG. 34A The diagram illustrates the binary release valve 116 in the open position, which is also shown in... FIG. 36B middle. FIG. 34B The diagram illustrates the progressive release valve 117 in the partially open position, which is also shown in... FIG. 37A As discussed above, the dual-release valve 116 is designed to open to a substantially open position when its set pressure is reached. On the other hand, the progressive-release valve 117 is designed to gradually open as the pressure increases above a certain threshold.

[0192] Now for reference FIG. 38Aand 37B It can be desirable to place a stent 118 around the cylindrical balloon 113. For example, the stent 118 can be used as both a receiver and transmitter of electrical signals. Such uses include, but are not limited to, use as an ECG lead, transmitting signals related to autonomic activity, and receiving neuromodulation signals. The stent 118 can be self-expanding and can be made of an electrically conductive material. The stent 118 can be integrated into the cylindrical flow restriction element 112 and / or can be removably coupled to the cylindrical flow restriction element 112.

[0193] Reference is now made to FIG. 38A and 38B , illustrating a cylindrical flow restriction element 130. As shown in these figures, the cylindrical flow restriction element 130 includes a balloon occluder 131 and a release valve 132, both integrated in a stent 118. The release valve 132 and the balloon occluder 131 are positioned adjacent to each other within the stent 118. FIG. 38B depicts the cylindrical flow restriction element 130 in its expanded position, occluding flow within the SVC. FIG. 38B depicts the occlusion device in its contracted position, allowing flow through the SVC. As FIG. 39A illustrates, the balloon occluder 131 can be coupled to the release valve 132 and can contract towards the release valve 132 when contracted. The release valve 132 can be hinged to the stent 118 and can open to allow blood flow when a certain pressure is reached within the SVC. The release valve 132 can be constructed using any of the techniques, designs, and materials disclosed above with respect to release valves.

[0194] Reference is now made to FIG. 39B and 39B , illustrating a cylindrical flow restriction element 133. As shown in these figures, the cylindrical flow restriction element 133 includes a cylindrical balloon occluder 134 and a release valve 135, both integrated in a stent 118. The cylindrical balloon occluder 134 can be expanded to conform to the shape of the stent 118. As shown in FIG. 39A , the cylindrical balloon occluder 134 can have a portion along an outer surface coupled to an outer surface of the stent 118. The release valve 135 can be coupled to the cylindrical balloon occluder 134. The cylindrical balloon occluder 134 can define an inner lumen 136 through which blood can pass if the release valve 135 is open, when expanded.

[0195] FIG. 39BA cylindrical flow restriction element 133 is depicted with a cylindrical balloon occluder 134 in an inflated configuration. When inflated, the cylindrical balloon occluder 134 restricts flow within the SVC. When the cylindrical balloon occluder 134 is inflated, the release valve 135 can open as needed to release any overpressure in the SVC. FIG. 40A A cylindrical flow restriction element 133 is depicted in a deflated configuration. When deflated, the cylindrical flow restriction element 133 allows flow through the SVC. In the deflated configuration, the cylindrical balloon occluder 134 is reduced in size and moves towards the portion of the stent wall that it is coupled with. Similarly, when the cylindrical flow restriction element 133 is in the deflated configuration, the release valve 135 moves towards the stent 118. The cylindrical balloon occluder 134, which has a reduced size when deflated, allows blood to flow around the deflated balloon occluder 134 through the stent 118.

[0196] Referring now to FIG. 32-3 and 40B , a cylindrical flow restriction element 137 is depicted. The cylindrical flow restriction element 137 includes a stent 118 and a release valve 138. Unlike the occlusion device depicted in FIG. 40B 9, the cylindrical flow restriction element 137 does not include a balloon. Instead, the release valve 138 can be directly coupled to the stent 118, as shown in FIG. 32-3 . The stent 118 can be an expandable stent and can be anchored to the inner wall of the SVC. The release valve 138 can take the form of, and have similar features to, any of the release valves discussed above with respect to FIG. 41 9. The cylindrical flow restriction element 137 can completely eliminate flow in the SVC until a certain threshold pressure is reached in the SVC, at which point the release valve 138 can open to allow flow from the SVC to the right atrium.

[0197] Referring now to FIG. 32 , coupling the cylindrical flow restriction element 112 in FIG. 41 to a filter 126 is depicted. The filter 126 can be placed downstream of the cylindrical flow restriction element 112. When the release valve 115 is closed, blood can accumulate in the central lumen 114 of the cylindrical balloon 113, which results in a stagnant blood column, leading to thrombus formation. When the release valve 115 opens, the thrombus can be released into the right atrium, which can lead to serious problems, and even death. The filter 126 can be directly supported by the catheter, or by structural features of the cylindrical flow restriction element 112, such as the cylindrical balloon 113, the release valve 115, or the stent 118 (if applicable), and can be used to capture thrombus. For example, the filter 126 can be coupled to the cylindrical balloon 113 at the downstream end of the cylindrical flow restriction element 112, as shown in FIG. 42AThe filter 126 can be integrated into any of the flow limiting elements described herein. It is understood that the filter 126 can be integrated into any of the flow limiting elements described herein.

[0198] To determine whether the SVC is completely occluded or to what extent the SVC is occluded, traditional methods can be employed that include injecting a contrast agent into the patient and observing the movement of the contrast agent under fluoroscopy. Alternatively, a pressure sensor can be positioned relative to the occlusion balloon as discussed herein and the pressure waveform can be analyzed to determine whether the SVC is occluded. For example, the CardioMEMS® HF System pressure sensor can be obtained from Abbott, St. Paul, Minnesota. The pressure sensor can be in wireless communication with, for example, an implanted controller. The pressure waveform can also be analyzed to determine the patient's filling pressures, diastolic conditions, and / or other heart conditions or indications. For example, the waveform can be analyzed to detect a pronounced 'C-V' wave, which is indicative of tricuspid regurgitation due to volume overload. In another example, the waveform can detect an 'A' wave, which is suggestive of complete heart block, ventricular tachycardia (VT), or pulmonary arterial hypertension. The systems described herein can be used as a diagnostic monitoring tool by analyzing the waveform and can respond accordingly using the SVC occlusion techniques described herein. TM HF System pressure sensor can be obtained from Abbott, St. Paul, Minnesota. The pressure sensor can be in wireless communication with, for example, an implanted controller. The pressure waveform can also be analyzed to determine the patient's filling pressures, diastolic conditions, and / or other heart conditions or indications. For example, the waveform can be analyzed to detect a pronounced 'C-V' wave, which is indicative of tricuspid regurgitation due to volume overload. In another example, the waveform can detect an 'A' wave, which is suggestive of complete heart block, ventricular tachycardia (VT), or pulmonary arterial hypertension. The systems described herein can be used as a diagnostic monitoring tool by analyzing the waveform and can respond accordingly using the SVC occlusion techniques described herein.

[0199] FIG. 42A A pressure sensor 140 that can generate a pressure waveform is illustrated. The pressure sensor 140 can be incorporated into the catheter 31 and can be disposed at a location proximate to the occlusion balloon to provide a pressure measurement indicative of the jugular venous pressure (JVP). The pressure sensor 156 can optionally be incorporated into the catheter 31 distal of the occlusion balloon. FIG. 42B A user of the system illustrated in FIG. 1 can monitor the waveform readings from the pressure sensor 140 and determine when the waveform changes from phasic to non-phasic. When the occlusion balloon is deflated, the pressure waveform will change phase with the heartbeat, as illustrated in curve 141 in FIG. 1. When the occlusion balloon is inflated, then the pressure waveform tends to flatten out. In this way, it can be determined whether the SVC is occluded without the need to inject a contrast agent and without the patient being in a cathlab or under X-ray. Likewise, the pressure waveform can be used to determine when to actuate the flow limiting element and when to stop actuation of the flow limiting element. FIG. 4A

[0200] Another alternative method for determining SVC occlusion using X-ray / fluoroscopy is to use two pressure sensors on opposite sides of the occlusion device. For example, the CardioMEMS® HF System pressure sensor discussed above can be used on one side of the occlusion device and a second pressure sensor can be used on the other side of the occlusion device. The pressure sensors can be used to determine whether the SVC is occluded by comparing the pressure waveforms from the two pressure sensors. For example, if the pressure waveforms are the same, then the SVC is occluded. If the pressure waveforms are different, then the SVC is not occluded. FIG. 4A A system with a catheter 31 is illustrated that includes a flow limiting element 32, a sensor 42, and a sensor 43. As discussed above, the sensor 42 can be a pressure sensor and the sensor 43 can be a flow sensor. The system can be used to determine whether the SVC is occluded by analyzing the pressure waveform from the pressure sensor 42 and the flow waveform from the flow sensor 43. For example, if the pressure waveform is the same as the flow waveform, then the SVC is occluded. If the pressure waveform is different than the flow waveform, then the SVC is not occluded. FIG. 4A ​As shown in FIG. 6, sensor 42 is positioned distal to flow restriction element 32, while sensor 43 is positioned proximal to flow restriction element 32. Sensors 42 and 43 can be pressure sensors, and as explained above, can be used to determine the degree of occlusion caused by flow restriction element 32 by, for example, monitoring the pressure differential across flow restriction element 32. The pressure differential value can be indicative of the amount or degree of occlusion. Likewise, the pressure differential can be used to determine when to actuate the flow restriction element and when to stop actuation of the flow restriction element.

[0201] While FIG. 43A One arrangement of sensors is illustrated, but it should be understood that other arrangements of sensors can be used to obtain relevant information. As FIG. 43A As shown in FIG. 6, an optional sensor arrangement includes a catheter 31 that can be introduced into the vasculature of a patient via a delivery device such as introducer sheath 144. Catheter 31 preferably extends into the SVC, through the right atrium into the heart, extends into the right ventricle, and through the pulmonary valve into the pulmonary artery. Sensors 145, 146, and 147 can be positioned along catheter 31 such that sensor 145 is positioned within flow restriction element 32 to measure the pressure within flow restriction element 32 (i.e., balloon pressure), sensor 146 is positioned along catheter 31 distal to flow restriction element 32 and within the SVC to measure the SVC or right atrial 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 the pulmonary artery pressure. To measure the pressure above or near flow restriction element 32, sensor 148 can be placed directly on the distal end of sheath 144 or otherwise incorporated into the distal end of sheath 144 at which introducer sheath 144 enters the SVC. The pressure measured by sensor 148 is indicative of the JVP. Catheter 31 can include multiple lumens that serve as inflation lumens, actuation lumens between the controller and flow restriction element 32 and / or sensors 145, 146, and 147, and / or for electrical communication. Introducer sheath 144 can also include a lumen for electrical communication between sensor 148 and the controller.

[0202] Referring FIG. 43A and 44, a sensor can be used to detect contact of the flow restriction element with the SVC wall. In particular, sensor 233 can optionally be disposed on the outside of the flow restriction element (e.g., on the outside of an inflatable balloon). Sensor 233 can generate a signal or signal change when the flow restriction element is in contact with the SVC wall. For example, sensor 233 can be a pressure sensor and / or a conductivity sensor that detects contact with the SVC wall. Alternatively, a sensor can optionally be positioned within the flow restriction element to detect contact with the SVC wall. For example, sensor 145 can be positioned within the flow restriction element. Sensor 145 can be a pressure sensor and can detect a change in pressure within the flow restriction element indicative of contact with the SVC wall. In yet another example, electrodes can optionally be positioned proximally and distally of the flow restriction element, as shown in FIG. 43B and 44 For example, sensors 148 and 146 can be electrodes for sensing an electrical parameter such as conductance, which can be measured continuously as the flow restriction element is actuated. A significant change in the electrical parameter can indicate that the SVC is completely occluded by the flow restriction element contacting the SVC wall. It will be appreciated that any combination of sensors 233, 145, 146, 148, and / or any other sensor described herein can be used.

[0203] Referring now to FIG. 43C , the SVC occlusion system can optionally include sensors 234 and 235, which can be disposed on catheter 31, which can be disposed within a delivery device such as introducer sheath 144, and / or sensor 236, which can be disposed on flow restriction element 32. Sensor 234 can be disposed proximally of the flow restriction element, and sensor 235 can be disposed distally of the flow restriction element. Sensor 236 can be disposed on the outside of the flow restriction element such that when the flow restriction element is fully occluded, sensor 236 is in contact with the SVC wall. Alternatively, sensor 236 can be printed on the flow restriction element. Sensors 234, 235, and 236 can measure admittance, impedance, and conductance to determine the degree of occlusion. For example, sensor 236 can indicate that the flow restriction element is contacting the SVC wall based on a change in an electrical parameter detected when flow restriction element 32 is in contact with the SVC wall. In addition, sensors 234 and 235 can measure impedance or conductance to determine whether blood is flowing through the SVC. For example, impedance can increase when flow restriction element 32 is inflated and thus occludes the SVC, and impedance can decrease when flow restriction element 32 is deflated and thus does not occlude the SVC. Thus, a change in impedance can indicate that the SVC is occluded. These two measurements can then be used to determine whether the flow restriction element is fully occluding the SVC.

[0204] The sensor 236 can also be used to determine the diameter of the left ventricle when measuring a pressure-volume loop in the heart. It can be appreciated that the SVC occlusion system can include the sensor 236 in addition to the sensors 234 and 235, or can include only the sensor 236 or the sensors 234 and 235.

[0205] Referring now to FIG. 4A , the SVC occlusion system can optionally include sensors 237 and 238 that can be used to determine whether the flow restriction element is occluding the SVC. Similar to the embodiment shown in FIG. 43D , the sensor 237 can be disposed on the catheter 31 proximal to the flow restriction element 32 and the sensor 238 can be disposed on the catheter 31 distal to the flow restriction element 32. The catheter 31 can be introduced into the vasculature of a patient via the introducer sheath 144. The sensors 237 and 238 can be pressure sensors or optical sensors. For example, the sensors 237 and 238 can each continuously measure the pressure proximal and distal to the flow restriction element and generate first and second signals indicative of the pressure. The difference between the pressure signals proximal and distal to the flow restriction element can be indicative of the degree of occlusion of the SVC. Alternatively, the sensors 237 and 238 can together form an optical sensor, with one sensor functioning as a light source and the other sensor functioning as a light receiver and / or detector. For example, the sensor 237 or 238 can detect light at a frequency that is transmittable through blood but occluded by the flow restriction element. Thus, a reduction in detected light can indicate that the SVC is partially or completely occluded.

[0206] Referring now to FIG. 43E , the SVC occlusion system can optionally include a pressure switch 239. The pressure switch 239 can be disposed proximal or distal to the flow restriction element and can be connected to one or more lumens 240. Alternatively, the pressure switch 239 can be disposed within the flow restriction element 32. The lumens 240 can be in fluid communication with the pressure switch 239 and can further include an open end disposed proximal to the flow restriction element and another open end disposed distal to the flow restriction element. The lumens 240 can extend through the flow restriction element 32 and / or can be positioned along the catheter 31, which can be disposed within a delivery device such as the introducer sheath 144. The pressure switch 239 can generate a signal when a predetermined pressure differential is reached, which can indicate that the SVC is occluded. For example, the pressure switch 239 can determine the pressure differential between the open end of the lumens 240 proximal to the flow restriction element 32 and the open end of the lumens 240 distal to the flow restriction element 32.

[0207] Referring now to FIG. 43FThe SVC occlusion system can optionally include a stretch meter 246. The stretch meter 246 can be a stretch meter, a stress meter, a strain meter, and / or any other meter or sensor that generates a signal indicative of the stress, strain, or stretch of the material. The stretch meter 246 can be disposed only on the catheter 31, which can be disposed within the introducer sheath 144; or can extend over a portion of the catheter 31 and over a portion of the flow restriction element 32. The strain meter 246 can be configured to measure small changes in force, stress, strain, stretch of the material. When the flow restriction element expands to fully occlude the SVC, the flow restriction element and the catheter proximal to the flow restriction element will be pulled in the proximal direction. Detecting a positive change in force or pressure in the proximal direction can indicate that the SVC is fully occluded.

[0208] Referring now to FIG. 44 The SVC occlusion system can optionally include a sensor 247, which can be an accelerometer for detecting changes in motion. The sensor 247 can be disposed within the flow restriction element 32 or proximal to the flow restriction element 32 on the catheter 31, which can be disposed within the introducer sheath 144. When the flow restriction element expands to fully occlude the SVC, the flow restriction element and the catheter proximal to the flow restriction element can remain in a relatively stable position compared to the flow restriction element that is not expanded. Detecting no motion or a decrease in motion can indicate that the SVC is fully occluded.

[0209] Referring now to FIG. 44 Yet another alternative embodiment is described that includes an introducer sheath 144. FIG. 43A The embodiment illustrated in FIG. 43A is similar to the embodiment in FIG. 43A , except that the flow restriction element 32 and sensors 145 and 146 are also incorporated into the introducer sheath 144. Similar to the device illustrated in FIG. 44Similar to the device of FIG. 1, catheter 31 can be introduced via introducer sheath 144 and extend through the right atrium and into the pulmonary artery. Sensor 147 is preferably disposed at the distal end of catheter 31 such that it is located within the pulmonary artery and measures pulmonary artery pressure. Introducer sheath 144 can include a plurality of lumens that 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 148. Catheter 31 can also include a lumen for electrical communication between sensor 147 and the controller.

[0210] In the embodiment of FIG. 2, flow limiting element 32 can be selectively inflated and deflated independent of the presence of catheter 31. Because flow limiting element 32 and sensors 145, 146, and 148 are disposed on introducer sheath 144, therapeutic treatment involving inflation and deflation of flow limiting element 32 to selectively occlude the SVC can be accomplished without the introduction of catheter 31. Furthermore, sensors 148 and 146 can be used to determine the pressure differential across flow limiting element 32, whether or not catheter 31 is deployed. FIG. 45 In the embodiment of FIG. 3, flow limiting element 32 can be selectively inflated and deflated independent of the presence of catheter 31. Because flow limiting element 32 and sensors 145, 146, and 148 are disposed on introducer sheath 144, therapeutic treatment involving inflation and deflation of flow limiting element 32 to selectively occlude the SVC can be accomplished without the introduction of catheter 31. Furthermore, sensors 148 and 146 can be used to determine the pressure differential across flow limiting element 32, whether or not catheter 31 is deployed.

[0211] FIG. 49 Now referring to FIG. 4, yet another embodiment of an SVC occlusion system constructed in accordance with the principles of the present application is described. Catheter 31 preferably includes two occlusion balloons - an azygos vein occlusion balloon 142 and an SVC occlusion balloon 143. Sensors 129, 139, and 149 can also be disposed on catheter 31 such that sensor 129 is disposed proximate azygos vein occlusion balloon 142 to measure pressure distal of azygos vein occlusion balloon 142, sensor 139 is disposed between azygos vein occlusion balloon 142 and SVC occlusion balloon 143 to measure pressure between azygos vein occlusion balloon 142 and SVC occlusion balloon 143, and sensor 149 is disposed distal of SVC occlusion balloon 143 to measure pressure distal of SVC occlusion balloon. Moreover, sensor 145 is positioned within SVC occlusion balloon 143 to measure 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 pressure within azygos vein occlusion balloon 142 (i.e., azygos vein occlusion balloon pressure). Furthermore, pressure differentials across azygos vein occlusion balloon 142 and SVC occlusion balloon 143 can be determined using sensors 129 and 139, and 139 and 149, respectively. The pressure differential values can be indicative of the amount or degree of occlusion.

[0212] ​The azygos vein 16 drains the posterior portion of the thoracic cavity into the SVC. When the SVC is obstructed, the azygos vein can provide an alternative pathway to the right atrium, thereby naturally shunting blood flow from the occluded SVC back to the right atrium. Specifically, if the SVC is occluded below the origin of the azygos vein, the pressure build-up above the portion of the SVC that is occluded can cause a percentage of venous blood to move retrograde through the azygos vein into the thoracic cavity. The azygos vein occlusion balloon 142 can be positioned in the SVC adjacent to the azygos vein such that inflation of the azygos vein occlusion balloon 142 restricts or prevents blood flow from the SVC into the azygos vein. The SVC occlusion balloon 143 can be positioned below the azygos vein, distal to the azygos vein occlusion balloon 142, such that inflation of the SVC occlusion balloon 143 occludes the SVC but allows blood flow into the azygos vein. The catheter 31 can include multiple lumens that are used as inflation and / or actuation lumens between the controller and the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143.

[0213] The azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 can be selectively and independently inflated and deflated. For example, the azygos vein occlusion balloon 142 can be deflated while the SVC occlusion balloon 143 is inflated; the azygos vein occlusion balloon 142 can be inflated while the SVC occlusion balloon 143 is deflated; or both balloons can be inflated or deflated simultaneously. The azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 can also be inflated completely or partially, depending on how much flow back to the right atrium is desired.

[0214] When the SVC occlusion balloon 143 is inflated and the azygos vein occlusion balloon 142 is deflated, the SVC opens above the SVC occlusion balloon 143 and allows blood to travel through the azygos vein to the right atrium. If further reduction of flow back to the right atrium (further reduction of preload) is desired, the azygos vein occlusion balloon 142 can be inflated, thereby occluding the azygos vein and preventing it from acting as a natural shunt.

[0215] The systems and methods of the present invention can be used alone as described in the above examples, or in combination with other devices configured to assist heart function. For example, SVC occlusion according to the principles of the present invention can 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, vein, artery) pump, whether for full heart support or for temporary assistance, thereby allowing for synchronous or asynchronous (venous and arterial) unloading for preload and afterload of the heart, respectively. For example, SVC occlusion according to the principles of the present invention can be used in combination with an Impella® pump available from Abiomed, Inc. of Danvers, Massachusetts, as described in further detail below with respect to Abiomed, Inc. cardiac pump, as described in further detail below with respect to FIG. 49 cardiac pump, as described in further detail below with respect toFIG. 46 and 51 -54 illustrates an SVC occlusion system combined with exemplary RVAD, LVAD, and IABP systems.

[0216] The system of this invention can also be coupled to other devices, such as biventricular pacemakers and neuromodulation devices. For example, biventricular pacemakers are designed to resynchronize cardiac function; if SVC occlusion advantageously alters the interaction between the RV and LV, biventricular pacing may become more effective. Similarly, SVC occlusion therapy can be used in conjunction with neuromodulation devices, giving the system a significant combined effect in stimulating vagal efferent pathways, thereby enhancing the efficacy of the neuromodulation device. A further potential application could be unmasking right ventricular failure after equipping patients with LVADs. By modulating venous return to the right ventricle, it is possible to reduce overload and thus “modulate” the right ventricular myocardium to tolerate the enhanced venous return driven by the LVAD.

[0217] Although the flow-limiting element 32 is described above as being positioned within the SVC and expanding and contracting within the SVC, alternatively, therapeutic occlusion of the SVC as described herein can be achieved by selectively contracting the SVC using a cuff wrapped around the outside of the SVC. Now refer to FIG. 47A The diagram illustrates the cuff 150 that wraps around the SVC. (Example) FIG. 47A As further depicted in -D, the cuff 150 may include a strap 151, a blocking element 152, and a locking element 153. The blocking element 152 may be incorporated into the strap 151, such that the blocking element 152 is... FIG. 47B The outer surface of the strip 151 in the diagram and FIG. 46 In the diagram, the inner surface of the band 151 extends outward. The inner side or inner surface of the band 151 is the side facing the SVC, and the outer side or outer surface of the band 151 is the side facing away from the SVC.

[0218] The strap 151 may be generally rectangular in shape. The locking element 153 may be any well-known system for removably attaching one side of the strap 151 to the other side of the strap 151. For example, the strap 151 may have a magnetic locking element for securely fastening the cuff 150 to the SVC. The air line 154 may be connected at one end to the sealing element 152 and at the other end to a controller. The sealing element preferably has elastic properties such that it expands when the air line 154 delivers air or other fluid to the sealing element 152. When expanded, the sealing element 152 may expand outward from the inside of the strap 151.

[0219] Refer again FIG. 48The cuff 150 can be wrapped around the SVC and tightly locked on the SVC using the locking element 153. After the cuff 150 is locked in place on the SVC, the occluding element 152 can be selectively inflated and thus expanded toward the SVC by delivering fluid through the air line 154. Since the band 151 is substantially inelastic, inflation of the occluding element 152 will result in expansion of the occluding element 152 and compression of the SVC, thereby restricting flow through the SVC. Thus, occlusion of the SVC can be achieved as the occluding element 152 expands and encroaches into the SVC, which causes the SVC to bunch inward. Thus, by selectively deflecting and inflating the occluding element 152, therapeutic occlusion of the SVC described herein can be achieved.

[0220] The controller 33 is programmed to cause the flow restricting element 32 to at least partially occlude the SVC for a first predetermined time interval and then to deflate, e.g., shrink, 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 greater than one minute, between two and eight minutes, or between four and six minutes. For example, the first predetermined time interval can be five minutes, plus or minus one 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 can be at least 5 times longer, at least 10 times longer, at least 20 times longer, or at least 30 times longer than the second predetermined time interval. In some data described herein, for example, the occlusion time interval is 5 minutes and the deflation time interval is 10 seconds. In some embodiments, the controller 33 is programmed to cause the flow restricting element 32 to completely occlude the SVC during the first predetermined time interval. The controller 33 can be programmed to cause the flow restricting element 32 to transition from an occluded state for the first predetermined time interval to a deflated state for the second predetermined time interval, for multiple cycles throughout the course of treatment. As further described herein, the controller 33 can be programmed to automatically adjust the timing of the first predetermined time interval (e.g., to a third predetermined time interval) and / or adjust the timing of the second predetermined time interval (e.g., to a fourth predetermined time interval) and / or in response to user input, e.g., in response to a parameter sensed by the sensor(s). Further adjustments to the time intervals throughout the course of treatment will be understood by those skilled in the art.

[0221] Reference is now made to FIG. 48FIG. 3 illustrates an alternative exemplary system 30' in accordance with the present application. System 30' is similar to system 30 and includes a catheter 31 having a flow restriction element 32 disposed on a distal portion 34. System 30' differs from system 30 in that catheter 31 is removably coupled to an external controller system 200 at a proximal end 35. For example, catheter 31 can be decoupled from controller 33 and coupled to external controller system 200 during a hospital visit so that a clinician can directly monitor and adjust the operation of flow restriction element 32. Catheter 31 can include an optional distal floating balloon 201 disposed on distal portion 34 distal to flow restriction element 32. As shown in FIG. 3, distal floating balloon 201 can be positioned within a patient's pulmonary artery. FIG. 49

[0222] External controller system 200 includes a display 202, such as a graphical user interface, electrically coupled to an inflation source 203 and an external controller 204. Display 202 communicates with inflation source 203 and external controller 204 to display information about the operation of system 30', such as important physiological or system parameters for review or adjustment by a clinician; or alerts generated by external controller 204. A clinician can review the data displayed on display 202 to troubleshoot malfunctions or adjust system parameters via the graphical user interface.

[0223] Inflation source 203 includes a drive mechanism, such as a motor, pump, for actuating flow restriction element 32. Inflation source 203 further includes a source of inflation media, such as a gas or fluid, such that the drive mechanism can transfer the inflation media between inflation source 203 and flow restriction element 32 via a flow restriction element connector 209 in response to commands from external controller 204. Furthermore, when partially externalized, catheter 31 provides a failsafe design because only flow restriction element 32 can be inflated to provide occlusion when the proximal end of catheter 31 is coupled to external controller 204. This quick-disconnect coupling at proximal end 35 allows the catheter to be quickly disconnected from external controller 204 for cleaning and / or emergency situations.

[0224] External controller 204 includes a processor programmed to control signals to the drive mechanism of inflation source 203 and a memory for storing instructions thereon. External controller 204 also includes a power source, such as a battery, which provides the power necessary to operate the processor, inflation source 203, and display 202. Optionally, external controller 204 can receive power via a cord plugged into a source of electrical power, such as an electrical outlet.

[0225] ​Catheter 31 can be coupled at proximal end 35 to a distal floating balloon connector 205 for fluid communication with a source of inflation medium, such as a gas or a fluid, such that inflation medium can be transferred between the source of inflation medium and distal floating balloon 201 in response to commands from external controller 204, thereby anchoring distal floating balloon 201 within the patient's pulmonary artery. Catheter 31 can also be coupled at proximal end 35 to a thermistor connector 206 for communication with a cardiac output (CO) monitor for measuring and monitoring temperature, and to a pulmonary artery pressure connector 207 for communication with a CO monitor for measuring and monitoring pulmonary artery pressure.

[0226] External controller 204 can be coupled at proximal end 35 to catheter 31 via a right atrial pressure connector 208 for measuring and monitoring right atrial pressure. External controller 204 can also be coupled at proximal end 35 to catheter 31 via a flow restriction element connector 209 for measuring and monitoring the amount of inflation medium transferred between inflation source 203 and flow restriction element 32, such as the pressure within flow restriction element 32. External controller 204 can also be coupled to a jugular vein pressure connector 210 for measuring and monitoring the jugular vein pressure from the sheath tube side port.

[0227] The processor of external controller 204 can include a data transmission circuit as described above that monitors input from external sensors, for example, located on catheter 31, and provides that signal to the processor. The processor is programmed to receive input from the data transmission circuit and adjust the interval during which flow restriction element 32 is held in an expanded state, or adjust the degree of occlusion caused by flow restriction element 32. Thus, for example, catheter 31 can have one or more optional sensors positioned within the distal portion 34 of the catheter to measure parameters such as 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 transmission circuit of external controller 204, which can pre-process the input signal, for example, decimate and digitize the output of the sensors, before providing it to the processor. The signal provided to the processor allows for assessment of the efficacy of flow restriction element 32, for example, by displaying the reduction in venous pressure during occlusion and during patency, and the clinician can use this signal to determine how much occlusion is needed to adjust venous blood return based on the severity of the patient's congestion. As will be appreciated by those of ordinary skill in the art, system 30' can employ any combination of flow restriction elements and sensors as described above.

[0228] Reference is now made to FIG. 50described above, an SVC occlusion system 30 having a flow restriction element 32 at a distal portion 34 of a catheter 31 can be positioned within the SVC to at least partially intermittently occlude the SVC, and an LVAD system 211 can be positioned on the left side of the heart, providing full hemodynamic support. In one example, the LVAD system 211 is an Impella® heart pump available from Abiomed, Inc. of Danvers, Massachusetts. The LVAD system 211 schematically includes an inflow end 212, an outflow end 213, an impeller pump 214, and an anchor 215 disposed on a distal portion of a catheter 216. For example, the anchor 215 can be a pigtail anchor. During operation, the inflow end 212 is positioned in the left ventricle, and the outflow end 213 is positioned in the ascending aorta. When the impeller pump 214 is actuated, blood in the left ventricle is pumped through the inflow end 212 and out into the aorta via the outflow end 213, thereby mimicking the natural path of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion. For example, the impeller pump 214 can deliver up to 5.0 L / min of forward blood flow from the left ventricle to the aorta. As will be appreciated by those of ordinary skill in the art, any suitable pump can be used. The Impella® heart pump available from Abiomed, Inc. of Danvers, Massachusetts. The LVAD system 211 schematically includes an inflow end 212, an outflow end 213, an impeller pump 214, and an anchor 215 disposed on a distal portion of a catheter 216. For example, the anchor 215 can be a pigtail anchor. During operation, the inflow end 212 is positioned in the left ventricle, and the outflow end 213 is positioned in the ascending aorta. When the impeller pump 214 is actuated, blood in the left ventricle is pumped through the inflow end 212 and out into the aorta via the outflow end 213, thereby mimicking the natural path of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion. For example, the impeller pump 214 can deliver up to 5.0 L / min of forward blood flow from the left ventricle to the aorta. As will be appreciated by those of ordinary skill in the art, any suitable pump can be used.

[0229] Additionally, the LVAD system 211 includes a controller 217 configured to be operably coupled to the catheter 216 to actuate the pump 214 to pump blood from the left ventricle to the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. The controller 217 and the controller 33 can be the same and / or incorporated into the same housing unit, such that a single controller is operably coupled to both the flow restriction element 32 and the pump 214. Concurrently with the controller 217 actuating the pump 214 to pump blood from the left ventricle to the aorta, the controller 33 can actuate the flow restriction element 32 to at least partially occlude the SVC.

[0230] FIG. 51 Results obtained in an animal model demonstrating (1) baseline model; (2) LVAD model; and (3) LVAD + SVC occlusion system model left ventricle (“LV”) total volume - LV pressure are presented. Comparing model (3) to models (1) and (2) it is apparent that the SVC occlusion system described herein in combination with a transvalvular LVAD (Impella® available from Abiomed, Inc. of Danvers, Massachusetts) provides improved hemodynamic support. ​​The combined use of cardiac pumps ("CP") results in a reduction in cardiac preload ("CP") and left ventricular wall tension ("LVWT"), demonstrating improved functionality and efficiency in reducing preload induced by LVADs. Furthermore, transvalvular LVADs can operate at lower pump rates while still providing adequate systemic cardiovascular support, thereby reducing the likelihood of LVAD-related adverse events.

[0231] Now for reference FIG. 52 This describes an SVC occlusion system in combination with a transvalvular RVAD. For example, as described above, an SVC occlusion system 30 having a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an RVAD system 218 can be positioned distal to the flow-limiting element 32 of catheter 31, providing comprehensive hemodynamic support. In one example, the RVAD system 218 is available from Danvers, Massachusetts. Impella A cardiac pump. The RVAD system 218 schematically includes an inlet end 219, an outlet end 220, an impeller pump 221, and an anchor 222 disposed on the distal portion of a catheter 223. For example, the anchor 222 may be a pigtail anchor. During operation, the outlet end 220 is positioned in the pulmonary artery, and the inlet end 219 is positioned distal to the flow-limiting element 32 in the SVC. When the impeller pump 221 is actuated, blood in the SVC is pumped through the inlet end 219 and discharged via the outlet end 220 into the pulmonary artery, thereby mimicking the natural path of blood flow and unloading the right ventricle. For example, the impeller pump 221 can deliver a positive blood flow of up to 5.0 L / min from the SVC to the pulmonary artery. As will be appreciated by those skilled in the art, any suitable pump can be used.

[0232] Additionally, controller 33 can be configured to be operatively coupled to RVAD system 218 to actuate pump 221 to pump blood from SVC to pulmonary artery, thereby unloading the right ventricle. Thus, controller 33 can simultaneously actuate flow-limiting element 32 to at least partially block SVC and pump 221 to pump blood from SVC to pulmonary artery.

[0233] Now for reference FIG. 53 This describes an SVC occlusion system in combination with an optional transvalvular RVAD. For example, as described above, an SVC occlusion system 30 having a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an RVAD system 218 can be positioned on the right side of the heart to provide full hemodynamic support. In one example, the RVAD system 218 is available from Danvers, Massachusetts. Impella Heart pump. The RVAD system 218 illustratively includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222 disposed on a distal portion of a catheter 223. The anchor 222 can be a pigtail anchor, for example. During operation, the inflow end 219 is positioned in the inferior vena cava (IVC) and the outflow end 220 is positioned in the pulmonary artery. When the impeller pump 221 is actuated, blood within the IVC is pumped through the inflow end 219 and out into the pulmonary artery via the outflow end 220, thereby mimicking the natural pathway of blood flow and unloading the right ventricle. The impeller pump 221 can deliver up to 5.0 L / min of forward blood flow from the IVC to the pulmonary artery, for example. As will be appreciated by those of ordinary skill in the art, any suitable pump can be used.

[0234] In addition, the RVAD system 218 includes a controller 224 configured to be operably coupled to the catheter 223 to actuate the pump 221 to pump blood from the IVC to the pulmonary artery to unload the right ventricle. The controller 224 and the controller 33 can be the same and / or incorporated into the same housing unit, such that a single controller is operably coupled to the flow limiting element 32 and the pump 221. Concurrently with the controller 224 actuating the pump 221 to pump blood from the IVC to the pulmonary artery, the controller 33 can actuate the flow limiting element 32 to at least partially occlude the SVC.

[0235] Reference is now made to FIG. 53 and 54 The SVC occlusion system can be combined with a ventricular assist device (VAD). As shown in FIG. 54 , the SVC occlusion system 30 having the flow limiting element 32 at the distal portion 34 of the catheter 31 can be positioned within the SVC to at least partially intermittently occlude the SVC, and the LVAD system 225 can be positioned transapically on the left side of the heart, providing comprehensive hemodynamic support. Alternatively, as shown in FIG. 55 , the SVC occlusion system 30" having the flow limiting element 32 directly placed on or otherwise incorporated into the distal end of the introducer sheath 144 can be positioned within the SVC to at least partially occlude the SVC, and the LVAD system 225 can be positioned on the left side of the heart. The SVC occlusion system 30" can be similar to the SVC occlusion system 30, but the introducer sheath 144 has the flow limiting element 32 disposed on a distal portion of the introducer sheath 144.

[0236] In one example, the LVAD system 225 can be a HeartWare® HVAD available from HeartWare, Inc. of Miami Lakes, Florida. TM HVAD TMSystem. LVAD system 225 illustratively includes an inflow end 226, an outflow end 227, and a pump 228, and can be implanted near the apex of the left ventricle. During operation, inflow end 226 can be positioned in the left ventricle and outflow end 227 can be positioned in the ascending aorta. When pump 228 is actuated, blood within the left ventricle can be pumped through inflow end 226 and out 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.

[0237] LVAD system 225 can additionally include a controller 229, which can be configured to be operably coupled to pump 228 to actuate pump 228 to pump blood from the left ventricle to the aorta. Controller 229 and controller 33 can be the same and / or incorporated into the same housing unit, such that a single controller is operably coupled to flow limiting element 32 and pump 228. Controller 33 can actuate flow limiting element 32 to at least partially occlude the SVC at the same time that controller 229 actuates pump 228 to pump blood from the left ventricle to the aorta. As will be appreciated by one of ordinary skill in the art, any suitable ventricular assist device (VAD) can be used with the SVC occlusion systems described herein.

[0238] The combination of the SVC occlusion system with a VAD (e.g., an RVAD or an LVAD) can reduce the VAD flow rate needed in a patient to achieve the same hemodynamic response. This will reduce the required pump speed, thereby reducing potential complications associated with higher pump speeds needed to generate higher flow rates.

[0239] Because right ventricular overload can occur during or after LVAD implantation, SVC occlusion using the SVC occlusion systems described herein (e.g., SVC occlusion systems 30, 30', and 30") can be used to reduce right ventricular volume. For example, intermittent occlusion of the SVC after LVAD implantation can help to unload the right ventricle as the LVAD reaches operational speed and / or output.

[0240] Referring now to FIG. 56 , an exemplary procedure for conditioning the heart and reducing right ventricular volume is shown. At step 241, a catheter can be inserted into the SVC. The catheter can include a flow limiting element, such as a balloon, disposed on a distal end. This step can include positioning catheter 31, or alternatively introducer sheath 144, into the SVC, as described above. At step 242, the flow limiting element can be actuated to at least partially occlude the SVC. For example, this step can involve actuating flow limiting element 32 to at least partially occlude the SVC. Actuation can include inflating the balloon and / or intermittently inflating the balloon (e.g., inflating for 5 minutes and deflating the balloon for 30 minutes), as described above.

[0241] At step 243, the LVAD device can be implanted at or near the left ventricle or otherwise deployed at or near the left ventricle. This can involve, for example, transapical positioning of the LVAD system 225 on the left side of the heart. Step 243 can occur after step 242, after the flow limiting element is actuated. Alternatively, step 242 can occur during or prior to step 242. At step 244, the healthcare provider or technician controlling the flow limiting element 32 can wait for a certain period of time and / or program the controller 33 to wait for a set period of time after actuation of the flow limiting element at step 242. As described above, it can be beneficial to at least partially occlude the SVC for a certain period of time (e.g., five minutes). The amount of time can be based on measuring one or more parameters associated with the heart (e.g., pressure, volume, load) and determining that the one or more measured parameters are within a predetermined threshold range(s). Upon falling within the predetermined threshold range(s), the flow limiting element 32 can be stopped by the clinician and / or automatically stopped by the controller. After waiting for a certain period of time at step 244, actuation of the flow limiting device can be terminated at step 245. For example, the flow limiting element 32 can be a balloon that deflates after a set period of time. As described above, the flow limiting element 32 can be intermittently actuated to occlude the SVC. Thus, steps 242, 244, and 245 can be repeated to reduce the volume of fluid in the right ventricle. In this manner, the SVC occlusion device can be used to offload the overburdened right ventricle prior to, during, and / or after implantation or deployment of the LVAD.

[0242] Referring now to FIG. 54 , an SVC occlusion system in combination with an intra-aortic balloon pump (IABP) is described. For example, as described above, the SVC occlusion system 30 having the flow limiting element 32 at the distal portion 34 of the catheter 31 can be positioned within the SVC to at least partially intermittently occlude the SVC, and the IABP 230 can be positioned in the descending aorta. The IABP can include a flow limiting element 231 and a catheter 232 coupled to the flow limiting element 231. The flow limiting element 231 schematically includes a balloon that is capable of transitioning between a collapsed state and an expanded deployed state that allows transluminal placement. The flow limiting element 231 is preferably sized and shaped such that, in the expanded state, it partially or completely occludes flow in the aorta. The catheter 232 can be coupled to the controller 33 at a proximal end. The controller 33 houses a drive mechanism 36 for independently actuating the flow limiting element 32 and the flow limiting element 231. As described above, the flow limiting element 32 can be intermittently actuated to occlude the SVC, and the flow limiting element 231 can be intermittently actuated to occlude the aorta. Thus, steps 242, 244, and 245 can be repeated to reduce the volume of fluid in the right ventricle. In this manner, the SVC occlusion device can be used to offload the overburdened right ventricle prior to, during, and / or after implantation or deployment of the LVAD. FIG. 57AAs shown in FIG. 23, flow restriction element 231 and flow restriction element 32 can be coupled to the same controller, such that a single controller is operably coupled to flow restriction element 32, flow restriction element 231, and pump 221. However, it should be appreciated that flow restriction element 32 and flow restriction element 231 can be coupled to different controllers and / or different pumps. During operation, flow restriction element 231 will be positioned within the descending aorta and will intermittently expand and contract. The expansion can be timed to coincide with diastole, and the contraction timed to coincide with systole. When flow restriction element 231 contracts, a suction effect is created in the aorta, which facilitates the transfer of blood from the left ventricle to the aorta during systole.

[0243] Reference is now made to FIG. 57A - C, respectively, illustrating a normal heart, a compensated heart, and a decompensated heart, each illustrating a cross-section of the mitral valve. As shown in FIG. 57B As shown in FIG. 23, flow restriction element 231 and flow restriction element 32 can be coupled to the same controller, such that a single controller is operably coupled to flow restriction element 32, flow restriction element 231, and pump 221. However, it should be appreciated that flow restriction element 32 and flow restriction element 231 can be coupled to different controllers and / or different pumps. During operation, flow restriction element 231 will be positioned within the descending aorta and will intermittently expand and contract. The expansion can be timed to coincide with diastole, and the contraction timed to coincide with systole. When flow restriction element 231 contracts, a suction effect is created in the aorta, which facilitates the transfer of blood from the left ventricle to the aorta during systole. FIG. 57C As shown in FIG. 23, flow restriction element 231 and flow restriction element 32 can be coupled to the same controller, such that a single controller is operably coupled to flow restriction element 32, flow restriction element 231, and pump 221. However, it should be appreciated that flow restriction element 32 and flow restriction element 231 can be coupled to different controllers and / or different pumps. During operation, flow restriction element 231 will be positioned within the descending aorta and will intermittently expand and contract. The expansion can be timed to coincide with diastole, and the contraction timed to coincide with systole. When flow restriction element 231 contracts, a suction effect is created in the aorta, which facilitates the transfer of blood from the left ventricle to the aorta during systole. FIG. 57C As shown in FIG. 23, flow restriction element 231 and flow restriction element 32 can be coupled to the same controller, such that a single controller is operably coupled to flow restriction element 32, flow restriction element 231, and pump 221. However, it should be appreciated that flow restriction element 32 and flow restriction element 231 can be coupled to different controllers and / or different pumps. During operation, flow restriction element 231 will be positioned within the descending aorta and will intermittently expand and contract. The expansion can be timed to coincide with diastole, and the contraction timed to coincide with systole. When flow restriction element 231 contracts, a suction effect is created in the aorta, which facilitates the transfer of blood from the left ventricle to the aorta during systole. FIG. 58 As shown in FIG. 23, flow restriction element 231 and flow restriction element 32 can be coupled to the same controller, such that a single controller is operably coupled to flow restriction element 32, flow restriction element 231, and pump 221. However, it should be appreciated that flow restriction element 32 and flow restriction element 231 can be coupled to different controllers and / or different pumps. During operation, flow restriction element 231 will be positioned within the descending aorta and will intermittently expand and contract. The expansion can be timed to coincide with diastole, and the contraction timed to coincide with systole. When flow restriction element 231 contracts, a suction effect is created in the aorta, which facilitates the transfer of blood from the left ventricle to the aorta during systole.

[0244] Using the SVC occlusion systems described herein (i.e., SVC occlusion system 30, SVC occlusion system 30', and SVC occlusion system 30") can treat regurgitation in an overloaded heart. For example, as described above, introducing the SVC occlusion system into the SVC and intermittently actuating flow restriction element 32 (e.g., occlusion time intervals of 5 minutes and contraction time intervals of 10 seconds) reduces the overload of the heart. As the volume of the heart is reduced, coaptation can be achieved by the valve leaflets that were previously unable to seal due to the overload. Thus, using the SVC occlusion systems in the manner described herein can reduce fluid overload in the heart and ultimately reduce or eliminate regurgitation in one or more valves such as the mitral valve, the aortic valve, and / or the tricuspid valve.

[0245] It should also be appreciated that the use of the SVC occlusion system 30" or any other occlusion system described herein to occlude the SVC can result in increased urine output, further reducing fluid overload. For example, the use of the SVC occlusion system 30" or any other occlusion system described herein can involve actuating (e.g., inflating) the flow restriction element such that the flow restriction element occludes and even stretches the superior vena cava and / or the superior vena- right atrial junction, causing vagal nerve stimulation and resulting in increased urine output. Furthermore, reducing fluid overload using the techniques and SVC occlusion systems described herein can increase the number of patients eligible for heart surgery. For example, patients suffering from an overloaded heart due to the degree of leaflet separation rather than a suitable candidate for a valve clip can become suitable candidates for the surgery after using the SVC occlusion system and heart volume reduction.

[0246] Referring now to FIG. 44 , the SVC occlusion system 30" is illustrated and is similar to the system shown in FIG. 59 . The SVC occlusion system 30" can include an introducer sheath 144 having a distal portion 255 and a proximal portion 256. The introducer sheath 144 can be a flexible tube. The distal portion 255 can include a flow restriction element 32 disposed on or otherwise incorporated into the introducer sheath 144. The distal portion 255 can be configured to be placed in the SVC. The introducer sheath 144 can be coupled to a controller 33 at the proximal end 256. The controller 33 can be programmed to intermittently actuate the flow restriction element 32. The introducer sheath 144 can include one or more lumens and can also include a fluid lumen for inflating the flow restriction element 32.

[0247] Referring now to FIG. 59 , the SVC occlusion system 30" is shown with the distal portion 255 positioned in the SVC. In addition, a separate delivery catheter 260 is shown extending through the IVC, through the right atrium, and into the left atrium. The delivery catheter 260 can be introduced, for example, into the femoral vein or any other vein. The delivery catheter 260 can have a distal region 261 designed for delivering a valve clip, such as valve clip 262. The valve clip 262 can be removably coupled to the distal region 261 and designed to clip together valve leaflets to treat regurgitation. As shown in FIG. 57B , the valve clip 262 can be used to clip together mitral valve leaflets. In one example, the valve clip 262 can be the MitraClip® valve clip available from Abbott Laboratories TM . However, those skilled in the art will appreciate that the valve clip 262 can be any device that couples one or more valve leaflets in close proximity to one another.

[0248] As explained above, when the heart is overloaded, asFIG. 60 and 57C As shown in , increased volume in the heart can cause the valve leaflets to separate, causing regurgitation. To deploy the valve clip 262 to treat the regurgitation, the valve leaflets cannot be separated too far from each other. In the event that the valve leaflets are separated too far for the valve clip 262 to be deployed, the SVC occlusion system can be used to reduce the volume of the heart. For example, the LVEDV can be monitored while using the SVC occlusion system. With the heart offloaded, the valve clip 262 can be properly installed. For example, once the LVEDV is reduced to a certain point, the likelihood of successful implantation of the valve clip can be increased. Thus, the SVC occlusion system described herein facilitates implantation of a valve clip.

[0249] Referring now to FIG. 59 , a method for conditioning the heart and reducing the volume of the heart to perform a cardiac procedure (e.g., deployment of a mitral clip) is shown. At step 271, a catheter can be inserted into the SVC. For example, as shown in FIG. 58 , the SVC occlusion system 30" can be inserted into the patient, and the distal portion 255 with the flow limiting element 32 can be disposed within the SVC. At step 272, the flow limiting element can be actuated to at least partially occlude the SVC. For example, as shown in FIG. 59 , and described in detail above, the controller 33 can actuate the flow limiting element 32, causing the flow limiting element 32 to expand to at least partially occlude the SVC.

[0250] At step 273, a healthcare provider or technician can generate data related to the patient's heart. For example, the healthcare provider or technician can use medical imaging, such as fluoroscopy or any other well-known type of medical imaging to generate image data. Other well-known methods can be used to generate data related to the heart, such as ultrasound or electrocardiogram (ECG). From the generated data, the healthcare provider or technician can determine information about the patient's heart or a portion thereof (such as the right ventricle and / or the left ventricle), including volume and / or pressure. For example, the healthcare provider or technician can determine the volume of the patient's heart or a portion thereof (e.g., the right ventricular volume). Optionally, the healthcare provider or technician can take into account the separation between the leaflets of a valve, such as the mitral valve.

[0251] In step 274, the healthcare provider or technician may confirm that the generated data or data corresponding to the generated data meets a predetermined threshold or is otherwise within an acceptable range. For example, using the generated data, the healthcare provider or technician may calculate or infer the size or volume of the right ventricle and confirm that the size or volume meets a predetermined threshold or is otherwise within an acceptable range. After performing step 274, in step 275, the healthcare provider or technician may perform cardiac surgery. For example, as FIG. 60 As shown in the document, healthcare providers or technicians can deploy valve clip 262.

[0252] FIG. 60 The methods described herein can be used in conjunction with a variety of other cardiac surgeries, including but not limited to the deployment and / or implantation of valves or cardiac prostheses, the deployment and / or implantation of cardiac pumps (e.g., LVADs), cardiac or valvular surgery (e.g., quadrilateral resection), and / or coronary revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). FIG. 61 Step 275 of performing cardiac surgery may optionally involve deploying annulusoplasty ring 282, such as FIG. 61 As shown in [the image / document]. Now refer to [the image / document]. ​ For example, the distal portion 255 of the SVC occlusion system 30” may be located within the SVC, and the delivery catheter 280 may extend through the IVC, through the right atrium, and into the left atrium. The delivery catheter 280 may be introduced into the femoral vein or any other vein. The delivery catheter 280 may have a distal region 281 for delivering the annuloplasty ring 282. In one example, the annuloplasty ring 282 may be a Carpentier-Edwards Physio II ring available from Edwards Lifesciences. However, those skilled in the art will understand that the annuloplasty ring 282 may be any ring or band used to restore the valve annulus to its proper size.

[0253] exist Figure 60 Step 275, performing cardiac surgery, may optionally include deploying a valve prosthesis 292, such as... Figure 62 As shown in [the image / document]. Now refer to [the image / document]. Figure 62 For example, the distal portion 255 of the SVC occlusion system 30” may be located within the SVC, and the delivery catheter 290 may extend through the IVC, through the right atrium, and into the left atrium. The delivery catheter 290 may be introduced into the femoral vein or any other vein. The delivery catheter 290 may have a distal region 291 for delivering the valve prosthesis 292. For example, the valve prosthesis 292 may be any valve prosthesis, such as a transcatheter prosthetic heart valve or stent.

[0254] Although Figure 59 ,61 and 62 both show delivery catheters extending through the IVC for performing cardiac procedures, but the delivery catheter can alternatively extend through the SVC. Referring now to Figure 63 , a distal portion 255 of the SVC occlusion system 30" is illustrated with the distal portion 255 disposed within the SVC. A delivery catheter 300 is illustrated extending through the introducer sheath 144 and out the distal portion 255. Similar to the delivery catheter 260, the delivery catheter 300 can deliver a valve clip 301 that is removably coupled to a distal region 302 and deploy the valve clip 262 in the same manner as described above with respect to Figure 59 . It is also understood that the annuloplasty ring 282 described with respect to Figure 61 , the valve prosthesis 292 described with respect to Figure 62 , including but not limited to a bioprosthetic heart valve, or any other prosthesis, bioprosthesis, or surgical device can be delivered to the heart via a delivery catheter extending through the introducer sheath 144.

[0255] It is to be understood that the foregoing description is intended to illustrate and not to limit the scope of the application, which is defined by the scope of the appended claims. Other embodiments are within the scope of the following claims.

Claims

1. A device for occluding the superior vena cava (SVC) in a patient, the device comprising: A catheter, which includes a distal region and is configured to be disposed in the SVC; A flow-limiting element is disposed on the distal region of the conduit and configured to be selectively actuated; A pressure switch is disposed on the distal region of the conduit and includes a first lumen and a second lumen, the first lumen having a first open end disposed proximal to the flow-limiting element, and the second lumen having a second open end disposed distal to the flow-limiting element. The pressure switch is configured to generate a signal to indicate the degree to which the flow-limiting element blocks the SVC when the pressure difference between the first lumen and the second lumen reaches a predetermined pressure difference threshold. and A controller, operably coupled to the conduit and configured to: When the pressure difference between the first lumen and the second lumen reaches the predetermined pressure difference threshold, a signal is received from the pressure switch. and The current-limiting element is intermittently actuated based on the signal to at least partially block the SVC.

2. The apparatus of claim 1, wherein the controller is configured to contract the current-limiting element based on the signal.

3. The apparatus of claim 1, wherein the controller is configured to intermittently actuate the current limiting element to at least partially block the SVC for a predetermined first time interval and to reduce the current limiting element for a predetermined second time interval.

4. The apparatus of claim 3, wherein the controller is configured to modify the first time interval based on the signal.

5. The apparatus of claim 3, wherein the controller is configured to modify the first time interval based on the patient's heart rate.

6. The apparatus of claim 1, wherein the controller is configured to reduce cardiac preload during the interval, which is sufficient to improve cardiac performance as measured by at least one of the following: reduced cardiac filling pressure, increased left ventricular relaxation, increased left ventricular volume, increased left ventricular stroke volume, increased relaxation effect, reduced left ventricular stiffness, or reduced cardiac strain.

7. The apparatus of claim 1, wherein the controller is configured to treat heart failure.

8. The device according to claim 1, wherein the current-limiting element is an inflatable balloon.

9. The apparatus of claim 1, wherein the current-limiting element comprises a release valve having an open position and a closed position.

10. The apparatus of claim 1, wherein the controller is configured for implantation.

11. The apparatus of claim 1, wherein the controller includes a data transmission circuit configured to receive the signal.

12. The apparatus of claim 11, wherein the data transmission circuitry is configured to communicate the signal to a patient's computing device for display to the patient.

13. The apparatus of claim 1, wherein the controller is programmed to send an alert status to a clinician monitoring the patient based on the signal via the cellular communication capability of the computing device.

14. The device of claim 1, wherein the catheter includes one or more sensors for detecting the patient's heart rate.

15. The apparatus of claim 1, further comprising one or more external power sources electrically communicating with the controller and configured to provide power to the controller.

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