System and method for selectively occluding superior vena cava for treating heart conditions

Abstract

To provide a system and a method for selectively occluding the superior vena cava so as to provide good treatment of a heart disease.SOLUTION: A system and a method are provided for treating conditions such as heart failure and / or pulmonary hypertension by at least partially occluding a blood flow through a superior vena cava for an interval spanning multiple cardiac cycles. A catheter with an occlusion device is provided along with a controller that actuates a drive mechanism to provide at least partial occlusion of the patient's superior vena cava, which reduces cardiac filling pressures and induces a favorable shift in a patient's Frank-Starling curve towards healthy heart functionality and improved cardiac performance. The system may include sensors to determine a degree of occlusion of the superior vena cava. The occlusion system may be used to reduce volume in a heart and facilitate a cardiac procedure. The occlusion system may be used to relieve an overloaded chamber during and / or after deploying a VAD.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Application No. 62 / 939,524, filed November 22, 2019, the entire contents of which are incorporated herein by reference. This application is also related to U.S. Patent Application No. 16 / 402,194, filed May 2, 2019, now U.S. Patent No. 10,842,975, a continuation of U.S. Patent Application No. 15 / 203,437, filed July 6, 2016, now U.S. Patent No. 10,279,152, a continuation of U.S. Patent Application No. 14 / 828,429, filed August 17, 2015, now U.S. Patent No. 9,393,384, the entire contents of each of which are incorporated herein by reference. This application also claims priority to U.S. Provisional Application Nos. 62 / 642,569, filed March 13, 2018, and 62 / 576,529, filed October 24, 2017, the entire contents of each of which are incorporated herein by reference, and is a continuation of U.S. Provisional Application No. 14 / 828,429, filed August 17, 2015, now U.S. Patent No. 10,279,152, filed July 2016, now U.S. Patent No. 9,393,384. This application relates to U.S. Patent Application No. 16 / 168,357, filed October 23, 2018, now U.S. Patent No. 10,758,715, a national stage application of PCT / US2016 / 047055, filed August 15, 2016, which is a continuation-in-part of U.S. Patent Application No. 15 / 203,437, filed October 6, 2018, and is also a continuation-in-part of U.S. Patent Application No. 15 / 753,300, filed February 17, 2018, now U.S. Patent No. 10,842,974.

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

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

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

[0005] Although the heart can often initially respond successfully to increased workload due to hypertension or contractile tissue damage, over time, this stress induces compensatory cardiomyocyte hypertrophy and ventricular wall remodeling. Specifically, over the next several months after the initial cardiac injury, the damaged portion of the heart typically begins to remodel as the heart struggles to continue pumping blood, accompanied by a loss of muscle mass or reduced contractility. This, in turn, leads to overwork of the myocardium, resulting in progressive thinning, enlargement, and further overload in the damaged area. Concurrently, the ejection fraction of the damaged ventricle decreases, reducing cardiac output, and mean ventricular pressure and volume become larger throughout the cardiac cycle, signaling heart failure. Not surprisingly, once a patient's heart enters this progressive, endless downward spiral, their quality of life is severely affected and their risk of morbidity skyrockets. Depending on many factors, including the patient's previous physical condition, age, sex, and lifestyle, patients may experience one or several hospitalizations, at considerable cost to the patient and to the societal health care system, until they die from cardiac arrest or one of many comorbidities, including stroke, kidney failure, liver failure, or pulmonary hypertension.

[0006] Currently, no device-based solutions exist that specifically target preload reduction to slow the progression of heart failure. While pharmaceutical approaches are available as a palliative to alleviate heart failure symptoms, no pharmaceutical procedures exist that halt or reverse the progression of heart failure. Furthermore, existing pharmaceutical approaches are systemic in nature and do not address the local effects that remodeling has on cardiac structure. Therefore, it would be desirable to provide systems and methods for treating heart failure that can halt, and more preferably, reverse, the progression of cardiac remodeling, which in turn has consequences associated with this disease.

[0007] Applicant notes that there have been several attempts in the prior art to resolve heart failure. Prior to Applicant's invention described herein, there have been no commercially available, effective devices to treat this disease. Below are described several known examples of systems and methods for treating various symptoms of heart failure, but none appear to attempt or be 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 severe side effects.

[0008] For example, U.S. Patent No. 4,546,759 to Solar describes a triple-balloon catheter designed for implantation, in which a distal balloon intermittently occludes the superior vena cava, a proximal balloon intermittently occludes the inferior vena cava, and a middle balloon expands in synchronization with the onset of right ventricular systole, thereby increasing the amount of blood ejected from the right ventricle. The patent states that the system is designed to expand and contract in synchronization with normal cardiac rhythm, reducing the load on the right ventricle and allowing any damage or defect in the right ventricle to heal. The patent does not describe or suggest that the proposed adjustment of blood flow into or out of the right ventricle affects either LVEDV, LVEDD, or LVEDP, nor does it describe or suggest that such adjustment can be used to prevent or reverse the progression of acute or chronic heart failure.

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

[0010] U.S. Patent Application Publication No. 2010 / 0331876 to Cedeno (Patent Document 3) describes a system and method for treating congestive heart failure by regulating venous blood return through the inferior vena cava, similar to the structure described in the U.S. patent application by Gelfand. The system described in the U.S. patent application by Cedeno describes a fixed-volume balloon placed within the inferior vena cava that restricts blood flow into the IVC. The degree of obstruction changes as the blood vessel expands and contracts during inspiration and expiration, allowing normal venous blood return. The patent application further describes that heart failure symptoms improve within three months of use of the claimed system. While the system and method described in the U.S. patent application by Cedeno appear promising, the applicant has identified a number of potential drawbacks to such systems during his own research. During the course of his own research, the applicant discovered that complete occlusion of the inferior vena cava not only reduces left ventricular volume but also significantly reduces left ventricular systolic pressure, resulting in reduced systemic blood pressure and cardiac output. Furthermore, complete occlusion of the inferior vena cava may promote venous congestion in the kidneys, liver, and mesenteric veins, and venous congestion is a major cause of renal failure in patients with congestive heart failure.

[0011] The approach of partial or complete occlusion of the inferior vena cava to alter blood filling pressure to the heart and improve cardiac function has several significant limitations. First, the IVC must be accessed via the femoral or internal jugular vein. Approaching via the femoral vein requires the patient to remain supine, rendering them nonambulatory. Approaching via the jugular or subclavian vein requires the device to traverse the superior vena cava and right atrium, thereby penetrating the heart, potentially increasing the risk of right atrial injury and inducing arrhythmias, resulting in supraventricular tachycardia or bradycardia due to heart block. Second, the IVC approach described by Cedeno et al. relies on several highly variable parameters, particularly in congestive heart failure care centers: 1) IVC diameter, which is often dilated in patients with heart failure; b) intermittent IVC occlusion (complete or partial) causes injury by increasing renal venous pressure, which reduces glomerular filtration rate and exacerbates renal dysfunction; and c) dependency on the patient's respiratory capacity, which is often severely impaired in HF (heart failure). The traditional breathing pattern in HF, known as Cheynes-Stokes breathing, is characterized by intermittent apneic periods, which can cause the IVC to collapse, leading to complete balloon occlusion, resulting in decreased systemic blood pressure and increased renal venous pressure; d) When sustained cardiac unloading is required to see clinical improvement or beneficial changes in cardiac structure or function, IVC occlusion is ineffective because sustained IVC occlusion reduces blood pressure and renal function. Third, the approach defined by Cedeno requires customization of the balloon according to the size of the IVC, which can vary widely. Fourth, many heart failure patients have IVC filters due to their increased propensity for deep vein thrombosis, which hinders the widespread application of IVC therapy.

[0012] Pulmonary hypertension (PH) also accounts for a major cause of morbidity and mortality worldwide. As mentioned above, heart failure is a common cause of pulmonary hypertension, but pulmonary hypertension can also be caused by primary lung disease. Today, pharmacological treatments can reduce pulmonary artery systolic pressure (PASP), improve symptoms, and ultimately improve survival rates for patients with pulmonary hypertension. However, there are drawbacks to pharmacological treatments, such as cost and side effects.

[0013] In view of the aforementioned shortcomings of known systems and methods for regulating venous return to treat heart failure, it would be desirable to provide systems and methods for treating acute and chronic heart failure that reduce the risk of exacerbating comorbidities associated with the disease.

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

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

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

[0017] Yet another concern is that an overloaded heart can experience remodeling and wall deformation, ultimately resulting in a loss of valve coaptation. Without proper valve coaptation, the valve will not seal properly and blood may flow back through the valve, resulting in regurgitation. Regurgitation can cause shortness of breath, fatigue, and tachycardia and / or flutter. It would be desirable to provide systems and methods for treating regurgitation.

[0018] Yet another concern with overload is that it complicates cardiac procedures, such as procedures for correcting regurgitation. For example, clips may be used to connect valve leaflets that no longer seal. However, if the intracardiac volume is too large, deploying the clips may not be possible because the leaflets may be too far apart. It would also be desirable to provide a system that reduces the intracardiac volume for performing cardiac procedures.

[0019] Overload is also known to occur during and / or after placement of a ventricular assist device (VAD). For example, the right ventricle may become overloaded during and / or after placement of a left ventricular assist device (LVAD). A right ventricular assist device (RVAD) may be used to address this issue. However, RVADs involve the placement and / or deployment of a second heart pump, which brings additional risks of complications and infection. It would also be desirable to provide a system for placing a VAD that reduces intracardiac volume. [Prior art documents] [Patent documents]

[0020] [Patent Document 1] U.S. Patent No. 4,546,759 [Patent Document 2] US Patent Application Publication No. 2006 / 0064059 [Patent Document 3] US Patent Application Publication No. 2010 / 0331876 Summary of the Invention [Means for solving the problem]

[0021] In view of the shortcomings of known systems and methods for treating heart failure, it would be desirable to provide systems and methods for treating acute and / or chronic heart failure that can prevent, and more preferably reverse, the progression of cardiac remodeling that in turn leads to the consequences associated with this disease.

[0022] It would further be desirable to provide systems and methods for preventing or reversing the progression of cardiac remodeling in patients suffering from heart failure that are practical for ambulatory and / or chronic use.

[0023] It would further be desirable to provide a system and method for treating heart failure that reduces the risk of exacerbating co-morbidities associated with the disease, such as venous congestion, which leads to renal and hepatic complications.

[0024] It would also be desirable to provide a system and method for treating heart failure that can improve the quality of life for patients suffering from this disease, thereby reducing the need for hospital readmissions and the associated burden on the social healthcare network.

[0025] It would further be desirable to provide systems and methods for treating pulmonary hypertension and improving the quality of life of patients suffering from this disease, as well as systems and methods for treating heart attack, acute heart failure, chronic heart failure, heart failure with preserved ejection fraction, right heart failure, restrictive and constrictive cardiomyopathies, and cardiorenal syndromes (Types 1-5).

[0026] These and other advantages are provided by the present disclosure, which provides systems and methods for modulating venous blood return to the heart via the superior vena cava ("SVC") over a time interval encompassing several cardiac cycles, reducing ventricular overload and reducing cardiac preload and pulmonary artery pressure without increasing renal venous pressure. In accordance with the principles of the present disclosure, venous modulation via the SVC can be used to reduce LVEDP, LVEDV, LVEDD, RVEDP, and / or RVEDV, and prevent or reverse ventricular myocardial remodeling. Counterintuitively, applicants have found in preliminary animal studies that intermittent partial occlusion of the SVC does not lead to stagnation of cerebral blood flow or observable adverse side effects. More importantly, applicants' preliminary animal studies have revealed that occlusion of the SVC results in significant reductions in both RVEDP and LVEDP while improving total cardiac output and without significant reductions in left ventricular systolic pressure ("LVSP"). Thus, unlike the approach described in the aforementioned published Cedeno patent application, the present disclosure provides beneficial reductions in LVEDP, LVEDV, LVEDD, RVEDP, and / or RVEDV with negligible impact on LVSP, but with improved stroke volume (cardiac output) and reduced risk of venous congestion leading to increased comorbidities. The systems and methods described herein provide acute improvements in blood filling pressures to the heart and cardiac function, benefiting patients at risk for acute decompensated heart failure.

[0027] Targeting SVC blood flow (rather than IVC blood flow) has several significant advantages. First, placing the device within the SVC avoids the use of the femoral vein and avoids penetrating the heart. This allows for the development of a fully implantable, yet portable, system for treating acute or chronic conditions. Second, SVC occlusion can be intermittent or continuous, depending on the amount of unloading required. Unlike IVC occlusion, continuous SVC occlusion can preserve systemic blood pressure and improve cardiac output. This maintains unloading of both the right and left ventricles, which can acutely improve hemodynamics and have long-term beneficial effects on cardiac structure and function. Third, unlike IVC occlusion, SVC occlusion does not vary with patient respiration. Fourth, by deploying an internal regulator of SVC occlusion driven by mean right atrial pressure or the pressure difference across the occlusion balloon, SVC devices can be programmed and personalized to each patient's condition. Fifth, by placing the device within the SVC, the device can be used in patients with existing IVC filters.

[0028] According to another aspect of the present disclosure, partial or total intermittent occlusion of the SVC over multiple cardiac cycles is predicted to allow the myocardium to heal, reducing myocardial wall stress and thereby preventing or reversing remodeling, a sign of progressive heart failure. While not wishing to be bound by theory, Applicant believes that intermittent occlusion of the SVC, when achieved over a period of hours, days, weeks, or months, can transition the heart from a Starling curve indicative of heart failure with a reduced ejection fraction to a Starling curve with an LVEDP and LVEDP more indicative of normal cardiac function. Accordingly, Applicant's preliminary animal studies suggest that use of the system of the present invention over a period of hours, days, weeks, or months, e.g., 3-6 months, not only prevents the downward spiral typical of the disease, but also restores cardiac function sufficiently to allow a patient to discontinue use of the system of the present disclosure, pharmaceutical treatment, or both.

[0029] According to another aspect of the present disclosure, a system is provided that includes a catheter having a flow-restricting member configured to be placed in or on the SVC and a controller that controls activation of the flow-restricting member. The controller is preferably programmed to receive inputs indicative of fluctuations in a patient's hemodynamics and adjust activation / deactivation of the flow-restricting member in response to the inputs. Fluctuations in a patient's hemodynamics may be caused by the patient's walking. The controller can be programmed at the time of catheter implantation to maintain complete 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, where the preset number of cardiac cycles or time interval can be continuously adjusted by the controller in response to the patient's heart rate input. The controller can further receive signals from the sensors and / or electrodes indicative of sensed parameters indicative of hemodynamics, such as blood flow velocity, blood volume, and pressures, including blood filling pressures, to the heart, and the controller can continuously adjust the preset number of cardiac cycles or time interval in response to the sensed parameter(s).

[0030] In one preferred embodiment, the catheter is configured to be implanted intravascularly (e.g., via the patient's left subclavian vein) and the flow restricting member is positioned within the SVC, just proximal to the right atrium. The proximal end of the catheter can be coated or impregnated with an antimicrobial agent to allow for sustained catheter use with reduced risk of infection at the site where the catheter is passed percutaneously. The controller is preferably battery-powered and includes a quick-connect coupling that can operably couple the controller's actuation mechanism to the flow restricting member. In a preferred embodiment, the controller is small enough to allow the patient to wear the controller in a brace around their shoulder. Unlike known systems that confine patients to a bed or an emergency care facility, the disclosed system allows patients to ambulate and perform most daily activities, thereby improving patients' quality of life and increasing their compliance with treatment regimens. In one embodiment, the controller is configured to be implanted at a suitable site within the patient's body, for example, subcutaneously below the clavicle. In such embodiments, the implantable controllers are configured to communicate bidirectionally with an external controller, e.g., a mobile device or a system-specific device. The external controllers can be configured to charge the batteries of the implantable controllers, e.g., via respective induction coils in each controller, and can receive data representing sensed parameters, which can include heart rate, blood flow velocity, blood volume, and pressure, including blood filling pressure, to the heart. One or more external power sources can be in electrical communication with the implantable controllers and further configured to provide power to the controllers and charge the batteries of the implantable controllers. The one or more external power sources can generate an alert when the power of the one or more external power sources falls below a threshold power amount.

[0031] In a preferred embodiment, the flow-restricting element comprises a non-compliant or semi-compliant balloon or balloons attached to the distal region of the catheter, and the controller activates the balloons by periodically inflating and deflating the balloons to selectively completely or partially occlude the SVC and / or the azygos vein. For example, the controller can be programmed to intermittently activate the flow-restricting element to at least partially occlude the SVC for a first predetermined time interval and deflate for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval can be at least five times longer than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes, while the second predetermined time interval is 1-30 seconds. In another embodiment, the flow-restricting element can comprise a membrane-covered umbrella, basket, or other mechanical arrangement that can be rapidly transitioned between deployed and deflated positions, e.g., by a drive system connected to the controller. In still further embodiments, the flow restricting member may take the form of a butterfly valve or a ball valve, provided that the flow restricting member does not create a stagnant flow area within the SVC when in the deflated or open position. In still further embodiments, the flow restricting member comprises a cuff configured to be applied to the exterior of the SVC and operates by narrowing or occluding the SVC when inflated.

[0032] The system of the present invention can include a sensor positioned on a catheter placed within the venous or arterial vasculature to measure the patient's heart rate or blood pressure. The sensor preferably generates an output signal that is used as an input to the controller to adjust the degree or timing of occlusion caused by the flow restrictor. In another embodiment, the controller can be configured to connect to a third-party heart rate or blood pressure sensor, such as a commonly used sensor for sports enthusiasts, e.g., a Fitbit, via the patient's smartphone using available wireless standards such as Bluetooth. In this embodiment, the cost, size, and complexity of the controller can be reduced by integrating the controller with commercially available third-party components.

[0033] According to another aspect of the present disclosure, a method of controlling blood flow in a patient includes inserting and guiding a venous occlusion device into a vena cava of the patient, coupling the occlusion device to a controller worn externally by the patient or implanted within the patient, and intermittently activating the venous occlusion device over a time interval comprising multiple cardiac cycles to prevent or reverse the progression of myocardial remodeling over a period of minutes, hours, days, weeks, or months.

[0034] According to another aspect of the present disclosure, a system for use in conjunction with a ventricular assist device (VAD) to improve the efficiency and functionality of the VAD and reduce the risk of adverse side effects of the VAD is provided. The system includes a catheter having a proximal end and a distal region, the catheter sized and shaped for placement (e.g., intravascular placement, such as via a patient's subclavian or jugular vein) such that the distal region is positioned within the patient's superior vena cava (SVC). The system also includes a flow-restricting member, such as an SVC occlusion balloon disposed on the distal region of the catheter, that is selectively activated to at least partially occlude the SVC, and a controller operably coupled to the catheter that intermittently activates the flow-restricting member to at least partially occlude the SVC for a time interval comprising one or more cardiac cycles, thereby reducing cardiac preload and pulmonary artery pressure and improving cardiac performance. For example, the controller may reduce cardiac preload sufficiently during the time interval to improve cardiac performance as measured by at least one of reduced blood filling pressure to the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain.

[0035] The system may further include a first pressure sensor disposed on the catheter proximal to the flow restricting member, the first pressure sensor outputting a first pressure signal, and a second pressure sensor disposed on the catheter distal to the flow restricting member, the second pressure sensor outputting a second pressure signal, and the controller generates a first signal corresponding to a difference between the first and second pressure signals, the first signal indicating a degree of occlusion of the flow restricting member. Alternatively, the system may include a pressure switch disposed on the catheter and having a first lumen with a first open end disposed proximal to the flow restricting member and a second lumen with a second open end disposed at the flow restricting member. The pressure switch may be configured to generate a signal indicating a pressure difference between the first and second lumens. The controller may include data transfer circuitry configured to receive the signal and communicate the signal to a patient's computing device for display to the patient.

[0036] The controller can use the first signal to determine when to activate the flow restricting member to at least partially occlude the SVC and when to cease activation of the flow restricting member. The controller can also be programmed to activate an alarm based on the first signal as a safety signal for the operator. The controller can also be programmed to transmit an alert condition to a clinician monitoring the patient via the cellular communication capabilities of the computing device. In one embodiment, the controller is configured to be implanted subcutaneously within a patient at an appropriate site, for example, subclavian.

[0037] The controller can also be programmed to intermittently activate the flow restricting member to at least partially occlude the SVC for a first predetermined time interval and contract for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval can be at least 10 times greater than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes, while the second predetermined time interval is 1-10 seconds. The controller can be programmed to vary the first predetermined time interval based on a signal or based on the patient's heart rate.

[0038] In one preferred embodiment, the flow restricting element is an inflatable cylindrical balloon, the 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 of 30 to 60 mmHg, allowing fluid to flow through the SVC to the patient's right atrium. The system can further include an azygos vein occlusion balloon disposed on the catheter proximal to the flow restricting element. The azygos vein occlusion balloon can be selectively activated to at least partially occlude the patient's azygos vein, and the azygos vein occlusion balloon and the SVC occlusion balloon can be independently activated. The system also allows operation of the VAD at slower speeds to achieve hemodynamic responses equal to or greater than the hemodynamic responses of the VAD alone at higher speeds.

[0039] The system can also include a left ventricular assist device (LVAD), the LVAD including a catheter having a proximal end and a distal region, the distal region having an inflow end and an outflow end, the catheter sized and shaped for placement via a patient's femoral artery, with the inflow end positioned within the patient's left ventricle and the outflow end positioned within the patient's aorta. The LVAD also includes a pump, e.g., an impeller pump, positioned on the distal region of the catheter, the pump being selectively actuable to pump blood from the left ventricle through the inflow end and eject blood into the aorta through the outflow end, an LVAD controller operably coupled to the LVAD to actuate the pump to pump blood from the left ventricle into the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. An LVAD controller operably coupled to the catheter of the system can regulate the activation and deactivation of the flow restricting member to at least partially occlude the SVC while the LVAD controller operates the pump to pump blood from the left ventricle into the aorta.

[0040] Alternatively, or in addition, the system can further include a right ventricular assist device (RVAD) including a pump, e.g., an impeller pump, that can be selectively activated to pump blood from the SVC through the inflow end of the RVAD and eject blood into the pulmonary artery through the outflow end of the RVAD. The controller is also operably coupled to the RVAD and can activate the pump to pump blood from the SVC into the pulmonary artery, thereby unloading the right ventricle. For example, the controller can activate a flow restricting member to at least partially occlude the SVC simultaneously with the controller activating the pump to pump blood from the SVC into the pulmonary artery.

[0041] In another preferred embodiment, the RVAD includes a catheter having a proximal end and a distal region, the distal region having an inflow end and an outflow end, the catheter sized and shaped for placement via a patient's femoral artery, with the outflow end positioned within the patient's pulmonary artery and the inflow end positioned within the patient's IVC. The RVAD also includes a pump, e.g., an impeller pump, positioned on the distal region of the catheter, which can be selectively activated to pump blood from the IVC through the inflow end and eject blood into the pulmonary artery through the outflow end, and an RVAD controller operably coupled to the RVAD to activate the pump to pump blood from the IVC into the pulmonary artery, thereby unloading the right ventricle. The RVAD controller operably coupled to the catheter of the system can regulate activation and deactivation of a flow restricting member to at least partially occlude the SVC while the RVAD controller activates the pump to pump blood from the IVC into the pulmonary artery.

[0042] The system may also be used to alter a patient's heart and perform a cardiac procedure. This approach may involve inserting a first catheter including a flow restricting member into the patient's superior vena cava (SVC) such that the flow restricting member is positioned within the SVC, and at least partially occluding the SVC by activating the flow restricting member within the SVC. The cardiac procedure may be performed on the patient's heart prior to, within, and / or after at least partially occluding the SVC. The flow restricting member may be deactivated and reactivated within the SVC prior to or during the cardiac procedure. Activation of the flow restricting member may stimulate the vagus nerve and increase the patient's urinary flow.

[0043] A parameter related to the patient's heart may be measured to generate a first measured parameter, which may be used to determine whether the measured parameter meets a predetermined threshold. Determining the measured parameter may include receiving a first signal from a first sensor positioned in the SVC and receiving a second signal from a second sensor positioned in the SVC. The first sensor may be an electrode and may be positioned on a catheter proximal to the flow restricting member. The second sensor may also be an electrode and may be positioned on a catheter distal to the flow restricting member. A cardiac procedure may be performed if the measured parameter is determined to meet the predetermined threshold. Partial and / or complete SVC occlusion helps make the heart more susceptible to a successful cardiac procedure. The cardiac procedure may be a procedure distinct from partial / total SVC obstruction, such as implantation of a cardiac prosthesis (e.g., artificial valve, regurgitation reduction device, clip, ring, ventricular assist device (VAD), etc.), using a commercially available system and / or coronary artery reconstruction using percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

[0044] If the first measured parameter is determined not to meet the predetermined threshold, the operating parameter may be altered and a second parameter may be measured. The second parameter may be measured to generate a second measured parameter, which may be used to determine whether the second measured parameter meets the predetermined threshold. The cardiac procedure may be performed if the second measured parameter is determined to meet the predetermined threshold.

[0045] The system may further include inserting a second catheter, adapted for performing a cardiac procedure, into the heart via the inferior vena cava catheter (IVC), the second catheter being positioned within and along at least a portion of the first catheter.

[0046] The system may also be used to reduce volume overload in a patient's heart. For example, a catheter including a flow-restricting member (e.g., a balloon) may be inserted into the patient's superior vena cava (SVC) such that the flow-restricting member is positioned within the SVC. A left ventricular assist device (LVAD) may also be implanted in the patient's left ventricle. The flow-restricting member may be activated within the SVC to at least partially occlude the SVC during or after implantation of the LVAD. The flow-restricting member may then be deflated for a set period of time following the step of implanting the LVAD. Activation of the flow-restricting member may reduce intracardiac pressure and / or the volume of blood flow within the right ventricle.

[0047] A method for reducing volume overload may include receiving a signal from one or more sensors. The method may include receiving a first signal from an accelerometer disposed on the catheter, the first signal indicating a flow restricting member at least partially occluding the SVC. The flow restricting member may be deactivated based on the first signal. Alternatively, the method may include receiving a first signal from a sensor disposed on the flow restricting member, the first signal indicating contact between the SVC and the flow restricting member. In another embodiment, the method may include generating light from a light disposed on the catheter proximal to the flow restricting member, determining a first signal from a light sensor disposed on the catheter distal to the flow restricting member, and determining the degree of occlusion of the flow restricting member based on the first signal. In another embodiment, the method may include receiving a signal from a stretch gauge disposed on a portion of the catheter, the flow restricting member, or both the catheter and the flow restricting member. The flow restricting member may be deactivated 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 exemplary aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the following drawings and detailed description. The present invention provides, for example, the following items. (Item 1) 1. A method of altering a patient's heart to perform a cardiac procedure, the method comprising: inserting a catheter comprising a flow restricting member into the patient's superior vena cava (SVC) such that the flow restricting member is positioned within the SVC; at least partially occluding the SVC by actuating the flow restrictor within the SVC; measuring a cardiac parameter of the patient and generating a measured parameter; determining whether the measured parameter meets a predetermined threshold; performing the cardiac procedure on the patient's heart if the measured parameter is determined to meet the predetermined threshold; A method comprising: (Item 2) 2. The method of claim 1, wherein determining that the measured parameter meets the predetermined threshold occurs before performing any portion of the cardiac procedure. (Item 3) Item 14. The method of item 1, wherein actuating the flow restricting member within the SVC occurs simultaneously with performing at least a portion of the cardiac procedure. (Item 4) 2. The method of claim 1, wherein actuating the flow restricting member within the SVC occurs prior to performing the cardiac procedure on the patient's heart. (Item 5) 2. The method of claim 1, wherein performing the cardiac procedure includes implanting a clip in a heart valve. (Item 6) 2. The method of claim 1, wherein performing the cardiac procedure includes implanting a prosthetic valve annulus. (Item 7) 2. The method of claim 1, wherein performing the cardiac procedure comprises implanting a valve prosthesis. (Item 8) 2. The method of claim 1, wherein performing the cardiac procedure comprises implanting a left ventricular assist device (LVAD). (Item 9) 2. The method of claim 1, further comprising introducing a second catheter into the heart via the patient's inferior vena cava (IVC), the second catheter adapted to perform the cardiac procedure. (Item 10) 2. The method of claim 1, further comprising introducing a second catheter into the heart via the patient's superior vena cava (SVC), the second catheter adapted to perform the cardiac procedure. (Item 11) Item 11. The method of item 10, wherein the second catheter is positioned within the catheter along at least a portion of the catheter. (Item 12) determining that the measured parameter does not meet the predetermined threshold; modifying an operating parameter after determining that the measured parameter does not meet a predetermined threshold; Item 1, the method of claim 1 further comprising: (Item 13) measuring a second parameter related to the patient's heart to generate a second measured parameter; determining whether the second measured parameter meets the predetermined threshold; and Item 13. The method of item 12, further comprising: (Item 14) 14. The method of claim 13, further comprising verifying that the second measured parameter meets a predetermined threshold, wherein verifying that the second measured parameter meets the predetermined threshold occurs before performing the cardiac procedure on the patient's heart. (Item 15) 10. The method of claim 1, further comprising at least partially occluding the SVC by deactivating the flow restricting member and reactivating the flow restricting member within the SVC prior to or during the cardiac procedure. (Item 16) Item 12. The method of item 1, wherein actuating the flow restricting member within the SVC stimulates the vagus nerve and increases urinary flow in the patient. (Item 17) Determining the measured parameter comprises: receiving a first signal from a first sensor disposed within the SVC; receiving a second signal from a second sensor disposed within the SVC, the first sensor being an electrode disposed on the catheter proximal to the flow restricting member and the second sensor being an electrode disposed on the catheter distal to the flow restricting member; The method according to item 1, comprising: (Item 18) 1. A method of reducing cardiac volume overload in a patient, the method comprising: inserting a catheter comprising a flow restricting member into the patient's superior vena cava (SVC) such that the flow restricting member is positioned within the SVC; implanting a left ventricular assist device (LVAD) in the patient's left ventricle; at least partially occluding the SVC by actuating the flow restrictor within the SVC; deactivating the flow restricting member for a period of time after implanting the LVAD. A method comprising: (Item 19) 20. The method of claim 18, wherein actuating the flow restricting member reduces pressure within the patient's heart. (Item 20) Item 19. The method of item 18, wherein actuating the flow restricting member reduces the volume of fluid in the right ventricle. (Item 21) 20. The method of claim 18, wherein actuating the flow restricting member within the SVC occurs during implantation of the LVAD. (Item 22) Item 19. The method of item 18, wherein activating the flow restricting member within the SVC occurs after implanting the LVAD. (Item 23) Item 19. The method of item 18, wherein actuating the flow restricting member comprises inflating a balloon within the SVC. (Item 24) determining a first signal from an accelerometer disposed on the catheter, the first signal being indicative of the flow restricting member at least partially occluding the SVC; further comprising Item 19. The method of item 18, wherein the flow restricting member is deactivated based on the first signal. (Item 25) receiving a first signal from a sensor disposed on the flow restricting member, the first signal indicating contact between the SVC and the flow restricting member; further comprising Item 19. The method of item 18, wherein the flow restricting member is deactivated based on the first signal. (Item 26) generating light from using a first light disposed on the catheter proximal to the flow restricting member; determining a first signal from an optical sensor disposed on the catheter distal to the flow restricting member; determining a degree of obstruction of the flow restricting member based on the first signal; Item 19. The method of item 18, further comprising: (Item 27) receiving a first signal from a stretch gauge disposed on one or more of the catheter and the flow restricting member, the first signal indicating a degree of occlusion by the flow restricting member; further comprising Item 19. The method of item 18, wherein the flow restricting member is deactivated based on the first signal. (Item 28) 1. A device for occluding the superior vena cava (SVC) of a patient, comprising: a catheter configured to be positioned within the SVC, the catheter comprising a distal region; a flow restricting member disposed on a distal region of the catheter and configured to be selectively actuated; a pressure switch disposed on a distal region of the catheter, the pressure switch comprising a first lumen with a first open end disposed proximal to the flow restricting member and a second lumen with a second open end disposed distal to the flow restricting member, the pressure switch configured to generate a signal indicative of a pressure difference between the first lumen and the second lumen; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC based on the signal; and An apparatus comprising: (Item 29) Item 29. The apparatus of item 28, wherein the controller is configured to contract the flow restricting member based on the signal. (Item 30) Item 29. The device of item 28, wherein the controller is configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a first predetermined time interval and to contract the flow restricting member for a second predetermined time interval. (Item 31) Item 31. The apparatus of item 30, wherein the controller is configured to vary the first time interval based on the signal. (Item 32) Item 31. The apparatus of item 30, wherein the controller is configured to vary the first time interval based on a patient's heart rate. (Item 33) Item 29. The apparatus of item 28, wherein the controller is configured to sufficiently reduce cardiac preload during the interval to improve cardiac performance as measured by at least one of reduced blood filling pressure on the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac strain. (Item 34) Item 29. The apparatus of item 28, wherein the controller is configured to treat heart failure. (Item 35) Item 29. The device of item 28, wherein the flow restricting member is an inflatable balloon. (Item 36) Item 29. The device of item 28, wherein the flow restricting member comprises a relief valve having an open position and a closed position. (Item 37) Item 29. The apparatus of item 28, wherein the controller is configured for implantation. (Item 38) Item 29. The apparatus of item 28, wherein the controller comprises a data transfer circuit configured to receive the signal. (Item 39) Item 39. The apparatus of item 38, wherein the data transfer circuitry is configured to communicate the signal to a patient's computing device for display to the patient. (Item 40) 30. The apparatus of claim 28, wherein the controller is programmed to transmit an alert status based on the signal to a clinician monitoring the patient via a cellular communication capability of the computing device. (Item 41) 29. The apparatus of claim 28, wherein the catheter comprises one or more sensors for detecting the patient's heart rate. (Item 42) Item 29. The apparatus of item 28, further comprising one or more external power sources in electrical communication with the controller and configured to provide power to the controller. (Item 43) 1. A device for occluding a superior vena cava (SVC) in a patient, the device comprising: a catheter having a distal region configured to be positioned within the SVC; a flow restricting member disposed on a distal region of the catheter and configured to be selectively actuated; a first sensor disposed on the catheter proximal to the flow restricting member and configured to output a first signal; a second sensor disposed on the catheter distal to the flow restricting member and configured to output a second signal; a controller operably coupled to the catheter and configured to intermittently actuate the flow restricting member to at least partially occlude the SVC based on the first signal and the second signal; An apparatus comprising: (Item 44) Item 44. The apparatus of item 43, wherein the first sensor and the second sensor are pressure sensors, and the controller is configured to determine a difference value based on the first signal and the second signal, and generate a first output based on the difference value to indicate a degree of obstruction of the flow restricting member. [Brief explanation of the drawings]

[0049] The features and advantages of the present disclosure will become apparent from the detailed description of the embodiments of the present disclosure presented below when read in conjunction with the accompanying drawings.

[0050] [Figure 1A] FIG. 1A is a frontal, partially cut-away view of the major arteries and veins of the heart.

[0051] [Figure 1B] FIG. 1B shows the vena cava, including the main vein that connects to the vena cava.

[0052] [Figure 2A] 2A and 2B are graphs showing Frank-Starling curves corresponding to normal and diseased cardiac conditions. [Figure 2B] 2A and 2B are graphs showing Frank-Starling curves corresponding to normal and diseased cardiac conditions.

[0053] [Figure 3] FIG. 3 is a graph of exemplary pressure-volume loop curves illustrating the relationship between left ventricular pressure and left ventricular volume throughout the cardiac cycle in a patient with normal cardiac function and in a patient suffering from congestive heart failure.

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

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

[0056] [Figure 4C] FIG. 4C is a diagram of the power supply and charging base.

[0057] [Figure 5] 5A-5B are schematic diagrams of the catheter of FIGS. 4A and 4B, in which the flow restricting member includes a cylindrical balloon with an altered anchoring member, showing the flow restricting member in an expanded and contracted state, respectively.

[0058] [Figure 6] FIG. 6 is a schematic diagram of the catheter of FIGS. 4A and 4B, in which the flow restricting member includes a mechanically actuated, membrane-covered basket.

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

[0060] [Figure 8] 8A and 8B are schematic diagrams of a flow restricting member comprising a spherical balloon shown in an expanded and deflated state, respectively.

[0061] [Figure 9] 9A and 9B are schematic diagrams of a flow restrictor member including a spring-loaded plug shown in an expanded and contracted state, respectively.

[0062] [Figure 10] 10A and 10B are schematic diagrams of a flow restrictor member including another embodiment of a spring-loaded plug shown in an expanded and contracted state, respectively.

[0063] [Figure 11] FIG. 11 shows graphs and tables showing left ventricular (LV) pressures and LV volumes over several consecutive heart rates in a porcine model following complete occlusion of the inferior vena cava (IVC).

[0064] [Figure 12] FIG. 12 shows graphs and tables showing LV pressures and LV volumes over several consecutive heart rates in a porcine model following partial occlusion of the superior vena cava (SVC).

[0065] [Figure 13] FIG. 13 is a graph showing the variation of pressure with left ventricular volume during occlusion and release of the superior vena cava (SVC) in a pig suffering from heart failure in accordance with the principles of the present disclosure. [Figure 14] FIG. 14 is a graph showing the change in pressure with right ventricular volume during occlusion and release of the superior vena cava (SVC) in a pig suffering from heart failure in accordance with the principles of the present disclosure.

[0066] [Figure 15] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 16] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 17] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 18] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 19] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 20] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 21] Figures 15-22 show the results of the study on test pigs suffering from heart failure. [Figure 22] Figures 15-22 show the results of the study on test pigs suffering from heart failure.

[0067] [Figure 23-1] 23A and 23B show the clinical pressure changes in left ventricular end-diastolic pressure and left ventricular end-systolic pressure during the deflation time of a one-minute episode of sustained SVC obstruction, in accordance with the principles of the present disclosure. [Figure 23-2] Figure 23C illustrates the clinical pressure change in left ventricular volume and ventricular stroke during the collapse time of a one-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 23D illustrates the clinical pressure change in ventricular stroke work during the collapse time of a one-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0068] [Figure 24-1] 24A and 24B show the clinical pressure changes in left ventricular end-diastolic pressure and left ventricular end-systolic pressure during the deflation time of a 5-minute episode of sustained SVC obstruction, in accordance with the principles of the present disclosure. [Figure 24-2] Figure 24C illustrates the clinical pressure change in left ventricular volume and ventricular stroke during the collapse time of a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 24D illustrates the clinical pressure change in ventricular stroke work during the collapse time of a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0069] [Figure 25-1] Figure 25A shows the clinical pressure change in left ventricular end-diastolic pressure during the deflation time of a 10-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 25B shows the clinical pressure change in left ventricular end-systolic pressure during the deflation time of a 10-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. [Figure 25-2]Figure 25C illustrates the clinical pressure change in left ventricular volume and ventricular stroke during the deflation time of a 10-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 25D illustrates the clinical pressure change in ventricular stroke during the deflation time of a 10-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0070] [Figure 26-1] Figures 26A-26C show clinical pressure changes in pulmonary capillary wedge pressure observed during a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 26B shows clinical pressure changes in pulmonary artery pressure observed during a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 26C shows clinical pressure changes in right atrial pressure observed during a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. [Figure 26-2] Figures 26A-26C show clinical pressure changes in pulmonary capillary wedge pressure observed during a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 26B shows clinical pressure changes in pulmonary artery pressure observed during a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure. Figure 26C shows clinical pressure changes in right atrial pressure observed during a 5-minute episode of continuous SVC obstruction in accordance with the principles of the present disclosure.

[0071] [Figure 27-1] Figure 27A shows the clinical pressure change of systolic pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure, Figure 27B shows the clinical pressure change of diastolic pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure, and Figure 27C shows the clinical pressure change of mean arterial pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure. [Figure 27-2] FIG. 27D shows the clinical pressure changes in mean pulmonary artery pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure. [Figure 27-3] FIG. 27E shows the clinical pressure changes of mean pulmonary capillary wedge pressure during 5 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure.

[0072] [Figure 28A] FIG. 28A shows the clinical pressure changes in mean pulmonary artery pressure during 10 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure. [Figure 28B] FIG. 28B shows the clinical pressure changes in mean arterial pressure during 10 minutes of continuous SVC occlusion in accordance with the principles of the present disclosure.

[0073] [Figure 29] FIG. 29 illustrates cardiac output before and during obstruction of the SVC in accordance with the principles of the present disclosure.

[0074] [Figure 30] FIG. 30 illustrates pulmonary artery systolic pressure with and without SVC obstruction in accordance with the principles of the present disclosure.

[0075] [Figure 31] FIG. 31 is a prophetic example of how SVC obstruction according to the principles of the present disclosure is expected to alter the spectrum of diseases.

[0076] [Figure 32] FIG. 32 is a perspective view of a cylindrical flow restrictor member.

[0077] [Figure 33] FIG. 33 is a cross-sectional view of a cylindrical flow restriction member showing a relief valve.

[0078] [Figure 34] 34A-B are cross-sectional views of a cylindrical flow restriction member with binary and progressive relief valves.

[0079] [Figure 35] FIG. 35 is a top view of a cylindrical flow restrictor member with a relief valve in a closed position.

[0080] [Figure 36] 36A-B are top views of a cylindrical flow restriction member having a binary relief valve and a progressive relief valve in the open position.

[0081] [Figure 37] 37A-B are perspective and cutaway views of a cylindrical flow restricting member engaged with a stent.

[0082] [Figure 38] 38A-B are top views of a cylindrical flow restricting member with a balloon occluder in inflated and deflated positions.

[0083] [Figure 39] 39A-B are top views of a cylindrical flow restricting member with a cylindrical balloon occluder in inflated and deflated positions.

[0084] [Figure 40] 40A-B are perspective and cutaway views of a stent coupled to a relief valve.

[0085] [Figure 41] FIG. 41 is a cutaway view of a cylindrical flow restrictor connected to a filter.

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

[0087] [Figure 43A] 43A-F are diagrams of an introducer sheath entering the SVC, a flow restricting member within the SVC, a catheter, and one or more sensors. [Figure 43B] 43A-F are diagrams of an introducer sheath entering the SVC, a flow restricting member within the SVC, a catheter, and one or more sensors. [Figure 43C]43A-F are diagrams of an introducer sheath entering the SVC, a flow restricting member within the SVC, a catheter, and one or more sensors. [Figure 43D] 43A-F are diagrams of an introducer sheath entering the SVC, a flow restricting member within the SVC, a catheter, and one or more sensors. [Figure 43E] 43A-F are diagrams of an introducer sheath entering the SVC, a flow restricting member within the SVC, a catheter, and one or more sensors. [Figure 43F] 43A-F are diagrams of an introducer sheath entering the SVC, a flow restricting member within the SVC, a catheter, and one or more sensors.

[0088] [Figure 44] FIG. 44 is a diagram of an introducer sheath placed in the SVC, a flow restricting member incorporated within the introducer sheath, and a catheter placed within the heart.

[0089] [Figure 45] FIG. 45 is a diagram of an occlusion system having an azygos vein occlusion balloon and a second occlusion balloon placed in the SVC.

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

[0091] [Figure 47] 47A-B show views of the outside and inside of the occlusion cuff, and FIGS. 47C-D show perspective views of the occlusion cuff.

[0092] [Figure 48] FIG. 48 is another exemplary system constructed in accordance with the principles of the present disclosure.

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

[0094] [Figure 50] FIG. 50 is a graph showing the enhancement of unloading capacity for SVC obstruction when used in combination with a transvalvular LVAD.

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

[0096] [Figure 52] FIG. 52 shows an SVC occlusion system in combination with another transvalvular RVAD.

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

[0098] [Figure 54] FIG. 54 shows an SVC occlusion system with a flow restricting member placed on an introducer sheath in combination with an LVAD.

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

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

[0101] [Figure 57] Figure 57A shows a normal heart, Figure 57B shows a chronically compensated heart, and Figure 57C shows a decompensated heart.

[0102] [Figure 58] FIG. 58 shows an SVC occlusion system with a flow restricting member disposed on an introducer sheath that is placed within the SVC.

[0103] [Figure 59] FIG. 59 shows an SVC occlusion system with a flow restricting member disposed on an introducer sheath placed in the SVC and a delivery catheter for deploying a valve clip via the IVC.

[0104] [Figure 60] FIG. 60 is a flowchart of an exemplary method of deploying an SVC occlusion system within the SVC and performing a cardiac procedure.

[0105] [Figure 61] FIG. 61 shows an SVC occlusion system with a flow restricting member disposed on an introducer sheath placed in the SVC and a delivery catheter for deploying the prosthetic valve annulus via the IVC.

[0106] [Figure 62] FIG. 62 shows an SVC occlusion system with a flow restricting member disposed on an introducer sheath placed in the SVC and a delivery catheter for transcatheter prosthesis deployment via the IVC.

[0107] [Figure 63] FIG. 63 shows an SVC occlusion system with a flow restricting member disposed on an introducer sheath placed within the SVC and a delivery catheter placed within the introducer sheath. DETAILED DESCRIPTION OF THE INVENTION

[0108] Detailed Description of the Invention 1A and 1B, the human anatomy for which the present disclosure is designed to deploy and operate will be described in connection with the systems and methods of the present disclosure.

[0109] 1A, deoxygenated blood returns to the heart 10 via the vena cava 11, which includes the superior vena cava 12 and the inferior vena cava 13, which connect to the heart's right atrium 14. From the right atrium 14, blood travels through the tricuspid valve 15 to the right ventricle 16, which pumps the blood to the lungs via the pulmonary artery 17. Oxygenated blood returns from the lungs via the pulmonary veins to the left atrium 18. The oxygenated blood then flows into the left ventricle 19, which pumps the blood to the rest of the body via the aorta 20.

[0110] As shown in Figure 1B, the superior vena cava 12 is located at the top of the vena cava 11, while the inferior vena cava 13 is located at the bottom of the vena cava. Figure 1B also shows the azygos vein 16 and some of the major veins that connect to the vena cava. As described herein, obstruction of the inferior vena cava 13 can pose a risk of venous congestion and, in particular, potential blockage or enlargement of the hepatic and / or adrenal veins, which can worsen, rather than improve, the patient's cardiovascular status and overall health.

[0111] In accordance with one aspect of the present disclosure, Applicant has determined that selective intermittent occlusion of the superior vena cava ("SVC") poses fewer potential harmful risks than occlusion of the inferior vena cava ("IVC"). Furthermore, Applicant's animal and human studies have demonstrated that controlling venous return to the right ventricle by partially or completely occluding the SVC beneficially reduces RVEDP, RVEDV, LVEDP, and LVEDV without adversely reducing left ventricular systolic pressure (LVSP).

[0112] Applicant understands that selective intermittent occlusion of the SVC, compared with IVC occlusion, will reduce the risk of worsening renal congestion, a major cause of "cardiorenal" syndrome. Cardiorenal syndrome is impaired renal function due to volume overload and neurohormonal activation in patients with heart failure. Volume overload can occur where a weakened heart cannot pump as much blood, leading to less blood flow through the kidneys. With less blood flow through the kidneys, less blood is filtered by the kidneys and less water is released through urination, causing excess volume to be retained in the body. With excess volume, the heart pumps increasingly inefficiently, and the patient ultimately dies as the body becomes progressively more congested.

[0113] Applicant understands that IVC obstruction generally reduces the kidney's ability to filter fluid by reducing blood flow through the kidney because the obstructed IVC increases pressure in the renal veins. IVC obstruction also causes blood to stagnate, preventing otherwise deoxygenated blood from returning to the heart. As a result, renal function may be excessively reduced, exacerbating congestion. However, SVC obstruction ultimately improves renal function by increasing blood flow to the kidney. Specifically, by reducing blood flow into the right atrium through SVC obstruction, the volume within the left ventricle is ultimately reduced, allowing muscle fibers to stretch within normal ranges, naturally increasing contractility and allowing the heart to pump more fluid into the kidney. The kidneys can then extract water, which can be removed from the body via urination. It should further be understood that during SVC obstruction, a negative pressure sink is created within the right atrium caused by the sudden reduction in right atrial pressure and volume. As a result, blood flow from the renal vein can be accelerated, enhancing renal decongestion, facilitating blood flow across the kidney, and increasing urine output. Thus, SVC occlusion can benefit patients with heart failure and / or cardiorenal syndrome by reducing cardiac and pulmonary pressures and facilitating decongestion.

[0114] Additionally, while SVC implantation allows for device implantation in the superior phrenic artery, superior phrenic artery devices cannot be used in the IVC without penetrating the heart and traversing the right atrium. Furthermore, SVC occluder implantation avoids the need for groin access required for IVC implantation, which limits mobility and makes portable devices impractical for short- or long-term use. Furthermore, whereas small changes in IVC occlusion (duration or degree) can cause more dramatic changes in preload reduction and therefore total cardiac output / systemic blood pressure, the disclosed systems and methods allow for predictable, fine-tuned reduction in venous return (preload reduction).

[0115] Applicant understands that intermittent occlusion of the SVC (i.e., cardiopulmonary unloading) over a period of time (e.g., minutes, hours, days, weeks, or months) will beneficially allow a patient's heart to halt or recover from myocardial remodeling. Applicant's animal and human studies have shown that the system allows the myocardium to shift from a pressure-stroke volume curve indicative of heart failure toward a pressure-stroke volume curve that more closely resembles that of a healthy heart.

[0116] In general, the disclosed systems and methods can be used to treat any disease and improve cardiac function by preventing or reversing myocardial remodeling, particularly those conditions in which a patient suffers from heart failure. Such conditions include, but are not limited to, systolic heart failure, diastolic (non-systolic) heart failure, decompensated heart failure in patients with ADHF (adult-heart-deficient heart failure), chronic heart failure, acute heart failure and pulmonary hypertension, heart attack, heart failure with preserved ejection fraction, right-sided heart failure, restrictive and constrictive cardiomyopathy, and cardiorenal syndromes (types 1-5). The disclosed systems and methods can also be used as prophylactic measures to mitigate the aftermath of acute right or left ventricular myocardial infarction, pulmonary hypertension, RV failure, post-open-heart surgery shock, or post-orthotopic heart transplant (OHTx) rejection, or otherwise for cardiorenal applications and / or to treat renal dysfunction, liver dysfunction, or lymphatic congestion. Additionally, the systems and methods of the present disclosure may reduce hospitalizations caused by various illnesses described herein, including at least acute exacerbations.

[0117] The relationship between left ventricular pressure or volume and stroke volume is often referred to as the Frank-Starling relationship or "Starling curve" and is illustrated in Figures 2A-2B. This relationship demonstrates that cardiac stroke volume depends on preload, contractility, and afterload. Preload refers to the volume of blood returning to the heart, contractility is defined as the intrinsic ability of the myocardium to contract, and afterload is determined by vascular resistance and impedance. In heart failure due to diastolic or systolic dysfunction, reduced stroke volume leads to increased volume and pressure within the left ventricle, which can result in pulmonary edema. Increased ventricular volume and pressure also result in increased workload and increased myocardial oxygen consumption. This overworking of the heart leads to deterioration of cardiac function as the heart becomes increasingly oxygen-deprived due to a mismatch between supply and demand. Furthermore, as volume and pressure build up within the heart, contractile function deteriorates due to myocardial stretching. This condition is referred to as "congestive heart failure."

[0118] Referring to Figure 2, a series of Starling curves are shown, with the top curve (Curve 1) representing normal cardiac function. As can be seen, stroke volume increases with increasing LVEDP or LVEDV and begins to flatten out, i.e., the slope of the curve decreases only at very high pressures or volumes. The middle curve (Curve 2) shows a patient who has just suffered an acute myocardial infarction ("AMI"), with a reduced stroke volume at each value of LVEDV or LVEDP. However, because the heart is just beginning to experience overload caused by the local effects of the infarction, overall ventricular contractility is still relatively good, and stroke volume remains relatively high at low LVEDP or low LVEDV. In contrast, patients with previous cardiac injury experience a gradual decline in cardiac function as myocardial remodeling progresses over time, compensating for the increased workload and reduced oxygen uptake, as shown in the bottom curve (Curve 3) in Figure 2A. As noted above, this results in a progressive decrease in stroke volume as the ventricles expand due to generally greater volumes and pressures at each stage of the cardiac cycle. As can be seen by comparing curves 1 and 3, stroke volume continues to decrease as LVEDP or LVEDV increases until the heart eventually fails or the patient dies from cardiovascular disease.

[0119] FIG. 2B provides another formulation of the Frank-Starling curve, i.e., curve 6, illustrating the difference in function between a healthy heart and one with heart failure. Line 7 represents the Frank-Starling curve for a normal, healthy heart up to point 8. As described with respect to FIG. 2A, for a normal heart, as end-diastolic volume increases, stroke volume increases. However, for a healthy heart, beyond point 8, increases in end-diastolic volume no longer result in increases in stroke volume, and continued increases in end-diastolic volume do not result in further increases in stroke volume. This phenomenon is illustrated by the flat, solid line extending substantially horizontally beyond point 8. The decreasing dashed line 9 extending beyond point 8 in FIG. 2B represents the Frank-Starling curve for a patient with heart failure. Dashed line 9 indicates that for a patient with heart failure, further increases in end-diastolic volume do not result in a nearly flat stroke volume; instead, stroke volume decreases. Therefore, increased EDV in HF patients leads to a further reduction in SV, leading to a downward spiral of cardiac function and, ultimately, death. Figure 2B reflects a phenomenon referred to as "diastolic ventricular interaction," which is caused in part by the structural arrangement of the cardiac chambers. As explained, for example, in an article by J. Atherton et al. entitled "Diastolic ventricular interaction in chronic heart failure" (Lancet 1997; 349:1720-24), the pericardium constrains the extent to which the ventricles of a failing heart can expand. Thus, as right ventricular end-diastolic volume increases, this inevitably causes a reduction in left ventricular end-diastolic volume. As reported in that article, the reduction in right ventricular diastolic filling caused by external lower body suction allows for increased left ventricular diastolic filling.

[0120] Applicant has realized that the aforementioned phenomenon can be advantageously utilized in the context of the present disclosure to improve cardiac performance. Specifically, in the presence of heart failure and pulmonary hypertension, right ventricular congestion due to increased volume overload can reduce LV stroke volume and cardiac output by pushing the interventricular septum toward the left ventricular cavity. By occluding blood flow through the SVC, right ventricular pressure and volume are reduced. This, in turn, will shift the interventricular septum away from the LV cavity, allowing for increased left ventricular stroke volume and enhanced cardiac output. For these reasons, SVC occlusion according to the principles of the present disclosure can preferably alter diastolic ventricular interactions and enhance cardiac output. Specifically, with respect to diastolic heart failure, SVC occlusion according to the principles of the present disclosure can provide reduced blood filling pressures to the heart, increased LV relaxation (tau), increased LV capacitance, increased myocardial relaxation, reduced LV stiffness, and reduced cardiac strain. The effect of the present disclosure's SVC occlusion can thus be visualized as a shift in dashed line 9 of the Frank-Starling curve 6 in FIG. 2B for a patient with heart failure toward a lower EDV, which, in effect, moves cardiac performance upward and more closely toward the flat portion of the curve extending beyond point 8 for a healthy patient. The systems and methods of inducing at least partial intermittent SVC occlusion of the present invention in patients with HF thus improve cardiac function by moving the patient's cardiac contractility toward the healthy range of the Frank-Starling curve for patients with HF.

[0121] FIG. 3 shows an exemplary pressure-volume loop for a normal heart, labeled "normal," corresponding to curve 1 in FIG. 2B, and an exemplary pressure-volume loop for a heart suffering from congestive heart failure, labeled "CHF" (curve 3 in FIG. 2B). For each loop, the end-diastolic ventricular volume and intraventricular pressure correspond to the lower right-hand corner of the loop (point A), while the upper left-hand corner of each loop corresponds to the beginning of systole (point B). The stroke volume of each pressure-volume loop corresponds to the area enclosed within the loop. Therefore, the most beneficial venoregulatory therapy is one that maximizes stroke volume by reducing volume and pressure at point A without causing a negligible reduction at point B.

[0122] According to one aspect of the present disclosure, the systems and methods of the present disclosure are designed to alter or shift a patient's cardiac Starling curve toward the left on the diagram of FIG. 2B (or shift the pressure-volume loop of FIG. 3 toward the left and downward) over the course of treatment over a period of hours, days, weeks, or months. This is done by intermittently completely or partially occluding the SVC (superior vena cava) to reduce the volume of blood entering the right ventricle, and therefore the pressure, that must then be pumped out of the left ventricle. Preliminary animal studies by the applicant have shown that such intermittent occlusion, maintained over several cardiac cycles, reduces myocardial workload and wall stress throughout the cardiac cycle, reduces myocardial oxygen consumption, and improves contractile function.

[0123] 4A, a preferred system 30 of the present disclosure will now be described. System 30 includes a catheter 31 having a flow restricting member 32 connected to a controller 33 that is programmed to intermittently activate flow restricting member 32. As described below, system 30 can optionally be configured to transfer information to and from a conventional computing device 45, such as a smartphone, laptop, smartwatch, or tablet, e.g., an Apple iPhone® 5 or iPad®, sold by Apple Inc. of Cupertino, California, that has installed thereon a special-purpose application for communicating with and / or controlling controller 33.

[0124] Preferably, catheter 31 comprises a flexible tube having a distal portion 34 configured for placement within the SVC (superior vena cava). Distal portion 34 includes a flow restricting member 32 that, in use, is placed within a patient's superior vena cava 12 (see FIG. 1B ) to selectively obstruct blood flow into the right atrium 14. In this embodiment, flow restricting member 32 comprises a balloon that can transition between a deflated state, e.g., to enable intravascular placement, and an expanded, deployed state. Flow restricting member 32 is preferably sized and shaped such that, in the expanded state, flow restricting member 32 partially or completely occludes flow within the SVC. Catheter 31 is coupled at its proximal end 35 to a controller 33 that houses a drive mechanism 36 (e.g., motor, pump) to operate flow restricting member 32, a processor 37 that is programmed to control signals driving mechanism 36, and optional sensors 42 that monitor the patient's physiological parameters, such as heart rate or blood pressure.

[0125] The controller 33 can include a source of inflation medium 48 (e.g., gas or fluid), and the drive mechanism 36 can transfer the inflation medium between the source and the flow restricting member 32 in response to commands from the processor 37. When the flow restricting member 32 is inflated with the inflation medium, it partially or completely occludes venous blood flow through the SVC; when the inflation medium is withdrawn, the flow restricting member 32 contracts, relieving the occlusion and allowing blood flow through the SVC again. The flow restricting member 32 can be a balloon, preferably comprising an elastic or semi-elastic material, such as nylon, which allows the degree of inflation of the balloon to be adjusted to achieve the desired degree of partial or complete occlusion of the SVC. The catheter 31 also has a fail-safe design when partially external, in that when the proximal end of the catheter 31 is connected to the controller 33, only the flow restricting member 32 can be inflated to achieve occlusion. Such a quick release coupling 40 at the proximal end 35 allows for quick release of the catheter from the controller 33 for flushing and / or emergency procedures.

[0126] The controller 33 preferably further includes a power source 39 (e.g., a battery), which provides the necessary power to operate the processor 37, the drive mechanism 36, and the data transfer circuit sensor 38. The controller 33 is sized and weighted so that it can be worn in a brace under the patient's clothing, allowing the system to be used while the patient is ambulatory, or the controller 33 can be implanted within the patient. As described herein below, the processor 37 includes a memory 41 that stores computer software that operates the controller 33. The controller 33 can be configured to be implanted at a suitable location within the patient's body, for example, subcutaneously below the collarbone. In such an embodiment, the implantable controller is configured to bidirectionally communicate with an external controller, such as a computing device 45 or a system-specific device. The external controller can be used to charge the batteries of the implantable controllers, for example, via respective induction coils within or coupled to each controller, and can receive data representing sensed parameters derived from the patient's ambulatory movements, such as heart rate, blood flow velocity, blood volume, and pressure, including blood filling pressure, to the heart.

[0127] In one embodiment, data transfer circuitry 38 monitors input from, for example, external sensors located on catheter 31 and provides those signals to processor 37. Processor 37 is programmed to receive input from data transfer circuitry 38 and adjust the time period over which flow restricting element 32 remains open or the degree of occlusion caused by flow restricting element 32. Thus, for example, catheter 31 may include optional sensors 42 located within distal region 34 of the catheter to measure parameters such as heart rate, blood flow velocity, blood volume, blood filling pressure to the heart, and pressures including central venous pressure. The outputs of sensors 42 are relayed to data transfer circuitry 38 of controller 33, which preprocesses the input signals, for example, decimating and digitizing the outputs of sensors 42, before providing the outputs to processor 37. The signals provided to processor 37 allow for evaluation of the effectiveness of the flow restricting element, for example, by indicating the drop in venous pressure during occlusion and patency, which can be used by the patient or clinician to determine what degree of occlusion is necessary to adjust venous return based on the severity of the patient's congestion. Sensors 43 can also be incorporated into catheter 31 proximal to flow restricting element 32 to measure parameters such as heart rate, blood flow velocity, blood volume, blood filling pressure to the heart, and pressures including central venous pressure. Sensors 43 can be used to determine the degree of occlusion caused by element 32, for example, by monitoring the pressure drop across the flow restricting element.

[0128] As another example, catheter 31 may include electrodes 44 for detecting the patient's heart rate. It is anticipated that it may be desirable to adjust the time interval during which SVC occlusion is maintained in response to the patient's ambulation, with this adjusted time interval typically reflecting the patient's hemodynamic status via detected physiological parameter(s), such as heart rate, blood flow velocity, blood volume, cardiac filling pressure, and / or pressure, including central venous pressure. Accordingly, electrodes 44 provide signals to data transfer circuitry 38, which in turn processes the signals for use by program routines executed by processor 37. For example, if occlusion is maintained for a time programmed during initial system setup to reflect the patient being stationary, e.g., if the flow restricting member is deployed for five seconds and then released for two seconds before re-deploying, it may be desirable to shorten the occlusion time interval to four seconds or longer, depending on the patient's degree of physical activity as detected by changes in heart rate, blood flow velocity, blood volume, cardiac filling pressure, and / or pressure, including central venous pressure, above or below predetermined thresholds. Alternatively, processor 37 may be programmed to maintain partial or total SVC occlusion for a preset number of cardiac cycles determined at the time of initial catheter implantation. Sensor inputs provided to data transfer circuitry 38, such as hemodynamics, may be used to adjust the duty cycle of the flow restricting member in response to the degree of motion detected in the patient. After adjustments are made for the predetermined occlusion time interval, processor 37 may be programmed to maintain partial or total SVC occlusion for a preset number of cardiac cycles.

[0129] The data transfer circuitry 38 may also be configured to provide bidirectional data transfer, e.g., by incorporating wireless circuitry to transfer data from the controller 33 to an external unit for display, review, or adjustment. For example, the data transfer circuitry may include Bluetooth® circuitry, which allows the controller 33 to communicate with the patient's computing device 45. In this manner, the controller may transmit information regarding system function directly to the computing device 45, thereby enabling vital physiological or system parameters to be displayed using an appropriately configured mobile application. The patient may also review the data displayed on the screen of the computing device 45 to determine whether they need to seek medical assistance to correct a malfunction or adjust a system parameter. Furthermore, the mobile application resident on the computing device 45 may be configured to automatically initiate an alert via a cellular network to a clinician monitoring service.

[0130] Optionally, data transfer circuitry 38 can be configured to synchronize receiving data from other mobile applications on computing device 45, thereby reducing the cost and complexity of the inventive system. For example, there are many third-party vendors of monitors on the market that measure physiological parameters in real time, such as Fitbit, Inc. of San Francisco, California, and the Charge HR wristband monitor, which measures physical activity and heart rate. According to one aspect of the present disclosure, data transfer circuitry 38 can be programmed to receive input from such third-party monitors via wireless communication with computing device 45, and processor 37 can be programmed to control actuation of drive mechanism 36 in response to the input. In this embodiment, the catheter need not include any sensors 42, 43, or electrodes 44, thereby significantly simplifying the construction of catheter 31 and fitting 40.

[0131] The catheter 31 can include an anchoring member 46 configured to secure the flow restricting member 32 within the SVC. The anchoring member 46 can be collapsible so that it can be delivered in a contracted state and can expand upon release from a delivery device, e.g., a sheath. The anchoring member 46 can be coupled to the catheter proximal or distal to the flow restricting member 32 and / or can be coupled to the flow restricting member 32. The system shown in FIG. 4A can effectively change the patient's cardiac contractility to the healthy range of the Frank-Starling curve shown in FIG. 2A.

[0132] Referring now to FIG. 4B, the controller 33 is illustrated as being implanted at an appropriate site within the patient's body. As shown in FIG. 4B, an external power source 47 can be configured to charge the implantable controller's power source 39 (e.g., a battery). For example, the external power source 47 can transcutaneously charge the power source 39 via a respective induction coil. The external power source 47 can also be integrated into a garment or appliance worn by the patient. Specifically, the external power source 47 can be stored in a pocket or holder configured to receive the external power source 47. When the garment or appliance is worn by the patient, the pocket or holder is designed to store the external power source 47 in close proximity to the battery 39 for efficient transcutaneous charging. More than one external power source 47 can be integrated into the garment to provide redundant power. The one or more external power sources can be permanently integrated into the garment or appliance, or can be removably engaged with the garment or appliance so that each external power source can be individually detached and attached. For example, as shown in Figure 4B, two external power sources 47 can be integrated into specially designed pockets in a vest 64. The vest 64 includes wires 66 attached to the vest 64 to allow electrical communication between the two external power sources.

[0133] The power supply 47 can issue an alert when the available power voltage reaches or falls below a certain power threshold. For example, the power supply 47 can have a visual and / or audible indicator to alert the patient or caregiver. The visual indicator can be an LED lighting system or display embedded in the surface of the power supply 47, which visually displays information about the available power voltage. The audible indicator can be a speaker embedded in the power supply 47, which sounds an alert when the available power voltage reaches a predetermined threshold. A signal indicating that the available power voltage of the power supply 47 has reached a predetermined threshold can also or alternatively be sent to an external device, such as the computing device 45, and / or directly to the controller 33, and then sent from the controller 33 to the external device, such as the computing device 45, which can be programmed to initiate a visual or audible alert. A further power supply 47 supplies power to the power supply 39 when the primary power source runs out of power to ensure a continuous supply of power to the power supply 39. The power source 47 may include a processor with memory for transcutaneously transmitting and transcutaneously receiving data from the processor 37. The processor of the power source 47 may be used to reprogram the processor 37 and / or store information regarding operating parameters that may later be downloaded by an external device, such as the computing device 45.

[0134] Each external power source 47 can be housed in a wall outlet or charging base 65, shown in FIG. 4C , for electrical connection to charge the external power source. The charging base 65 can be electrically connected to a wall outlet and can be configured to simultaneously charge one or more external power sources 47. To enable continuous connection of the power sources 39 to a given power source, the external power sources 47 are periodically removed from the vest and charged, such that at least one external power source 47 is electrically connected to the power source 39 while other external power sources 47 are being charged by the charging base 65. Additionally, by enabling the system to interface with commercially available heart rate monitors and smartphones and / or tablets, the system offers both reduced cost and reduced complexity.

[0135] Referring now to Figures 5A and 5B, a preferred embodiment of a catheter 31' will be described, which is configured similarly to the catheter 31 of Figures 4A and 4B, except for a modified anchoring member. As shown in Figure 5A, where the flow restricting member 32' is in an expanded, fully occluded state, and as shown in Figure 5B, where the flow restricting member 32' is in a contracted state, the catheter 31' can include radially expanding anchoring arms 49. The anchoring arms 49 are configured, for example, upon emergence from a delivery sheath, to expand radially and contact the inner wall of the superior vena cava 12 to anchor the flow restricting member 32' within the superior vena cava 12.

[0136] Referring now to FIG. 6, another embodiment in which the occlusion portion can include a wire basket is described. The flow restricting element 50 can be formed from a biocompatible material, such as nickel-titanium or stainless steel, and includes a plurality of axially or helically extending wires 51 that, when compressed, are biased to expand radially outward. The flow restricting element 50 preferably includes a biocompatible coating that, in its expanded state, partially or completely occludes flow into the SVC. The wires 51 can be coupled at their distal ends 52 to the distal ends 53 of the control wires 54 and attached at their proximal ends 56 to rings 55. The rings 55 are positioned to slide over the control wires 54, causing the wires 51 to expand radially outward when the control wires 54 are pulled proximally relative to the sheath 57 (see FIGS. 5A and 5B). As shown in FIG. 5B, when a predetermined force is applied to the proximal end of the control wire 54 by the drive mechanism 36, the control wire 54 retracts proximally relative to the catheter sheath 57, transitioning the flow restricting member 50 to its expanded, deployed state. Alternatively, when the drive mechanism 36 is deactivated, the spring force applied by the wire 51 pulls the control wire 54 proximally, allowing the wire 51 to return to its uncompressed, deformed state, lying substantially flat against the control wire 54. As noted above, the flow restricting member 50 incorporates a "fail-safe" design, such that the flow restricting member reverts to the collapsed, contracted state shown in FIG. 5A when the catheter 31 is disconnected from the drive mechanism 36. In this embodiment, the drive mechanism 36 can be a motor, which can be a linear motor, a rotary motor, a solenoid piston, or a wire motor.

[0137] The flow restricting member 50 can be configured to bias the flow restricting member to a contracted position when the catheter 31 is disconnected from the controller 33, and to transition the flow restricting member 50 to an expanded, deployed state only when the catheter is connected to the controller 33 and the processor outputs a signal to the drive mechanism 36 to expand the flow restricting member.

[0138] 7, catheter 31 preferably includes at least three lumens 60, 61, and 62. Lumen 60 can be used as an inflation lumen and / or for delivery of operating wire 54 extending between flow restricting member 32 / 50 and drive mechanism 36 of controller 33. Lumen 61 allows any sensors 42, 43 or electrodes to communicate with data transfer circuitry 38 and any lumen 62 to allow delivery of medication (e.g., drugs) to the heart.

[0139] In operation, the catheter 31 including the flow restricting member 32 / 50 is inserted into the patient's subclavian vein and guided to the patient's SVC, for example, to a location proximal to the ostium of the right atrium (see FIG. 1A). Using surgical techniques known in the art, the flow restricting member 32 / 50 can be inserted and secured to the patient's desired venous location. Proper positioning of the device can be confirmed, for example, using vascular ultrasound. Alternatively, the flow restricting member 32 / 50 can be inserted into a jugular vein or even a peripheral vein under fluoroscopic or ultrasound guidance and guided to the SVC.

[0140] Once the catheter 31 and flow restricting member 32 / 50 are positioned at the desired location, the controller 33 initiates a process in which the occlusion member expands and contracts to intermittently occlude and reopen blood flow into the SVC. The degree to which the flow restricting member obstructs blood flow can be adjusted by adjusting the degree to which the flow restricting member expands radially and over the duration of the occlusion, e.g., over the number of heartbeats. For example, in some embodiments, the flow restricting member can obstruct blood flow into the SVC by a minimum of 50% to a maximum of 100% at any given location. Blood flow impedance can be determined by measuring, for example, pressure drop, pressure fluctuation drop, or visually using ultrasound, using methods known in the art.

[0141] According to one aspect of the present disclosure, the controller 33 includes software stored in the memory 41 that controls the timing and duration of the sequential expansion and contraction of the flow restricting member 32 / 50. As described above, the program routine executed by the processor 37 can use the patient's cardiac cycle as an input. For example, in some embodiments, the software can be configured to activate the flow restricting member 32 / 50 to maintain partial or complete occlusion of the SVC over multiple cardiac cycles, e.g., four or more consecutive heartbeats of the subject. The controller 33 can accept as input the output of the electrodes 44 representing the patient's electrocardiogram (ECG) via the data transfer circuitry 38, or alternatively, the controller 33 can receive such input wirelessly from a third-party heart rate application running on the patient's smartphone, allowing the software executing on the processor 37 to adjust the duration and / or degree of occlusion delivered by the system 30 depending on the patient's heart rate. Thus, for example, if a patient is physically exerting, the duration or degree of obstruction caused by the flow restrictor can be reduced to allow oxygenated blood to replenish the patient's upper extremities more quickly. Alternatively, if the patient's heart rate indicates that they are not exercising, the degree of obstruction of the SVC can be increased to reduce the resting workload on the heart. Alternatively, or in addition, system 30 can accept inputs via data transfer circuitry 38 from optional sensors 42 and 43 or values ​​measured by third-party applications and devices, such as a blood pressure cuff, that indicate the patient's blood pressure, allowing controller 33 to adjust flow through the SVC in response to the patient's blood pressure.

[0142] Controller 33 can be programmed to instruct the flow restricting element to expand when a sensed parameter falls outside a predetermined range and / or exceeds or falls below a predetermined threshold. For example, controller 33 can instruct the flow restricting element to expand when right atrial ("RA") pressure is sensed by optional sensors 42 and / or 43 to be within a predetermined range, e.g., 15-30 mmHg, 18-30 mmHg, 20-30 mmHg, 20-25 mmHg, or exceeds a predetermined threshold, e.g., 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. As another example, controller 33 may direct the flow restricting element to open when the mean pulmonary artery ("PA") pressure detected by any of sensors 42 and / or 43 falls within a predetermined range, e.g., 15-30 mmHg, 18-30 mmHg, 20-30 mmHg, 20-25 mmHg, or exceeds a predetermined threshold, e.g., 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. The predetermined range and / or predetermined threshold may be patient-specific, and controller 33 may be programmed and reprogrammed for individual patients.

[0143] Next, with reference to Figures 8-10, we will describe another form of intravenous flow restricting element suitable for use in occluding the SVC. While Figures 4-6 depict a cylindrical flow restricting element, other shapes may be used, as will be apparent to those skilled in the art. Additionally, anchoring elements may be incorporated, although not illustrated in Figures 8-10. Each pair of Figures 8A, 8B, 9A, 9B, and 10A, 10B illustrates each flow restricting element as having a collapsed, contracted state (Figures 8A, 9A, and 10A), in which the flow restricting element does not significantly impede blood flow, and an expanded, deployed state (Figures 8B, 9B, and 10B), in which the flow restricting element partially or completely occludes blood flow through the SVC.

[0144] Specifically, with reference to Figures 8A and 8B, a catheter 70 includes a balloon 71 attached to a distal end 72. Balloon 71 is shown as having a circular ball shape.

[0145] 9A and 9B, a catheter 80 includes a flow restricting member 81 that includes a spring-loaded plug 82 formed from a biocompatible material (e.g., beryllium) and having a tapered conical shape. The spring-loaded plug 82 is captured in its collapsed, contracted state within a sheath 83 disposed 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 delivery of the catheter 80, the spring-loaded plug 82 is captured in its low-profile state within the sheath 83, allowing blood flow into the SVC. To expand the spring-loaded plug 82, force is applied via a control wire 86 to pull the plug 82 out of the sheath 83. In the previous embodiment, removing the proximal force from the proximal end of the operating wire 86 urges the plug 81 back into the sheath 83, holding the flow restricting member 82 in its collapsed, contracted state when disconnected from the controller 33.

[0146] 10A and 10B, catheter 90 illustrates yet another embodiment of an occlusion device 91 in the form of a spring-loaded plug 92. Spring-loaded plug 92, similar to plug 82 of FIGS. 9A and 9B, has a tapered conical shape and is mounted within a sheath 93 that is disposed at the distal end 94 of catheter 90. When a distal force is applied to the proximal end of catheter 90 from drive mechanism 36, spring-loaded plug 92 is pushed out of the distal end of sheath 94 and expands to occlude the SVC. When the distal force is removed, spring-loaded plug 92 retracts to its collapsed, contracted state within sheath 94, allowing blood to flow substantially unimpeded through the SVC.

[0147] Applicant has found that animal studies have demonstrated that a system constructed and operated in accordance with the methods of the present SVC occlusion system offers significant advantages over known IVC systems for treating heart failure. Preliminary animal studies performed on a porcine model one week after myocardial infarction are described below.

[0148] Referring to FIG. 11 , changes in LV pressure and LV volume over several consecutive heart rates in a porcine model after complete occlusion of the inferior vena cava (IVC), as suggested in the aforementioned published Cedeno patent application, are shown. Specifically, the IVC was completely occluded for approximately 30 seconds, during which time left ventricular end-diastolic pressure (corresponding to the lower right corner of the hysteresis loop) and left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) decreased during each consecutive heart rate. Once the IVC occlusion was relieved, LV pressure rapidly increased to pre-occlusion levels (i.e., similar to the first half of the pressure and volume traces). Because the IVC occlusion therapy proposed by Cedeno reduces systolic pressure, the therapy can lead to a reduction in ejection fraction during systole, potentially with dangerous consequences for the patient. Furthermore, IVC occlusion can result in renal and hepatic venous congestion, which can lead to complications often associated with congestive heart failure and worsen, rather than improve, them.

[0149] Referring to Figure 12, changes in LV pressure and LV volume over several consecutive heart rates in a porcine model after partial occlusion of the superior vena cava (SVC), as described in accordance with the principles of the present disclosure, are shown. Specifically, the SVC was partially occluded for approximately 30 seconds, during which time left ventricular end-diastolic pressure (corresponding to the lower right corner of the hysteresis loop) decreased, while left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) remained substantially unchanged during each consecutive heart rate. LV pressure rapidly increased to pre-occlusion levels once the SVC occlusion was relieved (i.e., similar to the first half of the pressure and volume traces). Advantageously, the presently disclosed method of partially occluding the SVC appears to have little or no effect on ejection fraction during systole, but reduces wall stress within the ventricle during diastole. Furthermore, as explained in more detail below, SVC occlusion will be well tolerated by the patient, will not contribute to renal or hepatic venous congestion, and will not exacerbate complications often associated with congestive heart failure, including liver failure and renal failure.

[0150] 13-14 are graphs illustrating how pressure changes with left and right ventricular volumes during superior vena cava (SVC) occlusion and release in pigs undergoing treatment for heart failure in accordance with the principles of the present disclosure. As shown in these graphs, SVC occlusion significantly reduced left ventricular (LV) volume (from 240 mL to 220 mL) and LV diastolic pressure (from 25 mmHg to 10 mmHg). SVC occlusion was also associated with a reduction in LV systolic pressure (from 94 mmHg to 90 mmHg). SVC occlusion was also associated with a reduction in right ventricular (RV) volume (from 230 mL to 210 mL), a reduction in diastolic pressure (from 12 mmHg to 4 mmHg), and a reduction in RV systolic pressure (from 27 mmHg to 16 mmHg). Advantageously, SVC occlusion with the systems and methods described herein reduces the volume of both ventricles, lowering diastolic (filling) pressure without adversely affecting systemic blood pressure (LV systolic pressure). These findings suggest that SVC occlusion may have a significant beneficial effect on the interaction of both ventricles, thereby improving ventricular compliance and, therefore, ventricular filling pressures by reducing diastolic filling pressures to both ventricles, resulting in increased stroke volume and cardiac output, which are primary goals in treating patients with heart failure.

[0151] 15 includes graphs demonstrating that superior vena cava (SVC) occlusion according to the principles of the present disclosure improves cardiac function in a pig study. Each of these graphs compares the results of partial inferior vena cava (IVC) occlusion (left side of each graph) with complete SVC occlusion (right side of each graph). The graphs show the measured left ventricular (LV) stroke volume, cardiac output, LV contractility, LV diastolic pressure, LV systolic pressure, and end-systolic volume.

[0152] 16 is a graph showing that SVC occlusion according to the principles of the present disclosure did not adversely affect systolic blood pressure in three test pigs. These graphs compare the LV end-systolic pressure (mmHg) after complete vena cava occlusion (1 minute) in the case of complete IVC occlusion (left side of each study result) with the LV end-systolic pressure (mmHg) after complete vena cava occlusion (1 minute) in the case of complete SVC occlusion (right column of each study result). Compared to IVC occlusion, SVC occlusion resulted in a smaller decrease in LV end-systolic pressure.

[0153] 17 is a graph showing that SVC occlusion according to the principles of the present disclosure did not adversely affect LV diastolic filling pressure in three test pigs. The graphs compare LV end-diastolic pressure (mmHg) after complete vena cava occlusion (1 minute) in the case of complete IVC occlusion (left side of each study) with LV end-diastolic pressure (mmHg) after complete vena cava occlusion (1 minute) in the case of complete SVC occlusion (right side of each study). Compared to IVC occlusion, SVC occlusion resulted in a smaller decrease in LV end-diastolic pressure.

[0154] 18 is a graph showing that SVC occlusion according to the principles of the present disclosure improves LV stroke volume in three test pigs. The graph compares the LV stroke volume (mL / beats) after complete vena cava occlusion (1 minute) in the case of complete IVC occlusion (left side of each study result) with the LV stroke volume (mL / beats) after complete vena cava occlusion (1 minute) in the case of complete SVC occlusion (right side of each study result). LV stroke volume increases with SVC occlusion compared to the decrease with IVC occlusion.

[0155] 19 is a graph showing the improvement in LV contractility following SVC occlusion according to the principles of the present disclosure in three test pigs. The graphs compare LV contractility (mmHg / sec) following complete vena cava occlusion (1 minute) in the case of complete IVC occlusion (left side of each study result) with LV contractility (mmHg / sec) following complete vena cava occlusion (1 minute) in the case of complete SVC occlusion (right side of each study result). LV contractility is increased during SVC occlusion compared to decreased LV contractility during IVC occlusion.

[0156] Figure 20 shows four graphs showing LV total volume and LV pressure with IVC occlusion (upper left), RV total volume and RV (right ventricular) 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). Figure 20 shows that compared to IVC occlusion, SVC occlusion can significantly reduce LV diastolic pressure and RV diastolic pressure without significantly reducing LV systolic pressure.

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

[0158] FIG. 22 is a graph showing left subclavian venous pressure and renal venous pressure measured in a pig subjected to SVC occlusion according to the principles of the present disclosure. Line 108 shows the left subclavian venous pressure after measurements with SVC occlusion, while line 110 shows the renal venous pressure after measurements with SVC occlusion. The measured change in left subclavian venous pressure is 5 mmHg to 12 mmHg during SVC occlusion. FIG. 22 shows that the proximal left subclavian venous pressure is nominally higher during SVC occlusion.

[0159] The results of further animal studies performed on a porcine model over various occlusion periods are shown in Figures 23A-26C. Referring now to Figures 23A-23D, clinical pressure changes in left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular stroke work, respectively, during the deflation period of a one-minute episode of continuous SVC occlusion in a porcine model are shown. Specifically, the controller was programmed to cause the flow-restricting element to at least partially occlude the SVC for one minute and then contract, e.g., deflate, for one second. As shown in Figures 23A-23D, one minute of SVC occlusion may not be sufficient to result in a steady-state reduction in ventricular volume after the deflation period.

[0160] 24A-24D, clinical pressure changes in left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular stroke work, respectively, during the deflation period of a 5-minute episode of continuous SVC occlusion in a porcine model are shown. Specifically, the controller was programmed to cause the flow-restricting element to at least partially occlude the SVC for 5 minutes and then contract, e.g., deflate, for 1 second. As shown in FIGS. 24A-24D, ventricular volume reached a clear steady-state reduction after the deflation period as a result of the 5-minute SVC occlusion.

[0161] Referring now to Figures 25A-25D, clinical pressure changes in left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular stroke work, respectively, are shown during the deflation period of a 10-minute episode of continuous SVC occlusion in a porcine model. Specifically, the controller was programmed to cause the flow-restricting element to at least partially occlude the SVC for 10 minutes and then contract, e.g., deflate, for 1 second. Comparing Figures 25A-25D with Figures 24A-24D reveals that the advantage of 10 minutes of SVC occlusion over 5 minutes of SVC occlusion is not significant in this model. Therefore, for patient safety reasons, 5 minutes of SVC occlusion was used during initial clinical studies, such as the Tufts IRB-approved protocol described below with reference to Figures 26A-26C, while 10 minutes of occlusion in human subjects is described in more detail below with reference to Figures 28A-B.

[0162] Encouraged by the animal studies, applicants performed preliminary human trials and observed that a system constructed and operated according to the methods of the present SVC occlusion system provides significant benefits. Figures 26A-26C show the clinical pressure changes observed during a 5-minute episode of continuous SVC occlusion in three human patients enrolled in a Tufts IRB-approved protocol. Specifically, the three patients underwent 5-minute continuous SVC occlusion with acute neurological and cardiac monitoring and a 30-day neurological evaluation (Table 1). [Table 1]

[0163] As can be seen from Figures 26A-26C and in Table 1, pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, and right atrial pressure changed significantly during the 5-minute episode of SVC occlusion and had residual effects after balloon release. As a result of the study, all patients benefited hemodynamically because there was a decrease in all blood filling pressures, including capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure. It was observed that more congested patients experienced an increase in mean arterial pressure (MAP). The net effect of these hemodynamic changes was a reduction in cardiopulmonary pressure and an increase in systemic pressure perfusing vital organs, including the kidneys.

[0164] Encouraged by the above-described preliminary porcine and human results, the applicant conducted further testing on three patients who were subjects of the study described above with respect to FIGS. 26A-26C, in addition to two new patients. Five human patients, each with heart failure, were subjected to the above-described SVC occlusion system. Specifically, the five patients underwent five minutes of continuous SVC occlusion. The baseline parameters of the five patients are shown in Table 2 below. The third patient had the lowest New York Heart Association (NYHA) functional class of 2. The results of the third patient suggest that application of the SVC occlusion system may preferably be used for patients with NYHA functional class of heart failure level 3 and above. [Table 2]

[0165] Figures 27A-27E show the change in systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), mean pulmonary artery (MPA) pressure, and pulmonary capillary wedge pressure (PCWP) from baseline measurements for each of five patients during and after occlusion. In Figures 27A-27D, the change in systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), and mean pulmonary artery (MPA) pressure is shown minute by minute during a five-minute occlusion. In Figure 27E, the change in pulmonary capillary wedge pressure (PCWP) is shown during and after the five-minute occlusion.

[0166] The changes in systolic pressure are shown in Figure 27A. As shown in Figure 27A, patients 1, 2, and 5 generally experienced an increase in SP during occlusion, while patients 3 and 4 generally experienced a decrease in systolic pressure. The changes in diastolic pressure are shown in Figure 27B. As shown in Figure 27B, diastolic pressure during SVC occlusion generally increased for patients 1, 2, and 5 and generally decreased for patients 3 and 4.

[0167] The change in mean atrial pressure is shown in FIG. 27C. As shown in FIG. 27C, mean arterial pressure generally increased during SVC occlusion for patients 1, 2, and 5, and generally decreased for patients 3 and 4. The change in mean pulmonary artery pressure is shown in FIG. 27D. As shown in FIG. 27D, mean pulmonary artery pressure decreased during SVC occlusion for each patient; note the absence of a data point for the fourth patient at the fourth minute. The change in pulmonary capillary wedge pressure (PCWP) is shown at 5 minutes and after release in FIG. 27E. As shown in FIG. 27E, pulmonary capillary wedge pressure decreased for all patients at 5 minutes of SVC occlusion, indicating a decrease in blood filling pressure for each patient during occlusion.

[0168] As observed in the study described with respect to Figures 26A-26C, the study shown in Figures 27A-27E showed that all five patients benefited hemodynamically, as there was a decrease in blood filling pressures, e.g., capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure, and furthermore, as in the study described above with respect to Figures 26A-26C, more congested patients generally experienced an increase in mean arterial pressure (MAP). Also, in many cases, at least some of the patients had residual effects after occluder release.

[0169] Next, with reference to Figures 28A-28B, similar to the study described above with respect to Figures 25A-25D, Applicant also studied the effects of prolonged SVC occlusion on human subjects. Specifically, the controller was programmed to cause the SVC flow restricting element to at least partially occlude the SVC for 10 minutes. Prior to the 10-minute occlusion, the SVC was occluded for a 5-minute period and then allowed to rest for a 5-minute period. The change in mean pulmonary artery pressure and mean atrial artery pressure from baseline measurements before occlusion (i.e., after 5 minutes of rest) was measured at each minute from 1 to 10 minutes of occlusion and after release. As shown in Figures 28A-B, the effects observed during the 5-minute occlusion persisted throughout the entire 10-minute occlusion period without any reduction in the effect of "cardiopulmonary unloading."

[0170] Figure 28A shows the change in mean pulmonary artery pressure. As shown in Figure 28A, mean pulmonary artery pressure decreased throughout the occlusion, reaching its lowest level during the last two minutes of occlusion. Figure 28B shows the change in mean arterial pressure during occlusion. As shown in Figure 28B, mean arterial pressure generally decreased during occlusion, but it fluctuated, rising above the baseline measurement at 1 minute and then rising again at 4 and 5 minutes.

[0171] Next, with reference to FIG. 29, applicant also conducted more extensive testing involving the use of the disclosed systems and methods over successive occlusion periods resulting in the prevention or reversal of further myocardial remodeling and degeneration. Specifically, adult male pigs were subjected to a heart attack by occluding the left anterior descending artery (LAD) for 120 minutes, followed by reopening of the occluded artery. Repeated cycles of SVC occlusion were then performed, occluding the SVC for 5 minutes and deflating the occlusion device for 30 minutes. The repeated cycles were repeated and performed over an 18-hour period. Cardiac output was measured after each cycle of SVC occlusion. FIG. 29 shows the results of the repeated cycles of SVC occlusion.

[0172] As shown in Figure 29, cardiac output was at its lowest point after LAD infarction but before SVC occlusion treatment. After 1 hour of treatment, cardiac output returned to baseline levels. Cardiac output continued to gradually increase from 1 hour to 18 hours of treatment, reaching maximum cardiac output at 18 hours. These findings suggest for the first time that mechanically reducing cardiac pressure and volume (i.e., unloading) by intermittently occluding the SVC and then discontinuing the occlusion (i.e., recovery) after acute cardiac injury can condition the myocardium, allowing periods of exercise and rest. In this way, repeated cycles resemble interval training high-intensity workouts (e.g., sprints) followed by rest. Repeated cycles strengthen the heart and improve cardiac output and function. While the occlusion-to-rest ratio was 10:1 (5 minutes on, 30 seconds off), it should be understood that other ratios may also produce beneficial results. For example, a range of 5-20 minutes of occlusion to 10-100 seconds of rest may be beneficial. It should further be appreciated that occluding the SVC for up to 95% of an hour may be beneficial. Thus, the SVC occlusion systems described herein may alternatively or additionally be used to post-infarction treat damage to the heart from infarction and enhance recovery through myocardial unloading.

[0173] As mentioned above, the SVC occlusion systems described herein can alternatively or additionally be used to treat pulmonary hypertension because occlusion of the SVC can result in a reduction in pulmonary artery pressure. While heart failure is a common cause of pulmonary hypertension, pulmonary hypertension can also be caused by primary lung disease. It should 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.

[0174] Next, with reference to FIG. 30, applicant observed that implantation of an SVC occlusion system in five patients with pulmonary hypertension due to heart failure resulted in a significant reduction in pulmonary artery systolic pressure (PASP). The patients underwent a five-minute SVC occlusion to mechanically reduce (i.e., unload) cardiac pressure and volume. As shown in FIG. 30, SVC occlusion significantly reduced PASP below the level of moderate pulmonary hypertension, defined as a high PASP of greater than 50 mmHg. Thus, the SVC occlusion system described herein can be implanted to treat pulmonary hypertension. As discussed above with reference to FIGS. 26B and 27D, applicant also observed that implantation of an SVC occlusion system resulted in a reduction in mean pulmonary artery pressure in each patient.

[0175] The benefits observed in the aforementioned animal and human studies suggest that continuous SVC occlusion can be used to treat any cardiac injury, including, but not limited to, acute heart failure due to heart attack, myocarditis, valvular insufficiency, volume overload, or congestive heart failure, as well as many other acute or chronic cardiac injuries. In one example, the SVC occlusion system described herein can be used to shift the Frank-Starling curve shown in FIG. 2A toward line 7, which represents a healthy patient, by acutely arresting or reversing the heart failure system, e.g., in an acute treatment setting. In this way, patients will see immediate improvements in increased cardiac performance and further ongoing improvements in myocardial function throughout the course of treatment. To prolong the effects of the system, the SVC occlusion system can be implanted within the patient for long-term use. Because the SVC occlusion system described herein can be implanted or worn by the patient continuously and in an ambulatory setting rather than being confined to bed, patients can receive the benefits of the system for a much longer period of time compared to acute treatment.

[0176] 31 is a prophetic example of how SVC obstruction according to the principles of the present disclosure is predicted to change across the disease spectrum. For example, major benefits include better patient hemodynamics, faster recovery, and reduced patient length of stay (LOS). Over time, SVC obstruction can significantly slow disease progression.

[0177] Referring now to FIG. 32, an alternative flow restricting member is shown. One undesirable effect of SVC occlusion is an increase in venous blood pressure upstream of the occlusion device. It is well known that high cephalic venous pressure can lead to various unwanted effects. To reduce this risk of excessive pressure buildup upstream of the flow restricting member, a relief valve can be integrated into the flow restricting member, as shown in FIG. 33, to allow fluid flow from the SVC to the right atrium. The relief valve can be unidirectional, allowing blood flow only in the direction of the right atrium. The relief valve is preferably configured to open at pressures within the SVC of 30 to 60 mmHg. However, it should be understood that the relief valve can be designed and configured to open at other pressures within the SVC.

[0178] The flow restricting member shown in FIG. 32 can be used in conjunction with a system similar to that shown in FIGS. 4A-4B. As shown in FIG. 32, the flow restricting member can be a cylindrical flow restricting member 112. The cylindrical flow restricting member 112 can include a cylindrical balloon 113 that can be inflated and deflated by pumping fluid from a catheter into the cylindrical balloon 113. The flow restricting member 112 can be sized and configured to fit within the SVC and can conform to the contours of the inner wall of the SVC. The flow restricting member 112 can be delivered to the SVC over a catheter. The cylindrical balloon 113 can be introduced into the SVC in a deflated configuration. Upon arriving at the SVC, the cylindrical balloon 113 can be inflated to block or restrict blood flow within the SVC.

[0179] The cylindrical balloon 113 can define an internal lumen 114 when the cylindrical balloon 113 is inflated. When the relief valve 115 is open and the cylindrical balloon 113 is inflated, blood can pass through the cylindrical balloon 113. The internal lumen 114 can extend from one end of the cylindrical balloon 113 to the other. While the internal lumen 114 can have a consistent cylindrical shape throughout, it should be understood that the size and shape of both the cylindrical balloon 113 and the internal lumen 114 can vary. Additionally, the internal lumen 114 need not be aligned with the center of the balloon and can even adopt a non-circular shape.

[0180] Referring now to FIG. 33 , a cutaway view of the cylindrical flow restricting member 112 is shown. As shown in FIG. 33 , a relief valve 115 can be coupled to the inner wall of the cylindrical balloon 113 within the central lumen 114. The relief valve 115 can include a single flow blocking member or multiple flow blocking members (e.g., multiple flexible leaflets) that cooperate to block blood flow through the central lumen 114. The relief valve 115 can be coupled to the center of the cylindrical flow restricting member 112, or alternatively, can be located adjacent to or at the upstream or downstream end of the cylindrical flow restricting member 112. For example, the relief valve 115 can be located at the upstream end of the cylindrical flow restricting member 112 farthest from the patient's right atrium. This configuration can avoid pooling of blood or a stagnant column of blood within the central lumen 114, which can occur if the relief valve 115 is located in the center or downstream region of the central lumen 114.

[0181] The relief valve 115, shown in FIG. 33 in the closed position, can be designed to open at a certain pressure. For example, the relief valve 115 can be designed to open at a pressure of 30-40 mmHg. However, it should be understood that other pressures may also be desirable. Below the pressure at which the relief valve 115 is designed to open, the relief valve 115 can block fluid flow through the central lumen 114. Above the pressure at which the relief valve 115 is designed to open, the relief valve 115 can reduce cephalic venous pressure by allowing blood to pass through the inner lumen 114.

[0182] The relief valve 115 can be constructed from any suitable biocompatible material, including, but not limited to, elastomers, rigid or flexible polymers, metals, and any combination thereof. The functionality of the relief valve 115 can depend solely on the valve material and design (i.e., elasticity, stiffness, thickness) and / or can be dictated by mechanical, electrical, and / or magnetic characteristics. The threshold at which the valve allows fluid to flow may be predetermined by the valve design and / or may be mechanically adjustable.

[0183] Referring now to Figures 34A and 34B, two different relief valve designs are shown within the inner lumen 114 of the cylindrical flow restrictor member 112. The binary relief valve 116 shown in Figure 34A maintains a substantially closed position until a given force is applied, causing it to rapidly transition to a substantially open position. The force at which the relief valve 116 transitions from the closed position to the open position is preferably 30-60 mmHg, although it should be understood that this pressure can be any pressure. To achieve binary (i.e., on / off) functionality, the binary relief valve can include a notched section designed to transition in response to a given force. By opening and allowing fluid to pass, the resilience or other mechanical characteristics of the material can cause the binary relief valve 116 to recoil to the closed position in response to releasing the pressure. It should be understood that this binary functionality can be achieved using various other designs and / or by incorporating other materials. For example, the relief valve 132 of Figures 38A-B can also achieve binary functionality.

[0184] A progressive relief valve 117, such as that shown in Figure 34B, is designed to gradually open with increasing pressure. This functionality can be achieved, for example, by leaflets having a constant thickness or a progressively thinner cross-section as they move from the inner wall of the cylindrical balloon 113 toward the center of the inner lumen 114. However, it should be understood that any valve design that allows for a progressive increase in fluid flow in response to increasing pressure can be used as a progressive relief valve.

[0185] 35, a top view of the cylindrical flow restricting member 112 is shown. The relief valve 115, shown here in a closed position, prevents blood flow through the inner lumen of the cylindrical balloon 113 as long as the pressure remains below a certain threshold. Although a relief valve design having four flexible leaflets or flaps is shown, any relief valve design that can be coupled within the inner lumen 114 of the cylindrical balloon 113 can be used, including valves with fewer / more leaflets.

[0186] 36A and 36B, top views of the cylindrical flow restricting member 112 are shown. FIG. 36A shows the binary relief valve 116 in its open position, also shown in FIG. 34A. FIG. 36B shows the progressive relief valve 117 in a partially open position, also shown in FIG. 34B. As discussed above, the binary relief valve 116 is designed to open to a generally open position in response to reaching its set pressure. On the other hand, the progressive relief valve 117 is designed to gradually open as pressure increases above a certain threshold.

[0187] 37A and 37B, it may be desirable to place a stent 118 around the cylindrical balloon 113. The stent 118 can, for example, act as both a receiver and a transmitter of electrical signals. Such uses include, but are not limited to, acting as an ECG lead, emitting signals related to autonomic activity, and receiving neuromodulation signals. The stent 118 can be self-expanding and made from a conductive material. The stent 118 can be integral with and / or removably coupled to the cylindrical flow restricting member 112.

[0188] Referring now to Figures 38A and 38B, a cylindrical flow restricting member 130 is shown. As shown in these figures, the cylindrical flow restricting member 130 includes a balloon occluder 131 and a relief valve 132, both of which are integral with the stent 118. The relief valve 132 and the balloon occluder 131 are located adjacent to one another within the stent 118. Figure 38A shows the cylindrical flow restricting member 130 in its expanded position, which occludes blood flow within the SVC. Figure 38B shows the occlusion device in its deflated position, which allows blood flow through the SVC. As shown in Figure 38B, the balloon occluder 131 can be coupled to the relief valve 132 and can contract toward the relief valve 132 when deflated. The relief valve 132 can be hingedly connected to the stent 118 and can open to allow blood flow when a certain pressure is achieved within the SVC. The relief valve 132 may be constructed using any of the techniques, designs, and materials described above for relief valves.

[0189] 39A and 39B, a cylindrical flow restricting member 133 is shown. As shown in these figures, the cylindrical flow restricting member 133 includes a cylindrical balloon occluder 134 and a relief valve 135, both of which are integral with the stent 118. The cylindrical balloon occluder 134 can be inflated to conform to the shape of the stent 118. As shown in FIG. 39B, the cylindrical balloon occluder 134 can have an outer surface that is coupled to the stent 118 along a portion of the outer surface. The relief valve 135 can be coupled to the cylindrical balloon occluder 134. When inflated, the cylindrical balloon occluder 134 can define an inner lumen 136 through which blood can pass when the relief valve 135 is open.

[0190] FIG. 39A shows a cylindrical flow restricting member 133 with a cylindrical balloon occluder 134 in an expanded configuration. When inflated, the cylindrical balloon occluder 134 restricts blood flow within the SVC. When the cylindrical balloon occluder 134 is inflated, a relief valve 135 can open on demand to relieve any excess pressure within the SVC. FIG. 39B shows the cylindrical flow restricting member 133 in a deflated configuration. When deflated, the cylindrical flow restricting member 133 allows blood flow through the SVC. In the deflated configuration, the cylindrical balloon occluder 134 reduces in size and moves toward the portion of the stent wall to which it is coupled. Similarly, the relief valve 135 moves toward the stent 118 when the cylindrical flow restricting member 133 is in the deflated configuration. The cylindrical balloon occluder 134 , which has a reduced size when deflated, allows blood to flow around the inflated balloon occluder 134 and through the stent 118 .

[0191] 40A and 40B, a cylindrical flow restricting member 137 is shown. The cylindrical flow restricting member 137 includes a stent 118 and a relief valve 138. Unlike the occlusion devices shown in FIGS. 32-39, the cylindrical flow restricting member 137 does not include a balloon. Instead, the relief valve 138 can be directly coupled to the stent 118, as shown in FIG. 40B. The stent 118 can be an expandable stent and can be anchored to the inner wall of the SVC. The relief valve 138 can take a similar form and have similar features to any of the relief valves described above with respect to FIGS. 32-39. The cylindrical flow restricting member 137 can totally exclude blood flow within the SVC until a certain threshold pressure is achieved within the SVC, at which point the relief valve 138 can open to allow blood flow from the SVC to the right atrium.

[0192] Referring now to FIG. 41 , the cylindrical flow restricting member 112 of FIG. 32 is shown coupled to a filter 126. The filter 126 can be located downstream of the cylindrical flow restricting member 112. When the relief valve 115 is closed, blood can pool within the central lumen 114 of the cylindrical balloon 113, creating a stagnant blood column and potentially leading to thrombosis. When the relief valve 115 is open, blood clots can be released into the right atrium, potentially causing serious problems and even death. The filter 126 can be supported either directly by the catheter or by structural features of the cylindrical balloon 113, relief valve 115, or cylindrical flow restricting member 112, such as a stent 118, if applicable, and can serve to trap blood clots. For example, the filter 126 can be coupled to the cylindrical balloon 113 at the downstream end of the cylindrical flow restricting member 112, as shown in FIG. 41 . It should be understood that the filter 126 may be integral with any of the flow restricting members described herein.

[0193] To determine whether the SVC is completely occluded or the degree to which it is occluded, a traditional method can be employed which involves injecting a contrast agent into the patient and observing the movement of the contrast agent under fluoroscopy. Alternatively, a pressure sensor can be placed on the occlusion balloon as described herein and the pressure waveform can be analyzed to determine whether the SVC is occluded. For example, CardioMEMS TMHF System pressure sensors are available from Abbott (St. Paul, Minnesota). The pressure sensors can communicate wirelessly with, for example, an implanted controller. The pressure waveforms can also be analyzed to determine the patient's blood filling pressure, diastolic status, and / or other cardiac conditions or signs. For example, the waveforms can be analyzed to detect prominent "CV" waves, which indicate tricuspid regurgitation due to volume overload. In another example, the waveforms can detect "A" waves, which suggest complete heart block, ventricular tachycardia (VT), or pulmonary hypertension. The systems described herein can be used as diagnostic monitoring tools by analyzing the waveforms and responding accordingly using the SVC occlusion techniques described herein.

[0194] FIG. 42A shows a pressure sensor 140 capable of generating a pressure waveform. The pressure sensor 140 can be incorporated into the catheter 31 and positioned proximal to the occlusion balloon to provide a pressure measurement indicative of jugular venous pressure (JVP). A pressure sensor 156 can optionally be incorporated into the catheter 31 distal to the occlusion balloon. A user of the system shown in FIG. 42A can monitor the waveform reading from the pressure sensor 140 and determine when the waveform changes from phasic to non-phasic. When the occlusion balloon is deflated, the pressure waveform will fluctuate in phase with the heart rate, as shown by curve 141 in FIG. 42B. When the occlusion balloon is inflated, the pressure waveform flattens. In this manner, whether the SVC is occluded can be determined without the need for contrast injection and without the patient entering a catheterization lab or being exposed to X-rays. The pressure waveform can also be used to determine when to activate and deactivate a flow restricting element.

[0195] Another configuration for using x-ray / fluoroscopy to determine SVC obstruction employs two pressure sensors on opposite sides of an obstruction device. For example, FIG. 4A, discussed above, shows a system having a catheter 31 including a flow restricting member 32, and sensors 42 and 43. As shown in FIG. 4A, sensor 42 is positioned distal to flow restricting member 32, and sensor 43 is positioned proximal to flow restricting member 32. Sensors 42 and 43 can be pressure sensors and, as discussed above, can be used to determine the degree of obstruction caused by flow restricting member 32, for example, by monitoring the pressure differential across flow restricting member 32. The pressure differential value can indicate the amount or degree of obstruction. The pressure differential can also be used to determine when to activate and deactivate the flow restricting member.

[0196] While FIG. 4A illustrates one arrangement of sensors, it should be understood that other arrangements of sensors may be used to obtain relevant information. As shown in FIG. 43A , another sensor arrangement includes a catheter 31 that may be introduced into a patient's vascular system via a delivery device such as an introducer sheath 144. The catheter 31 preferably extends into the SVC, enters the heart via the right atrium, extends into the right ventricle, and enters the pulmonary artery via the pulmonary valve. Sensors 145, 146, and 147 may be positioned along the catheter 31, with sensor 145 positioned within the flow restricting member 32 to measure pressure within the flow restricting member 32 (i.e., balloon pressure), sensor 146 positioned along the catheter 31 distal to the flow restricting member 32 and within the SVC to measure SVC or right atrial pressure, and sensor 147 positioned along the catheter 31 distal to sensor 146 to measure pulmonary artery pressure. To measure the pressure above or proximal to the flow restricting member 32, a sensor 148 can be placed directly on or otherwise incorporated into the distal end of the introducer sheath 144 where it enters the SVC. The pressure measured by the sensor 148 indicates the JVP. The catheter 31 can include multiple lumens used as an inflation lumen, an actuation lumen, and / or for electrical communication between a controller and the flow restricting member 32 and / or sensors 145, 146, and 147. The introducer sheath 144 can also include a lumen for electrical communication between the sensor 148 and the controller.

[0197] 43A and 44, a sensor may be used to detect contact of the SVC wall by the flow restricting member. Specifically, sensor 233 may optionally be positioned on the exterior of the flow restricting member (e.g., on the exterior of an inflatable balloon). Sensor 233 may generate a signal or a change in a signal when the flow restricting member contacts the SVC wall. For example, sensor 233 may be a pressure sensor and / or a conductivity sensor that detects contact with the SVC wall. Alternatively, a sensor may optionally be positioned within the flow restricting member to detect contact with the SVC wall. For example, sensor 145 may be positioned within the flow restricting member. Sensor 145 may be a pressure sensor and may detect a pressure change within the flow restricting member that indicates contact with the SVC wall. In yet another example, electrodes may optionally be positioned proximal and distal to the flow restricting member, as shown in FIGS. 43A and 44. For example, sensors 148 and 146 may be electrodes used to detect an electrical parameter, such as conductance, that can be continuously measured as the flow restricting member is activated. A large change in the electrical parameter may indicate a complete occlusion of the SVC caused by the flow restricting member contacting the SVC wall. It should be understood that any combination of sensors 233, 145, 146, 148, and / or any other sensors described herein may also be used.

[0198] Referring now to FIG. 43B , the SVC occlusion system may alternatively include sensors 234 and 235, which may be disposed on catheter 31, which may be disposed within a delivery device such as introducer sheath 144, and / or sensor 236, which may be disposed on flow restricting member 32. Sensor 234 may be disposed proximal to the flow restricting member, and sensor 235 may be disposed distal to the flow restricting member. Sensor 236 may be disposed on the exterior of the flow restricting member such that sensor 236 contacts the SVC wall when the flow restricting member is fully occluded. Alternatively, sensor 236 may be printed on the flow restricting member. Sensors 234, 235, and 236 may measure admittance, impedance, and conductance to determine the degree of occlusion. For example, sensor 236 may indicate that the flow restricting member is contacting the SVC wall based on a change in an electrical parameter detected in response to contact of flow restricting member 32 with the SVC wall. Sensors 234 and 235 may also measure impedance or conductance to determine whether blood is flowing through the SVC. For example, impedance may increase when flow restricting member 32 is inflated, thus occluding the SVC, and may decrease when flow restricting member 32 is deflated, thus no longer occluding the SVC. A change in impedance may therefore indicate that the SVC is occluded. These two measurements may then be used to determine whether the flow restricting member is completely occluding the SVC.

[0199] Sensor 236 may also be used to determine the diameter of the left ventricle when measuring a pressure-volume loop within the heart. It should be understood that an SVC occlusion system may include both sensor 236 and sensors 234 and 235, or may include only sensor 236 or sensors 234 and 235.

[0200] Referring now to FIG. 43C, the SVC occlusion system may alternatively include sensors 237 and 238 that can be used to determine whether the flow restricting member is occluding the SVC. Similar to the embodiment shown in FIG. 4A, sensor 237 may be positioned on catheter 31 proximal to flow restricting member 32, and sensor 238 may be positioned on catheter 31 distal to flow restricting member 32. Catheter 31 may be introduced into the patient's vasculature via introducer sheath 144. Sensors 237 and 238 may be pressure sensors or optical sensors. For example, sensors 237 and 238 may continuously measure pressure proximal and distal to the flow restricting member, respectively, and generate first and second signals indicative of the pressure. The difference between the pressure signals proximal and distal to the flow restricting member may indicate the degree of occlusion of the SVC. Alternatively, sensors 237 and 238 may together form an optical sensor, with one sensor acting as a light source and the other sensor acting as a light receiver and / or detector. For example, sensors 237 or 238 may detect light at certain frequencies that are transmitted through blood but blocked by the flow restrictor. Thus, a decrease in detected light may indicate partial or complete blockage of the SVC.

[0201] Referring now to FIG. 43D , the SVC occlusion system may alternatively include a pressure switch 239. The pressure switch 239 may be positioned proximal or distal to the flow restricting member and may be connected to one or more lumens 240. Alternatively, the pressure switch 239 may be positioned within the flow restricting member 32. The lumen 240 may be in fluid communication with the pressure switch 239 and may further include an open end positioned proximal to the flow restricting member and another open end positioned distal to the flow restricting member. The lumen 240 may extend through the flow restricting member 32 and / or may be positioned along the catheter 31, which may be positioned within a delivery device such as the introducer sheath 144. The pressure switch 239 may generate a signal when a predetermined pressure differential is reached, which may indicate that the SVC is occluded. For example, the pressure switch 239 may determine the pressure difference between the open end of the proximal lumen 240 of the flow restricting member 32 and the open end of the distal lumen 240 of the flow restricting member 32 .

[0202] Referring now to FIG. 43E, the SVC occlusion system may alternatively include a stretch gauge 246. The stretch gauge 246 may be a stretch gauge, a stress gauge, a strain gauge, and / or any other gauge or sensor that generates a signal indicative of material stress, strain, or stretch. The stretch gauge 246 may be disposed within the introducer sheath 144, or may be disposed solely on the catheter 31, extending over a portion of the catheter 31 and over a portion of the flow restricting member 32. The strain gauge 246 may be configured to measure small changes in force, stress, strain, or material stretch. When the flow restricting member expands and completely occludes the SVC, the flow restricting member and the catheter proximal to the flow restricting member will be pulled proximally. Detecting a positive change in force or pressure in the proximal direction may indicate that the SVC is completely occluded.

[0203] 43F, the SVC occlusion system may alternatively include a sensor 247, which may be an accelerometer for detecting changes in movement. The sensor 247 may be located proximal to the flow restricting member 32 on the catheter 31, which may be located within the flow restricting member 32 or within the introducer sheath 144. When the flow restricting member is expanded to completely occlude the SVC, the flow restricting member and the catheter proximal to the flow restricting member may remain in a relatively stable position compared to an unexpanded flow restricting member. Detecting a lack of movement or a decrease in movement may indicate that the SVC is completely occluded.

[0204] Referring again to FIG. 44, yet another embodiment including an introducer sheath 144 is described. The embodiment shown in FIG. 44 is similar to that of FIG. 43A, except that the flow restricting member 32 and sensors 145 and 146 are also incorporated into the introducer sheath 144. Similar to the device shown in FIG. 43A, a sensor 148 can be positioned above or proximal to the flow restricting member 32 to measure pressure above or proximal to the flow restricting member 32, indicative of JVP. A sensor 145 is positioned within the flow restricting member 32 to measure pressure within the flow restricting member 32 (i.e., balloon pressure). A sensor 146 is positioned near the distal end of the introducer sheath 144, distal to the flow restricting member 32 and positioned within the SVC, to measure SVC or right atrial pressure. Also similar to the device shown in FIG. 43A, a catheter 31 can be introduced through the introducer sheath 144 and extended through the right atrium and into the pulmonary artery. Sensor 147 is preferably located at the distal end of catheter 31, which is positioned in the pulmonary artery to measure pulmonary artery pressure. Introducer sheath 144 may include multiple lumens used as inflation lumens, working lumens, and / or for electrical communication between the controller and flow restricting member 32 and / or sensors 145, 146, and 148. Catheter 31 may also include lumens for electrical communication between sensor 147 and the controller.

[0205] 44, flow restricting member 32 can be selectively inflated and deflated independent of the presence of catheter 31. When flow restricting member 32 and sensors 145, 146, and 148 are disposed on introducer sheath 144, therapeutic treatment involving inflation and deflation of flow restricting member 32 to selectively occlude the SVC can be achieved without the introduction of catheter 31. Furthermore, the pressure differential across flow restricting member 32 can be determined using sensors 148 and 146, regardless of whether catheter 31 is deployed.

[0206] 45, yet another embodiment of an SVC occlusion system constructed in accordance with the principles of the present disclosure is described. Catheter 31 preferably includes two occlusion balloons: an azygos vein occlusion balloon 142 and an SVC occlusion balloon 143. Sensors 129, 139, and 149 may also be disposed on catheter 31, with sensor 129 disposed proximal to azygos vein occlusion balloon 142 to measure the pressure distal to the azygos vein occlusion balloon 142, sensor 139 disposed between azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 to measure the pressure between the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143, and sensor 149 disposed distal to the SVC occlusion balloon 143 to measure the pressure distal to the SVC occlusion balloon. Additionally, sensor 145 is disposed within SVC occlusion balloon 143 to measure the pressure within SVC occlusion balloon 143 (i.e., the SVC occlusion balloon pressure), and sensor 155 is disposed within azygos vein occlusion balloon 142 to measure the pressure within azygos vein occlusion balloon 142 (i.e., the azygos vein occlusion balloon pressure). Additionally, the pressure differential across azygos vein occlusion balloon 142 and SVC occlusion balloon 143 can be determined using sensors 129 and 139, and 139 and 149, respectively. The pressure differential value can indicate the amount or degree of occlusion.

[0207] The azygos vein 16 drains the posterior chest into the SVC. When the SVC is blocked, the azygos vein can naturally shunt the obstructed SVC blood flow back to the right atrium by providing an alternative route to the right atrium. Specifically, if the SVC is obstructed below the origin of the azygos vein, pressure built up above the obstructed portion of the SVC can cause a percentage of venous blood to retrograde into the chest via the azygos vein. An azygos vein occlusion balloon 142 can be positioned within the SVC adjacent to the azygos vein, and inflation of the azygos vein occlusion balloon 142 restricts or prevents blood flow from the SVC into the azygos vein. An SVC occlusion balloon 143 can be positioned below the azygos vein distal to the azygos vein occlusion balloon 142, and inflation of the SVC occlusion balloon 143 occludes the SVC but allows blood flow into the azygos vein. The catheter 31 may include multiple lumens that are used as inflation and / or working lumens between the controller and the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 .

[0208] 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 fully or partially inflated depending on the amount of backflow into the right atrium desired.

[0209] When SVC occlusion balloon 143 is inflated and azygos vein occlusion balloon 142 is deflated, the SVC opens above SVC occlusion balloon 143 and blood is allowed to proceed through the azygos vein into the right atrium. If it is desired to further reduce backflow into the right atrium (further reduce preload), azygos vein occlusion balloon 142 can be inflated to occlude the azygos vein and prevent it from acting as a natural shunt.

[0210] The systems and methods of the present disclosure can be used alone, as described in the examples above, or in combination with other devices configured to assist cardiac function. For example, SVC occlusion according to the principles of the present disclosure can be used in combination with pumps such as intra-aortic balloon pumps ("IABPs") or percutaneous or surgical left ventricular assist devices ("LVADs"), right ventricular assist devices ("RVADs"), or any other cardiovascular (i.e., cardiac, venous, arterial) pumps, whether used for total cardiac support or temporary support, to enable synchronous or asynchronous (venous and arterial) unloading of cardiac preload and afterload, respectively. For example, SVC occlusion according to the principles of the present disclosure can be used in combination with an Impella® heart pump available from Abiomed® (Danvers, Massachusetts), as described in further detail below with reference to FIG. 49. FIGS. 49 and 51-54 illustrate an SVC occlusion system combined with exemplary RVAD, LVAD, and IABP systems.

[0211] The disclosed system can also be coupled to other devices, such as biventricular pacemakers and neuromodulation devices. For example, biventricular pacemakers are designed to resynchronize cardiac function, and SVC occlusion preferably alters RV and LV interactions, thereby making biventricular pacing more efficient. Similarly, SVC occlusion therapy can be used in conjunction with neuromodulation devices, and the present system enhances the effectiveness of the neuromodulation device by having a significant combined effect in stimulating the efferent vagus nerve. A further potential application may be in addressing right ventricular failure after a patient has been fitted with an LVAD. By adjusting the amount of venous return to the right ventricle, it may be possible to "condition" the right ventricular myocardium and tolerate the enhanced venous return being pumped by the LVAD by reducing overload.

[0212] While flow restricting member 32 is described above as being positioned within the SVC and inflated and deflated therein, therapeutic occlusion of the SVC as described herein can alternatively be achieved using a cuff wrapped around the exterior of the SVC to selectively restrain the SVC. Referring now to FIG. 46, cuff 150 is shown wrapped around the SVC. As further shown in FIGS. 47A-D, cuff 150 can include strap 151, occlusion member 152, and locking member 153. Occlusion member 152 can be incorporated into strap 151, such that occlusion member 152 extends outward from both the outer surface of strap 151 shown in FIG. 47A and the inner surface of strap 151 shown in FIG. 47B. The inner or inner surface of strap 151 is the side that faces the SVC, and the outer or outer surface of strap 151 is the side that faces away from the SVC.

[0213] The strap 151 may be generally rectangular in shape. The locking member 153 may be any known system for removably attaching one side of the strap 151 to another side of the strap 151. For example, the strap 151 may have a magnetic locking member that firmly secures the cuff 150 to the SVC. An air line 154 may connect to the occlusion member 152 on one end and to a controller on the other end. The occlusion member preferably has elastic properties that allow it to expand when the air line 154 pumps air or other fluid into the occlusion member 152. When inflated, the occlusion member 152 may expand outward from the inside of the strap 151.

[0214] Referring again to FIG. 46 , strap 151 of cuff 150 can be wrapped around the SVC and firmly anchored onto the SVC using anchoring member 153. In response to locking cuff 150 in place on the SVC, occlusion member 152 can be selectively inflated by pumping fluid through air line 154, thus expanding toward the SVC. Because strap 151 is substantially inelastic, inflation of occlusion member 152 will restrict blood flow through the SVC by causing expansion of occlusion member 152 and compression of the SVC. Thus, occlusion of the SVC can be achieved when occlusion member 152 expands and penetrates into the SVC, causing it to collapse inward. Thus, by selectively deflating and inflating occlusion member 152, therapeutic occlusion of the SVC as described herein can be achieved.

[0215] The controller 33 is programmed to cause the flow restricting member 32 to at least partially occlude the SVC for a first predetermined time interval and then to contract, e.g., deflate, for a second predetermined time interval, e.g., at least 1 second, less than 1 minute, or 1 to 30 seconds. Preferably, the first predetermined time interval is greater than 1 minute, 2 to 8 minutes, or 4 to 6 minutes. For example, the first predetermined time interval can be 5 minutes plus or minus 1 minute. The first predetermined time interval is also preferably significantly longer than the second predetermined time interval. For example, the first predetermined time interval can be at least 5 times longer, at least 10 times longer, at least 20 times longer, or at least 30 times longer than the second predetermined time interval. In some data described herein, for example, the occlusion time interval is 5 minutes, while the deflation time interval is 10 seconds. In some embodiments, the controller 33 is programmed to cause the flow restricting member 32 to completely occlude the SVC during the first predetermined time interval. The controller 33 can be programmed to transition the flow restricting member 32 from an occluded state for a first predetermined time interval to a deflated state for a second predetermined time interval over a number of cycles throughout the course of treatment. As described further herein, the controller 33 can be programmed to automatically (e.g., in response to parameters detected by the sensor(s)) and / or in response to user input, cause the flow restricting member 32 to adjust the timing of the first predetermined time interval (e.g., to a third predetermined time interval) and / or adjust the timing of the second predetermined time interval (e.g., to a fourth predetermined time interval). As will be understood by one of ordinary skill in the art, further adjustments of the time intervals can be made throughout the course of treatment.

[0216] Referring now to FIG. 48 , another exemplary system 30′ of the present disclosure is described. System 30′ is similar to system 30 and includes a catheter 31 having a flow restricting member 32 disposed on a distal portion 34. System 30′ differs from system 30 in that catheter 31 is removably coupled at its proximal end 35 to an external controller system 200. For example, catheter 31 can be disconnected from controller 33 and coupled to external controller system 200 during a clinic visit, allowing a clinician to directly monitor and adjust the operation of flow restricting member 32. Catheter 31 can include an optional distal flotation balloon 201 disposed on distal portion 34, distal to flow restricting member 32. As shown in FIG. 48 , distal flotation balloon 201 can be positioned within the patient's pulmonary artery.

[0217] The external controller system 200 includes a display 202, e.g., a graphical user interface, electrically coupled to an inflation source 203 and an external controller 204. The display 202 communicates with the inflation source 203 and the external controller 204 and displays information regarding the functioning of the system 30′, e.g., key physiological or system parameters, or alerts generated by the external controller 204, for review or adjustment by a clinician. The clinician can review the data displayed on the display 202 and correct malfunctions or adjust system parameters via the graphical user interface.

[0218] The inflation source 203 includes a drive mechanism, e.g., a motor, a pump, that actuates the flow restricting member 32. The inflation source 203 further includes a source of inflation medium, e.g., gas or fluid, and the drive mechanism can transfer the inflation medium between the inflation source 203 and the flow restricting member 32 via the flow restricting member connector 209 in response to commands from the external controller 204. The catheter 31 also provides a fail-safe design in that, when partially external, the flow restricting member 32 can be inflated to provide an occlusion only when the proximal end of the catheter 31 is connected to the external controller 204. This quick-release connection at the proximal end 35 allows the catheter to be quickly unclamped from the external controller 204 for irrigation and / or emergency situations.

[0219] The external controller 204 includes a processor that is programmed to control signals to the drive mechanism of the inflation source 203 and a memory that stores instructions thereon. The external controller 204 also includes a power source, such as a battery, that provides the power needed to operate the processor, inflation source 203, and display 202. Alternatively, the external controller 204 can receive power via a source of electrical energy, such as an electrical cord that plugs into an electrical outlet.

[0220] The catheter 31 can be coupled at its proximal end 35 to a distal flotation balloon connector 205 for fluid communication with a source of inflation medium, e.g., gas or fluid, which can be transferred between the source of inflation medium and the distal flotation balloon 201 in response to commands from an external controller 204 to anchor the distal flotation balloon 201 within the patient's pulmonary artery. The catheter 31 can also be coupled at its proximal end 35 to a thermistor connector 206 for communicating with a cardiac output (CO) monitor to measure and monitor temperature, and to a pulmonary artery pressure connector 207 for communicating with a CO monitor to measure and monitor pulmonary artery pressure.

[0221] The external controller 204 can be coupled to the catheter 31 at the proximal end 35 via a right atrial pressure connector 208 to measure and monitor right atrial pressure. The external controller 204 can also be coupled to the catheter 31 at the proximal end 35 via a flow restricting member connector 209 to measure and monitor the amount of inflation medium transferred between the inflation source 203 and the flow restricting member 32, e.g., the pressure within the flow restricting member 32. The external controller 204 can also be coupled to a jugular venous pressure connector 210 to measure and monitor jugular venous pressure coming from the sheath side port.

[0222] The processor of the external controller 204 may include a data transfer circuit, as described above, that monitors input from external sensors, for example, located on the catheter 31, and provides the signals to the processor. The processor is programmed to receive input from the data transfer circuit and adjust the time period during which the flow restricting member 32 remains open or the degree of obstruction caused by the flow restricting member 32. Thus, for example, the catheter 31 may include one or more optional sensors located within the distal portion 34 of the catheter to measure parameters such as heart rate, blood flow velocity, blood volume, blood filling pressure to the heart, and pressures including central venous pressure. The sensor outputs are relayed to the data transfer circuit of the external controller 204, which may preprocess the input signals, for example, decimating and digitizing the sensor outputs, before providing them to the processor. The signals provided to the processor allow for evaluation of the effectiveness of the flow restricting member 32, for example, by indicating reduced venous pressure during obstruction and patency, and can be used by a clinician to determine the amount of obstruction required to regulate venous return based on the severity of the patient's congestion. As will be appreciated by those skilled in the art, the system 30' can employ any combination of flow restrictors and sensors as described above.

[0223] Referring now to FIG. 49 , an SVC occlusion system in combination with a transvalvular LVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, as described above, and an LVAD system 211 can be positioned on the left side of the heart to provide full hemodynamic support. In one example, the LVAD system 211 is an Impella CP® heart pump available from Abiomed® (Danvers, Massachusetts). The LVAD system 211 includes an inflow end 212, an outflow end 213, an impeller pump 214, and an anchor 215, which are positioned, for example, on the distal portion of a catheter 216. For example, the anchor 215 can be a pigtail anchor. During operation, the inflow end 212 is positioned within the left ventricle, and the outflow end 213 is positioned within the ascending aorta. When the impeller pump 214 is activated, blood in the left ventricle is pumped out through the inflow end 212 and ejected into the aorta through the outflow end 213, thereby mimicking the natural path of blood flow, relieving the left ventricle of load, and increasing coronary and systemic perfusion. For example, the impeller pump 214 can pump up to 5.0 L / min of forward blood flow from the left ventricle into the aorta. As will be appreciated by those skilled in the art, any suitable pump can be used.

[0224] LVAD system 211 also includes a controller 217 operably coupled to catheter 216 and configured to operate pump 214 to pump blood from the left ventricle into the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. Controller 217 and controller 33 can be the same and / or incorporated into the same housing unit, with a single controller operably coupled to flow restricting member 32 and pump 214. Controller 33 can operate flow restricting member 32 to at least partially occlude the SVC while controller 217 operates pump 214 to pump blood from the left ventricle into the aorta.

[0225] Figure 50 presents results obtained in animal models demonstrating left ventricular ("LV") total volume, i.e., LV pressure, for (1) a baseline model, (2) an LVAD model, and (3) an LVAD + SVC occlusion system model. As is evident from comparing model (3) with models (1) and (2), reductions in cardiac preload ("CP") and left ventricular wall tension ("LVWT") result from the use of an SVC occlusion system as described herein in combination with a transvalvular LVAD (Impella CP® heart pump available from Abiomed®, Danvers, Massachusetts), demonstrating improved functionality and efficiency in preload reduction induced by an LVAD. Additionally, transvalvular LVADs can be operated at lower pumping rates while achieving sufficient systemic cardiovascular support, thus reducing the potential for adverse events associated with the LVAD.

[0226] Referring now to FIG. 51 , an SVC occlusion system in combination with a transvalvular RVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, as described above, and an RVAD system 218 can be positioned distal to the flow restricting member 32 on the catheter 31 to provide full hemodynamic support. In one example, the RVAD system 218 is an Impella RP® heart pump available from Abiomed® (Danvers, Massachusetts). The RVAD system 218 includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222, which are positioned, for example, on a distal portion of a catheter 223. For example, the anchor 222 can be a pigtail anchor. During operation, the outflow end 220 is positioned within the pulmonary artery, and the inflow end 219 is positioned within the SVC distal to the flow restricting member 32. When the impeller pump 221 is activated, blood in the SVC is pumped out through the inflow end 219 and ejected into the pulmonary artery through the outflow end 220, thereby mimicking the natural path of blood flow and relieving the load on the right ventricle. For example, the impeller pump 221 can pump up to 5.0 L / min of forward blood flow from the SVC to the pulmonary artery. As will be appreciated by those skilled in the art, any suitable pump can be used.

[0227] Controller 33 may also be operably coupled to RVAD system 218 and configured to unload the right ventricle by actuating pump 221 to pump blood from the SVC into the pulmonary artery. Thus, controller 33 may simultaneously actuate flow restricting member 32 to at least partially occlude the SVC and actuate pump 221 to pump blood from the SVC into the pulmonary artery.

[0228] Referring now to FIG. 52 , an SVC occlusion system in combination with another transvalvular RVAD is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, as described above, and an RVAD system 218 can be positioned on the right side of the heart to provide full hemodynamic support. In one example, the RVAD system 218 is an Impella CP® heart pump available from Abiomed® (Danvers, Massachusetts). The RVAD system 218 includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222, which are positioned, for example, on a distal portion of a catheter 223. For example, the anchor 222 can be a pigtail anchor. During operation, the inflow end 219 is positioned within the inferior vena cava (IVC), and the outflow end 220 is positioned within the pulmonary artery. When the impeller pump 221 is activated, blood in the IVC is pumped through the inflow end 219 and discharged into the pulmonary artery through the outflow end 220, thereby mimicking the natural path of blood flow and relieving the load on the right ventricle. For example, the impeller pump 221 can pump a forward blood flow of up to 5.0 L / min from the IVC to the pulmonary artery. As will be understood by one skilled in the art, any suitable pump can be used.

[0229] RVAD system 218 also includes a controller 224 operably coupled to catheter 223 and configured to actuate pump 221 to pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle. Controller 224 and controller 33 can be the same and / or incorporated into the same housing unit, with a single controller operably coupled to flow restricting member 32 and pump 221. Controller 33 can actuate flow restricting member 32 to at least partially occlude the SVC while controller 224 actuates pump 221 to pump blood from the IVC to the pulmonary artery.

[0230] 53 and 54, an SVC occlusion system may be combined with a ventricular assist device (VAD). As shown in FIG. 53, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 may be placed within the SVC to at least partially occlude the SVC intermittently, as described above, and an LVAD system 225 may be placed transapically on the left side of the heart to provide full hemodynamic support. Alternatively, as shown in FIG. 54, an SVC occlusion system 30'' having a flow restricting member 32 mounted directly on or otherwise incorporated into the distal end of an introducer sheath 144 may be placed within the SVC to at least partially occlude the SVC, and an LVAD system 225 may be placed on the left side of the heart. The SVC occlusion system 30'' may be similar to the SVC occlusion system 30, but may have an introducer sheath 144 with a flow restricting member 32 positioned on a distal portion of the introducer sheath 144.

[0231] In one example, the LVAD system 225 is a HeartWare LVAD system available from HeartWare, Inc. (Miami Lakes, Florida). TM HVAD TM LVAD system 225 may be an LVAD system. LVAD system 225 includes an inflow end 226, an outflow end 227, and a pump 228, which may be implanted, for example, near the apex of the left ventricle. In operation, inflow end 226 may be located in the left ventricle, and outflow end 227 may be located in the ascending aorta. When pump 228 is activated, blood in the left ventricle may be pumped through inflow end 226 and ejected into the aorta through outflow end 227, thereby mimicking the natural path of blood flow, relieving the left ventricle of load, and increasing coronary and systemic perfusion.

[0232] LVAD system 225 may also include a controller 229 operably coupled to pump 228 and configured to operate pump 228 to pump blood from the left ventricle into the aorta. Controller 229 and controller 33 may be the same and / or incorporated into the same housing unit, with a single controller operably coupled to flow restricting member 32 and pump 228. Controller 33 may operate flow restricting member 32 to at least partially occlude the SVC at the same time that controller 229 operates pump 228 to pump blood from the left ventricle into the aorta. As will be appreciated by one of ordinary skill in the art, any suitable ventricular assist device (VAD) may be used in conjunction with the SVC occlusion systems described herein.

[0233] The combination of an SVC occlusion system with a VAD (e.g., an RVAD or LVAD) can reduce the required flow rate of the VAD and achieve the same hemodynamic response in the patient, thereby reducing the required pump speed and potentially reducing the complications associated with the higher pump speed required to generate the higher flow rate.

[0234] Because right ventricular overload can occur during or after LVAD implantation, occlusion of the SVC using the SVC occlusion systems described herein (e.g., SVC occlusion systems 30, 30', and 30'') can be used to reduce the volume within the right ventricle. For example, intermittent occlusion of the SVC following LVAD implantation serves to unload the right ventricle while the LVAD is brought up to operating speed.

[0235] Referring now to FIG. 55 , an exemplary process for altering the heart to reduce right ventricular volume is shown. In step 241, a catheter may be inserted into the SVC. The catheter may include a flow-restricting member, such as a balloon, disposed on its distal end. This step may involve placing the catheter 31, or alternatively, the introducer sheath 144, into the SVC, as described above. In step 242, the flow-restricting member may be actuated to at least partially occlude the SVC. For example, this step may involve actuating the flow-restricting member 32 to at least partially occlude the SVC. Actuation may involve inflating the balloon as described above and / or intermittently inflating the balloon (e.g., inflating for 5 minutes and deflating for 30 minutes).

[0236] In step 243, an LVAD device may be implanted or otherwise deployed in or near the left ventricle. This may involve, for example, transapically positioning the LVAD system 225 on the left side of the heart. Step 243 may occur after the flow restricting member is activated in step 242. Alternatively, step 242 may occur during or before step 242. In step 244, the healthcare provider or technician controlling the flow restricting member 32 may wait a period of time after activating the flow restricting member in step 242, and / or the controller 33 may be programmed to wait a set period of time. As described above, it may be beneficial to at least partially occlude the SVC for a period of time (e.g., 5 minutes). The amount of time may 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. In response to being within the predetermined threshold range, the flow restricting member 32 may be deactivated by the clinician and / or automatically by the controller. After waiting a period of time in step 244, activation of the flow restricting device may be terminated in step 245. For example, flow restricting member 32 may be a balloon that is deflated after a set period of time. As described above, flow restricting member 32 may be intermittently activated to occlude the SVC. Thus, steps 242, 244, and 245 may be repeated to reduce the volume of blood flow within the right ventricle. In this manner, an SVC occlusion device may be used to unload an overloaded right ventricle before, during, and / or after LVAD implantation or deployment.

[0237] Referring now to FIG. 56 , an SVC occlusion system in combination with an intra-aortic balloon pump (IABP) is described. For example, an SVC occlusion system 30 having a flow restricting member 32 on a distal portion 34 of a catheter 31 can be placed in the SVC to at least partially and intermittently occlude the SVC, as described above, and an IABP 230 can be placed in the descending aorta. The IABP can include a flow restricting member 231 and a catheter 232 coupled to the flow restricting member 231. The flow restricting member 231 comprises a balloon that can transition between a deflated state and an expanded, deployed state, for example, to enable intravenous placement. The flow restricting member 231 is preferably sized and shaped so that, in its expanded state, it partially or completely occludes blood flow in the aorta. The catheter 232 can be coupled at its proximal end to a controller 33. The controller 33 houses a drive mechanism 36 that independently actuates the flow restricting member 32 and the flow restricting member 231. As shown in FIG. 54 , flow restricting member 231 and flow restricting member 32 can be connected to the same controller, with a single controller operably connected to flow restricting member 32, flow restricting member 231, and pump 221. However, it should be understood that flow restricting member 32 and flow restricting member 231 can be connected to different controllers and / or different pumps. In operation, flow restricting member 231 is positioned within the descending aorta and will intermittently inflate and deflate. Inflation can be timed to coincide with diastole, and deflation can be timed to coincide with systole. As flow restricting member 231 deflates, a suction effect is created within the aorta, facilitating the transfer of blood from the left ventricle to the aorta during systole.

[0238] Referring now to Figures 57A-C, a normal heart, a compensated heart, and a decompensated heart are shown, each showing a cross-section of the mitral valve. As shown in Figure 57A, a normal heart does not develop mitral regurgitation (MR). In fact, a normal heart has normal preload, normal left atrial (LA) volume, normal left ventricular (LV) volume and contractility, normal wall stress, normal total stroke volume (TSV), and normal forward stroke volume. As shown in Figure 57B, a chronically compensated heart instead develops increased preload, increased LA volume and pressure, increased LV volume, increased contractility, eccentric hypertrophy, and increased TSV, but experiences normal wall stress and FSV. As indicated by arrow 250, such a chronically compensated heart develops mitral regurgitation. Referring now to Figure 57C, a decompensated heart is shown. As shown in Figure 57C, a decompensated heart develops increased preload, significantly increased LV volume, decreased contractility, significantly increased wall stress, decreased TSV, and decreased FSV. As indicated by arrow 251, such a decompensated heart develops mitral regurgitation. As will be appreciated by those skilled in the art, other heart valves, such as the tricuspid valve, can develop similar abnormalities that can result in regurgitation (e.g., tricuspid regurgitation).

[0239] Using the SVC occlusion systems described herein (i.e., SVC occlusion system 30, SVC occlusion system 30′, and SVC occlusion system 30″), regurgitant flow within an overloaded heart can be treated. For example, introducing an SVC occlusion system into the SVC and intermittently activating flow restricting member 32 as described above (e.g., a 5-minute occlusion time interval and a 10-second systolic time interval) relieves the overload within the heart. With the reduction in intracardiac volume, coaptation can be achieved by valve leaflets that previously could not seal due to the overload. Thus, using an SVC occlusion system in the manner described herein reduces blood flow overload within the heart and may ultimately reduce or eliminate regurgitant flow within one or more valves, such as the mitral, aortic, and / or tricuspid valves.

[0240] It should be appreciated that occluding the SVC using SVC occlusion system 30″ or any other occlusion system described herein may result in increased urinary flow and further alleviate blood flow overload. For example, use of SVC occlusion system 30″ or any other occlusion system described herein may involve activating (e.g., inflating) the flow restricting member such that it occludes the superior vena cava and / or the superior ductus caval-right atrial junction and further stretches it, thereby causing vagal stimulation and resulting in increased urinary flow. Reducing blood flow overload using the techniques and SVC occlusion system described herein may also increase the number of patients eligible for cardiac procedures. For example, a patient suffering from an overloaded heart who would not have been a suitable candidate for a valve clip due to a degree of leaflet separation may become a suitable candidate for the procedure after use of the SVC occlusion system and reduction of intracardiac volume.

[0241] Referring now to FIG. 58, an SVC occlusion system 30″ is shown and is similar to the system shown in FIG. 44. The SVC occlusion system 30″ may include an introducer sheath 144 having a distal portion 255 and a proximal portion 256. The introducer sheath 144 may be a flexible tube. The distal portion 255 may include a flow restricting member 32 disposed on or otherwise incorporated into the introducer sheath 144. The distal portion 255 may be configured for placement within the SVC. The introducer sheath 144 may be coupled at its proximal end 256 to a controller 33. The controller 33 may be programmed to intermittently activate the flow restricting member 32. The introducer sheath 144 may include one or more internal lumens and may include a fluid lumen for inflating the flow restricting member 32.

[0242] Referring now to FIG. 59 , SVC occlusion system 30″ is shown with distal portion 255 positioned within the SVC. Also shown is a separate delivery catheter 260 extending via the IVC, through the right atrium, and into the left atrium. Delivery catheter 260 may be introduced, for example, into the femoral vein, or any other vein. Delivery catheter 260 may have a distal region 261 designed to deliver a leaflet clip, such as leaflet clip 262. Leaflet clip 262 may be removably coupled to distal region 261 and designed to clamp the leaflets together to treat regurgitation. As shown in FIG. 59 , leaflet clip 262 may be used to clip the mitral valve leaflets together. In one example, leaflet clip 262 is a MitralClip available from Abbott Laboratories. TM However, those skilled in the art will appreciate that leaflet clip 262 may be any device that joins one or more leaflets in close proximity to one another.

[0243] As described above, when the heart is overloaded, as shown in FIGS. 57B and 57C, an increase in intracardiac volume can cause the leaflets to separate, resulting in regurgitation. To deploy the leaflet clips 262 to treat regurgitation, the leaflets must not separate too far from one another. If the leaflet separation is too great to allow for the leaflet clips 262 to be deployed, the intracardiac volume may be reduced using an SVC occlusion system. For example, the LVEDV may be monitored while employing the SVC occlusion system. With the heart unloaded, the leaflet clips 262 may be properly deployed. For example, once the LVEDV has been reduced to a certain point, an improved likelihood of successful leaflet clip implantation may be achieved. Thus, the SVC occlusion system described herein facilitates leaflet clip implantation.

[0244] Referring now to FIG. 60 , a method of altering the heart and reducing cardiac volume to perform a cardiac procedure (e.g., deployment of a mitral valve clip) is shown. In step 271, a catheter may be inserted into the SVC. For example, as shown in FIG. 59 , an SVC occlusion system 30″ may be inserted into a patient, and a distal portion 255 having a flow restricting member 32 may be positioned within the SVC. In step 272, the flow restricting member may be actuated to at least partially occlude the SVC. For example, as shown in FIG. 58 and described in detail above, the controller 33 may actuate the flow restricting member 32, thereby inflating the flow restricting member 32 and at least partially occluding the SVC.

[0245] In step 273, a healthcare provider or technician may generate data regarding the patient's heart. For example, the healthcare provider or technician may use a medical imaging technique such as fluoroscopy or any other known type of medical imaging technique to generate image data. Other known methods for generating data regarding the heart, such as ultrasound or an electrocardiogram (ECG), may also be used. From the generated data, the healthcare provider or technician may determine information regarding the patient's heart or a portion thereof, such as the right and / or left ventricle, including volume and / or pressure. For example, the healthcare provider or technician may determine the volume of the patient's heart or a portion thereof (e.g., right ventricular volume). Alternatively, the healthcare provider or technician may consider the spacing between the cusps of a valve, such as the mitral valve.

[0246] In step 274, the healthcare provider or technician may verify that the generated data or data corresponding to the generated data meets a predetermined threshold or otherwise falls within an acceptable range. For example, using the generated data, the healthcare provider or technician may calculate or estimate the size or volume of the right ventricle and verify that the size or volume meets a predetermined threshold or otherwise falls within an acceptable range. After performing step 274, in step 275, the healthcare provider or technician may perform the cardiac procedure. For example, as shown in FIG. 59 , the healthcare provider or technician may deploy a valvular clip 262.

[0247] The process described in FIG. 60 may be used in conjunction with various other cardiac procedures, which may include, but are not limited to, deploying and / or positioning a valve or cardiac prosthesis, deploying and / or positioning a heart pump (e.g., an LVAD), cardiac or valve surgical procedures (e.g., a quadrant resection), and / or coronary revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Performing the cardiac procedure in step 275 of FIG. 60 may alternatively involve deploying a prosthetic valve annulus 282, as shown in FIG. 61. Next, with reference to FIG. 61, the distal portion 255 of the SVC occlusion system 30'' may be positioned within the SVC, and a delivery catheter 280 may extend, for example, via 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. Delivery catheter 280 may have a distal region 281 for delivering prosthetic valve annulus 282. In one example, prosthetic valve annulus 282 may be a Carpentier-Edwards Physio II ring available from Edwards Lifesciences. However, one skilled in the art will understand that prosthetic valve annulus 282 may be any ring or band used to restore a valve annulus to its proper dimensions.

[0248] Performing the cardiac procedure in step 275 of FIG. 60 may alternatively involve deploying a valve prosthesis 292, as shown in FIG. 62. Next, with reference to FIG. 62, the distal portion 255 of the SVC occlusion system 30'' may be positioned within the SVC, and a delivery catheter 290 may extend, for example, via 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. The valve prosthesis 292 may be any valve prosthesis, such as, for example, a transcatheter artificial heart valve or a stent.

[0249] Although Figures 59, 61, and 62 all show delivery catheters used to perform cardiac procedures extending through the IVC, the delivery catheter may alternatively extend through the SVC. Referring now to Figure 63, the distal portion 255 of the SVC occlusion system 30'' is shown positioned within the SVC. The delivery catheter 300 is shown extending out from the distal portion 255 through the introducer sheath 144. Similar to the delivery catheter 260, the delivery catheter 300 may deliver a leaflet clip 301 that is removably coupled to the distal region 302 and deployed in the same manner as the leaflet clip 262 as described above with respect to Figure 59. It should be understood that the artificial valve annulus 282 described with respect to FIG. 61, the valve prosthesis 292, including but not limited to the bioprosthetic heart valve described with respect to FIG. 62, or any other prosthetic, bioprosthetic, or surgical device, can be delivered to the heart via a delivery catheter extending through the introducer sheath 144.

[0250] It should be understood that the foregoing description is illustrative, but not limiting, of the scope of the invention, which is defined by the appended claims. Other embodiments are within the scope of the following claims.

Claims

1. An apparatus for occluding a patient's superior vena cava (SVC), the apparatus comprising: a catheter configured to be positioned within the SVC, the catheter comprising a distal region; a flow restricting member disposed on the distal region of the catheter and configured to be selectively actuated; a pressure switch disposed on the distal region of the catheter, the pressure switch comprising a first lumen with a first open end disposed proximal to the flow restricting member and a second lumen with a second open end disposed distal to the flow restricting member, the pressure switch configured to generate a signal indicative of a pressure difference between the first lumen and the second lumen; a controller operably coupled to the catheter, the controller configured to intermittently actuate the flow restricting member to at least partially occlude the SVC based on the signal; and An apparatus comprising:

2. The device described in claim 1, wherein the catheter is equipped with one or more sensors for detecting the patient's heart rate.

3. The device described in claim 1, wherein the flow-restricting member is an inflatable balloon.

4. The device described in claim 1, wherein the flow restricting member comprises a relief valve having an open position and a closed position.

5. The instrument of claim 1, wherein the pressure switch is configured to determine the pressure difference between the first lumen and the second lumen and to generate the signal when the pressure difference between the first lumen and the second lumen reaches a predetermined pressure difference threshold.

6. The device described in claim 5, wherein the signal indicates the degree of obstruction of the SVC by the flow restricting member.

7. The device described in claim 1, wherein the controller is configured to contract the flow restricting member based on the signal.

8. The device described in claim 1, wherein the controller is configured to intermittently actuate the flow restricting member to at least partially occlude the SVC for a predetermined first time interval and to contract the flow restricting member for a predetermined second time interval.

9. The apparatus described in Claim 8, wherein the controller is configured to change the first time interval based on the signal.

10. The device described in claim 8, wherein the controller is configured to vary the first time interval based on the patient's heart rate.

11. The device of claim 1, wherein the controller is configured to sufficiently reduce cardiac preload during the interval to improve cardiac performance as measured by at least one of reduced blood filling pressure on the heart, increased left ventricular relaxation, increased left ventricular capacitance, increased left ventricular stroke volume, increased myocardial relaxation, reduced left ventricular stiffness, or reduced cardiac tension.

12. The device of claim 1, wherein the controller is configured to treat heart failure.

13. The device of claim 1, wherein the controller is configured for implantation.

14. The device of claim 1, wherein the controller comprises a data transfer circuit configured to receive the signal.

15. The apparatus of claim 14, wherein the data transfer circuitry is configured to communicate the signal to the patient's computing device for display to the patient.

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

17. The instrument of claim 1, further comprising one or more external power sources, the one or more external power sources being in electrical communication with the controller, and the one or more external power sources being configured to provide power to the controller.

Images