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

Abstract

The invention provides systems and methods for selectively occluding the superior vena cava to treat cardiac conditions. Systems and methods are provided for treating a condition, such as heart failure and / or pulmonary arterial hypertension, by at least partially occluding flow through the superior vena cava for an interval across multiple heart cycles. A catheter having an occlusion device is provided, as well as a controller that actuates a drive mechanism to provide at least partially occlude the superior vena cava of a patient, which reduces heart filling pressure and induces advantageous displacement of the patient's Frank-Starling curve towards healthy cardiac functionality and improved cardiac performance. The system may include a sensor to determine a degree of occlusion of the superior vena cava. The occlusion system may be used to reduce heart volume and facilitate cardiac surgery. A plugging system may be used to mitigate overloaded chambers during and / or after deployment of the VAD.

Description

[0001] This application is a divisional application. The original application was filed on November 19, 2020, with application number 2020800901938 and invention title "System and method for selectively occluding the superior vena cava to treat heart disease".

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

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

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

[0005] Heart failure can be caused by any of a variety of triggering events. It can occur due to ischemic heart disease, hypertension, valvular heart disease, infection, hereditary cardiomyopathy, pulmonary hypertension, or under conditions of metabolic stress, including pregnancy. Heart failure can also occur without a clear cause—also known as idiopathic cardiomyopathy. The term heart failure includes left ventricular failure, right ventricular failure, or biventricular failure.

[0006] While the heart can initially respond successfully to increased workload due to high blood pressure or loss of contractile tissue, over time this stress triggers compensatory cardiomyocyte hypertrophy and ventricular wall remodeling. Specifically, in the months following the initial cardiac injury, the damaged portion of the heart typically begins to remodel as the heart struggles to continue pumping blood with reduced muscle mass or lower contractility. This, in turn, often leads to overwork of the myocardial layers, causing the damaged area of ​​myocardium to become increasingly thinner, larger, and further overloaded. Simultaneously, the ejection fraction of the damaged ventricle decreases, resulting in reduced central output and increased mean intraventricular pressure and volume throughout the cardiac cycle—signs of heart failure. Unsurprisingly, once a patient's heart enters this progressive, self-sustaining spiral of deterioration, their quality of life is severely impacted, and their risk of developing heart disease increases dramatically. Depending on multiple factors, including the patient's prior health condition, age, sex, and lifestyle, the patient may experience one or more hospital admissions, incurring significant costs for both the patient and the healthcare system. Ultimately, the patient may die from cardiac arrest or any of the various complications, including stroke, kidney failure, liver failure, or pulmonary hypertension.

[0007] Currently, there are no device-based solutions specifically targeting preload reduction to limit the progression of heart failure. Medical approaches can be used as palliative measures to alleviate heart failure symptoms, but there are no medical pathways to halt or reverse heart failure. Furthermore, existing medical approaches are systemic in nature and do not address the localized effects of cardiac remodeling 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 cardiac remodeling effects that generate the cascade effects associated with this disease.

[0008] The applicant notes that the prior art includes several attempts to address heart failure. Prior to the applicant's invention as described herein, there were no effective commercially available devices for treating this condition. Several known examples of systems and methods previously known for treating various aspects of heart failure are described below, but none appear to be designed or capable of reducing left ventricular end-diastolic volume (“LVEDV”), left ventricular end-diastolic pressure (“LVEDP”), left ventricular end-diastolic diameter (“LVEDD”), right ventricular end-diastolic volume (“RVEDV”), or right ventricular end-diastolic pressure (“RVEDP”) without causing potentially serious side effects.

[0009] For example, U.S. Patent No. 4,546,759 to Solar describes a three-balloon catheter designed for placement such that the distal balloon intermittently occludes the superior vena cava, the proximal balloon intermittently occludes the inferior vena cava, and the intermediate balloon expands synchronously with right ventricular contraction, thereby enhancing blood ejection from the right ventricle. The patent describes the system as expanding and contracting synchronously with a normal heart rhythm and designed to reduce right ventricular load to allow for healing of right ventricular injury or defects. The patent does not describe or imply that the proposed regulation of flow in and out of the right ventricle will affect LVEDD, LVEDD, or LVEDP, nor does it describe or imply that it can be used to inhibit or reverse acute / chronic heart failure.

[0010] US Patent Publication No. 2006 / 0064059, issued to Gelfand, describes a system and method aimed at reducing the area of ​​myocardial infarction and / or myocardial remodeling following acute myocardial infarction by reducing stress in the heart wall. The system described in the patent comprises a catheter having a proximal portion and a distal portion, the proximal portion having an occlusion balloon configured for placement in the inferior vena cava, and the distal portion being configured for placement in the pulmonary artery via the tricuspid and pulmonary valves. The patent application describes that by partially occluding the inferior vena cava, the system regulates the amount of blood entering the ventricle and thus reduces ventricular load, thereby allowing for faster recovery and reducing the spread of myocardial infarction. The system described by Gelfand includes sensors mounted on the catheter, which are read by a controller to adjust the regulation of blood flow into the heart and other measured parameters within predetermined limits. The patent application does not describe or imply that the system can be used to treat, inhibit, or reverse congestive heart failure when the heart has undergone extensive remodeling, which is typically observed during repeated hospitalizations to resolve symptoms of congestive heart failure.

[0011] US Patent Publication No. 2010 / 0331876, issued to Cedeno, describes a system and method, similar to the design described by Gilvan, aimed at treating congestive heart failure by modulating venous return through the inferior vena cava. The system described by Cedeno describes a fixed-volume balloon placed in the inferior vena cava that restricts blood flow within the IVC. The degree of occlusion varies with the expansion and contraction of the vessel during inspiration and expiration, thereby correcting for venous return. The patent application further describes that heart failure symptoms improve within three months of using the claimed system. While the system and method described by Cedeno appear promising, the applicant has identified several potential drawbacks of such systems during their own research. The applicant has observed during their research that complete occlusion of the inferior vena cava not only reduces left ventricular volume but also significantly reduces left ventricular systolic pressure, thereby reducing systemic blood pressure and cardiac output. In addition, complete occlusion of the inferior vena cava may increase venous congestion in the renal veins, hepatic veins, and mesenteric veins; venous congestion is a major cause of renal failure in patients with congestive heart failure.

[0012] Methods involving partial or complete occlusion of the intraventricular cavity (IVC) to regulate cardiac filling pressure and improve cardiac function have several major limitations. First, the IVC must be accessed via the femoral vein or the internal jugular vein. If accessed via the femoral vein, the patient will need to remain supine and immobile. If accessed via the jugular or subclavian vein, the device will have to traverse the vena cava and right atrium, requiring cardiac puncture, which carries a potential risk of right atrial injury, including arrhythmias such as supraventricular tachycardia or bradycardia due to cardiac conduction block. Secondly, the IVC approach described by Serdano and colleagues relies on several highly variable parameters (especially in the context of congestive heart failure): 1) IVC diameter, which is typically dilated in patients with heart failure; b) intermittent (complete or partial) IVC occlusion can be harmful due to increased renal venous pressure, which reduces glomerular filtration rate and worsens renal insufficiency; c) dependence on the patient's respiratory capacity, which is often severely impaired in heart failure (HF) (the typical breathing pattern in HF is called Cheynes-Stokes respiration, defined by intermittent periods of apnea where the IVC may constrict and the balloon will form a complete occlusion, resulting in lower systemic blood pressure and higher renal venous pressure); d) if long-term cardiac unloading is required to produce clinical improvement or beneficial changes in cardiac structure or function, then IVC occlusion will be ineffective because continuous IVC occlusion will harm blood pressure and renal function. Thirdly, the approach defined by Serdano would require balloon customization depending on the potentially highly variable IVC size. Fourth, many patients with heart failure have IVC filters due to an increased tendency for deep vein thrombosis, which will hinder the widespread use of IVC therapy.

[0013] Pulmonary hypertension (PH) is also a leading cause of morbidity and mortality worldwide. As mentioned above, while heart failure is a common cause of PH, it can also be caused by primary lung diseases. Currently, drug treatments can lower pulmonary artery systolic blood pressure (PASP) and improve symptoms and ultimate survival in patients with PH. However, drug treatments have drawbacks, such as cost and side effects.

[0014] In view of the aforementioned drawbacks of previously known systems and methods for regulating venous return to address heart failure, it is desirable to provide systems and methods for treating acute and chronic heart failure that reduce the risk of exacerbation of complications associated with the disease.

[0015] Furthermore, there is a desire to provide systems and methods for treating acute and chronic heart failure that can inhibit or reverse cardiac remodeling and are practical for use in chronic and / or non-bedridden patients.

[0016] Furthermore, there is a desire to provide systems and methods for treating heart failure that allow patients with this condition to have an improved quality of life, thereby reducing the need for hospital admissions and length of hospital stays, as well as the associated burden on social healthcare networks.

[0017] It is also hoped that systems and methods will be provided that allow for the treatment of pulmonary hypertension and cardiorenal syndrome.

[0018] Another concern is that an overloaded heart may undergo remodeling and deformation of the valve walls, eventually reducing valve engagement. Without proper valve engagement, the valves will not seal properly, and blood may flow back through the valves, causing regurgitation. Regurgitation can cause shortness of breath, fatigue, and rapid and / or fluttering of the heart. It is hoped that systems and methods for treating regurgitation can be provided.

[0019] Another problem with overload is that it complicates cardiac surgeries, such as those correcting regurgitation. For example, clips can be used to couple valve leaflets that are no longer sealed. However, if the heart chamber volume is too large, clips may be impossible to deploy because the leaflets are too far apart. There is also a desire to provide systems that reduce the heart volume to perform cardiac surgeries.

[0020] Overload is known to occur during and / or after the installation of a ventricular assist device (VAD). For example, the right ventricle may become overloaded during and / or after the installation of a left ventricular assist device (LVAD). A right ventricular assist device (RVAD) can be used to address this issue. However, this involves the installation and / or deployment of a second heart pump, leading to an increased risk of complications and infection. It is also desirable to provide a system that reduces the volume of the heart chambers and allows for the installation of a VAD. Summary of the Invention

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

[0022] Furthermore, there is a desire to provide practical systems and methods for the use of non-bedridden and / or chronic patients to inhibit or reverse cardiac remodeling in patients with heart failure.

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

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

[0025] Further, it is desired to provide systems and methods for treating pulmonary hypertension, which allow patients suffering from the disease to have an improved quality of life. In addition, it is desired to provide systems and methods for treating heart attack, acute heart failure, chronic heart failure, heart failure with preserved ejection fraction, right heart failure, systolic and restrictive cardiomyopathy, and cardiorenal syndrome (types 1-5).

[0026] This invention offers these and other advantages. This disclosure provides systems and methods for modulating venous return to the heart through the superior vena cava (“SVC”) across intervals spanning several cardiac cycles, thereby reducing ventricular overload and decreasing cardiac preload and pulmonary artery pressure without increasing renal venous pressure. According to the principles of the invention, venous modulation via the SVC can be used to reduce LVEDP, LVEDV, LVEDD, RVEDP, and / or RVEDV, and to inhibit or reverse ventricular myocardial remodeling. Contrary to intuition, the applicant has observed in preliminary animal studies that intermittent partial occlusion of the SVC does not result in cerebral blood flow stagnation or observable adverse side effects. More importantly, the applicant’s preliminary animal studies reveal that SVC occlusion causes a significant reduction in RVEDP and LVEDP, while increasing total cardiac output without a significant reduction in left ventricular systolic pressure (“LVSP”). Therefore, unlike the methods described in the previously published Serdano patent application, this invention provides a beneficial reduction in LVEDP, LVEDV, LVEDD, RVEDP, and / or RVEDV, with a negligible effect on LVSP, but increases stroke volume and reduces the risk of venous congestion leading to increased complications. The systems and methods described herein provide acute improvements in cardiac filling pressure and function to benefit patients at risk of acute decompensated heart failure.

[0027] Targeting SVC blood flow (optionally IVC blood flow) offers several key advantages. First, device placement within the SVC eliminates the need for femoral vein access and cardiac puncture. This allows for the development of a fully implantable system for acute or chronic therapy that does not even require bed rest. Second, SVC occlusion can be intermittent or long-term, depending on the desired unloading value. Unlike IVC occlusion, long-term SVC occlusion maintains systemic blood pressure and increases cardiac output. This allows for continuous unloading of both the right and left ventricles, potentially enabling acute hemodynamic benefits and long-term beneficial effects on cardiac structure or function. Third, unlike IVC occlusion, SVC occlusion is not dependent on patient respiration. Fourth, SVC occlusion internal modulators driven by right atrial mean pressure or the pressure differential across the occlusion balloon can be programmed and personalized for each patient's condition. Fifth, by placing the device within the SVC, it can be used in conjunction with existing IVC filters for patients.

[0028] According to another aspect of the invention, it is anticipated that intermittent closure of the SVC, either partially or completely, over multiple cardiac cycles allows for myocardial healing, thereby inhibiting or reversing the remodeling of symptoms of heart failure development due to reduced myocardial wall stress. Not wishing to be bound by theory, the applicant believes that intermittent closure of the SVC allows, after periods of implementation lasting hours, days, weeks, or months, the heart to shift from a Starling curve indicative of heart failure with a decreased ejection fraction towards a Starling curve indicative of LVEDP and LVEDP, which are more indicative of normal cardiac function. Therefore, the applicant's preliminary animal studies demonstrate that the system of the present invention, after use for periods of hours, days, weeks, or months (3 to 6 months), can not only inhibit the typical spiral progression of the disease but also enable the heart to recover function sufficiently to allow the patient to discontinue use of the system of the present invention, pharmaceutical treatments, or both.

[0029] According to another aspect of this disclosure, a system including a catheter and a controller is provided, the catheter having a flow-limiting element configured for placement in or on a semi-ventricular ventricular cap (SVC), the controller being used to control actuation of the flow-limiting element. Preferably, the controller is programmed to receive inputs indicative of fluctuations in the patient's hemodynamic state and, in response to said input, adjust the actuation / deactivation of the flow-limiting element. Fluctuations in the patient's hemodynamic state may be caused by the patient's non-bedridden activity. The controller can be programmed at catheter insertion time 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, and this predetermined number of cycles or time interval can be continuously adjusted by the controller in response to the patient's heart rate input. The controller can additionally receive signals from sensors and / or electrodes indicative of sensed parameters reflecting hemodynamic state, such as blood flow rate, blood volume, pressure including cardiac filling pressure, and the controller can continuously adjust the predetermined number of cycles or time interval in response to the sensed parameters (one or more).

[0030] In a preferred embodiment, the catheter is configured for intravascular implantation (e.g., via the patient's left subclavian vein), such that the flow-limiting element is placed in the SVC proximal to the right atrium. The proximal end of the catheter may be coated or impregnated with an antibacterial agent to extend catheter use and reduce the risk of infection at the site of percutaneous catheter penetration. Preferably, the controller is battery powered and includes a quick-connect coupling that allows the controller's actuation mechanism to be operatively coupled to the flow-limiting element. In a preferred embodiment, the controller is small enough that it can be worn by the patient in harness near the shoulder. Compared to previously known systems that confine patients to a bed or acute care equipment, the system of the present invention is configured to allow patients to perform most daily activities without being bedridden, thereby enhancing their quality of life and improving patient compliance during treatment using the system of the present invention. In one embodiment, the controller is configured for implantation in a suitable location within the patient's body, such as a subcutaneous implantation below the clavicle. In such embodiments, the implantable controller is configured for bidirectional communication with an external controller, such as a mobile device or a system-specific device. An external controller may be configured to charge the battery of the implantable controller, for example, via a corresponding induction coil in each controller, and may receive data indicating sensed parameters, including heart rate, blood flow rate, blood volume, and pressure including cardiac filling pressure. One or more external power sources may be in electrical communication with the implantable controller and may also be configured to provide power to the controller to charge the battery of the implantable controller. One or more external power sources may generate an alarm when the level of the one or more external power sources falls below a threshold level.

[0031] In a preferred embodiment, the flow-limiting element includes one or more incompatible or semi-compatible balloons attached to the distal region of the catheter, such that the controller actuates the balloons by periodically inflating and deflating them to selectively and completely or partially occlude the SVC and / or azygos vein. For example, the controller may be programmed to intermittently actuate the flow-limiting element to at least partially occlude the SVC for a first predetermined time interval and contract for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval may be at least five times greater than the second predetermined time interval. For example, the first predetermined time interval may be 4-6 minutes, while the second predetermined time interval is 1-30 seconds. In an alternative embodiment, the flow-limiting element may include a membrane covering, basket, or other mechanical arrangement capable of rapidly transitioning between an expanded and contracted position, for example, via a drive system connected to the controller. In a further embodiment, the flow-limiting element may be in the form of a butterfly valve or ball valve, provided that the flow-limiting element does not create a stagnant zone in the SVC when in the contracted or open position. In yet another embodiment, the flow-limiting element includes a cuff configured to be applied to the outside of the SVC and operated by narrowing or occluding the SVC upon expansion.

[0032] The system of this invention may include a sensor placed on a catheter for placement within a venous or arterial tube to measure a patient's heart rate or blood pressure. Preferably, the sensor generates an output signal that serves as an input to a controller to adjust the degree or timing of the blockage created by the current-limiting element. In another embodiment, the controller may be configured to couple to a third-party heart rate or blood pressure sensor, such as those commonly used by sports enthusiasts, via a readily available wireless standard like Bluetooth, through the patient's smartphone. 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 this disclosure, a method for controlling blood flow in a patient includes: inserting and guiding a venous occlusion device into and into the patient's vena cava; coupling the occlusion device to a controller worn externally or implanted internally by the patient; and intermittently activating the venous occlusion device over intervals of multiple cardiac cycles, such that myocardial remodeling is inhibited or reversed after a period of several minutes, hours, days, weeks, or months.

[0034] According to another aspect of this disclosure, a system is provided for use in conjunction with a ventricular assist device (VAD) to improve the efficiency and functionality of the VAD and reduce the risk of adverse effects from the VAD. The system includes a catheter having proximal and distal zones, the catheter being sized and shaped to be placed (e.g., intravascularly via the patient's subclavian or jugular vein) to position the distal zone in the patient's superior vena cava (SVC). The system also includes a flow-limiting element, such as an SVC occlusion balloon, disposed on the distal zone of the catheter, which is selectively actuated to at least partially occlude the SVC, and a controller operatively coupled to the catheter to intermittently actuate the flow-limiting element to at least partially occlude the SVC, continuously across the intervals of one or more cardiac cycles, thereby reducing cardiac preload and pulmonary artery pressure to improve cardiac performance. For example, the controller can reduce cardiac preload during the interval, which is sufficient to improve cardiac performance as measured by at least one of the following: reduced cardiac filling pressure, increased left ventricular relaxation, increased left ventricular capacity, increased left ventricular stroke volume, increased lusitropy, reduced left ventricular stiffness, or reduced cardiac strain.

[0035] The system may further include a first pressure sensor disposed proximal to the flow-limiting element of the catheter, the first pressure sensor outputting a first pressure signal, and a second pressure sensor disposed on the catheter and distal to the flow-limiting element, the second pressure sensor outputting a second pressure signal, wherein the controller generates a first signal corresponding to the difference between the first and second pressure signals, the first signal indicating the degree of occlusion of the flow-limiting element. Optionally, the system may include a pressure switch disposed on the catheter having a first lumen and a second lumen, the first lumen having a first open end disposed proximal to the flow-limiting element, and the second lumen having a second open end disposed on the flow-limiting element. The pressure switch may be configured to generate a signal indicating the pressure difference between the first and second lumens. The controller may include a data transmission circuit configured to receive signals and communicate the signals to the patient's computing device for display to the patient.

[0036] The controller can use a first signal to determine when to actuate the current-limiting element to at least partially block the SVC and when to stop actuation of the current-limiting element. The controller can also be programmed to activate an alarm based on the first signal as a safety signal for the operator. Furthermore, the controller can be programmed to send alarm status messages to clinicians monitoring the patient via the cellular communication capabilities of a computing device. In one embodiment, the controller is configured for implantation at a suitable location within the patient, for example, subcutaneously below the clavicle.

[0037] Furthermore, the controller can be programmed to intermittently actuate the current-limiting element to at least partially block the SVC for a first predetermined time interval and constrict it for a second predetermined time interval over multiple cardiac cycles. The first predetermined time interval can be at least ten times greater than the second predetermined time interval. For example, the first predetermined time interval can be 4-6 minutes, while the second predetermined time interval is 1-10 seconds. The controller can be programmed to modify the first predetermined time interval based on the signal or based on the patient's heart rate.

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

[0039] Additionally, the system may include a left ventricular assist device (LVAD), comprising a catheter having proximal and distal sections, the distal section having an inlet and an outlet, the catheter being sized and shaped for placement via the patient's femoral artery such that the inlet is positioned in the patient's left ventricle and the outlet in the patient's aorta. The LVAD also includes a pump, such as an impeller pump, disposed on the distal section of the catheter, wherein the pump can be selectively actuated to pump blood from the left ventricle through the inlet and drain blood into the aorta via the outlet; and an LVAD controller operatively 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. Simultaneously with the LVAD controller actuating the pump to pump blood from the left ventricle into the aorta, the LVAD controller operatively coupled to the system's catheter can modulate the activation and deactivation of a flow-limiting element to at least partially occlude the SVC.

[0040] Optionally or additionally, the system may further include a right ventricular assist device (RVAD), which includes a pump, such as an impeller pump, that can be selectively actuated to pump blood from the SVC through the inflow end of the RVAD and drain the blood into the pulmonary artery via the outflow end of the RVAD. A controller may also be operatively coupled to the RVAD to actuate the pump to pump blood from the SVC into the pulmonary artery, thereby unloading the right ventricle. For example, while the controller actuates the pump to pump blood from the SVC into the pulmonary artery, the controller may actuate a flow-limiting element to at least partially block the SVC.

[0041] In another preferred embodiment, the RVAD includes a catheter having proximal and distal regions, the distal region having an inflow end and an outflow end, the catheter being sized and shaped to be placed via the patient's femoral vein, thereby positioning the outflow end in the patient's pulmonary artery and the inflow end in the patient's intraventricular ventricle (IVC). The RVAD also includes a pump, such as an impeller pump, disposed on the distal region of the catheter, wherein the pump can be selectively actuated to pump blood from the IVC through the inflow end and drain blood into the pulmonary artery via the outflow end; and an RVAD controller operatively coupled to the RVAD to actuate the pump to pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle. Simultaneously with the RVAD controller actuating the pump to pump blood from the IVC to the pulmonary artery, the RVAD controller of the catheter operatively coupled to the system can modulate the activation and deactivation of a flow-limiting element to at least partially occlude the SVC.

[0042] This system can also be used to modulate a patient's heart and perform cardiac surgery. The method may involve inserting a first catheter, including a flow-limiting element, into the patient's superior vena cava (SVC), such that the flow-limiting element is positioned within the SVC, and actuating the flow-limiting element within the SVC to at least partially occlude the SVC. Cardiac surgery can be performed on the patient's heart before, during, and / or after at least partial occlusion of the SVC. The flow-limiting element can be deactivated and reactivated within the SVC before or during cardiac surgery. Actuation of the flow-limiting element can stimulate the vagus nerve and increase the patient's urine flow.

[0043] Parameters related to the patient's heart can be measured to generate a first measurement parameter, which can be used to determine whether the measurement parameter meets a predetermined threshold. Determining the measurement parameter may include receiving a first signal from a first sensor disposed within the SVC and a second signal from a second sensor disposed within the SVC. The first sensor may be an electrode and may be disposed proximal to the flow-limiting element of the catheter. The second sensor may also be an electrode and may be disposed distal to the flow-limiting element of the catheter. If the measurement parameter is determined to meet the predetermined threshold, cardiac surgery can be performed. Partial and / or complete SVC closure helps make the heart more likely to undergo successful cardiac surgery. Cardiac surgery may be different from partial / complete SVC closure, such as the implantation of a cardiac prosthesis using a commercially available system (e.g., a prosthetic valve, regurgitation reduction device, clip, ring, ventricular assist device (VAD), etc.) and / or coronary revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

[0044] If the first measurement parameter is determined to not meet a predetermined threshold, the actuation parameter can be changed, and a second parameter can be further measured. The second parameter can be measured to generate a second measurement parameter, which can be used to determine whether the second measurement parameter meets the predetermined threshold. If it is determined that the second measurement parameter meets the predetermined threshold, cardiac surgery can be performed.

[0045] The system may also include inserting a second catheter into the heart via a lower venous catheter (IVC), which may be adapted to perform cardiac surgery. The second catheter may be positioned within the first catheter along at least a portion of the first catheter.

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

[0047] Methods for reducing volumetric overload may include receiving signals from one or more sensors. The method may include receiving a first signal from an accelerometer disposed on the conduit, indicating that a flow-limiting element at least partially blocks the SVC. The flow-limiting element may be stopped based on the first signal. Optionally, the method may include receiving a first signal from a sensor disposed on the flow-limiting element, indicating contact between the SVC and the flow-limiting element. In another embodiment, the method may include generating light from a lamp disposed proximal to the flow-limiting element in the conduit, determining a first signal from a light sensor disposed distal to the flow-limiting element in the conduit, and determining the degree of blockage of the flow-limiting element based on the first signal. In another embodiment, the method may include receiving a signal from a stretcher disposed on the conduit, the flow-limiting element, or a portion of both the conduit and the flow-limiting element. The flow-limiting element may be stopped based on the received signal.

[0048] The foregoing description of the invention is merely illustrative and is not intended to be limiting in any way. Other aspects, embodiments, and features will become apparent from the following drawings and detailed description, in addition to the illustrative aspects, embodiments, and features described above. Attached Figure Description

[0049] The features and advantages of the present invention will become apparent from the following detailed description of embodiments of the present disclosure, presented in conjunction with the accompanying drawings, in which: Figure 1A It is a frontal view showing a partial rupture of the heart's major arteries and veins.

[0050] Figure 1B The diagram illustrates the vena cava, which contains the major veins associated with it.

[0051] Figure 2A and 2B The graph illustrates the Frank-Starling curves for normal and diseased heart conditions.

[0052] Figure 3 This is an exemplary pressure-volume loop plot comparing left ventricular pressure and left ventricular volume throughout the entire cardiac cycle for patients with normal cardiac function and patients with congestive heart failure.

[0053] Figure 4A This is a schematic diagram of a system constructed according to the principles of the present invention.

[0054] Figure 4B This is a schematic diagram of an implantable system constructed according to the principles of the present invention.

[0055] Figure 4C This is a diagram of the power supply and charging base.

[0056] Figures 5A to 5B yes Figure 4A and Figure 4B A schematic diagram of a catheter, wherein the flow-limiting element includes a cylindrical balloon with a modified anchoring member, shown in both expanded and contracted states.

[0057] Figure 6 yes Figure 4A and Figure 4B A schematic diagram of a conduit, wherein the flow-limiting element includes a membrane-covered basket that is mechanically actuated.

[0058] Figure 7 yes Figure 4A and Figure 4B Cross-sectional view of the conduit.

[0059] Figure 8A and 8B It is a schematic diagram of a flow-limiting element including a spherical balloon shown in its expanded and contracted states, respectively.

[0060] Figure 9A and 9B It is a schematic diagram of a current-limiting element including a spring-loaded plug shown in its expanded and contracted states, respectively.

[0061] Figure 10A and 10B This is a schematic diagram of a current-limiting element including an optional embodiment of a spring-loaded plug shown in its expanded and contracted states, respectively.

[0062] Figure 11 The graphs and tables shown depict left ventricular (LV) pressure and LV volume during multiple consecutive heartbeats in a pig model following complete occlusion of the inferior vena cava (IVC).

[0063] Figure 12 The graphs and tables shown depict LV pressure and LV volume during multiple consecutive heartbeats in a pig model following partial occlusion of the superior vena cava (SVC).

[0064] Figure 13-14 It is a graph showing the pressure changes with left ventricular volume and right ventricular volume during superior vena cava (SVC) occlusion and release in pigs with heart failure, according to the principles of the present invention.

[0065] Figures 15 to 22 The test results are shown for the test pigs suffering from heart failure.

[0066] Figures 23A to 23D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the reduction time of a one-minute segment of continuous SVC occlusion, according to the principle of the present invention, are illustrated respectively.

[0067] Figures 24A to 24D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the reduction time of a five-minute segment of continuous SVC occlusion, according to the principles of the present invention, are illustrated respectively.

[0068] Figures 25A to 25D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the reduction time of a continuous ten-minute segment of SVC occlusion, according to the principles of the present invention, are illustrated respectively.

[0069] Figures 26A to 26C The clinical pressure changes of pulmonary capillary wedge pressure, pulmonary artery pressure, and right atrial pressure observed during a five-minute segment of continuous SVC occlusion, according to the principles of the present invention, are illustrated separately.

[0070] Figures 27A to 27E The clinical pressure changes of systolic blood pressure, diastolic blood pressure, mean arterial pressure, mean pulmonary artery pressure, and mean pulmonary capillary wedge pressure during five minutes of continuous SVC occlusion according to the principles of the present invention are illustrated separately.

[0071] Figures 28A to 28B The clinical pressure changes of mean pulmonary artery pressure and mean arterial pressure during a continuous ten-minute SVC occlusion period, according to the principles of the present invention, are illustrated separately.

[0072] Figure 29 The diagram illustrates cardiac output before and during SVC occlusion according to the principles of the present invention.

[0073] Figure 30 The diagram illustrates pulmonary artery systolic pressure during SVC closure and non-closure according to the principles of the present invention.

[0074] Figure 31 This is a predictive example of how SVC closure according to the principles of the present invention may alter disease progression.

[0075] Figure 32 This is a perspective view of a cylindrical current-limiting element.

[0076] Figure 33 This is a cross-sectional view showing the cylindrical current-limiting element of the release valve.

[0077] Figure 34A -B is a cross-sectional view of a cylindrical current-limiting element with a binary release valve and a progressive release valve.

[0078] Figure 35 It is a top view of a cylindrical current-limiting element with a release valve in the closed position.

[0079] Figure 36A -B is a top view of a cylindrical current-limiting element with a binary release valve in the open position and a progressive release valve.

[0080] Figure 37A -B is a perspective and sectional view of the cylindrical current-limiting element that engages with the bracket.

[0081] Figure 38A -B is a top view of a cylindrical flow-limiting element with a balloon occluder in both expanded and contracted positions.

[0082] Figure 39A -B is a top view of a cylindrical flow-limiting element with a cylindrical balloon occluder in both expanded and contracted positions.

[0083] Figure 40A -B is a perspective and cross-sectional view of the stent coupled to the release valve.

[0084] Figure 41 This is a cross-sectional view of a cylindrical current-limiting element coupled to a filter.

[0085] Figure 42A It is a cross-sectional perspective view of a cylindrical current-limiting element coupled to a conduit containing a sensor, and Figure 42B This is an example phasic curve.

[0086] Figure 43A -F is a view of the guide sheath entering the SVC, the current-limiting element inside the SVC, the conduit, and one or more sensors.

[0087] Figure 44 This is a view of the guide sheath located within the SVC, the flow-limiting element incorporated into the guide sheath, and the catheter located within the heart.

[0088] Figure 45 This is a view of an occlusion system with an azygos vein occlusion balloon and a second occlusion balloon located within the SVC.

[0089] Figure 46 This is a view of the occlusion cuff wrapped around the SVC.

[0090] Figure 47A -B is a view of the outer and inner sides of the occlusion cuff, and Figure 47C -D is a perspective view of the occlusion cuff.

[0091] Figure 48 This is an optional exemplary system constructed according to the principles of the present invention.

[0092] Figure 49 The diagram illustrates the SVC occlusion system combined with translobe LVAD.

[0093] Figure 50 This diagram illustrates how the unloading capacity of the SVC blockade is enhanced when used in combination with a cross-lobe LVAD.

[0094] Figure 51 The diagram illustrates the SVC occlusion system combined with the translobe RVAD.

[0095] Figure 52 The diagram illustrates the SVC occlusion system in combination with the optional translobe RVAD.

[0096] Figure 53 The diagram illustrates the SVC plugging system combined with LVAD.

[0097] Figure 54 The diagram illustrates an SVC plugging system combined with LVAD, which includes a current-limiting element located on the guide sheath.

[0098] Figure 55 This is a flowchart of an exemplary method for deploying an SVC occlusion system in the SVC and implanting an LVAD in the left ventricle.

[0099] Figure 56 The diagram illustrates the SVC occlusion system combined with the intra-aortic balloon pump (IABP).

[0100] Figure 57A -C illustrates the normal heart, the chronically compensated heart, and the decompensated heart, respectively.

[0101] Figure 58 The diagram illustrates an SVC plugging system, which includes a current-limiting element located on a guide sheath within the SVC.

[0102] Figure 59 The diagram illustrates an SVC occlusion system, which includes a flow-limiting element located on a guide sheath within the SVC and a delivery catheter for deploying valve clips via the IVC.

[0103] Figure 60 This is a flowchart of an exemplary method for deploying an SVC occlusion system in an SVC and performing cardiac surgery.

[0104] Figure 61 The diagram illustrates an SVC occlusion system, which includes a flow-limiting element located on a guide sheath within the SVC and a delivery catheter for deploying annulusoplasty rings via the IVC.

[0105] Figure 62 The diagram illustrates an SVC occlusion system, which includes a flow-limiting element located on a guide sheath within the SVC and a delivery catheter for deploying a transcatheter prosthesis via the IVC.

[0106] Figure 63The diagram illustrates an SVC occlusion system, which includes a flow-limiting element located on a guide sheath within the SVC and a delivery catheter located within the guide sheath. Detailed Implementation

[0107] refer to Figure 1A and 1B The description of the human anatomical structures in which the present invention is designed to be placed and operated serves as the context for the systems and methods of the present invention.

[0108] More precisely, reference Figure 1A Deoxygenated blood returns to the heart 10 via the vena cava 11, which includes the superior vena cava 12 and the inferior vena cava 13, which connect to the right atrium 14 of the heart. Blood moves from the right atrium 14 through the tricuspid valve 15 to the right ventricle 16, where it is pumped to the lungs via the pulmonary artery 17. Oxygenated blood returns from the lungs to the left atrium 18 via the pulmonary veins. The oxygenated blood then enters the left ventricle 19, which pumps blood to the rest of the body via the aorta 20.

[0109] like Figure 1B As shown, 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 The study also shows some connections of the azygos vein 16 and other major veins to the inferior vena cava. As noted in this paper, occlusion of the inferior vena cava 13 may lead to venous congestion, and specifically, occlusion or dilation of the hepatic veins and / or adrenal veins may worsen rather than improve a patient's cardiovascular condition and overall health.

[0110] According to one aspect of the invention, the applicant has determined that selective intermittent occlusion of the superior vena cava (“SVC”) carries fewer potential adverse risks than occlusion of the inferior vena cava (“IVC”). Furthermore, the applicant’s animal and human studies have revealed that controlling right ventricular venous return by partial or complete occlusion of the SVC advantageously reduces RVEDP, RVEDV, LVEDP, and LVEDV without adversely reducing left ventricular systolic pressure (LVSP).

[0111] The applicant understands that selective intermittent occlusion of the SVC site, compared to IVC occlusion, reduces the risk of worsening renal congestion, a major cause of cardiorenal syndrome. Cardiorenal syndrome is impaired kidney function caused by volume overload and neurohormonal activation in patients with heart failure. Volume overload can occur when a weak heart cannot pump enough blood, leading to less blood flowing through the kidneys. With less blood flowing through the kidneys, less blood is filtered, and less water is excreted through urine, resulting in excess volume remaining in the body. With this excess volume, the heart pumps with decreasing efficiency, and as the body gradually becomes increasingly congested, the patient eventually spirals towards death.

[0112] The applicant understands that IVC closure typically reduces blood flow through the kidneys as the pressure in the renal veins increases with the closure, thus reducing the kidneys' ability to filter fluid. IVC closure further causes blood back-up and otherwise prevents deoxygenated blood from returning to the heart. As a result, kidney function may also decrease, and congestion may worsen. However, SVC closure ultimately increases flow to the kidneys, thereby improving kidney function. Specifically, by reducing flow into the right atrium via SVC closure, the volume of the left ventricle is ultimately reduced, which allows muscle fibers to stretch within normal limits. This naturally increases the rate of contraction and allows the heart to drive more fluid to the kidneys. The kidneys can then extract water, which can be removed from the body through urination. It should be further understood that during SVC closure, the sudden decrease in right atrial pressure and volume creates a negative pressure buildup in the right atrium. As a result, flow from the renal veins can be accelerated, thereby enhancing renal decongestion and promoting blood flow across the kidneys, increasing urine output. Therefore, SVC closure can benefit patients with heart failure and / or cardiorenal syndrome by reducing pressure on the heart and lungs and promoting congestion relief.

[0113] Furthermore, implantation in the SVC allows for the implantation of a supraseptal device, which is impossible in the IVC without cardiac puncture and passage through the right atrium. Additionally, implantation of the occluder in the SVC avoids the need for groin access required for IVC implantation, which would restrict mobility and thus prevent the use of non-ambulatory devices for short or long periods. Moreover, even minor changes (in time or degree) in IVC occlusion can lead to a reduction in preload and therefore a more drastic change in total cardiac output / systemic blood pressure, whereas the system and method of the present invention, as desired, allow for a finely tuned reduction in venous return (preload reduction).

[0114] The 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 advantageously allow the patient's heart to cease or recover from myocardial remodeling. The applicant's animal and human studies indicate that the system enables the myocardial layer to shift from a pressure-to-cardiac output curve indicative of heart failure towards a pressure-to-cardiac output curve more closely approximating that of a healthy heart.

[0115] In general, the systems and methods of the present invention can be used to treat any disease to improve cardiac function by inhibiting or reversing myocardial remodeling, and more specifically, 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, patients with decompensated heart failure (ADHF), chronic heart failure, acute heart failure and pulmonary hypertension, heart attack, heart failure with preserved ejection fraction, right heart failure, systolic and restrictive cardiomyopathy, and cardiorenal syndrome (types 1-5). The systems and methods of the present invention can also be used to prevent or alleviate the consequences of acute right or left ventricular myocardial infarction, pulmonary hypertension, RV failure, post-cardiotomy shock, or orthotopic heart transplant (OHTx) rejection, or otherwise for cardiorenal applications and / or treatment of renal insufficiency, hepatic insufficiency, or lymphatic congestion. Furthermore, the systems and methods of the present invention can reduce hospital stays caused by the various diseases described herein, including at least acute exacerbations.

[0116] The relationship between left ventricular pressure or left ventricular volume and stroke volume is commonly referred to as the Frank-Starling relationship or the "Starling curve," and is illustrated graphically. Figure 2A-2B This relationship indicates that stroke volume depends on preload, contractility, and afterload. Preload refers to the volume of blood returning to the heart; contractility is defined as the inherent capacity of the myocardium to contract; and afterload is determined by vascular resistance and impedance. In heart failure due to diastolic or systolic dysfunction, decreased stroke volume leads to increased volume and pressure in the left ventricle, which can cause pulmonary edema. Increased ventricular volume and pressure also lead to increased workload and myocardial oxygen consumption. This overexertion of the heart leads to deterioration of cardiac function as the heart becomes increasingly hypoxic due to the mismatch between supply and demand. Furthermore, as the volume and pressure within the heart increase, systolic function deteriorates due to the stretching of the myocardium. This condition is called "congestive heart failure."

[0117] refer to Figure 2AThe diagram shows a series of Starling curves, with the top curve (Curve 1) depicting the operation of a normal heart. As the curves show, stroke volume increases with increasing LVEDP or LVEV, and only begins to flatten at extremely high pressures or volumes, i.e., the slope of the curve decreases. Patients who have just experienced an acute myocardial infarction (“AMI”), as indicated by the middle curve (Curve 2), will show decreased stroke volume at each LVEV or LVEDP value. However, because the heart is only beginning to experience overload from the local effects of the infarction, the myocardial contractility of the entire ventricle remains relatively good, and stroke volume remains relatively high at low LVEDP or LVEV. In contrast, patients with past cardiac injury may experience progressive deterioration of cardiac function as the myocardial layer remodels over time to compensate for the increased workload and reduced oxygen availability, as indicated by… Figure 2A The lowest curve (curve 3) depicts this. As noted above, as the ventricles expand due to the generally higher volume and pressure during each phase of the cardiac cycle, this can lead to a gradual decrease in cardiac output. As will be observed from a comparison of curves 1 and 3, cardiac output continues to decline as LVEDP or LVEDV climbs, until eventually heart failure or the patient dies from circulatory-related disease.

[0118] Figure 2B A Frank-Starling curve is provided, with optional formulation for curve 6, which graphically illustrates the difference in function between a healthy heart and a heart in heart failure. Line 7, up to point 8, plots the Frank-Starling curve for a normal, healthy heart. (See also: Regarding...) Figure 2A The discussion focuses on how, for a normal heart, stroke volume increases with increasing end-diastolic volume. However, for a healthy heart, beyond point 8, increases in end-diastolic volume no longer lead to an increase in stroke volume, and continued increases in end-diastolic volume do not result in a further increase in stroke volume. This phenomenon is illustrated by the solid horizontal line extending substantially horizontally beyond point 8. Figure 2B In the diagram, dashed line 9, extending beyond 8, represents the Frank-Starling curve for patients with heart failure. Dashed line 9 indicates that for patients with heart failure, further increases in end-diastolic volume do not result in a substantially flat cardiac output, but rather a decrease in cardiac output. Therefore, increasing EDV in HF patients leads to a further decrease in SV, which causes a spiral decline in cardiac function and ultimately death. Figure 2BThis reflects a phenomenon known as "diastolic ventricular interaction," which arises in part from the structural arrangement of the heart chambers. As discussed, for example, in the article by J. Atherton et al. entitled "Diastolic ventricular interaction in chronic heart failure," Lancet 1997; 349:1720-24, the pericardium limits the extent to which the ventricles of a failing heart can expand. Therefore, an increase in right ventricular end-diastolic volume necessarily leads to a decrease in left ventricular end-diastolic volume. As reported in that article, the reduction in right ventricular diastolic filling caused by external lower body suction allows for an increase in left ventricular diastolic filling.

[0119] The applicant understands that the foregoing phenomena can be advantageously utilized in the context of this invention to improve cardiac performance. Specifically, in cases of heart failure and pulmonary hypertension, right ventricular congestion due to increased volume overload can push the interventricular septum membrane toward the left ventricular cavity, thereby reducing LV stroke volume and cardiac output. By blocking the flow through the SVC, right ventricular pressure and volume can be reduced. This, in turn, causes the interventricular septum to shift away from the LV cavity, allowing for increased left ventricular stroke volume and enhanced cardiac output. For these reasons, SVC closure according to the principles of this invention can advantageously alter diastolic ventricular interaction and enhance cardiac output. Specifically, regarding diastolic heart failure, SVC closure according to the principles of this invention can provide a reduction in cardiac filling pressure, increased LV tau, increased LV volume, increased loosening effect, reduced LV stiffness, and reduced cardiac strain. Therefore, the effect of SVC closure according to the present invention can be visualized as... Figure 2B In patients with heart failure, the dashed line 9 of the Frank-Starling curve 6 shifts towards a lower EDV, which effectively moves cardiac performance upwards and closer to the flat portion of the curve that extends beyond point 8 in healthy patients. Therefore, the system and method of the present invention for at least partial intermittent SVC occlusion in HF patients improves cardiac function by shifting the patient's cardiac contractility towards the healthy range of the patient's Frank-Starling curve.

[0120] Figure 3 The diagram schematically shows the pressure-volume loop of a normal heart, labeled "Normal," corresponding to... Figure 2B Curve 1 in the figure, and the pressure-volume loop of the heart suffering from congestive heart failure, are labeled "CHF". Figure 2B(Curve 3 in the diagram). For each loop, the ventricular volume and pressure at end-diastole correspond to the lower right corner of the loop (point A), while the upper left corner of each loop corresponds to the start of cardiac contraction (point B). The stroke volume of each pressure-volume loop corresponds to the area enclosed within the loop. Therefore, the most beneficial venous regulation range is to reduce the volume and pressure at point A without causing a negligible reduction at point B, thereby maximizing stroke volume.

[0121] According to one aspect of the invention, the system and method are designed to cause the Starling curve of a patient's heart to... Figure 2B The diagram is shifted or transformed to the left (or made to) Figure 3 (The pressure-volume loop in the heart shifts to the left and downward). This can be accomplished by intermittently and completely or partially occluding the SVC to reduce the volume of blood entering the right ventricle and then having to be pumped through the left ventricle, thus reducing pressure. The applicant's preliminary animal studies indicate that such intermittent occlusion, maintained for several cardiac cycles, reduces workload and wall stress in the myocardial layer throughout the cardiac cycle, reduces myocardial oxygen consumption, and improves contractile function.

[0122] Now for reference Figure 4A The present invention describes an exemplary system 30. System 30 includes a conduit 31 having a current-limiting element 32 coupled to a controller 33, the controller being programmed to intermittently actuate the current-limiting element 32. As discussed below, system 30 can be configured as needed to bidirectionally transmit information with a conventional computing device 45, such as a smartphone, laptop, smartwatch, or tablet computer, such as an Apple iPhone 5 or iPad available from Apple Inc., Cupertino, California, on which a dedicated application is installed to communicate with and / or control the controller 33.

[0123] Preferably, the catheter 31 includes a distal portion 34 configured as a flexible tube for placement in the SVC. The distal portion 34 includes a flow-limiting element 32, which, in use, is placed in the patient's superior vena cava 12 (see [link to documentation]). Figure 1B This selectively blocks blood flow into the right atrium 14. In this embodiment, the flow-limiting element 32 exemplarily includes a balloon capable of transitioning between a constricted state and an expanded state, allowing for transluminal placement. The flow-limiting element 32 is preferably sized and shaped such that it partially or completely blocks blood flow in the expanded SVC. The catheter 31 is coupled at its proximal end 35 to a controller 33, which houses a drive mechanism 36 (e.g., a motor, pump) for actuating the flow-limiting element 32, a processor 37 programmed to control signals to the drive mechanism 36, and optionally sensors 42 for monitoring physiological parameters such as the patient's heart rate or blood pressure.

[0124] The controller 33 may include an inflatable media source 48 (e.g., gas or fluid), and an actuation mechanism 36 may transfer the inflatable media between the source and the flow-limiting element 32 in response to a command from the processor 37. When the flow-limiting element 32 is filled with the inflatable media, the flow-limiting element partially or completely occludes venous blood flow through the SVC; when the inflatable media is withdrawn, the flow-limiting element 32 deflates to release the occlusion, thereby allowing blood flow to be restored in the SVC. The flow-limiting element 32 may be a balloon, preferably comprising a compliant or semi-compliant material, such as nylon, which allows the balloon's inflation degree to be adjusted to achieve the desired degree of partial or complete occlusion of the SVC. Additionally, the catheter 31 provides a fail-safe design when partially external, such that the flow-limiting element 32 only inflates to provide occlusion when the proximal end of the catheter 31 is coupled to the controller 33. Such a quick disconnect coupling 40 at the proximal end 35 allows the catheter to be quickly disconnected from the controller 33 for cleaning and / or emergency procedures.

[0125] The controller 33 preferably also includes a power supply 39 (e.g., a battery) that provides the power required to operate the processor 37, drive mechanism 36, and data transmission circuitry 38. The controller 33 may be sized and weighted such that it can be worn in clothing under the patient's garments, allowing the system to be used when the patient is not bedridden or allowing the controller 33 to be implanted in the patient's body. As discussed below, the processor 37 includes a memory 41 for storing computer software to operate the controller 33. The controller 33 may be configured for implantation in a suitable location within the patient's body, such as subcutaneous implantation under the clavicle. In this embodiment, the implantable controller is configured for bidirectional communication with an external controller, such as a computing device 45 or a system-specific device. The external controller may be used to charge the battery of the implantable controller, for example, through a corresponding induction coil in or coupled to each controller, and may receive data indicating parameters sensed from the patient's non-bedridden activity, including heart rate, blood flow rate, blood volume, and pressure including cardiac filling pressure.

[0126] In one implementation, data transmission circuitry 38 monitors input from, for example, an external sensor positioned on catheter 31 and provides the signal to processor 37. Processor 37 is programmed to receive input from data transmission circuitry 38 and adjust the interval at which the flow-limiting element 32 is maintained in an expanded state, or to adjust the degree of occlusion created by the flow-limiting element 32. Thus, for example, catheter 31 may have an optional sensor 42 positioned within the distal portion 34 of the catheter to measure parameters such as heart rate, blood flow rate, blood volume, and pressures including cardiac filling pressure and central venous pressure. The output of sensor 42 is relayed to data transmission circuitry 38 of controller 33, which may preprocess the input signal, for example, by extracting and digitizing the output of sensor 42, before supplying it to processor 37. Providing the signal to processor 37 allows the effectiveness of the flow-limiting element to be assessed, for example, by displaying the reduction in venous pressure during occlusion and during patency, and can be used by a patient or clinician to determine the degree of occlusion required to regulate venous return based on the severity of congestion in the patient. Additionally, sensor 43 may be included on catheter 31 near flow-limiting element 32 to measure parameters such as heart rate, blood flow rate, blood volume, and pressure including cardiac filling pressure and central venous pressure. Sensor 43 can be used, for example, to determine the degree of occlusion caused by element 32 by monitoring the pressure drop across the flow-limiting element.

[0127] As another example, catheter 31 may include electrode 44 for sensing a patient's heart rate. The applicant understands that the interval for maintaining the occlusion of the SVC may need to be adjusted in response to a patient's non-laminar activity, which is typically reflected in the patient's hemodynamic status through sensed physiological parameters such as heart rate, blood flow rate, blood volume, and pressure including cardiac filling pressure and / or central venous pressure. Therefore, electrode 44 may provide signals to data transmission circuitry 38, which then processes the facility signals for use by a programming routine executed by processor 37. For example, if a certain time during the initial system setup for maintaining the occlusion is programmed to reflect a patient at rest, such as causing the flow-limiting element to deploy for 5 seconds and then release for 2 seconds before re-deploying, then depending on the patient's level of physical activity, the occlusion interval may need to be reduced to 4 seconds or more, the level of physical activity detected by changes in heart rate, blood flow rate, blood volume, and pressure including cardiac filling pressure and / or central venous pressure above or below predetermined thresholds. Alternatively, processor 37 can be programmed to maintain a preset number of heart cycles for partial or complete occlusion in the SVC, as determined at the time of initial catheter implantation. Sensor inputs, such as hemodynamic status, provided to data transmission circuit 38 can also be used to adjust the operating cycle of the flow-limiting element in response to the detected level of patient activity. Furthermore, processor 37 can be programmed to maintain a preset number of heart cycles for partial or complete occlusion in the SVC after adjustment of a predetermined occlusion interval.

[0128] The data transmission circuit 38 can also be configured to provide bidirectional data transmission, for example, by including a wireless circuitry system to transmit data from the controller 33 to an external unit for display, viewing, or adjustment. For instance, the data transmission circuitry may include a Bluetooth circuitry system that enables the controller 33 to communicate with the patient's computing device 45. In this way, the controller can send information about system operation directly to the computing device 45 to display important physiological or system parameters using an appropriately configured mobile application. Additionally, the patient can view the data displayed on the screen of the computing device 45 and determine if they need medical assistance to address dysfunction or adjust system parameters. Furthermore, the mobile application residing on the computing device 45 can be configured to automatically initiate monitoring services to clinicians via a cellular telephone network.

[0129] Optionally, the data transmission circuit 38 can be configured to synchronize to receive data from other mobile applications on the computing device 45, thereby reducing the cost and complexity of the system of the present invention. For example, several third-party vendors, such as Fitbit, Inc., San Francisco, California, market monitors that measure real-time physiological parameters, such as the Charge HR wristband monitor, which measures physical activity and heart rate. According to one aspect of this disclosure, the data transmission circuit 38 can be programmed to receive input from such a third-party monitor via wireless communication with the computing device 45, and the processor 37 can be programmed to control the activation of the drive mechanism 36 in response to said input. In this embodiment, the catheter need not include optional sensors 42, 43, or electrodes 44, thereby greatly simplifying the construction of the catheter 31 and coupling 40.

[0130] The catheter 31 may include an anchoring member 46 configured to anchor the flow-limiting element 32 within the SVC. The anchoring member 46 is retractable for delivery in a retracted state and can be immediately expanded after release from a delivery device, such as a sheath. The anchoring member 46 may be coupled to the catheter proximal or distal to the flow-limiting element 32 and / or may be coupled to the flow-limiting element 32. Figure 4A The system shown in the image can effectively shift the patient's cardiac contraction rate to... Figure 2A Within the healthy range of the Frank-Starling curve illustrated in the diagram.

[0131] Now for reference Figure 4B The display shows that the controller 33 is implanted in the patient's body at the appropriate location. Figure 4BAs shown, an external power source 47 can be configured to charge a power supply 39 (e.g., a battery) of an implantable controller. For example, the external power source 47 can charge the power supply 39 transdermally via a corresponding induction coil. The external power source 47 can be integrated into clothing or garments worn by the patient. Specifically, the external power source 47 can be placed in a pocket or fastener configured to house the external power source 47. When the patient wears the clothing or garment, the pocket or fastener can be designed to place the external power source 47 close to the battery 39 for efficient transdermal charging. More than one external power source 47 can be integrated into the clothing to provide additional power. The one or more external power sources can be permanently integrated into the clothing or garment or can be detachably attached to the clothing or garment, such that each external power source can be individually removed and attached. For example, two external power sources 47 can be integrated into, for example, Figure 4B The vest 64 shown has specially designed pockets. The vest 64 may contain wires 66 incorporated within the vest 64 to allow electrical communication between two external power sources.

[0132] Power supply 47 may generate an alarm when the available power supply reaches or falls below a certain threshold level. For example, power supply 47 may have a visual indicator and / or an auditory indicator to provide a warning to the patient or caregiver. The visual indicator may be an LED lighting system or a display embedded in the surface of power supply 47, which visually provides information about the available power supply. The auditory indicator may be a speaker embedded in power supply 47 that emits an alarm sound when the available power supply reaches a certain threshold. The signal indicating that the available power supply of power supply 47 has reached a certain threshold may also, or optionally, be directly transmitted to an external device such as computing device 45, and / or to controller 33 and then from controller 33 to the external device such as computing device 45, which may be programmed to activate the visual or audio alarm. Additional power supply 47 may supply power to power supply 39 when the main power supply is unavailable to ensure a continuous power supply to power supply 39. Power supply 47 may include a processor with memory for transdermal data transmission and for receiving data from processor 37. The processor of power supply 47 can be used to reprogram processor 37 and / or store information about operating parameters, which will later be downloaded by an external device such as computing device 45.

[0133] Each external power source 47 can be positioned to connect to a wall power outlet or Figure 4CThe dock charger 65 shown is electrically connected to charge the external power source. The dock charger 65 is electrically connected to a wall outlet and can be configured to charge one or more external power sources 47 simultaneously. To allow the power supply 39 to remain continuously connected to power, the external power sources 47 can be periodically disconnected from the vest and charged, such that at least one external power source 47 is electrically connected to the power supply 39 while the other external power sources 47 are charging in the dock charger 65. Furthermore, 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.

[0134] Now for reference Figure 5A and 5B Describes an exemplary embodiment of catheter 31', wherein catheter 31' is configured similar to Figure 4A and Figure 4B The conduit 31 only has a modified anchoring component. For example... Figure 5A As shown, when the current limiting element 32' is in an extended fully blocked state, and as Figure 5B As shown, when the flow-limiting element 32' is in the constricted state, the catheter 31' may include a radially extended anchoring arm 49. The anchoring arm 49 is configured to extend radially, for example, when exposed from the delivery sheath, to contact the inner wall of the superior vena cava 12 and anchor the flow-limiting element 32' therein.

[0135] Now for reference Figure 6 The description describes an alternative implementation in which occlusion may include a wire basket. The flow-limiting element 50 may be formed of a biocompatible material such as nickel-titanium or stainless steel and includes a plurality of axially or helically extending wires 51, which are biased to expand radially outward when compressed. The flow-limiting element 50 preferably includes a biocompatible membrane cover such that it partially or completely occludes blood flow in the dilated SVC. The wires 51 may be coupled at a distal end 52 to a distal end 53 of an actuating wire 54 and attached to a ring 55 at a proximal end 56 of the wires. The ring 55 is positioned to slide on the actuating wire 54 such that it pulls the actuating wire 54 in a proximal direction against a sheath 57 (see [reference]). Figure 5A and 5B When ), wire 51 extends radially outward. For example... Figure 5B As shown, in response to a force applied to the proximal end of the actuation wire 54 via the drive mechanism 36, the actuation wire 54 retracts proximally against the sheath 57 of the conduit; thereby causing the current-limiting element 50 to transition to its extended state. Conversely, when the drive mechanism 36 is deactivated, the spring force applied by the wire 51 pulls the actuation wire 54 proximally, thereby allowing the wire 51 to return to its uncompressed state, thus resting substantially flat against the actuation wire 54. As noted above, the current-limiting element 50 has a "fail-safe" design, allowing the current-limiting element to recover when the conduit 31 is decoupled from the drive mechanism 36. Figure 5AThe image shows a converged / contracted state. In this embodiment, the drive mechanism 36 can be a motor, which can be a linear motor, a rotary motor, an electromagnetic piston, or a wire motor.

[0136] The current limiting element 50 may be configured such that it is biased to a constricted position when the conduit 31 is disconnected from the controller 33, such that the current limiting element 50 can only transition to an expanded state when the conduit is coupled to the controller 33, and the processor signals the drive mechanism 36 to expand the current limiting element.

[0137] Now for reference Figure 7 The catheter 31 preferably includes at least three lumens 60, 61, and 62. Lumen 60 may serve as an expansion lumen and / or for carrying an actuation line 54 extending between the flow-limiting elements 32 / 50 and the drive mechanism 36 of the controller 33. Lumen 61 allows optional sensors 42, 43, or electrodes to communicate with the data transmission circuitry 38, and optional lumen 62 is used for delivering pharmacological agents (e.g., drugs) to the heart.

[0138] During the procedure, catheter 31, equipped with flow-limiting elements 32 / 50, is inserted into the patient's subclavian vein and guided to the patient's SVC, for example, at a location proximal to the right atrial inlet (see [reference]). Figure 1A Techniques known in the art can be used to insert and fix the flow-limiting element 32 / 50 at the desired venous location within the patient. Proper positioning of the device can be confirmed using, for example, vascular ultrasound. Alternatively, the flow-limiting element 32 / 50 can be inserted and guided to the SVC via the jugular vein or even a peripheral vein under fluoroscopic or ultrasound guidance.

[0139] Once catheter 31 and flow-limiting elements 32 / 50 are positioned as desired, controller 33 immediately initiates the process of expanding and contracting the occlusion element to intermittently block and restore blood flow in the SVC. The degree to which the flow-limiting element impedes blood flow can be adjusted by regulating the radial expansion of the flow-limiting element, as well as the time interval of occlusion, such as the number of heartbeats. For example, in some embodiments, the flow-limiting element can impede blood flow in the SVC at any point from at least 50% to 100%. The impedance of the blood flow can be confirmed using methods known in the art, such as by measuring a decrease in pressure, a decrease in pressure fluctuations, or visually using ultrasound.

[0140] According to one aspect of this disclosure, controller 33 includes software stored in memory 41 that controls the timing and duration of the continuous expansion and contraction of current-limiting elements 32 / 50. As described above, a programming routine running on processor 37 can be used as input to the patient's cardiac cycle. For example, in some embodiments, the software can be configured to actuate current-limiting elements 32 / 50 to maintain partial or complete occlusion of the SVC over multiple cardiac cycles, such as four or more consecutive heartbeats of the subject. Controller 33 can accept the output of electrode 44 as input via data transmission circuitry 38, representing the patient's electrocardiogram (ECG), or alternatively, can receive such input wirelessly from a third-party heart rate application running on the patient's smartphone, allowing the software running on processor 37 to adjust the occlusion interval and / or degree provided by system 30 in response to the patient's heart rate. Thus, for example, if the patient is physically active, the timing or degree of occlusion produced by the current-limiting elements can be reduced to allow for more rapid replenishment of oxygenated blood to the patient's upper limbs. Conversely, if the heart rate indicates the patient is not active, the degree of SVC occlusion can be increased to reduce the resting workload on the heart. Optionally or additionally, system 30 may receive input via data transmission circuit 38, a value representing the patient's blood pressure measured by optional sensors 42 and 43 or third-party applications and devices such as blood pressure cuffs, such that controller 33 regulates blood flow through the SVC in response to the patient's blood pressure.

[0141] The controller 33 can be programmed to expand the current-limiting element when the sensed parameter exceeds a predetermined range and / or is above or below a predetermined threshold. For example, the controller 33 can cause the current-limiting element to expand when the optional sensors 42 and / or 43 sense that the right atrial (“RA”) pressure is within a predetermined range of 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg, 20 to 25 mmHg, or above a predetermined threshold of 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. As another example, controller 33 can cause the flow-limiting element to expand when optional sensors 42 and / or 43 sense that the mean pulmonary artery (“PA”) pressure is within a predetermined range of 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg, 20 to 25 mmHg, or above a predetermined threshold of 15 mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg, etc. The predetermined range and / or predetermined threshold can be patient-specific, and controller 33 can be programmed and reprogrammed for individual patients.

[0142] Referring now to Figures 8 to 10, alternative forms of endovenous flow-limiting elements suitable for occluding SVCs are described. As will be apparent to those skilled in the art, although Figures 4 to 6 depict cylindrical flow-limiting elements, other shapes may be used. Additionally, although not illustrated in conjunction with anchoring members in Figures 8 to 10, anchoring members may be included. In each pair of attachments... Figure 8A , 8B In figures 9A, 9B and 10A, 10B, paired figures depict each current-limiting element in a convergent-contraction state. Figure 8A , 9A and 10A) and extended deployment state ( Figure 8B , 9B (and 10B), in the converging contraction state, the flow-limiting element does not significantly impede blood flow, and in the expanding state, the flow-limiting element partially or completely blocks blood flow through the SVC.

[0143] Specifically, reference Figure 8A and 8B The catheter 70 includes a balloon 71 attached to the distal end 72. The balloon 71 is shown as having a spherical shape.

[0144] Now for reference Figure 9A and 9B The catheter 80 includes a flow-limiting element 81 comprising a spring-loaded plug 82 formed of a biocompatible material (e.g., beryllium) and having a tapered conical shape. The spring-loaded plug 82 is retracted in a convergent, contracted state within a sheath 83 located at the distal end 84 of the catheter 80. More specifically, the apex of the conical plug 82 is positioned adjacent to the proximal end 85 of the sheath 83. During catheter delivery, the spring-loaded plug 82 is retracted within the sheath 83 in its low-profile state to allow blood flow. To expand the spring-loaded plug 82, a force is applied via an actuation line 86 to withdraw the plug 82 from the sheath 83. As in the previous embodiment, when the proximal force is removed from the proximal end of the actuation line 86, the plug 82 is biased back to the sheath 83, such that the flow-limiting element 81 remains in its convergent, contracted state when disconnected from the controller 33.

[0145] refer to Figure 10A and 10B The conduit 90 depicts a further alternative embodiment of the sealing device 91, which takes the form of a spring-loaded plug 92. The spring-loaded plug 92 is similar to... Figure 9A and 9BA spring-loaded plug 82, having a tapered conical shape, is housed within a sheath 93 located at the distal end of a catheter 90. In response to a distal guiding force applied to the proximal end of the catheter 90 by a drive mechanism 36, the spring-loaded plug 92 is pushed out of the distal end of the sheath 94 and expands to block the SVC. When the distal guiding force is removed, the spring-loaded plug 92 retracts to its convergent contraction state within the sheath 94, thereby allowing blood to flow substantially unimpeded through the SVC.

[0146] The applicant has observed in animal testing that the method of constructing and operating the SVC occlusion system according to the invention provides significant advantages over previously known IVC systems for the treatment of heart failure. Preliminary animal trials in a pig model one week after myocardial infarction are described below.

[0147] refer to Figure 11 This study demonstrates changes in LV pressure and LV volume over multiple consecutive heartbeats in a porcine model following complete occlusion of the inferior vena cava (IVC), as described in a previously published Serdano patent application. Specifically, the IVC is completely occluded for approximately 30 seconds, during which time the 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) decrease during each consecutive heartbeat. Upon removal of the IVC occlusion, the LV pressure rapidly rises to pre-occlusion levels (i.e., similar to the first half of the pressure and volume trace). Because Serdano's proposed IVC occlusion therapy reduces systolic pressure, this therapy can lead to a decrease in ejection fraction during systole, with potentially dangerous consequences for patients. Furthermore, IVC occlusion can cause congestion of the renal and hepatic veins, which may cause and exacerbate rather than improve complications commonly associated with congestive heart failure.

[0148] refer to Figure 12 This illustrates the changes in LV pressure and LV volume during multiple consecutive heartbeats in a porcine model following partial occlusion of the superior vena cava (SVC), as described in accordance with the principles of the invention. Specifically, the SVC is partially occluded for approximately 30 seconds, during which time the left ventricular end-diastolic pressure (corresponding to the lower right corner of the hysteresis loop) decreases, while the left ventricular systolic pressure (corresponding to the upper left corner of the hysteresis loop) remains substantially constant during each consecutive heartbeat. Upon removal of the SVC occlusion, the LV pressure rapidly rises to pre-occlusion levels (i.e., similar to the first half of the pressure and volume traces). Advantageously, the method of partial SVC occlusion of the present invention exhibits minimal or no effect on the ejection fraction during cardiac systole, but reduces wall stress in the ventricles during cardiac diastole. Furthermore, as discussed in more detail below, SVC occlusion will be well tolerated by patients, will not promote congestion of the renal or hepatic veins, and will not exacerbate complications commonly associated with congestive heart failure, including liver and kidney failure.

[0149] Figures 13 to 14 This is a graph showing the changes in pressure during superior vena cava (SVC) occlusion and ventricular release, respectively, with varying left and right ventricular volumes, according to the principles of the invention, in pigs treated for heart failure. As shown in the figure, SVC occlusion causes a significant reduction in left ventricular (LV) volume (240 to 220 mL) and a reduction in LV diastolic pressure (25 to 10 mmHg). SVC occlusion is also associated with a reduction in LV systolic pressure (94 to 90 mmHg). SVC occlusion also reduces right ventricular (RV) volume (230 to 210 mL), diastolic pressure (12 to 4 mmHg), and RV systolic pressure (27 to 16 mmHg). Advantageously, SVC occlusion according to the system and method described herein reduces biventricular volume and diastolic (filling) pressure without negatively affecting systemic blood pressure (LV systolic pressure). These findings suggest that SVC closure has potentially important and beneficial effects on biventricular interaction, allowing for increased ventricular compliance by reducing diastolic filling pressure in both ventricles. This improves ventricular filling and leads to increased stroke volume and cardiac output, which are primary goals in the treatment of patients with heart failure.

[0150] Figure 15 The diagrams include figures demonstrating the improvement in cardiac function in test pigs by superior vena cava (SVC) occlusion according to the principles of the invention. Each figure shows the result of partial inferior vena cava (IVC) occlusion (left side of each figure) compared to complete SVC occlusion (right side of each figure). The graphs display measurements of left ventricular (LV) stroke volume, cardiac output, LV systolic rate, LV diastolic blood pressure, LV systolic blood pressure, and end-systolic volume.

[0151] Figure 16 This is a graph showing that SVC closure according to the principles of the present invention does not impair systolic blood pressure in three test pigs. The graph shows the LV end-systolic pressure (mmHg) of complete IVC closure (left side of each study) compared to complete SVC closure (right column of each study) at 1 minute. Compared to IVC closure, the reduction in LV end-systolic pressure using SVC closure is smaller.

[0152] Figure 17 This is a graph showing that SVC occlusion according to the principles of the present invention does not impair LV diastolic filling in three test pigs. The graph shows LV end-diastolic pressure (mmHg) after complete IVC occlusion (left side of each study) versus complete SVC occlusion (right side of each study) for 1 minute. The reduction in LV end-diastolic pressure using SVC occlusion is smaller compared to IVC occlusion.

[0153] Figure 18This is a graph showing the increase in LV stroke volume achieved by SVC closure according to the principles of the present invention in three test pigs. The graph shows the LV stroke volume (mL / stroke) of complete IVC closure (left side of each study) versus complete SVC closure (right side of each study) for 1 minute. LV stroke volume increased with SVC closure compared to IVC closure, which resulted in reduced LV stroke volume.

[0154] Figure 19 This is a graph showing the improvement in LV contraction rate by SVC occlusion according to the principles of the present invention in three test pigs. The graph shows the LV contraction rate (mmHg / s) of complete vena cava occlusion (1 minute) compared to complete SVC occlusion (right side of each study) with complete IVC occlusion (left side of each study). The LV contraction rate is increased by SVC occlusion compared to the reduced LV contraction rate with IVC occlusion.

[0155] Figure 20 It consists of four graphs depicting the total LV volume and LV pressure of IVC closure (top left), the total RV volume and RV pressure of IVC closure (top right), the total LV volume and LV pressure of SVC closure (bottom left), and the total RV volume and RV pressure of SVC closure (bottom right). Figure 20 The diagram illustrates that, compared to IVC closure, SVC closure provides a significant reduction in LV and RV diastolic blood pressure without a significant reduction in LV systolic blood pressure.

[0156] Figure 21 This includes two graphs depicting pulmonary artery and renal vein pressures measured in test pigs for IVC closure (left) and SVC closure (right). Line 100 shows the pulmonary artery pressure measured for IVC closure, while line 102 shows the measured renal vein pressure. Line 104 shows the pulmonary artery pressure measured for SVC closure, while line 106 shows the measured renal vein pressure. The maximum renal vein pressure measured for IVC closure was 22 mmHg, while the maximum renal vein pressure measured for SVC closure was 7 mmHg. Figure 21 This indicates that, compared to IVC closure, SVC closure reduces pulmonary artery pressure without increasing renal vein pressure.

[0157] Figure 22 This is a graph depicting the left subclavian vein pressure and renal vein pressure measured in pigs undergoing SVC occlusion according to the principles of the present invention. Line 108 shows the left subclavian vein pressure measured for SVC occlusion, while line 110 shows the measured renal vein pressure. The variation in left subclavian vein pressure measured during SVC occlusion was 5 to 12 mmHg. Figure 22 This indicates that the pressure in the proximal left subclavian vein increased nominally during SVC occlusion.

[0158] exist Figure 23A-26CThe results of additional animal tests conducted on the pig model at various closure periods are shown. Now refer to... Figures 23A to 23D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the contraction time of a one-minute segment of continuous SVC occlusion in a porcine model were depicted. Specifically, the controller was programmed to cause the current-limiting element to at least partially occlude the SVC for one minute, and then contract, for example, contract for one second. Figures 23A to 23D The study showed that a one-minute SVC occlusion may not be sufficient to cause a steady-state decrease in ventricular volume after the reduction in time.

[0159] Now for reference Figures 24A to 24D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the contraction time of a five-minute segment of continuous SVC occlusion in a porcine model were depicted. Specifically, the controller was programmed to cause the current-limiting element to at least partially occlude the SVC for five minutes, and then contract, for example, to contract for one second. Figures 24A to 24D As shown in the study, due to the five-minute SVC occlusion, the ventricular volume reached a significant steady-state decrease after the time was reduced.

[0160] Now for reference Figures 25A to 25D The clinical pressure changes of left ventricular end-diastolic pressure, left ventricular end-systolic pressure, left ventricular volume, and ventricular work output during the contraction time of a ten-minute segment of continuous SVC occlusion in a porcine model were depicted. Specifically, the controller was programmed to cause the current-limiting element to at least partially occlude the SVC for ten minutes, and then contract, for example, contract for one second. By comparison... Figures 25A to 25D and Figures 24A to 24D In this model, the advantage of 10-minute SVC occlusion over 5-minute SVC occlusion was not significant. Therefore, considering patient safety, 5-minute SVC occlusion was used during the initial clinical study, as shown in the reference below. Figures 26A to 26C The description refers to the Tufts IRB-approved protocol, but the following is about... Figure 28A -B describes the ten-minute occlusion in human subjects in more detail.

[0161] Encouraged by animal testing, the applicant conducted preliminary human tests and observed that the method of constructing and operating the SVC occlusion system according to the present invention provides significant benefits. Figures 26A to 26C Clinical stress changes observed during consecutive five-minute segments of SVC occlusion in three patients enrolled in a Tufts IRB-approved protocol are depicted. Specifically, the three patients underwent five-minute consecutive SVC occlusions, along with acute neurological and cardiac monitoring and a 30-day neurological assessment (Table 1).

[0162] Table 1 If possible Figures 26A to 26C As observed in Table 1, significant changes were observed in pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, and right atrial pressure during the five-minute segment of SVC occlusion, with residual effects after balloon deflation. As a result of this study, all patients experienced hemodynamic benefits due to a decrease in all filling pressures, such as CWP and mean pulmonary artery (PA) pressure. Patients with greater congestion were observed to experience an increase in mean arterial pressure (MAP). The net effect of these hemodynamic changes was a decrease in cardiopulmonary pressure and an increase in systemic pressure perfused with vital organs, including the kidneys.

[0163] Encouraged by the aforementioned preliminary results in pigs and humans, in addition to the two new patients, the applicant conducted further tests on three other patients, who were mentioned above... Figures 26A-26C The test subjects discussed. Five patients, each with heart failure, underwent the SVC closure system described above. Specifically, the five patients experienced five minutes of continuous SVC closure. The baseline parameters of the five patients are shown in Table 2 below. The third patient had the lowest New York Heart Association (NYHA) functional class of 2. The results from the third patient indicate that the application of the SVC closure system is preferably used for patients with heart failure and an NYHA functional class of 3 or higher.

[0164] Table 2 Figures 27A-27E The graph illustrates the changes in systolic blood pressure (SP), diastolic blood pressure (DP), mean arterial pressure (MAP), mean pulmonary artery (MPA) pressure, and pulmonary capillary wedge pressure (PCWP) for each of the five patients measured from baseline during and after occlusion. Figures 27A-27D The figure shows the minute-by-minute changes in systolic (SP), diastolic (DP), mean arterial pressure (MAP), and mean pulmonary artery (MPA) pressure during the five-minute occlusion period. Figure 27E The results show the changes in pulmonary capillary wedge pressure (PCWP) at five minutes after occlusion and after occlusion.

[0165] exist Figure 27A The diagram illustrates the changes in systolic blood pressure. For example... Figure 27A The data shows that patients 1, 2, and 5 generally experienced an increase in SP during the occlusion period, while patients 3 and 4 generally experienced a decrease in systolic blood pressure. Figure 27B The diagram illustrates the changes in diastolic blood pressure. For example... Figure 27B The results showed that diastolic blood pressure generally increased in patients 1, 2, and 5 during SVC occlusion, and generally decreased in patients 3 and 4.

[0166] exist Figure 27C The diagram illustrates the changes in mean arterial pressure. (For example...) Figure 27C The results showed that mean arterial pressure generally increased in patients 1, 2, and 5 during SVC occlusion, and generally decreased in patients 3 and 4. Figure 27D The diagram illustrates the changes in mean pulmonary artery pressure. (For example...) Figure 27D As shown, it should be noted that although there was no data point for a fourth patient at the fourth minute, the mean pulmonary artery pressure decreased for each patient during SVC closure. Figure 27E The graph illustrates the changes in pulmonary capillary wedge pressure (PCWP) at five minutes and after release. Figure 27E The study showed that the pulmonary capillary wedge pressure decreased in all patients five minutes after SVC occlusion, indicating a decrease in filling pressure for each patient during occlusion.

[0167] For example, regarding Figures 26A-26C The observations made in the study discussed Figures 27A-27E The study, illustrated in the diagram, showed that all five patients benefited hemodynamically due to a decrease in filling pressures such as capillary wedge pressure (CWP) and mean pulmonary artery (PA) pressure, and further as described above regarding... Figures 26A-26C In the studies discussed, patients with more congestion generally experienced an increase in mean arterial pressure (MAP). Furthermore, in many cases, at least some patients experienced residual effects after occluder release.

[0168] Now for reference Figures 28A-28B , and the above about Figures 25A-25D Similar to the studies discussed, the applicant also investigated the effects of prolonged SVC occlusion on human subjects. Specifically, the controller was programmed to at least partially occlude the SVC with the SVC flow-limiting element for ten minutes. Prior to the ten-minute occlusion, the SVC was occluded for a five-minute period, followed by a five-minute rest period. Changes in mean pulmonary artery pressure and mean arterial pressure were measured every minute from the baseline before occlusion (i.e., after the five-minute rest period) and after venting. Figure 28A As shown in -B, the effect observed during the five-minute closure persisted throughout the ten-minute closure without any attenuation of the "cardiopulmonary unloading" effect.

[0169] Figure 28A The graph illustrates the changes in mean pulmonary artery pressure. For example... Figure 28AThe study showed that the mean pulmonary artery pressure decreased throughout the closure and even reached its lowest level during the last two minutes of the closure. Figure 28B The graph illustrates the changes in mean arterial pressure during closure. For example... Figure 28B As shown, mean arterial pressure generally decreased during occlusion, although it fluctuated, but rose above baseline measurements in the first minute and then rose again in the fourth and fifth minutes.

[0170] Now for reference Figure 29 The applicant also conducted broader testing involving the use of the system and method of the present invention during successive occlusion periods, resulting in the inhibition or reversal of further myocardial remodeling and degeneration. Specifically, adult male pigs experienced a heart attack by occluding the left anterior descending artery (LAD) for 120 minutes, followed by reopening the blocked artery. A repetitive cycle of SVC occlusion was then performed, occluding the SVC for 5 minutes and then reducing the occlusion device for 30 minutes. This repetitive cycle was repeated for 18 hours. Cardiac output was measured after each cycle of SVC occlusion. Figure 29 The diagram illustrates the results of the repetitive cycle of SVC blocking.

[0171] like Figure 29 The results showed that cardiac output was at its lowest point after LAD infarction but before SVC closure therapy. One hour after treatment, cardiac output had returned to baseline levels. Cardiac output gradually increased from one hour to eighteen hours after treatment, reaching its maximum at eighteen hours. These findings demonstrate for the first time that, following acute cardiac injury, mechanically reducing cardiac pressure and volume (i.e., unloading) by intermittently closure of the SVC and subsequently stopping the closure (i.e., retraction) can modulate the myocardium, allowing for periods of exercise and rest. In this way, repetitive cycles are analogous to interval training of high-intensity exercise (e.g., sprinting), followed by rest. Repetitive cycles can strengthen the heart and improve cardiac output and function. Although the closure-to-rest ratio was 10:1 (5 minutes on, 30 seconds off), it should be understood that other ratios may produce beneficial results. For example, a ratio range of 5–20 minutes of closure to 10–100 seconds of rest may be beneficial. It should also be understood that closure of the SVC for up to one hour (95%) may be beneficial. Therefore, the SVC occlusion system described herein can be optionally or additionally used post-infarction to treat cardiac injury from infarction to enhance recovery through myocardial unloading.

[0172] As mentioned above, the SVC closure system described in this article can be used optionally or additionally to treat pulmonary hypertension because SVC closure can lead to a decrease in pulmonary artery pressure. Although heart failure is a common cause of pulmonary hypertension, pulmonary hypertension can also be caused by primary lung disease. It is important to understand that the SVC closure system can be used to treat pulmonary hypertension regardless of whether the cause is heart failure.

[0173] Now for reference Figure 30 The applicant observed that implantation of the SVC occlusion system in five patients with pulmonary hypertension due to heart failure resulted in a significant reduction in pulmonary artery systolic blood pressure (PASP). Patients underwent five minutes of SVC occlusion to mechanically reduce cardiac pressure and volume (i.e., unload). Figure 30 As shown in the study, SVC closure can significantly reduce PASP to below the level of moderate pulmonary hypertension, defined as a PASP increase of 50 mmHg or higher. Therefore, the SVC closure system described in this paper can be implanted to treat pulmonary hypertension. (As mentioned above...) Figure 26B as well as Figure 27D In addition, the applicant observed that implantation of the SVC occlusion system resulted in a decrease in the mean pulmonary artery pressure per patient.

[0174] The benefits observed in the aforementioned animal and human trials suggest that continuous SVC occlusion can be used to treat any cardiac injury, including but not limited to acute cardiac injuries caused by heart attack, myocarditis, valvular insufficiency, volume overload, or congestive heart failure, as well as many other acute or chronic cardiac injuries. In one instance, the SVC occlusion system described herein can be used urgently, for example, in an emergency setting, to halt or reverse a heart failure system, thereby... Figure 2A The Frank-Starling curve in the diagram shifts towards line 7, representing a healthy patient. In this way, the patient will see an immediate improvement in cardiac performance, with further and sustained improvement in myocardial function throughout the treatment. To prolong the effects of the system, the SVC closure system can be implanted in the patient for long-term use. Because the SVC closure system described in this article can be implanted or worn by the patient continuously and in an ambulatory state, rather than being confined to the bed, the patient can receive the benefits of the system for a much longer period of time compared to acute care.

[0175] Figure 31 These are predictive examples of how SVC closure, based on the principles of the present invention, is expected to alter disease progression. Key benefits include, for example, improved patient hemodynamics, faster recovery, and reduced length of hospital stay (LOS). Over time, SVC closure may significantly slow disease progression.

[0176] Now for reference Figure 32 The diagram illustrates the optional flow-limiting elements. One undesirable effect of SVC occlusion is increased venous blood pressure upstream of the occlusion device. High cephalic venous pressure is well-known to cause various undesirable effects. To reduce the risk of excessive pressure buildup upstream of the flow-limiting element, a release valve can be integrated into the flow-limiting element, such as... Figure 33 As shown, this allows fluid to flow from the SVC to the right atrium. The release valve can be unidirectional, allowing blood to flow only in the direction of the right atrium. The release valve is preferably configured to open when the pressure in the SVC is between 30 and 60 mmHg. However, it should be understood that the release valve can be designed and configured to open at other pressures in the SVC.

[0177] Figure 32 The current-limiting element shown in the diagram can be used with Figures 4A-4B Similar systems illustrated in the diagram are used together. For example... Figure 32 As shown, the flow-limiting element can be a cylindrical flow-limiting element 112. The cylindrical flow-limiting element 112 may include a cylindrical balloon 113, which can be inflated and deflated by delivering fluid from a catheter to the cylindrical balloon 113. The size of the flow-limiting element 112 can be set and configured to fit within the SVC and conform to the contours of the inner wall of the SVC. The flow-limiting element 112 can be delivered to the SVC via a catheter. The cylindrical balloon 113 can be introduced into the SVC in a deflated configuration. Upon reaching the SVC, the cylindrical balloon 113 can inflate to impede or restrict blood flow within the SVC.

[0178] When the cylindrical balloon 113 inflates, it defines an inner lumen 114. When the release valve 115 opens and the cylindrical balloon 113 inflates, blood can flow through it. The inner lumen 114 can extend from one end of the cylindrical balloon 113 to the other. Although the inner lumen 114 can always have a consistent cylindrical shape, it should be understood that both the size and shape of the cylindrical balloon 113 and the inner lumen 114 can vary. Furthermore, the inner lumen 114 does not need to be aligned with the center of the balloon and can even be non-cylindrical.

[0179] Now for reference Figure 33 This shows a cross-sectional view of the cylindrical current-limiting element 112. (See image.) Figure 33As shown, the release valve 115 can be coupled to the inner wall of the cylindrical balloon 113 within the central lumen 114. The release valve 115 may include a single or multiple flow-impeding elements (e.g., multiple flexible leaflets) working in concert to impede blood flow through the central lumen 114. The release valve 115 may be coupled to the center of the cylindrical flow-limiting element 112, or may optionally be positioned closer to or located upstream or downstream of the cylindrical flow-limiting element 112. For example, the release valve 115 may be positioned upstream of the cylindrical flow-limiting element 112 furthest from the patient's right atrium. This configuration can prevent blood pooling or columnar flow within the central lumen 114, which may occur when the release valve 115 is positioned in the central or downstream region of the central lumen 114.

[0180] Figure 33 The release valve 115, illustrated in the closed position, can be designed to open under certain pressures. For example, the release valve 115 can be designed to open under pressures between 30 and 40 mmHg. However, it should be understood that other pressures may also be desirable. Below the pressure at which the release valve 115 is designed to open, the release valve 115 may impede fluid flow through the central lumen 114. Above the pressure at which the release valve 115 is designed to open, the release valve 115 may allow blood to pass through the lumen 114, thereby reducing pressure in the cephalic vein.

[0181] The release valve 115 can be made of any suitable biocompatible material, including but not limited to elastomers, rigid or flexible polymers, metals, and any combination thereof. The function of the release valve 115 may depend solely on the valve's material and design (i.e., elasticity, stiffness, thickness), and / or may be defined by mechanical, electrical, and / or magnetic characteristics. The threshold for fluid flow permitted by the valve can be predetermined through valve design and / or can be mechanically adjustable.

[0182] Now for reference Figure 34A and 34B Two different release valve designs are shown within the cavity 114 of the cylindrical current-limiting element 112. Figure 34AThe binary relief valve 116 shown remains substantially closed until it rapidly transitions to a substantially open position when a given force is applied. The force required to transition the relief valve 116 from the closed to the open position is preferably between 30 and 60 mmHg, but it should be understood that this pressure can be any pressure. To achieve the binary (i.e., on / off) function, the binary relief valve may include a cutout portion designed to open (give-way) in response to a given force. Upon opening and allowing fluid to pass through to release pressure, the elasticity or other mechanical properties of the material may cause the binary relief valve 116 to spring back to the closed position. It should be understood that this binary function can be achieved by using a variety of other designs and / or by incorporating other materials. For example, Figure 38A The release valve 132 in -B can also achieve binary functionality.

[0183] like Figure 34B As shown, the progressive release valve 117 is designed to open gradually with increasing pressure. This function can be achieved, for example, using valve leaflets with a constant thickness or a gradually thinning cross-section as the leaflets move from the inner wall of the cylindrical balloon 113 toward the center of the lumen 114. However, it should be understood that any valve design that gradually allows increased fluid flow in response to increasing pressure can be used as a progressive release valve.

[0184] Now for reference Figure 35 The image shows a top view of the cylindrical flow-limiting element 112. As long as the pressure remains below a certain threshold, the release valve 115, shown here in the closed position, prevents flow through the lumen of the cylindrical balloon 113. Although a release valve design with four flexible leaflets or flaps is depicted, any release valve design that can be coupled within the lumen 114 of the cylindrical balloon 113, including valves with fewer / more leaflets, can be used.

[0185] Now for reference Figure 36A and 36B The image shows a top view of the cylindrical current-limiting element 112. Figure 36A The diagram illustrates the binary release valve 116 in the open position, which is also shown in... Figure 34A middle. Figure 36B The diagram illustrates the progressive release valve 117 in the partially open position, which is also shown in... Figure 34B As discussed above, the dual-release valve 116 is designed to open to a substantially open position when its set pressure is reached. On the other hand, the progressive-release valve 117 is designed to gradually open as the pressure increases above a certain threshold.

[0186] Now for reference Figure 37Aand 37B It may be desirable to place the stent 118 around the cylindrical balloon 113. For example, the stent 118 can be used as both a receiver and transmitter of electrical signals. Such uses include, but are not limited to, using it as an ECG lead, transmitting signals related to autonomic activity, and receiving neuromodulation signals. The stent 118 may be self-expanding and may be made of conductive material. The stent 118 may be integrated into and / or may be removably coupled to the cylindrical current-limiting element 112.

[0187] Now for reference Figure 38A and 38B The diagram illustrates the cylindrical flow-limiting element 130. As shown in these figures, the cylindrical flow-limiting element 130 includes a balloon occluder 131 and a release valve 132, both integrated within a stent 118. The release valve 132 and the balloon occluder 131 are positioned adjacent to each other within the stent 118. Figure 38A A cylindrical flow-limiting element 130 is depicted in its enlarged position, which blocks the flow within the SVC. Figure 38B A blocking device in its reduced position is depicted, which allows flow through the SVC. (As shown) Figure 38B As illustrated, the balloon occluder 131 can be coupled to the release valve 132 and can contract toward the release valve 132 when deflated. The release valve 132 can be hinged to the stent 118 and can open to allow blood flow when a certain pressure is reached within the SVC. The release valve 132 can be constructed using any of the techniques, designs, and materials disclosed above regarding the release valve.

[0188] Now for reference Figure 39A and 39B The diagram illustrates a cylindrical current-limiting element 133. As shown in these figures, the cylindrical current-limiting element 133 includes a cylindrical balloon occluder 134 and a release valve 135, both integrated within a stent 118. The cylindrical balloon occluder 134 can be inflated to conform to the shape of the stent 118. Figure 39B As shown, the cylindrical balloon occluder 134 may have a portion of its outer surface coupled to the outer surface of the stent 118. A release valve 135 may be coupled to the cylindrical balloon occluder 134. The cylindrical balloon occluder 134 may define an inner lumen 136 when inflated, through which blood can pass if the release valve 135 opens.

[0189] Figure 39AA cylindrical flow-limiting element 133 is depicted, wherein a cylindrical balloon occluder 134 is in an inflated configuration. When inflated, the cylindrical balloon occluder 134 restricts flow within the SVC. During the inflatation of the cylindrical balloon occluder 134, a release valve 135 can be opened as needed to release any overpressure within the SVC. Figure 39B The diagram illustrates a cylindrical flow-limiting element 133 in a reduced configuration. When reduced, the cylindrical flow-limiting element 133 allows flow through the SVC. In the reduced configuration, the cylindrical balloon occluder 134 is reduced in size and moves toward a portion of the stent wall coupled to the cylindrical balloon occluder 134. Similarly, when the cylindrical flow-limiting element 133 is in the reduced configuration, the release valve 135 moves toward the stent 118. The reduced size of the cylindrical balloon occluder 134 when reduced allows blood to flow around the reduced balloon occluder 134 through the stent 118.

[0190] Now for reference Figure 40A and 40B The diagram illustrates a cylindrical current-limiting element 137. The cylindrical current-limiting element 137 includes a support 118 and a release valve 138. (The last sentence appears to be incomplete and possibly refers to a different element.) Figure 32-3 Unlike the occlusion devices illustrated in Figure 9, the cylindrical flow-limiting element 137 does not include a balloon. Instead, the release valve 138 can be directly coupled to the stent 118, as shown below. Figure 40B As shown in the diagram. Stent 118 can be an expandable stent and can be anchored to the inner wall of the SVC. Release valve 138 can be taken as described above. Figure 32-3 9. Any form of release valve discussed and having similar characteristics. The cylindrical flow-limiting element 137 can completely eliminate flow in the SVC until a certain threshold pressure is reached in the SVC, at which point the release valve 138 can open to allow flow from the SVC to the right atrium.

[0191] Now for reference Figure 41 The diagram illustrates the process of... Figure 32 The cylindrical flow-limiting element 112 is coupled to the filter 126. The filter 126 may be placed downstream of the cylindrical flow-limiting element 112. When the release valve 115 is closed, blood can accumulate in the central lumen 114 of the cylindrical balloon 113, causing a stagnant blood column and potentially leading to thrombus formation. When the release valve 115 opens, the thrombus may leak into the right atrium, potentially causing serious problems and even death. The filter 126 may be directly supported by the catheter or by structural features of the cylindrical flow-limiting element 112, such as the cylindrical balloon 113, the release valve 115, or the stent 118 (if applicable), and may be used to capture thrombi. For example, the filter 126 may be coupled to the cylindrical balloon 113 at the downstream end of the cylindrical flow-limiting element 112, as... Figure 41As shown in the figure. It should be understood that filter 126 can be integrated into any current-limiting element described herein.

[0192] To determine whether the SVC is completely occluded or to what extent, conventional methods can be used, which involve injecting contrast agent into the patient and observing its movement under a fluorescein microscope. Alternatively, a pressure sensor can be positioned relative to the occlusion balloon as discussed herein, and the pressure waveform can be analyzed to determine whether the SVC is occluded. For example, CardioMEMS... TM The HF System pressure sensor is available from Abbott, St. Paul, Minnesota. The pressure sensor can communicate wirelessly with, for example, an implanted controller. Pressure waveforms can also be analyzed to determine a patient's filling pressure, diastolic status, and / or other cardiac conditions or indications. For example, waveform analysis can detect a prominent 'C-V' wave, which indicates tricuspid regurgitation due to volume overload. In another instance, the waveform may detect an 'A' wave, suggesting complete cardiac conduction block, ventricular tachycardia (VT), or pulmonary hypertension. The system described herein can be used as a diagnostic monitoring tool by analyzing waveforms and can respond accordingly using the SVC closure technique described herein.

[0193] Figure 42A The diagram illustrates a pressure sensor 140 that can generate a pressure waveform. The pressure sensor 140 can be incorporated into catheter 31 and positioned near the occlusion balloon to provide a pressure measurement indicating jugular venous pressure (JVP). A pressure sensor 156 can optionally be incorporated into catheter 31 distal to the occlusion balloon. Figure 42A Users of the illustrated system can monitor waveform readings from pressure sensor 140 and determine when the waveform changes from phase to non-phase. As the occlusion balloon shrinks, the pressure waveform will change phase with the heartbeat, such as... Figure 42B The pressure waveform is illustrated in curve 141. As the occlusion balloon inflates, the pressure waveform flattens. In this way, it is possible to determine whether the SVC is occluded without the need for contrast agent injection and without the patient being in a cardiac catheterization laboratory or under X-ray. Similarly, the pressure waveform can be used to determine when to actuate the flow-limiting element and when to de-actuate it.

[0194] Another alternative method for determining SVC occlusion using X-ray / fluorescence microscopy is to use two pressure sensors on opposite sides of the occlusion device. For example, as discussed above... Figure 4A The system with conduit 31 is illustrated. Conduit 31 includes a flow-limiting element 32, a sensor 42, and a sensor 43. For example... Figure 4AAs shown, sensor 42 is located distal to the flow-limiting element 32, while sensor 43 is located proximal to the flow-limiting element 32. Sensors 42 and 43 can be pressure sensors and, as explained above, can be used to determine the degree of blockage caused by the flow-limiting element 32 by, for example, monitoring the pressure difference across the flow-limiting element 32. The pressure difference value can indicate the amount or degree of blockage. Similarly, the pressure difference can be used to determine when to actuate the flow-limiting element and when to stop its actuation.

[0195] Although Figure 4A This diagram illustrates one sensor arrangement, but it should be understood that other sensor arrangements can be used to obtain relevant information. For example... Figure 43A As shown, an optional sensor arrangement includes catheter 31, which can be introduced into the patient's vascular system via a delivery device such as guide sheath 144. Catheter 31 preferably extends into the SVC, enters the heart through the right atrium, extends into the right ventricle, and enters the pulmonary artery through the pulmonary valve. Sensors 145, 146, and 147 can be positioned along catheter 31 such that sensor 145 is positioned within a flow-limiting element 32 to measure pressure within the flow-limiting element 32 (i.e., balloon pressure), sensor 146 is positioned along catheter 31 distal to the flow-limiting element 32 and within the SVC to measure SVC or right atrial pressure, and sensor 147 is positioned along catheter 31 distal to sensor 146 such that sensor 147 is positioned within the pulmonary artery and measures pulmonary artery pressure. To measure the pressure above or near the flow-limiting element 32, sensor 148 may be placed directly on or otherwise incorporated into the distal end of sheath 144, where the guide sheath 144 enters the SVC. The pressure measured by sensor 148 indicates JVP. Conduit 31 may include multiple cavities serving as expansion cavities, actuation cavities, and / or for electrical communication between the controller and the flow-limiting element 32 and / or sensors 145, 146, and 147. Guide sheath 144 may also include cavities for electrical communication between sensor 148 and the controller.

[0196] refer to Figure 43A and 44The sensor can be used to detect contact between the current-limiting element and the SVC wall. Specifically, sensor 233 can optionally be disposed on the exterior of the current-limiting element (e.g., on the exterior of the inflatable balloon). When the current-limiting element contacts the SVC wall, sensor 233 can generate a signal or a signal change. For example, sensor 233 can be a pressure sensor and / or a conductivity sensor that detects contact with the SVC wall. Alternatively, the sensor can optionally be positioned within the current-limiting element to detect contact with the SVC wall. For example, sensor 145 can be positioned within the current-limiting element. Sensor 145 can be a pressure sensor and can detect pressure changes within the current-limiting element that indicate contact with the SVC wall. In yet another example, electrodes can optionally be located proximal and distal to the current-limiting element, such as... Figure 43A and 44 As shown in the diagram. For example, sensors 148 and 146 can be electrodes for sensing electrical parameters such as conductance, which can be continuously measured when the current-limiting element is actuated. A significant change in the electrical parameters may indicate complete SVC blockage caused by the current-limiting element contacting the SVC wall. It should be understood that any combination of sensors 233, 145, 146, 148 and / or any other sensors described herein can be used.

[0197] Now for reference Figure 43B The SVC occlusion system may optionally include sensors 234 and 235 and / or sensor 236. Sensors 234 and 235 may be disposed on catheter 31, which may be arranged within a delivery device such as a guide sheath 144. Sensor 236 may be disposed on a flow-limiting element 32. Sensor 234 may be disposed proximally to the flow-limiting element, and sensor 235 may be disposed distally to the flow-limiting element. Sensor 236 may be disposed externally to the flow-limiting element such that it contacts the SVC wall when the flow-limiting element is fully occluded. Optionally, sensor 236 may be printed on the flow-limiting element. 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-limiting element is contacting the SVC wall based on changes in electrical parameters detected when the flow-limiting element 32 contacts the SVC wall. Furthermore, sensors 234 and 235 may measure impedance or conductance to determine whether blood is flowing through the SVC. For example, the impedance may increase when the current-limiting element 32 expands and thus blocks the SVC, and the impedance may decrease when the current-limiting element 32 shrinks and thus does not block the SVC. Therefore, the change in impedance may indicate that the SVC is blocked. These two measurements can then be used to determine whether the current-limiting element is completely blocking the SVC.

[0198] Sensor 236 can also be used to determine the diameter of the left ventricle when measuring the pressure-volume loop in the heart. It is understood that an SVC occlusion system may include sensor 236 as well as both sensors 234 and 235, or may include only sensor 236 or sensors 234 and 235.

[0199] Now for reference Figure 43C The SVC blocking system may optionally include sensors 237 and 238, which can be used to determine whether the current-limiting element is blocking the SVC. Similar to... Figure 4A In the embodiment shown, sensor 237 can be positioned proximal to the flow-limiting element 32 of catheter 31, and sensor 238 can be positioned distal to the flow-limiting element 32 of catheter 31. Catheter 31 can be introduced into the patient's vascular system via guide sheath 144. Sensors 237 and 238 can be pressure sensors or light sensors. For example, sensors 237 and 238 can continuously measure the pressure proximal and distal to the flow-limiting element, respectively, and generate first and second signals indicating the pressure. The difference between the pressure signals proximal and distal to the flow-limiting element can indicate the degree of occlusion of the SVC. Alternatively, sensors 237 and 238 can together form a light sensor, with one sensor acting as a light source and the other as a light receiver and / or detector. For example, sensor 237 or 238 can detect light of such frequency that it is permeable to blood but blocked by the flow-limiting element. Therefore, a reduction in detected light may indicate that the SVC is partially or completely blocked.

[0200] Now for reference Figure 43D The SVC occlusion system may optionally include a pressure switch 239. The pressure switch 239 may be located proximal to or distal to the flow-limiting element and may be connected to one or more lumens 240. Optionally, the pressure switch 239 may be located within the flow-limiting element 32. The lumen 240 may be in fluid communication with the pressure switch 239 and may further include an open end located proximal to the flow-limiting element and another open end located distal to the flow-limiting element. The lumen 240 may extend through the flow-limiting element 32 and / or may be positioned along a conduit 31, which may be located within a delivery device such as a guide sheath 144. The pressure switch 239 may generate a signal when a predetermined pressure difference 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 lumen 240 proximal to the flow-limiting element 32 and the open end of the lumen 240 distal to the flow-limiting element 32.

[0201] Now for reference Figure 43EThe SVC occlusion system may optionally include a tensile tester 246. The tensile tester 246 may be a tensile tester, stress gauge, strain gauge, and / or any other measuring instrument or sensor that generates a signal indicating the stress, strain, or stretch of the material. The tensile tester 246 may be located solely on the conduit 31, which may be disposed within the guide sheath 144; or it may extend over a portion of the conduit 31 and a portion of the flow-limiting element 32. The strain gauge 246 may be configured to measure small changes in force, stress, strain, or stretch of the material. When the flow-limiting element expands to completely occlude the SVC, the flow-limiting element and the conduit proximal to the flow-limiting element will be pulled in a proximal direction. Detection of a positive change in force or pressure in the proximal direction may indicate that the SVC is completely occluded.

[0202] Now for reference Figure 43F The SVC occlusion system may optionally include a sensor 247, which may be an accelerometer for detecting changes in motion. The sensor 247 may be located within the flow-limiting element 32 or proximal to the flow-limiting element 32 in the conduit 31, which may be located within the guide sheath 144. When the flow-limiting element expands to completely occlude the SVC, the flow-limiting element and the conduit proximal to the flow-limiting element can remain in a relatively stable position compared to an unexpanded flow-limiting element. Detection of no motion or reduced motion may indicate that the SVC is completely occluded.

[0203] Now for reference Figure 44 This describes yet another alternative implementation including the guide sheath 144. Figure 44 The implementation method illustrated in the diagram and Figure 43A The implementation is similar to that in the previous one, except that the current-limiting element 32 and sensors 145 and 146 are also incorporated into the guide sheath 144. Figure 43A Similar to the device illustrated in the diagram, sensor 148 can be positioned above or near the flow-limiting element 32 and can measure the pressure above or near the flow-limiting element 32, which indicates the JVP. Sensor 145 is positioned within the flow-limiting element 32 to measure the pressure within the flow-limiting element 32 (i.e., balloon pressure). Sensor 146 is positioned near the distal end of the guide sheath 144, distal to the flow-limiting element 32 and positioned within the SVC to measure the SVC or right atrial pressure. Furthermore, with... Figure 43ASimilar to the device illustrated in the diagram, catheter 31 can be introduced via guide sheath 144 and extends through the right atrium into the pulmonary artery. Sensor 147 is preferably positioned distal to catheter 31 such that it is located within the pulmonary artery and measures pulmonary artery pressure. Guide sheath 144 may include multiple cavities that serve as expansion cavities, actuation cavities, and / or for electrical communication between the controller and current-limiting element 32 and / or sensors 145, 146, and 148. Catheter 31 may also include cavities for electrical communication between sensor 147 and the controller.

[0204] exist Figure 44 In this embodiment, the flow-limiting element 32 can selectively expand and contract independently of the presence of the catheter 31. Since the flow-limiting element 32 and sensors 145, 146, and 148 are arranged on the guide sheath 144, treatment involving the expansion and contraction of the flow-limiting element 32 to selectively occlude the SVC can be performed without introducing the catheter 31. Furthermore, sensors 148 and 146 can be used to measure the pressure difference across the flow-limiting element 32, regardless of whether the catheter 31 is deployed.

[0205] Now for reference Figure 45 This describes yet another embodiment of the SVC occlusion system constructed according to the principles of the present invention. The 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 arranged on the catheter 31 such that sensor 129 is positioned close to the azygos vein occlusion balloon 142 to measure pressure distal to the azygos vein occlusion balloon 142, sensor 139 is positioned between the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 to measure pressure between the two balloons, and sensor 149 is positioned distal to the SVC occlusion balloon 143 to measure pressure distal to the SVC occlusion balloon. Furthermore, sensor 145 is positioned within SVC occlusion balloon 143 to measure the pressure within SVC occlusion balloon 143 (i.e., SVC occlusion balloon pressure), and sensor 155 is positioned within azygos vein occlusion balloon 142 to measure the pressure within azygos vein occlusion balloon 142 (i.e., azygos vein occlusion balloon pressure). Additionally, sensors 129 and 139, and 139 and 149, can be used to measure the pressure difference across azygos vein occlusion balloon 142 and SVC occlusion balloon 143, respectively. The pressure difference value can indicate the amount or degree of occlusion.

[0206] The azygos vein 16 drains the posterior portion of the thoracic cavity into the SVC. When the SVC is blocked, the azygos vein can provide an alternative pathway to the right atrium, thus naturally shunting the blocked SVC blood flow back to the right atrium. Specifically, if the SVC is blocked below the origin of the azygos vein, the pressure buildup above the blocked portion of the SVC may cause a certain percentage of venous blood to retrogradely move into the thoracic cavity through the azygos vein. The azygos vein occlusion balloon 142 can be positioned within the SVC adjacent to the azygos vein, such that its expansion restricts or prevents blood flow from the SVC into the azygos vein. The SVC occlusion balloon 143 can be positioned below the azygos vein, distal to the azygos vein occlusion balloon 142, such that its expansion blocks the SVC but allows blood flow into the azygos vein. The catheter 31 may include multiple lumens that serve as expansion lumens and / or actuation lumens between the controller and the azygos vein occlusion balloon 142 and the SVC occlusion balloon 143.

[0207] 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 deflate while the SVC occlusion balloon 143 can inflate; the azygos vein occlusion balloon 142 can inflate while the SVC occlusion balloon 143 deflates; or both balloons can inflate or deflate simultaneously. The azygos vein occlusion balloon 142 and the SVC occlusion balloon 143 can also be fully or partially inflated, depending on how much flow is needed back into the right atrium.

[0208] When the SVC occlusion balloon 143 inflates and the azygos vein occlusion balloon 142 deflates, the SVC opens above the SVC occlusion balloon 143, allowing blood to flow through the azygos vein into the right atrium. If it is desired to further reduce the flow returning to the right atrium (further reduce preload), the azygos vein occlusion balloon 142 can be inflated to occlude the azygos vein and prevent it from acting as a natural shunt.

[0209] The systems and methods of the present invention 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 invention can be used in combination with pumps such as an intra-aortic balloon pump (“IABP”) or a percutaneous or surgical left ventricular assist device (“LVAD”), right ventricular assist device (“RVAD”), or any other cardiovascular (i.e., cardiac, venous, arterial) pump, whether for total cardiac support or for temporary assistance, thereby allowing synchronous or asynchronous (venous and arterial) unloading of cardiac preload and afterload, respectively. For example, SVC occlusion according to the principles of the present invention can be used in combination with an Impella® cardiac pump available from Abiomed®, Danvers, Massachusetts, as described below. Figure 49 Further detailed description. Figure 49 and51 -54 illustrates an SVC occlusion system combined with exemplary RVAD, LVAD, and IABP systems.

[0210] The system of this invention can also be coupled to other devices, such as biventricular pacemakers and neuromodulation devices. For example, biventricular pacemakers are designed to resynchronize cardiac function; if SVC occlusion advantageously alters the interaction between the RV and LV, biventricular pacing may become more effective. Similarly, SVC occlusion therapy can be used in conjunction with neuromodulation devices, giving the system a significant combined effect in stimulating vagal efferent pathways, thereby enhancing the efficacy of the neuromodulation device. A further potential application could be unmasking right ventricular failure after equipping patients with LVADs. By modulating venous return to the right ventricle, it is possible to reduce overload and thus “modulate” the right ventricular myocardium to tolerate the enhanced venous return driven by the LVAD.

[0211] Although the flow-limiting element 32 is described above as being positioned within the SVC and expanding and contracting within the SVC, alternatively, therapeutic occlusion of the SVC as described herein can be achieved by selectively contracting the SVC using a cuff wrapped around the outside of the SVC. Now refer to Figure 46 The diagram illustrates the cuff 150 that wraps around the SVC. (Example) Figure 47A As further depicted in -D, the cuff 150 may include a strap 151, a blocking element 152, and a locking element 153. The blocking element 152 may be incorporated into the strap 151, such that the blocking element 152 is... Figure 47A The outer surface of the strip 151 in the diagram and Figure 47B In the diagram, the inner surface of the band 151 extends outward. The inner side or inner surface of the band 151 is the side facing the SVC, and the outer side or outer surface of the band 151 is the side facing away from the SVC.

[0212] The strap 151 may be generally rectangular in shape. The locking element 153 may be any well-known system for removably attaching one side of the strap 151 to the other side of the strap 151. For example, the strap 151 may have a magnetic locking element for securely fastening the cuff 150 to the SVC. The air line 154 may be connected at one end to the sealing element 152 and at the other end to a controller. The sealing element preferably has elastic properties such that it expands when the air line 154 delivers air or other fluid to the sealing element 152. When expanded, the sealing element 152 may expand outward from the inside of the strap 151.

[0213] Refer again Figure 46The cuff 150, with its strap 151, can be wrapped around the SVC and secured tightly to it using the locking element 153. After the cuff 150 is properly secured to the SVC, the occlusion element 152 can be selectively expanded, thus extending toward the SVC by delivering fluid through the air line 154. Since the strap 151 is substantially inelastic, the expansion of the occlusion element 152 will result in the expansion of the occlusion element 152 and the compression of the SVC, thereby restricting flow through the SVC. Thus, occlusion of the SVC can be achieved when the occlusion element 152 expands and encroaches into the SVC, causing the SVC to converge inward. Therefore, therapeutic occlusion of the SVC described herein can be achieved by selectively deflecting and expanding the occlusion element 152.

[0214] The controller 33 is programmed to cause the current-limiting element 32 to at least partially block the SVC for a first predetermined time interval, and then contract, for example, reduce, a second predetermined time interval, for example, at least one second, less than one minute, or one to thirty seconds. Preferably, the first predetermined time interval is greater than one minute, between two and eight minutes, or between four and six minutes. For example, the first predetermined time interval can be five minutes, plus or minus one minute. Furthermore, the first predetermined time interval is preferably significantly longer than the second predetermined time interval. For example, the first predetermined time interval can be at least 5 times, at least 10 times, at least 20 times, or at least 30 times longer than the second predetermined time interval. In some data described herein, for example, the blocking time interval is 5 minutes, while the contraction time interval is 10 seconds. In some embodiments, the controller 33 is programmed to cause the current-limiting element 32 to completely block the SVC during the first predetermined time interval. The controller 33 can be programmed to cause the current-limiting element 32 to transition from a blocking state lasting for the first predetermined time interval to a contraction state lasting for the second predetermined time interval, continuously cycling multiple times throughout the treatment process. As further described herein, controller 33 may be programmed to cause current-limiting element 32 to automatically (e.g., in response to parameters sensed by one or more sensors) adjust the timing of a first predetermined time interval (e.g., up to a third predetermined time interval) and / or adjust the timing of a second predetermined time interval (e.g., up to a fourth predetermined time interval) and / or in response to user input. As those skilled in the art will understand, the time intervals may be further adjusted throughout the treatment process.

[0215] Now for reference Figure 48The present invention describes an alternative exemplary system 30ʹ. System 30ʹ is similar to system 30 and includes a catheter 31 having a flow-limiting element 32 disposed on a distal portion 34. System 30ʹ differs from system 30 in that the catheter 31 is removably coupled to an external controller system 200 at its proximal end 35. For example, the catheter 31 can be decoupled from the controller 33 and coupled to the external controller system 200 during a hospital visit, allowing clinicians to directly monitor and adjust the operation of the flow-limiting element 32. The catheter 31 may include an optional distal floating balloon 201 disposed on the distal portion 34 distal to the flow-limiting element 32. Figure 48 As shown in the diagram, the distal floating balloon 201 can be positioned within the patient's pulmonary artery.

[0216] The external controller system 200 includes a display 202, such as a graphical user interface, electrically coupled to the enlargement source 203 and the external controller 204. The display 202 communicates with the enlargement source 203 and the external controller 204 to display information about the operating system 30', such as important physiological or system parameters for clinicians to review or adjust; or alarms generated by the external controller 204. Clinicians can review the data displayed on the display 202 to troubleshoot or adjust system parameters via the graphical user interface.

[0217] The expansion source 203 includes a drive mechanism, such as a motor or pump, for actuating the flow-limiting element 32. The expansion source 203 further includes a source of the expansion medium, such as gas or fluid, such that the drive mechanism can, in response to a command from an external controller 204, transfer the expansion medium between the expansion source 203 and the flow-limiting element 32 via the flow-limiting element connector 209. Furthermore, when partially external, the conduit 31 provides a fail-safe design because the flow-limiting element 32 can be expanded to provide a seal when the proximal end of the conduit 31 is coupled to the external controller 204. This quick-disconnect coupling at the proximal end 35 allows the conduit to be rapidly disconnected from the external controller 204 for cleaning and / or emergency situations.

[0218] The external controller 204 includes a processor programmed to control signals to the drive mechanism of the expansion source 203 and a memory for storing instructions thereon. The external controller 204 also includes a power source, such as a battery, which provides the power required to operate the processor, the expansion source 203, and the display 202. Optionally, the external controller 204 may receive power via a wire plugged into a power source, such as a power outlet.

[0219] The catheter 31 may be coupled at its proximal end 35 to a distal floating balloon connector 205 for fluid communication with a source of an expansion medium, such as gas or fluid, allowing the expansion medium to be transferred between the source of the expansion medium and the distal floating balloon 201 in response to a command from an external controller 204, thereby anchoring the distal floating balloon 201 within the patient's pulmonary artery. The catheter 31 may also be coupled at its proximal end 35 to a thermistor connector 206 for communication with a cardiac output (CO) monitor for measuring and monitoring temperature, and to a pulmonary artery pressure connector 207 for communication with a CO monitor for measuring and monitoring pulmonary artery pressure.

[0220] External controller 204 can be coupled to catheter 31 at proximal end 35 via right atrial pressure connector 208 for measuring and monitoring right atrial pressure. External controller 204 can also be coupled to catheter 31 at proximal end 35 via flow-limiting element connector 209 for measuring and monitoring the amount of expansion medium, such as pressure within flow-limiting element 32, transmitted between expansion source 203 and flow-limiting element 32. External controller 204 can also be coupled to jugular vein pressure connector 210 for measuring and monitoring jugular vein pressure from the sheath-side port.

[0221] The processor of the external controller 204 may include the data transmission circuitry described above, which monitors input from, for example, an external sensor located on catheter 31 and provides that signal to the processor. The processor is programmed to receive input from the data transmission circuitry and adjust the interval during which the flow-limiting element 32 remains in an expanded state, or to adjust the degree of occlusion caused by the flow-limiting element 32. Thus, for example, catheter 31 may have one or more optional sensors positioned within the distal portion 34 of the catheter to measure parameters such as heart rate, blood flow rate, blood volume, and pressures including cardiac filling pressure and central venous pressure. The sensor outputs are relayed to the data transmission circuitry of the external controller 204, which may preprocess the input signal before providing it to the processor, for example, by decimated and digitized the sensor outputs. For example, by displaying the reduction in venous pressure during occlusion and patency, the signal provided to the processor allows for the assessment of the effectiveness of the flow-limiting element 32, and clinicians can use this signal to determine how much occlusion is needed to regulate venous return based on the severity of the patient's congestion. As will be understood by those skilled in the art, system 30ʹ may employ any combination of current-limiting elements and sensors as described above.

[0222] Now for reference Figure 49This describes an SVC occlusion system in combination with a transvalvular LVAD. For example, as described above, an SVC occlusion system 30 with a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an 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® in Danvers, Massachusetts. The LVAD system 211 schematically includes an inflow end 212, an outflow end 213, an impeller pump 214, and an anchor 215 disposed on the distal portion of catheter 216. For example, the anchor 215 may be a pigtail anchor. During operation, the inflow end 212 is positioned in the left ventricle, and the outflow end 213 is positioned in the ascending aorta. When impeller pump 214 is actuated, blood in the left ventricle is pumped through inlet 212 and outflowed through outlet 213 into the aorta, mimicking the natural path of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion. For example, impeller pump 214 can deliver forward blood flow from the left ventricle to the aorta at a rate of up to 5.0 L / min. As will be understood by those skilled in the art, any suitable pump can be used.

[0223] Additionally, the LVAD system 211 includes a controller 217 configured to be operatively coupled to catheter 216 to actuate pump 214 to pump blood from the left ventricle to the aorta, thereby unloading the left ventricle and increasing coronary and systemic perfusion. Controller 217 and controller 33 may be identical and / or incorporated into the same housing unit, such that a single controller is operatively coupled to flow-limiting element 32 and pump 214. Simultaneously with controller 217 actuating pump 214 to pump blood from the left ventricle to the aorta, controller 33 may actuate flow-limiting element 32 to at least partially occlude the SVC.

[0224] Figure 50Results obtained in animal models are presented, demonstrating left ventricular (“LV”) total volume – LV pressure in (1) the baseline model; (2) the LVAD model; and (3) the LVAD+SVC closure system model. A comparison of model (3) with models (1) and (2) clearly shows that combining the SVC closure system described herein with a transvalvular LVAD (available from Abiomed®'s Impella CP® cardiac pump from Danvers, Massachusetts) results in reduced cardiac preload (“CP”) and left ventricular wall tension (“LVWT”), demonstrating improved functionality and efficiency in terms of LVAD-induced preload reduction. Furthermore, the transvalvular LVAD can operate at a lower pump rate while providing adequate systemic cardiovascular support, thereby reducing the likelihood of LVAD-related adverse events.

[0225] Now for reference Figure 51 This describes an SVC occlusion system in combination with a transvalvular RVAD. For example, as described above, an SVC occlusion system 30 having a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an RVAD system 218 can be positioned distal to the flow-limiting element 32 of catheter 31, providing comprehensive hemodynamic support. In one example, the RVAD system 218 is an Impella RP® cardiac pump available from Abiomed® in Danvers, Massachusetts. The RVAD system 218 schematically includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222 disposed on the distal portion of catheter 223. For example, the anchor 222 can be a pigtail anchor. During operation, the outflow end 220 is positioned in the pulmonary artery, and the inflow end 219 is positioned distal to the flow-limiting element 32 in the SVC. When impeller pump 221 is actuated, blood in the SVC is pumped through inlet 219 and outflowed via outlet 220 into the pulmonary artery, mimicking the natural path of blood flow and unloading the right ventricle. For example, impeller pump 221 can deliver a positive blood flow of up to 5.0 L / min from the SVC to the pulmonary artery. As will be appreciated by those skilled in the art, any suitable pump can be used.

[0226] Additionally, controller 33 can be configured to be operatively coupled to RVAD system 218 to actuate pump 221 to pump blood from SVC to pulmonary artery, thereby unloading the right ventricle. Thus, controller 33 can simultaneously actuate flow-limiting element 32 to at least partially block SVC and pump 221 to pump blood from SVC to pulmonary artery.

[0227] Now for reference Figure 52This describes an SVC occlusion system in combination with an optional transvalvular RVAD. For example, as described above, an SVC occlusion system 30 with a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an RVAD system 218 can be positioned on the right side of the heart to provide full hemodynamic support. In one example, the RVAD system 218 is an Impella CP® heart pump available from Abiomed® in Danvers, Massachusetts. The RVAD system 218 schematically includes an inflow end 219, an outflow end 220, an impeller pump 221, and an anchor 222 disposed on the distal portion of catheter 223. For example, the anchor 222 may be a pigtail anchor. During operation, the inflow end 219 is positioned in the inferior vena cava (IVC), and the outflow end 220 is positioned in the pulmonary artery. When impeller pump 221 is actuated, blood within the IVC is pumped through inlet 219 and outflowed into the pulmonary artery via outlet 220, mimicking the natural pathway of blood flow and unloading the right ventricle. For example, impeller pump 221 can deliver a positive blood flow of up to 5.0 L / min from the IVC to the pulmonary artery. As will be understood by those skilled in the art, any suitable pump can be used.

[0228] Furthermore, the RVAD system 218 includes a controller 224 configured to be operatively coupled to catheter 223 to actuate pump 221 to pump blood from the IVC to the pulmonary artery, thereby unloading the right ventricle. Controller 224 and controller 33 may be identical and / or incorporated into the same housing unit, such that a single controller is operatively coupled to flow-limiting element 32 and pump 221. Simultaneously with controller 224 actuating pump 221 to pump blood from the IVC to the pulmonary artery, controller 33 may actuate flow-limiting element 32 to at least partially block the SVC.

[0229] Now for reference Figure 53 and 54 The SVC occlusion system can be combined with a ventricular assist device (VAD). For example... Figure 53 As shown, an SVC occlusion system 30 with a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an LVAD system 225 can be positioned transapically on the left side of the heart to provide comprehensive hemodynamic support. Optionally, as Figure 54As shown, an SVC occlusion system 30'' with a flow-limiting element 32 placed directly on or otherwise incorporated into the distal end of the guide sheath 144 can be positioned within the SVC to at least partially occlude the SVC, and the LVAD system 225 can be positioned on the left side of the heart. The SVC occlusion system 30'' can be similar to the SVC occlusion system 30, but the guide sheath 144 has a flow-limiting element 32 disposed on the distal portion of the guide sheath 144.

[0230] In one example, the LVAD system 225 may be the HeartWare™ HVAD™ system, available from HeartWare, Inc., Miami Lakes, Florida. The LVAD system 225 schematically includes an inlet 226, an outlet 227, and a pump 228, and may be implanted near the apex of the left ventricle. During operation, the inlet 226 may be positioned in the left ventricle, and the outlet 227 may be positioned in the ascending aorta. When the pump 228 is actuated, blood in the left ventricle can be pumped through the inlet 226 and out through the outlet 227 into the aorta, mimicking the natural pathway of blood flow, unloading the left ventricle, and increasing coronary and systemic perfusion.

[0231] The LVAD system 225 may additionally include a controller 229, which may be configured to be operatively coupled to a pump 228 to actuate the pump 228 to pump blood from the left ventricle to the aorta. Controller 229 and controller 33 may be identical and / or incorporated into the same housing unit, such that a single controller is operatively coupled to the flow-limiting element 32 and the pump 228. Simultaneously with controller 229 actuating pump 228 to pump blood from the left ventricle to the aorta, controller 33 may actuate the flow-limiting element 32 to at least partially occlude the SVC. As will be understood by those skilled in the art, any suitable ventricular assist device (VAD) may be used with the SVC occlusion system described herein.

[0232] The combination of an SVC occlusion system with a VAD (e.g., RVAD or LVAD) can reduce the VAD flow rate required to achieve the same hemodynamic response in a patient. This reduces the required pump speed, thereby reducing the potential complications associated with higher pump speeds required to generate higher flow rates.

[0233] Since right ventricular overload can occur during or after LVAD implantation, SVC closure using the SVC closure systems described herein (e.g., SVC closure systems 30, 30', and 30) can be used to reduce right ventricular volume. For example, intermittent closure of the SVC after LVAD implantation helps to unload the right ventricle as the LVAD reaches its operating velocity and / or output.

[0234] Now for reference Figure 55 This illustrates an exemplary procedure for regulating the heart and reducing right ventricular volume. In step 241, a catheter may be inserted into the SVC. The catheter may include a flow-limiting element, such as a balloon, positioned distally. This step may include positioning catheter 31, or optionally guide sheath 144, into the SVC as described above. In step 242, the flow-limiting element may be actuated to at least partially occlude the SVC. For example, this step may involve actuating flow-limiting element 32 to at least partially occlude the SVC. Actuation may include inflating the balloon and / or intermittently inflating the balloon (e.g., inflating for 5 minutes and deflating the balloon for 30 minutes) as described above.

[0235] In step 243, the LVAD device may be implanted in or near the left ventricle, or otherwise deployed in or near the left ventricle. This may involve, for example, positioning the LVAD system 225 transapically on the left side of the heart. Step 243 may occur after step 242, when the flow-limiting element is actuated. Alternatively, step 242 may occur during or before step 242. In step 244, the healthcare provider or technician controlling the flow-limiting element 32 may wait for a set time period and / or program the controller 33 to wait for a set time period after the flow-limiting element is actuated in step 242. As described above, it may be beneficial to at least partially block the SVC for a period of time (e.g., five minutes). The time amount may be based on measuring one or more parameters associated with the heart (e.g., pressure, volume, load) and determining that one or more measured parameters are within a predetermined threshold range (one or more). When falling within the predetermined threshold range (one or more), the flow-limiting element 32 may be stopped by a clinician and / or automatically stopped by the controller. After waiting for a certain period of time in step 244, the actuation of the flow-limiting device can be terminated in step 245. For example, the flow-limiting element 32 can be a balloon that shrinks after a set period of time. As described above, the flow-limiting element 32 can be actuated intermittently to occlude the SVC. Therefore, steps 242, 244, and 245 can be repeated to reduce the fluid volume in the right ventricle. In this way, the SVC occlusion device can be used to offload an overloaded right ventricle before, during, and / or after LVAD implantation or deployment.

[0236] Now for reference Figure 56This describes a SVC occlusion system in combination with an intra-aortic balloon pump (IABP). For example, as described above, an SVC occlusion system 30 with a flow-limiting element 32 at the distal portion 34 of catheter 31 can be positioned within the SVC to at least partially and intermittently occlude the SVC, and an IABP 230 can be positioned in the descending aorta. The IABP may include a flow-limiting element 231 and a catheter 232 coupled to the flow-limiting element 231. The flow-limiting element 231 schematically includes a balloon capable of switching between a constricted state and an expanded state that allows transluminal placement. The size and shape of the flow-limiting element 231 are preferably configured such that, in the expanded state, it partially or completely occludes flow in the aorta. The catheter 232 may be coupled proximally to a controller 33. The controller 33 houses a drive mechanism 36 for independently actuating the flow-limiting element 32 and the flow-limiting element 231. Figure 54 As shown, current-limiting element 231 and current-limiting element 32 can be coupled to the same controller, such that a single controller can be operatively coupled to current-limiting element 32, current-limiting element 231, and pump 221. However, it should be understood that current-limiting element 32 and current-limiting element 231 can be coupled to different controllers and / or different pumps. During operation, current-limiting element 231 will be positioned within the descending aorta and will intermittently expand and contract. Expansion can be timed to coincide with cardiac diastole, and contraction can be timed to coincide with cardiac contraction. When current-limiting element 231 contracts, a suction effect is created in the aorta, which facilitates blood transfer from the left ventricle to the aorta during cardiac contraction.

[0237] Now for reference Figure 57A -C, illustrating a normal heart, a compensated heart, and a decompensated heart, with each diagram showing the cross-section of the mitral valve. For example... Figure 57A As shown, a normal heart does not experience mitral regurgitation (MR). In fact, a normal heart includes normal preload, normal left atrial (LA) volume, normal left ventricular (LV) volume and contractile rate, normal wall stress, normal total cardiac output (TSV), and normal forward cardiac output. Figure 57B As shown, chronically compensated hearts experience increased preload, increased LA volume and pressure, increased LV volume, increased systolic rate, eccentric hypertrophy, and increased TSV, but with normal wall stress and FSV. As indicated by arrow 250, this type of chronically compensated heart experiences mitral regurgitation. Now refer to... Figure 57C The diagram illustrates decompensated heart disease. Figure 57CAs shown, decompensated hearts experience increased preload, significantly increased LV volume, decreased systolic rate, significantly increased wall stress, lower TSV, and lower FSV. As indicated by arrow 251, such decompensated hearts experience mitral regurgitation. As those skilled in the art will understand, other heart valves, such as the tricuspid valve, may experience similar abnormalities that can lead to regurgitation (e.g., tricuspid regurgitation).

[0238] The SVC occlusion system described herein (i.e., SVC occlusion system 30, SVC occlusion system 30', and SVC occlusion system 30'') can be used to treat regurgitation in an overloaded heart. For example, as described above, introducing the SVC occlusion system into the SVC and intermittently actuating the flow-limiting element 32 (e.g., occlusion interval of 5 minutes and systolic interval of 10 seconds) reduces cardiac overload. As the heart volume decreases, engagement can be achieved through the valve leaflets, which previously could not seal due to overload. Therefore, using the SVC occlusion system in the manner described herein can reduce fluid overload in the heart and ultimately reduce or eliminate regurgitation in one or more valves such as the mitral, aortic, and / or tricuspid valves.

[0239] It should also be understood that using the SVC closure system 30'' or any other closure system described herein to occlude the SVC can result in increased urine flow, further reducing fluid overload. For example, the use of the SVC closure system 30'' or any other closure system described herein may involve actuating (e.g., enlarging) the flow-limiting element such that the flow-limiting element occludes and even stretches the superior vena cava and / or superior venous canal-right atrial junction, thereby causing vagal nerve stimulation and resulting in increased urine flow. Furthermore, using the techniques described herein and the SVC closure system to reduce fluid overload can increase the number of patients eligible for cardiac surgery. For example, patients with overloaded hearts who are suitable candidates for the procedure due to the degree of leaflet separation rather than valve clips may become suitable candidates for the procedure after using the SVC closure system and reducing cardiac volume.

[0240] Now for reference Figure 58 The diagram illustrates the 30'' SVC plugging system and its connection to... Figure 44The system shown is similar. The SVC occlusion system 30'' may include a guide sheath 144 having a distal portion 255 and a proximal portion 256. The guide sheath 144 may be a flexible tube. The distal portion 255 may include a flow-limiting element 32 disposed on or otherwise incorporated into the guide sheath 144. The distal portion 255 may be configured to be placed within the SVC. The guide sheath 144 may be coupled to a controller 33 at the proximal end 256. The controller 33 may be programmed to intermittently actuate the flow-limiting element 32. The guide sheath 144 may include one or more lumens and may also include a fluid lumen for expanding the flow-limiting element 32.

[0241] Now for reference Figure 59 The image shows the distal portion 255 of the SVC occlusion system 30 located within the SVC. Additionally, a separate delivery catheter 260 is shown, extending through the IVC, through the right atrium, and into the left atrium. The delivery catheter 260 can be introduced, for example, through the femoral vein or any other vein. The delivery catheter 260 may have a distal region 261 designed for delivering valve clips, such as valve clip 262. Valve clip 262 can be removably coupled to the distal region 261 and designed to clamp the valve leaflets together to treat regurgitation. Figure 59 As shown, valve clip 262 can be used to clamp the mitral valve leaflets together. In one example, valve clip 262 can be a Mitral clip available from Abbott Laboratories. TM However, those skilled in the art will understand that the valve clip 262 can be any device that couples one or more valve leaflets close together to each other.

[0242] As explained above, when the heart is overloaded, such as Figure 57B and 57C As shown, increased volume in the heart can lead to leaflet separation, resulting in regurgitation. For the deployment of valve clip 262 to treat regurgitation, the leaflets cannot be too far apart. In cases where leaflet separation is too great to allow for valve clip 262 deployment, an SVC closure system can be used to reduce the heart volume. For example, LVEDV can be monitored during SVC closure. With the heart unloaded, valve clip 262 can be correctly implanted. For example, once LVEDV decreases to a certain point, the likelihood of successful valve clip implantation increases. Therefore, the SVC closure system described herein facilitates valve clip implantation.

[0243] Now for reference Figure 60 This illustrates a method for adjusting the heart and reducing its volume to perform cardiac surgery (e.g., deployment of a mitral valve clip). In step 271, a catheter can be inserted into the SVC. For example, as... Figure 59As shown, the SVC occlusion system 30'' can be inserted into the patient's body, and the distal portion 255 having the flow-limiting element 32 can be positioned within the SVC. In step 272, the flow-limiting element can be actuated to at least partially occlude the SVC. For example, as... Figure 58 As shown in the diagram and described in detail above, the controller 33 can actuate the current limiting element 32, thereby causing the current limiting element 32 to expand to at least partially block the SVC.

[0244] In step 273, the healthcare provider or technician may generate data related to the patient's heart. For example, the healthcare provider or technician may use medical imaging, such as fluoroscopy or any other well-known type of medical imaging, to generate image data. Other well-known methods may be used to generate heart-related data, such as ultrasound or electrocardiogram (ECG). Based on the generated data, the healthcare provider or technician may determine information about the patient's heart or a portion thereof (such as the right ventricle 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). Optionally, the healthcare provider or technician may consider separation between the leaflets of a valve (such as the mitral valve).

[0245] In step 274, the healthcare provider or technician may confirm that the generated data or data corresponding to the generated data meets a predetermined threshold or is otherwise within an acceptable range. For example, using the generated data, the healthcare provider or technician may calculate or infer the size or volume of the right ventricle and confirm that the size or volume meets a predetermined threshold or is otherwise within an acceptable range. After performing step 274, in step 275, the healthcare provider or technician may perform cardiac surgery. For example, as Figure 59 As shown in the document, healthcare providers or technicians can deploy valve clip 262.

[0246] Figure 60 The methods described herein can be used in conjunction with a variety of other cardiac surgeries, including but not limited to the deployment and / or implantation of valves or cardiac prostheses, the deployment and / or implantation of cardiac pumps (e.g., LVADs), cardiac or valvular surgery (e.g., quadrilateral resection), and / or coronary revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Figure 60 Step 275 of performing cardiac surgery may optionally involve deploying annulusoplasty ring 282, such as Figure 61 As shown in [the image / document]. Now refer to [the image / document]. Figure 61For example, the distal portion 255 of the SVC occlusion system 30'' may be located within the SVC, and the delivery catheter 280 may extend through the IVC, through the right atrium, and into the left atrium. The delivery catheter 280 may be introduced into the femoral vein or any other vein. The delivery catheter 280 may have a distal region 281 for delivering the annuloplasty ring 282. In one example, the annuloplasty ring 282 may be a Carpentier-Edwards Physio II ring available from Edwards Lifesciences. However, those skilled in the art will understand that the annuloplasty ring 282 may be any ring or band used to restore the valve annulus to its proper size.

[0247] exist Figure 60 Step 275, performing cardiac surgery, may optionally include deploying a valve prosthesis 292, such as... Figure 62 As shown in [the image / document]. Now refer to [the image / document]. Figure 62 For example, the distal portion 255 of the SVC occlusion system 30'' can be located within the SVC, and the delivery catheter 290 can extend through the IVC, through the right atrium, and into the left atrium. The delivery catheter 290 can be introduced into the femoral vein or any other vein. The delivery catheter 290 may have a distal region 291 for delivering the valve prosthesis 292. For example, the valve prosthesis 292 can be any valve prosthesis, such as a transcatheter prosthetic heart valve or stent.

[0248] Although Figure 59 , 61 Both 62 and 63 show that the delivery catheter used to perform cardiac surgery extends through the IVC, but the delivery catheter may optionally extend through the SVC. See now for reference. Figure 63 The distal portion 255 of the SVC occlusion system 30'' is illustrated as having a distal portion 255 disposed within the SVC. The delivery catheter 300 is illustrated as extending through the guide sheath 144 and extending beyond the distal portion 255. Similar to the delivery catheter 260, the delivery catheter 300 can deliver a valve clip 301, which is removably coupled to the distal region 302 and in accordance with the aforementioned... Figure 59 The valve clip 262 is deployed in the same manner. It should also be understood that, regarding... Figure 61 The description of annulusoplasty ring 282, regarding Figure 62 The described valve prosthesis 292 (including, but not limited to, a biological prosthesis heart valve) or any other prosthesis, biological prosthesis or surgical device may be delivered to the heart via a delivery catheter that extends through the guide sheath 144.

[0249] It should be understood that the foregoing description is intended to illustrate but not limit the scope of the invention, which is defined by the appended claims. Other embodiments are within the scope of the appended claims.

Claims

1. A method for modulating a patient's heart to perform cardiac surgery, the method comprising: A catheter including a flow-limiting element is inserted into the patient's superior vena cava (SVC), such that the flow-limiting element is disposed within the SVC; Actuate the current-limiting element within the SVC, thereby at least partially blocking the SVC; Measure parameters related to the patient's heart to generate measurement parameters; Determine whether the measured parameters meet a predetermined threshold; and If the measured parameters are determined to meet the predetermined threshold, the cardiac surgery is performed on the patient's heart.

2. The method of claim 1, wherein determining that the measurement parameter satisfies the predetermined threshold occurs before any part of the cardiac surgery is performed.

3. The method of claim 1, wherein actuation of the current-limiting element within the SVC occurs simultaneously with at least a portion of the cardiac surgery.

4. The method of claim 1, wherein actuation of the current-limiting element within the SVC occurs prior to performing the cardiac surgery at the patient's heart.

5. The method of claim 1, wherein performing the cardiac surgery includes implanting a clip at the heart valve.

6. The method of claim 1, wherein performing the cardiac surgery includes implanting an annuloplasty ring.

7. The method of claim 1, wherein performing the cardiac surgery includes implanting a valve prosthesis.

8. The method of claim 1, wherein performing the cardiac surgery includes implanting a left ventricular assist device (LVAD).

9. 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 being adapted to perform the cardiac procedure.

10. 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 being adapted to perform the cardiac procedure.

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