CROSS-REFERENCE TO RELATED APPLICATION(S) This application claims the benefit of priority of U.S. Provisional Patent Application Serial No. 62/492,046, filed April 28, 2017. The entire content of this application is hereby incorporated by reference herein.

BACKGROUND OF THE INVENTION

Patients with functional single ventricle physiology (SV) are commonly palliated to a surgically altered circulation where the heart serves as a pump to a patient's systemic arterial vasculature, which is termed "Fontan circulation" and/or total cavopulmonary connection (TCPC). For simplicity sake, Fontan circuit represents surgically altered anatomy in patients with functional single ventricle heart disease where systemic venous return drains to the pulmonary vascular bed of the patient with bypass of the subpulmonary ventricle. Unfortunately, patients with a Fontan circuit often endure a range of complications relating to deranged physiologic factors including increased venous pressure and congestion and decreased cardiac output. These complications can lead to a reduced life expectancy and numerous clinical sequalae including decreased exercise tolerance and limited activity for the patient.

Figure 1 illustrates a simplified presentation of a normal cardiovascular anatomy. As is illustrated, the subpulmonary (typically morphologic right ventricle) and systemic (typically morphologic left) ventricles work together as the pump to a patient's arterial system. The subpulmonary ventricle pumps deoxygenated blood to the lungs and the systemic ventricle pumps oxygenated blood to the body.

Figure 2 is a simplified presentation of a cardiovascular anatomy of a patient where the systemic venous return bypasses the subpulmonary ventricle and drains directly into the pulmonary vasculature, which is the basis of the Fontan circulation. As is illustrated, a single ventricle pumps oxygenated blood and the deoxygenated blood is returned to the lungs via the superior vena cava (SVC), inferior vena cava (IVC) and pulmonary artery (PA). Stated another way, Fontan circulation bypasses the subpulmonary ventricle such that systemic venous blood returns directly and passively to the pulmonary circuit. At present, SV patients commonly undergo a series of procedures that ultimately result in completion of the Fontan circuit. Early in life, a patient may receive a systemic-to-pulmonary arterial shunt, pulmonary artery band, or no intervention to regulate pulmonary blood flow. Later, usually around 4-6 months of age, patients received a superior cavopulmonary

anastomosis (also known as the bidirectional Glenn procedure (BDG)), which involves interrupting the cavo-atrial connection between the superior vena cava (SVC) and atrium and creating an anastomosis between an/the SVC(s) and pulmonary artery (PA). The surgeon will usually eliminate other sources of pulmonary blood flow (to the extent possible) including takedown of the initial procedure, if performed. After the superior cavopulmonary anastomosis procedure, the venous return from the upper body flows directly into the pulmonary vasculature via the cavopulmonary connection, without the aid of a subpulmonary ventricle. The goal of this procedure is to volume unload the heart, but the patient remains cyanotic because deoxygenated blood from the inferior vena cava (IVC) returns directly to the heart and mixes with oxygenated blood returning from the pulmonary veins. Usually, another surgical intervention is needed to redirect the venous return from the IVC to the pulmonary vascular bed, completing the Fontan circuit to improve systemic oxygen saturations.

In addition to the required surgeries, a patient with a Fontan circuit has various disadvantages including increased systemic venous pressure, venous congestion and/or decreased cardiac output (CO). Further, many patients experience complications including exercise intolerance, arrhythmias, hepatic dysfunction/injury, protein-losing enteropathy, venous thrombi, ascites, peripheral edema, plastic bronchitis, and/or early and late mortality. Nearly all of these complications are related to venous hypertension, venous congestion, and low CO, which are unavoidable with the Fontan circuit. In many instances, the patient develops the above complications over time and they continue to worsen, resulting in a "failing Fontan" physiology, which has a high incidence of mortality. Further, there is a shortened life-expectancy for SV patients with a Fontan circuit.

SUMMARY OF THE INVENTION

One aspect of the invention provides a biological pump including: a reservoir comprising a biomaterial, an inlet and an outlet; a first valve coupled to said inlet; and a force generator coupled to said reservoir and configured to compress said reservoir. This aspect of the invention can have a variety embodiments. The biomaterial can include biological materials. The biological materials can be rendered minimally thrombogenic.

The biological pump can further include a second valve coupled to the outlet.

The reservoir can be configured to be passively filled at venous pressure. The reservoir can be configured to be passively filled at a pressure range from about 2 mmHg to

about 10 mmHg.

The reservoir can have a volumetric capacity within a range of about 10 mL to about 270 mL.

The force generator can be one of a mechanical device or an engineered muscle. The mechanical device can be a balloon compression device. The engineered muscle can include one or more selected from the group consisting of: myocardial muscle tissue, skeletal muscle tissue, striated muscle tissue and smooth muscle tissue.

The reservoir can further include a cell-based lining. The reservoir can further include an endothelialized lining.

The force generator can compress the reservoir based on a heart rhythm of a patient.

The biological pump can further include a signaling device communicatively coupled to said force generator. The signaling device can be configured to instruct said force generator to compress said reservoir. The signaling device can include a pacemaker or other device programmed to generate an output signal determined from one or more input signals selected from the group consisting of: electrical signals of a heart and electrical signals from an accelerometer.

The biological pump can be configured to provide flow to the pulmonary vascular bed of a patient. The biological pump can be configured to provide pulsatile flow to the pulmonary vascular bed of a patient. The biological pump can be configured to decrease central venous pressure in a patient.

The biomaterial can include a biocompatible synthetic material or biocompatible processed naturally-derived material.

Another aspect of the invention provides a method of assisting a patient with a Fontan circuit. The method includes implanting a biological pump as described herein into a chest cavity of a patient. Another aspect of the invention provides a method of assisting a patient with a Fontan circuit. The method includes implanting the biological pump as described herein within a Fontan circuit of said patient.

This aspect of the invention can have a variety of embodiments. Implanting the biological pump as described herein within said Fontan circuit of said patient can include:

coupling said inlet to at least one of an inferior vena cava (IVC), superior vena cava (SVC) and a graft of said patient; and coupling said outlet to said pulmonary arterial vasculature.

Another aspect of the invention provides a method of fabricating a biological pump or circulatory assist device. The method includes: forming a reservoir including an inlet and an outlet; coupling a first valve to the inlet; and coupling a force generator to an outer surface of the reservoir.

BRIEF DESCRIPTION OF THE DRAWINGS

For a fuller understanding of the nature and desired objects of the present invention, reference is made to the following detailed description taken in conjunction with the

accompanying drawing figures wherein like reference characters denote corresponding parts throughout the several views.

FIG. 1 is a prior art illustration of a common cardiovascular anatomy.

FIG. 2 is a prior art illustration of a Fontan circulation.

FIG. 3 is an exemplary biological pump according to an embodiment of the invention. FIG. 4 is an exemplary biological force generator according to an embodiment of the invention.

FIG. 5 is an exemplary biological pump having a signaling device according to an embodiment of the invention.

FIG. 6 is an illustration of a Fontan circulation augmented by a biological pump according to embodiments of the invention.

FIGS. 7A-7C depict various embodiments of the placement of a biological pump according to embodiments of the invention.

FIGS. 8A-8B depict method flow charts according to embodiments of the invention. DEFINITIONS

The instant invention is most clearly understood with reference to the following definitions.

As used herein, the singular form "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

Unless specifically stated or obvious from context, as used herein, the term "about" is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. "About" can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about.

As used in the specification and claims, the terms "comprises," "comprising,"

"containing," "having," and the like can have the meaning ascribed to them in U.S. patent law and can mean "includes," "including," and the like.

Unless specifically stated or obvious from context, the term "or," as used herein, is understood to be inclusive.

Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 (as well as fractions thereof unless the context clearly dictates otherwise).

DETAILED DESCRIPTION OF EMB ODEVIENT S THE INVENTION

Many improvements have been made to improve the efficiency of the Fontan circuit in an attempt to lessen the effects of or eliminate the complications above. However, many of these improvements include additional surgeries and/or may lead to other complications. There are no clinically approved therapies that address the underlying problem of a lack of a subpulmonary ventricle which (in patients with biventricular anatomy) maintains pulsatile, relatively high pulmonary arterial pressures and/or reduces systemic venous pressures and congestion. As such, there is the continued need for innovation to recapitulate the effect of the subpulmonary ventricle for SV patients. Applicants assert that, by assisting the Fontan circuit with a biological pump, they will be able to improve cardiovascular status by providing pulsatile pulmonary blood flow, improving cardiac preload, and/or decreasing central venous pressures. The goals for these improvements for cardiovascular status include, but are not limited to: improved hemodynamic status for patients as a bridge to organ transplant or improved hemodynamic status for patients as a destination therapy. The present disclosure describes a biological pump, as well as other features, to improve the hemodynamics of the Fontan circuit in SV patients, assisting blood flow to the pulmonary vascular bed, and/or lessening systemic vascular pressures and congestion.

A biological pump can be implanted between the systemic venous return and the pulmonary arterial vasculature to assist with blood flow to the lungs of the patient. In various embodiments, the biological pump is a circulatory assist device. Further, in various

embodiments, a biological pump can be configured to augment the hemodynamic status of patients with a Fontan circuit, changing it from a passive flow circuit to a dynamic, pulsatile circuit capable of delivery of deoxygenated blood to the pulmonary vasculature, including under suboptimal downstream conditions.

Figure 3 illustrates an exemplary embodiment of a biological pump 100. In one embodiment, the biological pump 100 is configured to be implemented within the Fontan circuit of a patient. The biological pump 100 can include a reservoir 110 and a force generator 120. The reservoir 110 includes an inlet 112, an outlet 114, and a biomaterial (e.g., biologic, non- biologic and/or non-thrombogenic). The biological pump 100 further includes a first valve 116 coupled to the inlet 112. The force generator 120 is coupled and configured to compress the reservoir 110. Each of these elements are described below in greater detail.

The reservoir 110 can be configured to hold a volume of blood before the blood is propelled to the lungs of a patient for oxygenation. Deoxygenated blood fills reservoir 110 through the inlet 112 and is expelled out of the reservoir 110 through the outlet 114. The first valve 116 is positioned within the inlet 112 and is configured such that as blood is expelled through the outlet 114 with mild, minimal, or no regurgitated blood through the inlet 112. In one embodiment, a second valve 118 is coupled to outlet 114 and is configured to limit regurgitation as blood fills the reservoir 110 through inlet 112. In various embodiments, the second valve 118 is configured to be minimally obstructive to allow expulsion of blood from the reservoir 110 to the outlet 114. In one embodiment, reservoir 110 is configured to be passively filled at normal physiologic systemic venous pressure. For example, reservoir 110 may be configured to be passively filled at a pressure within a range of about 2 mmHg to about 10 mmHg. In other embodiments, reservoir 110 may be filled at pressures above 10 mmHg. In various

embodiments, the pressure at which reservoir 110 is filled is at least partially based on physiologic patient factors such as volume status, hydration, etc.

Without being bound by theory, filling at normal physiologic systemic venous pressure is advantageous over existing devices that aim to assist blood flow in the Fontan circuit and seek to generate increased pulmonary arterial blood pressures or flows, but require relatively high systemic venous pressures to promote device filling after ejection of blood from the device. In another embodiment, the device can create a pressure gradient between the pulmonary arterial vasculature and the systemic veins to maintain pulmonary pressures high enough to drive blood flow through the pulmonary capillary bed and decrease systemic venous pressures to (near) physiologic pressures, which typically range between 2 mmHg and 8 mmHg. In another embodiment, the device decreases systemic venous congestion.

In many embodiments, the reservoir 110 includes a biomaterial. In other embodiments, the reservoir 110 includes an endothelialized lining that is configured to line the surface of the reservoir 110 that is in contact with the patient's blood. In various embodiments, the biomaterial is a polymer, biologically derived tissue (e.g., allogenic or xenogenic tissue), decellularized tissue, or autologous tissue. In one or more embodiments, the biomaterial is an engineered tissue that decreases the likelihood of device thrombosis and/or infection. In one embodiment, the blood-contact surface of the reservoir 110 is recapitulated endothelium. Further, the

reservoir 110 may be an endothelialized engineered tissue.

The reservoir 110 can be generated through tissue engineering techniques. The reservoir 110 can be configured as a living tissue such that when it is implanted within a user, it becomes a non-synthetic augmentation to the patient's cavopulmonary anatomy. In one embodiment, biocompatible scaffolding materials and physiologically relevant cells are used to generate the reservoir 110. In various embodiments, the reservoir 110 has properties such as mechanical compliance and elasticity, structural resilience, a device-blood interface with characteristics of a selectively permeable barrier, and modulation of immune/inflammatory response and clot formation. In one embodiment, the biological pump 100 is implanted into the chest of the patient, where at least including the reservoir 110 is an endothelialized tissue. In such an embodiment, cells are seeded on a scaffolding material, which may undergo in vitro conditioning. Various cell sources (e.g., autologous or non-autologous) may be used for the endothelization of the reservoir 110, which is a component of the biological pump 100. For example, endothelial cells from human umbilical vein, circulating endothelial progenitor cells from venipuncture, isolation of cells from veni-biopsy, mononuclear cells from bone marrow, amniotic fluid stem cells, amniotic membrane stem cells, embryonic stem cells, induced pluripotent stem cells and the like. The cells may be seeded onto scaffolding material and cultured in a bioreactor to produce living endothelium.

Various materials may be used for the biomaterial scaffolding structure of the

reservoir 110. In one embodiment, the reservoir 110 includes a material selected from one of biocompatible synthetic polymers, including polymer composites, (e.g., polyglutamic acid, polylactic acid, and/or poly e-caprolactone) and/or decellularized tissues such as heart, urinary bladder, gallbladder, small intestine and/or other tissue {e.g., porcine small intestinal

submucosa). Reservoir 110 may include one or more materials that have a biological

compatibility and can support cell attachment, cell recruitment, growth, proliferation, differentiation and a variety of other functions. Further, the material forming the reservoir 110 can be mechanically resilient, have a low immunogenicity, and have adequate degradative properties suitable for tissue engineering.

In one embodiment, after the reservoir 110 is implanted within a patient, the reservoir will appreciate patient cell recruitment and will remodel over time. As such, the blood-contact surface of the reservoir 110 will be indistinguishable from the host vascular endothelium to maintain vascular homeostasis within the reservoir.

In some embodiments, the reservoir 110 has a volumetric capacity corresponding to the physiological features of the patient. For example, the reservoir 110 can have a volumetric capacity that corresponds to the approximate volume of the right ventricle of a patient. In various embodiments, the reservoir 110 has a volumetric capacity in the range of about 10 milliliters (mL) to about 270 mL. In various embodiments, the volumetric capacity of the reservoir 110 may be within a range of about 40 milliliters per meter squared (mL/m ² ) to about 150 mL/m ² relative to a patient's body surface area. In one or more embodiments, the volumetric capacity of the reservoir 110 may be less than 10 mL or greater than 270 mL. In various embodiments, the volumetric capacitive of the reservoir 110 increases as a patient ages and/or grows. Further, the volumetric capacity of the reservoir 110 can be sufficient to at least partially reduce excess venous congestion of a patient to an acceptable range.

In one embodiment, the reservoir 1 10 adapts according to changes within the patient. For example, the capacity of the reservoir may increase as the patient grows, thereby meeting the changing needs of blood volume delivery due to larger size of the patient.

As is illustrated in Figure 3, the first valve 116 can be disposed within the inlet 112. In one or more embodiments, the biological pump 100 further includes a second valve 118 that can be disposed within outlet 114. The second valve 118 is optional, and in various embodiments, biological pump 100 includes the first valve 116 and does not include the second valve 118.

Valves 116, 118 can be check valves that allow flow in only one direction. Such a valve can include one or more members such as leaflets, flaps, balls, and the like that move to allow flow and the desired direction, but form a seal to prevent flow in the opposite direction. One example of such a valve is an artificial trileaflet valve such as described in International

Publication No. WO 2015/171743 and U.S. Patent Application Publication No. 2014/0005773. Other exemplary check valves include a duckbill valve, a reed valve, a diaphragm check valve, a flapper valve, and the like. Still other exemplary check-valve architectures are described in Peter Smith & R. W. Zappe, Valve Selection Handbook 153-69 (5th ed. 2004).

The first valve 116 can allow blood to flow into the reservoir 110 under normal systemic venous pressure. When force generator 120 is actuated, the pressure in reservoir 110 increases. First valve 116 prevents backflow and regurgitation so that ejection of blood is focused unidirectionally downstream and out through outlet 114 into the pulmonary vasculature.

In one embodiment, the second valve 118 prevents or limits blood filling the

reservoir 110 from flowing through the outlet 114 during the first period. Further, the second valve 118 allows blood to be expelled from the reservoir 110 via outlet 114 when the reservoir is compressed during the second period.

In one embodiment, the first valve 116 is disposed at any position such that is able to control flow through inlet 112. For example, the first valve 116 can be disposed at a distal end of the inlet 112 such that the inlet 112 is between valve 116 and the reservoir 110. In another example, the first valve 116 is disposed at a proximal end of inlet 112 such the first valve 116 is between the inlet 112 and the reservoir 110. Further, in various embodiments, the second valve 118 may be disposed at any position such that is able to control flow through outlet 114. For example, the second valve may be disposed at a distal end of the outlet 114 such that the outlet 114 is between second the valve 118 and reservoir 110, at a proximal end of the outlet such that the second valve is between the reservoir 110 and the outlet 114, or at any point along outlet 114.

The biological pump 100 of Figure 3 can further include a force generator 120 configured to compress the reservoir 110. The force generator 120 can compress the reservoir 110 to expel the deoxygenated blood within the reservoir 110 into pulmonary vasculature of a patient. After compressing the reservoir 110, the force generator 120 relieves external pressure, allowing the reservoir 110 to fill.

The force generator 120 can include a mechanical device or an engineered muscle. In one embodiment, the force generator 120 comprises a mechanical device which produces a compressive force utilizing an actuator mechanism. For example, the actuator mechanism may be a hydraulic-, pneumatic-, motor-, memory-alloy-, or active-polymer-based systems. Force generators 120 of mechanical origin include balloon compression or soft robotic device that can be secured around the reservoir 110. Exemplary soft robotics devices are described in U.S. Patent Application Publication No. 2016/0346449. An inflatable cuff used to supplement the heart is described in U.S. Patent Application Publication 2011/0270331. Further, the mechanical device may be battery- or non-battery-operated.

In other embodiments, the force generator 120 includes an engineered muscle such as myocardial muscle tissue, skeletal muscle tissue, other striated muscle tissue, and smooth muscle tissue. In various embodiments, the force generator 120 includes genetically engineered muscle having characteristics of at least one of cardiomyocytes and/or skeletal myocytes. A force generator including myocardial tissue can be developed using tissue engineering techniques and autologenic, allogenic or xenogenic donation of cells or a variety of undifferentiated cells.

Undifferentiated cells may include stem or progenitor cells. Suitable cells include cardiac progenitor cells, reprogrammed cells, embryonic stem cells (ES) cells, induced pluripotent stem cells (iPS cells) or the like. In one embodiment, the cells are cultured on a biologically compatible scaffold, differentiated to a myocyte phenotype (e.g., smooth, cardiac, striated, or skeletal) and conditioned in vitro to produce a functional living tissue. In one embodiment, the scaffold on which the engineered muscle is built is the contralateral side of the endotheliazed blood contact surface of the biological pump 100.

In one embodiment, a force generator including skeletal or cardiac muscle can be developed using tissue engineering techniques and allogenic donation of cells or a variety of stem cells. Suitable stem cells include myoblasts, reprogrammed cells, ES cells, iPS cell or the like. In one embodiment, the cells are cultured on a biologically compatible scaffold, differentiated to a skeletal or cardiac myocyte phenotype, and conditioned in vitro to produce a functional living muscle-like tissue. Further, in one embodiment, a contralateral side of the endothelialized blood contact surface of the biological pump 100 is used as the scaffold on which the engineered muscle of the force generator 120 is built.

In various embodiments, the force generator 120 is coupled to the reservoir 110 such that force generator 120 is sufficiently able to compress the reservoir 110 and eject blood volume. In one embodiment, the compressive action of the force generator 120 is based on muscle contraction and relaxation. In one embodiment, force generator 120 can wrap around at least a portion of the reservoir, providing force along at least one plane. For example, as is shown in Figure 4, engineered muscle can be disposed along three or more different planes and configured to provide different types of force. A first portion of the engineered muscle 410 provides vertical contractile force. A second portion of engineered muscle 420 provides horizontal contractile force. A third portion of the engineered muscle 430 provides orthogonal contractile force. A portion of the engineered muscle can provide a circumferential force. In other embodiments, the engineered muscle may be disposed in other configurations, such that force may be applied along other planes. The biological pump 440 illustrates engineering muscle "wrapping" around the reservoir 110, such that force may be applied along different planes.

In the embodiment of Figure 5, a biological pump 500 includes a signaling device 530 coupled to the force generator 520 and configured to instruct the force generator 520 when to compress and relax. In one embodiment, the signaling device 530 is or is in communication with a pacemaker or a biological automaticity source. The signaling device 530 may provide a signal to the force generator 520 to initiate compression of the reservoir 510. In one embodiment, the signaling device 530 provides an electrical stimulus causing cellular depolarization within the force generator 520 and instigating activation of the force generator 520. The signaling device 530 may instruct the force generator 520 to compress the reservoir 510 in synchrony with the phases of the patient's heart rhythm. In one embodiment, the signaling device 530 is configured to detect electrical signals from the patient's heart. As such, the signaling device 530 may detect an atrial electrical event and/or ventricular electrical event and initiate the force generator 520. In one embodiment, signaling device 530 initiates the force generator 520 after detecting an atrial electrical event and/or ventricular electrical event and an offset or delay period. For example, the signaling device 530 may be configured to detect an atrial electrical event and initiate the force generator 520 to function after a delay (50-300 milliseconds). Such functionality is similar to the function of AV delay in pacemakers. Further, the signaling device 530 may be configured to detect a ventricular electrical event to either initiate (after an appropriate delay) or inhibit the force generator 520. In one or more

embodiments, the signaling device 530 has a one or more protective mechanisms to prevent over- or under-signaling to the force generator 520. In other embodiments, the signaling device 530 instructs the force generator 520 to compress the reservoir based on an external stimulus and/or timing. This timing may be predetermined and programed within signaling device 530 and, in various embodiments, the timing may be updated. Signaling device 530 can employ various ratios to achieve a desired result. For example, signaling device 530 can actuate force generator 520 in a 1 : 1 ratio relative to the patient's heartbeat. Other suitable ratios include 2: 1 (i.e., one actuation per every two heartbeats), 3 : 1, and the like (both in whole-number and fractional ratios). In another embodiment, the signal may be independent of the patient's heart rate. In another embodiment, the signal may be adjusted based on other patient-specific factors (e.g. changes in rate of signal based on input from an accelerometer detecting changes in patient activity/movement).

Instructions generated by the signaling device 530 can specify one or more parameters. Alternatively, the signaling device 530 can simply emit a sufficient electrical impulse to cause the force generator 520 to actuate as desired. For example, the signaling device can periodically emit electrical current causing the force generator 520 to compress and expel blood from reservoir 510. After the current terminates, the force generator 520 can relax and return to an expanded position as the reservoir 510 fills within the force generator 520.

Signaling device 530 can include or can be communicatively coupled with one or more feedback devices in order to control actuation of the force generator 520. Exemplary feedback devices include pressure sensors (e.g., to measure pressure within the reservoir 510 or elsewhere in the body), strain sensors (e.g., to measure expansion of the reservoir 510), electrodes (e.g., electrocardiogram (ECG) leads to measure electrical signals from the heart), and the like.

Suitable ECG leads are described in U.S. Patent Application Publication 201 1/0270331.

In various embodiments, the biological pump is implanted within the chest cavity of patient with a Fontan circuit to assist return of deoxygenated blood to the pulmonary vascular bed. As is shown in Figure 6, a biological pump 600 can be implanted between the systemic venous return 610 and pulmonary arterial vasculature 620 of a patient. Further, in one embodiment, an inlet of the biological pump 600 (e.g., inlet 1 12) is coupled to at least one of an inferior vena cava (IVC) or other large venous structure or graft returning blood from the lower half of the body and a superior vena cava SVC) or other large venous structure or graft returning blood from the upper half of the body of the patient. In other embodiments, the inlet is coupled both the IVC and the SVC. Further, an output of the biological pump (e.g., outlet 1 14) is coupled to pulmonary arterial vasculature 620 of the patent.

Figures 7A - 7C illustrate various embodiments of how a biological pump 100 may be implemented within a patient. As is illustrated by the embodiment of Figure 7A, a biological pump 700A is coupled between the IVC and pulmonary arterial vasculature or other large vessel supplying blood flow to the pulmonary vascular bed (MP A, RPA and/or LP A) of a patient. In such an embodiment, an inlet of the biological pump 700A is coupled to the IVC and an outlet of biological pump 700A is coupled to the pulmonary arterial vasculature. In the embodiment of Figure 7B, a biological pump 700B is coupled between the SVC and the pulmonary arterial vessels (RPA and LP A) of a patient. In one particular embodiment, an inlet of the biological pump 700B is coupled to the SVC of a patient and an output of the biological pump 700B is coupled to the pulmonary arterial vasculature of the patient. In the embodiment of Figure 7C, a biological pump 700C is coupled between the IVC and SVC and the pulmonary arterial vasculature (RPA and LP A) the patient. Specifically, in one embodiment, an inlet of the biological pump 700C is coupled to the SVC and IVC and an output of the biological pump 700C is coupled to the pulmonary arterial vasculature of a patient. While the above embodiments disclose a single biological pump, in various embodiments, more than one biological pump may be implemented within a patient. Figures 8A and 8B illustrate a method for assisting a patient with TCPC. At step 802, a biological pump is implanted between the systemic venous return and pulmonary arterial vasculature of a patient. For example, the inlet 1 12 of biological pump 100 can be coupled to the systemic venous return and an outlet of the biological pump 100 can be coupled to the pulmonary arterial vasculature of the patient. As is shown by 804 in Figure 8B, implanting the biological pump within a patient may further include coupling an inlet of the biological pump to at least one of an IVC and an SVC of a patient. In one embodiment, an inlet of a biological pump (e.g., inlet 1 12) is coupled to the IVC of a patient. In another embodiment, an inlet of a biological pump (e.g., inlet 1 12) is coupled to an SVC of a patient. In yet another embodiment, an inlet a biological pump (e.g., inlet 1 12) is coupled to both the IVC and SVC of a patient. At step 806, an outlet (e.g., outlet 1 14) of the biological pump can be coupled to a pulmonary arterial vasculature of the patient.

In various embodiments, the force generator 120 compresses the reservoir 1 10 during a first phase and relaxes during a second phase, allowing the reservoir 1 10 to be filled and return to its original shape. The first phase may be referred to a systolic or ejection phase and the second phase may be referred to a diastolic or filling phase. The systolic and diastolic phases may be synchronous with the heart rhythm of a patient. In one embodiment, during the systolic phase, the force generator 120 compresses the reservoir 1 10, reducing the inner volume of the reservoir 1 10, increasing the intraluminal pressure so that the intraluminal contents of the reservoir 1 10 are ejected through the outlet 1 14 toward the pulmonary circulation. Further, the first valve 1 16 can close during the systolic phase to limit blood from escaping through the inlet, e.g. inlet 1 12. During the diastolic phase, the force generator 120 relieves the compression of the reservoir 1 10. Further, during the diastolic phase, the first valve 1 16 opens and blood enters into the reservoir 1 10 via the inlet 1 12. In those embodiments including the second valve 1 18, the second valve 1 18 is open during the systolic phase and is closed during the diastolic phase. The diastolic phase is then followed by a systolic phase and the cycle is repeated such that blood may be captured and provided to the pulmonary circulation of the patient.

In one embodiment, blood returning from the systemic capillary beds of the body (capillary beds 630 of Figure 6) fills the reservoir 1 10 during the diastolic phase. During the diastolic phase, a negative pressure can exist within the reservoir 1 10, e.g., due to resiliency of the reservoir 1 10 or force applied by force generator 120, such that the reservoir 1 10 may be filled. In another embodiment, the reservoir 110 is filled by venous pressure causing blood to accumulate within reservoir 110. The systolic phase may begin when the volume of the reservoir 110 satisfies a threshold volume, e.g., as measured by one or more feedback devices. In one embodiment, a flow sensor quantifies volume over time to calculate the volume of the reservoir. For example, a flow sensor may measure flow through the aorta. During the systolic phase, force generated by the force generator 120 overcomes downstream resistance within the outlet 114 and/or the pulmonary vascular bed and any downstream obstruction of the patient, and at least a portion of blood stored within the reservoir 110 is ejected through the outlet 114 into the pulmonary vasculature. In one embodiment, the force generated by the force generator 120 also overcomes any resistance due to the second valve 118 disposed within the outlet 114.

Further, during the systolic phase, the first valve 116 can be closed to prevent blood from being regurgitated through inlet 112. After at least a portion of blood has been ejected from the reservoir 110, the systolic phase ends and the diastolic phase begins and the reservoir 110 is refilled.

EQUIVALENTS

Although preferred embodiments of the invention have been described using specific terms, such description is for illustrative purposes only, and it is to be understood that changes and variations may be made without departing from the spirit or scope of the following claims.