Pressure unloading left ventricular assist device and methods for assisting human heart

Abstract

To provide assistive technology that can provide benefits of a bridge to transplantation and an alternative to heart transplantation and can preserve native left ventricular function and pulsatility to optimize chances for myocardial recovery.SOLUTION: An implantable pump 100 includes a rigid housing 101 with an oblate spheroid shape and having an inner chamber divided by a movable elastomeric membrane into: a gas sub-chamber which is connectable through a drive line to an external pneumatic source; and a blood sub-chamber which is connectable through a graft assembly to an anatomical heart. The housing includes: a blood port opening oriented at an angle and at the upper apex of the housing and connected to the blood sub-chamber; and a gas port opening to the gas sub-chamber that is situated at a lower apex of the housing.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] Related Applications and Priorities This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 62 / 800,208, entitled COUNTER-PULSATILE IMPLANTABLE PUMP, filed February 1, 2019, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Heart failure represents a major public health challenge with high morbidity, mortality, and costs. Heart failure, which is prevalent in 2% of the adult population in developed countries, has been singled out as the only cardiac disease with an escalating prevalence, with current annual healthcare costs in the United States of approximately $31 billion and estimated to reach $70 billion by 2030. Advanced heart failure accounts for the majority of resources spent on managing heart failure, with one-year mortality rates reaching approximately 80%. Patients with advanced heart failure have limited access to donor hearts for heart transplantation, and mechanical support devices are often the treatment of last resort.

[0003] Chronic mechanical circulatory support using left ventricular assist devices (LVADs) has been employed to provide a "bridge" to transplantation for patients with end-stage heart failure or as a permanent "heart transplant alternative" therapy. In rare cases, LVAD support appears to reverse cardiac remodeling to the point that a small number of patients can be weaned from the device after partial recovery of cardiac function, thus avoiding both transplantation and the long-term use of assist technologies. Unfortunately, clinically available LVADs bypass the left ventricle, creating severe ventricular unloading until the failing left ventricle is no longer able to generate sufficient pressure to overcome the arterial pressure generated by the LVAD itself. Additionally, pulsatile blood flow appears to be important for promoting myocardial recovery, whereas currently used continuous-flow LVADs are associated with a one-third reduction in recovery rates compared to older-generation pulsatile LVADs. In summary, clinically available LVADs unload and assist the left ventricle at the cost of severely suppressing native left ventricular function, and this prolonged suppression of function may promote fibrosis and sacrifice the heart's potential for native recovery.

[0004] Given the various problems with clinically available LVAD technologies, there exists a clinical need for assistive technologies that can provide the benefits of bridge-to-transplant and cardiac transplant alternative therapy, while preserving native left ventricular function and pulsatility to optimize the chances of myocardial recovery.

[0005] To address these needs for mechanical unloading-induced cardiac recovery, the present disclosure provides a novel pressure-unloaded LVAD (PULVAD), a novel implantable counterpulsation assist pump designed to unload a failing heart while maintaining both left ventricular contractile activity and pulsatility. Summary of the Invention

[0006] In various embodiments, the present disclosure provides a novel implantable counterpulsation LVAD designed to provide ventricular unloading by enhancing left ventricular performance and preserving pulsatility.

[0007] In a first embodiment, an implantable pump is provided. The implantable pump includes a rigid housing having an oblate spheroid shape and defining an interior chamber divided by a movable elastomeric membrane into an air subchamber connectable to an external air pressure source through a drive line and a blood subchamber connectable to an anatomical heart through a graft assembly. The housing includes a blood port opening to the blood subchamber, the blood port adjacent to the upper apex of the housing. In some embodiments, the blood port is oriented at an angle ranging from about 20 degrees to about 50 degrees relative to the through axis of the oblate spheroid. In some other embodiments, the blood port is oriented at an angle of about 0 degrees or ranging from about 1 degree to about 20 degrees relative to the through axis of the oblate spheroid. The housing also includes a gas port opening to the gas subchamber, the gas port being located at the lower apex of the housing.

[0008] In some implementations according to the first embodiment, one or both of the blood port and the gas port include an opening without a valve.

[0009] In some examples according to the first embodiment, the elastomeric membrane has a shape that generally conforms to the inner chamber and the hemoport and has an expanded volume that is less than the combined volume of the chamber and the hemoport. In some specific examples, the elastomeric membrane comprises a valve section, a cylindrical neck, and a cuff that interfaces with the housing connector.

[0010] In some examples according to the first embodiment, the pump further includes a housing connector and a graft assembly. In some particular examples, the graft assembly includes a graft conduit, a washer, and a graft connector. In some further examples, the graft connector is engagable with the housing connector by any one of threads, a snap fit, or a quick connector.

[0011] In some implementations according to the first embodiment, the blood portal and the graft conduit each have an interior surface, and each such interior surface has essentially the same diameter at the interior surface interface therebetween.

[0012] In some examples according to the first embodiment, the blood port has a blood port axis that intersects with a central axis through the rigid housing at an angle of about 0 to about 50 degrees, and in some examples according to the first embodiment, the gas port has an inner diameter in the range of about 1.5 mm to about 5 mm.

[0013] In a second embodiment, a drive line for a blood pump is provided, the drive line including a pair of conduits closely connected along at least a portion of the length of the drive line and divided at each of first and second ends of the drive line, the drive line further comprising a disk-shaped circumferential flange positioned between the first and second ends and beyond the division between the pair of conduits, the pair of conduits including a gas conduit attachable at a first end to a gas port of the implantable pump and a sensor conduit including a cardiac sensor for monitoring cardiac rhythm passing through the sensor conduit, the cardiac sensor including one or more of a plurality of electrodes and a fiber optic sensor, the cardiac sensor attachable at the first end to a clinical subject, and each of the gas conduit and sensor conduit attachable at its second end to a drive system capable of delivering gas flow through the drive line gas conduit in response to a cardiac driven signal.

[0014] In a third embodiment, a system for assisting blood flow is provided. The system includes:

[0015] (a) An implantable pump comprising a rigid housing having an oblate spheroidal shape and defining an interior chamber divided by a movable elastomeric membrane into an air subchamber connectable to an external air pressure source through a drive line and a blood subchamber connectable to an anatomical heart through a graft assembly, wherein the housing includes a blood port opening to the blood subchamber, the blood port being adjacent to the upper apex of the housing. In some embodiments, the blood port is oriented at an angle ranging from about 20 degrees to about 50 degrees relative to the through axis of the oblate spheroid. In some other embodiments, the blood port is oriented at an angle of about 0 degrees or ranging from about 1 degree to about 20 degrees relative to the through axis of the oblate spheroid. The housing also includes a gas port opening to the gas subchamber, the gas port being located at the lower apex of the housing.

[0016] (b) a housing connector attached to the blood portal and adapted to engage with the graft assembly;

[0017] (c) a graft assembly;

[0018] (d) a drive line comprising a gas conduit attachable at a first end to a gas port of the implantable pump, a sensor conduit, and a cardiac sensor passing therethrough for monitoring cardiac rhythm, wherein the cardiac sensor is attachable at the first end to a clinical subject, and the gas conduit and sensor conduit are each attachable at a respective second end to a drive system capable of delivering a gas flow through the drive line gas conduit in response to a signal driven by the cardiac sensor.

[0019] In some examples according to the third embodiment, the drive line gas conduit and the sensor conduit are continuous at their connection to the drive system and are split into two prior to attachment of the gas conduit to the gas port. In some specific examples, the sensor is selected from one or more of an electrode and a fiber optic sensor. In further examples, the sensor includes multiple electrodes.

[0020] In some implementations according to the third embodiment, the gas conduit portion of the drive line includes a disk-shaped circumferential flange.

[0021] In a fourth embodiment, a method for promoting blood flow is provided, the method comprising the steps of:

[0022] (a) Preparing a clinical subject to receive an implantable device, the clinical subject having a thoracic cavity including a heart with a pericardium, an ascending aorta, a pulmonary artery, a superior vena cava, and left and right lungs.

[0023] (b) providing an implantable pump having a rigid housing with an oblate spheroid shape, the housing including a blood port opening to the inner chamber, the blood port adjacent to the upper apex of the oblate spheroid. In some embodiments, the blood port is oriented at an angle between about 20 degrees and about 50 degrees relative to the through axis of the oblate spheroid. In some other embodiments, the blood port is oriented at an angle of about 0 degrees or between about 1 degree and about 20 degrees relative to the through axis of the oblate spheroid. The housing also includes a gas port opening to the inner chamber, the gas port located at the lower apex of the oblate spheroid and oriented perpendicular to the through axis of the oblate spheroid. The pump includes an internal elastomeric membrane that generally fits over the inner chamber and the blood port and has an expansion volume that is less than the combined volume of the chamber and the blood port.

[0024] (b) placing an implantable pump between the heart and the right lung of a clinical subject;

[0025] (c) Partial clamping of the ascending aorta of a clinical subject.

[0026] (d) Providing a graft assembly comprising a flexible graft conduit including a tissue attachment end and a pump attachment end comprising a washer and a graft connector.

[0027] (e) Attaching the tissue-attached end of the flexible graft conduit to the partially clamped aorta.

[0028] (f) providing a drive line having a gas conduit attachable at a first end to a gas port of the implantable pump, the drive line further including a sensor conduit and a cardiac sensor passing therethrough, the cardiac sensor comprising one or more of a plurality of electrodes and an optical fiber sensor, the cardiac sensor attachable at the first end to a clinical subject, the second end of the gas conduit and the second end of the sensor conduit attachable to a drive system for delivering a gas flow through the drive line gas conduit in response to a signal driven by the cardiac sensor, the drive line including a circumferential disk-shaped flange.

[0029] (g) passing the drive line through the incision in the clinical subject with the flange abutting the incision.

[0030] (g) Attaching the gas conduit to the gas port of the pump.

[0031] (h) placing each of one or more of the plurality of electrodes and fiber optic sensors on the anatomical structure of clinical interest selected from the portion of the pericardium and within one of the pulmonary artery and artery;

[0032] (i) connecting a second end of the drive line conduit to the drive system;

[0033] (j) Attaching the implantable pump to the graft assembly by engagement between the graft connector and the housing connector on the blood port of the pump.

[0034] (k) Removing the clamp from the clinical subject's aorta to allow blood flow from the heart through the graft into the blood pump and actuating the drive system.

[0035] In some examples according to the fourth embodiment, the method does not require the use of cardiopulmonary bypass.

[0036] In some examples according to the fourth embodiment, the blood ports of the pump are oriented within the anatomy of the clinical target at an angle that allows for anatomical fit and attachment to the ascending aorta while reducing the possibility of kinking of the graft conduit and compression of the superior vena cava.

[0037] In a fifth embodiment, an implantable device for assisting blood flow is provided, the device comprising:

[0038] (i) a rigid housing having an oblate spheroid shape and including a blood portal section and a gas port section, the top and the gas port section defining a chamber within the rigid housing having an oblate spheroid shape;

[0039] (1) the blood portal section comprises a blood portal having a cylindrical shape and defining a through channel between an exterior of the rigid housing and the chamber, the blood portal having a blood portal axis intersecting a central axis passing through the top of the rigid housing and the gas port section;

[0040] (2) a rigid housing, the gas port section having an inner surface including a base, the base having a plurality of grooves and a gas port defining a gas flow conduit between an exterior of the rigid housing and the chamber, the gas port having a gas port axis perpendicular to the rigid housing axis;

[0041] (ii) an elastomeric membrane having a valve section, a cylindrical neck, and a cuff that interfaces with the housing connector, the elastomeric membrane having a shape that generally fits the chamber and the blood portal and has an expanded volume that is less than the combined volume of the chamber and the blood portal, wherein the chamber comprises a dead volume of about 3 cc to about 10 cc when the elastomeric membrane is at its maximum expanded volume;

[0042] (iii) a housing connector attached to the blood portal and adapted to engage the graft assembly;

[0043] (iv) a graft assembly comprising a graft conduit, a washer, and a graft connector engageable with the housing connector.

[0044] Other features and advantages of the present invention will be apparent from the following more detailed description of the preferred embodiment, which illustrates, by way of example, the principles of the invention. [Brief explanation of the drawings]

[0045] The foregoing and other objects and advantages of the present invention will become apparent from the following detailed description when considered in conjunction with the accompanying drawings, in which like reference characters designate like parts throughout the several views. [Figure 1] FIG. 1 is a side view of an implantable pump. [Figure 2] FIG. 1 is a cross-sectional side view of an implantable pump. [Figure 3] FIG. 1 is an exploded perspective view of an implantable pump. [Figure 4] FIG. 1 is a diagram of a section of the housing of an implantable pump. [Figure 5] FIG. 1 is a diagram of a section of the housing of an implantable pump. [Figure 6] FIG. 1 is a diagram of a section of the housing of an implantable pump. [Figure 7]FIG. 1 is a diagram of a section of the housing of an implantable pump. [Figure 8] FIG. 1 is a diagram of a section of the housing of an implantable pump. [Figure 9] FIG. 1 is a diagram of the components of an implantable pump. [Figure 10] FIG. 1 is a diagram of the components of an implantable pump. [Figure 11] FIG. 1 is a view of a second section of the housing of the implantable pump. [Figure 12] FIG. 1 is a view of a second section of the housing of the implantable pump. [Figure 13] FIG. 1 is a view of a second section of the housing of the implantable pump. [Figure 14] FIG. 1 is a view of a second section of the housing of the implantable pump. [Figure 15] FIG. 1 is a view of a second section of the housing of the implantable pump. [Figure 16] FIG. 1 is a schematic diagram of a system including an implantable pump and a drive line. [Figure 17] 1 is a schematic diagram of a heart. [Figure 18] 1 is a schematic diagram of a system including an implantable pump and drive line in the context of human anatomy. [Figure 19] FIG. 2 is a schematic diagram of a drive line. [Figure 20] Results regarding cardiac pressure unloading using the disclosed implantable device are provided. [Figure 21] Results are provided regarding the optimization of cardiac mechanoenergetics using the disclosed implantable device. [Figure 22] Cardiac blood pressure results using the disclosed implantable device are provided. [Figure 23] Results regarding cardiac contractility in failing LV using the disclosed implantable device are provided. [Figure 24]Results are provided regarding coronary blood flow in failing hearts using the disclosed implantable device. DETAILED DESCRIPTION OF THE INVENTION

[0046] Disclosed herein is an implantable pump device for assisting blood flow, more specifically a novel implantable counterpulsation LVAD designed to provide ventricular unloading with enhanced left ventricular performance and preservation of pulsatility for both short-term (e.g., 1 week) or long-term (e.g., 6 months) implantation.

[0047] As further described herein, implantable devices are advantageous in simplifying surgery and reducing harmful trauma to native heart tissue, particularly compared to the implantation of other assist pumps. While clinically available intrathoracic LVAD devices are known to typically require cardiopulmonary bypass, the surgical approach that can be used to implant the disclosed pump eliminates the need for cardiac bypass during implantation. Furthermore, because the device is not attached to or inserted into the heart, the device may be implanted via a sternotomy and partial clamping of the aorta, whereby an anastomosis is used to attach the device's flexible graft to the partially clamped aorta and allow for proper degassing before releasing the aortic clamp. Therefore, use of the disclosed device eliminates the need for heart-lung machines, oxygenators, and the like typically used in open-heart bypass. Furthermore, the device requires only one anatomical connection to the aorta. This allows the device to be simply turned off and, after proper preparation, the cropped ends of the gas port tubing and electrodes buried subcutaneously without the need for reoperation to explant the device. Furthermore, device implantation intentionally avoids the coring or damage to cardiac tissue that is typical of most LVAD implantations. Indeed, most other mainstream LVADs connect to the ventricular apex, which requires surgical incision of the myocardium, and they involve the use of electrodes implanted in the core region of the myocardium. The device is attached to the ascending aorta without damaging the myocardium, and the electrode lead, when used, is attached using a myocardial lead attached to the pericardium. Use of the device allows for the prospect of restoring the heart's native function.

[0048] Additional advantages of the device relate to its design, including how it is designed to fit between the heart and right lung and how the pump's blood ports are angled to allow for anatomic fit and attachment to the aorta while reducing the possibility of kinking of the graft connector or compression of the superior vena cava. The device also does not incorporate any valves. Instead, blood flows in and out of the device along the same path. This approach enhances cleaning of the blood-contacting surfaces of the device, minimizes blood stasis, and reduces the possibility of thrombus formation. The device also has essentially no moving parts other than a polyurethane membrane that elastically deforms in response to fluid movement on the respective gas and blood sides of the membrane. Additionally, the device is unique in the number of electrodes used to sense the cardiac cycle and the regions placed on the pericardium. Currently, five electrodes are placed on the pericardium to provide signals for triggering the device. Multiple locations within the pericardium, as opposed to locations on the epicardium, allow for more reliable signal detection and do not damage the epicardial layer of the heart. The device also incorporates a novel drive line that delivers both electrical signals and pneumatic power to the device. The drive line exits through the abdominal wall and incorporates a flexible flange that helps stabilize the exit site and reduce the chance of tube formation and exit site infection. Additionally, the device is uniquely designed to be driven by most commercial IABP drivers, whereas other LVADs require expensive, proprietary, dedicated drivers. These and other advantages are described herein.

[0049] As shown in the following examples, the disclosed implantable pump offers significant advantages over conventional LVADs, making it particularly attractive as a bridge to myocardial recovery. First, the device provides partial left ventricular pressure unload, promoting a favorable hemodynamic state of significantly reduced afterload and physiologically regulated reduced preload. This favorable hemodynamic state allows for simultaneous improvement of native left ventricular function. In contrast, clinically used LVADs significantly reduce left ventricular preload (driving native left ventricular function toward the lower left of the Frank-Starling curve) while maintaining excess afterload (generated by the LVAD itself). In this way, conventional LVADs unload the left ventricle at the expense of suppressing native left ventricular function, which sacrifices recovery and potentially promotes fibrosis. Second, PULVAD support generates pulsatile blood flow, which is associated with higher rates of recovery compared to currently used continuous-flow LVADs. Third, the disclosed device provides a relatively simple and safe implantation / explantation procedure without requiring either extracorporeal circulation or myocardial disruption, which are disadvantageous characteristics of typical LVAD insertion and removal. Fourth, the wide availability of drive consoles (PULVADs are driven by standard IABP consoles) makes PULVADs a widely accessible therapeutic approach that can be easily implemented in most hospitals. Fifth, the absence of complex electromechanical components and valves should (at least from a theoretical standpoint) result in a reduced risk of thrombus formation and LVAD-related complications.

[0050] 1-19, referenced herein, illustrate various embodiments of the present invention and the manner in which they may be assembled, each with like reference numerals referring to like components in accordance with the reference numeral guidance provided in the drawings and this specification.

[0051] Components and Systems of Implantable Pump 100 Referring now to the drawings, an implantable pump 100 is shown in FIG. 1. The implantable pump 100 includes a rigid housing 101 having an oblate spheroidal shape with a blood port 125 and a gas port 147. The rigid housing 101 defines an inner chamber 160 divided into a gas subchamber 163 and a blood subchamber 162 by a movable elastomeric membrane 200. In use, when connected to a drive source that provides gas flow to the pump based on signals from the heart, the pump operates by displacement of the elastomeric membrane 200 to alternately fill with blood and expel blood back into the clinical subject's body in synchronization with the flow of gas into and out of the gas subchamber 163. According to various embodiments, the inner chamber 160 has a volume ranging from about 15 cc to about 100 cc, or from about 40 cc to about 90 cc, or from about 50 cc to about 80 cc, or from about 60 cc to about 70 cc. The volume of the inner chamber 160 is configured to meet the anatomical requirements of the recipient of the implantable pump 100. As such, it is contemplated that the implantable pump 100 may be provided in a range of sizes with various possible ranges of inner chamber 160 volumes. The volume of the inner chamber 160 is configured to adequately accommodate the stroke volume delivered by the drive unit (i.e., the volume of fluid displaced from the blood subchamber 162 as a result of the inflow of gas into the gas subchamber 163). For example, if a 50 cc stroke volume is delivered by the driver, the inner chamber 160 may be 40% larger (total volume of 70 cc) to minimize the possibility of the elastomeric membrane 200 contacting the inner wall of the blood port portion of the rigid housing 101 upon full inflation of the elastomeric membrane 200. Alternatively, if the stroke volume provided by the driver needs to be reduced to slowly wean the patient from support, the inner chamber 160 can be sized to facilitate adequate blood exchange and minimize the possibility of hemostasis and blood thrombosis. For example, an inner chamber 160 having a total volume of 70 cc operating at a stroke volume of 35 cc will exchange 50% of the blood with each stroke and still allow adequate cleaning of the walls of the blood subchamber 162 to minimize blood stasis.

[0052] The gas subchamber 163 is connectable from the drive line 600 to a gas port 147 that leads to an external air pressure source, e.g., an intra-aortic balloon implantable pump driver (IABP driver). The blood subchamber 162 is connectable to the anatomical heart via the blood port 125, e.g., through a graft assembly 400 including a flexible Dacron® graft. In some examples, one or both of the blood port 125 and the gas port 147 include valveless openings. For example, as shown in the embodiment depicted in the drawings, the blood port 125 and the gas port 147 each have valveless openings. Advantageously, the absence of valves in the illustrated embodiment eliminates the potential failure point presented by valves and reduces the possibility of thrombus formation.

[0053] Referring again to the drawings, according to the illustrated embodiment of implantable pump 100, rigid housing 101 is formed in two sections. Referring now to FIG. 2, rigid housing 101 is formed in two sections, including blood port 125 section 120 and gas port 147 section 140. Each of blood port 125 section 120 and gas port section 140 is shown in FIGS. 4-8 and 11-15, respectively. As shown, blood port 125 section 120 and gas port section 140 each form approximately half of rigid housing 101 and are joined at an engaging mating 121, 141 interface therebetween, the engagement being located approximately at or below the centerline of the oblate spheroid in a plane perpendicular to central axis 102 of rigid housing 101. As shown in FIGS. 5 and 15, each of blood port section 120 and gas port section 140 has a circular cross-sectional shape, and the two sections do not have the same overall shape. Gas port section 140 is configured to allow a larger total volume than blood port section 120, and therefore has a different shape and overall dimensions than gas port section 140. Referring again to Figure 2, the distance from the central plane of the oblate spheroid to the dome of gas port section 140 (i.e., to the lower apex of the oblate spheroid) is greater than the distance to the dome of blood port section 120 (i.e., to the upper apex of the oblate spheroid). Also, the radius of curvature of blood port section 120 is greater than the radius of curvature of gas port section 140.

[0054] Of course, it will be understood that in other embodiments, the rigid housing 101 may be divided in another manner, for example, along the central axis 102, or divided in some other manner. Furthermore, it will be understood that in some embodiments, the rigid housing 101 may be one piece or formed from more than two pieces. As shown, the mating interface between the blood port 125 section 120 and the gas port section 140 includes a snap-fit engagement, with the mating fittings 121, 141 each having a complementary shape including snap-fit teeth 122, 142 and a recess suitable for retaining a bead of sealant, such as an adhesive. Of course, in other embodiments, the mating fittings 121, 141 may be engaged by means other than a snap-fit, and in one example, may include complementary threads or other mating features commonly known in the art for joining two pieces having a generally circular cross-section.

[0055] Referring again to the drawings, according to various embodiments, rigid housing 101 includes a blood port 125 adjacent the top apex of rigid housing 101 and opening to blood subchamber 162, with blood port axis 127 oriented at an angle relative to central axis 102 of rigid housing 101. In various embodiments, the angle is in the range of about 0 degrees (i.e., perpendicular / normal to central axis 102) to about 50 degrees, or about 20 degrees to about 50 degrees, or about 35 degrees to about 45 degrees. In some specific embodiments, as shown in the representative embodiment shown in the drawings, the angle is about 45 degrees. Of course, the angle may be any angle from and including 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, and 50 degrees, including any subrange therebetween and any increment between 1 degree and 5 degrees. Thus, in some embodiments, the blood port is oriented at an angle relative to the through-axis of the oblate spheroid that is in the range of about 20 degrees to about 50 degrees. In some other embodiments, the blood-ports are oriented at an angle that is about 0 degrees or that is in the range of about 1 degree to about 20 degrees relative to the through axis of the oblate spheroid.

[0056] Referring again to the drawings, according to various embodiments, the rigid housing 101 includes a gas port 147 that opens to a gas subchamber 163, which in the illustrated embodiment is the inner chamber 160 outside the sac-shaped elastomeric membrane 200. According to various embodiments, the gas port 147 is located at the lower apex of the rigid housing 101. As shown, the gas port 147 is oriented perpendicular to the central axis 102 of the oblate spheroid. It will be appreciated that in alternative embodiments, the gas port 147 may be angled downward at an angle ranging from about 1 degree to about 60 degrees relative to the central axis 102 of the rigid housing 101. In the illustrated embodiment, the gas port 147 includes a receiver 150 for attaching a hose for connecting the pump to a drive line 600, which in turn is connected to a drive system for delivering gas to the pump. The receiver 150 is in the form of a frusto-conical hose barb 151 that includes a taper at the exit end of the gas port 147, and has a wide base with a diameter greater than the outer diameter of the gas port 147 where it exits the base 145 of the rigid housing 101. Of course, other forms of engagement other than the hose barb 151 may be employed.

[0057] In various embodiments, the gas port 147 defines a gas flow conduit 148 that is generally cylindrical. In some non-limiting examples, for example, according to embodiments of the implantable pump 100 described in the examples of the present disclosure, the gas port 147 can have an inner diameter ranging from about 1 mm to about 5 mm, and in some embodiments, from about 1.5 mm to about 2.0 mm. In some specific examples, the gas port 147 has an inner diameter of less than 2 mm, for example, about 1.8 mm. It will be understood that these dimensions are merely representative of embodiments made and tested in accordance with the present disclosure, and other possible dimensions may be employed. Advantageously, the inventors have discovered benefits that can be obtained when employing gas flow path features that facilitate reducing the inflation air pressure within the inner chamber 160 (i.e., the gas sub-inner chamber 160 / 163) to a pressure just above the natural blood pressure of a clinical subject benefiting from the implantable pump 100 (i.e., a relatively small pressure differential exists between the blood side and the air side of the elastomeric membrane 200). As further described herein, the system including the implantable pump 100 and drive line 600 includes additional features that enable the delivery of gas in an efficient manner to achieve a controlled pressure differential within the pump.

[0058] Referring again to the drawings, according to various embodiments, the implantable pump 100 also includes an elastomeric membrane 200, as shown, for example, in FIG. 3 and in FIGS. 9 and 10. The elastomeric membrane 200 in the illustrated embodiment of the implantable pump 100 defines the blood subchamber 162. In some embodiments, the elastomeric membrane 200 has a shape that generally conforms to the internal chamber 160 and the blood port 125 and has an expanded volume that is less than the combined volume of the internal chamber 160 and the blood port 125. Of course, in other embodiments, the elastomeric membrane 200 may be a sheet attached within the internal chamber 160, for example, secured between the edges of individual sections of the rigid housing 101, or otherwise attached to an internal structure (not shown) on the wall of the rigid housing 101. Referring again to the drawings, as shown in FIGS. 3, 9, and 10, the elastomeric membrane 200 is generally sac-shaped. As shown, the elastomeric membrane 200 includes a valve 210 section, a cylindrical neck 220, and a cuff 230 that interfaces with a connector on the rigid housing 101. As shown, the elastomeric membrane 200 is shaped and adapted to fit within the interior chamber 160 and is attached to the hemo-port 125, for example, by attachment through a connector on the rigid housing 101. As shown in Figures 2 and 3, in some embodiments, the elastomeric membrane 200 includes the cuff 230 and is secured to the rigid housing 101 connector.

[0059] According to the illustrated embodiment, the elastomeric membrane 200 has an expanded volume that is less than 100% of the total volume of the inner chamber 160 and the blood port 125 through the channel 126. In some specific examples, the maximum expanded volume of the blood subchamber 162 defined by the elastomeric membrane 200 allows for a dead volume 161 within the inner chamber 160 of at least about 3 cc to about 20 cc. The dead volume 161 may be slightly larger, for example, up to about 25 cc. The elastomeric membrane 200 is formed from any material suitable for contact with blood, such as medical-grade polyurethane. Other examples of suitable materials may include injection-molded liquid silicone rubber and thermoplastic elastomers. Referring now to FIGS. 4 and 5, the rigid housing 101 includes one or more molded features in the form of grooves 146 within the inner chamber 160 on the inner surface 143, which serve to ensure minimal interstitial space unoccupied by the elastomeric membrane 200 when fully expanded. As shown in the drawings, grooves 146 include a series of circumferential rings joined by radially aligned grooves 146 within base 145 on the inner surface of inner chamber 160, which interconnect to gas flow conduits 148 that are connected to gas ports 147. With this design, grooves 146 are fluidly connected to the gas flow paths such that inflow and outflow gases are not blocked by elastomeric membrane 200 at any time during an inflation or deflation cycle (REVIEW). Advantageously, grooves 146 further ensure that a vacuum is not created and that elastomeric membrane 200 contacts inner surface 143 at base 145 of inner chamber 160. It will be understood that more or fewer grooves may be used and that grooves 146 may have other shapes, configurations, and dimensions suitable to provide dedicated spaces that resist contact with elastomeric membrane 200. It will also be appreciated that structures other than grooves may be used, so long as the structure is in communication with the gas flow conduit 148 to ensure that the elastomeric membrane 200 does not collapse and block the movement of gas out through the gas port 147.

[0060] According to the embodiment shown in the drawings, the elastomeric membrane 200 is configured to be smaller than the shape of the gas port section 140, resulting in an interstitial space or dead volume 161 within the base 145 when the elastomeric membrane 200 is fully contracted. As the membrane expands, the space between the inner wall of the gas port section 140 and the elastomeric membrane 200 allows for radial movement and expansion of the elastomeric membrane 200, minimizing the formation of buckles within the elastomeric membrane 200 as it fully expands. This serves to minimize stress on the elastomeric membrane 200 and the possibility of fatigue failure. According to some embodiments, the elastomeric membrane 200 can be bonded over at least a portion of its outer surface to the inner wall of the blood port section 120 of the rigid housing 101, with this bonding being achieved by a medically appropriate sealant. This bond can serve to further secure the elastomeric membrane 200 within the inner chamber 160, minimizing buckling and concentrating bending of the elastomeric membrane 200 to its underside, which is directly opposite the base 145 of the gas subchamber 163.

[0061] Referring again to the drawings, the implantable pump 100 further includes a rigid housing 101 connector and graft assembly 400, as shown in FIG. 3. As shown, the housing connector 300 is used to secure the elastomeric membrane 200 at its cuff 230 to the hemo-port 125 of the rigid housing 101. The housing connector 300 includes a generally ring shape that is engageable with the cylindrical hemo-port 125 and, in some embodiments, includes fenestrations 302. The housing connector may be epoxied to the hemo-port. The fenestrations 302, located radially around the housing connector, provide a mechanical interlock and increase surface area to facilitate a more secure bond, which facilitates securement of the housing connector 300 to the hemo-port 125. The illustrated embodiment of the housing connector 300 also includes a circumferential groove 303 that receives the cuff 230 of the elastomeric membrane 200 for securement to the end of the hemo-port 125. In some other embodiments, the engagement between elastomeric membrane 200 and housing connector 300 may be achieved by other means. Additionally, in some embodiments in which elastomeric membrane 200 is not in the form of a sac, housing connector 300 may not be in contact with elastomeric membrane 200. Referring again to the drawings, for example, as shown in FIG. 3 , housing connector 300 also includes external threads 301 suitable for mating with corresponding threads 431 in graft connector 430, described below. Of course, it will be understood that the engagement between housing connector 300 and graft connector 430 may be other than threaded, and in some alternative embodiments, the two components may be engageable by other means known in the art, such as using a snap fit or a twist connection.

[0062] Referring again to the drawings, the implantable pump 100 further includes a graft assembly 400. In some specific embodiments, the graft assembly 400 has a tissue attachment end 411, a pump attachment end 412, and includes a graft conduit 410, a washer 420, and a graft connector 430. As shown, the graft connector 430 is a nut having internal threads 431 complementary to the threads 301 on the rigid housing 101 connector. In some embodiments, the graft connector 430 and the housing connector 300 may have alternative configurations, with the housing connector 300 including internal threads and the graft connector 430 including external threads for engagement therebetween. Also, of course, as mentioned herein with respect to the housing connector 300, the two connectors may engage by means other than complementary threads. The illustrated graft assembly 400 also includes a washer 420. 2, a washer 420 is integrated into the pump attachment end 412 of the graft conduit 410 to provide hoop strength that prevents collapse of the graft conduit 410 and facilitates its fixation within the graft connector 430. In some embodiments, the graft material of the graft conduit 410 is first stretched and folded over the washer 420 and secured with thin sutures where the two layers of graft material overlap.

[0063] Referring again to the drawings, the graft assembly 400 further includes a graft conduit 410 that is flexible and has a generally cylindrical shape suitable for surgical attachment to biological tissue, such as the aorta of the heart. The graft conduit 410 is provided suitable for trimming at its tissue attachment end 411 to achieve a length and specific angle selected by the surgeon for attachment to the aorta. The graft conduit 410 may be formed of any material suitable for contact with blood-based biological materials, such as one or more gelatin-sealed woven polyester grafts and flexible Dacron® materials. When engaged with the housing connector 300, the graft assembly 400 provides a continuous blood flow path 500 defined by the lumen of the conduit 410 and the through-channel 126 of the blood port 125. In the illustrated embodiment, the blood port 125 and the graft conduit 410 each have an inner surface, and each such inner surface has essentially the same diameter at the inner surface interface 501 therebetween, whereby the inner surface interface 501 between the engaged blood port 125, housing connector 300, and graft assembly 400 provides zero step down so that the continuous blood flow path 500 has a uniform diameter.

[0064] Referring again to the drawings, various embodiments also provide a novel drive line 600 attachable to the implantable pump 100 to form a blood pump system. The drive line 600 provides an interface between the pump and a drive system configured to provide gas flow to the pump based on cardiac function signals obtained through a sensor implanted in a clinical subject. FIG. 16 shows a representative example of an embodiment of a pump connected to an embodiment of the drive line 600. As shown, the drive line 600 includes a linear integration of a gas conduit 630 and a sensor conduit 640 along at least a portion of its length, with the drive line 600 having a first end including respective first ends of the gas conduit 630 and the sensor for connection to the patient in communication with the implantable pump 100, and a second end for attachment to a driver.

[0065] In some embodiments, the gas conduit 630 portion of the drive line 600 includes a disk-shaped circumferential flange 660 adapted to be positioned beneath the skin or dermis at the drive line exit site of a clinical subject in which the implantable pump 100 is implanted. The circumferential flange 660 is designed to provide a conformable transition of the drive line 600 and reduce exit site trauma and infection, and may be made from any suitable material, including, for example, medical-grade silicone. The drive line 600 may further include an intermediate connection hub, whereby the second ends of the gas conduit 630 and the sensor conduit 640 may be disconnected from the patient-contacting end. The drive line 600 may also include an integrated patient safety circuit to limit any harmful current that may flow to the patient.

[0066] 19, drive line 600 includes a pair of conduits comprising a gas conduit 630 and a sensor conduit 640 closely connected along at least a portion of the length of drive line 600 and divided at drive line division 650 into first and second ends 610 and 620 of drive line 600, respectively, and drive line 600 further includes a circumferential disk-shaped flange 660 positioned between first end 610 and second end 620 prior to drive line division 650 between the pair of conduits. Referring now to FIG. 16, first end 610 of gas conduit 630 is attachable to gas port 147 of implantable pump 100, and first end 710 of sensor conduit 640 is attachable to an anatomical site of a clinical subject. Each of the gas conduits 630 is attachable to a drive system at a second end 620, and the gas and sensor connections at the second ends 620 are in turn connected to external cables and air lines that are connectable to the drive system.

[0067] Referring again to the drawings, the gas conduit 630 includes an internal gas flow channel that may be integrally formed within the conduit or may include tubing within the conduit. The flow channel communicates through connection with the gas port 147 of the implantable pump 100 to deliver gas inflow and outflow and includes attachment features at each of its first and second ends suitable for secure connection to the implantable pump 100 and driver, respectively. In various embodiments, the gas flow channel has an inner diameter ranging from about 1 mm to about 4 mm and includes an attachment feature at its first end. The gas conduit 630 is attachable to the implantable pump 100 at the gas port 147 in a manner that allows for airflow restriction into the pump to control inflation air pressure within the pump to just exceed blood pressure. Thus, the gas conduit 630 is adapted to allow for a step-down in flow channel diameter from the flow channel of the conduit to the gas port 147 of the pump.

[0068] In some alternative embodiments, the gas conduit 630 may be provided in more than one section along the length of the drive line 600, for example, as a "two-piece" embodiment in which the length of the gas conduit 630 includes a separate tube, e.g., a tube having a smaller diameter than the diameter near the second drive attachment end 620 of the gas conduit 630. The use of a coupler, such as a double-barb connector, at the end of the second tube may facilitate replacement of the tube with a new tube having the same or a different inner diameter. Of course, it will be understood that the step-down design is only one option for gas flow control between the driver, drive line 600, and implantable pump 100, and that in other embodiments there may be more or fewer step-down features, and that in some embodiments the flow channel and gas flow conduit 148 may have the same diameter. According to various embodiments, drive line 600 includes a gas conduit 630 that may include one or a series of tubes such that the inner diameter along the length of drive line 600 may be continuous with the inner diameter of gas port 147 (e.g., 1 mm to 5 mm, or 1.8 mm), or in some embodiments, may include a step-up to a larger diameter (e.g., greater than 2 mm) as gas conduit 630 approaches second end 620 of drive line 600.

[0069] 19, the sensor conduit 640 includes a cardiac sensor 700 for monitoring the cardiac rhythm of a clinical subject. In various embodiments, the cardiac sensor 700 is selected from one or more of a plurality of electrodes and a fiber optic sensor. As illustrated in FIGS. 16 and 18, the cardiac sensor 700 is a plurality of electrodes, and as specifically shown, the plurality includes five electrodes 751.

[0070] In some alternative embodiments, the sensor 700 may include fewer or more electrodes, which may be selected for placement on portions of the clinical subject's anatomy other than the pericardium. In some embodiments, the sensor 700 may include one or more pressure-type or other sensors suitable for detecting non-electrical cardiac function, which may be placed within the lumen of one or more anatomical blood vessels. According to the illustrated embodiment, the use of electrodes, specifically myocardial electrodes, provides favorable results for the implantable pump 100 because it allows for interfacing with a wide range of conventional IABP drive units, most (if not all) of which require five cutaneous ECG leads. It is well known in the art that conventional IABP drive units use five ECG leads to coordinate the timing of inflation / deflation of a balloon implanted in the patient's vasculature. When used with this implantable pump 100, the use of five electrodes 751 affixed to the pericardium of the subject's heart avoids the need for a custom driver for the pump. Also, commercially available IABP units have pacing algorithms that sense five cutaneous leads and automatically select the optimal signal from among the leads, thus avoiding the need to rely on the development of new driver systems. These units can also trigger inflation / deflation based on aortic pressure sensed using, for example, a fiber optic sensor, thus supporting alternative embodiments of drive line 600 that use one or more fiber optic sensors placed within the lumen of the clinical subject. This disclosure is not limiting in the sense that a variety of possible cardiac sensors may be selected and used with any of a variety of known and possible custom drivers that provide gas flow functionality in response to signals from the clinical subject.

[0071] surgical technique According to the present disclosure, in various embodiments, a surgical procedure for promoting blood flow to support a diseased and / or damaged heart is provided. In some examples, the clinical subject is a human patient. According to this procedure, the clinical subject is first prepared to receive an implantable pump 100, whereby access to the thoracic cavity is achieved to allow placement of the blood implantable pump 100 in fluid communication with the patient's ascending aorta. Referring to the drawings, FIG. 17 is a schematic diagram illustrating possible placement locations of electrodes on the pericardium of the heart, and FIG. 18 is a schematic diagram showing the implantable pump 100 attached to the aorta of a human subject and the connected drive line 600 attached to the pump and passing through the subject's skin at a flange.

[0072] An implantable pump 100 is provided in accordance with embodiments disclosed herein. In one embodiment, the implantable pump 100 includes a rigid housing 101 having an oblate spheroid shape and an internal chamber 160, the rigid housing 101 including a blood port 125 opening into the internal chamber 160, the blood port 125 adjacent the upper apex of the oblate spheroid and oriented at an angle of about 0 to about 50 degrees relative to the central axis 102 of the oblate spheroid, and a gas port 147 opening into the internal chamber 160, the gas port 147 located at the lower apex of the oblate spheroid and having a gas port axis 149 oriented perpendicular to the central axis 102 of the oblate spheroid. The implantable pump 100 includes an internal elastomeric membrane 200 that generally fits within the internal chamber 160 and the blood port 125 and has an expanded volume that is less than the combined volume of the internal chamber 160 and the blood port 125. In an initial placement step, the implantable pump 100 is positioned between the clinical subject's heart and right lung, followed by at least partially clamping the clinical subject's ascending aorta.

[0073] A graft assembly 400 is provided that includes a flexible graft conduit that includes a tissue attachment end 411 and an implantable pump attachment end 412 that includes a washer 420 and a graft connector 430. The tissue attachment end 411 of the flexible graft conduit is anastomosed to the partially clamped aorta and ready for attachment to the implantable pump 100.

[0074] A drive line 600 is provided, including a gas conduit 630 attachable at a first end to a gas port 147 of the implantable pump 100, a sensor conduit 640, and a cardiac sensor passing therethrough, the cardiac sensor comprising one or more of a plurality of electrodes and a fiber optic sensor. The drive line 600 includes a flexible flange at a point along its length. The drive line 600 is then passed through an incision on the clinical subject's body with the flange abutting the incision outside the body. The gas conduit 630 of the drive line 600 is then attached to the gas port 147 of the implantable pump 100. Each of the one or more of the plurality of electrodes and fiber optic sensor is positioned on an anatomical structure of the clinical subject selected from a portion of the pericardium and within one of the pulmonary artery and the artery. In a specific example, the cardiac sensor includes a plurality of electrodes 750, e.g., five electrodes, each of which is attached to the pericardium of the clinical subject, as shown in FIGS. 17 and 18 . The electrodes may be myocardial electrodes. The gas conduit 630 and sensor conduit 640 of the drive line 600 are then attached to the drive system.

[0075] Once the drive components are in place and connected, the implantable pump 100 is affixed to the graft assembly 400 by engagement between the graft connector 430 and the rigid housing 101 connector on the blood port 125 of the implantable pump 100. The blood port 125 of the implantable pump 100 is ideally oriented at an angle within the clinical subject's anatomy to allow a close anatomical fit of the implantable pump 100 between the heart and right lung and attachment to the ascending aorta without kinking of the graft conduit and without superior vena cava compression. The clamp is then released from the clinical subject's aorta to allow blood to flow from the heart through the graft and into the implantable pump 100, and the drive system is activated to provide support to the heart.

[0076] Ideally, the surgical procedure is performed without the use of cardiopulmonary bypass. [Example]

[0077] Example 1: Surgical Procedure and Experimental Protocol Seven farm pigs weighing 80-90 kg were studied using the disclosed implantable device (referred to herein as "PULVAD"). All animals underwent a median sternotomy and implantation of a PULVAD into the ascending aorta. The device was connected to a conventional IABP drive console with a flexible drive line. A temporary pacemaker lead was implanted into the pericardium for ECG monitoring, and the PULVAD was synchronized based on the ECG to provide diastolic aortic pressure augmentation. Animals were instrumented with 1) catheters in the common carotid artery (to record aortic pressure) and the right external jugular vein (to monitor right atrial pressure and administer fluids), 2) a Millar pressure-tip catheter to record LV pressure, 3) four piezoelectric crystals (implanted subepicardially in the LV) to measure LV volume, and 4) a Doppler flow probe placed around the left anterior descending (LAD) artery to measure blood flow. Baseline measurements of aortic and LV pressures were obtained. Myocardial ischemia was then induced by ligation of the mid-LAD artery for 1 hour, followed by reperfusion. After 15 minutes of hemodynamic stabilization during reperfusion, ventilation was paused at expiration, and the following parameters were recorded without PULVAD support: arterial and LV pressures, heart rate, double product (systolic arterial pressure Å to heart rate), distance between piezoelectric crystals (for LV volume calculation), ejection fraction (EF), SV, cardiac output (CO), stroke work (SW) (area within the pressure-volume loop), dP / dTmax, dP / dTmin, and LAD blood flow. The PULVAD was then turned on, and the aforementioned parameters were recorded once a new hemodynamic steady state was achieved with the PULVAD on. The duration of PULVAD support (until a new hemodynamic steady state was achieved) varied from 30 to 60 seconds. The inferior vena cava was then gradually partially occluded, and a family of pressure-volume loops (during preload reduction) was obtained without PULVAD support and during PULVAD support (after the first 30-60 seconds) to determine the end-systolic pressure-volume relationship (ESPVR) and the end-diastolic pressure-volume relationship (EDPVR). The slope of the ESPVR was used to calculate a load-independent index of maximum contractile elastance (Emax).From ESPVR and EDPVR, pressure-volume area (PVA) (a proxy of myocardial oxygen consumption calculated as the area contained within the systolic segment of the ESPVR, EDPVR, and pressure-volume loop) was measured. The ratio of SW to PVA was calculated as an index of the energy efficiency of LV mechanical performance. The experiment was terminated after successful collection of at least three consecutive recordings (with the PULVAD off and on) with the heart in electrical fibrillation. Data were analyzed with CardioSoftPro software (Sonometrics Corporation, London, Canada).

[0078] Example 2: Statistical Analysis Data are presented as mean ± standard deviation in the text and tables, and as mean ± standard error of the mean in the figures. Data obtained from continuous recordings (with PULVAD on, without PULVAD support, and after 30–60 seconds of PULVAD support) were compared using paired t-tests. The coefficient r was calculated to examine the presence of correlations between variables by linear regression analysis. All tests were two-sided, and a p-value <0.05 was considered statistically significant.

[0079] Example 3: Pressure unloading left ventricular assist device support provides marked left ventricular pressure unloading Referring to the drawings, Figure 20 shows that the PULVAD provides severe pressure unloading of the failing LV. A: Aortic pressure waveforms without PULVAD support (PULVAD off) and with PULVAD support (PULVAD on). The PULVAD reduced systolic aortic pressure (112 to 95 mmHg [top], 85 to 65 mmHg [bottom]) and end-diastolic pressure (85 to 65 mmHg [top], 60 to 35 mmHg [bottom]). Note that the magnitude of the PULVAD-induced afterload reduction is similar across a wide range of systolic aortic pressure. Despite the dramatic reduction in systolic aortic pressure, mean aortic pressure remains normal due to the diastolic pressure augmentation provided by the PULVAD. * systolic aortic pressure, ■ end-diastolic pressure, # diastolic pressure augmentation. Quantitative analysis of PULVAD-induced changes in systolic arterial pressure (B), end-diastolic arterial pressure (C), and double product (D) (*p<0.05 compared with PULVAD off). PULVAD, pressure-unloading left ventricular assist device.

[0080] Left anterior descending artery ligation resulted in the induction of acute HF, manifested as a significant increase in LV end-diastolic pressure (baseline: 9.3 ± 1.4 mmHg, acute HF: 16.4 ± 5.6 mmHg; p < 0.001). Pressure-unloading left ventricular assist device support provided severe pressure unloading of the failing LV, manifested as a significant decrease in LV afterload, with systolic aortic pressure decreasing by 19.2 ± 8.6 mmHg, end-diastolic aortic pressure decreasing by 22.3 ± 10.7 mmHg bpm, and the double product decreasing by 1094 ± 921 mmHg bpm (Figure 20, Table 1). Representative aortic pressure waveforms without and with PULVAD counterpulsation are provided in Figure 20A, demonstrating the dramatic PULVAD-induced decrease in systolic and end-diastolic aortic pressure and an increase in diastolic arterial pressure.

[0081] Example 4: Pressure-unloaded left ventricular assist device support optimizes left ventricular mechanoenergetics Referring again to the figures, Figure 21 shows that PULVAD optimizes LV mechanoenergetics (improving mechanical performance and reducing energy expenditure) in acute HF. Quantitative analysis of PULVAD-induced changes in EF (A), CO (B), SV (C), SW (D), pressure-volume area (E), and the ratio of SW to pressure-volume area (F) (*p<0.05 compared to PULVAD off). G: Representative pressure-volume loops of a failing porcine LV without PULVAD support (PULVAD off) and during brief PULVAD support (PULVAD on). PULVAD support produces a dramatic shift of the pressure-volume loop to the bottom (severe pressure unloading) and to the left (indirect volume unloading). Additionally, PULVAD support optimizes LV mechanoenergetics, increasing SV and EF while simultaneously decreasing stroke work (measured as the area within the loop). CO is cardiac output, EF is ejection fraction, HF is heart failure, PULVAD is pressure unloading left ventricular assist device, PVA is pressure-volume area, SV is stroke volume, and SW is stroke work. [Table 1]

[0082] HF is heart failure, LAD is left anterior descending artery, PULVAD is pressure unloading left ventricular assist device, and PVA is pressure-volume area.

[0083] Pressure-unloading left ventricular assist device support improved the mechanical performance of the failing LV, manifested as significant increases in LVEF, SV, and CO (Figure 21, A–C, Table 1). PULVAD-induced enhancement of LV mechanical performance was accompanied by a concomitant decrease in SW and total LV energy expenditure (measured by PVA) (Figure 21, D and E, Table 1). In addition, PULVAD support optimized LV mechanoenergetic efficiency, as indicated by an increase in the SW-to-PVA ratio (Figure 21F, Table 1). Furthermore, PULVAD support resulted in indirect volume unloading of the LV, as there was a significant decrease in LV EDV (and consequently, LV end-diastolic pressure) (Table 1). This indirect volume unloading of the LV can be rationalized as follows: In the setting of PULVAD-induced improved LV systolic performance, LV preload (i.e., LV end-diastolic volume) is physiologically adjusted to the minimum level required for the LV to eject enough SV to meet peripheral needs, as determined by the Frank-Starling law.

[0084] Figure 21G shows representative pressure-volume loops of a failing porcine LV without and during PULVAD support. Pressure-unloading left ventricular assist device support produces a dramatic shift in the pressure-volume loop to the bottom (severe pressure unloading) and to the left (indirect volume unloading). In addition, PULVAD support optimizes LV mechanoenergetics, increasing SV and EF while simultaneously decreasing SW (measured as the area within the loop).

[0085] Example 5: Pressure-unloading left ventricular assist device support improves left ventricular contractility Referring again to the figures, Figure 22 shows the PULVAD effect on dP / dTmax and dP / dTmin. Quantitative analysis of PULVAD-induced changes in dP / dTmax (A) and dP / dTmin (B) (*p<0.05 compared to PULVAD off). C-F: PULVAD-induced changes in dP / dTmax and dP / dTmin significantly correlated with PULVAD-induced reductions in systolic and end-diastolic arterial pressure during ischemia. PULVAD, pressure-unloading left ventricular assist device.

[0086] In the acute HF setting, PULVAD support induced a significant decrease in dP / dTmax and a significant increase in dP / dTmin. However, dP / dTmax and dP / dTmin are load-dependent (they improve with increasing afterload), and we have previously shown that counterpulsation-induced afterload reductions (using an IABP) significantly correlate with changes in dP / dT. Changes in dP / dTmax and dP / dTmin during PULVAD support significantly correlated with PULVAD-induced decreases in systolic and end-diastolic arterial pressure (used as markers of cardiac afterload) (Figure 22). Therefore, the decrease in dP / dTmax and increase in dP / dTmin observed during PULVAD support should be attributed to pressure unloading (i.e., a decrease in cardiac afterload) rather than interpreted as a PULVAD-induced deterioration in LV systolic and diastolic function.

[0087] Referring again to the figures, Figure 23 shows that PULVAD support improves contractility of the failing LV. A: Family of pressure-volume loops without and after short-term PULVAD support (at reduced preload). Maximum elastance (Emax, i.e., the slope of the end-systolic pressure-volume relationship) increases after PULVAD support. The dashed line on the right indicates the slope of the solid line on the left (PULVAD off). B: Quantitative analysis of PULVAD-induced changes in Emax (compared to PULVAD off, *p<0.05). PULVAD, pressure-unloaded left ventricular assist device. PULVAD support induced a significant increase in Emax, manifested as a steeper slope of ESPVR (Figure 23, Table 1), suggesting improved contractility of the failing LV.

[0088] Example 6: Pressure-unloaded left ventricular assist device support increases left anterior descending artery blood flow in reperfused myocardium Referring again to the figures, Figure 24 shows that PULVAD increases coronary artery blood flow in failing hearts. A: LAD blood flow waveforms without and with brief PULVAD support during reperfusion. Note the dramatic enhancement in diastolic blood flow (denoted by *) induced by PULVAD. Quantitative analysis of PULVAD-induced changes in mean LAD blood flow (B), systolic LAD blood flow (C), and diastolic LAD blood flow (D) (*p<0.05 compared to PULVAD off). LAD left anterior descending artery; PULVAD is a pressure-unloading left ventricular assist device. Figure 24A shows representative LAD blood flow recordings with and without PULVAD support in the acute HF setting. PULVAD support reduced LAD blood flow during systole (from 32.5 ± 13.9 to 11.0 ± 28.0 ml / min, p = 0.090) but dramatically increased LAD blood flow during diastole (from 62.4 ± 31.4 to 98.3 ± 36.3, p = 0.001), resulting in a significant net increase in mean LAD blood flow (from 50.8 ± 23.4 to 64.6 ± 24.2, p = 0.034) (Figure 24, B–D; Table 1). The decrease in systolic LAD blood flow and dramatic increase in diastolic blood flow reflect PULVAD-induced changes in aortic blood pressure (i.e., a decrease in systolic pressure and an augmentation of diastolic pressure, respectively). These findings are consistent with the notion that in the reperfused ischemic heart (in which coronary autoregulation is severely impaired), perfusion pressure (rather than myocardial oxygen demand) is the primary determinant of coronary flow. 14 , 15 In contrast, blood flow in the common carotid artery remained unaffected by PULVAD support (PULVAD off: 88.0 ± 55.8 vs. PULVAD on: 85.1 ± 56.1, p = 0.173), indicating an intact autoregulatory capacity of the cerebral circulation.

[0089] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. The term "proximal," as used in reference to any object, refers to the portion of the object closest to the operator of the object (or some other described point of reference), and the term "distal" refers to the portion of the object farthest from the operator of the object (or some other described point of reference). The term "operator," particularly in connection with the delivery of health care, means and refers to any professional or paraprofessional who provides clinical care to a medical patient.

[0090] Unless otherwise indicated, all numbers expressing quantities, properties, and the like used in the specification, drawings, and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless otherwise indicated, the numerical properties set forth in the specification and claims are approximations that may vary depending upon the preferred properties desired in embodiments of the invention. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the general inventive concept are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from deviations found in their respective measurements.

[0091] Although the disclosed embodiments are described and illustrated in the drawings in the context of the human spine, it should be understood by those skilled in the art that all or various aspects of the embodiments herein may be used in connection with other species and in any species on other parts of the body where deep access within tissue is desirable.

[0092] Unless expressly excluded herein, all such combinations and subcombinations are intended to be within the scope of the general inventive concept. Furthermore, although various alternative embodiments (such as alternative materials, structures, configurations, methods, devices and components, form, fit and function alternatives, etc.) may be described herein with respect to various aspects, concepts, and features of the invention, such descriptions are not intended to be a complete or exhaustive list of available alternative embodiments, whether currently known or later developed.

[0093] Those skilled in the art may readily adopt one or more of the aspects, concepts, and features of the present invention into additional embodiments and use within the scope of the general inventive concept, even if not explicitly disclosed herein. In addition, while some features, concepts, and aspects of the present invention may be described herein as being preferred arrangements or methods, such description is not intended to imply that such features are required or necessary unless explicitly stated. Furthermore, while example or representative values and ranges may be included to aid in understanding the present disclosure, such values and ranges should not be construed in a limiting sense, and are intended to be significant values or ranges only when explicitly stated.

[0094] Additionally, while various aspects, features, and concepts may be expressly identified herein as being inventive or forming part of an invention, such identification is not intended to be exclusive; rather, there may be aspects, concepts, and features of an invention that are fully described herein without being expressly identified as such or as part of a particular invention. The description of an exemplary method or process is not limited to including every step as required in all cases, or to the order in which steps are presented so that they are construed as required or needed, unless explicitly stated.

Claims

1. 1. A method for promoting blood flow, comprising: (a) preparing a clinical subject to receive an implantable device, said clinical subject having a thoracic cavity including a heart with a pericardium, an ascending aorta, a pulmonary artery, a superior vena cava, and left and right lungs; (b) providing an implantable pump including a blood port and a gas port; (c) placing the implantable pump between the heart and the right lung of the clinical subject; (d) partially clamping the ascending aorta of the clinical subject; (e) providing a graft assembly comprising a flexible graft conduit including a tissue attachment end and a pump attachment end comprising a washer and a graft connector; (f) attaching the tissue attachment end of the flexible graft conduit to the partially clamped aorta; (g) providing a drive line comprising a gas conduit attachable at a first end to the gas port of the implantable pump, the drive line further comprising a sensor conduit and a cardiac sensor passing therethrough, the cardiac sensor comprising one or more of a plurality of electrodes and a fiber optic sensor, the cardiac sensor attachable at the first end to the clinical subject, a second end of the gas conduit and a second end of the sensor conduit attachable to a drive system for delivering a gas flow through the drive line gas conduit in response to a signal driven by the cardiac sensor, the drive line including a disk-shaped circumferential flange; (h) passing the drive line through the incision in the clinical subject with the flange abutting the incision; (i) attaching the gas conduit to the gas port of the pump; (j) placing each of one or more of the plurality of electrodes and fiber optic sensors on the anatomical structure of clinical interest selected from the portion of the pericardium and within one of a pulmonary artery and an artery; (k) connecting the second end of the drive line to the drive system; (l) attaching the implantable pump to the graft assembly by engagement between the graft connector and a housing connector on the blood port of the pump; (m) removing the clamp from the aorta of the clinical subject to allow blood flow from the heart through the graft into the implantable pump and actuating the drive system.

2. the implantable pump comprises a rigid housing having an oblate spheroidal shape; the rigid housing defines an interior chamber divided into an air subchamber and a blood subchamber by a movable elastomeric membrane; the air subchamber is connectable to an external air pressure source through the drive line; the blood subchamber is connectable to an anatomical heart through a graft assembly; the rigid housing includes a blood port that opens to the blood subchamber; The blood port is adjacent to the upper apex of the rigid housing and oriented at an angle ranging from about 0 degrees to about 50 degrees relative to the through axis of the oblate spheroid, the rigid housing further comprising a gas port opening to the gas subchamber, the gas port being located at the lower apex of the rigid housing.

10. The method for promoting blood flow according to claim 1.

3. 3. The method for promoting blood flow of claim 2, wherein one or both of the blood port and the gas port comprises an opening without a valve.

4. 3. The method for promoting blood flow of claim 2, wherein the elastomeric membrane has a shape that generally conforms to the interior chamber and the hemoport and has an expanded volume that is less than the combined volume of the chamber and the hemoport.

5. 3. The method for promoting blood flow of claim 2, wherein the blood-ports are oriented at an angle in the range of about 20 degrees to about 50 degrees relative to the oblate spheroid shape.

6. The method for promoting blood flow according to claim 2 , further comprising a housing connector and a graft assembly.

7. The method for promoting blood flow according to claim 6 , wherein the graft assembly comprises a graft conduit, a washer, and a graft connector.

8. The method for promoting blood flow according to claim 7 , wherein the graft connector is engagable with the housing connector by any one of threads, a snap fit, or a quick connector.

9. 8. The method for promoting blood flow according to claim 7, wherein the blood port and the graft conduit each have an interior surface, each such interior surface having essentially the same diameter at the interior surface interface therebetween.

10. 3. The method for promoting blood flow of claim 2, wherein the blood port has a blood port axis that intersects with a central axis through the rigid housing at an angle ranging from about 35 degrees to about 45 degrees.

11. The method for promoting blood flow according to claim 2 , wherein the gas port has an inner diameter ranging from about 1.5 mm to about 2 mm.

12. 2. The method for promoting blood flow of claim 1, wherein the gas conduit and the sensor conduit are closely connected along at least a portion of the length of the drive line and split at each of first and second ends of the drive line, the gas conduit being attachable at a first end to the gas port of the implantable pump, and the cardiac sensor monitors cardiac rhythm through the sensor conduit.

13. the implantable pump comprising the rigid housing, the housing connector, the graft assembly, and the cardiac sensor; the rigid housing has an oblate spheroidal shape and defines an inner chamber divided by a movable elastomeric membrane into an air subchamber connectable to an external air pressure source through the drive line and a blood subchamber connectable to an anatomical heart through the graft assembly; the housing includes a blood port opening to the blood subchamber, the blood port being located adjacent an upper apex of the housing and oriented at an angle ranging from about 20 degrees to about 50 degrees relative to a through axis of the oblate spheroid shape; the housing also includes a gas port opening to the gas subchamber, the gas port being located at a lower apex of the housing; the housing connector is adapted to attach to the blood port and engage with the graft assembly; and the cardiac sensor monitors cardiac rhythm; 10. The method for promoting blood flow according to claim 1.

14. 14. The method for promoting blood flow of claim 13, wherein the gas conduit and sensor conduit of the drive line are continuous in their connection to the drive system and are split into two prior to the attachment of the gas conduit to the gas port.

15. 14. The method for promoting blood flow of claim 13, wherein the sensor is selected from one or more of an electrode and a fiber optic sensor.

16. 16. The method for promoting blood flow of claim 15, wherein the sensor comprises a plurality of electrodes.

17. 14. The method for promoting blood flow of claim 13, wherein the gas conduit of the drive line includes a circumferential flange having a disk shape.

18. 10. The method for promoting blood flow of claim 1, wherein the method does not require the use of cardiopulmonary bypass.

19. 20. The method for promoting blood flow of claim 18, wherein the blood ports of the pump are oriented within the anatomy of the clinical target at an angle that allows for anatomical fit and attachment to the ascending aorta while reducing the possibility of kinking of the graft conduit and superior vena cava compression.

20. the implantable pump is a device for assisting blood flow, (i) a rigid housing having an oblate spheroid shape and comprising a blood portal section and a gas port section, the blood portal and gas port sections defining a chamber within the rigid housing having an oblate spheroid shape; (1) the blood portal section has a cylindrical shape and includes the blood port defining a through channel between an exterior of the rigid housing and the chamber, the blood portal section having a blood portal axis intersecting a central axis passing through the blood portal and gas port sections of the rigid housing; (2) a rigid housing, the gas port section having an inner surface including a base, the base including a plurality of grooves and the gas port defining a gas flow conduit between the exterior of the rigid housing and the chamber, the gas port having a gas port axis perpendicular to a central axis of the rigid housing; (ii) an elastomeric membrane comprising a valve section, a cylindrical neck, and a cuff that interfaces with the housing connector; the elastomeric membrane has a shape that generally conforms to the chamber and the blood portal section; the elastomeric membrane has an expanded volume that is less than a combined volume of the chamber and the blood portal section; an elastomeric membrane, when the elastomeric membrane is at its maximum expanded volume, the chamber comprising a dead volume of about 3 cc to about 10 cc; (iii) a housing connector attached to the blood portal section and adapted to engage a graft assembly; 10. The method for promoting blood flow of claim 1, comprising: (iv) a graft assembly comprising a graft conduit, a washer, and a graft connector engageable with the housing connector.

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