|Número de publicación||US20050234289 A1|
|Tipo de publicación||Solicitud|
|Número de solicitud||US 11/143,542|
|Fecha de publicación||20 Oct 2005|
|Fecha de presentación||2 Jun 2005|
|Fecha de prioridad||26 Jun 2003|
|También publicado como||CA2530574A1, CN1838971A, EP1644060A2, US7494459, US20040267086, US20060142634, US20060211909, WO2005000160A2, WO2005000160A3|
|Número de publicación||11143542, 143542, US 2005/0234289 A1, US 2005/234289 A1, US 20050234289 A1, US 20050234289A1, US 2005234289 A1, US 2005234289A1, US-A1-20050234289, US-A1-2005234289, US2005/0234289A1, US2005/234289A1, US20050234289 A1, US20050234289A1, US2005234289 A1, US2005234289A1|
|Inventores||Mark Anstadt, George Anstadt, Stuart MacDonald, Jeffrey Helfer|
|Cesionario original||Anstadt Mark P, Anstadt George L, Macdonald Stuart G, Helfer Jeffrey L, Anstadt George W|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (81), Citada por (15), Clasificaciones (19), Eventos legales (1)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
This application is a divisional application of copending patent application U.S. Ser. No. 10/607,434, filed on Jun. 26, 2003, the disclosure of which is incorporated herein by reference.
This invention relates in one embodiment to devices that deliver at least one therapeutic agent directly and preferentially to a desired tissue to be treated, and more particularly to devices for delivering a therapeutic agent to a heart while providing assistance to the pumping function of the heart.
1. Field of the Invention
A therapeutic apparatus for delivering at least one therapeutic agent directly and preferentially to a desired tissue to be treated in a living body.
2. Description of Related Art
Traditional medical and surgical treatment of patients with failing pump function of the heart is limited to blood-contacting devices which are technically difficult to install and result in complications related to such blood contact as well as technical aspects of device installation. Inadequate cardiac output remains a cause of millions of deaths annually in the United States. Mechanical devices are proving to be a practical therapy for some forms of sub-acute and chronic low cardiac output. However, all currently available devices require too much time to implant to be of value in acute resuscitation situations, resulting in loss of life before adequate circulatory support can be provided. Furthermore, other non-blood contacting devices similar to the current invention provide inadequate augmentation of cardiac function. Mechanical cardiac assistance devices generally operate by providing blood pumping support to the circulation to assist the failing heart.
A number of mechanical techniques for assisting heart function by compressing its outer epicardial surface have been described and studied. These methods have focused on improving cardiac performance by assisting the systolic (positive pumping) function of the heart. Such techniques have been described as “direct cardiac compression” (DCC). DCC methods have been investigated only in the laboratory setting, and there are no uses of such devices in human subjects known to the applicants. Investigations regarding DCC have focused primarily on left ventricular (LV) systolic and diastolic performance. Examples of DCC techniques include, but are not limited to, cardiomyoplasty (the technique of wrapping skeletal muscle around the heart and artificially stimulating it), the Cardio support system (Cardio Technologies, Inc., Pinebrook, N.J.) and the “Heart Booster” (Abiomed, Inc., Danvers, Mass.). Cumulative results from laboratory investigations using these devices have all resulted in similar findings. Specifically, DCC has been shown to enhance left ventricular (LV) pump function without any apparent change in native LV oxygen consumption requirements; thereby, DCC has been shown to improve LV pump function without increasing myocardial oxygen consumption and/or requiring extra work from the heart.
DCC devices have been shown to only benefit hearts with substantial degrees of LV failure. Specifically, DCC techniques only substantially improve the systolic function of hearts in moderate to severe heart failure. In addition, the benefits of DCC techniques are greater when applied to the relatively dilated or enlarged LV. Therefore the relative degree of assistance provided by DCC improves as heart failure worsens and the heart enlarges or dilates from such failure. DCC techniques clearly have a negative effect on diastolic function (both RV and LV diastolic function). This is exhibited by reductions in diastolic volume that, in part, explains DCC's inability to effectively augment the heart without at least moderate degrees of failure. This also explains DCC's efficacy being limited to sufficient degrees of LV size and/or dilatation, with significant dependence on preload, and/or ventricular filling pressures. Thus, DCC requires an “adequate” degree of heart disease and/or heart failure to benefit the heart's function. In addition, DCC devices have negative effects on the dynamics of diastolic relaxation and, in effect, reduce the rate of diastolic pressure decay (negative dP/dt max), increasing the time required for ventricular relaxation. This better explains why DCC techniques require substantial degrees of LV and RV loading (i.e. increased left and right atrial pressure or “preload”) to be effective, as such increases serve to augment ventricular filling. This latter point is particularly true with smaller heart size and/or less ventricular distension.
The critical drawbacks to DCC methods are multi-factorial and are, in part, summarized in the following discussion. First, and foremost, these techniques do not provide any means to augment diastolic function of the heart necessary to overcome their inherent drawback of “effectively” increasing ventricular stiffness. This is illustrated by the leftward shifts in the end-diastolic pressure-volume relationship (EDPVR) during DCC application. This effect on the EDPVR is seen with DCC devices in either the assist or non-assist mode. Clearly, RV diastolic function is impaired to a far greater degree by DCC due to the nature both the RV wall and intra-cavity pressures. Furthermore, studies of DCC devices have all overlooked the relevant and dependent impact these techniques have on right ventricular dynamics, septal motion and overall cardiac_function. Because the right ventricle is responsible for providing the “priming” blood flow to the left ventricle, compromising right ventricular function has a necessary secondary and negative impact on left ventricular pumping function when these load-dependent devices are utilized. Furthermore, the ventricular septum lies between the right and left ventricle and is directly affected by the relevant forces placed on both the RV and LV. Another related and fundamental drawback to DCC devices is their inability to continuously monitor ventricular wall motion and chamber dynamics that are intuitively critical to optimizing the assist provided by such mechanical actions on the right and left ventricular chambers which behave in an complex, inter-related fashion. Finally, studies regarding DCC methods have failed to adequately examine the effects of these devices on myocardial integrity.
The Direct Mechanical Ventricular Assist device (hereinafter abbreviated as DMVA) is an example of one type of mechanical cardiac assistance device. In general, a DMVA system comprises two primary elements: (a) a Cup having dynamic characteristics and material construction that keep the device's actuating liner membrane or diaphragm closely conformed to the exterior surface (or epicardium) of the heart throughout systolic and diastolic actuation, and (b) a Drive system and control system combination that cyclically applies hydraulic pressure to a compression and expansion liner membrane or membranes located on the interior surfaces of the Cup in a manner that augments the normal pressure and volume variations of the heart during systolic and diastolic actuation. The cyclic action of the device cyclically pushes and pulls on the left and right ventricles of the heart.
By providing this cyclic motion at the appropriate frequency and amplitude, the weakened, failing, fibrillating, or asystolic heart is driven to pump blood in a manner which approximates blood flow generated by a normally functioning heart. Pushing inwardly on the exterior walls of the heart compresses the left and right ventricles into systolic configuration(s), thereby improving pump function. As a result, blood is expelled from the ventricles into the circulation. Immediately following each systolic actuation, the second phase of the cycle applies negative pressure to the liner membrane to return the ventricular chambers to a diastolic configuration by pulling on the outer walls of the heart. This is termed diastolic actuation and allows the ventricular chambers to refill with blood for the next compression.
In the preferred embodiment of the present invention, the Cup is installed on the heart typically by using apical vacuum assistance, i.e. vacuum applied to the apex of the Cup. Such a preferred embodiment enables a non-traumatic and technically simple means of cardiac attachment of the Cup device in the patient and facilitates diastolic actuation. To install the Cup, the heart is exposed by a chest incision. The Cup is positioned over the apex of the heart in a position such that the apex of the heart is partially inserted therein. A vacuum is applied to the apex of the Cup, thereby pulling the heart and the Cup together, such that the apices of the Cup and the heart, and the inner wall of the Cup and the epicardial surface of the heart become substantially attached. Connections are then completed for any additional sensing or operational devices (typically integrated into a single interface cable) if the particular Cup embodiment comprises such devices. This procedure can be accomplished in minutes, and it is easy to teach to individuals with minimal surgical expertise.
Effective DMVA requires that the Cup and Drive system satisfy multiple and complex performance requirements. Preferred embodiments of the Cup of the present invention satisfy these critical performance requirements in a manner that is superior to prior art DMVA devices.
Heretofore, a number of patents and publications have disclosed Direct Mechanical Ventricular Assist devices and other cardiac assistance devices, the relevant portions of which may be briefly summarized as follows:
U.S. Pat. No. 2,826,193 to Vineberg discloses a Ventricular Assist device that is held to the heart by a flexible draw-string. Vineberg uses a mechanical pump to supply systolic pressure to the heart to assist the heart's pumping action.
U.S. Pat. No. 3,034,501 to Hewson discloses a similar Ventricular Assist device, comprised of silastic, which permits varying pressures to be exerted on various portions of the heart. U.S. Pat. No. 3,053,249 to Smith discloses a Ventricular Assist device capable of delivering systolic pressure to a heart. The Smith device utilizes adhesive straps to attach the device to the heart.
U.S. Pat. No. 3,233,607 to Bolie illustrates a Direct Assist device that varies the level of systolic pressure depending on the changes of blood flow occasioned by exercise. The Bolie device claims to be fully implantable. U.S. Pat. No. 3,449,767 to Bolie discloses a system for controlling the pressure delivered to the balloons that control the DMVA unit.
U.S. Pat. No. 3,279,464 to Kline teaches a method of manufacture of a Ventricular Assist device. Kline's device provides only systolic pressure to the heart.
U.S. Pat. No. 3,371,662 to Heid discloses a Ventricular Assist device in the form of a cuff. The cuff may be implanted with defibrillating electrodes.
U.S. Pat. No. 3,376,863 to Kolobow illustrates a Ventricular Assist device that delivers systolic pressure to the heart. The Kolobow device possesses an expandable collar about the periphery of the device's opening. The heart may be sealed within the device by expanding the collar.
U.S. Pat. No. 3,455,298 of Anstadt discloses a Direct Mechanical Ventricular Assist device capable of delivering both systolic and diastolic pressures. The diastolic action is achieved by use of a vacuum. A second vacuum source functions to hold the device to the heart. Anstadt further defines the geometry of the device in U.S. Pat. No. 5,199,804. The geometry of the invention is described so as to accommodate hearts of various sizes as well as prevent the heart from being expelled from the device during the systolic expansion of the bladders.
U.S. Pat. No. 3,478,737 of Rassman discloses a Ventricular Assist device in the form of a cuff.
U.S. Pat. No. 3,513,836 to Sausee discloses a Ventricular Assist device that delivers systolic pressure to the heart by a multiplicity of bladders. Increasing the pressure in selected bladders may preferentially pressure selected portions of the heart.
U.S. Pat. No. 3,587,567 to Schiff discloses a Direct Mechanical Ventricular Assist device that is capable of delivering both systolic and diastolic pressures to a heart. The device may further comprise electrodes that permit defibrillation of the heart. The device is held to the heart by a mild vacuum pressure, which also supplies the diastolic action.
U.S. Pat. No. 3,613,672 to Schiff discloses a cup with a flexible outer shell that allows for the insertion of the device through a relatively small surgical incision. The patent also discloses the use of sensors, such as electrocardiogram equipment, in conjunction with the cup. Additional reference may be had to U.S. Pat. Nos. 3,590,815 and 3,674,381 also to Schiff.
U.S. Pat. No. 4,048,990 to Goetz discloses a Ventricular Assist device that delivers both systolic and diastolic pressures to a heart. The outer shell of the Goetz device is inflatable, so as to allow installation with minimal trauma to the patient.
U.S. Pat. No. 4,448,190 to Freeman discloses a Ventricular Assist device that delivers systolic pressure to a heart by means of a strap physically attached to the heart. A similar device is disclosed in U.S. Pat. Nos. 5,383,840 and 5,558,617 to Heilman. The Heilman patent discloses the use of defibrillation devices and materials that promote tissue in-growth to assist in adhering the device to the heart.
U.S. Pat. No. 4,536,893 to Parravicini discloses a Ventricular Assist device in the form of a cuff that applies pressure to selected portions of the heart. The patent also discloses the use of sensors, such as an electrocardiograph, in conjunction with the cuff.
U.S. Pat. No. 4,621,617 to Sharma discloses a Ventricular Assist device wherein the heart is disposed within two sheets of metal. An electromagnetic field draws the sheets together, thus compressing the heart.
U.S. Pat. No. 4,684,143 to Snyders discloses a Ventricular Assist device with a collapsible outer shell. Such a device may be installed with minimal trauma to the patient.
Additional reference may be had to U.S. Pat. Nos. 5,169,381 and 5,256,132 also to Snyders.
U.S. Pat. No. 4,979,936 to Stephenson discloses a fully implantable Ventricular Assist device. Stephenson's device comprises a first bladder fluidly connected to a second bladder. The first bladder is disposed within a muscle, while the second bladder is disclosed next to or around the heart. The muscle may then be electrically contracted, thus, forcing fluid out of the first bladder and into the second bladder. The expansion of the second bladder thus compresses the heart.
U.S. Pat. No. 5,273,518 to Lee discloses a fully implantable Ventricular Assist device similar to the muscle powered devices mentioned above. U.S. Pat. Nos. 5,098,442 and 5,496,353 to Grandjean, U.S. Pat. No. 5,562,595 to Neisz, U.S. Pat. Nos. 5,658,237, 5,697,884, and 5,697,952 to Francischelli, U.S. Pat. No. 5,716,379 to Bourgeois and U.S. Pat. No. 5,429,584 to Chiu disclose a similar device. U.S. Pat. No. 5,364,337 to Guiraudon discloses a means for controlling the contraction of the muscle, which in turn, controls the compression of the heart.
U.S. Pat. No. 5,098,369 to Heilman discloses a Ventricular Assist device that is comprised of materials that allow for tissue in-growth, thus adhering the device to the heart. The use of defibrillating electrodes and electrocardiographs are also disclosed.
U.S. Pat. No. 5,131,905 to Grooters discloses a Ventricular Assist device that applies systolic pressure to the heart. The Grooters device is held in position around the heart by a plurality of straps.
U.S. Pat. Nos. 5,385,528, 5,533,958, 5,800,334, and 5,971,911 to Wilk disclose a Direct Mechanical Ventricular Assist device suitable for emergency use. The inflatable device may be quickly installed in an emergency situation through a small incision. U.S. Pat. No. 6,059,750 to Fogarty discloses a similar device.
U.S. Pat. No. 5,713,954 to Rosenberg discloses a Ventricular Assist device in the form of a cuff that provides systolic pressure to a heart. The disclosed cuff is suitable for applying pressure to specified portions of the heart, may be equipped with EKG sensors, and is fully implantable.
U.S. Pat. Nos. 5,738,627 and 5,749,839 to Kovacs disclose a Direct Mechanical Ventricular Assist device that provides both systolic and diastolic pressure to a heart. The disclosed cup adheres to the heart by way of a vacuum, which also provides diastolic pressure to the heart. The opening of the device is equipped with an inflatable collar. When inflated, the collar provides a seal to assist in establishing the vacuum.
U.S. Pat. No. 6,076,013 to Brennan discloses a cup that senses electrical activity within the heart and provides electrical stimulation to assist the heart in its contractions.
U.S. Pat. No. 6,110,098 to Renirie discloses a method for treatment of fibrillation or arrhythmias through the use of subsonic waves.
U.S. Pat. No. 6,206,820 to Kazi discloses a Ventricular Assist device that compresses only the left ventricle and allows the other cardiac regions to expand in response to the contraction.
U.S. Pat. No. 6,238,334 to Easterbrook discloses a Ventricular Assist device that provides both systolic and diastolic pressure to a heart. Easterbrook discloses the use of a cup to apply a substantially uniform pressure to the heart's surface, which is necessary to avoid bruising of the muscle issue. Through the reduction of transmural pressure, a substantially lower driving pressure may be utilized. This assists to avoid traumatizing heart tissue.
U.S. Pat. No. 6,251,061 to Hastings discloses a Ventricular Assist device that provides systolic pressure to a heart through the use of ferrofluids and magnetic fields.
U.S. Pat. No. 6,432,039 to Wardle discloses a Ventricular Assist device that comprises a multiplicity of independently inflatable chambers that delivery systolic pressure to selected portions of a heart. Wardle also discloses the use of redundant “recoil” inflatable balloons.
U.S. Pat. No. 6,464,655 to Shashinpoor discloses a fully implantable robotic hand for selectively compressing the ventricles of a heart. The robotic hand is programmable via a microprocessor.
U.S. Pat. No. 6,328,689 to Gonzalez and U.S. Pat. No. 6,485,407 to Alferness disclose a flexible jacket adapted to be disposed about a lung. By applying expansive and compressive forces, the lung may be assisted.
Optimal DMVA performance requires that the Cup be properly fit on the heart, be adequately sealed against the ventricular epicardium, and that the volume vs. time displacement profile of the Cup liner(s) produces the desired ventricular dynamics to achieve optimal, dynamic systolic and diastolic conformational changes of the ventricular myocardium. The optimum pressure-flow drive mechanics will vary from patient to patient, depending upon such factors as the actual fit of the Cup to the heart, the specific nature of the patient's disease, and the patient's normal cardiac rhythm. These factors make it difficult to pre-operatively define the optimum liner time-displacement profiles or hydraulic drive unit control parameters capable of satisfying every patient's unique DMVA requirements.
It is well known that diseased heart tissue can be very fragile, i.e. such tissue is of lower resistance to shear forces and/or less tensile strength than healthy heart tissue. Thus physicians lacking due caution can easily perforate or injure diseased hearts with their fingers while applying gentle pressure during open heart massage by the high pressure at a finger tip adjacent to a low pressure or pressure void between fingers. This previous example describes an acute or rapidly induced emergency situation. However, the persistent application of forces to the heart can also cause potentially catastrophic damage to the heart by fatiguing and severely bruising the heart muscle and/or abrading the heart surface, which can ultimately prevent the heart from functioning.
Direct mechanical ventricular actuation (DMVA) is a means of providing ventricular actuation to achieve biventricular compression (termed “systolic actuation”) and active biventricular dilatation (termed “diastolic actuation”). In one embodiment, DMVA utilizes continuous suction to maintain a seal between the actuating diaphragm and the surface of the heart, which enables the device not only to compress the heart, but also effectively provide diastolic actuation by virtue of the diaphragm maintaining attachment to the epicardial surface during the phase of ventricular actuation. Therefore, DMVA overcomes major drawbacks of DCC devices by augmenting diastolic function. This is essential, given that any such DCC device that encompass the ventricles and applies external forces will have inherently negative impacts on diastolic function. The present invention overcomes this, by enhancing diastolic function as demonstrated by an increased rate of diastolic pressure decay and an associated reduced time constant for active ventricular chamber dilatation (“diastolic actuation”).
The general principles of effective ventricular compression and ventricular dilatation can only be delivered in an optimal fashion if the effects on both right and left ventricular function are taken into account and such forces are applied in the appropriate temporal and spatial distribution, which is dictated by the material characteristics and delivery of the appropriate drive mechanics using appropriately fashioned pressure and/or flow dynamic profiles. These drive dynamics and material characteristics of the diaphragm and housing of the device are also critical in achieving the best functional result, with the least cardiac trauma.
The appropriate dynamic fit of the DMVA device and its interaction with the heart throughout the actuating cycle is critical, and mandates that RV/LV dynamics are monitored. In particular, fit of the device in the diastolic mode must allow for adequate expansion of both the LV and RV chambers, with particular attention to the RV due to its lower-pressure, compliant properties. Inadequate size and/or diastolic assist will predominantly compromise RV filling, resulting in diminished RV output, and in turn, reductions in overall cardiac output. In contrast, systolic actuation places emphasis on adequate degrees of LV compression. Adequate LV chamber compression requires attention to regulation of variables including maximum systolic drive volume delivery, maximum systolic pressure, and systolic duration.
More simply stated, adequate LV compression is that degree of compression that results in LV stroke volumes approximately equal to optimal RV stroke volumes. The inter-relationship of these chambers dictates that both RV and LV chambers need to be monitored. Appropriate RV and LV actuation by the DMVA system requires active, real-time measurement of both operational parameters and hemodynamic responses, which are utilized in the DMVA adaptive control algorithms to achieve optimal pump function and other more sophisticated operations such as device weaning and analysis of myocardial recovery.
Functional interactions between the right ventricle and left ventricle under mechanical systolic and diastolic actuation are relatively complex and difficult to describe and/or characterize. These are dynamic interactions that are not necessarily predictable based on pre-measured variables, but rather depend on a broad number of physiologic variables. These interactions are not independent; thus the behavior of one chamber has an impact on the other. Continuous monitoring of these two chambers allows the drive control to utilize an adaptive algorithm to constantly alter DMVA control parameters to achieve optimal cardiac actuation and hemodynamic output. Examples of this include, but are not limited to adjustment of pressure/volume relationships to maintain balanced RV/LV output, control of pressure rise times to avoid herniation of the right ventricle, and reduction of negative drive pressure during diastole based on loss of contact between the DMVA liner and the heart wall.
The variability of a broad range of physiologic states across the patient population will dictate that these and other parameters will require responses that may be somewhat unique to each patient. Thus parametric control that benefits from broad demographic information, from physician input, and from real-time patient response data will result in the best outcome for the individual patient.
Therefore a heart-assist device is needed that does not cause damage to the heart as a result of its mechanical action on the heart. There also exists a need for a sensing and control means to ensure that such a device (1) is properly positioned and/or installed on the heart, (2) adequately seals against the heart, (3) achieves the desired systolic and diastolic action at installation and over the implanted life of such device, (4) operates within desired parameters to achieve optimal cardiovascular support, and (5) detects changes, such as impending device failure, in time to take corrective action.
There is also a need for a process to accomplish the above tasks very quickly, in order to avoid brain death and other organ damage. The inherent ability of the DMVA Cup of the present invention to be installed in a very short period of time with no surgical connection to the cardiovascular system of the patient needed enables the Cup of the present invention to save patients who require acute resuscitation, as well as to minimize the number of failed resuscitations due to improper installation or drive mechanics.
There is also a need for a device that does not contact the blood so that anticoagulation countermeasures are not needed, and so that the potential for infection within the blood is reduced.
Accordingly, embodiments of the present invention are provided that meet at least one or more of the following objects of the present invention.
It is an object of this invention to provide a Direct Mechanical Ventricular Assist device that does not do damage to the heart as a result of its mechanical action on the heart.
It is a further object of this invention to provide a Direct Mechanical Ventricular Assist device that is technically straightforward to properly install on the heart.
It is an additional object of this invention to provide a Direct Mechanical Ventricular Assist device that may be installed on the heart and rendered functional by a procedure that is accomplished in a few minutes.
It is another object of this invention to provide a Direct Mechanical Ventricular Assist device that adequately seals against the heart, thereby enabling more precise operation of the device.
It is an additional object of this invention to provide a Direct Mechanical Ventricular Assist device that drives the systolic and diastolic action of the heart within precisely defined and controlled parameters.
It is a further object of this invention to provide a Direct Mechanical Ventricular Assist device that provides a healing environment within the body of the patient, including the heart itself.
It is another object of this invention to provide a Direct Mechanical Ventricular Assist device that provides measurements of the systolic and diastolic action of the heart to which it is fitted.
It is a further object of this invention to provide a Direct Mechanical Ventricular Assist device that provides an image of the functioning heart to which it is fitted.
It is a further object of this invention to provide a Direct Mechanical Ventricular Assist device that contains sensors and provides sensory feedback relative to the functioning heart to which it is fitted.
It is another object of this invention to provide a Direct Mechanical Ventricular Assist device that can provide electrical signals to the heart to pace the systolic and diastolic functions thereof.
It is an object of this invention to provide a Direct Mechanical Ventricular Assist device that has no direct contact with circulating blood, thereby reducing the risk for thrombogenic and bleeding complications, decreasing the potential for infection of the blood, and eliminating the need for anticoagulation that has many serious complications, especially in patients with serious cardiovascular disease and recent surgery.
It is another object of this invention to provide electrophysiological support, such as pacing and synchronized defibrillation, that can be integrated with mechanical systolic and diastolic actuation.
It is another object of the present invention to provide a DMVA device that can augment cardiac function without any surgical insult to the heart and/or great vessels.
It is another object of the present invention to provide a DMVA device that can put the heart to rest so that it can heal itself from an acute insult while having an improved flow of oxygenated blood.
It is a further object of the present invention to provide a DMVA device having a detachable liner, which can thus enable the DMVA device to be removed from the patient with no trauma to the heart of the patient.
It is a further object of the present invention to provide a DMVA device having a therapeutic liner or seal, thereby enabling the direct administration of therapeutic agents to the heart of the patient.
It is a further object of the present invention to provide a DMVA device that allows dynamic monitoring of the operation thereof, and the resultant right ventricle and left ventricle actuation, to permit optimization of pump function of the heart.
It is a further object of the present invention to provide a DMVA device comprising a volumetrically regulated fluid drive utilizing drive flow/volume sensors integrated with sensing and analysis of DMVA device/biventricular interactions, thereby enabling optimization of resulting biventricular actuation.
It is a further object of the present invention to provide a DMVA device comprising a pressure regulated drive that regulates DMVA drive mechanics independent of volume, utilizing analysis of drive pressure dynamics integrated with analysis of volume changes with the cup and within the right and left ventricles.
It is an object of this invention to provide an apparatus for delivering at least one therapeutic agent directly and preferentially to a desired tissue to be treated.
It is an object of this invention to provide a Direct Mechanical Ventricular Assist apparatus for delivering at least one therapeutic agent directly and preferentially to a heart while providing assistance to the pumping function of such heart.
In accordance with the present invention, there is provided a therapeutic apparatus for delivering at least one therapeutic agent directly and preferentially to a desired tissue to be treated, said apparatus comprising at least one membrane comprised of means to deliver said agent to said desired tissue, said membrane being in contact with at least a part of said desired tissue to be treated; and at least one shell surrounding said membrane, said shell isolating said membrane from tissues other than said desired tissue to be treated.
In embodiments of the invention, the therapeutic agent may be selected from the group consisting of anti-inflammatory agents, gene therapy agents, gene transfer agents, stem cells, chemo-attractants, cell regeneration agents, ventricular remodeling agents, anti-infection agents, tumor suppressants, tissue and/or cell engineering agents, imaging contrast agents, tissue staining agents, nutrients, and mixtures thereof.
In one embodiment, the membrane may be formed as a liner in which the therapeutic agent is impregnated. The liner may comprise multiple layers separated by a gap, which contains the therapeutic agent. In one embodiment, the liner may be detachable from the rest of the apparatus.
In another embodiment, the apparatus is a direct mechanical ventricular assistance apparatus comprising a liner in which the membrane is formed. In an alternate embodiment, the direct mechanical ventricular apparatus comprises a seal containing the therapeutic agent, either impregnated therein, or contained in a cavity therein. The seal may be detachable from the rest of the apparatus. In a further embodiment, the direct mechanical ventricular apparatus may comprise at least one sensor measuring at least one parameter.
The DMVA device of the present invention described above is advantageous because compared to other prior art devices, it precisely drives the mechanical actuation of the ventricular chambers of the heart without damaging the tissue thereof, or the circulating blood; it may be installed by a simple procedure that can be quickly performed; it provides functional performance and image data of the heart; and it can provide electrophysiological monitoring and control of the heart, including pacing and cardioversion-defibrillation electrical signals to help regulate and/or synchronize device operation with the native electrical rhythm and/or contractions thereof. As a result of the invention, a greater variety of patients with cardiac disease can be provided with critical life-supporting care, under a greater variety of circumstances, including but not limited to, resuscitation, bridging to other therapies, and extended or even permanent support. Finally the device can support the heart through a period of acute injury and allow healing that results, in some conditions, to full recovery of unsupported heart function, which has not been achieved by any other device.
The invention will be described by reference to the following drawings, in which like numerals refer to like elements, and in which:
The present invention will be described in connection with a preferred embodiment, however, it will be understood that there is no intent to limit the invention to the embodiment described. On the contrary, the intent is to cover all alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.
For a general understanding of the present invention, reference is made to the drawings. In the drawings, like reference numerals have been used throughout to designate identical elements.
In describing the present invention, a variety of terms are used in the description. Standard terminology is widely used in cardiac art. For example, one may refer to Bronzino, J. D., The Biomedical Engineering Handbook, Second Edition, Volume I, CRC Press, 2000, pp. 3-14 and 418-458; or Essential Cardiology, Clive Rosendorf M.D., ed., W.B. Saunders Co., 2001, pp. 23-699, the disclosures of which are incorporated herein by reference.
As used herein, the term Cup is meant to indicate the Direct Mechanical Ventricular Assist device of the present invention, such device comprising a cup-shaped outer shell. The terms Cup, DMVA Cup, DMVA device, and DMVA apparatus are used interchangeably in this specification and are intended to denote the overall Direct Mechanical Ventricular Assist device of the present invention in its various embodiments, unless specifically noted otherwise.
As used herein, the abbreviation LV is meant to denote the term “left ventricle”, or “left ventricular” and the term RV is meant to denote the term “right ventricle, or “right ventricular”, as appropriate for the particular context.
“Right” and “left” as used with respect to the ventricles of the heart are taken with respect to the right and left of the patient's body, and according to standard medical practice, wherein the left ventricle discharges blood through the aortic valve into the aorta, and the right ventricle discharges blood through the pulmonic valve into the pulmonary artery. However, the Figures of the instant application, which depict the present invention and the heart contained therein are taken as viewed facing the patient's body. Accordingly, in such Figures, the left ventricle depicted in any such Figure is to the right, and vice-versa just as is done in convention when viewing radiographs and figures of related organs in the medical field. For the sake of clarity in such Figures, the left and right ventricles are labeled “LV” and “RV”, respectively.
As used herein, the terms “normal heart”, and “healthy heart” are used interchangeably, and are meant to depict a nominal, unafflicted human heart, not in need of DMVA assistance or other medical care.
As used herein, the term cardiac function is meant to indicate a function of the heart, such as the pumping of blood in systemic and pulmonary circulation; as well as other functions such as healing and regeneration of the heart following a traumatic event such as e.g., myocardial infarction. Parameters indicative of such functions are physical parameters, including but not limited to blood pressure, blood flow rate, blood volume, and the like; and chemical and biological parameters such as concentrations of oxygen, carbon dioxide, lactate, etc.
As used herein, the term cardiac state is meant to include parameters relating to the functioning of the heart, as well as any other parameters including but not limited to dimensions, shape, appearance, position, etc.
Critically important to the effective operation of DMVA is the continuous monitoring of changes in both right and left ventricular geometry (e.g. RV and LV end systolic and end diastolic volumes and-dimensional characteristics); 2) Ventricular dynamics (e.g. dynamic changes in chamber size, flow velocities, calculated pressure gradients and wall motion alterations throughout the DMVA cycle); 3) ventricular interactions (the dependent effects that items 1 and 2 have on one another; 4) device/cardiac interactions (e.g. the relationship between the device's actuating diaphragm and the epicardial surface throughout the actuating cycle, and e.g. the effects on conformational changes in ventricular wall contour, RV herniation).
Therefore, in one embodiment of the present invention depicted in
There are a number of control algorithms that the DMVA drive control will implement in achieving optimal cardiac actuation. For example, the ongoing changes in pulmonary and systemic vascular resistance and flow velocities occur during DMVA support are, in part, dictated by the right and left ventricles' response to external actuating forces. The force delivery from the drive can be adjusted in response to these measured variables to both achieve more favorable hemodynamics, and ensure force delivery is adequate to overcome the inherent resistance characteristics of the pulmonary and systemic vascular beds and valvular structures. The systolic and diastolic actuating forces need to be adjusted in order to achieve an optimal biventricular effect. These forces are adjusted (change in pressure/time and/or change in volume/time) to effect incremental parts of both the systolic and diastolic actuating phases. Some generic examples of such drive dynamic optimization are explained in the following paragraphs.
The early part of systolic actuation primarily focuses on right ventricular dynamics. Visualization of the right ventricular chamber implies that early systolic compressive forces are relatively gentle and allow maximal compression of the right ventricle. Compression of the right ventricle must focus on avoiding and/or reducing the degree of right ventricular herniation that is the result of abrupt early systolic compression. Such RV herniation seen at the base (upper edge) of the device essentially allows blood to accumulate in that portion of the right ventricular free wall that is bulging outside of the device. Such herniation of blood is associated with equal reductions in pulmonary blood flow and overall reduced cardiac output as these reductions in flow are mirrored by reduced left ventricular filling.
The later half of the systolic actuation cycle focuses on maximum left ventricular compression, while avoiding excessive left ventricular compression. Some key characteristics of left ventricular compression include achieving that degree of left ventricular compression, which results in the greatest ventricular ejection without allowing endocardial (inner) surfaces of the heart to touch one another. If the LV is not adequately compressed, blood will accumulate within the lungs and lead to pulmonary edema.
Both the absolute degree of systolic compressive force and the timing of systolic compression are altered in an effort to maximize left ventricular emptying characteristics. By following these principles, left ventricular forward flow is maximized (as evidenced by the greatest reduction in left ventricular volume during compression) while trauma associated with contact of the inner ventricular chambers is avoided. In other words, with optimal LV compression (systolic actuation) there is always a fluid medium between the inner surfaces of the heart. Excessive forces can lead to excessive displacement of left ventricular blood allowing the inner surfaces to touch one another and traumatize one another. Likewise, excessive forces during early compression result in herniation and friction between the right ventricular free wall and septum within the right ventricular chamber.
Similarly, right and left ventricular dynamics are monitored to insure optimal diastolic actuation. A fundamental principle of optimal DMVA assistance is accomplishing right and left ventricular diastolic actuation, while achieving maximal diastolic volumes. This is achieved by increasing the negative dP/dt (change in pressure/change in time) and/or dV/dt (change in volume/change in time) to achieve an optimal diastolic actuation that augments the rate of diastolic filling and overcomes the inherent otherwise negative (constrictive) effects of DCC, or any compression methods. Such diastolic actuation is adjusted to that point where maximal −dP/dt is achieved without allowing separation between the actuating diaphragm and epicardial surface of the heart.
Any separation of the actuating diaphragm from the epicardial surface of the heart indicates that the negative applied forces during that phase of the actuating cycle are too abrupt and need to be delivered in a more gradual fashion. Separation of the liner from the heart during diastolic actuation essentially removes the actuating force from the epicardium resulting in the heart growing passively and/or going in a non-assisted manner. The details of embodiments of the DMVA apparatus of the present invention comprising means for sensing of left and right ventricular chambers and the related changes/drive control algorithms in drive mechanics will be detailed to a greater extent subsequently in this specification.
The preferred material characteristics will also be further defined subsequently in this specification. However, general characteristics are provided in the following paragraphs. The optimal characteristics for the liner may best be generally described as that which has near “isotropic” behavior. In other words, the liner material acts on the ventricular muscle in a manner that allows the ventricular muscle to change its conformational shape in a manner that best follows the heart's natural tendencies. In this manner, the material does not “deform” the heart outside of a range dictated by the muscle's natural tendency to change conformation when such external forces are applied.
However, this is not to say that the heart is compressed in a manner that replicates the normal beating state. On the contrary, the systolic and diastolic conformational changes that result from DMVA actuation clearly differ to some degree from what one expects during contraction and dilatation of an otherwise normal functioning heart. However, it is important that the liner and Cup shell materials allow the myocardium to undergo such mechanically induced conformational changes in a manner that permits the muscle to deform based on its physical characteristics and tendencies. Less ideal materials lead to more potential trauma and have their own tendency to fold and deform in a manner that alters the heart's “natural” tendency and these types of material characteristics lead to myocardial injury.
The compliant nature of the device housing permits it to constantly change shape in response both to the actuating forces applied to the heart and changes in the heart's size and/or shape. This characteristic contributes to decreased ventricular trauma, ease of application as the housing can be deformed to fit through small incisions, and important dynamic conformational changes that constantly respond to the heart's changing shape. The housing of the device is constructed of a flexible material that has appropriate compliance and elastic properties that allow it to absorb the systolic and diastolic actuating forces in a manner that somewhat buffers the effect of the liner on the heart. (For example, abrupt reductions in drive fluid pressure are dampened such that cavitation and disengagement with the heart are avoided, and during systole, abrupt increases in drive fluid pressure are dampened such that bruising of the heart are avoided.) The unique qualities of this housing lessen the risk for inadvertent excessive forces to be applied to the heart at any time of the cycle. The shell conforms to the dynamic changes in the right and left ventricles throughout compression and relaxation cycles as well as overall, ongoing changes related to variances in heart size over time which occur as a consequence of continued mechanical actuation and related “remodeling” effects on the heart.
Sensor and Control Related Aspects of the Invention
The present invention also comprises a method for utilizing sensors and sensor data to (1) help install DMVA devices and to (2) assess cardiac performance under the influence of DMVA. The sensor data so obtained helps real-time verification that the device has been properly installed, and is operating properly and achieving desired cardiac performance. The sensory data also allows the operating parameters of the Cup to be adjusted in real time to respond to changing physiology of the patient's cardiovascular system. There are at least ten sensor and control related aspects to the present invention, all of which are described herein:
These aspects of the present invention will be described briefly here in the specification, and in more detail subsequently, with reference to the drawings.
Invention aspect 1: A method for using sensor data in conjunction with cardiac assist devices is briefly described as follows, and subsequently described in detail with reference to
Step 5: Actuate DMVA device using predetermined settings from steps 1 and 2.
Invention Aspect 2: Sensor data. The sensor data collected in Step 6 of the preceding method of Invention Aspect 1 preferably includes without limitation the types of data listed below. The specific sensor types and sensor locations (also see Invention Aspect 5) will subsequently be described in more detail in conjunction with
Invention Aspect 3: DMVA feedback control parameters. The above sensor data can be used to control DMVA operation and cardiac performance. In the present invention these parameters preferably include without limitation the following device control parameters, which will subsequently be described in more detail with reference to
Invention Aspect 4: DMVA feedback control methods and algorithms. The above sensor data of invention aspect #2 can be analyzed to control DMVA operation and cardiac performance in multiple ways including without limitation the following device control methods and algorithms, some of which will subsequently be described in more detail with reference to
Invention Aspect 5: Specific sensor types and sensor locations. Specific sensor types to obtain DMVA operational data and patient data include the following, which are subsequently described in more detail in this specification with reference to FIGS. 6A-13:
Specific sensor locations to obtain DMVA operational data and patient data include the following:
Invention Aspect 6: Contrast agents to enhance sensor sensitivity and specificity. The minimal dimensions of components of the DMVA device, such as the Cup liner, make such components difficult to image with ultrasound, MRI, and X-ray imaging procedures. In further embodiments of the present invention, imaging contrast agents are incorporated into critical components of the Cup to enhance the images obtained thereof. Such imaging contrast agents may include ultrasonic contrast agents, magnetic resonance imaging contrast agents, and radiopaque contrast agents, and are subsequently described in more detail in this specification with reference to
Invention Aspect 7: Sensor interfaces. The sensors integrated into the DMVA device can be linked to external data recording, data analysis, and data reporting systems in several ways, including without limitation the following means:
Invention Aspect #8: User interfaces. The user interfaces used with the present invention include without limitation the following means to provide information to the health care professional:
Invention Aspect #9: Sensor data recording and analysis capabilities. Specific data recording and analysis capabilities of the present invention are dependent upon the type of data being recorded and analyzed and include the following, to be described subsequently in detail in this specification with reference in particular to FIGS. 6A-15:
Invention Aspect 10: Specific device performance measures appropriate for sensing. Critical DMVA system performance parameters which are indicative of the quality of system performance and suitable for measurement include the following, to be described subsequently in detail in this specification with reference in particular to FIGS. 6A-15:
In summary, therefore, the DMVA device of the present invention in its numerous embodiments is a device that provides mechanical assistance to the ventricles of the heart, comprising electronic digital and/or analog and/or image sensing means to sense operational parameters thereof or of the myocardium; data acquisition means to acquire data on such parameters; computing means to analyze such parametric data, and to derive and/or select algorithms to control to drive fluid volume and/or pressure of the drive fluid thereof, thereby controlling the driving of the ventricles of the heart. With regard to physical structure, the DMVA device of the present invention in its numerous embodiments comprises an integrated drive system that controls the pressure and/or flow rate of drive fluid delivered thereto and withdrawn therefrom, and a shell and liner which contact and displace the ventricles of the heart in an atraumatic manner, i.e. a manner that does not cause trauma to the tissue of the heart.
The DMVA device of the present invention will now be described in detail, with reference to
It is to be understood that the
In the following description of
Several preferred features of the DMVA apparatus and method of the present invention are illustrated in curve 1020 of
Another preferred feature of the DMVA apparatus and method is the ability thereof to compress the left ventricle to a lesser end systolic volume 1024 than the normal heart LV end-systolic volume 2024. Thus, although in one embodiment, the cardiac cycle in DMVA assistance begins at a lower LV end diastolic volume 1022, it achieves a correspondingly lower LV end systolic volume 1024, so that the total blood volume displaced from the left and right ventricles (stroke volume) is comparable to that of a normal heart. In spite of this further compression of the heart by one embodiment of the DMVA device, such device achieves the compression in a manner that does not significantly bruise of abrade the heart, as will be described subsequently in this specification.
In the embodiment depicted in
Such sensors, algorithms, and features enable the DMVA device and method to be adapted as required to provide assistance to an unhealthy heart in a manner that is optimal for the particular disorder afflicting such heart.
Curve 1030 (dashed line) depicts the LV volume of the assisted unhealthy heart, which is provided assistance by the DMVA device. The DMVA device is fitted and programmed to operate at a lesser end diastolic volume 1032 than the end diastolic volume 3032 of the unhealthy heart, which benefits the unhealthy heart by reducing myocardial stretch and/or wall tension. The embodiment depicted in
In the DMVA embodiment depicted in
In the embodiment depicted in
Thus, as indicated by the sequence of
Subsequently, active diastolic assistance is provided to the right ventricle, as for the left ventricle assistance described and shown in
Curve 1040 depicts the RV volume of the assisted unhealthy heart, which is provided assistance by the DMVA device. In the embodiment depicted in
Another preferred feature of the DMVA apparatus and method is the ability thereof to pressurize the left ventricle to a greater peak systolic pressure 1054 than the normal heart LV maximum systolic pressure 2054. Yet another preferred feature is the ability to attain greater relative increases and decreases in pressure (dP/dt) as indicated by slopes 1056 and 1058 respectively, when compared to those of a healthy heart. Such capabilities enable the DMVA device to be more effectively matched to the requirements of the particular unhealthy heart needing assistance but are also adjusted to the lowest incremental rise required in order to reduce the likelihood of cardiac injury. The DMVA apparatus of the present invention is thus atraumatic with respect to the heart.
In the embodiment depicted in
Another feature of the DMVA apparatus and method is the production of pressure in the right ventricle to a greater peak systolic pressure 1064 than the normal heart RV maximum systolic pressure 2064. It can be seen that the pressure difference 1065 between these peak systolic pressures is greater than the corresponding difference 1057 between the peak systolic pressure 1054 of the assisted heart and the peak systolic pressure 2054 of the normal heart (see
In the embodiment depicted in
With regard to the timing of blood flows of the DMVA assisted heart, it can be seen by reference to
It is to be understood that plots 1098 and 1099 of
Referring again to
In one embodiment to be described subsequently in this specification, the ventricular emptying and ventricular filling blood flows are inferred from a sensor in the DMVA device, which measures the flow of drive fluid delivered to and from such device. In another embodiment, such flows are detected by sensors in the pulmonary artery (RV) and descending aorta (LV). (In the latter case, correction factors must be applied to account for blood flow out of the brachiocephalic, left common carotid, and left subclavian arteries.)
It can also be seen that in the preferred embodiment, the DMVA apparatus of the present invention applies a force uniformly to the heart around the circumference thereof, such that the heart is compressed in a manner that renders the heart with a substantially circular cross section and with a minimum diameter at the plane defined by line 2E-2E of
In instances where such excessive compression is sustained over a number of cycles, and particularly if the DMVA Cup 100 is undersized for the particular heart 30, misalignment of the heart within the Cup may occur as depicted in
In the present invention, the basic design of the Cup completely encompasses the heart from the atrio-ventricular groove (A-V groove) to the apex of the heart. Such a construction affords several advantages. A first advantage, enabled by liners of the present invention working with the Cup shell of the present invention, is the ability of the internal liner to compress or dilate the heart with a motion and force that is perpendicular to the heart tissue as previously described. A second advantage of the Cup's dynamic geometry of the present invention is the ability of the device to act and conform to both right and left ventricles in both systolic and diastolic assist, thereby supporting both pulmonary and systemic circulation. A third advantage is the ability of the device to better maintain both right ventricle and left ventricle function.
The Cup's dynamic geometry, and the fluid drive control means of the DMVA device of the present invention further provide for a full range of compression of the heart during systole, and a full range of expansion of the heart during diastole. This capability enables the DMVA device to provide a full range of Systolic Pressure-Volume Relationships and Diastolic Pressure-Volume Relationships that can be incorporated into drive control algorithms and result in optimal RV and LV pump performance. The present invention also provides total circulatory support without direct blood contact, thereby decreasing the risk of thromboembolic complications including clotting, strokes, and other associated severe morbidity, and in some cases death, as well as significant blood cell lysis, which can adversely affect blood chemistry and patient health. This feature also eliminates the need for anti-coagulation drugs which reduces the risk for bleeding.
The present invention is a device that can be placed more rapidly than other existing devices from the start of the procedure, and therefore enables the unique ability to acutely provide life-sustaining resuscitative support, as well as continued short to long term support, as deemed necessary. All other cardiac assist device products (approved or in clinical trials) known to the applicants require surgical implantation with operative times that far exceed the ability of the body to survive without circulation. Physicians will welcome a device that can be placed when routine resuscitation measures are not effective. The number of failed resuscitations in the U.S. annually is estimated to be on the order of hundreds of thousands. The device of the instant invention can support the circulation indefinitely as a means of bridge-to-recovery, bridging to other blood pumps, bridging to transplant, or long-term total circulatory support.
The present invention utilizes a seal design that facilitates the sealability and long-term reliability of the seal. Specific critical seal design features include the seal length, thickness, shape, and durometer; and the location of the seal against the heart at the atrio-ventricular (AV) groove thereof. Additionally, one embodiment of the present invention utilizes a seal material that promotes the controlled infiltration of fibrin, which further improves the sealability and long-term reliability of the seal. Embodiments of the present invention also utilize a liner material that promotes the controlled infiltration of fibrin, which further improves diastolic action and helps to minimize motion of the liner against the heart, which further minimizes abrasion between the liner and heart tissues. In all instances, the degree of infiltration of fibrin is limited, so the DMVA Cup can be easily removed, once the patient has recovered or can safely be bridged to another therapy.
In a further embodiment, the present invention also utilizes a liner that is biodegradable and/or one that becomes permanently attached to the heart's surface (with or without biodegradable properties) such that the device can be removed by detaching the housing from the liner and the liner left in place. Such a liner can then instill favorable mechanical properties to the heart and/or provide drugs or other therapies (e.g., gene therapy etc. as described in greater detail elsewhere in this specification). Such therapeutic agents include but are not limited to anti-inflammatory agents, gene therapy agents, gene transfer agents, stem cells, chemo-attractants, cell regeneration agents, ventricular remodeling agents, anti-infection agents, tumor suppressants, tissue and/or cell engineering agents, imaging contrast agents, tissue staining agents, nutrients, and mixtures thereof. Such agents may be diffused or embedded throughout all or part of the liner, or alternatively, such agents may be contained within a gap formed within a liner comprising a first membrane in contact with the DMVA drive fluid, and a second membrane in contact with the heart, wherein the second membrane is permeable to the agent or agents.
Thereby, the Cup serves a dual purpose of support of the heart for a period of time, and incorporating a therapeutic liner that is responsible for continued treatment of the underlying disorder. The liner can simply provide additional structural integrity through its mechanical properties, serve as a delivery agent, or a combination of both. Furthermore, the liner may simply be inert in its action once the Cup is removed, but provides a simple, safe means of device detachment without otherwise risking bleeding or trauma to the heart that might result if it is removed. In yet another embodiment, and in the case wherein the seal has been caused to be ingrown with myocardial tissue but the remainder of the liner is not ingrown with such tissue, removal of the liner is effected by separation from the seal. Thus only the seal will be left attached to the heart after Cup removal.
Many existing cardiac assist devices, such as Left Ventricular Assist Devices (LVADs) require surgically perforating the cardiac chambers and/or major vessels. The present invention eliminates the need to perforate the heart or major vascular structures, and provides the ability to easily remove the device, leaving no damage to the heart and circulatory system once the heart heals and cardiac function is restored, or when the patient can safely be bridged to another therapy.
Existing cardiac assist devices, such as Left Ventricular Assist Devices (LVADs), which include axial flow pumps, produce blood flow that is non-physiologic and not representative of physiological pulsatile blood flow. The present invention avoids this condition and creates a near-normal physiological pulsatile blood flow with blood passing through the natural chambers and valves of the native heart, which is more beneficial for vital end-organ function and/or resuscitation, particularly as it relates to restoring blood flow following a period of cardiac arrest or low blood flow.
Furthermore, the present invention provides a controllable environment surrounding the heart, which can be used to apply pharmaceutical and tissue regeneration agents, even at localized concentrations that would not be tolerated systemically. This can be accomplished with or without use of a cup liner that is left on the heart following device removal, depending on the needs of the patient.
Furthermore, the present invention is able to augment heart function as is required to create and maintain required hemodynamic stability in a manner that is synchronized with the heart's native rhythm and in a manner that can alter the native rhythm toward a more favorable state. The purely complimentary nature of this support relieves the stress on the heart and promotes its healing.
As previously described, it is known that application of forces to the heart can cause potentially serious, irreversible damage to the heart by fatiguing and severely bruising the heart muscle, which can ultimately prevent it from functioning. The present invention avoids this very serious and potentially life-threatening condition by controlling the direction of forces applied to the heart and by controlling the magnitude of the difference between adjacent forces applied to the heart.
In operation of prior art device 2, a fluid is pumped into cavity 6, thereby displacing liner 10 inwardly from shell wall 4. This displacement forces ventricle wall 40 inwardly a corresponding displacement, thereby resulting in systolic action of the heart. However, it is noted that operation of the prior art device produces several effects that are undesirable. In
This displacement is a consequence of several factors relating to the manner in which the liner 10 is joined to the shell wall 4 and to the properties of the liner material, which can produce localized non-uniformities in the stretching of the liner. The resulting displacement of point 16 and point 46 away from each other, and point 18 and point 48 away from each other produces localized shear stresses in these regions, which is very undesirable as previously indicated. In addition, such displacement also results in slippage of the liner along the surface of the ventricle wall, which over time can result in the undesirable abrading of the surface of the ventricle wall.
It is also known that there are shear stresses created along the circumferential direction of the ventricle wall, i.e. in the horizontal direction in the ventricle wall. Without wishing to be bound to any particular theory, applicants believe that these stresses are due to the tendency of the liners of prior art devices to self-subdivide during systolic action into nodes, wherein uniform portions of the liner are displaced inwardly, divided by narrow bands of the liner that are displaced outwardly. In one embodiment described in U.S. Pat. No. 5,119,804 of Anstadt, four such nodes are observed to be present when the device is operated without being fitted to a heart.
It is also apparent that regions 42 and 44 of ventricle wall 40, which are contiguous with upper region 12 and lower region 14 where elastic liner 10 is joined to wall 4, are subjected to intermittent high bending and shear stresses as a result of the repeating transitions between systolic and diastolic action of the device 2. Such intermittent bending and shear stresses can fatigue the heart tissue in these regions 42 and 44, and are thus clearly undesirable.
In the preferred embodiment, liner 510 is provided with an upper rolling diaphragm section 520 and a lower rolling diaphragm section 570, the effect of which is to apply uniform pressure (positive or negative) to the surface of the heart that substantially eliminates stresses in cardiac tissue that otherwise result from the action of prior art devices previously described. In operation, liner 510 is completely unloaded and the action of the working fluid on the heart is purely hydrostatic and normal to the wall 40 thereof. In other words, this embodiment of the present invention prevents the formation of substantial forces within the heart muscle by applying forces to the heart that are perpendicular to and uniform over the surface of the heart. This embodiment also ensures that the magnitude of the difference between adjacent forces is very small, as the fluid pressure within cavity 310 is isotropic. The use of such rolling diaphragm, as well as preferred liner materials to be subsequently described in this specification, eliminate the formation of shear forces within the heart muscle which leads to bruising damage to the heart tissue which in turn leads to muscle fatigue and potential failure of the heart. Thus the DMVA apparatus of the present invention is atraumatic, i.e. the apparatus does not inflict any injury upon the heart.
Rolling diaphragm sections 520 and 570 at the top and bottom of liner 510 are intended to reduce shear stresses in cardiac tissue that otherwise would result from the action of the DMVA Cup 100. Regardless of how elastic the material chosen for the liner 510 is there will be some stress induced in cardiac tissue if the prior art liner configuration is used. As described previously, this is because there will be some central axis where there is no vertical motion (slip) or shear stress relative to the adjacent heart wall, but above and below this axis the liner will expand during systole and contract during diastole while the heart wall will not change in exactly the same manner. Thus, the only way known to the applicants to reduce this lateral shear stress is to create a situation where the liner is completely unloaded and the force of the working fluid on the heart is purely hydrostatic, or normal to the surface. This is a critical capability of one DMVA device of the present invention.
The rolling diaphragm geometry follows the approach used in traditional rolling diaphragm pumps and fluid-to-fluid isolators. The design also greatly reduces stress concentrations at the extreme upper and lower points where the liner 510 attaches to shell 110, thus increasing the reliability of liner 110, further enabling the use of materials that may previously not have been considered because of their susceptibility to fatigue failure in a prior art liner configuration.
Referring again to
In one embodiment, rolling diaphragm liner is directly bonded to DMVA Cup shell wall 112 at upper section 520 and lower section 570 thereof.
As a result of such liner structures for upper joint region 512 and lower joint region 514, the maximum deflection of rolling diaphragm liner 510 at the upper joint region 512 and lower joint region 514 is reduced. Stated another way, the bending of the diaphragm at joint regions 512 and 514 is distributed over a larger length of the rolling diaphragm liner 510. The effect of this design is to reduce the bending strain at any one point in the diaphragm 510 as it is actuated. Reducing the bending strain substantially increases the life of diaphragm 510 and therefore significantly improves its reliability.
Even at the maximum displacement of liner 510, it can be seen that at the interstice 8 of liner 510 and ventricle wall 40, point 316 in liner 510 and point 46 in ventricle wall 40 have remained substantially contiguous with each other, and point 318 in liner 310 and point 48 in ventricle wall 40 have remained substantially contiguous with each other; and that the radius of curvature in upper region 42 and lower region 44 of ventricle wall 40 is substantially greater than such radius of curvature resulting from the use of the prior art device as depicted in
Referring again to
In the preferred embodiment of apparatus 102, liner 510 is deployed against ventricle walls 40 by a progressive rolling action as indicated by arrows 516 and 518. In contrast, prior art DMVA devices deploy the liner against the ventricle walls exclusively by an elastic and non-isotropic stretching of such liner, resulting in shear forces and/or abrasive slippage of such liner along the ventricle walls, as previously described. Thus the rolling diaphragm liner 501 of one embodiment of apparatus 102 has significant advantages over prior art DMVA devices.
Referring again to
A more detailed description of Invention Aspect 1, which is a method for using sensor data in conjunction with cardiac assist devices, is now presented.
In step 902, the patient's pre-DMVA cardiovascular state of health is established, which provides a baseline from which to assess improvement in patient health as a result of DMVA. Subsequently, in step 904 required performance improvement objectives are established. In step 904, the patient's existing pre-DMVA cardiovascular state of health is compared to normal cardiac performance for the patient's population group and clinical condition. The difference between the patient's baseline performance and normal population group and clinical condition is used to help establish DMVA performance improvement objectives.
Step 906 is an optional pre-check of the DMVA device to verify critical aspects of performance. In step 908, the DMVA device is surgically installed in the patient. The DMVA device is subsequently actuated using predetermined settings in step 910, based upon data from steps 902 and 904.
In step 912, the DMVA device is operated, and sensor data is collected to verify such factors as follows: proper positioning of the DMVA device on the heart; proper sealing of the DMVA device against the heart; the absence of excessive fluid between the heart and the inner wall of the DMVA device, and that the DMVA control parameters are achieving the desired systolic and diastolic action. Sensors and data acquisition means for performing such data collection are described later in this specification.
In step 914, acquired data on the performance of the DMVA Cup device, and on the condition of the patient are analyzed by computer/process controller means. Included in step 914 is the integration of other cardiovascular data (e.g. blood pressure), other cardiovascular devices (e.g. pacemakers, balloon pump, etc.) and/or the effects of initiation of other features incorporated into the Cup such as e.g., pacing electrodes.
Initial DMVA control parameters, such as the volume and timing of fluid delivery to the DMVA Cup, may not achieve optimum hemodynamic performance. Thus in step 916, the DMVA control parameters are adjusted to achieve desired hemodynamic performance (e.g., achievement and verification of balanced RV and LV outputs, optimization of such outputs to ensure adequate overall cardiac output, and optimization to avoid cardiac injury, thereby ensuring atraumatic operation of the DMVA apparatus). Such adjustment may be an iterative process as indicated by step 918, wherein steps 912, 914, and 916 are repeated. In such an iteration, additional sensor data is collected (a second step 912) and analyzed (a second step 914) after the initial adjustment of DMVA control parameters to determine if additional adjustment (a second step 916) is required. This sub-process (step 918) is repeated until desired hemodynamic performance is achieved.
In one embodiment of method 900 of
With the DMVA device properly installed in the patient, and operating at an optimal steady-state condition, all surgical procedures are completed and the patient is placed into recovery in step 922. The condition of the patient and the performance of the DMVA device is then monitored as an ongoing process, with further intervention or adjustment of DMVA parameters made as required in step 924. Specific methods and apparatus to monitor the cardiac performance and overall condition of the patient are well known and are described elsewhere in this specification.
More detailed descriptions of Invention Aspect 4, which is directed to methods and algorithms for specific feedback control of the DMVA Cup are now presented, with reference in particular to
Diastole is then initiated in step 944 by applying vacuum to the DMVA drive fluid at a low level (e.g. −100 mm Hg) for 0.5 seconds. Such vacuum is maintained until data input to the DMVA controller indicates that the RV and LV are 90% refilled. The vacuum is then released in step 948. In an optional step 950, the vacuum is sustained for a brief additional period in order to adjust the size of the dilated heart to a slightly larger state.
A more detailed description of Invention Aspect 5, which is directed to Specific sensor types and sensor locations is now presented with reference to
In the DMVA Cup 103 of
In operation, sensor 1210 provides an approximately conical field of view 1299 of heart 30, resulting from the propagation of ultrasound as indicated by arcs 1298, and the reflection of such ultrasound back to tip 1212 by the objects within shell 112. Such reflected ultrasound is used by data acquisition and analysis means to provide images of the DMVA Cup shell 110, cavities 117 and 119, liner 114, and right and left ventricles 34 and 32 of heart 30. In particular, ultrasonic probe 1210 enables the capturing, observation, and measurement of changes in LV and RV geometry, LV and RV volume, relative RV/septal and LV/septal interactions, cup-epicardial interactions, and localized blood flow velocities in the ventricles, atria, and aorta, and evaluations of these variables to achieve optimal DMVA drive settings under a variety of physiologic conditions.
Reference may be had to the volume, pressure, and flow relationships of
In yet another embodiment of the present invention depicted in
In yet another embodiment of the present invention depicted in
In a yet further embodiment of the present invention, the ultrasound image is not provided by a single sensor such as sensor 1210, but is provided by one or more pairs of individual piezoelectric crystals that are placed on either side of the heart, and utilize time-of-flight measurements and simple linear echo measurements to detect the position of tissue/fluid interfaces relative to themselves. Referring to
In yet another embodiment of the present invention (not shown) an external ultrasound probe is used as above.
Referring again to
Referring again to
Referring again to
In yet another embodiment of the present invention (not shown) an external MRI coil is used as in the foregoing description.
The quality of MR images is also dependent upon the strength of the static field used by the MRI system. Higher field strength systems (e.g. 3.0 or 4.5 Tesla field strength) provide greater image quality than lower field strength systems (e.g. 0.5 or 1.5 Tesla field strength). However, the maximum signal provided by the MRI coil of the present invention enables images to be obtained in lower strength with image quality equivalent to the quality of image obtained in higher strength systems. This is particularly important since lower strength “open MR” systems enable the physician to interact with patient during MRI, and these systems would be one type of MRI system used to help guide the installation and assessment of the DMVA Cup. The signal from embedded coil 1230/1240 can be obtained through a connection such the type illustrated in
Referring again to
Referring again to
In yet another embodiment of the present invention, an external X-ray imaging procedure, such as Conventional X-radiography or Computed Tomography, is used to collect the following types of data during and following installation of the Cup: anatomical data, such as motion of the heart wall, fit of the Cup to the heart; hemodynamic data, such as blood flow rate, and/or blood pressure; and functional data, such as cardiac ejection fraction.
In an embodiment where the DMVA control unit device is positioned outside the body, electro-physiological signals are delivered to the DMVA control device either percutaneously through the skin such as with a puncture, or transcutaneously through the skin such as via telemetry pulses.
In an embodiment where the DMVA control unit device is positioned inside the body, electro-physiological signals are delivered to the DMVA control device through electrical conductors (not shown), optical wave guides (not shown), such as fiber optic cables (not shown), or via telemetry pulses.
In yet another embodiment of the present invention, electrical sensors 1262-1274 can be cardiac pacing electrodes, electrical sensors, or both, placed on or within the liner 611 of Cup 105, or on or within shell wall 112 of Cup 105, for patients who require active management of their cardiac disrhythmia. Electrodes and/or sensors 1262-1274 can be used without limitation in the following ways:
In yet another embodiment of the present invention, electrical sensors can be cardioversion-defibrillation electrodes, electrical sensors, or both, placed on or within the Cup liner or Cup wall, for patients at risk of fibrillation or unnatural heart rhythm. These electrodes can be used without limitation in the following ways:
In yet another embodiment of the present invention, a pacemaker (not shown) and/or cardioverter-defibrillator (not shown) are integrated directly into the DMVA control device.
Additionally, the array of electrodes 1281-1287 can be used to apply complex cyclic three-dimensional electrical stimulation in a phased manner to heart tissues. Such stimulation can be used to optimize synchronization of the natural rhythm of the heart with the DMVA device, or to stimulate the heart slightly out of phase with the DMVA device in the use of a training algorithm to be described subsequently.
In one embodiment electrodes 1281-1288 disposed on the inner surface of the Cup shell wall 112 are small ‘dots’. In another embodiment, electrodes 1281-1288 are larger ‘patches’. In yet another embodiment, electrodes 1281-1288 are formed from a network of filaments, or a combination of dots, patches, and/or filaments. Referring again to
Electrodes 1281-1288, or electrodes in other configurations as previously described are applied to the liner via adhesive, mechanical attachment, or by being co-molded on the internal surface of the liner. Electrode material may be a biocompatible metal such as titanium or gold, or it may be a conductive polymer such as polypyrrole, or a carbon-doped or metal-doped non-conductive polymer, or a conductive paste containing a fine metal powder or other conductor. In one embodiment, electrodes 1281-1288, and/or conductors 1289, and/or ring 1280 are applied to the inner surface of Cup shell wall 162 by use of a direct circuit writing method and apparatus, such as a MicroPen applicator manufactured by OhmCraft Incorporated of Honeoye Falls, N.Y. Such an applicator is disclosed in U.S. Pat. No. 4,485,387 of Drumheller, the disclosure of which is incorporated herein by reference. The use of this applicator to write circuits and other electrical structures is described in e.g. U.S. Pat. No. 5,861,558 of Buhl et al, “Strain Gauge and Method of Manufacture”, the disclosure of which is incorporated herein by reference. In a further embodiment, a protective overcoating is applied to such electrodes, conductors, and ring, or to the entire inner surface of Cup shell 160.
In another embodiment electrodes 1281-1288, and/or conductors 1289, and/or ring 1280 are manufactured as an integral part of the Cup wall 162, and are electrically conductive through the entire thickness of the Cup wall material. Electrodes 1281-1288 may take the form of ‘dots’, ‘patches’, filaments, or a combination thereof.
In a further embodiment, Cup shell wall 162 is sufficiently porous and/or thin such that electrical conduction will occur through an otherwise non-conductive shell wall material.
Depending upon the configuration of electrodes 1281-1288, the material, placement, and the method of manufacture, electrical conductors/leads 1289 may be on the inner or outer surface of the shell wall 162, or may be embedded therein. Leads 1289 may be made of electrically conductive wire, or of an electrically conductive native polymer or a non-conductive native polymer that is doped with carbon, metal, or other electrically conductive additive, or a conductive paste containing a fine metal powder or other conductor, as previously described. Leads 1289 may connect one or more electrodes individually or in combination. Leads may be further coated or treated or shielded in order to prevent leakage of electrical current and to minimize EMI interference with sensor signals. Such coatings and treatments are described e.g., in U.S. patent application Ser. Nos. 10/384,288, and 10/369,429, the disclosures of which are incorporated herein by reference.
In general, leads 1289 are collected in a region of the Cup shell 160 that minimizes flexure of such leads 1289 and any adverse effect on the liner or on the heart. In the preferred embodiment, leads 1289 are collected near the apex 161 of the Cup. A connector (not shown) may be used to provide ease of Cup installation, but in one embodiment there is no connector per se, in order to eliminate risk of circuit degradation or unintended cross-talk between electrodes.
In another embodiment (not shown), operational data on the patient and on the performance of the DMVA device is provided by externally positioned electrophysiological sensors/electrodes. These sensors/electrodes can include without limitation skin mounted EKG sensors and pacing electrodes, skin mounted cardioversion defibrillation (CD) sensors and electrodes, or temporary pacing and CD leads such as percutaneously installed or transesophageally delivered sensors and electrodes. These sensors and electrodes can be used without limitation in the following ways:
Other arrangements of such electrodes will be apparent to those skilled in the art. Such arrangements may include those performed in standard practice of electrocardiography, which is described in Bronzino, J. D., The Biomedical Engineering Handbook, Second Edition, Volume I, CRC Press, 2000, pp. 3-14 and 418-458; and in Essential Cardiology, Clive Rosendorf M.D., ed., W.B. Saunders Co., 2001, pp. 23-699.
The purpose of any DMVA device is to maintain cardiac output. This output may be characterized by stroke volume (the volume of blood expelled from the heart during each systolic interval) and pressure at which this volume is delivered from the heart. In yet another embodiment of the present invention, working fluid pressure and/or flow rate sensors are integrated into the Cup and/or Cup drive assembly to collect data that can be used to control the inflation/deflation of Cup liner, which in turn enables control of stroke volume and blood pressure.
Alternately, the volume of working fluid delivered to Cup 108 can be measured directly by placing a flow rate sensor(s) 1269 within liner inflation/deflation duct 322 to measure the rate of flow of working fluid into or out of Cup 108 as indicated by arrows 399. Alternately, the flow of working fluid into Cup 108 can be determined by calculating the volumetric displacement of pump 330. In one embodiment wherein pump assembly 330 of DMVA device 108 comprises a piston pump, such volumetric displacement is determined by multiplying the cross-sectional area of the bore 332 of pump cylinder 332 or of pump piston 334 by pump stroke 336 due to piston driver 338. It is to be understood that similar means can be used to determine volumetric displacement of other types of fluid pumping devices.
Sensor output from sensors 1261, 1263, 1265, and 1267, and/or other sensors described previously or subsequently in this specification, is delivered to the DMVA device control unit 1301, which in turn directs the inflation and deflation of the Cup liner 114 as required to provide the desired amount of cardiac output. In one embodiment, ultrasound sensors as described previously and shown in
In other embodiments, blood pressure is controlled in a number of ways, including the use of Cup working fluid flow rate sensors. The vascular structure of the body has a variable resistance to blood flow as the body opens and closes resistance vessels depending upon a variety of internal and external factors. Typically, resistance does not change much in a minute. However, a sudden change such as e.g. a precipitous decrease in ambient temperature will produce a very rapid change in resistance, due to such factors as the diameter, length, and geometry of arteries, veins, etc. which restrict the flow of blood. Therefore increasing or decreasing the rate of Cup liner inflation against this hemodynamic resistance will either increase or decrease systolic blood pressure, respectively. Likewise, increasing or decreasing the rate of Cup liner deflation against this hemodynamic resistance will either increase or decrease diastolic blood pressure, respectively. Since the rate of flow of working fluid into the Cup liner directly controls liner inflation and deflation, measurement and control of Cup working fluid flow rate sensors can also be used to control blood pressure. In yet another preferred embodiment, the Cup working fluid consists essentially of an electro-rheological fluid (e.g. isotonic saline) that provides a unique and easily detectable flow rate signature.
In another embodiment, blood pressure is controlled by use of Cup working fluid pressure sensors. Since Cup liner inflation or deflation is dependent upon the pressure at which the working fluid is delivered to or removed from the liners, it is possible to use measurement and control of DMVA working fluid pressure to control blood pressure. Specifically, the higher or lower Cup liner inflation or deflation pressures can be used to control systolic or diastolic blood pressure, respectively.
In the embodiment depicted in
Referring again to
In one such embodiment (not shown) a circumferential cavity connects an external source of pressurized therapeutic agent with a highly permeable center layer of the liner. In another embodiment, the size, shape, and surface energy of the cavity wall are designed to permit passive capillary movement of therapeutic agent from an external source to a highly permeable center layer of the liner. In a third embodiment, the same approach is taken, but with an active valve between the external source and the cavity, in order to control flow of therapeutic agent. In a fourth embodiment the size, shape, and surface energy of the cavity wall are designed to permit passive capillary movement of therapeutic agent from an external source to the highly permeable center layer of the liner, but the relative surface energy of the wall surface is controllable by external means in order to modulate flow of therapeutic agent.
In the embodiment depicted in
In the embodiment depicted in
In the embodiment depicted in
In one embodiment the Cup controller receives pressure data from sensors 1112-1126 depicted in
In the embodiment depicted in
In another embodiment depicted in
In another embodiment depicted in
In another embodiment depicted in
In yet another embodiment of the present invention (not shown), blood pressure and/or blood flow rate sensors located in the patient's circulatory system are used to provide data to the DMVA control system, or the physician, for use in controlling and operating the DMVA Cup. Such sensors may include, but are not necessarily limited to a catheter (such as a Swan-Ganz catheter) located in the patient's right atrium, right ventricle, or pulmonary artery. Alternatively, sensors can also be located within the descending aorta (measuring the pressure and/or flow rate of blood delivered from the left ventricle), or the right atrium or superior vena cava (measuring the pressure and/or flow rate of blood delivered to the right ventricle). Sensor measurements are fed back to the DMVA control unit, which in turn regulates Cup liner inflation and deflation to maintain desired blood pressure and flow rate, as previously described.
It is to be understood that additional sensors could be installed in the Cup assembly, or elsewhere within the body, and connected to the control unit. These sensors would include without limitation sensors for measuring tissue oxygenation (i.e. detection of ischemic tissues—particularly tissues undergoing silent ischemia), blood oxygenation, tissue temperature, or other physiological parameters. Additional physiological data obtained by conventional measurement means that could be used to control Cup operation include without limitation respiratory rate and body physical motion.
A more detailed description of Invention Aspect 6, which is directed to imaging contrast agents incorporated into critical components of the Cup to enhance the images obtained thereof is now presented with reference in particular to
In one embodiment, ultrasonic contrast agents are added to the surface of or imbibed into the liner of the Cup, making the thin liner much easier to visualize under ultrasonic imaging. Enhancing the liner image is critical to assess fit of the liner to the heart. One example of a suitable ultrasonic contrast agent is to ultrasound is ECHO-COAT® ultrasound echogenic coating from STS Biopolymers of Rochester N.Y. The thin, polymeric nature and very high ultrasonic contrast of this material lends itself well to the polymeric nature of the Cup and Cup liner. It is to be understood that any other component of the DMVA device could also be treated with ultrasonic contrast agent to enhance its image profile.
In another embodiment, ultrasonic contrast agents are incorporated into the working fluids used to inflate and deflate the Cup liners, to help visualize liner inflation and deflation performance. In yet another embodiment, ultrasonic contrast agents can also be incorporated into the blood flowing into and around the heart.
In similar embodiments of this particular invention (not shown), MRI contrast agents are utilized without limitation according to the following descriptions.
In one embodiment, MRI contrast agents are added to the surface of or imbibed into the liner of the Cup, making the thin liner much easier to visualize under magnetic resonance imaging. Enhancing the liner image is critical to assess proper fit of the liner to the heart. One example of a suitable MRI contrast agent is gadoliniurn. The thin and very high MR contrast of this material, and its ability to be easily attached to or imbibed into the polymeric Cup and Cup liner make this material a desirable choice. It is to be understood that any other component of the DMVA device could also be treated with MRI contrast agent to enhance its image profile.
In another embodiment, MRI contrast agents can be incorporated into the working fluids used to inflate and deflate the Cup liners, to help visualize liner inflation and deflation performance. In yet another embodiment, MRI contrast agents can also be incorporated into the blood flowing into and around the heart.
One example of an MRI contrast agent includes nano-particulate particles, including nano-magnetic particles. Nano-magnetic particles can be applied as thin-films (typically on the order of one micron in thickness) to objects to make them more visible under MRI. These particles act by temporarily storing MRI RF energy and re-radiating this energy away once the RF field is turned off, similarly to the way that the hydrogen nuclei (i.e. protons) in tissues behave. However, the nano-magnetic coatings have a relaxation time (similar to the spin-lattice relaxation time of a proton), i.e. the time it takes for the nano-magnetic particles to release the energy obtained from the RF pulse back to their surroundings in order to return to their equilibrium state, that is different from that of body tissues, thereby enabling the nano-magnetic coating to be visualized under MRI. Such a coating can be applied on or within the surfaces of the DMVA device, such as the surface or interior of the liners, to enable these components or features to be visualized under MRI. Such nano-magnetic coatings and materials are described e.g., in U.S. patent application Ser. Nos. 10/384,288, and 10/369,429, the disclosures of which are incorporated herein by reference.
In a similar embodiment of this particular invention (not shown), radiopaque (i.e. X-ray) contrast agents are utilized without limitation according to the following descriptions.
In one embodiment, radiopaque contrast agents are added to the surface of or imbibed into the liner of the Cup, making the thin liner much easier to visualize under ultrasonic imaging. Enhancing the liner image is critical to assess proper fit of the liner to the heart. One example of a suitable radiopaque contrast agent is Omnipaque™, a non-ionic aqueous solution of isohexol, N,N′-Bis(2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl)-acetamido]-2,4,6-triiodo-isophthalamide made by the Amersham Health Corporation of Princeton, N.J. The very high X-ray contrast of this material, and its ability to be easily attached to or imbibed into the polymeric Cup and Cup liner make this material a desirable choice. It is to be understood that any other component of the DMVA device could also be treated with a radiopaque contrast agent to enhance its image profile.
In another embodiment, radiopaque contrast agents can be incorporated into the working fluids used to inflate and deflate the Cup liners, to help visualize liner inflation and deflation performance. In yet another embodiment, radiopaque contrast agents can also be incorporated into the blood flowing into and around the heart.
A contrast agent such as described above is applied to the inner surface 201 of the shell 110 in order to enhance imaging of the shell wall. A contrast agent is also applied to the outer surface 613 of liner 114 in order to enhance imaging thereof. Alternatively, the latter contrast agent may be applied to the inner surface of liner 114, but the use of the outer surface 613 may be preferred in order to avoid potential biocompatibility issues. Imaging of liner surface 613 provides measurements of the shape of the exterior of the heart itself. By monitoring this shape over time, the performance of the heart under DMVA assist may be analyzed. In a similar manner, imaging of both the liner surface 613 and the shell surface 201 provides measurements of the volume contained in lumen 310; this may also be monitored in order to analyze the performance of the heart under DMVA assist.
Most imaging techniques benefit from the use of reference points, comprising the same image enhancing materials as described above, that are used to offset drift in the imaging system electronics, or shifts in alignment of the object being imaged that would otherwise degrade the accuracy of measurement by the imaging technique. In the embodiment shown, multiple reference points 203 are shown in one possible position at the upper periphery of the cup shell 110. Alternatively, or additionally, one or more reference points 205 near the apex of the cup shell 110 may be employed to provide further information for purposes of referencing the imaging system during use. These reference points 203 and 205 may be in other locations, and may be extended as linear or surface elements in order to optimize the referencing process for a specific imaging method.
A more detailed description of embodiments of the present invention pertaining to Invention Aspect 3 (DMVA feedback control parameters), Invention Aspect 4 (DMVA feedback control methods and algorithms), Invention Aspect 9 (Sensor data recording and analysis capabilities), and Invention Aspect 10 (Specific device performance measures appropriate for sensing) is now presented with reference to
DMVA Cup 109 further comprises seal sensor 1122 connected via line 1123; upper cavity pressure sensor 1112 connected via line 1113; lower cavity pressure sensor 1114 connected via line 1115; drive fluid lumen/cavity pressure sensor 1118 connected via line 1119; and internal pressure sensor 1120 connected via a line (not shown). Vacuum port 211 of DMVA Cup 109 is connected to drive system vacuum pump 302 by line 301. Fluid drive port 220 of DMVA Cup 109 is connected to drive system DMVA fluid drive pump 304 by line 303. In an embodiment wherein seal 720 is an active seal, as in active seal 820 of
In a further embodiment, DMVA Cup 109 further comprises cardiac sensor 1260 connected to control system 1300 via line 1261, which may be any of a variety of electrical, optical, chemical, or other sensors that directly measure some parameter associated with cardiac performance and/or cardiac tissue status. In addition to sensors traditionally used for these purposes, this embodiment provides for measurement of blood components such as CRP (C-Reactive Protein, an indicator of tissue damage due to trauma or overwork) or Lactate (an indicator of muscle fatigue), or other markers that can be used to determine the level of stress in cardiac tissue, the degree of healing of damaged cardiac tissue, the degree of regeneration of cardiac tissue, or a combination of these. Cardiac sensor 1260 may also be used to measure the presence or concentration of a therapeutic agent. Cardiac sensor 1260 is connected to control system 1300 via line 1261.
In the preferred embodiment, control system 1300 comprises numerous subsystems and subcomponents, including microcontroller 1302 connected to programmable logic controller 1304 via interconnect line 1305, and connected to external transceiver 1306 via interconnect line 1307. Control system 1300 is in communication with patient 90 via transceived signal 1309 (such as e.g. a patient alert signal) and via line 1311. Control system 1300 is in communication with physician 92 via transceived signal 1313 (such as e.g. a physician alert signal) and via line 1315. Drive fluid pump 304 is in communication with controller 1300 via line 311. Vacuum pump 302 is in communication with controller 1300 via line 309. Seal actuator 306 is in communication with controller 1300 via line 307.
In a further embodiment, vacuum port 211, DMVA drive fluid port 220, and various sensor lines 305, 1113, 1115, 1119, and 1123 are integrated into a single multi-conduit, multi-wire connecting cable preferably entering the Cup shell 220 near the apex 161 (see
In yet a further embodiment, the line or lines connected to the DMVA cup are provided with a coating of an anti-infection agent and/or an anti-inflammatory agent. Descriptions of suitable agents may be found at e.g., “Preventing Complications of Intravenous Catheterization” New England Journal of Medicine, Mar. 20, 2003, 1123. In addition, at http://link.springer-ny.com/link/service/journals/00284/bibs/33nlpl.html, there is described a hydrogel/silver coating that reduces adherence of E-coli (hydrogel effect) and reduces growth (silver); at http://www.infectioncontroltoday.com/articles/291feat3.html there is described several antimicrobial surface treatments such as chlorhexidine-silver sulfadiazine, minocycline, and rifampin, as well as silver compounds (chloride or oxide). Those skilled in the art will be aware of a variety of such anti-infection and anti-inflammatory agents, each having specific beneficial properties, and each that may be used individually or in combination.
With such a comprehensive fluid drive system 300 and control system 1300 interfaced with DMVA Cup 109, it will be apparent that a wide range of data acquisition, and Cup control and operating algorithms are possible. Further embodiments of the DMVA Cup of the present invention are directed to advanced control and use of such Cup device in cardiac regeneration.
Algorithm 1510, in combination with various embodiments of the DMVA Cup described in this specification, may be designed to provide the heart with and/or assist the heart in biochemical regeneration, and/or cardiac training, and/or therapeutic recovery, as will be presently described and shown in
The accepted practice of treating congestive heart failure (CHF) and other degenerative cardiac diseases has in the past been to attempt to slow the progress of disease (e.g. drug therapies and multi-chamber heart pacing), to compensate for the disease (e.g. restricted life style, oxygen support, mechanical ventricular assist devices), or in some cases to replace the diseased heart. The inability of the heart to recover from its diseased state, and the resulting inevitability of physical decline, morbidity, and death, have for some time been reluctantly accepted by the medical community, and society at large.
Recent parallel advances in cardiac medicine and in regenerative medicine have led some researchers to speculate as to whether some of the effects of CHF might be even more effectively delayed or compensated by use of regenerative medical treatment on the heart itself. However, the working premise of the instant invention goes well beyond the improved outcomes that are predicted based on results from prior art approaches. It is proposed that the entire course of CHF may in many cases be made totally reversible, and that an individual treated under the process of this invention may recover completely from CHF.
The aspects of this approach include the following:
For the purpose of this disclosure, a first-order control algorithm element is defined as one that uses a single input to modify a single output, based on a predetermined mathematical relationship. For a system having ‘n’ inputs that are one-for-one related to outputs, the control algorithm is simple, having (n) elements that may be updated on a sequential or parallel basis. For a system comprising ‘n’ inputs and ‘m’ outputs, and where there is no one-for-one relationship, the maximum set of elements will be (m)×(n). While in theory these elements could be updated on a sequential or parallel basis, it becomes obvious that for any other than an extremely simple and linear system, the order and frequency of update will have a significant impact on the response of the system. The variability coming from this approach, especially if used to control a biological process, will result in an indeterminate result.
Second Order Algorithm Elements
For the purpose of this disclosure, a second-order control algorithm element is defined as one that uses multiple inputs to modify a single output, based on a predetermined relationship. In the case of ‘n’ inputs and ‘m’ outputs, each of the control elements will be far more complex, but there will be only (m) elements and the algorithm will be far more robust, especially if used to control a biological process.
Algorithm Updating and Adaptation Process
The biological process that the algorithm of this invention is intended to control is not the human heart, per se. The biological process this algorithm is intended to control is the healing of the heart, and the recovery from a degenerative cardiac disease such as congestive failure.
Thus, the cardiac regenerative algorithm or ‘treatment algorithm’ will not be one that is based on a premise of norms, stability, and control limits. Rather, the treatment algorithm of this invention will be based on a premise of gradual migration of a large set of parameters from a state of disease to a state of health. Each of these states, ‘disease’ and ‘health’, have a number of parameters each of which may vary over a range of values over time. In addition, the pathway from disease to health will vary from individual to individual. Thus for the purpose of creating an algorithm to guide the system in a manner that effectively moves this individual's heart from a diseased state to a healthy state, a fixed set of control equations will not suffice. What is required is an adaptive algorithm that continually updates itself, having ‘knowledge’ of a variety of pathways from disease to health that results from 1) generalized demographic information, used in combination with 2) detailed historical information on the individual, and 3) frequent pathway analysis and correction.
Given the adaptive nature of the treatment algorithm, there is an increased possibility of ‘traps’ along the particular pathway that is being followed. The term ‘trap’ refers to a local optimum that precludes movement of the algorithm to the global optimum solution for the individual. In some cases a pathway trap may stall the process of healing, and in others it may have even more serious negative consequences. Thus the treatment algorithm also has failsafe measures built into it that monitor its progress and if a trapping situation is sensed, corrective actions and/or alarms can be activated.
Core Treatment Algorithm Model
The core treatment algorithm model 1520 may be updated from time to time, at a number of levels. However, the updating of the core model should not be confused with the behavior of a working algorithm 1540 that is constantly modifying its set points based on a variety of inputs. The working algorithm 1540 is intended to adapt to changes in patient state, to take advantage of information relating to a large population of patients in order to predict some aspects of patient response to therapy, to accept changes in control parameters from the attending physician, and to monitor its own performance. However, all of these aspects of the working algorithm 1540 are based on protocols in the core algorithm model that are fixed. These core algorithm protocols may only be changed upon a version update that is beyond access to the patient or the physician.
Physician Inputs and Outputs 1524 are provided for use in the working algorithm. Inputs are provided such that the attending physician will be presented with an interactive software program that does the following:
Outputs are provided such that feedback to the physician will be timed to match level of urgency:
The working algorithm 1540 is intended to adapt based on the following sets of conditions and inputs for algorithm adaptation 1530:
The algorithm adaptation process 1530 has the following characteristics:
It accepts inputs listed above and modifies the working algorithm 1540 accordingly.
The working algorithm 1540 uses real-time inputs to control real-time operation of the therapeutic device. Inputs include:
The working algorithm controls the following aspects of therapeutic device function:
The working algorithm 1540 is fixed in its behavior over short periods between updates from the algorithm adaptation process 1530. However, the working algorithm 1540 is a complex, second-order control system that not only uses in the inputs listed above, but also analyzes the relationships between those inputs and is able to react in a non-linear fashion.
Patient Inputs & Outputs 1548
The patient will be provided with an input/output device that permits entry of information that may improve the effectiveness of the treatment. Examples of inputs include the following:
The I/O device permits communication output to the patient. Examples of outputs include the following:
This (“Failsafe”) subroutine acts as a secondary safety feature, providing redundant measures to ensure the safety of the patient. It is not a redundant controller and does not affect the operation of the primary working algorithm. Rather, it has a baseline set of parameter limits, and parameter-to-parameter limits that can be modified by the physician at the outset. During initialization of the system, the failsafe algorithm 1549 (as modified by the physician) is compared against the working algorithm 1540 (as modified by the physician, and by input of patient history and demographic information) to determine if there are operational inconsistencies. Once the overall system is initialized and started, the failsafe algorithm 1549 monitors the control outputs of the working algorithm 1540 on a real-time basis and reacts to both limits that are exceeded, and trends in performance that are approaching limits in a manner that is inconsistent with nominal operation. It then provides an appropriate warning or alarm output to the physician and/or patient, as appropriate.
Individual Patient History 1532: Patient history input 1532 is a set of numerical values that describe or quantify a variety of prior aspects of the individual patient preceding the implementation of the DMVA apparatus, the specific cardiac disease being treated, and other health-related factors that may be important to proper operation of the working algorithm 1540, and especially as the interval training 1555 aspects are utilized. Typical elements in patient history include the following: history of cardiac disease conditions such as pulmonary hypertension, systemic hypertension, dilated cardiomyopathy, congestive heart failure, and myocardial infarction; hereditary factors; smoking or substance abuse; and history of other large organ diseases.
Demographic Information 1534: Any individual patient, healthy or unhealthy, provides opportunity for retrospective analysis of their responses to disease and to treatment (physical, bio/chemical, electromechanical, etc.). But the individual patient history provides only the opportunity for retrospective analysis, and no opportunity for predictive analysis. A database of demographic information, i.e. predictive numerical parameters, provides the opportunity for prediction of the individual patient's response to the above stimuli by comparison to others with similar conditions and an analysis of the outcomes from specific pathways chosen in treatment. The kinds of demographic information useful to the working algorithm include information such as age, race/ethnicity, and gender. Therapeutic Response 1536: Input parameters shown in
The therapeutic response factors 1536 are used as inputs to the algorithm adaptation process 1530 as a means of indicating the recent and longer-term effectiveness of the working algorithm 1540 (as currently configured) to stabilize, heal, and/or regenerate the heart. Use of these therapeutic response factors along with patient history and demographic information, are analyzed by the algorithm adaptation process 1530 to either continue or modify the current working algorithm 1540.
The therapeutic response function 1536 may also periodically provide status and trend data to the physician and/or the patient, as appropriate.
Electrophysiology input 1542 includes one-dimensional data 1571, two-dimensional-dimensional data 1572, and three-dimensional data 1573. One-dimensional data 1571 entails typical electrophysiological signals such as are used in controlling pacemakers and cardio-defibrillators. These are typically point measurements made by sensors that contact cardiac tissue at specific parts. With regard to two-dimensional data 1572, the electrophysiology of heart function is not a set of distinct traditional nerve pathways connecting a set of points in the heart tissue. Rather, it involves a wave front that propagates through the tissue in a very complex way. By making electrophysiological measurements at multiple distributed surface sites (and conversely providing the opportunity for pacing the heart at these multiple sites), more information may be collected regarding the state of tissue at specific locations within the heart. This information may be key to application of regenerative therapies and specifically to the use of “training” regimens. See, for example, U.S. Pat. No. 5,674,259, “Multifocal leadless apical cardiac pacemaker,” the disclosure of which is incorporated herein by reference. With regard to three-dimensional data, reference may be had to, “When Time Breaks Down—The Three-Dimensional Dynamics of Electrochemical Waves and Cardiac Arrhythmias”, Arthur T. Winfree, Princeton University Press, ISBN 0-691-02402-2, the disclosure of which is incorporated herein by reference.
Bio/Chemical Markers 1544
Lactate 1574: Lactate is well known as a marker for muscle fatigue. It may be measured directly via a chemical analysis of blood. It may also be measured by spectroscopic means. If the latter approach is taken it may also be measured directly in cardiac tissue thus providing a feedback mechanism for the degree of stress involved in a cardiac muscle training regimen.
C-Reactive Protein 1575: CRP is produced in the liver in response to inflammation and/or tissue damage. The biochemical pathway resulting in an increase in CRP concentration appears to be somewhat complex. Thus it is unlikely to find a precursor molecule at the heart that would be an early indicator of cardiac tissue damage due to excess physical exertion, or some other form of impending damage to the heart.
PO2 1576: Concentration of oxygen and carbon dioxide in arteries, capillaries, and veins supporting cardiac tissue may be an important indication of tissue health, and the ability of the heart to do effective pumping work.
PCO2 1577: See above for PO2.
As stated previously, the present invention avoids the production of stress forces within the heart muscle by applying forces to the heart that are perpendicular to the surface of the heart, while also ensuring that the magnitude of the difference between adjacent forces is very small. In other words, the application of the force to the heart is substantially uniform, taken over a distance scale that is relevant to the imposition of significant (i.e. traumatic) shear stress on the heart muscle. In particular, the applied force is uniform circumferentially, i.e. around the heart, such that the heart is compressed to form a core shape with a substantially circular cardiac core diameter as previously described. Each of these features eliminates the formation of shear forces within the heart muscle, which leads to bruising damage to the heart tissue which leads to muscle fatigue and potentially failure of the heart. The DMVA device of the present invention is thus atraumatic with respect to the heart.
Specific features of the present invention which provide these capabilities include the following:
A. Near-Isotropic Liner Material
Liner materials that are near-isotropic will expand uniformly from internal pressure or vacuum applied by the internal working fluid. This uniform expansion or contraction prevents “less stiff” portions of the liner from “ballooning” into the heart tissue and creating higher forces on the heart tissue, relative to “more stiff” adjacent portions of the liner, which would cause shear stresses throughout the heart wall and bruising of heart tissue, which would ultimately lead to damage to the heart tissue. Over time, this damage could lead to total failure of the heart.
In addition, some materials either stiffen after being flexed or stretched (“strain hardening”), or weaken after flex or stretch (strain softening). In metals, this results from changes in grain structure, and in elastomers, it results from changes in polymer chain bonds. Optimal materials for the DMVA Cup liner and shell are “strain neutral”, and maintain original properties after repeated cyclic loadings. The near-isotropic and strain neutral liner avoids this problem by enabling all areas of the liner to expand at the same rate and preventing areas of the liner from “ballooning” into the myocardium and creating shear stresses within the heart tissue. Furthermore, isotropic materials allow the heart to be actuated (compressed and dilated) in a manner dictated by the tissue characteristics, and pressure points are minimized as the material does not fold or bend in a non-uniform fashion. In one embodiment, a suitable near-isotropic and strain neutral elastic material is a heat curable liquid silicone rubber sold, by the NuSil Technology Company, of Carpenteria, Calif.
B. Fatigue-Resistant Liner Material
Fatigue of the liner material would create a “weak spot” such as described above, and result in shear within the heart tissue. Liner materials that are fatigue-resistant ensure that the liner will avoid “weak spots” and prevent a difference in forces from being applied to the heart tissue and the shear stresses that such differences create.
C. Dynamic Cup Shell Structure and Material.
The compliant nature of the preferred Cup shell of the present invention results in the constantly adaptation of the shape thereof in response both to the actuating forces applied to the heart and changes in the heart's size and/or shape. This characteristic contributes to decreased ventricular trauma, ease of application as the housing can be deformed to fit through small incisions, and important dynamic conformational changes that constantly respond to the heart's changing shape.
The housing (shell) of the device is constructed of a flexible material that has appropriate compliance and elastic properties that allow it to absorb the systolic and diastolic actuating forces in a manner that somewhat buffers the effect of the liner on the heart. The unique qualities of this housing lessen the risk for inadvertent excessive forces to be applied to the heart at any time of the cycle. The shell conforms to the dynamic changes in the right and left ventricles throughout compression and relaxation cycles as well as overall, ongoing changes related to variances in heart size over time which occur as a consequence of continued mechanical actuation and related “remodeling” effects on the heart.
In one embodiment, the Cup shell consists essentially of the aforementioned liquid silicone rubber polymer having a wall thickness of between about 2 millimeters and about 8 millimeters. It is preferable to form the Cup shell with walls as thin as possible while retaining the desired dynamic capabilities.
D. Liner Design Improvements:
In another embodiment, the requirement for an isotropic or near-isotropic material is greatly reduced or eliminated by the provision of a liner ltat applies a uniform force to the heart without undergoing elastic deformation. one such a liner is a rolling diaphragm liner that is deployed against ventricle walls of the heart by a progressive rolling action, as described previously in this specification and shown in
2. Absence of Surface Abrasion
The Cup liner described above creates a near-zero shear stress or minimum-slip condition at liner-myocardium interface, similar to the “rolling interface” that exists between mechanical gears. This no-slip condition minimizes or eliminates abrasion of the heart tissue, which over time can result in serious damage to the heart tissue.
Referring again to
Assembly 530 comprises seal 720, upper rolling diaphragm section 520, liner membrane 540, and lower rolling diaphragm section 570. In the preferred embodiment, seal 720 is formed with a structure similar to seal 730 of
In one embodiment, rolling diaphragm liner is directly bonded to DMVA Cup shell wall 112 at upper section 520 and lower section 570 thereof.
In the preferred embodiment, surfaces 576 and 134 are bonded, while surfaces 574 and 132 are not bonded. With such a structure, rim 572 of lower rolling diaphragm section 570 is free to flex as indicated by arrow 199 when liner membrane 540 is displaced outwardly and inwardly, thereby widely distributing stress within lower rolling diaphragm section 570, such that fatigue of the material thereof is greatly diminished. Thus the safety, reliability and longevity of the DMVA device 101 are significantly enhanced.
It is known that sudden changes in cross-section of components that undergo repetitive bending result in stress-concentrations that reduce fatigue life of such components.
A number of approaches are traditionally taken to effect stress relief, but one of the simplest is a gradual change in section. Thus it can be seen that there is a continuous, gradual thinning of the liner material in the progression from the rim 572, from surface 576 upwardly to the portion thereof bounded by surface 574, an on through transition section 578 to liner membrane 540 in order to achieve such a reduction in stress concentration.
Other means of bonding liner 510 to shell wall 112 will be suitable and will be apparent to those skilled in the art, with the exact choice of means depending upon the particular material selections for Cup shell 110 and liner 510. One example of a material suited for both shell 110 and liner 510 is MED4850 Liquid Silicone Rubber. One example of an adhesive well suited for bonding elements consisting essentially of this material is MED1-4213. Both of these materials are products of the NuSil Technology Company of Carpenteria, Calif.
Arrows 682, 683, 689, and 684 indicate the linkage between motion of liner membrane 681 and seal 685 during systole and diastole that results from pressurization of the cavity 123 between shell 110 and liner 670 with DMVA drive fluid. During systole, liner membrane moves as indicated by arrow 683, and seal 685 moves as indicated by arrow 684; such that during systole, seal 685 is relatively looser on the heart (not shown). During diastole, liner membrane 681 moves as indicated by arrow 682, and seal 685 moves as indicated by arrow 689; such that during diastole, seal 685 is relatively tighter on the heart. Thus the “self-bailing” efficiency of active seal 685 is improved. This effect results directly from the shapes, dimensions and materials chosen for liner/seal 670. It will be apparent to those skilled in the art that there are many variants of liner seal 670 with regard to material thicknesses and bend configurations comprising at least one bend that will achieve the same result, i.e. the linkage between motion of liner membrane 681 and seal 685 as indicated by arrows 682, 683, 689, and 684, an that such variants are to be considered within the scope of the present invention.
Referring again in particular to the upper portion of
When the DMVA Cup is to be installed upon a heart, the Cup is slipped over the heart, such that heart tissue 39 is placed in sliding contact with seal 730. During installation (D.I.), seal 730 bends at midsection 734, and apex 736 is displaced downwardly by the downward sliding action of heart tissue 39 indicated by arrow 99, as indicated in the second part of the sequence labeled D.I.
As the heart is slipped into the DMVA Cup, and the portion of maximum girth of the heart passes seal 730, seal 730 begins to recoil in the tapered midsection 734, thereby drawing apex 736 upwardly as indicated by arrow 98. The third graphic of
Seal 730 is configured such that apex 736 is in tension against heart tissue 39. In addition to such tension, the pressure differential that is present between the outside and inside of the Cup wall during diastole further enhances engagement and sealing contact between heart tissue 39 and seal 730. As a result of such tension and engagement, after seal 730 has been thus engaged with the heart for a period of time, tissue ingrowth occurs, such that apex 736 becomes embedded in heart tissue 39, as indicated by apex 737 shown in phantom in
Seal 730 is preferably formed of a deformable elastic polymer. In one embodiment, seal 730 is made of a silicone polymer known commercially as Silastic, or Liquid Silicone Rubber. One example of a material suited for seal 730 is MED4850 Liquid Silicone Rubber. One example of an adhesive well suited for bonding elements consisting essentially of this material is MED1-4213. Both of these materials are products of the NuSil Technology Company, of Carpenteria, Calif.
In a further embodiment, seal 730 is provided with a coating of a biocompatible thin film to facilitate such ingrowth and adhesion of tissue.
Seal 740 is a less-preferred design, compared to seal 730 of
In the next view down in
In one embodiment (not shown), seal 750 is provided with water soluble adhesive applied to surface 753, which temporarily bonds surface 753 to the outer surface of shell 110 of the DMVA Cup 100 (see e.g.,
In yet another embodiment depicted in
In a further embodiment, annulus 772 is filled with a fluid containing a therapeutic drug or other therapeutic agent, and the material of seal 770 is permeable to such drug or agent, or provided with microscopic pores for the passage of the drug therethrough, so that the drug may be delivered directly to the heart. Such therapeutic agents include but are not limited to anti-inflammatory agents, gene therapy agents, gene transfer agents, stem cells, chemo-attractants, cell regeneration agents, ventricular remodeling agents, anti-infection agents, tumor suppressants, tissue and/or cell engineering agents, imaging contrast agents, tissue staining agents, nutrients, and mixtures thereof.
With proper choice of the shape of active seal 820 with respect to the heart to which the DMVA Cup is fitted, to the shape and size of cavity 826, and to the relative thickness and elastic moduli of inner wall 828 and outer wall 830 of cavity 826, pressurization of cavity 826 may be used to force seal 820 inwardly against the heart wall (not shown). In one embodiment, this pressurization is timed to coincide with action of the Cup so that seal 820 is relatively relaxed during systole and relatively tight during diastole.
Referring again to
In various embodiments, liner 852 is further specialized, in terms of material, surface texture, surface lubricity, elasticity and fatigue resistance, and either inducement or inhibition of tissue in-growth. These forms of specialization may be localized in specific areas of the liner. In one embodiment, upper liner region 853 and lower liner region 854 are shaped to optimize fatigue resistance and to minimize local and general shear stress in the heart, both at the heart wall surface and within the cardiac muscle, as described previously in this specification. Since the design of a rolling diaphragm will likely result in some rubbing contact between layers of the same material, the core material—or a coating applied thereto—is chosen to optimize the wear characteristics thereof. Thus, for example, a coating of a fluoropolymer such as polytetrafluoroethylene may be applied to regions 853 and 854.
Liner membrane 855 is the region of liner 852 that is in constant physical contact with the heart. Depending upon whether the specific Cup 850 is indicated for acute or chronic use, the liner membrane 855 may be provided with a particular surface texture, topically applied materials, or imbibed materials, to either enhance or inhibit tissue in-growth into the surface thereof. In one embodiment depicted in
In a further embodiment, a surface texture 859 is provided on the outer surface of inner layer 858 to enhance tissue in-growth into the surface thereof. Such a surface texture may be created by the primary manufacturing process (e.g. injection molding), by a secondary mechanical process (e.g. abrasion, scoring, extrusion, or calendaring), by a chemical process (e.g. etching or solvent softening), by plasma treatment, by a direct writing device, or by a combination of these and other processes.
Referring again to
Referring yet again to
DMVA Cup shell 240 comprises a cup-shaped wall 242, drive fluid port 220 in communication with cavity 310, and vacuum port 211. Drive fluid port 220 connects the cavity 310 between shell 240 and liner 852 with a local or remote fluid drive subsystem 360 that pumps drive fluid to act on the heart (not shown) through liner membrane 855. Drive fluid port 220 also provides access for internal pressure measurements. Port 220 may be a simple tube accessing the lumen in one place, or alternately may have a network of small channels that provides uniform flow to all areas of the cavity 310. Cross-section and internal shape changes may be optimized to minimize friction losses in order to maximize Cup energy efficiency.
Vacuum port 211 connects the internal cavity 128 of the Cup shell 240 to a local or remote vacuum subsystem 350 that may be used to generate negative differential pressure (“vacuum”) between the interior 128 and exterior of the Cup 153 in order to retain the Cup 153 on the heart (not shown). Some Cup and seal designs may not require vacuum at all. Other Cup and seal designs used for acute applications may use a vacuum pump as part of vacuum system 360. In one embodiment, the pump is a bi-directional pump 352, the pumping action of which can be alternated between pressure and vacuum, so that the Cup 153 can be easily removed from the patient. Pump 352 is connected to DMVA drive unit or controller 1310 (see
Yet other Cup and seal designs may require vacuum during and shortly following installation, but make use of tissue in-growth for long-term retention. In this last case vacuum port 211 may be disconnected from its vacuum source at a time when retentive vacuum is no longer needed to secure the Cup 153 on the heart. In some circumstances, where applied vacuum is not used for either installation or retention, where tissue in-growth either does not occur or can be countered for reasons of Cup removal, and where the innate negative pressure created by the ‘self-bailing’ nature of the Cup seal 860 makes Cup removal difficult or impossible, a valve 356 connected to controller 1310 by wiring 358 provides for active venting of vacuum from the Cup interior at the time of Cup removal.
In another embodiment, vacuum system 350 comprises vacuum pump 360 connected to vacuum port 211 of Cup shell 240 through valve 362. Valve 362 is preferably a three way valve, with a first position closing off flow into/out of vacuum port 211, a second position allowing flow from vacuum port 211 to pump 360, and a third position venting port 211 to the external atmosphere. Pump 360 is connected to DMVA drive unit or controller 1310 via wires 364, and valve 362 is connected to DMVA drive unit or controller 1310 via wires 366.
In a further embodiment, means are provided in the DMVA apparatus for enhanced aspiration of fluid from any volumes formed between the heart and the liner or between the heart and the interior surface of the Cup shell wall. Referring to
In such a circumstance, one means of enhancing aspiration of such fluid out of volumes 51 and/or 53 is to provide drainage grooves 142 on the interior wall of the Cup shell 110 near vacuum port 111. Such grooves are preferably disposed radially from port 111, with the number of aspiration grooves preferably being between four and twelve. In a further embodiment, a grating or screen is provided or formed integrally in shell 110 at the entry of port 111 to prevent the apex of the heart from being sucked into port 111 and deformed. Such a similar use of drainage grooves and a grating in a batch fluid delivery device is described at column 7 lines 46-61 of U.S. Pat. No. 5,205,722, the disclosure of which is incorporated herein by reference. In yet a further embodiment, a plurality of raised ribs are provided disposed radially outwardly from vacuum port 111 on the inner surface of Cup shell 110, which prevent the occlusion of port 111 by apex 38 of heart 30, thereby achieving substantially the same result as the grooves 142 of
In a further embodiment (not shown), aspiration ports are provided within the Cup shell wall, preferably disposed either in proximity to port 111, and/or in proximity to seal 113. Such ports are connected within cup shell 110 either to vacuum port 111, or to another vacuum port (not shown) provided for aspiration. In another embodiment, such aspiration ports are provided in a seal comprising a cavity, such as seal 820 of
Referring again to
Referring again to
Upper section 262 of shell outer wall 261 is joined to lower section 266 of outer shell wall 261 at bond area 265. Inner shell wall 271 is joined to outer shell wall 261 at upper bond area 269, at lower bond area 270, and at the contact surfaces between ribs 253 and inner shell wall 271 and outer shell wall 261. Several alignment features 263, 264, and 267 are provided on inner shell wall 271 and outer shell wall 261 to facilitate alignment thereof prior to and during bonding therebetween.
Shell 280 is preferably provided with attachment features to ensure a strong bond between the subcomponents thereof. Referring to
Pump assembly 410 may be any suitable pumping mechanism, which is designed to alternatingly deliver a fluid outwardly through conduit 402 as indicated by arrow 498, and withdraw a fluid inwardly through conduit 402 as indicated by arrow 499. In one embodiment, the DMVA drive fluid delivered and withdrawn into cavity 310 of DMVA apparatus 156 is a compressible fluid, i.e. a gas such as e.g., air. In another embodiment, the DMVA drive fluid is an incompressible liquid.
In the preferred embodiment, pump assembly 410 comprises a reciprocating pump, such as a piston pump comprising a reciprocating piston, or a diaphragm pump comprising a reciprocating diaphragm. Such a reciprocating pump is preferable, because such a pump inherently comprises a fluid reservoir 412 contained within a housing 414, and a reciprocating element 416 driven by reciprocating drive means 418, as indicated by bi-directional arrow 497. Such a reciprocating pump assembly does not require a separate fluid reservoir and valving means to switch the direction of fluid flow, and can thus be made as a very compact assembly.
In the preferred embodiment, reciprocating drive means 418 comprises a linear actuator that is capable of providing bi-directional linear motion. Such a linear actuator may be any of a variety of linear actuator devices, including but not limited to a standard alternating current or direct current continuous or stepper type electric motor engaged with the following: a ball-screw or other rotational-to-linear mechanism, a rack and pinion, a cam linkage, a four bar or other linkage, a crankshaft, or a hydraulic or pneumatic power source. Alternatively, such linear actuator may comprise an electrical solenoid; an inchworm drive using piezoelectric, electrostrictive, or other short-range linear power source; an electrostrictive or electroactive polymer artificial muscle (EPAM) such as e.g., a silicone EPAM or a polyurethane EPAM; or a skeletal muscle affixed to reciprocating element 416, sustained by an artificial capillary bed, and driven by an electrical stimulus. For a detailed description of EPAMs, reference may be had to SPIE Proceedings Volume 3669, Smart Structures and Materials 1999: Electroactive Polymer Actuators and Devices, and in particular, paper 3669-01, Electroactive polymer actuators and devices by S. G. Wax et al, the disclosure of which is incorporated herein by reference. Actuator shaft 417 connects any of these actuator devices to reciprocating element 416.
Alternatively, reciprocating drive means 418 may comprise a camshaft engaged directly with reciprocating element 416, as described in U.S. Pat. No. 5,368,451 of Hammond, the disclosure of which is incorporated herein by reference. Such camshaft driven reciprocating means may further include means to vary the timing and duration of the reciprocation thereof, as is practiced in providing variable reciprocation of objects such as e.g., automotive engine valves. Such variable timing enables the programming and control of a wide range of systolic and diastolic actuation conditions as described previously in this specification. In yet another embodiment, reciprocating drive means 418 may be hydraulic and may comprise a closed loop reciprocating fluid system as described in U.S. Pat. No. 5,205,722 of Hammond, the disclosure of which is incorporated herein by reference. Such a reciprocating fluid system may be coupled to reciprocating element 416, or it may be coupled directly to conduit 402, thereby directly reciprocating liner 530 in systolic and diastolic actuation.
Referring again to
Referring again to
In the preferred embodiment, the secondary fluid contained in cavity 426 is preferably a gas, either at a neutral pressure, or at negative pressure with respect to the implant environment. As reciprocating plate 416 displaces the DMVA drive fluid in cavity 412, thereby displacing liner membrane 540, the secondary fluid in cavity 426 will undergo expansion. This will require increased force on actuator shaft 417 during systole, but will also provide useful force during diastole to pull DMVA drive fluid back through conduit 402, thus pulling the liner 540 and expanding the heart (not shown). In this embodiment the use of positive or negative pressure in the secondary fluid in cavity 426 is somewhat immaterial, since the compressible nature of the gas will not affect the energy efficiency of the cyclic process. However, in order to keep physical forces and resulting wear to a minimum, the pressure is best selected to be about neutral (physiologic pressure) at the center of the stroke of the actuator shaft 417. In another less preferred embodiment not shown, cavity 426 containing the secondary fluid may be ‘vented’ to the interior of the body of the patient, but contained within an expandable envelope, fluid bag, or other sealed collection means.
Referring again to
In another embodiment (not shown), DMVA apparatus comprises a longer flexible conduit 402, thus providing greater separation of pump assembly 410 from Cup shell 170, so that pump assembly 410 may be implanted at a more distal location within the body. In either instance, DMVA apparatus 156 is provide as an assembly that is entirely implantable within the body. In another embodiment, conduit 402 is provided with a biocidal anti-infection and/or anti-inflammatory coating as described previously in this specification.
In a further embodiment (not shown), pump assembly 410 of DMVA apparatus 156 is provided with means to heat or cool the DMVA drive fluid contained within cavity 412. Such means provides the DMVA apparatus with the capability of using chilled DMVA drive fluid to cool the heart and the blood pumped therefrom, and hence to also cool the brain and other organs during resuscitation efforts. Such cooling is a well-established method to significantly extend the period that the brain can withstand anoxia, and is thus uniquely suited to the use of the DMVA apparatus and method of resuscitation. Accordingly, such a capability may greatly enhance the clinical effectiveness in acute resuscitations using the DMVA apparatus of the present invention.
It will be apparent that pump housing 414 provides structural support for elements contained therein, such as piston/reciprocating element 416, diaphragm 420, seals not shown, motor and/or linear actuator or other reciprocating means 418, and any sensors (not shown). In addition, pump housing 414 must be secured to Cup shell wall 172 in a manner that guarantees reliable operation under physiologic conditions and under physical exercise, and obviously must be biocompatible. The diameter of pump housing 414 and the linear travel of reciprocating element 416 are selected to provide sufficient volume so as to displace a large heart in a normal manner. In the preferred embodiment, the typical displacement volume of pump assembly 410, defined approximately by the cross sectional area of reciprocating element 416 times the stroke length of reciprocating element 416, will be on the order of 150 to 250 cubic centimeters.
In the embodiment depicted in
Referring again to
Pump assembly 430 further comprises a valve 431 disposed in conduit 404 between pump housing 434 and Cup shell 180, and connected to controller 450 via line 456. DMVA apparatus further comprises a pressure sensor 1118 disposed in cavity 119, and connected to controller 450 via line 458.
Implanted battery 460 is preferably a rechargeable battery, and is provided with recharging means 470. In one embodiment, recharging means 470 comprises an internal inductive coil 471 connected directly to implanted battery 460, or connected through controller 450 via line 451 as indicated in
In operation, pump assembly 430 operates on the principle of fluid phase change from liquid to gas, and from gas to liquid. A flash pump fluid having a low boiling point and high vapor pressure is contained in cavity 446, and is alternatingly boiled and condensed. Boiling of fluid in cavity 446 produces an expanding pressurized vapor that flows through conduit 404 and displaces liner 114 in systolic actuation; condensation of fluid in cavity 446 results in the withdrawal of vapor from conduit 404 and the retraction of liner 114 in diastolic actuation, with the effects of boiling and condensation being indicated by bi-directional arrow 496. Valve 431 is controlled by controller 450 to adjust the volume and flow rate of the vapor as it flows between pump cavity 432 and Cup cavity 119.
The pump fluid in cavity 446 is chosen to have a boiling point (or flash point) slightly above physiologic temperature. One fluid that has appropriate thermodynamic properties is ethyl bromide (C2H5Br), with a boiling point at 1 atm of 38.4 degrees Centigrade (° C.), and having a vapor pressure of 2 atm at 60.2° C. Since the positive pressure needed in order to displace the DMVA drive fluid to provide systolic blood pressure is on the order of 0.17 atm (˜125 mm Hg), a temperature rise of 3.7° C. above its 38.4° C. boiling point will be sufficient to drive liner 114 in systolic actuation.
To perform the boiling portion of the cycle (systolic actuation), electrical current is supplied from controller 450 to resistive filaments 438, thereby rapidly heating such filaments, preferably to a temperature of about 39° C. Pump fluid immediately surrounding filaments 438 instantaneously flashes to vapor at a pressure sufficient to displace liner 114 in systolic actuation. The condensation portion of the cycle (diastolic actuation) is performed subsequently, when electrical current through filaments 438 is ceased. Fins 437 and 439 rapidly conduct heat from the liquid and vapor within cavity 446, resulting in rapid withdrawal and condensation of the vapor within cavity 119 such that diastolic actuation is achieved. By proper selection of size and spacing of both fins 437 and 439, and filaments 438, this thermodynamic cycle can be made to occur extremely quickly, and can be controlled by valve 431 or by modulating electrical current input to the filaments 438, or a combination of both.
Properties, requirements, materials, and/or characteristics of various components of pump assembly 430 will now be described.
Referring again to
In the preferred embodiment, filaments 438 are preferably formed of fine wire or other resistive material. Such material is chosen to have a negative thermal coefficient of electrical resistivity, thus permitting uniform heating of the entire filament length, irrespective of minor fluctuations in cross-section that would otherwise result in non-uniform heating along the length thereof.
Some liquid-vapor flashing fluid materials with appropriate thermodynamic properties (e.g. ethyl bromide) are not biocompatible and may also permeate materials such as silastic and other flexible polymers. Accordingly, a barrier to such material coming in contact with the liner and shell of the DMVA Cup is provided by reciprocating element 436 disposed between the pump fluid cavity 446 and DMVA drive fluid reservoir 432. It will be apparent that reciprocating element must be made of a material that is impermeable and insoluble to the pump fluid and the DMVA drive fluid. In circumstances where the liquid-vapor flashing fluid material is biocompatible and does not permeate Cup materials, the flash pump may be used to directly reciprocate the liner 114 of the apparatus 157.
Conduit 404 between the cup shell 170 and the pump assembly 430 may be either short (as shown) or longer, depending upon the preferred placement of pump assembly 430. It will be apparent that the cup shell 180 must surround the subject heart, but a location chosen for the pump assembly 430 will be based on a comfortable body cavity that has heat-sink properties, on proximity to the cup shell 180 (to minimize friction losses in conduit 404) and on proximity to battery 460, recharging means 470, and controller 450. In general, pump assembly 430 is designed to be comfortably implanted and to be biocompatible. The overall size for a pump assembly 430 that delivers a DMVA drive fluid volume of 250 cubic centimeters is preferably on the order of 600 to 800 cubic centimeters.
Another factor to be considered is the amount of thermal energy that is dissipated into the patient having an implanted flash pump 430. Simply put, any device that provides energy to physically pump the heart via a heart cup or other related assist device will, in addition to the physical pumping of blood, dissipate mechanical and/or electrical energy that is used in the operation thereof. The end result is a modest amount of thermal energy or heat that must be dissipated by the body. While use of the physical phenomenon of liquid flashing into gas gives the impression of substantial heating, such is not the case, as condensation of the vapor in the diastolic portion of the cycle occurs at near-physiologic temperature. Accordingly, a flash pump may be designed to have the same or better energy efficiency as a mechanical pump, thus requiring the same amount of body heat dissipation, or less.
In operation, small rechargeable battery 460 is used to continue operation of DMVA Cup 157 during periods when the primary external battery pack 482 is being replaced, or when emergency backup power is required due to malfunction. In one embodiment, DMVA apparatus comprises two redundant batteries 482 for increased reliability. External battery pack 482 is preferably a rechargeable lithium battery pack, which typically has up to 80% capacity after 500 charge/discharge cycle. Such a battery pack 482 weighing approximately 5 lb has the capacity to store sufficient energy for operation of DMVA apparatus 157 over a full day. Battery pack 482 may be conveniently recharged during sleep cycle or at other times.
In operation, implanted inductive charging coil 471 is used to power DMVA apparatus 157 and to keep implanted battery 460 charged. Implanted inductive charging coil 471 is preferably placed subcutaneously, with such coil 471 inductively coupled to external coil 473. Coils 473 and 471 must transfer approximately 10-25 watts of electrical power, depending upon overall system efficiency and upon the degree of patient dependence on DMVA apparatus 157.
In operation, implanted controller 450 performs multiple control functions as follows: overall power management for the implanted part of the system, particularly pump assembly 430; real time control of the operation DMVA Cup 157, based on programming and on sensor data; and control of DMVA fluid pressure delivered to cavity 310 during each systolic/diastolic cycle. External controller 480 performs multiple control functions as follows: overall power management for the DMVA system 157; output control data, other information, and alarms to remote transceiver 490; and control of the recharging process for primary battery pack 482.
It will be apparent that the entire power supply and control system of DMVA apparatus 157 can be used in a like manner to power and control the DMVA apparatus 156 of
It is, therefore, apparent that there has been provided, in accordance with the present invention, a method and apparatus for Direct Mechanical Ventricular Assistance (DMVA), and a therapeutic apparatus for delivering at least one therapeutic agent directly and preferentially to a desired tissue to be treated. While this invention has been described in conjunction with preferred embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.
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|Clasificación de EE.UU.||600/16, 623/3.1|
|Clasificación internacional||A61N1/362, A61M1/10, A61F, A61F2/00, A61N1/05|
|Clasificación cooperativa||A61M1/106, A61M2230/202, A61F2/2481, A61M2230/04, A61M2205/3334, A61M1/1068, A61M2205/3331, A61N1/05, A61M1/1086, A61M2230/205|
|Clasificación europea||A61M1/10R, A61M1/10E50B|
|17 Jul 2009||AS||Assignment|
Owner name: MYOCARDIOCARE, INC.,COLORADO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BIOPHAN TECHNOLOGIES, INC.;REEL/FRAME:022970/0941
Effective date: 20090716