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Ann Thorac Surg 1999;68:768-774
© 1999 The Society of Thoracic Surgeons
a Allegheny General Hospital, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania, USA
Address reprint requests to Dr Savage, Department of Cardiothoracic-Vascular Surgery, Rush University, Suite 1156, 1725 West Harrison St, Chicago, IL 60612
Presented at the Fourth International Conference on Circulatory Support Devices for Severe Cardiac Failure, Houston, TX, Oct 3–5, 1997.
Abstract
Background. The AB-180 circulatory support system is a small, durable, efficient centrifugal pump with low thrombogenic potential. The device was designed to provide a fully implantable, left ventricular assist system for short-term support to address the issues of systemic anticoagulation, thrombus formation, infection, and cost.
Methods. Extensive bench and animal studies were performed to validate the mechanical integrity of the device and its functionality as an implant.
Results. These studies demonstrated anticoagulation requirements, established operating guidelines, incorporated safety systems, and demonstrated safety and efficacy.
Conclusions. The AB-180 fulfills the stated goals on initial evaluation. A phase I human trial is underway.
The AB-180 circulatory support system (AB-180 CSS) is a ventricular assist system under development by Cardiac Assist Technologies, Inc (Pittsburgh, PA). The AB-180 CSS is a small, durable, efficient, implantable centrifugal pump, with low thrombogenic potential, designed for use in patients in cardiogenic shock. Its development as a short-term ventricular assist device is a direct extension of the use of the centrifugal pump, developed for cardiopulmonary bypass, to support patients with postcardiotomy cardiogenic shock [1]. The device is designed to fully support patients with a 1.3- to 2.4-m2 body surface area by providing flows of up to 6 L/min. Though potentially useful for long-term support, the AB-180 CSS will first be tested as a means of left ventricular support in the setting of postcardiotomy cardiogenic shock (PCCS).
The AB-180 CSS fills from the left atrium and empties into the aorta (Fig 1). The rotor is powered by an electromagnetic coupling. The external communicating line, which exits through the skin to the controller, contains an electrical connection to power and monitor the status of the pump, a thick-walled latex tubing to conduct heparinized water into the rotor housing, and a hard-wall polyethylene occluder balloon air line. The occluder prevents retrograde flow from the aorta to the left atrium in the event of pump failure. External equipment includes a small controller, a bag of heparinized sterile water, and a monitoring device for the sterile water bag.
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Despite improvements in myocardial protection, the incidence of PCCS, resistant to pharmacological therapy and support with an intraaortic balloon pump, is 1%–2% and is most commonly due to left ventricular insufficiency. Current therapy in the US is the use of commercially available centrifugal pumps (designed for intraoperative use for cardiopulmonary bypass, adapted to the postoperative setting) or the ABIOMED BVS 5000 (ABIOMED Inc, Danvers, MA).
The AB-180 CSS was developed to address four major problems with current devices: (1) The requirement for high levels of systemic anticoagulation; (2) device-related thrombus formation and systemic embolization; (3) infection; and (4) the high cost of use.
The AB-180 CSS decreases the requirement for systemic anticoagulation and decreases the likelihood of thrombus formation by a localized infusion of heparin into the pump. This results in a high concentration of heparin within the device. In addition, the small surface area of blood contact within the pump reduces thrombosis and fibrinolysis potential. Pump volume including the inflow cannula and outflow graft is only 44 cc.
The risk of infection is addressed by the implantability of the pump; the only external connection is a small-diameter external communicating line. In the setting of PCCS, the sternum is closed, and the patient can be removed from mechanical ventilation and possibly ambulate. This may reduce the incidence of mediastinal wound infection and pneumonia.
The AB-180 CSS is designed to be easy to use so that the device can be controlled by a patient’s nurse. This combined with low manufacturing costs may lower the overall cost of mechanical support for PCCS.
In addition to addressing the problems stated above, it is postulated that the AB-180 CSS might allow quicker recovery of the heart by providing better decompression than currently available systems. This is discussed below.
Components of the AB-180 CSS
The system
The AB-180 CSS (Fig 2) is composed of a centrifugal pump and an electronic controller, which drives the AB-180 CSS pump’s brushless DC motor, monitors pump function, controls infusion of a heparin/water solution, and activates an occluder safety system.
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A solution of sterile water and heparin is infused to lubricate the impeller shaft/seal interface and provides a high local concentration of anticoagulant within the pump. The fluid is administered with an eccentric cam pump, through customized infusion tubing, attached to a standard intravenous infusion bag containing water and heparin. The fluid is delivered at a mean pressure of 150 mm Hg (range 20–500 mm Hg). The low fluid alarm sounded when less than 100 mL of fluid from a 1,000-mL bag remained, allowing 10 hours before the lubricant was used completely.
Retrograde flow is a recognized hazard of centrifugal pumps when placed in a left atrial to aortic configuration. To prevent retrograde flow should the pump fail, an occluder system was designed. The current configuration utilizes an air pump, integral to the AB-180 CSS controller, that inflates a balloon catheter placed over the outflow graft. In the event of pump failure, a triggering signal activates the air pump that inflates the balloon.
The AB-180 CSS provides a range from 0.5 to 6.0 L/min over a mean arterial pressure range of 60–90 mm Hg, with a minimum of 5 mm Hg left atrial filling pressure by regulated rotation of the impeller at speeds of 2,200 to 4,500 rpm.
The AB-180 CSS controller
The AB-180 CSS controller is a microprocessor-based device using integrated circuits and proprietary software that controls: (1) the rate of rotation of the impeller within the pump (rpm); (2) the alarm systems; (3) the infusion pump for the lubrication line; and (4) an occluder that prevents retrograde flow through the pump should it stop.
Research and development
Beginning in 1992, a series of bench tests, studies in sheep and human cadavers, were completed. Studies were conducted in the surgical laboratories at the Allegheny Singer Research Institute, Allegheny General Hospital (Pittsburgh, PA) and the Allegheny County Morgue. All animals involved in these studies received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication 85-23, revised 1985). Pertinent results of these studies are detailed below.
Normal sheep studies
A total of 46 normal sheep studies were performed, 11 chronic. The specific purpose of these studies were to: (1) test the components of the AB-180 CSS system; (2) develop anesthetic and surgical techniques for implant and explant, and postinsertion care protocols to achieve long-term support; (3) determine the physiologic efficacy of the device; (4) accrue performance and laboratory data for preliminary evaluation of safety and efficacy; and (5) determine lubrication flow rates, fluid types, and anticoagulant requirements. Pertinent findings are detailed below, and explant analysis of chronic studies is detailed in Table 1.
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Acute myocardial infarction (AMI) sheep studies
The next stage of evaluation involved studies of sheep supported by the AB-180 CSS after the induction of a myocardial infarction by ligation of the left anterior descending coronary artery. The purpose was to demonstrate the safety and efficacy of the AB-180 CSS system supporting sheep, acutely (24–48 hours) and chronically (14 days), after the induction of left ventricular dysfunction. Studies were completed in 11 sheep ranging from 22 hours to 44 days. Pertinent findings are detailed below and explant analysis is detailed in Table 2.
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End organ function [4]
The brain was assessed by clinical observation during life and neuropathologic, gross, and microscopic studies after death. No abnormalities were found.
The lungs were assessed by clinical signs, serial arterial blood gas, and pH determinations for up to 3 days after operation, and by postmortem studies in all 11 sheep. Blood gas data were in the expected ranges in the immediate postoperative interval, except in the case of 1 animal with rumen bloat syndrome that caused respiratory distress and severe hypoxemia. No pump-related pathologic changes could be found at autopsy.
An assessment of liver function was made by serial serum enzyme determinations. The changes for creatinine kinase, alanine aminotransferase, and aspartate aminotransferase were significant and required 7–14 days for recovery or return to near normal levels, all of which is expected and has been evidenced in human studies of postcardiotomy support [5]. The microscopic studies of the liver, however, failed to show any evidence of injury to account for these large changes. In those animals that survived more than 6 days, there was no further evidence of enzyme or total bilirubin abnormalities.
An assessment of kidney function was made by serial measurement of the blood urea nitrogen and creatinine. Renal function tests were grossly abnormal in only 1 sheep, which died of non-device-related renal failure as determined by autopsy examination.
Blood trauma was not seen, as corroborated by average plasma-free hemoglobin values less than 15 mg/dL (hemolysis is evidenced by values greater than 40 mg/dL). Platelet level measurements demonstrated no evidence of thrombocytopenia.
Device events
Problems encountered included inadequate battery life, electromagnetic interference, retrograde flow, cannula kinking, and problems with filters and connections. These were addressed and led to design changes.
Weaning
Weaning trials demonstrated that the AB-180 CSS pump speed can be reduced to 2,300 rpm over 35–40-minute intervals without clinical signs of heart failure or cerebral dysfunction.
Conclusions from animal experiments
The following conclusions were reached by reviewing the data from both the normal (1992–1994) and the AMI (1995–1996) sheep studies.
AB-180 CSS flow
The AB-180 CSS pump is capable of providing up to 5.7 L/min of flow to augment the arterial circulation.
Anatomic fit
In female sheep weighing 45–55 kg, the AB-180 CSS fits into the left anterior-inferior hemithorax without compromise or injury to any adjacent anatomic structure.
Biocompatibility
There is no evidence in gross or microscopic analyses at postmortem examination of any injury to adjacent anatomic structures, and there is no evidence of toxic injury to adjacent tissues by the materials used.
Blood trauma
Analysis of the available serial plasma-free hemoglobin concentrations and the platelet counts demonstrated that the AB-180 CSS pump does not cause excessive lysis of blood cells.
Lubricant flow, fluid type, and heparin delivery
The pump will operate for 14 days in sheep with lubricant flow rates of 2, 4, and 10 mL/h without significant wear of any part of the AB-180 CSS pump. Heparin delivery, in a solution of water at 83 IU/mL at a rate of 10 mL/h, is sufficient to maintain the pump free of thrombus or fibrin film and maintain an activated partial thromboplastin time (PTT) within the normal range for sheep.
Weaning
A long weaning protocol 8 hours without heparin is deleterious, and short intervals (35–40 minutes) of incremental speed reduction after heparin administration result in no thrombosis problems.
Alarms
The major alarms for pump failure, AC failure, high lubrication line pressure, and low sterile water infusion volume performed appropriately.
Characteristics of flow through the pump
Flow patterns and areas of stasis
Dye washout studies were performed both by infusion through the inflow cannula and through the lubrication line. In both cases, washout was rapid (within a few seconds) with no areas of stasis identified.
Flow prediction
In its current configuration, the AB-180 CSS is not equipped with a flow sensor. Instead, based on established standards, flow is predicted on the basis of loading conditions and the pump’s speed. It can be expected with 95% confidence that AB-180 CSS pump flow can be predicted within 0.7 L/min at high pump speeds and within 0.4 L/min at low pump speeds. A flow nomograph is used to estimate flow from the known values of left atrial (pulmonary capillary wedge) pressure, arterial pressure, and pump speed. Total cardiac output can be determined using a pulmonary artery catheter.
Minimal flow to prevent back flow and stasis during weaning
Concern was raised by the FDA that there would be the potential for back flow and possible stasis during the process of weaning. In vivo and in vitro studies determined the minimum pump speeds required to prevent back flow and stasis.
Human anatomic fit
Detailed anatomical measurements were made to assess positioning and impingement of the AB-180 CSS on surrounding structures when placed in the right chest in a left atrial to aortic configuration. Data were obtained from 18 autopsy studies performed on 13 men and 5 women. The heights ranged from 1.57 to 1.91 m (average = 1.75 m). The weights ranged from 50 to 116 kg (average = 72.4 kg), and the body surface area ranged from 1.54 to 2.25 m2 (average = 1.86 m2).
The conclusion drawn was that the design specifications of the AB-180 CSS are appropriate to the geometry of anatomic structures in fresh human cadavers of body size 1.54–2.25 m2. A satisfactory pump fit was found in all 18 studies.
Protocol for phase I clinical study
The AB-180 CSS is ready for clinical use. In the fall of 1997, a phase I study began, to test the system in humans in the setting of PCCS.
The objective of this trial is to assure that the AB-180 CSS is safe to use in the selected patient population without significant device-related adverse events. The study design is a prospective, nonrandomized, sequential, and observational series of 5 patients. The AB-180 CSS will be considered safe for further investigational use if: (1) There are no device-related neurological, hemolytic, or thromboembolic events resulting in death. (2) There are no device-related effects on adjacent anatomic structures requiring intervention that result in death. (3) Fewer than two reoperations are required to address device malfunction or failure. The AB-180 CSS will be considered effective if the following criteria are met: (1) Hemodynamic parameters demonstrate satisfactory circulatory support. (2) AB-180 CSS pump and controller parameters demonstrate intended operation. (3) AB-180 CSS pump explant analysis demonstrates evidence of minimal wear and thrombus formation.
Upon completion of the phase I trial, a phase II multicenter trial is planned to demonstrate the clinical efficacy of the AB-180 CSS in the treatment of PCCS.
Comment
The AB-180 CSS is designed to overcome the limitations of currently available assist devices used to acutely support the failing heart. This fully implantable device combines simplicity of operation, durability, and a low incidence of thromboembolic and hemorrhagic complications.
References
This article has been cited by other articles:
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  G. J. Endo, K. Kojima, K. Nakamura, Y. Matsuzaki, and T. Onitsuka Nitric oxide inhalation prompts weaning from the right ventricular assist device: Evaluation under continuous-flow biventricular assistance J. Thorac. Cardiovasc. Surg., October 1, 2002; 124(4): 739 - 749. [Abstract] [Full Text] [PDF]
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 B. W. Duncan Mechanical circulatory support for infants and children with cardiac disease Ann. Thorac. Surg., May 1, 2002; 73(5): 1670 - 1677. [Abstract] [Full Text] [PDF]
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J. A. Magovern, M. J. Sussman, A. H. Goldstein, G. W. Szydlowski, E. B. Savage, and S. Westaby Clinical results with the AB-180 left ventricular assist device Ann. Thorac. Surg., March 1, 2001; 71 (2007): S121 - S124. [Abstract] [Full Text] [PDF]
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