Reliability model from the in vitro durability tests of a left ventricular assist system.

A reliability test of the Novacor N100PC left ventricular assist system (LVAS) with valved conduits, including a pump/drive unit with compact controller and LVAS monitor was performed. The initial test objective was to demonstrate sufficient reliability for clinical use as a long-term circulatory support system. The subsequent objective, a test to failure, was intended to provide an assessment of the durability of the design and to determine the LVAS wearout modes. Testing began in April 1993 and was performed with 12 systems on gravity-feed mock circulatory loops. The pump/ drive units were submersed in body temperature saline for the duration of the test. Each of the LVAS units was operated at nominal afterloads of 75, 90, and 105 mm Hg, with test conditions varied to yield nominal pump outputs of 5.6, 7.1, and 8.3 L/min. Failure was defined as the inability of the LVAS to maintain an average pump output of 4 L/min or an average output pressure of 60 mm Hg. After 3 years, all systems remained on test, with durations of 2.3 to 3.0 years. Analysis of the testing to that date, using a constant hazard rate model, indicated a minimum demonstrated reliability of 94% at a 60% confidence level, or 86% at a 90% confidence level, for a 2 year mission time. This greatly surpasses the reliability level included in the STS-ASAIO Long-Term Mechanical Circulatory Support System Reliability Recommendation (80% reliability, 60% confidence level for a 1 year mission time). In the subsequent test-to-failure protocol, all systems ran failure-free for at least 3 years. System failures occurring at longer durations were caused by a single common cause: wear of the energy converter's armature support bearings and shafts. The wearout mode was gradual and could be diagnosed noninvasively before failure. An analysis using a Weibull model was performed, using the test durations of those devices that failed, those that were electively removed from test for analysis of the wear mode, and those that continued on test. As of April 1998, the test results showed a reliability, at a 60% confidence level, of >99.9% for a 1 year mission time, 99.5% for a 2 year mission, and 92.0% for a 3 year mission (>99.9%, 98.3%, and 85.9% for equivalent mission times, at a 90% confidence level). Systems continue on test after as long as 4.9 years.

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and The Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

Initial clinical experience with a wearable controller for the Novacor left ventricular assist system.

The Novacor left ventricular assist system (LVAS), an implanted electromechanically driven blood pump, has been used in an ongoing clinical trial as a bridge to cardiac transplantation since 1984. The initial configuration included a console based extracorporeal controller. Because patients supported by the device usually become rehabilitated and highly mobile, a wearable control system was developed for the ambulatory patient. Ergonomically designed for portability, comfort, and appearance, it offers the recipient greater mobility, improved self-image, and an enhanced quality of life. This wearable control system consists of a microprocessor based compact controller that drives the implanted pump/drive unit in synchronous counterpulsation to the native heart. Main and reserve rechargeable power packs, each incorporating a "smart" monitoring circuit with charge-level display and alarm, are capable of supporting the pump for as long as 7 hr. An LVAS monitor can be connected to the controller for device monitoring and adjustment or as a power supply in lieu of the main power pack. Clinical evaluation in patients with end-stage heart disease followed the same protocol as the console study. By April 4, 1994, 41 patients had been supported by the wearable system, including 9 patients currently being supported. Mean duration of use was 51 days (range, 1.5-143+ days), compared with 42 days for 170 console patients (range, 0-370 days). Survival to transplant was 66%, which was similar to the survival (60%) for the patients using the console. Post-transplant survival was 100%, compared with 90% for console patients (not significantly different). After recovering from implant surgery and pre-implant morbidity, device recipients had considerable freedom and mobility and were able to move freely within and outside the hospital. Recipients could readily switch between monitored and untethered operation and could manage power pack replacement and recharging.

Clinical evaluation of the Novacor totally implantable ventricular assist system. Current status.

The totally implantable Novacor left ventricular assist system (LVAS) is currently approaching clinical evaluation. In vivo testing and production are underway with National Institutes of Health (NIH) support. Activity over the past year has focused on manufacturing engineering, preproduction quality assurance, and in vivo experiment completion. Subsequent to successful completion of the NIH-sponsored, 2-year preclinical device readiness test (DRT), a number of refinements were identified and approved by the NIH technical/data review board. Most of these were necessitated by obsolescence or unavailability of electronic components and the decision to use only high reliability military (MIL) qualified electronic components and processes. A few additional refinements were identified to increase design margins, all of which were qualified by accelerated testing. The development of production processes, automated test programs, and MIL compliant environmental stress screening procedures was completed. Production of LVAS subsystems, including core electronic components (hybrids, application-specific integrated circuits, and surface mount boards), was initiated. Animal studies are underway. The clinical trial, at Presbyterian-University Hospital of Pittsburgh and St. Louis University Medical Center, awaits completion of in vivo experiments, protocol development, and Food and Drug Administration approval.

Chronic ovine evaluation of a totally implantable electrical left ventricular assist system.

The totally implantable Novacor left ventricular assist system (LVAS) comprises a pump/drive unit (VAD), electronic control and power subsystem (ECP), variable volume compensator (VVC), and belt skin transformer (BST). The system is now undergoing chronic in vivo evaluation. Cumulative animal testing of VAD, VVC, and BST subsystems are 12.1, 4.9, and 43 years, respectively. The longest implants were 279 days for the VAD, 767 days for the VVC, and 1,148 days for the BST. A chronic implant of the total system was electively terminated at 260 days. The LVAS was powered via the BST. Continuously monitored hemodynamic and pump parameters have demonstrated normal hemodynamics and LVAS operation. Periodic VVC determinations suggest a 0.8 ml/day diffusive gas loss. Tether-free operation has been demonstrated with an Ag-Zn battery backpack. The animal was healthy and free of infection as indicated by routine hematologic, biochemical and serum enzyme determinations. Hemolysis is minimal (plasma free hemoglobin less than 5 mg%). Pump output ranged from 7 to 8 L/min. Severe valve calcification was the reason for elective termination at 260 days. This preclinical in vivo experience, and in vitro reliability studies, demonstrate efficacy of the total system.

In vitro and in vivo testing of a totally implantable left ventricular assist system.

The totally implantable Novacor LVAS is being tested under NIH auspices to demonstrate safety and efficacy before clinical trials. Twelve complete systems (submerged in saline at 37 degrees C) are being tested, with an NIH goal of demonstrating 80% reliability for 2 year operation with a 60% confidence level. The systems, which are continuously monitored, are diurnally cycled between two output levels by automatically varying preload and afterload. Currently, 14.3 years of failure-free operation have been accumulated, with a mean duration of 14 months. Using an exponential failure distribution model, the mean time to failure (MTTF) is greater than 8.8 years, corresponding to a demonstrated reliability (for a 2 year mission time) of 80% (80% confidence level). Recent ovine experiments with VAS subsystems include a 767 day volume compensator implant, a 279 day pump/drive unit implant and a 1,448 day BST implant. The last 12 chronic pump/drive unit experiments had a mean duration of 153 days (excluding early postoperative complications). This compares favorably with the NIH goals for complete systems (5 month mean duration). Complete system experiments are currently underway.

Bioprosthetic valve calcification and pseudoneointimal proliferation in bovine and ovine models.

Both porcine (PX) and bovine pericardial (BP) valves have been used in the implantable Novacor left ventricular assist system (LVAS). Results from 58 chronic LVAS implants of greater than 7 days in calves and adult sheep are presented: the PX valve was used in 41 and the BP in 17. With PX valves, the maximum and mean assist durations were 161 and 54 days, respectively, in the calf and 279 and 129 days, respectively, in the sheep. The maximum and mean durations for BP valves were 93 and 38 days (calf) and 153 and 69 days (sheep). In bovine studies with PX valves, severe obstructive pseudoneointimal (PNI) proliferation in the Dacron inflow conduit was the primary cause for termination; valves exhibited moderate calcification. With BP valves, both PNI proliferation and severe valve calcification contributed to a declining pump output, leading to termination. In contrast to the bovine experience, PNI proliferation was not observed in ovine implants. BP valves still became calcified, as evidenced by a progressive decline in pump output (from about twelve weeks) and confirmed at termination. Valve calcification was minimal with the PX valves, even at 236 days. These results favor the adult ovine animal model for extended implants.

Evolution of the solenoid-actuated left ventricular assist system: integration with a pusher-plate pump for intra-abdominal implantation in the calf.

The performance of an implantable left ventricular assist system (LVAS) utilizing a pulsed solenoid energy converter and a pusher-plate blood pump has been characterized in vitro and in vivo. A microprocessor-based electronic control system makes the LVAS completely self-regulating over the range of operating conditions and provides considerable flexibility in various assist modalities. Over forty thousand hours of in vitro and in vivo operating experience has been accumulated with current systems, and significant progress has been acheived in system durability and reliability. A new toggle latch has provided nearly a year of failure-free operation on the bench, without measurable wear. Energy converter efficiencies of 50% have been demonstrated. In vivo evaluation has been highlighted by an animal experiment still in progress after nearly four months of fault-free, continuous synchronous pumping.

An implantable permanent left ventricular assist system for man.

A new implantable, electrically powered LV AS suitable for long-term use in man has been designed and is under development. The system is based on the well developed high-efficiency pulsed solenoid technology and a careful a priori systems approach to integration of the energy converter with a suitable blood pump. A novel dual pusher-plate sac-type blood pump with significant advantages in hemodynamics, antithrombogenicity and durability has been designed. The complementary energy converter, a pivoted-armature dual-gap solenoid, addresses weaknesses in previous designs while retaining all the good features of its forerunners and provides for the first time a truly integrated implantable circulatory assist system for man.

An intrathoracic solenoid drive system for chronic left ventricular bypass.

The performance of an implantable Left Ventricular Assist System (LVAS), utilizing an advanced solenoid energy converter, has been extensively studied in vivo. For optimum system efficiency, reliability and responsiveness, the energy converter and blood pump are integrated into a single compact unit, which is implanted intrathoracically in an 80 Kg calf. The MK19 LVAS is battery operated and controlled by a miniature analog computer and is completely self-regulating. The maximum hemodynamic power provided by this circulatory assist system is 4 watts with cardiac outputs up to 10 L/min and a total system efficiency of 30%. LVAS function has been studied in a series of 19 calf experiments progressing through acute, model and chronic evaluations. Development of the implantation protocols and hemodynamic characterization were achieved in a series of 8 acute experiments. Long-term studies were conducted for periods up to 43 days in a series, including 2 control experiments using non-functional models and 9 functional LVAS chronic experiments. Aortic, left ventricular and left atrial pressures, pulmonary artery flow and pump outflow were monitored with chronically implanted transducers. A dedicated minicomputer provided real-time hemodynamic analysis and continuous surveillance of physiologic and LVAS parameters. In acute studies and in the immediate post-operative period of chronic experiments, synchronous LVAS operation reduced peak LV pressures to 30 mm Hg with cardiac outputs of 5 to 7 L/min. In chronic studies, with recovery of normal LV function, long-term synchronous operation was maintained, without capture of the total cardiac output and with significantly reduced ventricular unloading.