Effect of age on outcomes after left ventricular assist device placement.

The influence of age on outcomes after left ventricular assist device (LVAD) implantation is not well studied. To address this question, we assessed 222 patients who underwent LVAD placement and were divided into quartiles based on age (years): group 1, or=60. Eighty-four patients died on LVAD support. Six- and 12-month survivals for the four groups of LVAD patients were 67.7, 73.7, 49.8, and 38.2, and 49.4, 57.3, 42.7, and 26.2, respectively (all P<.01). Older patients showed a higher risk of infections, embolic strokes, and respiratory complications. They were the least likely to undergo reoperations postimplantation (56%, 53%, 50%, 46%, P=.06). After adjusting for baseline differences between the groups, there was a trend toward increasing mortality with age, which did not reach significance (odds ratio 1.93; 95% confidence interval 0.95 to 3.92 for the oldest quartile as compared with the youngest). In conclusion, these results suggest in the absence of other high risk factors, age alone should not be used as an independent contraindication for LVAD implantation.

Flight experience with the Novacor LVAS.

As Novacor LVAS recipients continue to be discharged from the hospital to await cardiac transplantation, an increasing number of patients either need or desire to use air transportation. To date, two test experiences have been reported with the Novacor LVAS operating in a mock circulatory loop during air travel. One involved the transport of a mock loop on a medical helicopter, and another preceded an international flight of an LVAS recipient from Japan to the United States. In each situation, the LVAS, connected to a water-filled mock circulatory loop, was placed on the aircraft and instrumentation was checked to verify that there was no adverse effect on the Novacor equipment, or on aircraft systems, during flight. Novacor LVAS recipients have also been reported to have flown more than 37 commercial air transports throughout Europe, in both rotary and fixed wing aircraft, without incident. Laboratory testing of electromagnetic emissions were also conducted to include specific frequencies utilized by aircraft instrumentation. These tests show that the Novacor LVAS is well below the International Special Committee on Radio Interference (CISPR 11) emissions limits; these data can be provided to an air carrier anticipating transport of a Novacor recipient. Details of the results from the mock loop field testing, as well as the laboratory testing of electromagnetic emissions pertinent to air travel, are presented. This experience suggests that that there has been no impact on aircraft electronics from the LVAS, nor has the aircraft instrumentation generated any interference with the components of the Novacor LVAS.

The totally implantable novacor left ventricular assist system.

The Novacor Left Ventricular Assist System (LVAS) (Novacor Corp, Oakland, CA) was initially console-based and has been available since 1993 in a wearable configuration. It has been successfully used for the past 16 years as a bridge to cardiac transplantation in patients with end-stage congestive heart failure. The Stanford experience represents 53 patients (48 male, 5 female) with a mean age of 44 +/- 13 years (16 to 62) and a mean support time of 56 +/- 76 days (1 to 374). Complications with LVAS use consisted predominantly of bleeding (43%), infection, (30%), and embolic cerebrovascular events (24.5%). Sixty-six percent of the supported patients were successfully bridged to cardiac transplantation. In animal studies, 4 sheep had the totally implantable configuration in place for a cumulative duration of 1 year with 1 animal supported for 260 days. The next generation Novacor LVAS will be small, quiet, and fully implantable without the need for volume compensation. It will also provide physiologic pulsatile flow and will be fail-safe.

Economics of devices.

BACKGROUND: The economics of devices used for mechanical circulatory support not only involve the patient, the provider, and society as a whole, but also, importantly, the developers and manufacturers of these new technologies. The combined effects of years of development and testing with significant regulatory, reimbursement, and acceptance barriers make this a capital-intensive and high-risk endeavor. In addition, long-term circulatory support is, today, essentially limited to bridge to transplantation, a "market" of only $100 million. Competition is increasing, with new devices under development and entering clinical trials. CONCLUSIONS: Economic health for this new industry is dependent on expanding clinical indications to definitive or destination therapy, and perhaps other applications such as bridge to recovery and assisted medical therapies.

Mechanical circulatory support for advanced heart failure: effect of patient selection on outcome.

BACKGROUND: Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival. METHODS AND RESULTS: Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LVAS implantation: respiratory failure associated with septicemia (odds ratio 11.2), right heart failure (odds ratio 3.2), age >65 years (odds ratio 3.01), acute postcardiotomy (odds ratio 1.8), and acute infarction (odds ratio 1.7). For patients without any of these factors, the 1-year survival after LVAS implantation including the posttransplantation period was 60%; for the combined group with at least 1 risk factor, it was 24%. CONCLUSIONS: Careful selection, specifically implantation before patients become moribund, and improvement of management may result in improved outcomes of LVAS treatment for advanced heart failure.

Improved outcomes with an implantable left ventricular assist system: a multicenter study.

BACKGROUND: Cumulative experience with the Novacor wearable electric left ventricular assist system (LVAS) now exceeds 850 recipients. The pump inflow conduit (IFC) has been implicated in embolic complications. METHODS: Clinical outcomes were compared for two IFC designs in a retrospective, nonrandomized, multicenter study. The original IFC (woven, unsupported, crimped polyester: control group) and an alternative IFC (knitted, gelatin-sealed, integrally supported, uncrimped polyester: test group) were utilized upon availability in North American and European centers. Differences in cerebral embolism to 180 days postimplant were analyzed. RESULTS: Four hundred ninety patients implanted between August 1996 and August 1999, were studied. Two hundred eighty-eight received the control IFC and 202 received the test IFC. The groups (control, test) were well matched for age (48, 49 years), etiology (idiopathic 53%[152 of 288], 55% [112 of 202]; ischemic 34% [97 of 288], 33% [66 of 202]) and mean observation time (97, 91 days). The incidence of embolic cerebrovascular accidents (CVA) was 21% (60 of 288) in the control and 12% (24 of 202) in the test group (p = 0.010). Independent risk factors for embolic CVA were found to be preimplant acute myocardial infarction (odds ratio 4.3), age above 50 years (odds ratio 2.1), and ischemic etiology (odds ratio 1.7). There was no difference in survival between the groups (71% [205 of 288], 68% [137 of 202]). CONCLUSIONS: The alternative (test) IFC has significantly reduced the incidence of embolic CVA. This improvement is likely due to increased resistance to deformation at implant, improved neointimal adhesion, and more favorable blood flow characteristics within the conduit.

The Novacor left ventricular assist system: clinical experience from the Novacor registry.

The electrically powered Novacor left ventricular assist (LVAS) system was first used clinically as a bridge to transplant in 1984. The configuration has evolved to the current wearable model used clinically for the first time in 1993. In 1998, the inflow conduit was modified, reducing embolic events by 50%. Over 1100 implants have been performed worldwide with cumulative support greater than 300 patient years, and only 0.7% requiring replacement. The Novacor is a safe and effective device for bridge to transplant, bridge to recovery, or potentially permanent implant with reliable long-term support for periods as long as 4 years.

Long-term mechanical circulatory support with the wearable Novacor left ventricular assist system.

OBJECTIVE: As of July 1st 1999, 36 European patients have lived for more than 1 year supported by the Novacor wearable electric left ventricular assist system (LVAS). All were unresponsive to maximum medical therapy, prior to implantation. These patients offer an unique opportunity to evaluate the feasibility of long-term ambulatory mechanical circulatory support as a therapeutic option for patients in profound cardiac failure. METHODS: Data was obtained from the Novacor European Registry. RESULTS: At the time of implantation, median age was 55 (18-67) years. Aetiology was ischemic (9, 25%) or idiopathic (26, 72%) cardiomyopathy, and myocarditis (1, 3%). Median duration of LVAS support was 1.49 (1. 03-4.10) years. Eight recipients had LVAS support times >2 years, of which two were >3 years and one >4 years. The median time spent outside the hospital was 1.27 (0.58-3.83) years, representing 82% of the duration of LVAS support. No mechanical failure was observed during the entire observation period. One pump was replaced electively after 3.67 years due to pump driver wear-out. Twelve patients (33%) are currently on support while 17 were transplanted (14, 39%) or weaned (3, 8%). Seven (19%) patients died after a median of 1.24 years circulatory support. CONCLUSIONS: Experience with long-term Novacor LVAS recipients has demonstrated effective rehabilitation in this group of patients with refractory advanced heart failure. This suggests that LVAS therapy may offer a safe and realistic option for patients for whom no other effective therapy is available. The patient sub-population that would benefit most from this therapy remains to be defined.

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.

Protocol for releasing Novacor left ventricular assist system patients out-of-hospital.

Between September 1984 and April 1995, the Novacor left ventricular assist system (LVAS) has provided more than 13,000 days of mechanical circulatory support to cardiac transplant candidates in the United States and Europe. The duration of support of these 312 patients has ranged between 1 and 370 days, with an average support of 40 days, including use of the console based system and the wearable system. Of this group, 21% have been supported for more than 60 days, with an average support of 118 days. We have seen that patients who have been supported for more than 30 days have recovered from the effects of LVAS implant surgery and have shown a potential for rehabilitation from morbid congestive heart failure. Few changes to the pump settings or the medical orders have been needed after the third postoperative week. The reliability of the LVAS and the degree to which patients can be rehabilitated suggest that restricting patients to a hospital environment is unnecessary. In addition, the increasing wait for a donor heart, the quality of life that can be achieved, and the high cost of inpatient care make it desirable to discharge patients from the hospital and allow them to await a donor heart in a more home-like setting.

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Study overview. LVAS Study Group. Left Ventricular Assist System.

In this summary, the authors provide the background of and proposed protocol for a clinical evaluation of the safety and efficacy of the Novacor N120 Left Ventricular Assist System, sponsored by the National Heart, Lung, and Blood Institute. Although the clinical trial was never carried out, the protocol developed for this trial may be useful to other investigators considering a clinical trial of a circulatory support device. The protocol is summarized here and in five more detailed articles in this issue.

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Device explant protocol.

An explant protocol was developed to investigate the effects of implantation of a left ventricular assist system (LVAS) manufactured by Novacor Division, Baxter Healthcare Corporation on the function of end organs (such as the brain, the kidney, the liver), with particular interest in examining possible complications due to LVAS support. Emphasis was placed on an analysis at the time of device removal and/or autopsy of 1) the local LVAS-host interface; 2) remote cardiovascular and end-organ effects; and 3) the impact of chronic circulatory support on the native heart. To accomplish these objectives, tissue and device samples must be obtained in an appropriate fashion to ensure photographic documentation, microscopic examination, microbiologic and biochemical assays, and compliance with regulatory and manufacturer requirements. This article describes the techniques and protocol that were proposed to ensure the quality of device explant and tissue analysis.

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.