Peer M. Portner

Implantable electrical left ventricular assist systems: Bridge to transplantation and future

An implantable left ventricular assist system (LVAS) utilizing an electromechanically driven dual pusher-plate blood pump has been employed in a multiinstitutional trial as a bridge to cardiac transplantation. Under development for permanent circulatory support in patients with end-stage heart disease, the LVAS, in this application, derives power and control from an external console via a percutaneous lead. The LVAS was implanted in 20 patients (16 men, 4 women) who were hemodynamically unstable or in refractory cardiogenic shock. The mean age was 44.9 years (range, 25 to 63 years). Preoperative diagnosis was evenly divided between end-stage ischemic disease, cardiomyopathy, and acute myocardial infarction. Implanted in the left upper quadrant within the anterior abdominal wall, the blood pump was connected between the left ventricular apex and ascending aorta. Total support of the systemic circulation and substantial left ventricular unloading were achieved with synchronous counterpulsation for periods up to 90 days (mean, 22.7 days). All patients were stabilized hemodynamically. The mean preoperative cardiac index of 1.5 L/min/m2 increased by a factor of 2. Pulmonary arterial pressures decreased substantially. Serious complications occurred in 16 patients, precluding cardiac transplantation in 10. Most complications (greater than 70%) were in patients who did not receive transplants; the most common complication was bleeding. Twelve of 13 patients with LVAS implants for more than seven days were mobilized, and 4 were fully ambulatory and completely rehabilitated. Orthotopic cardiac transplantation was performed in 10 patients after implants ranging from two to 90 days (mean, 30.3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical Circulatory Support for Advanced Heart Failure

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 LV...

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 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.

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 long as 4 years.

Destination mechanical circulatory support: proposal for clinical standards

Mechanical circulatory support device (MCSDs) have evolved during the past 2 decades to become accepted bridging therapy for patients with irreversible hemodynamic deterioration while awaiting cardiac transplantation. More recently, based on the results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) study, MCSD therapy has become available as permanent or destination therapy for a restricted population of patients with advanced heart failure (AHF) not thought to be appropriate transplant candidates. The potential proliferation of new devices and the possible expansion of the target populations bring new responsibilities. Unlike pharmaceutical trials that have included thousands of patients, trials with MCSDs will continue to be performed on a relatively small scale because equipoise for randomization can be undermined by the unmasked nature of mechanical support, the logistics of study finances, and the continuous device improvements—all of which constrain trial size and duration. Currently, insufficient evidence beyond REMATCH criteria exists for refining potential long-term MCSD therapy candidate cohorts, and application of this challenging therapy is complicated further by the degree of institutional commitment, surgical expertise, multidisciplinary skills, available devices, and overall experience required for the successful application of mechanical circulatory support. The REMATCH trial was a landmark study that demonstrated the benefit of MCSDs in patients with AHF not eligible for transplantation. Patients supported with MCSDs had significantly better survival at 1 year than did patients with advanced end-stage heart failure who were treated medically (many with long-term parenteral inotropes). Although a survival benefit was clear, it was only over a 2-year time period, and morbidity was substantial, particularly with respect to infections, neurologic events, and pump malfunctions. These observations force us to consider carefully patient selection and the infrastructure of centers with strategies developed to provide this type of care. In the United States, the Food and Drug Administration (FDA) approval of the HeartMate From Columbia University, New York, New York; Cleveland Clinic Foundation, Cleveland, Ohio; Harvard University, Boston, Massachusetts; Stanford University, Stanford, California; University of Alabama at Birmingham, Birmingham, Alabama; University of California at Los Angeles, Los Angeles, California; University of Minneapolis, Minneapolis, Minnesota; Midwest Heart Specialists, Downers Grove, Illinois; Tufts–Northeast Medical Center, Boston, Massachusetts; University of Pittsburgh, Pittsburgh, Pennsylvania. Submitted February 7, 2002. Reprint requests: Mario C. Deng, MD, The Heart Failure Center and Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, Milstein Hospital Building, Room 5-407, 177 Fort Washington Avenue, New York, New York 10032. Telephone: 212-305-0200. Fax: 212-305-7439. E-mail: md785@columbia. edu J Heart Lung Transplant 2003;22:365–369 Copyright

Novacor left ventricular assist system long-term performance: comparison of clinical experience with demonstrated in vitro reliability.

Since the first implant of the Novacor wearable left ventricular assist system (LVAS) in 1993, median implant duration worldwide has increased from 93 days (max 2.2 years) to 202 days (max 4.1 years) in May 2001. In vitro reliability/durability testing of the Novacor LVAS has previously demonstrated a mean time to failure of 4.2 (3.04–5.59) years. These tests revealed a single failure mode—main bearing wear—with measurable symptoms gradually appearing before degradation of pump function. An ongoing clinical study of 37 recipients implanted for more than 1 year has shown that a simple noninvasive method of pump surveillance, derived from the in vitro experience, is well tolerated in the clinical setting. The overall clinical experience is consistent with in vitro reliability/durability tests that demonstrated 99.9%, 98.5%, and 87.4% freedom from wear at 1, 2, and 3 years (80% confidence). So far, the clinical study has shown 99.4%, 91.5%, and 91.5% freedom from wear at the same 1, 2, and 3 year intervals (95% confidence). Furthermore, the clinical findings have corroborated the in vitro experience that the wear mechanism is generally measurable and gradual, enabling elective clinical LVAS replacement or transplantation. Clinical valve performance was also monitored, using an exercise protocol and collecting comparative data on peak flows across the valves. It was determined that developing valve dysfunction could be diagnosed early and, in the failures that did occur (n = 2), these were related to the patient’s disease state. In conclusion, although clinical conditions exposed the LVAS to a wide range of different environmental and hydraulic stresses, the surveillance program described appears practical and reliable, and its findings broadly parallel those of the earlier in vitro study. Additional data needed to complete formal validation continue to be collected.

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.

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 converters 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.

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.