Thermo Cardiosystems Inc Research Articles

ROLE OF AN ABIOMED FOR SHORT-TERM SUPPORT AND BRIDGE TO TRANSPLANTATION

Purpose: Although HeartMate (ThermoCardiosystems Inc, Woburn, MA) is our preferred device for bridge to transplantation, we have gained experience using the ABIOMED (Danvers, MA) device for short-term mechanical support as well as a bridge to transplant in select patients. We retrospectively reviewed our 8-year experience with the ABIOMED device. Methods: From May 1994 to September 2002, 53 ABIOMED devices were implanted for short-term support in bridge-to-transplant patients. These included 16 LVADs, 21 RVADs, and 16 BIVADs. Mean age was 54±19 years for LVADs, 53±11 years for RVADs, and 40±23 years for BIVADs. Etiology of heart failure was CAD in 70% (36), ICM in 20% (10), and other in 10% (7). Duration of support was 4.8±3.5 (0–11) days for LVADs, 5.9±4.5 (0–17) days for RVADs, and 5.1±5.1 (0–20) for BIVADs. Survival while on support, successful bridging to transplantation, and post-transplant survival was calculated for each ABIOMED device. Results: Survival on support was 87.5% (14) for LVADs, 57.1% (12) for RVADs, and 50.0% (8) for BIVADs. Complete weaning was accomplished in 25.0% (4) of LVADs, 14.3% (3) of RVADs, and 12.5% (2) of BIVADs. Bridging to transplantation occurred in 12.5% (2) LVADs, 38.1% (8) RVADs, and 18.8% (3) BIVADs. Overall post-transplant 5-year survival was 64.5%; 66.7% for LVADs, 60.0% for RVADs and 66.7% for BIVADs. These results indicate that the ABIOMED can be used effectively for short-term stabilization and bridging-to-transplant in select patients.

Eosinophilic heart disease with vasculitis: supported by HeartMate left ventricular assist device and heart transplantation

Eosinophilic heart disease is rarely seen in clinical practice. We report a patient with eosinophilic heart disease who presented with acute myocardial infarction and congestive heart failure. Because of lack of a donor organ and progressive deterioration of his general condition in spite of intraaortic balloon pumping, a left ventricular assist device (HeartMate 1000 IP; Thermo Cardiosystems Inc, Woburn, MA) was implanted before development of irreversible multiple organ failure and was followed by heart transplantation.

HeartMate left ventricular assist devices: a multigeneration of implanted blood pumps.

The HeartMate family of implanted left ventricular assist devices (LVADs) developed by Thermo Cardiosystems, Inc. (TCI) span a time frame that goes back to the beginning of clinical use of mechanical circulatory support and will stretch well into the foreseeable future. Associated blood pump technology employed in the HeartMates range from an original pusher plate concept to the most advanced rotary pump devices. Starting initially with a pneumatic actuated pusher plate pump, clinical use of the HeartMate I began in 1986. In 1990, electric motor-actuated versions of the HeartMate I began to be used clinically. Presently, the HeartMate I has been implanted in some 2,300 patients worldwide, and this LVAD is a standard by which all others are currently measured. Following the HeartMate I is TCI's next-generation, the HeartMate II, a rotary-pump-based LVAD that uses an axial flow blood pump having blood immersed mechanical bearings. Clinical trials of the HeartMate II were initiated in 2000. The HeartMate III, representing TCI's next-generation LVAD, is structured around a centrifugal blood pump that uses a magnetically levitated rotating assembly. Compared to the HeartMate II, the HeartMate III has the potential for higher overall efficiency. The pump's operating life is not dependent on bearing wear. Given the significantly advanced LVAD technology represented by HeartMates II and III, coupled with the experience of HeartMate I, TCI is well-poised to keep its LVAD products as industry standards in the future.

Advanced mechanical circulatory support with the HeartMate left ventricular assist device in the year 2000

This paper describes the HeartMate left ventricular assist device (ThermoCardiosystems Inc, Woburn, MA) technology, which has been successfully introduced into the clinical arena with more than 2,400 implants as of the year 2000. The review summarizes the clinical experience, and identifies the benefits and limitations of the current state-of-the-art technology of the leading implantable circulatory support system.

HeartMate II left ventricular assist system: from concept to first clinical use

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Management of patients with end-stage heart disease treated with an implantable left ventricular assist device in a nontransplanting center

Objective: To describe the setup of a left ventricular assist device (LVAD) program in a nontransplanting center. Design: A prospective study from February 1993 to June 1999. Setting: A university hospital. Participants: Ten patients, 6 men, with a mean age of 44 years (range 16 to 63 years) and with end-stage heart failure resulting from dilated cardiomyopathy (n = 7) or ischemic heart disease (n = 3). Interventions: The patients received the TCI (Thermo Cardiosystems Inc, Woburn, MA) Heart Mate implantable assist device. Five patients had a pneumatic device, and 5 had an electric device. All except 1 patient with an electric device had the pump for an extended period. Measurements and Main Results: Median time on the ventilator was 6.2 days, and median time in the ICU was 14 days. Significant hemodynamic improvement was observed by echocardiography and invasive monitoring. Milrinone and epinephrine supplemented by prostaglandin E1 were the most commonly used drugs to avoid right-sided heart failure. Nine patients were transplanted after pump therapy of 241 days (median) (range, 56 to 873 days). One patient died because of endovascular infection and septicemia. Infectious complications were frequent, especially when the pump time was extended. Conclusions: The introduction of an LVAD program in a nontransplanting center can be achieved with good results. Intense collaboration with a transplant center is mandatory. The complication rate increased when treatment times were extended. Copyright © 2000 by W.B. Saunders Company

Mechanical Circulatory Support Sources of Emboli and Neurological Outcome

Long-term mechanical circulatory support devices are currently used as bridges to transplantation or myocar dial recovery and represent a major step forward in the treatment of end-stage heart failure. Examples of left ventricular assist devices/systems are Thoratec Labora tories (Berkley, CA), Baxter Novacor (Oakland, CA), and Thermo Cardiosystems Inc Heartmate (Woburn, MA). The CardioWest (Tucson, AZ) is the current total artifi cial heart device under clinical evaluation. These de vices are associated with neurological complications usually resulting from thromboembolic events to the cerebrum, cerebellum, or brainstem. The device itself is the commonest source of these emboli. Thrombus formation within the device occurs as a result of the interaction between the blood contacting surfaces of the device, the flow of blood through the device, and thrombotic tendency of the blood. There is a wide range of clinical presentation, from asymptomatic emboli detected by transcranial Doppler to devastating strokes. Strategies aimed to reduce the tendency to form throm bus are based on aggressive prevention with anticoagu lation and antiplatelet therapy and/or by design modifi cation. In particular, the use of a textured inner surface that encourages the formation of a pseudoneointima seems successful in reducing anticoagulation require ments and neurological complications.

Clinical experience with long-term use of implantable left ventricular assist devices: indications, implantation, and outcomes.

We describe our clinical experience with 205 implantable left ventricular assist devices at the Cleveland Clinic between December 1991 and January 2000, along with manufacturers' data submitted to the Food and Drug Administration. In patients with end-stage cardiac failure who are suitable candidates for transplantation, these devices serve as excellent bridges to transplantation. Recent modifications have increased pump reliability and reduced thromboembolic rates. The vented electric HeartMate (Thermocardiosystems Inc, Woburn, MA) and the Novacor (Baxter-Novacor, Oakland, CA) left ventricular assist systems allow patients to be discharged from the hospital while awaiting a donor heart. Experience with long-term support is providing insights into permanent implantation of these devices as destination therapy. Although infection remains a major impediment to long-term support, patient-pump interactions leading to changes in the coagulation and immune systems are being recognized, and these interactions may have important implications with respect to thromboembolism, infection, and sensitization to human leukocyte antigens (HLAs). Better understanding of these factors may eventually lead to the development of permanently implantable pumps as an alternative to transplantation.

Patch closure of the aortic anulus in a recipient of a ventricular assist device

Management of the prosthetic aortic valve continues to be a challenge in those patients who require left ventricular mechanical assistance. If left in situ, the indwelling mechanical prosthesis may increase the risk of cerebral thromboembolism. A frequent solution has been valve re-replacement with a bioprosthesis, which may reduce the thromboembolic risk but may not obviate the need for anticoagulation. We describe in this report our experience with such a patient and a novel approach to avoid valve re-replacement with patch closure of the aortic anulus. Clinical summary. A 55-year-old man who had received a Starr-Edwards aortic valve (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) some 25 years earlier had a massive anterolateral myocardial infarction. This resulted in severe mitral regurgitation, pulmonary edema, and cardiogenic shock. An angioplasty of the occluded left anterior descending coronary artery was performed successfully but did not restore ventricular function. He was transferred to our center intubated with an intra-aortic balloon pump in place and supported with multiple inotropic agents. After clinical stabilization and rapid work-up for transplantation had been completed, it became apparent that mechanical ventricular assistance was his only chance for survival until a donor heart became available. The patient underwent successful placement of a TCI HeartMate 1000 IP left ventricular assist device (LVAD; Thermo Cardiosystems Inc, Woburn, Mass). At the time of surgery, we thought that the existing prosthetic aortic valve should be removed to prevent the risk of perivalvular thromboembolism and the need for anticoagulation. A vertical aortotomy was performed anteriorly, which was later used for the outflow graft anastomosis. Attempts at permanent closure of the ball valve were unsuccessful because the ball could not be pierced with a needle. Through this exposure the struts of the valve were transected at their junction with the sewing ring and removed together with the ball valve, leaving the original and well-incorporated sewing ring in place. The aortic anulus

THE HEARTMATE II AXIAL FLOW LVAS

The HeartMate II (HMII) LVAS is an outgrowth of the NIH IVAS Contract that Nimbus and the University of Pittsburgh (UOP) have been working on the last several years. In 1997 Nimbus became part of Thermo Cardiosystems Inc. (TCI) and since then progress has been enhanced significantly on all phases of development. Efforts are now under way to complete qualification testing of the HMII for demonstration of readiness for human use. Key development issues have been: (1) continued refinement of the inflow/outflow cannulae, (2) completion of a wearable system driver and, (3) testing of a closed loop speed control system. The HMII uses TCI's FDA approved HeartMate VE support equipment consisting of batteries, power base unit, and clinical monitor. Packaging and sterilization validations for the pump and system driver have been completed. Cadaver fit studies at UOP have been conducted to verify implant site and fit, and over 20 in vivo experiments have been run to demonstrate biocompatability and auto speed control functionality. The first clinical application will be of a percutaneous system with only the pump implanted. A fully sealed system is also being developed using a new and refined transcutaneous energy transmission system. An implanted battery is under development using Lithium Ion cells from Wilson Greatbatch Ltd. Completing the sealed system is an implanted electronic driver, which uses radio telemetry to transmit diagnostic information across the skin.

Novacor left ventricular assist system versus heartmate vented electric left ventricular assist system as a long-term mechanical circulatory support device in bridging patients: A prospective study

Objective: Long-term mechanical circulatory support as a bridge-to-transplantation procedure and bridge to recovery is of increasing importance. The implantable left ventricular assist devices, Novacor N100 left ventricular assist system (Baxter Healthcare Corporation, Berkeley, Calif) and TCI HeartMate vented electric left ventricular assist system (Thermo Cardiosystems Inc, Woburn, Mass), have proved to be efficient devices in bridge-to-transplantation settings and for prolonged support. The two systems were compared with regard to reliability and morbidity. Methods: Between October 1996 and March 1998, a prospective, single-center study was done that included 40 patients, 20 of whom were treated with the Novacor system and 20 of whom were treated with the HeartMate device. The diseases were mainly dilated cardiomyopathy (13/9) and ischemic cardiomyopathy (6/10). There were no statistically significant differences between the two groups regarding age, sex, preoperative clinical blood chemistry values, hemodynamic data, or risk factors. Results: There were no statistically significant differences between the two groups with regard to postoperative hemodynamics, organ recovery, out-of-hospital support, and survival to heart transplantation. Mean duration of support was 235.3 ± 210 days for the Novacor group and 174.6 ± 175 days for the HeartMate group and mean out-of-hospital support was 241 ± 179 days and 166 ± 152 days for the two groups, respectively. Neurologic complications occurred significantly more often among the Novacor group, whereas the HeartMate group had a higher prevalence of infections and technical problems, which was statistically significant. Survival to transplantation was 65% for the Novacor group and 60% for the HeartMate group. Conclusions: Most patients had organ recovery with left ventricular assist system support, and a considerable number of patients in both groups underwent transplantation. However, both devices need revision to address the current problems, that is, thromboembolism for the Novacor device and infection and reliability for the HeartMate device. (J Thorac Cardiovasc Surg 2000;119:581-7)

Permanent Mechanical Replacement of the Left Ventricle

Patients with congestive heart failure have a poor prognosis and their care is expensive. Treatment with the HeartMate left ventricular assist device (Thermo Cardiosystems Inc, Woburn, MA) has indicated that life for such patients can be prolonged, quality of life increased, and cost of care decreased. Although currently approved only as a bridge to transplantation, the HeartMate and other such devices may one day offer permanent support of the left ventricle as an alternative to cardiac transplantation.

Chronic left ventricular support with a vented electric assist device

Based on the success of the pneumatically powered HeartMate (Thermo Cardiosystems Inc, Woburn, MA) left ventricular assist device, researchers at the Texas Heart Institute have begun conducting clinical studies of the vented electric model in bridge-to-transplantation procedures. Like the pneumatic device, the electric device is implanted intraperitoneally, but the blood pump is powered through a percutaneous lead that is connected to two rechargeable batteries. The batteries are worn in a shoulder holster; thus, patients are not tethered to a control console and are fully mobile. Two patients are currently undergoing left ventricular support with the vented electric HeartMate (duration of support, 315 days and 112 days) as they await cardiac transplantation, and they seem to be medically fit for outpatient care and follow-up. This technology may eventually allow selected patients to receive long-term support as a substitute for cardiac transplantation.

Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device

The Thermo Cardiosystems Inc (Woburn, MA) HeartMate 1000 IP left ventricular assist device (LVAD) has been evaluated as a bridge to transplantation in 34 patients for up to 324 days at seven clinical centers in the United States. Sixty-five percent of the patients underwent transplantation, 80% of whom were discharged from the hospital. Six additional control patients, transplant candidates who met the entrance criteria but who did not receive the device, were also included in the study. Although 3 (50%) of the control patients received transplants, all 6 died within 77 days of having met the LVAD inclusion criteria (100% mortality). Complications resulting from use of the device were comparable with those previously reported for all ventricular assist devices, except for thrombocmbolic events: bleeding, 39%; infection, 25%; and right heart failure, 21%. No devicerelated thromboembolic events occurred, although 1 patient experienced an event related to a mechanical aortic valve in the native heart. None of the complications had a significant negative association with outcome of the patient except for right heart failure. All survivors had a significant improvement in hepatic function before transplantation. Total bilirubin values were reduced by 60% during LVAD support. No significant differences were observed when total bilirubin values were compared at 30 and 60 days after LVAD support and at 30 and 60 days after transplantation in a cohort of 15 patients ( p > 0.05). The improvement in renal function was less predictable than that of hepatic function. Creatinine values decreased significantly before transplantation; however, the values measured at 30 and 60 days after transplantation were higher than those measured at the same intervals after LVAD support had been initiated, and this increase is presumably related to the immunosuppressive drugs. In conclusion, the HeartMate 1000 IP LVAD has been shown to be effective in supporting end-stage caidiomyopathy patients to transplantation. Thromboembolism, previously regarded as a serious complication with such devices, has not been a problem with this device. Additional patients are being enrolled into the study to further document the safety and effectiveness of this technology.

Neo-intimal development on textured biomaterial surfaces during clinical use of an implantable left ventricular assist device

Implantable left ventricular assist systems are being developed for long term clinical use. Prototype devices are currently used as extended mechanical bridges to cardiac transplantation. The Thermo Cardiosystems Inc. (TCI) pneumatic pusher plate left ventricular assist device (LVAD) features textured blood contacting surfaces to encourage the formation of an adherent fibrin-cellular coagulum. This serves as the foundation for the development of a neo-intimal lining. The TCI LVAD was implanted in 6 male patients (age range 22-53 years) between 1986 and 1988. The duration of implantation ranged from 1-41 days. No clinical thromboembolic events or pump-related thromboembolism occurred and none was evident at necropsy. The six device linings have been fully evaluated. Explanted devices were free of thrombus and calcification. Lining samples for light and electron microscopy were collected from areas of the diaphragm identical for flex and blood shear conditions and from high and low shear areas on the static housing. Islands of collagenous tissue were deposited on the static housing amongst compact fibrin. By day 13, cells populated the surface of the developing neo-intima overlying the diaphragm. By 41 days, the surface cell density increased and the cells became spindle shaped and relatively orientated in the high shear/flex area. Immunohistochemical techniques suggest that these cells are of mesenchymal origin. Textured blood contacting surfaces appear satisfactory in the preliminary clinical use of this device.