Michael P. Macris

Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart

Advances in technology and increased clinical need have led to the development of a new type of blood pump. The Jarvik 2000 Heart is an electrically powered, axial-flow left ventricular assist device that has been developed during the past 13 years. Unlike first-generation left ventricular assist devices, which were developed in the 1970s and were designed to totally capture the cardiac output, the Jarvik 2000 is designed to normalize the cardiac output by augmenting the function of the chronically failed heart for extended periods. Design iterations have been tested in 67 animals, and clinical trials have recently begun. Three patients have received the Jarvik 2000 as a bridge to transplantation, and 1 patient is being supported permanently outside the hospital. All 4 patients have improved from New York Heart Association functional class IV to class I, and 2 of them have been discharged from the hospital after heart transplantation. The experimental and clinical results indicate that the Jarvik 2000 can provide physiologic support with minimal complications and is reliable, biocompatible, and easy to implant.

Cardiac Transplantation in Patients over 60 Years of Age

Cardiac transplant programs have routinely excluded patients over 55 years of age from consideration as transplant candidates. The Texas Heart Institute modified this policy of using age as a contraindication to transplantation. Between July, 1982, and August, 1987, a total of 200 cardiac transplants were performed, 28 (14%) of which were in patients over 60 years of age, the eldest being 66 years old at the time of transplant. Our immunosuppressive regimen consisted primarily of cyclosporine and prednisone. In 1985, azathioprine was added in an effort to decrease dosages of cyclosporine, thereby decreasing its associated nephrotoxicity. The incidences of rejection and infection were 1.2 and 1.4 episodes/patient, respectively, for those over 60 years of age versus 1.7 and 1.3 episodes/patient, respectively, for those less than 60 years of age. Of the 28 patients, 23 are alive and well. Four deaths were caused by infection, and the other by diffuse coronary arteritis. The one-year actuarial survival for patients over 60 years of age was 83%, compared with 75% for the other transplant patients. We conclude that persons over 60 years of age can undergo cardiac transplantation with results equal to or perhaps better than those of other heart transplant patients. Our experience suggests that advanced age should not be considered a major contraindication to cardiac transplantation.

Use of a Left Ventricular Assist Device in an Outpatient Setting

The vented electric Heartmate LVAD (VE-LVAD) (Thermo Cardiosystems, Inc., Woburn, MA) is a reliable, fully portable system that allows selected patients with end-stage cardiomyopathy to undergo outpatient treatment while waiting for heart transplantation. This implantable, pusher-plate LVAD is actuated by an electric motor located within the pump housing. The patient wears external batteries and a system controller, which power and control the LVAD motor through a percutaneous lead. Since May 1991, four men have been supported with the VE-LVAD. They ranged in age from 33 to 50 years (mean, 44.3 years); two had idiopathic cardiomyopathy, and two had ischemic cardiomyopathy. Of the four patients, three underwent support of 196, 219, and 504 days; support in the fourth patient is ongoing at more than 90 days. All four patients were fully rehabilitated to New York Heart Association Class I status. Because they were well and fully mobile, the protocol was amended to allow these patients to leave the hospital in a four phase program that begins with 16 hr day passes and leads to hospital discharge. When patients leave the hospital, they are accompanied by trained family members or friends. The patients who have participated in the program have performed routine activities, attended social events, and spent the night at home. The VE-LVAD system seems safe and appropriate for the outpatient setting in selected patients. Patients have been able to manage the system without assistance from medical or engineering personnel. This initial positive experience with outpatient LVAD treatment demonstrates the potential for providing long-term cardiac support with this type of implantable technology.

Development of an Implantable Ventricular Assist System

BACKGROUND This study describes the present state of progress in the development of the Jarvik 2000 ventricular assist system. METHODS Designed for implantation in the human thorax, the system consists of a small (25 cm3, 90 g) intraventricular axial-flow blood pump that transmits power and data via internal electronics and a transcutaneous energy transfer system. The pump is powered by portable internal and external polymer lithium ion batteries. The only moving part, the pump rotor, contains a permanent magnet of a brushless direct-current motor that mounts an axial-flow impeller and partial magnetic thrust support, with blood-immersed radial and thrust bearings. The motor uses a redundant coil and electric lead design, which permits continued operation in case of wire breakage. RESULTS Seven calves have been supported for an average of 107 days (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist system. No physiologic complications have occurred. When its user is at rest, the pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour. Renal and hepatic functions have remained normal throughout the duration of all studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean, 6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed no damage related to the device. CONCLUSIONS These studies indicate that the Jarvik 2000 ventricular assist system is feasible in animals and holds promise for long-term support of patients.

In vivo evaluation of an intraventricular electric axial flow pump for left ventricular assistance.

In vivo studies have begun to evaluate a new intraventricular electric axial flow left ventricular assist device (LVAD), the Jarvik 2000, which is a small, valveless pump that is placed inside the left ventricle through the left ventricular apex. The operation, which is performed through a left thoracotomy, may be done without cardiopulmonary bypass and aortic cross-clamping. Outflow is provided through a 16 mm softly woven, Dacron graft anastomosed to the descending thoracic or abdominal aorta. Pump flow, which varies from 2 to 16 l/min in vitro, is changed by adjusting the speed of pump rotation. Preliminary studies were done to evaluate the ease of implantation, hematologic and anatomic compatibility, and pump performance. The device has been implanted in seven healthy, preconditioned calves (83-138 kg), one of which is currently undergoing support. The implantation procedure averaged 3 hours. There were no operative deaths, and blood transfusions were not required. Postoperatively, anticoagulation was achieved with heparin followed by warfarin sodium to maintain prothrombin time or partial thromboplastin time at 1.5-2.0 times baseline. In the six completed studies, support time ranged from 2 to 120 days (mean, 36 days). The seventh calf has been supported for 30 days. In the four long-term studies (20, 70, 120, > 30 days), the mean plasma free hemoglobin values during support were 11.0, 7.7, 6.6, and 3.4 mg/dl, respectively. Under normal conditions, the average daily flow rate ranged from 5 to 6 l/min. During treadmill exercise (10% grade, 1.5 km/h) lasting 20 minutes, peak flow rates exceeded 8 l/min. These pilot studies suggest that this intraventricular axial flow pump is relatively easy to implant, operate, and control. In addition, it is hemocompatible, provides physiologic flow rates, and may be able to provide long-term circulatory support.

Progress in the development of the ABIOMED total artificial heart.

The ABIOMED implantable total artificial hearts in the final phase of engineering development. The system has a compact electrohydraulically driven energy converter sandwiched between two blood pumps, an internal electronics pack, an internal battery, a transcutaneous energy transmission coil for power transmission, and external wearable electronics pack and battery. The current effort is to complete development of the system during 1996 in preparation for formal pre clinical testing of the device. In vivo studies with the current thoracic unit (ABH II) have achieved 108 days of survival verifying the thermal, physiologic, and hematologic compatibility of the system. The abdominal implantable electronics pack showed no thermal dissipation problem. System improvements include scaling down the size of the thoracic unit, and efficiency enhancement in the power and hybrid electronics. The new system (ABH III) retains the flow capacity of greater than 10 L/min. Size reduction results in an atrial to sternal dimension that would fit 98% and 75% of men and women, respectively.

Progress in the development of a transcutaneously powered axial flow blood pump ventricular assist system.

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 ± 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (∼1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.

Effect of prior cardiac surgery on survival after heart transplantation.

We conducted a retrospective analysis of 182 adult orthotopic heart transplant patients who underwent operations at our institution between July 1982 and October 1987 to determine whether prior cardiac operation affects survival. Group I included the 72 patients (39.6%) who had undergone a previous cardiac operation or operations and group II, the 110 (60.4%) who had not. The mean age of the patients in group I was 52.1 +/- 8.1 years and in group II, 46.1 +/- 10.2 years (p less than 0.01). The incidence of ischemic heart disease was 86.1% in group I and 29.1% in group II (p less than 0.01). All patients received cyclosporine-based immunosuppression. More patients in group I than in group II required reoperation for bleeding after transplantation: 18 (25.0%) versus 9 (8.2%) (p less than 0.01). The actuarial 1-year and 3-year survival rates were 77.6% and 66.5%, respectively, for group I and 77.1% and 66.3%, respectively, for group II. Because both groups had similar survival rates, we believe that prior cardiac operation in heart transplant recipients does not compromise long-term survival.

Retrospective analysis of infection in patients undergoing support with left ventricular assist systems.

Infection is a problem in patients undergoing support with left ventricular assist systems. To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Infection was defined as fever > 38 degrees C, white blood count > 12,000 cells/ml, and a need for antimicrobial therapy. Of the 56 patients, 25 (41%) had an infection. Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%). The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%). Of the positive cultures, 84% were bacterial and 16% fungal. There were no positive viral cultures. Positive cultures from left ventricular assist system related sites made up only 8.7% of the total. All but one of the patients with device related infections survived to transplantation. The long-term survival rate for patients in this group after transplantation was 77.8%. Two patients required surgical revision of the driveline because of infection. Both were free of infection postoperatively. Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days). In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.

Hospital charges for conventional therapy versus left ventricular assist system therapy in heart transplant patients.

An important goal of a left ventricular assist system (LVAS) is to provide long-term, safe, cost-effective mechanical circulatory support. The Heartmate LVAS (Thermo Cardiosystems, Inc., Woburn, MA), used in recent clinical trials as a bridge to transplantation, has proven extremely reliable for long periods, and its use has improved the survival rates in patients who subsequently received a donor heart. Patients who have been implanted with an LVAS often have significantly improved physical status and can leave the intensive care unit (ICU) and be treated at less expense elsewhere in the hospital. In this preliminary report, the authors analyzed hospital charges for three groups of patients: heart transplant patients who received conventional medical therapy before transplantation (Group 1), transplant patients who received in-hospital LVAS therapy (Group 2), and one patient who awaited transplantation at home while undergoing LVAS support. Group 1 patients (n = 6) received intraaortic balloon pump (IABP) support and inotropic therapy in an ICU before transplantation. Group 2 (n = 6) patients were receiving IABP support and inotropic therapy when the LVAS was implanted and eventually underwent heart transplantation. The length of hospital stay in Group 1 (51 days) was significantly shorter than in Group 2 (185 days). Mean hospital charge in Group 1 was