Daniel Tamez

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.

Design concepts and principle of operation of the HeartWare ventricular assist system.

Implantable left ventricular assist devices provide circulatory support for patients at risk of death from refractory, end-stage heart failure. Rotary blood pumps have been designed for increased reliability and smaller size for use in a broader population of patients than the first-generation pulsatile devices. The design concepts and principle of operation of the HeartWare System are discussed. The HeartWare Ventricular Assist System (HVAD) is a small centrifugal flow pump with a displacement volume of 50 ml and an output capacity of 10 L/min. A unique wide-blade impeller is suspended by hybrid passive magnets and hydrodynamic forces. An integrated inflow cannula is inserted into the left ventricle and is held in position by an adjustable sewing ring; the pump is positioned in the pericardial space. The 10-mm outflow graft is anastomosed to the ascending aorta. External system components include the microprocessor-based controller, a monitor, lithium-ion battery packs, alternating current and direct current power adapters, and a battery charger. Physiologic control algorithms are incorporated for safe operation. Preclinical life cycle tests have shown the HVAD to be highly reliable. This system design offers reliability, portability, and ease of use for ambulatory patients.

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.

In vivo evaluation of the HeartWare MVAD Pump

OBJECTIVE The current design trend for left ventricular assist devices (LVADs) is miniaturization, which aims to increase the treatable patient population and enable new treatment indications by reducing surgical trauma and the complications associated with device implantation. The MVAD Pump (HeartWare Inc, Framingham, MA) is a small, axial VAD that uses magnetic and hydrodynamic impeller technology and incorporates wide helical flow channels to minimize shear stress. In this study, we implanted the MVAD Pump in an ovine model to evaluate device hemocomaptiblity, biocompatibility, performance, and safety. METHODS The MVAD Pump was implanted in an ovine model (n = 9) for 90 days. The pump was implanted through a thoracotomy and secured to the LV apex with a gimbaled sewing ring, which allowed for intraoperative adjustment of the insertion depth and angle of the inflow cannula. Serum analytes and coagulation parameters were analyzed at specific intervals throughout the study period. Pump flow, speed, and power were recorded daily to monitor device performance. Sheep were electively euthanized at 90 days for pathologic and histologic analysis. RESULTS In this study, results demonstrated the safety, reliability, hemocompatability, and biocompatibility of the MVAD Pump. Nine animals were implanted for 90 ± 5 days. No complications occurred during surgical implantation. Seven of the 9 animals survived until elective sacrifice. Each sheep that survived to the scheduled explant appeared physically normal, with no signs of cardiovascular or other organ compromise. The 2 sheep that were euthanized early showed no evidence of device-related issues. CONCLUSIONS The MVAD Pump was successfully implanted through a thoracotomy and demonstrated excellent hemodynamic support with no device malfunctions throughout the study period.

Biventricular Continuous Flow VADs Demonstrate Diurnal Flow Variation and Lead to End-Organ Recovery

HeartWare continuous flow ventricular assist devices (HVAD) configured as biventricular assist devices maintain diurnal flow variation, lead to end-organ recovery, and provide for a successful bridge-to-heart transplantation in the first successful North American use of continuous flow biventricular assist devices.

Increase in circadian variation after continuous-flow ventricular assist device implantation

The circadian rhythm of varying blood pressure and heart rate is attenuated or absent in patients with severe heart failure. In 28 patients supported by a left ventricular assist device (LVAD) for at least 30 days, a restoration of the circadian rhythm was demonstrated by a consistent nocturnal decrease, and then increase, of the LVAD flow while at a constant LVAD speed. The return of the circadian rhythm has implications for cardiac recovery, and the observation indicates that the continuous-flow LVAD has an intrinsic automatic response to physiologic demands.

Baseline hemodynamic and echocardiographic indices in anesthetized calves.

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 ± 87.0 days; mean body weight, 106.9 ± 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 ± 12 beats per minute), mean aortic pressure (113.5 ± 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 ± 38.9 mm Hg), and mean pulmonary artery pressure (21.7 ± 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 ± 0.7 cm), left ventricular diastolic dimension (5.6 ± 0.8 cm), end-systolic intraventricular septal thickness (1.7 ± 0.2 cm), end-diastolic intraventricular septal thickness (1.2 ± 0.2 cm), ejection fraction (63 ± 10%), and fractional shortening (37 ± 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 ± 0.5 m/s and a cardiac index of 3.7 ± 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.

Early feasibility testing and engineering development of the transapical approach for the HeartWare MVAD ventricular assist system.

Implantation of ventricular assist devices (VADs) for the treatment of end-stage heart failure (HF) falls decidedly short of clinical demand, which exceeds 100,000 HF patients per year. Ventricular assist device implantation often requires major surgical intervention with associated risk of adverse events and long recovery periods. To address these limitations, HeartWare, Inc. has developed a platform of miniature ventricular devices with progressively reduced surgical invasiveness and innovative patient peripherals. One surgical implant concept is a transapical version of the miniaturized left ventricular assist device (MVAD). The HeartWare MVAD Pump is a small, continuous-flow, full-support device that has a displacement volume of 22 ml. A new cannula configuration has been developed for transapical implantation, where the outflow cannula is positioned across the aortic valve. The two primary objectives for this feasibility study were to evaluate anatomic fit and surgical approach and efficacy of the transapical MVAD configuration. Anatomic fit and surgical approach were demonstrated using human cadavers (n = 4). Efficacy was demonstrated in acute (n = 2) and chronic (n = 1) bovine model experiments and assessed by improvements in hemodynamics, biocompatibility, flow dynamics, and histopathology. Potential advantages of the MVAD Pump include flow support in the same direction as the native ventricle, elimination of cardiopulmonary bypass, and minimally invasive implantation.

HeartWare controller logs a diagnostic tool and clinical management aid for the HVAD pump.

Continuous-flow ventricular assist devices (VADs) are a viable therapy for the treatment of end-stage heart failure, offering support for bridge-to-transplantation and destination therapy. As support duration for VADs continues to rise, patient management and device maintenance will play an increasingly crucial role. The HeartWare Ventricular Assist System1 has currently been implanted in >4,000 patients worldwide. The HeartWare controller stores approximately 30 days of VAD data including pump rotational speed, power consumption, and estimated VAD flow. Routine assessment of controller log files can serve as a pump performance tool and clinical management aid, assisting the clinician to make accurate and timely diagnoses. Here, we discuss the controller’s data collection system as well as present the process for evaluation and reporting of controller log files to clinicians.

Infection and thrombosis in total artificial heart technology: past and future challenges--a historical review.

On the basis of animal testing and a single clinical implant during the 1960s, development of the total artificial heart (TAH) began in earnest in the 1970s. The goal was to produce a pump that could treat biventricular heart failure or any other condition that necessitated removal of the patients native heart. The early TAHs were pneumatically powered, with externalized drivelines. After undergoing in vivo evaluation in hundreds of sheep and calves at several centers (mainly the Utah Heart Institute), these pumps were implanted in humans, initially for permanent cardiac replacement and later for bridging to transplantation. In both the in vivo experimental setting and the clinical setting, infection and thrombosis were problematic, infection being encountered much more frequently than thrombosis in clinical cases. To minimize these problems, four research groups, funded by NIH, began in 1988 to develop permanent, transcutaneously powered, totally implantable, electromechanical TAHs. For the first time, TAH technology was able to minimize infection and thrombosis, as confirmed by current in vivo studies. These new TAHs will undergo preclinical, pre-IDE studies this year and clinical trials in the near future. This article briefly reviews the evolution of TAH technology, with an emphasis on the prevention and management of infection and thrombosis.