Mechanical heart support at the Deutsches Herzzentrum Berlin: Recent developments (2011)

Since the inception of the mechanical circulatory support (MCS) program at the Deutsches Herzzentrum Berlin (DHZB) in 1987, more than 1600 patients have received support with 18 different designs of technical blood pump systems, in accordance with the respective state of the art. At the beginning, pulsatile pneumatic extracorporeal ventricular assist devices (VAD) and implantable pneumatic total artificial hearts (TAH) were available, followed by pulsatile electromechanical implantable devices. At this time the assist program was based on three objectives: bridging to recovery, bridging to heart transplantation (HTx) and for permanent support. Very soon (in 1995) patients of advanced age – over 65 years – were included in the program. In 1998 rotary blood pumps with continuous flow entered the program, from 2006 edging out step by step the pulsatile systems. Today the implantable pulsatile systems have disappeared from the DHZB program, with the exception of the extracorporeal uni‐ or biventricular pneumatic EXCOR systems (Berlin Heart GmbH), which are the only systems available for newborns and children. The only approved total artificial heart is the CardioWest device, implanted in rare cases after explantation of the natural heart. Miniaturized rotary blood pumps, axial flow turbines or centrifugal radial flow pumps are leading today's market. The size and configuration of one of these pumps, the hydrodynamically and magnetically levitated HeartWare HVAD, allowed its application as a biventricular implantable assist device. The worldwide first clinical implantation of this system was performed at the DHZB in 2009. With the increasing number of patients needing immediate circulatory support and the stagnating or even decreasing number of donor hearts available for HTx, the extreme discrepancy means that other therapies are gaining increasing importance. The objectives of the MCS program therefore had to focus on permanent VADs, thus creating a growing population of long‐term outpatients with implanted systems, living with their families a near‐normal life. Within a quarter century VAD implantation has grown from an experimental procedure into an established and generally accepted therapy. Facing the rapidly increasing population of patients with end‐stage heart failure and the stagnating number of heart transplants, the use of VAD technology may represent the most advanced progress in cardiac care in the coming years. Further minaturization of the devices will allow the treatment of patients with a wide age spectrum, from newborn children to the elderly, even with biventricular support. The ultimate goal will be the development of a durable total artificial heart, based on the rotary blood pump technology, with transcutaneous energy transfer through the intact skin, guaranteeing the patients optimal quality of life for many years of support.     

Completely pulsatile high flow circulatory support with a constant-speed centrifugal blood pump: mechanisms and early clinical observations

OBJECTIVE: Various types of rotary blood pumps (axial flow, centrifugal) have been introduced into clinical use recently. These pumps have different pressure-flow characteristics, and some investigators have noted that a limited pump flow rate and less pulsatility are the problems with the axial flow devices. METHODS: A new implantable centrifugal blood pump was developed that has an extremely flat pressure-flow curve and is able to produce a significantly high pump flow rate of 20 l/min at a low pressure of 10-30mmHg. When the pressure difference between the left ventricle and aorta decreases during systole, an instant high peak flow is achieved, which results in a higher peak pressure in the aorta (systolic pressure). During the diastolic phase, the left ventricle-aorta pressure difference increases to maximum, and the pump flow rate decreases to minimum. Thus, the pump flow rate becomes completely pulsatile, and the high peak flow provides a higher mean pump flow rate. This pump was applied to two end-stage heart failure patients (dilated cardiomyopathy, New York Heart Association (NYHA) class IV, inotrope-dependent). RESULTS: The pump was observed to provide completely pulsatile high flow assistance of 6-9 l/min with a constant pump speed. Both patients are currently in NYHA class I after 1 year on the device with no major adverse events. CONCLUSION: The new centrifugal blood pump provides completely pulsatile high-flow circulatory support with a constant pump speed, which solves the current clinical problems with rotary blood pumps.     

Mock Circulation Loop to Investigate Hemolysis in a Pulsatile Total Artificial Heart

Hemocompatibility of blood pumps is a crucial parameter that has to be ensured prior to in vivo testing. In contrast to rotary blood pumps, a standard for testing a pulsatile total artificial heart (TAH) has not yet been established. Therefore, a new mock circulation loop was designed to investigate hemolysis in the left ventricle of the ReinHeart TAH. Its main features are a high hemocompatibility, physiological conditions, a low priming volume, and the conduction of blood through a closed tubing system. The mock circulation loop consists of a noninvasive pressure chamber, an aortic compliance chamber, and an atrium directly connected to the ventricle. As a control pump, the clinically approved Medos‐HIA ventricular assist device (VAD) was used. The pumps were operated at 120 beats per minute with an aortic pressure of 120 to 80 mm Hg and a mean atrial pressure of 10 mm Hg, generating an output flow of about 5 L/min. Heparinized porcine blood was used. A series of six identical tests were performed. A test method was established that is comparable to ASTM F 1841, which is standard practice for the assessment of hemolysis in continuous‐flow blood pumps. The average normalized index of hemolysis (NIH) values of the VAD and the ReinHeart TAH were 0.018 g/100 L and 0.03 g/100 L, respectively. The standard deviation of the NIH was 0.0033 for the VAD and 0.0034 for the TAH. Furthermore, a single test with a BPX‐80 Bio‐Pump was performed to verify that the hemolysis induced by the mock circulation loop was negligible. The performed tests showed a good reproducibility and statistical significance. The mock circulation loop and test protocol developed in this study are valid methods to investigate the hemolysis induced by a pulsatile blood pump.     

Physiologic Benefits of Pulsatile Perfusion During Mechanical Circulatory Support for the Treatment of Acute and Chronic Heart Failure in Adults

A growing population experiencing heart failure (100 000 patients/year), combined with a shortage of donor organs (less than 2200 hearts/year), has led to increased and expanded use of mechanical circulatory support (MCS) devices. MCS devices have successfully improved clinical outcomes, which are comparable with heart transplantation and result in better 1‐year survival than optimal medical management therapies. The quality of perfusion provided during MCS therapy may play an important role in patient outcomes. Despite demonstrated physiologic benefits of pulsatile perfusion, continued use or development of pulsatile MCS devices has been widely abandoned in favor of continuous flow pumps owing to the large size and adverse risks events in the former class, which pose issues of thrombogenic surfaces, percutaneous lead infection, and durability. Next‐generation MCS device development should ideally implement designs that offer the benefits of rotary pump technology while providing the physiologic benefits of pulsatile end‐organ perfusion.     

Outflow control for avoiding atrial suction in a continuous flow total artificial heart

Continuous flow blood pumps, such as axial flow and centrifugal pumps, have been gaining interest as circulatory devices for total artificial hearts (TAHs) because of their smaller size and simpler structure compared to pulsatile pumps. However, continuous flow pumps are more prone to atrial wall suction than pulsatile pumps are. Sudden increases in flow rate to meet changes in physiological demand, especially in the left pump, often cause atrial wall suction. In this study, a control algorithm to prevent atrial wall suction from occurring in the left atrium by controlling the rotational speed of the right pump, instead of reducing the cardiac output of the left pump, was developed and investigated. The method was tested in a mock circulatory system and in acute animal experiments with adult goats. Two centrifugal pumps were used to totally replace the circulatory function of the natural heart. The cardiac output of each pump was determined independently by a control algorithm running on a computer connected through a serial interface to the pump driving units. Results showed that left atrial wall suction could be prevented using this method, and that the method could be performed simultaneously with physiological control of the artificial heart.     

Hybrid Continuous‐Flow Total Artificial Heart

Clinical studies using total artificial hearts (TAHs) have demonstrated that pediatric and adult patients derive quality‐of‐life benefits from this form of therapy. Two clinically‐approved TAHs and other pumps under development, however, have design challenges and limitations, including thromboembolic events, neurologic impairment, infection risk due to large size and percutaneous drivelines, and lack of ambulation, to name a few. To address these limitations, we are developing a hybrid‐design, continuous‐flow, implantable or extracorporeal, magnetically‐levitated TAH for pediatric and adult patients with heart failure. This TAH has only two moving parts: an axial impeller for the pulmonary circulation and a centrifugal impeller for the systemic circulation. This device will utilize the latest generation of magnetic bearing technology. Initial geometries were established using pump design equations, and computational modeling provided insight into pump performance. The designs were the basis for prototype manufacturing and hydraulic testing. The study results demonstrate that the TAH is capable of delivering target blood flow rates of 1–6.5 L/min with pressure rises of 1–92 mm Hg for the pulmonary circulation and 24–150 mm Hg for the systemic circulation at 1500–10 000 rpm. This initial design of the TAH was successful and serves as the foundation to continue its development as a novel, more compact, nonthrombogenic, and effective therapeutic alternative for infants, children, adolescents, and adults with heart failure.     

Present status of the total artificial heart at the University of Tokyo

At the University of Tokyo, various types of total artificial heart (TAH) systems have been studied since 1959. At the present time, 2 types of implantable TAH have been developed. One is an undulation pump TAH (UPTAH) and the other is a flow transformed pulsatile TAH (FTPTAH). Using the UPTAH, 14 cases of implantation were performed in goats and 10 days' survival obtained. The new type of FTPTAH is under a prototype study. To prevent ring thrombus, a polyurethane membrane valve, a jellyfish valve, has been developed. The longest in vivo experiences with this valve in the TAH blood pump have been 312 days in the left side blood pump and 414 days in the right side blood pump. Conductance and arterial pressure based control (1/R control) can realize the physiological control of the TAH. Using 1/R control, 532 days of survival could be obtained in a goat with a paracorporeal TAH. The technique required to apply this control method to a implantable TAH is under development. We have proposed a new 5 year research project of the implantable TAH entitled "Comprehensive Basic Research on the Development of a Japanese Original Implantable Total Artificial Heart" to The Ministry of Welfare.     

Estimation of the Native Cardiac Output from a Rotary Blood Pump Flow: In Vitro Study

Abstract The rotary blood pump will be an implantable left ventricular assist device (LVAD) in the near future. However, the best control method and the interrelationship between the rotary blood pump and native heart functions are unclear. An estimation was made of the native heart cardiac output from the change of an LVAD's outflow waveform. The mock circulation loop was composed of an aortic compliance chamber, left arterial chamber, total artificial heart as a native heart, and a rotary blood pump that was placed as an LVAD with left ventricular drainage. The fast Fourier transform (FFT) technique was utilized to analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to examine a relation between the PPI and total artificial heart (TAH) output. The PPI increased with the increase of the TAH output; there was a positive correlation, and there was an inverse correlation between the PPI and the assist ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's outflow wave may indicate the native cardiac output.     

New versatile dual‐support pediatric heart pump

Mechanical circulatory support (MCS) devices for pediatric patients continue to lag in development behind those for adults. There is no heart pump with the design innovation to support dysfunctional states of heart failure and the anatomic heterogeneity of cardiac defects in pediatric patients. To address this unmet need, we are developing a versatile MCS technology with 2 separate blood pumps under 1 housing, whereby a centrifugal pump rotates around an axial pump. In this study, we advanced the design with a new inducer for the axial pump component and flat inlet volute for the centrifugal pump component. We conducted computational modeling of the design iterations, built prototypes, and tested their performance. The axial pump component was able to generate pressure rises of 1–112 mm Hg for 2–5 L/min at 10 000–14 000 RPM, and the centrifugal pump component produced pressure rises of 1–184 mm Hg for 2–5 L/min at 1750–3000 RPM. Shear stresses and blood damage estimations were less than  490 Pa and 0.5%, respectively. Axial and radial forces were also estimated to be less than 5 N for the axially and radially centered impellers. Data sets were repeatable, and data trends followed theoretical expectations. The new designs for the axial and centrifugal pumps enabled us to reduce the height of the pump while maintaining performance expectations. These findings support the continued development of this new medical device for pediatric patients.     

Design and Development Strategy for the Rotary Blood Pump

Development of an antitraumatic antithrombogenic and durable blood pump is a very difficult task. Based upon this author's experience of over 35 years in the development of various types of cardiac prostheses, development strategies for a rotary blood pump are described. A step-by-step development strategy is thus proposed. Initially, the development of a 2 day antitraumatic pump (Phase 1) would be made. Then, conversion of this pump to a 2 week antithrombogenic pump (Phase 2) should be attempted. After the successful development of the Phase 2 pump, the conversion of this device to a durable, implantable, and long-term blood pump (Phase 3) should be established. Based upon this development strategy, 2 rotary blood pumps, namely, the axial flow blood pump and the centrifugal blood pump, have been developed in less than 6 years with modest development costs.     

Component engineering for an implantable system

Component engineering is important for the development of implantable-type rotary blood pumps (RP). The authors are conducting elementary development of an implantable artificial heart. A sensor system detects information in the living body. An automatic control system performs the drive control. Energy is provided by a transcutaneous energy transmission system (TETS). Various artificial hearts are being created. Miniaturization resulting from an increase in operating frequency is planned. A vibrating flow pump (VFP) has a reduced size of pumping chamber because of the high-speed reciprocating movement. Undulation pump ventricular assist devices (UPVAD) are small, lightweight rotary pumps. VFPs are useful in the medical treatment of multiple organ failure (MOF). UPVADs are planned to be permanent-use RPs. The purposes of these two artificial hearts differ, although they have a common component. The authors are developing TETS by using amorphous fibers, making efficient power transmission possible. Control information input from a micro or nano sensor is realized. A control algorithm has been developed and baroreflex control has been successful. Artificial heart development, fully exploiting component engineering, continues.     

Development of the Undulation Pump Total Artificial Heart

Abstract: The undulation pump is a small size continuous flow displacement type blood pump that has been developed for an artificial heart. Using undulation pumps. 2 types of implantable total artificial hearts (TAHs), the undulation pump TAH (UPTAH) type 1 (UPTAH 1) and UPTAH type 2 (UPTAH 2) were developed. Both UP-TAHs were designed to be small enough to implant into the chest of a goat, the experimental animal. UPTAH 1 could be reduced in size to 75 mm in diameter and 78 mm in length. The weight was 520 g. UPTAH 2 could be reduced in size to 75 mm in diameter and 80 mm in length. The weight was 650 g. UPTAH 2 could be tested in an animal experiment using an adult female goat weighing 52.3 kg. The UPTAH 2 could be implanted successfully into the goat's chest with a good fit. The goat stood after the surgery and extubation and survived for 3 h and 40 min; thus, the potential of the UPTAH for a practical implantable TAH was demonstrated.     

Development of a flow-transformed pulsatile total artificial heart for total implantation

To realize a totally implantable total artificial heart (TAH), a new pulsatile TAH, the flow-transformed pulsatile TAH (FTPTAH), was developed. The system was composed of a single centrifugal pump (CFP) and two three-way valves. One port of each three-way valve was connected to the inlet and outlet of a CFP. The other two ports of each valve were connected to the right and left atrium, and the pulmonary artery and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow by switching the two three-way valves. A prototype and the secondary model in which the solenoid valves and a spool valve were included, respectively, were connected to a mock circulatory unit with the results that a pulsatile TAH with physiological flow wave form could be obtained from a single CFP, about 5 L/min of pulsatile output could be obtained alternately on the right and left side by switching the solenoid valves or a spool valve, and flow balance between the right and left could be easily controlled by the switching duration. The system is feasible for a totally implantable TAH because it does not need a compliance chamber and can be miniaturized.     

Rapid Speed Modulation of a Rotary Total Artificial Heart Impeller

Unlike the earlier reciprocating volume displacement–type pumps, rotary blood pumps (RBPs) typically operate at a constant rotational speed and produce continuous outflow. When RBP technology is used in constructing a total artificial heart (TAH), the pressure waveform that the TAH produces is flat, without the rise and fall associated with a normal arterial pulse. Several studies have suggested that pulseless circulation may impair microcirculatory perfusion and the autoregulatory response and may contribute to adverse events such as gastrointestinal bleeding, arteriovenous malformations, and pump thrombosis. It may therefore be beneficial to attempt to reproduce pulsatile output, similar to that generated by the native heart, by rapidly modulating the speed of an RBP impeller. The choice of an appropriate speed profile and control strategy to generate physiologic waveforms while minimizing power consumption and blood trauma becomes a challenge. In this study, pump operation modes with six different speed profiles using the BiVACOR TAH were evaluated in vitro. These modes were compared with respect to: hemodynamic pulsatility, which was quantified as surplus hemodynamic energy (SHE); maximum rate of change of pressure (dP/dt); pulse power index; and motor power consumption as a function of pulse pressure. The results showed that the evaluated variables underwent different trends in response to changes in the speed profile shape. The findings indicated a possible trade‐off between SHE levels and flow rate pulsatility related to the relative systolic duration in the speed profile. Furthermore, none of the evaluated measures was sufficient to fully characterize hemodynamic pulsatility.     

Mechanical Circulatory Support Devices for Pediatric Patients With Congenital Heart Disease

The use of mechanical circulatory support (MCS) devices is a viable therapeutic treatment option for patients with congestive heart failure. Ventricular assist devices, cavopulmonary assist devices, and total artificial heart pumps continue to gain acceptance as viable treatment strategies for both adults and pediatric patients as bridge‐to‐transplant, bridge‐to‐recovery, and longer‐term circulatory support alternatives. We present a review of the current and future MCS devices for patients having congenital heart disease (CHD) with biventricular or univentricular circulations. Several devices that are specifically designed for patients with complex CHD are in the development pipeline undergoing rigorous animal testing as readiness experiments in preparation for future clinical trials. These advances in the development of new blood pumps for patients with CHD will address a significant unmet clinical need, as well as generally improve innovation of the current state of the art in MCS technology.     

Magnetically Levitated Motor for Rotary Blood Pumps

Abstract: The noncontact rotary pumps under development for use as artificial heart pumps are highly efficient and can prevent thrombus formation. In these pumps magnetic bearings have been widely used to support the rotors to avoid any physical contact. The use of magnetic bearings, however, has led to requirements for the control of a large degree of freedom and for a separate driving motor. This paper introduces 2 types of levitated motors. each of which uses a combination of a rotary motor and a magnetic bearing. These motors are suitable for use in artificial blood pumps because they are small in size and can replace contact components. The radial type levitated motor has the merit of being small in size and capable of controlling the 2 degrees of freedom in the x and y directions. The axial type motor controls only one degree of freedom in the z direction. This paper also introduces the theoretical background of the functions of the motor and magnetic bearing. Experimental results of tests of the proposed motor show a great potential for its application in rotary blood pumps.     

Experimental and Numerical Investigation of an Axial Rotary Blood Pump

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near‐wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds‐averaged Navier–Stokes simulations‐computational fluid dynamics (URANS‐CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall‐particle image velocimetry technique, and the visualization of near‐wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS‐CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.     

Implantable artificial heart

Heart transplants have been decreasing globally due to the lack of available donor hearts. As a result, the increased use of artificial hearts is anticipated as an alternative therapy. Although biocompatibility issues, such as thrombus formation/thromboembolism and infection, are still the main cause of mortality associated with artificial hearts, more than 20 different types are now clinically available after a half-century of development and experimental trials. These devices range from extracorporeal pneumatic to implantable battery-powered artificial hearts. The early development of artificial hearts logically focused on volumetric pump designs incorporating functions similar to the natural heart. Today, development has shifted toward designs that are significantly different from the natural heart. These pumps utilize axial or centrifugal flow allowing for a much simpler design, which is smaller in size and has very few moving parts. With rapid advances in technology, this new generation of artificial heart pumps is beginning to emerge as an alternative to heart transplants.     

Do We Really Need Pulse? Chronic Nonpulsatile and Pulsatile Blood Flow: From the Exercise Response Viewpoints

Abstract: The response of the body and the blood pump was evaluated in animals with a pulsatile artificial heart (total artificial heart [TAH]) and those with a nonpulsatile artificial heart (nonpulsatile biventricular bypass [NPBVB]) subjected to the same exercise load. The animals used in this study were 5 calves implanted with a pusher–plate type TAH (45–206 days) and 5 calves implanted with a nonpulsatile centrifugal pump (34–99 days). The pre–exercise pump flow rate was 92. 1 ± 8. 1 ml/kg/min for the TAH group and 94. 8 ± 9. 1 ml/kg/min for the NPBVB group, with no significant difference between the two groups. The workload was administered at a rate of 1. 5 mph for 15 min. The artificial heart driving conditions were kept constant throughout the test period. Sequential changes in hemodynamic response and metabolism were determined before, during, and for 30 min after exercise. Both TAH and NPBVB calves showed excellent tolerance of the workload (1. 5 mph exercise); in NPBVB calves, oxygen demand was compensated for by an increase in the arteriovenous oxygen difference during exercise; and norepinephrine showed a greater response in the NPBVB group. Based on the results presented, the nonpulsatile pump seems to lend itself to a mechanically driven artificial heart of the complete implantation type because of its small size, high efficiency, and the lack of need for a compliance chamber.     

Artificial heart

Artificial heart or heart transplantation are required for the treatment of profound heart failure. Total artificial heart (TAH) and ventricular assist system (VAS) were developed from late 1950s and 2 extracorporeal pneumatic Japanese VASs (Toyobo VAS and Zeon VAS) were introduced to clinical field from 1980. Now, over 850 patients were applied several types of VASs including Japanese VASs. And 80% of heart transplant recipients were supported by VASs for 714 days (mean). Small size implantable left VAS (LVAS) are required and several types of non-pulsatile pump, including 2 Japanese made centrifugal pumps, are under clinical trials. And destination therapy by using implantable pulsatile LVAS for end-stage heart failure patients has been started in United States and is performed in United States and Europe. In near future, artificial heart and heart transplantation will be selected according to the conditions of the patients with profound heart failure.