Right ventricular assist system feedback flow control parameter for a rotary blood pump

At least 25-30% of patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure; therefore, an implantable biventricular assist system (BiVAS) with small centrifugal pumps is being developed. Many institutions are focusing and developing a control system for a left ventricular assist system (LVAS) with rotary blood pumps. These authors feel that the right ventricular assist system (RVAS) with rotary blood pumps should be developed simultaneously. A literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS. In this study, a calf with an implantable right ventricular assist system (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic recordings were taken every 5 min throughout the testing period, and blood gas analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and oxygen extraction (O2ER) were calculated and analyzed. Two different pump flows were investigated: Group 1 low assist (<3.5 L/min) and Group 2 high assist (>3.5 L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary artery (PA) flow increased during exercise; also, the heart rate and right atrial pressure (RAP) increased during exercise. There were no significant differences in the 2 groups. The PA flow correlates to the heart rate during exercise. In all of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no changes were observed during the different flow conditions; however, the DO2 of Group 2 was higher than that of Group 1. Because the implantable RVAS did not have pump flow changes during the test conditions, it was necessary to incorporate a flow control system for the implantable RVAS. During exercise with an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow rate.     

Therapeutic and Physiological Artificial Heart: Future Prospects

Abstract: Current left ventricular assist devices (LVADs) have demonstrated admirable results. However, approximately one-fourth of the patients who require LVADs suffer from right heart failure and require additional right ventricular (RV) assist devices (RVADs). The RV failure impairs the splanchnic circulation, subsequently developing into multiorgan failure (MOF). An aggressive application of a biventricular assist device (BVAD) is the best way to avoid and treat MOF because the BVAD reduces splanchnic congestion. Also, because the BVAD allows retention of the natural heart, recovery of the heart function can be expected after long-term assist. This benefit cannot be expected from conventional total artificial hearts. Although there are no implantable clinical BVAD systems in existence today, present advanced technologies in rotary blood pumps can enable these systems to be totally implantable. So, we should focus on developing a totally implantable BVAD system. The implantable BVAD will be a therapeutic and physiological total artificial heart, and it will be a common home health care device in the near future.     

Development of totally implantable pulsatile biventricular assist device

Approximately 10% to 15% of all patients implanted with left ventricular assist devices (LVADs) have required right heart support with another device. The necessity of aggressive biventricular support has already been proposed. Therefore, the totally implantable biventricular assist device (BVAD) was developed. The width of the BVAD main body was 87 mm, the thickness 67 mm, and the height 106 mm, while the weight was 785 g. The automatic control algorithm was developed to prevent lung edema and atrial rupture.     

The use of a biventricular assist device for postcardiotomy profound biventricular failure

A 58-year-old woman who could not be weaned from cardiopulmonary bypass was treated with a biventricular assist device (BVAD) using a centrifugal pump for the left side and a pneumatic pulsatile pump for the right side. At the initiation of the BVAD support, predominant right ventricular failure was recognized and therefore weaning was begun from the left side. The left ventricular assist device was discontinued after 87 h and the patient was finally weaned from the right ventricular assist device after 205 h. Despite the complete recovery of cardiac function, the patient developed renal failure followed by an intractable infection and died of multiple organ failure on the 59th postoperative day (POD).     

Control strategy for biventricular assistance with mixed-flow pumps

A left ventricular assist device (LVAD) is an effective method to rescue severe heart failure. Although some require a biventricular assist, the control method for the biventricular assist device (BVAD) with a rotary pump is rarely shown. The objective of this study was to investigate the strategy for controlling BVAD with rotary pumps by in vivo studies. Using 5 piglets, we set a BVAD through a left thoracotomy and made global ischemia for 30 min by clamping the base of the ascending aorta. After unclamping, the analysis of pumping performance acted for 6 h reperfusion. We set the target flow of the LVAD and set the right ventricular assist device (RVAD) speed limit as less than when the atrial collapse occurs. To detect the ventricular collapse without any specific sensor, we calculated the index of current amplitude from motor current waveform and simultaneous mean current value. In all cases, over 6 h of observation was performed, and the RVAD was weaned almost automatically.     

Assessing the calf pulmonary function during a long-term biventricular assist device study with a centrifugal blood pump

Pulmonary congestion due to inappropriate pump flow management is one major problem necessary to avoid during long-term biventricular assist device (BVAD) implantation. Our objective was to assess the effects of pulmonary arterial flow rate and flow rates of both (right and left) bypass pumps. Six healthy calves, which had been implanted with a BVAD system, were selected for this retrospective study. Pulmonary artery flows, both pump flow rates, oxygen saturation of the arterial blood, and pulmonary arterial pressures were assessed as parameters of pulmonary function as was routine clinical evaluation of respiratory rate and character and chest auscultation. The average pulmonary artery flow rate (PAF), systolic pressure of pulmonary artery (sPAP), and oxygen saturation were 148.8 ml/kg per min, 35.1 mm Hg, and 95.3%, respectively. Pulmonary dysfunction occurred in one case, in which the mean PAF, sPAP, and oxygen saturation were 169 ml/kg per min, 66.1 mm Hg, and 90.9%, respectively. The ratio for the right/left pump flow rate (R/L ratio) for the case having pulmonary dysfunction was 1.57 even though the ratio for the other cases was less than 1. Maintaining an R/L ratio less than 1 and/or PAF less than 160 ml/kg per min and PAP less than 50 mm Hg is recommended as the initial conditions to target to avoid pulmonary dysfunction during a BVAD implantation with a beating heart condition.     

Development of the Baylor Gyro Permanently Implantable Centrifugal Blood Pump as a Biventricular Assist Device

The Baylor Gyro permanently implantable centrifugal blood pump (Gyro PI pump) has been under development since 1995 at Baylor College of Medicine. Excellent results were achieved as a left ventricular assist device (LVAD) with survival up to 284 days. Based on these results, we are now focusing on the development of a biventricular assist device (BVAD) system, which requires 2 pumps to be implanted simultaneously in the preperitoneal space. Our hypothesis was that the Gyro PI pump would be an appropriate device for an implantable BVAD system. The Gyro PI 700 pump is fabricated from titanium alloy and has a 25 ml priming volume, pump weight of 204 g, height of 45 mm, and pump diameter of 65 mm. This pump can provide 5 L/min against 100 mm Hg at 2,000 rpm. In this study, 6 half-Dexter healthy calves have been used as the experimental model. The right pump was applied between the infundibular of the right ventricle and the main pulmonary artery. The left pump was applied between the apex of the left ventricle and the thoracic descending aorta. As for anticoagulation, heparin was administered at the first postoperative week and then converted to warfarin sodium from the second week after surgery. Both pump flow rates were controlled maintaining a pulmonary arterial flow of less than 160 ml/kg/min for the sake of avoidance of pulmonary congestion. Blood sampling was done to assess visceral organ function, and the data regarding pump performance were collected. After encountering the endpoint, which the study could not keep for any reasons, necropsy and histopathological examinations were performed. The first 2 cases were terminated within 1 week. Deterioration of the pump flow due to suction phenomenon was recognized in both cases. To avoid the suction phenomenon, a flexible conduit attached on the inlet conduit was designed and implanted. After using the flexible inflow conduit, the required power and the rotational speed were reduced. Furthermore, the suction phenomenon was not observed except for 1 case. There was no deterioration regarding visceral organ function, and pulmonary function was maintained within normal range except for 1 case. Even though the experimental animal survived up to 45 days with the flexible inflow conduit, an increase in power consumption due to thrombus formation behind the impeller became a problem. Lower rotational speed, which was probably produced by the effectiveness of the flexible inflow conduit, was speculated to be one of the reasons. And the minimum range of rotational speed was 1,950 rpm in these 6 BVAD cases and the previous 3 cases of LVAD. In conclusion, 6 cases of BVAD implantation were performed as in vivo animal studies and were observed up to 45 days. The flexible inflow conduit was applied in 4 of 6 cases, and it was effective in avoiding a suction phenomenon. The proper rotational speed of the Gyro PI 700 pump was detected from the viewpoint of antithrombogenicity, which is more than 1,950 rpm.     

Antithrombogenicity of the Gyro permanently implantable pump with the RPM dynamic suspension system for the impeller

In 1995, a group at Baylor College of Medicine started to develop the NEDO biventricular assist device (BVAD) using two Gyro permanently implantable (PI) centrifugal pumps. This pump consists of a sealless pump housing and an impeller supported with a double pivot bearing. In May 2001, an RPM dynamic suspension system (RPM-DS) for the impeller was developed to improve durability and antithrombogenicity without a complex magnetic suspension system. From March 2000 to March 2002, eight BVAD bovine experimental studies were performed for more than 1 month. Two pumps were implanted in two cases without the RPM-DS (group A) and in six cases with the RPM-DS (group B). In group A, the survival period was 45 and 50 days. The primary reason for termination was an increase in the requiring power, which was related to deposition of white thrombus on the bottom bearing. In group B, the survival period was 37, 48, 51, 60, 80, and 90 days. The reasons for termination were not related to thrombus formation. No thrombus was observed in the pumps except for one right pump. In that experiment, the thrombus formation may have occurred when that pump had a low flow rate at a level of 1 L/min for 6 hr. These studies demonstrate the apparent antithrombogenic effect of RPM-DS. The NEDO BVAD is ready to move into a 3-month preclinical system evaluation.     

The balance of the impeller-driver magnet affects the antithrombogenicity in the Gyro permanently implantable pump

The Gyro permanently implantable (PI) pump is activated magnetically when a double pivot bearing supported impeller is rotated at predetermined revolutions per minute (rpm). The male bearing shaft of the impeller is supported by the top and bottom female pivot bearing in a loosely mated fashion. The Gyro PI pump's impeller transfers to a floating condition when the rpm is increased. The design objective of the Gyro PI pump is to drive the impeller while maintaining a top contact position to prevent thrombus formation. As a left ventricular assist device (LVAD), the Gyro PI pumps achieved long-term survivals in calves without thrombus formation. However, thrombus formation occurred during a biventricular assist device (BVAD) implantation. Our hypothesis was that the impeller remaining in the bottom contact position during the BVAD experiment caused this thrombus formation. Therefore, a replica of the Gyro PI pump housing was fabricated from a transparent plastic to observe the floating conditions of the impeller. When simulating an LVAD animal experiment, the impeller was at a non-bottom contact position. However, when simulating the BVAD animal experiment, the impeller remained at the bottom contact position. This study shows that the magnet balance affects the antithrombogenicity in a Gyro PI pump.     

Implantation of one piece biventricular assist device by left thoracotomy in an ovine model

In this report, we describe an operative procedure for our implantable 1 piece biventricular assist device (BiVAD) based on a moving actuator mechanism, using an ovine model. Our implantable BiVAD is a volumetric coupled 1 piece unit including right and left blood sacs and an actuator assembly based on the moving actuator mechanism. The BiVAD was controlled by fixed rate control with 75 bpm for the most part. Both the left and the right full ejection modes with the maximum stroke angle were selected to minimize blood stasis in the blood sacs because of low assist flow condition. Three Corriedale sheep were used for the device implantation by a left thoracotomy incision. Cannulation was successfully performed in all cases. Although exposability of the right atrial appendage varied from animal to animal, the insertion of the cannula was easily performed. The cannulas were connected to the pump-actuator assembly in the preperitoneal pocket. All 3 animals survived the experimental procedure. During implantation of the device, in the 1 month survival animal, pump flow was maintained between 2.0 L/min and 2.5 L/min, mean aortic pressure was 90-110 mm Hg, and mean pulmonary artery pressure was 20-30 mm Hg. The left and right atrial pressure were maintained between 0 and 5 mm Hg. In conclusion, this ovine model for implantation of the 1 piece BiVAD can be an effective alternative for testing in vivo biocompatibility of the device although it needs more consideration for anatomical fittability for future human application.     

Development and Initial Testing of a Permanently Implantable Centrifugal Pump

Abstract: To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI-601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 Limin against 150 mm Hg at 2,500 rpm. The normalized index of hemo-lysis (NIH) value of this pump was 0.0028 g/100 L at 5 Limin against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.     

LVAD speed increase during exercise,which patients would benefit the most? A simulation study

Patients supported with a left ventricular assist device (LVAD) have impaired cardiovascular adaptations during exercise, resulting in reduced total cardiac output and exercise intolerance. The aim of this study is to report associations among these impaired cardiovascular parameters and exercise hemodynamics, and to identify in which conditions an LVAD speed increase can provide substantial benefits to exercise. A cardiorespiratory simulator was used to reproduce the average hemodynamics of LVAD patients at exercise. Then, a sensitivity study was conducted where cardiovascular parameters were changed individually ±20% of their baseline value at exercise (heart rate, left/right ventricular contractility, total peripheral resistance, and valve pathologies). Simulations were performed at a baseline LVAD speed of 2700 rpm and repeated at 3500 rpm to evaluate the benefits of a higher LVAD support on hemodynamics. Total cardiac output (TCO) was mostly impaired by a poor left ventricular contractility or vasodilation at exercise (−0.6 L/min), followed by a poor chronotropic response (−0.3 L/min) and by a poor right ventricular contractility (−0.2 L/min). LVAD speed increase better unloads the left ventricle and improves total cardiac output in all the simulated conditions. The most substantial benefits from LVAD speed increase were observed in case of poor left ventricular contractility (TCO + 1.6 L/min) and vascular dysfunction (TCO + 1.4 L/min) followed by lower heart rate (TCO + 1.3 L/min) and impaired right ventricular contractility (TCO + 1.1 L/min). Despite the presence of the LVAD, exercise hemodynamic is strongly depending on the ability of the cardiovascular system to adapt to exercise. A poor left ventricular inotropic response and a poor vascular function can strongly impair cardiac output at exercise. In these conditions, LVAD speed increase can be an effective strategy to augment total cardiac output and unload the left ventricle. These results evidence the need to design a physiological LVAD speed controller, tailored on specific patient’s needs.     

In Vitro and In Vivo Testing of an Implantable Motor-Driven Left Ventricular Assist Device

Abstract: A totally implantable motor-driven left ventricular assist device (LVAD) has been developed and tested. The performance of this LVAD was tested in a mock circulatory system. This pump provided 8 L/min of output against a mean afterload of 120 mm Hg with a filling pressure of 20 mm Hg when the pump was operated in the fill/empty mode. The right and left pumps were tested in a mock loop. The right pump afterload was kept in the range from 23–32 mm Hg. With increase in the left pump afterload, the pump power output varied from 1.64 to 2.37 W. The instantaneous motor power input varied from 22.6 to 30.6 W with the total system efficiency ranging from 6.7 to 9.4%. To date, 4 in vivo studies have been conducted for up to 12 h. Two animals survived 12 and 10 h, respectively. Termination was due to bleeding in 1 animal, vent tube obstruction in 1, and respiratory failure in 2. All animals died of technical failure. Another experiment is to be undertaken, and a newly designed cannula is now being manufactured.     

Centrifugal blood pump with a hydraulically-levitated impeller for a permanently implantable biventricular assist device

A permanently implantable biventricular assist device (BVAD) system has been developed with a centrifugal pump which is activated by a hydraulically-levitated impeller. The pump impeller floats hydraulically into the top contact position; this position prevents thrombus formation by creating a washout effect at the bottom bearing area, a common stagnant region. The pump was subjected to in vitro studies using a pulsatile mock circulation loop to confirm the impeller's top contact position and the swinging motion produced by the pulsation. Eleven in vivo BVAD studies confirmed that this swinging motion eliminated blood clot formation. Twenty-one pumps im-planted for up to three months did not reveal any thrombosis in the pumps or downstream organs. One exception was a right pump which was exposed to severe low flow due to the kinking of the outflow graft by the accidental pulling of the flow meter cable. Three ninety-day BVAD studies were achieved without thrombus formation.     

Axial Flow Ventricular Assist Device: System Performance Considerations

Abstract: A cooperative effort between Baylor College of Medicine and NASA/Johnson Space Center is under way to develop an implantable left ventricular assist device for either pulmonary or systemic circulatory support for more than 3 months' duration. Using methodical evaluation and testing, an implantable axial pump has been systematically improved. These improvements include the addition of an inducer as a pumping element in front of the impeller and the construction of an efficient brushless direct current motor. To date, less than 10 W of power is required to generate 5 L/min flow against 100 mm Hg. An index of hemolysis of 0.021 g/100 L has been achieved. Two-day in vivo feasibility studies in calves are under way to evaluate the antithrombogenic nature of the pump. Further improvements in system efficiency, hemolytic performance, and the antithrombogenic nature of the pump are expected with the use of empirical studies, computer flow modeling, and in vivo testing in calves.     

Assessment of right pump outflow banding and speed changes on pulmonary hemodynamics during biventricular support with two rotary left ventricular assist devices

The absence of an effective, easily implantable right ventricular assist device (RVAD) significantly diminishes long‐term treatment options for patients with biventricular heart failure. The implantation of a second rotary left ventricular assist device (LVAD) for right heart support is therefore being considered; however, this approach exhibits technical challenges when adapting current devices to produce the lower pressures required of the pulmonary circulation. Hemodynamic adaptation may be achieved by either reducing the rotational speed of the right pump impeller or reducing the diameter of the right outflow cannula by the placement of a restricting band; however, the optimal value and influence of changes to each parameter are not well understood. Hemodynamics were therefore investigated using different banding diameters of the right outflow cannula (3–6.5 mm) and pump speeds (500–4500 rpm), using two identical rotary blood pumps coupled to a pulsatile mock circulation loop. Reducing the speed of the right pump from 4900 rpm (for left ventricle support) to 3500 rpm, or banding the Ø10 mm (area 78.5 mm²) right outflow graft to Ø5.4 mm (22.9 mm²) produced suitable hemodynamics. Pulmonary pressures were most sensitive to banding diameters, especially when RVAD flow exceeded LVAD flow. This occurred between Ø5.3 and Ø6.5 mm (22.05–38.5 mm²) and speeds between 3200 and 4400 rpm, with the flow imbalance potentially leading to pulmonary congestion. Total flow was not affected by banding diameters and speeds below this range, and only increased slightly at higher values. Both right outflow banding or right pump speed reduction were found to be effective techniques to allow a rotary LVAD to be used directly for right heart support. However, the observed sensitivity to diameter and speed indicate that challenges may be presented when setting appropriate values for each patient, and control over these parameters is desirable.     

Current status of the gyro centrifugal blood pump--development of the permanently implantable centrifugal blood pump as a biventricular assist device (NEDO project)

The New Energy and Industrial Technology Development Organization (NEDO) project was started in 1995. The goal is the development of a multipurpose, totally implantable biventricular assist device (BVAD) that can be used for any patient who suffers from severe heart failure. Our C1E3 (two-week pump) centrifugal pump, called the Gyro pump, has three design characteristics: a magnetic coupling and double pivot bearing system, an eccentric inlet port, and secondary vanes on the bottom of the impeller. The pump was miniaturized. The C1E3 evolved into the NEDO PI-601, a totally implantable centrifugal pump for BVAD. The current NEDO PI-710 pump (five-year pump) system includes a centrifugal pump with pivot bearings, a hydraulically-levitated impeller, an rpm-controlled miniaturized actuator (all-in-one actuator plus controller), an emergency clamp on the left outflow, and a Frank-Starling-type flow control. The final mass production model is now finalized, and the final animal study and two-year endurance studies are ongoing.     

Centrifugal blood pumps for various clinical needs

During the past 10 years, different types of blood pumps were developed to address various clinical needs. The Nikkiso centrifugal blood pump was developed for cardiopulmonary bypass application. This blood pump has been widely used in Japan in more than 20% of the cardiopulmonary bypass procedures. The Kyocera C1E3 Gryo pump was developed for short-term circulatory assistance and extracorporeal membrane oxygenation application for up to 2 weeks. This blood pump has been clinically used for up to 28 days without any blood clot formation. Through Phase I of the Japanese government New Energy and Industrial Technology Development Organization (NEDO) program, a chronically implanted centrifugal pump for left ventricular assistance was developed. This pump has already demonstrated its effectiveness, safety, and durability as a 2 year blood pump through in vitro and in vivo experiments. Currently, it is in the process of being converted from an experimental to a clinical device. Through Phase II of the NEDO program, a permanently implantable biventricular assist centrifugal blood pump system is under development. It has demonstrated that the previously mentioned left ventricular assist device blood pump is easily converted into a right ventricular assist pump by simply adding a spacer between the pump and the actuator. This communication discusses the historical development strategies for centrifugal blood pumps and their current status for different clinical needs.     

In Vivo Evaluation of the Miniaturized Gyro Centrifugal Pump as an Implantable Ventricular Assist Device

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 ± 0.57 L/min, and input power of 6.16 ± 0.49 W, and the inside temperature of the actuator of 43.5 ± 0.52°C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.     

Right ventricular failure after left ventricular assist device implantation: the need for an implantable right ventricular assist device

Right ventricular failure after implantation of a left ventricular assist device is an unremitting problem. Consideration of portal circulation is important for reversing liver dysfunction and preventing multiple organ failure after left ventricular assist device implantation. To achieve these objectives, it is imperative to maintain the central venous pressure as low as possible. A more positive application of right ventricular assistance is recommended. Implantable pulsatile left ventricular assist devices cannot be used as a right ventricular assist device because of their structure and device size. To improve future prospects, it is necessary to develop an implantable right ventricular assist device based on a rotary blood pump.