Fifteen-year experience with Toyobo paracorporeal left ventricular assist system

Our 15-year experience of the Toyobo paracorporeal left ventricular assist system (LVAS) at Osaka University Hospital was reviewed. In total, 61 patients underwent Toyobo LVAS implantation from January 1992 to August 2007. Their mean age was 38.1 ± 16.9 years. The etiologies of heart failure were idiopathic dilated cardiomyopathy in 35 patients, ischemic cardiomyopathy in 15, myocarditis in 5, secondary cardiomyopathy in 4, and others in 2. Preoperatively, intubation was required in 41 patients (67.3%), an intra-aortic balloon pump was required in 38 (62.3%), and extracorporeal membrane oxygenation was required in 30 (49.2%). Four patients underwent heart transplantation and 11 underwent LVAS removal. Of those 11 patients, 4 were subjected to emergent removal because of device complications and all of them died. Of the 7 patients that underwent scheduled LVAS removal, heart failure recurred in 2 patients and reimplantation was required. In terms of major device-related complications, cerebral hemorrhage occurred in 16 patients (26.2%), cerebral infarction in 19 (31.1%), mediastinitis in 10 (16.4%), and inflow/outflow cannula exit site infection in 19 patients (31.1%). The actuarial survival rate of the patients operated on in the last 5 years of this study was 66.3% at 6 months and 45.9% at 1 year. Although the survival rate of patients supported by the Toyobo LVAS has recently improved, the morbidity rate is significant. Considering the current severe shortage of heart donors in Japan, it is important to introduce more durable devices with fewer complications and to establish the strategies for using the LVAS as a bridge to recovery.     

Terumo implantable left ventricular assist system: results of long-term animal study

The research group of Terumo Corporation, NTN Corporation, and the Setsunan University have been developing an implantable left ventricular assist system (T-ILVAS) featuring a centrifugal blood pump with a magnetically suspended impeller (MSCP). The present study describes results of chronic animal experiments using the MSCP. The MSCP has been tested ex vivo and in vivo in 6 sheep as a left heart bypass between the left ventricular apex and descending aorta. Ex vivo chronic sheep experiments using Model I demonstrated long-term durability, nonthrombogenicity, low hemolysis (<6 mg/dl), and excellent stability of the magnetic bearing with long-term survival for up to 864 days. Average pump flow rate was 4 L/min at a fixed rotational speed of 2000 rpm. Power spectral analyses of heart rate, aortic pressure, and blood temperature maintained normal 1/f fluctuation during the study. The retrieved pump was completely free from thrombus formation and there was no evidence of infarct in major organs. The implantable Model II was evaluated ex vivo in two sheep and intra-thoracically implanted in a sheep. These experiments were terminated at 70, 79, and 17 days due to blood leakage through the connector system within the housing. No thrombus formation was observed in any of the retrieved pumps. A modified Model II with a new connector system was subsequently intra-thoracically implanted in a sheep. The sheep survived for 482 days without any sign of thromboembolic complication or hemolysis at a fixed rotational speed of 1700 rpm and an average pump flow rate of 5 L/min. There was no intra-device thrombus formation or infarct in major organs. The Model III system, consisting of an implantable controller and a new MSCP with a reduced input power of 13 W, has been developed and implanted in a chronic sheep model. The MSCP was implanted in the left pleural space and the controller in the abdominal wall. The experiment is still in progress for more than 30 days without any significant complication to date. These animal studies strongly suggest the feasibility of the MSCP for use as long-term circulatory assist.     

Initial experience in Japan with HeartWare ventricular assist system

We describe the first clinical experiences in Japan with the HeartWare ventricular assist device (HVAD: HeartWare Inc., Miami Lakes, FL, USA) in patients awaiting heart transplantation. Nine patients (6 males, 3 females; mean 33.5 ± 7.8 years; New York Heart Association class III or IV) received the HVAD as a bridge to transplantation between 2011 and 2012. Six had dilated cardiomyopathy, 2 secondary cardiomyopathy, and 1 dilated phase hypertrophic cardiomyopathy. All operations were uneventful, with a mean operation time of 269 ± 77 min and cardiopulmonary bypass time of 121 ± 40 min. One required a temporary right ventricular assist device and was weaned on postoperative day 20, while another required pump exchange due to foreign tissue in the inflow. Mean support duration was 245 ± 162 days (range: 50–535 days) and mean pump blood flow at 1 month postoperatively was 4.8 ± 0.8 l/min. There was no mortality after 30 days, though 1 patient died during support due to cerebral hemorrhage. Presently, the others are waiting for heart transplantation without problems, except 1 who suffered from an active infection. There was no pump mechanical failure in any case. The HeartWare pump enables quick implantation with acceptable morbidity and mortality. Our preliminary results indicate that this left ventricular assist device is safe for circulatory assistance for heart transplant candidates in Japan.     

Inflammatory response after implantation of a left ventricular assist device: comparison between the axial flow MicroMed DeBakey VAD and the pulsatile Novacor device

The implantation of a ventricular assist device (VAD) is associated with a stimulation of the inflammatory system. We compared changes in the inflammatory response after implantation of a pulsatile Novacor left (L) VAD and the axial flow MicroMed DeBakey VAD. Six consecutive patients after implantation of a Novacor LVAD (NC) and six patients after implantation of a MicroMed DeBakey VAD (MD) were included in the investigation. Patients received LVADs for medically non treatable end-stage heart failure. Tumor necrosis factor alpha (TNF), C3a, C5a, interleukin 6 (IL-6), and neutrophil elastase were measured twice a week over a period of 3 months after implantation of the device. All tests were performed with an enzyme-linked immunosorbent assay. There was no significant difference in the clinical course of the two groups. All inflammatory parameters were elevated in both groups during the entire period of the investigation. There was no difference in TNF, polynuclear leukocyte elastase, or C3a levels between the two groups; however, IL-6 (NC: 23.6+/-37.6 pg/ml vs. MD: 63+/-114 pg/ml, p < 0.001) and C5a (NC: 708+/-352 microg/L vs. MD: 1,745+/-1,305 microg/L, p < 0.001) were increased significantly more in patients following implantation of the axial flow MicroMed DeBakey VAD. Compared with the pulsatile Novacor device, the implantation of the axial flow MicroMed DeBakey LVAD seems to be associated with an increased stimulation of one part of the inflammatory system. Further investigations are necessary for evaluation of the pathophysiologic mechanism and clinical implications of these findings.     

Biostability of Thoralon left ventricular assist device blood pumping sacs after long-term clinical use

The purpose of this paper is to investigate the biostability of Thoralon polyurethane blood pumping sacs that have been used for up to 14 months in the Thoratec ventricular assist device (VAD) in human subjects. Thoralon is a proprietary polyetherurethaneurea (PEUU) blended with siloxane based surface modifying additive (SMA). Samples of Thoralon blood sacs that were used in Thoratec LVAD pumps for 53, 171, 336, and 434 days were taken from three distinct regions identified as high flex, medium flex, and low flex for physicochemical analysis. Explanted samples exhibited a slight but not significant increase in physical properties. The molecular weight of the blood sacs had also increased significantly in all blood sacs regardless of duration of use. SEM images did not indicate any cracking, pitting, or surface erosion; however, in a small area of the high flex region of the 336 day sac some biofilm was seen. The Attenuated Total Reflectance Fourier Transform Infra Red Spectroscopy (ATR-FTIR) analysis showed no significant reduction of surface ether content. The surface chemistry analyzed using Electron Spectroscopy for Chemical Analysis (ESCA) also indicated no significant change compared with control. These results confirm the biostability of Thoralon for long-term clinical applications in the Thoratec VAD.     

Retrospective hemolysis comparison between patients with centrifugal biventricular assist and left ventricular assist devices

Little is known about the hemolysis rate in the case of concomitant implantation of two continuous flow pumps for the treatment of biventricular heart failure. We present a retrospective study comparing the hemolysis parameters in patients supported with one implantable centrifugal pump of the type HeartWare HVAD used as a left ventricular assist device (LVAD) and with two pumps as a biventricular assist device (BiVAD). A total of 20 consecutive patients who received HeartWare BiVAD (n = 10) and LVAD (n = 10) support at our institution between September 2009 and September 2010 were examined. Hemolysis- and anemia-related parameters were analyzed after 2 weeks, 5 weeks, 3 months, and 6 months of support. Preoperative levels of hemoglobin, lactate dehydrogenase (LDH), and total bilirubin were similar in both groups. There were no differences in LDH, plasma-free hemoglobin (fHB), or total bilirubin levels postoperatively for up to 6 months. Only the haptoglobin level was lower in BiVAD recipients up to 3 months after surgery: 2nd week (63.5 [range: 8-237] mg/dl vs. 151 [range: 11-263] mg/dl, p = 0.05), 5th week (67 [range: 8-196] mg/dl vs. 215 [range: 56-292] mg/dl, p = 0.046), and after 3rd month (42 [range: 8-205] mg/dl vs. 220 [range: 157-256] mg/dl, p = 0.048). Our retrospective analysis of BiVAD HeartWare and LVAD HeartWare recipients showed a lack of a clinically important degree of hemolysis when two centrifugal HeartWare pumps are used for biventricular support.     

Reliability model from the in vitro durability tests of a left ventricular assist system

A reliability test of the Novacor N100PC left ventricular assist system (LVAS) with valved conduits, including a pump/drive unit with compact controller and LVAS monitor was performed. The initial test objective was to demonstrate sufficient reliability for clinical use as a long-term circulatory support system. The subsequent objective, a test to failure, was intended to provide an assessment of the durability of the design and to determine the LVAS wearout modes. Testing began in April 1993 and was performed with 12 systems on gravity-feed mock circulatory loops. The pump/ drive units were submersed in body temperature saline for the duration of the test. Each of the LVAS units was operated at nominal afterloads of 75, 90, and 105 mm Hg, with test conditions varied to yield nominal pump outputs of 5.6, 7.1, and 8.3 L/min. Failure was defined as the inability of the LVAS to maintain an average pump output of 4 L/min or an average output pressure of 60 mm Hg. After 3 years, all systems remained on test, with durations of 2.3 to 3.0 years. Analysis of the testing to that date, using a constant hazard rate model, indicated a minimum demonstrated reliability of 94% at a 60% confidence level, or 86% at a 90% confidence level, for a 2 year mission time. This greatly surpasses the reliability level included in the STS-ASAIO Long-Term Mechanical Circulatory Support System Reliability Recommendation (80% reliability, 60% confidence level for a 1 year mission time). In the subsequent test-to-failure protocol, all systems ran failure-free for at least 3 years. System failures occurring at longer durations were caused by a single common cause: wear of the energy converter's armature support bearings and shafts. The wearout mode was gradual and could be diagnosed noninvasively before failure. An analysis using a Weibull model was performed, using the test durations of those devices that failed, those that were electively removed from test for analysis of the wear mode, and those that continued on test. As of April 1998, the test results showed a reliability, at a 60% confidence level, of >99.9% for a 1 year mission time, 99.5% for a 2 year mission, and 92.0% for a 3 year mission (>99.9%, 98.3%, and 85.9% for equivalent mission times, at a 90% confidence level). Systems continue on test after as long as 4.9 years.     

Multicenter experience: prevention and management of left ventricular assist device infections

Implantable left ventricular assist devices (LVADs) have demonstrated clinical success in both the bridge-to-transplantation and destination-therapy patient populations; however, infection remains one of the most common causes of mortality during mechanical circulatory support. Thus, serious LVAD infections may negate the benefits of LVAD implantation, resulting in decreased quality of life, increased morbidity and mortality, and increased costs associated with implantation. Prevention of device-related infection is crucial to the cost-effective use of mechanical circulatory support devices. Therefore, adherence to evidence-based infection control and prevention guidelines, meticulous surgical technique and optimal postoperative surgical site care form the foundation for LVAD associated infection prevention.     

左室辅助循环对急性左心衰犬肾素血管紧张素系统影响

目的:研究不同辅助流率对急性左心衰时肾素血管紧张素系统(RAS)的影响.方法:对20条急性左心衰犬进行高、中、低流量的180 min左室辅助,观察其对血液动力学及RAS的影响.结果:左室辅助循环可使急性左心衰犬平均左房压、血浆肾素、血管紧张素Ⅱ迅速下降,平均主动脉压、左室搏功指数均升高.结论:不同辅助流量对急性左心衰时左心血液动力学支持均有效,但以中流量效果最佳.神经内分泌因子是评价LVAD效果敏感而有效的指标.     

Japanese multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system

Implantable left ventricular assist device systems (LVAS) are increasingly being used to bridge patients to heart transplantation because of the limited number of available donor hearts. This prospective, multicenter trial was designed to evaluate the usefulness of the HeartMate vented electric (VE) LVAS as a bridge to transplantation in Japan. Between November 2001 and June 2003, six patients with end-stage heart failure [New York Heart Association (NYHA) class IV] were supported with the LVAS and five of the six were able to implement the evaluation (one dropped out). The five were men with an average age of 38.6 years and were supported for 2390 cumulative days (6.6 years). Average preimplant cardiac index improved from 1.93 l/min/m² to a 3.79 l/min/m² VAD flow index at the end of the clinical trial. All five patients improved to NYHA class I or II, survived more than 1 year, and one patient was discharged from the hospital. Mean LVAS support duration was 478 days (range 390–575 days) and four patients remain supported. One patient died from cardiac failure and sepsis. Device-related complications included: infections (four patients), thromboembolism (one patient), hemolysis (two patients), and repeat operation for bleeding (two patients). There was one case of inflow valve incompetence and two pump motor malfunctions. We conclude that the LVAS can effectively support patients as they await cardiac transplantation and offers improvement to the patient’s quality of life.     

A case of conversion of a NIPRO ventricular assist system to an EVAHEART left ventricular assist system

Bridge to bridge (BTB) is a promising strategy for the treatment of end-stage heart failure that involves the left ventricular assist system (LVAS). We describe our experience with the conversion of an extracorporeal ventricular assist system (VAS), the NIPRO VAS, to an implantable LVAS, the EVAHEART LVAS. A 32-year-old man underwent a NIPRO VAS implantation as a bridge to decision for a condition consistent with Interagency Registry for Mechanically Assisted Circulatory Support profile 1. He was later diagnosed with secondary cardiomyopathy due to cardiac sarcoidosis. During the period in which he had NIPRO VAS support, no significant bacterial cultures were obtained from the cannula-piercing site, and no systemic infection occurred. Approximately 5 months after the NIPRO VAS implantation, he underwent an EVAHEART LVAS implantation as a BTB. The procedure required technical modifications, including the anastomosis of outflow grafts, trimming of the apical cuff, and creation of a pump pocket. The operation was completed uneventfully. The patient completed the discharge program for awaiting heart transplantation at home. Approximately 6 months after the EVAHEART LVAS implantation, he continues to do well without any complications, including infection, and visits our hospital as an outpatient. Conversion to an implantable LVAS can be beneficial in carefully selected patients after ascertaining the operative indications and operation timing.     

In vitro evaluation of an implantable left ventricular assist device

The development of implantable left ventricular assist devices (LVADs) has almost reached the stage of providing permanent circulatory support in patients who are unsuitable for, or denied, the transplant option. As part of our ongoing haemodynamic evaluation of the Thermo Cardiosystems Inc. (Boston, USA) Mark 14 pneumatic LVAD, pressure-volume loops have been produced from in vitro studies using a modified National Heart Lung and Blood Institute (NHLBI, USA) mock circulatory loop. These studies have demonstrated that during certain phases of the pump cycle non-physiologically high and low pressures are generated within the LVAD. Such abnormal pressures may damage either the bioprosthetic valves in the LVAD or the native heart, and may have adverse effects on cardiovascular control mechanisms.     

Long-distance transportation of patients with a paracorporeal left ventricular assist system

In Japan, the heart transplantation program is specialized in only three institutions in Osaka and Tokyo. Therefore, a patient must be transferred to these hospitals for extended treatment, regardless of the distance. Trans-portation of the patient with a paracorporeal left ventricular assist system (Toyobo LVAS) is difficult because of its extremely large consumption of electric power. We planned to transfer a patient with a Toyobo LVAS for 600 km, but the patient was not transferred because he had a stroke. In order to find the best transportation method, various possi-bilities are evaluated; special ambulance car, Shinkansen (Super express train), fiexed-wing aircraft, medium-sized helicopter (belonging to private company or public aviation corps), and large helicopter (belonging to the Self-Defense Force). The special ambulance car the medium-sized helicopter may not be able to provide a stable electric power supply. There is a connecting traffic problem with the Shinkansen and the aircraft, depsite their sufficient electric power supply. The large Self-Defense Force helicopter seems to be the best option for us. Some aspects of the logistics and complexity of long-distance transportationare also commented on.     

Fibrinolytic activation during long-term support with the HeartMate II left ventricular assist device

Human physiologic responses to pulsatile left ventricular assist devices (LVADs) are well understood; responses to the newer continuous flow pumps are not. Therefore, we evaluated the long-term effects of continuous flow LVAD support on fibrinolytic activation. Twelve recipients of an axial flow LVAD as destination therapy were assessed for fibrinolytic activation at 1, 3, 6, 9, and 12 months postimplantation. The fibrinolytic response and changes were assessed in terms of fibrinogen, D-dimer, plasma free hemoglobin, international normalized ratio (INR), and red blood cell (RBC) sedimentation rate. Bleeding and thromboembolic events were recorded. All fibrinolytic response parameters were elevated at baseline; mean RBC sedimentation rate was 51.8 mm/h, mean D-dimer was 3.95 nmol/L, and the mean fibrinogen was 356 mg/dl. The D-dimer and fibrinogen levels increased after LVAD implantation but returned to near-normal levels by 12 months. Red blood cell sedimentation rates increased indicating ongoing inflammation. Plasma free hemoglobin values decreased and remained low, an indicator of low shear rates and hemolysis. Three nonfatal bleeding events but no thromboembolic events were observed. Fibrinolytic responses initially increase after LVAD implantation but then gradually normalize.     

Pseudointima in inflow and outflow conduits of a left ventricular assist system: possible role in clinical outcome

Activation of blood coagulation and thromboemboli have been shown to present significant clinical risks in patients supported with an left ventricular assist system (LVAS). The interaction of pseudointima (PI) with blood in the conduits of the device could be involved in these clinical complications. Our aim was to study the morphology of the PI versus duration of circulatory support. Novacor N 100 PC LVASs were explanted from 10 men and 2 women after a mean of 209 days (range 23-560 days) of circulatory assistance. PI in the inflow and outflow conduits were investigated with immunohistochemical assays. In the inflow conduits, a loosely adherent PI had built up from collagen type I and III fibers growing into and between fibrin deposits. Disorganized collagenous matrix and longitudinally oriented collagen fibers included alpha-smooth muscle actin positive cells with random orientation. Macrophages were concentrated in the fibrin and were dispersed throughout the extracellular matrix. In the outflow conduits, a thin, adherent PI was composed of regular collagen type I and III layers. Collagen type I fibers had grown into the woven Dacron and alpha-smooth muscle actin positive cells were oriented in the axis of the blood flow. Macrophages were concentrated in the Dacron and reached the inner collagen layers. Venous blood flow in the inflow conduits allows the development of a non endothelialized irregular collagenous matrix intermingled with fibrin and invaded by macrophages. These persistent structural features progress with duration of circulatory assistance and reflect matrix degradation and remodeling. The potential to release thromboembolic fragments from the non stable, thrombogenic PI may be involved in the thromboembolic or neurologic complications sustained by 5 of 12 patients who were on circulatory support for as long as 200 days.     

Use of aortic valvo-pumps placed in valve annulus for long-term left ventricular assist

To provide better anatomical fit and physiologic adaptation, three aortic valvo-pumps with different dimensions were developed. Each pump has a rotor with an impeller and drive magnets and a stator consisting of a motor coil with iron core and an outflow guide vane. The devices had outer diameters of 21 mm, 23 mm, and 25 mm, respectively, and weighted 27 g, 31 g, and 40 g, respectively. Laboratory testing demonstrated that the rotating speed for maintaining a diastolic pressure of 80 mm Hg at zero flow rate should be 17500 rpm, 15000 rpm, and 12500 rpm, respectively; the largest flow at these same speeds will be 5 l/min, 7 l/min, and 10 l/min, respectively, with approximately 50 mm Hg pressure head increase. Therefore, these three pumps may meet the hemodynamic requirements of patients with body weights of 40-60 kg, 60-80 kg, and 80-100 kg. The first in vivo trial exhibited that the 25 mm valvo-pump can be sewn onto the aortic valve annulus of a 80 kg body weight pig without harm to adjacent organ functions. The devices occupy no additional anatomic space and deliver the blood directly from ventricle to the aorta, thus producing less physiologic disturbance to the natural circulation. Neither connecting conduits nor bypass circuits are necessary, thus eliminating the most dangerous sites of thrombosis in traditional left ventricular assist devices.     

Initial experiences with the HeartMate vented electric left ventricular assist system in Japan

We report three consecutive cases of long-term circulatory support using the HeartMate vented electric (VE) left ventricular assist system (LVAS). The HeartMate VE LVAS dramatically improved the functional status and quality of life of these three patients with end-stage heart failure, and all were successfully bridged to transplantation after 659, 995, and 1055 days of support on the device. Only an antiplatelet agent was used for anticoagulation therapy, and no cerebrovascular event occurred. Although the pump stopped in two of these three patients 665 days and 491 days after implantation, both were supported by the backup pneumatic driver thereafter. The drive-line exit site became infected in one patient and thinning of the left ventricular wall due to an unknown cause occurred in one patient.