Surg Today DOI 10.1007/s00595-014-0957-6
REVIEW ARTICLE
Current status of third-generation implantable left ventricular assist devices in Japan, Duraheart and HeartWare Yoshiki Sawa
Received: 1 January 2014 / Accepted: 12 May 2014 Ó Springer Japan 2014
Abstract Recently, left ventricular assist devices (LVADs) have become a viable therapeutic approach as a bridge to cardiac transplantation, as well as destination therapy or as part of the bridge to recovery. In Japan, paracorporeal pneumatic devices are the only choice for such therapy, as implantable LVADs are not yet generally available due to device lag, which represents a serious problem in this field. Clinical trials of four different continuous-flow pumps, both axial and centrifugal flow types, were completed at about the same time, and two of those devices, DuraHeart and EVAHEART, have already been approved for use in Japan. Thus, reports of advanced treatment for severe heart failure with these devices are expected. The DuraHeart (Terumo Heart, Ann Arbor, MI, USA) and another device named the HeartWare (HeartWare Inc, Miami Lakes, FL, USA) are so-called thirdgeneration devices, as they have achieved miniaturization and improvements in performance from the use of magnetic levitation. Based on our experiences from both clinical research and experimental use, we herein discuss the DuraHeart and HeartWare devices, with a focus on the clinical outcomes and management strategies. Because of the long waiting period for heart transplantation in Japan, these two devices are considered to have important roles in the near future for the treatment of severe heart failure, and a comprehensive strategy for LVAD therapy including such third-generation implantable devices is expected.
Y. Sawa (&) Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2, Yamada-Oka, Osaka, Suita 565-0871, Japan e-mail: [email protected]
Keywords Left ventricular assist device Mechanical circulatory support Bridge to transplantation
Introduction The initial development of ventricular assist devices (VADs) began in the 1970s as a permanent treatment option for end-stage heart failure [1, 2]. However, from the mid 1980s, the focus of VAD development shifted to left ventricular support without heart resection, and left ventricular assist devices (LVADs) have since become a viable therapeutic approach as a bridge to cardiac transplantation (BTT) [3, 4]. LVADs provide effective BTT therapy for patients with end-stage heart failure, and are increasingly used for destination therapy (DT) [5–7]. Recently, reports of patients weaned from LVAD use due to recovery of cardiac function have also been increasing, and the concept of bridge to recovery (BTR) using an LVAD has become popular [8, 9]. First-generation LVADs provide pulsatile flow by employing a paracorporeal pulsatile pump device, which drains blood from the left atrium or left ventricle and sends it to the ascending aorta. In Japan, the Nipro LVAD (Nipro, Osaka, Japan) is the only available paracorporeal pneumatic device [10, 11]. Currently, this device is still used for biventricular support or pediatric patients weighing up to 20 kg after the introduction of an implantable device [12, 13]. In such cases, an implantable pulsatile pump is placed into a pocket created in the abdominal cavity and is connected by a driveline cable with a diameter of about 1 cm that passes outside the body. The benefit of this type of device is a high blood flow rate and a small controller, making it possible for patients to be mobile. The Nocavacor
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ventricular assist device (WorldHeart, Canada) [14] and Heart Mate I [15] are other types of implantable pulsatile flow pumps. These can reproduce the physiological hemodynamic status, although they have not shown favorable results due to the lack of miniaturization, the complexity of the device system and the requirement of a thick cable [16]. Thus, continuous-flow LVADs were developed to reduce the size of the pump and cable, and their less complex design was aimed to provide greater long-term mechanical reliability, leading to an improved usefulness in DT [7]. Until very recently, implantable LVADs have not been available in Japan due to device lag [17], which represents a serious problem in this field. Clinical trials of four types of continuous-flow pumps, both axial and centrifugal flow types, were completed at about the same time, and two of those devices, the DuraHeart (Terumo Heart, Ann Arbor, MI, USA) [18] and EVAHEART (SunMedical, Nagano, Japan) [19], have already been approved for use in Japan. Thus, reports of advanced treatment for severe heart failure with these devices are expected. The DuraHeart and another device named the HeartWare (HVAD; HeartWare Inc., Miami Lakes, FL, USA) are so-called third-generation devices, as they have achieved miniaturization and improvements in performance from the use of magnetic levitation. Based on our experiences from both clinical research [20] and experimental use, we herein discuss the DuraHeart and HVAD devices, with a focus on the clinical outcomes and management strategies.
DuraHeart The DuraHeart is the first LVAD to use magnetic levitation for the centrifugal pump, which allows for rotation of the impeller, without contact anywhere on the inner wall of the blood chamber (third-generation pump). In 1994, the development of a magnetic levitation centrifugal pump system was begun as a joint project by Kyoto University, NTN Corporation and Terumo. They achieved long-term support of 864 days in chronic animal experiments using the prototype [21], and confirmed its long-term durability and anti-thrombogenic characteristics. Thereafter, clinical development of the DuraHeart started in 1999, followed by clinical trials in Europe for use in BTT. The pump was approved and obtained the CE mark in Europe in January 2004. In addition, clinical BTT trials were started in February 2007 in the United States [22], and a clinical trial of six cases was started in Japan in October 2008 [20, 23]. The DuraHeart was finally approved in Japan, along with the EVAHEART, in December 2010, and approval for reimbursement from the national health insurance program
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Fig. 1 The blood pump of the DuraHeart (upper) device and the structure of the blood pump (lower)
started in April 2011, which signaled the dawn of a new era of treatment for severe heart failure in Japan. There are two types of third-generation continuous-flow pumps, the magnetic levitation type and magnetic bearing with dynamic pressure type. The DuraHeart (Fig. 1) is a magnetic levitation type centrifugal pump. By levitating the impeller by electromagnetic force to rotate it in the blood flood, the risk of thrombus formation and friction from the bearing are eliminated. The impeller is rotated by a magnetic coupling placed between a permanent magnet incorporated into the motor outside the blood chamber and a passive magnet incorporated into the ring of the motor, while the impeller remains fixed in the center of the blood chamber. A distance of 250 lm from the wall of the blood chamber is set for sufficient blood washout, which results in no mechanical friction in the blood chamber. Therefore, durability, anti-thrombogenic characteristics and low levels of hemolysis are expected with long-term use. If the magnetic levitation system becomes broken, the impeller can continue to rotate from the dynamic pressure generated by the pump housing as a safety back-up. This system is called hydrodynamic bearing driven by hydrodynamic
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Fig. 2 The DuraHeart. a Blood pump, b monitor and c controller and battery
Fig. 3 The intraoperative procedures during the implantation of a DuraHeart device. a Pledgetted sutures were placed on the apex of the left ventricle. b The myocardium was resected, and the cuff was
attached to the apex. c The DuraHeart pump was attached to the cuff and put into the pocket
power. Because of its low noise level, the pump flow rate can be most accurately determined by the amount of hematocrit and the rotational speed of the motor. The pump volume is 180 mL, while the device weight is 540 g, the diameter is 73 mm and the height is 46.2 mm. The rotation rate is variable from 1,200 to 2,400 rpm, with a stroke volume up to 10 L/min being possible. The normal rotational speed setting is 1,600–2,000 rpm, and the flow rate for adults is 4–6 L/min. The pump is made of titanium, with heparin coating applied to blood contact surfaces. The outside kit is composed of two batteries and a controller, and its total weight is 2,250 g. The inflow cannula has an inner diameter of 12 mm and an outer diameter of 14 mm, with three different lengths available depending on patient size (Fig. 2). The outflow graft is a Gelweave graft coated with gelatin, with inner and outer diameters of 12 and 14 mm, respectively. Pre-clotting is not needed with the DuraHeart.
pocket, and a percutaneous cable is initially pulled out from a small skin incision made in the right upper quadrant, then the cable is again pulled out from the left middle abdomen below the navel. This procedure is done to reduce the risk of infection from the cable, which extends to the pump, by increasing the subcutaneous portion. After establishing cardiopulmonary bypass and partial clamping of the ascending aorta, the outflow is anastomosed to the ascending aorta. Next, the apex of the left ventricle is cut out with a coring knife, and the cuff is sewn to the apex using 12 pairs of pledgetted sutures (Fig. 3a), followed by the insertion of the inflow cannula (Fig. 3b, c). The inner diameter of the cuff and the diameter of the outflow graft of the DuraHeart and Nipro LVAD are the same size, providing advantages when exchanging these devices [13].
Surgical technique The implantation technique used at Osaka University has been described in a previous report [20]. After a median sternotomy, a pump pocket is created in the preperitoneal fat layer in the upper left abdomen, and the diaphragm is dissected toward the apex. The device is placed in the
Device management The protocol at Osaka University states that the rpm of the DuraHeart should be set to provide adequate cardiac output and achieve normal left ventricular decompression [17]. We optimize the rpm using both hemodynamic and echocardiographic methods at the time of LVAD implantation, as well as before the patient is discharged from the hospital, and whenever clinical events, such as new symptoms or suction events, warrant further adjustment.
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For postoperative anticoagulation, warfarin is administered to maintain an international normalized ratio (INR) of 2.0–2.5, together with 100 mg of aspirin daily, once the patient is able to take oral medication. In addition, the intravenous administration of heparin is started 12 h after surgery to achieve an activated prothrombin time of 50–70 s unless significant bleeding has occurred [20]. Clinical experience We initially performed two DuraHeart implantations as part of a clinical research project at Osaka University in August 2008, and we had treated a total of 25 cases by November 2011 (Table 1). The mean age of our patients at the time of surgery was 40 ± 10 years (range 17–56 years), and there were 17 males and 8 females. The mean length of the operation for all patients was 404 ± 138 min, and the Table 1 Our cases implanted with the DuraHeart device
DCM dilated cardiomyopathy, dHCM dilated phase hypertrophic cardiomyopathy, CM cardiomyopathy, LVAD left ventricular assist device, RVAD right ventricular assist device, BiVAD biventricular assist device, HTx heart transplantation
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cardiopulmonary bypass time was 132 ± 65 min. The mean length of the operation for the five patients who initially underwent isolated DuraHeart implantation was 330 ± 98 min (205–492 min), and their mean cardiopulmonary bypass time was 137 ± 72 min (67–269 min). There were no cases of 30-day or inhospital mortality. The average duration of support was 615 ± 239 days (254–1,028 days). Two patients with fulminant myocarditis underwent conversion of the LVAD from a Nipro LVAD to a DuraHeart and JARVIK 2000 (Jarvik Heart, Inc, New York, NY, USA), which was implanted as a RVAD. [24]. One of those died on postoperative day 539 due to sepsis, while the other survived and eventually underwent heart transplantation. At present, seven patients have undergone heart transplantation, while all others are still alive and waiting for heart transplantation except for the BiVAD
Pt
Age
Sex
Diagnosis
Operation(s)
Outcome
Support duration (days)
1
45
Male
dHCM
LVAD
HTx
1,012
2
49
Male
ICM
LVAD
HTx
785
3
30
Male
dHCM
LVAD
Ongoing (Home)
4
26
Male
DCM
LVAD
Ongoing (Home)
982
5
35
Female
Myocarditis CM
BiVAD (DuraHeart LVAD ? Jarvik RVAD)
HTx
968
6
30
Female
Myocarditis CM
Death (sepsis)
539
7
34
Female
DCM
BiVAD (DuraHeart LVAD ? Jarvik RVAD) LVAD
HTx
872
8
46
Male
DCM
LVAD
Ongoing
832
9
53
Male
DCM
LVAD
Ongoing (Home)
825
10
28
Male
dHCM
LVAD
HTx
511
11
16
Male
dHCM
LVAD
HTx
574
12
17
Male
DCM
LVAD
Ongoing (Home)
748
13
25
Male
DCM
LVAD
Ongoing (Home)
730
14
35
Female
DCM
LVAD
HTx
443
15
21
Female
dHCM
LVAD
Ongoing (Home)
517
16
31
Male
ICM
LVAD
Ongoing (Home)
502
17
49
Male
ICM
LVAD
Ongoing (Home)
491
18
36
Male
LVAD
Ongoing
254
19
32
Female
Chronic rejection after HTx DCM
LVAD
Ongoing (Home)
460
20
40
Female
ARVC
LVAD
Ongoing (Home)
442
21
24
Male
dHCM
BiVAD (DuraHeart LVAD ? NIPRO RVAD)
Ongoing
419
22
37
Female
DCM
LVAD
Ongoing (Home)
408
23
43
Male
Becker secondary CM
LVAD
Ongoing (Home)
384
24
56
Male
DCM
LVAD
Ongoing (Home)
356
25
31
Male
DCM
LVAD
Ongoing (Home)
308
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patient described above. All but three patients were discharged from the hospital to home, one of whom had received a DuraHeart due to chronic rejection after transplantation, one with a Nipro RVAD and one whose household was in a remote area. We experienced nine cases of exchange from an extracorporeal Nipro LVAD to the DuraHeart. Six patients required a RVAD due to right heart dysfunction, three of whom were able to be weaned from that device and three of whom required BiVAD. We also encountered three cases in pressure mode due to partial disconnection of the cable, two of whom underwent a device exchange procedure and one of whom has been waiting in dynamic pressure mode for 267 days for heart transplantation as of the writing of this manuscript. Six cases develop LVAD-related infections, four of whom had an omentum flap, one of whom had a free latissimus dorsi flap and one of whom had a free thigh muscle flap. The infection was well controlled in all cases. Four patients had cerebrovascular events (two cases each of cerebral hemorrhage and cerebral infarction). Although DuraHeart implantation generally improved the quality of life of our patients, device infection or failure, right heart failure and cerebrovascular accidents are still considered to be potential problems. The System Interagency Registry for Mechanically Assisted Circulatory Support administered through INTERMACS to monitor the performance and usage of VADs has been introduced in the United States [25], while in Japan, the Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS) was started in 2012. In the near future, the long-term results of patients with an implantable ventricular assist device in Japan will be available through the J-MACS.
HeartWare (HVAD) The HVAD is a third-generation type of implantable VAD that can generate a high flow rate of up to 10 L/min. Due to the small (50 mL) pump body, the creation of a pump pocket is not required. The diameter of the drive line is thin, at 4.2 mm, and the weight of the pump itself is light at 160 g, while the outflow graft is only 10 mm. Together with one controller and two batteries, this compact device weighs 1.1 kg. The impellor is levitated by a magnetic hydrodynamic suspended system, and operates at 1,800–4,000 rpm [26] (Figs. 4, 5). The HVAD has received the CE mark based on good early results reported in Europe. In the United States, a large clinical study of the HVAD was recently completed, with feasibility reported, which was followed by approval by the FDA, while a clinical trial for destination therapy (Endurance trial) is
presently in progress. We conducted the first nine cases of HVAD implantation surgery in Japan as part of a clinical research study. The following is an overview of the perioperative management and surgical technique used for the HVAD cases. Surgical technique The following implantation technique is used at Osaka University: After a usual median sternotomy, cardiopulmonary bypass is established in the usual manner with the ascending aorta and bicaval cannulation. Creating a pump pocket is unnecessary for HVAD implantation. Basically, the operation is performed on a beating heart, and we begin with an apical procedure. First, the apex is lifted with a surgical towel, and the appropriate position of the inflow cuff is determined. We identify the location in a straight line in the direction of the mitral valve using transesophageal echocardiography. It is preferable to mark the appropriate position to place the cuff on the apex. We also mark the insertion point of the needle, the coring portion and the outer diameter of the cuff. Then, 12 sutures with large felt are placed evenly around the apex (Fig. 6a). We have found that it is better to simultaneously sew the sutures to the cuff and heart muscle. It is important to firmly secure the sutures to the myocardium in order to avoid bleeding, because it would be difficult to deal with bleeding from the left side of the apex. In addition, care should be taken to adjust the position of the fixed screw towards the surgeon’s side. We then attach a fibrin glue sheet (TacosealÒ) around the cuff to prevent further bleeding after appropriately tying the sutures. Next, with the patient in a head down position, the muscle of the apex is punched out using a coring device under ventricular rapid pacing (Fig. 6b). We examine the inside of the left ventricle to check for the presence of thrombi, and the trabecular portion is carefully removed as much as possible. After securing a sufficient lumen, the HVAD is quickly connected while preventing air contamination as much as possible (Fig. 6c). The position and direction of the HVAD, driveline and outflow graft are then adjusted, followed by fixing the device with screws. If the position is incorrect, it is easy to re-adjust by loosening the screws, which is also a great advantage in cases requiring replacement. After returning the position of the apex, the rapid pacing is stopped. As the next step, the outflow graft is directed to the ascending aorta so as to pass around the outside of the right atrium and along the acute margin, while adjusting the length by putting volume in the heart. An end-to-side anastomosis to the ascending aorta is performed under partial clamping of the ascending aorta using a 4–0 Prolene continuous suture, which is easy to use due to its small size
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(10 mm). A de-airing needle is inserted slightly on the head side of the anastomosis after declamping the ascending aorta. After performing the outflow graft anastomosis, the driveline is pulled to outside of the body using a dedicated device, which can be connected to the driveline from both sides.
Finally, the HVAD is started at 1,800 rpm while checking the de-airing using transesophageal echocardiography, and the rotational speed is gradually increased. It is often necessary to place an 18-G needle in the outflow graft to remove air in cases. with insufficient de-airing. Weaning from cardiopulmonary bypass is performed in the same manner as with other VADs using an appropriate mix of nitric oxide and inotropes, while paying attention for right ventricular failure. In most cases, the rotational speed of the HVAD at that time ranges from 2,400 to 2,600 rpm, and the flow should be adequate to ensure 4 L/min. Finally, the chest is closed in the usual manner. During HVAD implantation, the creation of a pump pocket is unnecessary, and the procedure is simple after determining the appropriate position of the cuff. As a result, it is possible to reduce both the cardiopulmonary bypass time and the total length of the operation time. Because of its compact size, we have experienced no problems with inserting the device into relatively small Japanese patients. Device management
Fig. 4 The blood pump of the HeartWare device (upper) and the structure of the blood pump (lower)
To manage an HVAD, a viscosity value in accordance with the appropriate hematocrit value at the time of setting the pump flow is entered, and it is necessary to change the number frequently in order to obtain the correct flow. The recommended rotational speed for this device is 2,400–3,200 rpm, and it is important to ensure that the flow remains above 2 L/min, and it is also better when the cardiac index is [2 L/min/m2. Since the pump flow is dependent on the afterload and preload, it is important to maintain an appropriate CVP and mean blood pressure, which should be kept at 90 mmHg or less. We usually check the flow, power consumption and flow pulsatility on the monitor. It is advisable to keep the power consumption within a range of 3–7 W. The flow pulsatility value is the difference between the maximum and minimum values of the flow waveform, and it is advisable to keep it at 2–4 L/min. A high flow pulsatility value may
Fig. 5 The HeartWare (HVAD). a Blood pump, b monitor and c controller and battery
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Fig. 6 The intraoperative procedures during the implantation of a HeartWare device. a Twelve pledgetted sutures were placed on the apex of the left ventricle. b The myocardium was resected using a coring device. c The HVAD pump was attached to the cuff
indicate adverse flow through the pump, while a low flow pulsatility may indicate a sucking problem. In addition, the HVAD is equipped with a Lavare cycle, a specific system mode. The purpose of this mode is to prevent thrombus formation by alternating the rotational speed of the pump, by 200 rpm lower for 2 s and 200 rpm higher for one second every 60 s. This should be activated after the patient’s condition becomes stable. For anticoagulation, the protocol of Osaka University Graduate School of Medicine calls for starting intravenous heparin from postoperative day 1. The activated partial thromboplastin time is then adjusted to a range of 40–50, then 50–60 after the amount of drainage is decreased. We start oral aspirin and warfarin once oral intake is possible. After the INR reaches 2.5–3.0, the intravenous heparin is stopped [27]. The general management is the same as with other VADs. We think that the incidence of driveline trouble will be lower due to the small diameter. Nevertheless, it is important to avoid cardiac tamponade or bleeding, and to appropriately treat right heart failure and control arrhythmia. The administration of appropriate antibiotics is also important. It is advisable to analyze all obtained data, and perform periodic systematic checks of the history of the flow and alarms, in order to ensure that any problems are identified as soon as possible. Clinical experience (Table 2) We have treated nine patients [six males, three females; mean 33.5 ± 7.8 years old; New York Heart Association (NYHA) class III or IV] with an HVAD as BTT. All device-related costs were supported by a Grant-in-Aid for scientific research from the Ministry of Health, Labor, and Welfare of Japan. Five had dilated cardiomyopathy, three had secondary cardiomyopathy and one had dilated phase hypertrophic cardiomyopathy. All pumps were placed in an intra-pericardial manner, and a pump pocket was not
required in any of the cases. The mean length of the operation for all patients was 269 ± 77 min, and the cardiopulmonary bypass time was 121 ± 40 min. The mean length of the operation for the five patients who initially underwent isolated HVAD implantation was 236 ± 39 min (194–294 min), and their mean cardiopulmonary bypass time was 112 ± 39 min (70–184 min). One patient 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. The mean support duration was 245 ± 162 days (50–535 days), and the mean pump blood flow at 1 month postoperatively was 4.8 ± 0.8 L/min. There was no mortality after 30 days, although one patient died during support due to cerebral hemorrhage. Presently, the others are waiting for heart transplantation without problems, except one patient who suffered from an active infection. There has been no pump mechanical failure in any case.
Future perspectives of the DuraHeart and HVAD in Japan Conversion from a Nipro VAD to the DuraHeart device Due to the so-called device lag problem in Japan, implantable VADs have not been available until very recently, and the Nipro LVAD, a paracorporeal pneumatic device, had been the only choice for most patients. As described in previous reports, long-term use of this LVAD can cause serious problems [11]. Considering the long waiting time for patients who have already undergone implantation with a Nipro LVAD, we believe that conversion to an implantable continuous-flow device will provide a safer bridge to transplantation and promises higher quality of life. We have now converted eight patients (four males and four females) from a Nipro paracorporeal LVAD to a DuraHeart device [13]. In those
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Surg Today Table 2 Our cases implanted with the HeartWare device
DCM dilated cardiomyopathy, dHCM dilated phase hypertrophic cardiomyopathy, CM cardiomyopathy, LVAD left ventricular assist device, RVAD right ventricular assist device, BiVAD biventricular assist device, HTx heart transplantation
Pt
Age
Sex
Diagnosis
Operation
Outcome
Support duration (days)
1
36
Male
DCM
LVAD
Ongoing (Home)
533
2
26
Male
Secondary CM
LVAD
Ongoing (Home)
458
3
29
Male
DCM
LVAD
Ongoing (Home)
401
4
40
Male
dHCM
LVAD ? temporary RVAD
Ongoing
370
5
47
Female
DCM
LVAD
Death (cerebral bleeding)
6
27
Male
Doxorubicininduced CM
LVAD
HTx
191
7
34
Female
Doxorubicininduced CM
LVAD
Ongoing (Home)
319
8
46
Male
DCM
LVAD
Ongoing (Home)
120
9
53
Male
DCM
LVAD
Ongoing
50
10
13
Female
dHCM
BiVAD (HeartWare ? HeartWare)
Ongoing
235
cases, the apical cuff of the Nipro was not exchanged because the size was the same as that of the DuraHeart. All conversion operations were performed safely, although three patients who had an infection in the Nipro LVAD cannulation site prior to conversion suffered later pocket infections, and one died because of sepsis. One of these patients underwent heart transplantation, and seven are currently awaiting heart transplantation at home. As noted above, in cases of conversion from a Nipro VAD to DuraHeart device, the apical cuff of the former can be used with the DuraHeart inflow conduit, so it is not necessary to replace the apical cuff, which allows for a shorter operation time and reduces the risk of bleeding. This is especially beneficial in cases of pure LVAD conversion. Even a superficial infection of the cannula exit site is considered to be a significant risk for the development of a refractory pocket infection after conversion, which can lead to fatal complications. Based on our experience, we now consider this procedure to be contraindicated in patients with any signs of infection at the Nipro LVAD cannula exit site. However, most of our conversion cases were safely performed, even in patients with infections. Considering that implantable LVADs provide superior long-term survival and quality of life, conversion is a reasonable decision for Nipro LVAD users who have no infection. Right heart support and support for children Because of the compact size of the HVAD, it can be used for various purposes. For example, it is suitable for the general Japanese population, whose body size is relatively smaller than that of Western populations. Furthermore, there are two possible future indications; right heart support and support for pediatric cases.
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In patients receiving LVAD support, up to 30 % of those with end-stage heart failure experience biventricular failure that requires biventricular support [21, 28–30]. In such cases, a biventricular assist device, which employs a bulky extracorporeal or implantable displacement pump, is required. However, we believe that the use of an implantable continuous-flow device provides safer BTT and promises a higher quality of life. Soon after the market launch of miniaturized LVADs, reports were published about attempts to use these devices for biventricular support [22, 31–33]. Krasbach et al. [31] reported 17 patients, two of whom underwent HVAD implantation for biventricular support. They concluded that two HeartWare HVADs can be used to form an implantable biventricular support system after a few important modifications of the implantation procedure for adjusting the right heart circulation. On the other hand, this small pump also has potential for use in children. Although a recent law in Japan now makes it possible for children to undergo heart transplantation, there are few options for those with terminal heart failure due to the shortage of donor hearts and the unavailability of VADs [24, 33, 34]. The implantable VAD systems suitable for adult patients are too large for use in pediatric patients, thus, paracorporeal systems are routinely utilized. Miera et al. [35] reported the cases of seven children between 6 and 16 years old who received implantation of an HVAD. All patients had multi-organ failure under inotropic support, and six were successfully bridged to cardiac transplantation. Not only were the outcomes good, but the morbidity rate during circulatory support was also low. During a total of more than 480 days of support, none of the patients suffered from an infection or thromboembolism. They concluded that the HeartWare assist system can
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be successfully used as a bridge to transplantation in children and adolescents with end-stage heart failure. At our institution, we treated a 13-year-old female with HVAD implantation as part of a clinical research study on severe heart failure in children. Initially, she underwent LVAD implantation, which resulted in the need for temporary right heart support with a centrifugal pump. However, the right-side heart function was not yet recovered, and weaning from the RVAD was thought to be difficult even after unloading the RV volume by use of a temporary centrifugal pump for 3 weeks. We decided to convert to an implantable device for the right heart, which was successfully performed. She is now on the waiting list for heart transplantation and is living at home.
Conclusion With no mechanical friction in the pump chamber as a result of the use of a magnetic levitation system in the DuraHeart, and a magnetic hydrodynamic suspended system in the HVAD, the third-generation implantable VADs are expected to provide long-term durability, with antithrombogenic characteristics and low hemolysis. In light of the long waiting period for heart transplantation in Japan, these devices will play important roles in the treatment of patients with severe heart failure. Furthermore, each has advantageous features making them applicable for specific situations. We anticipate the development of a comprehensive VAD therapy strategy that includes these implantable VADs in the near future.
References 1. Phillips SJ, Zorzi G, Jaron D, Freed P, Zoireff L, Aris A, et al. Experimental hemodynamic studies with a permanent ventricular assist device. The dynamic aortic patch. J Thorac Cardiovasc Surg. 1973;65:471–5. 2. Pierce WS, Brighton JA, O’Bannon W, Donachy JH, Phillips WM, Landis DL, et al. Complete left ventricular bypass with a paracorporeal pump: design and evaluation. Ann Surg. 1974;180: 418–26. 3. Pennock JL, Pierce WS, Campbell DB, Pae WE Jr, Davis D, Hensley F, et al. Mechanical support of the circulation followed by cardiac transplantation. J Thorac Cardiovasc Surg. 1986;92(6): 994–1004. 4. Farrar DJ, Hill JD, Gray LA Jr, Pennington DG, McBride LR, Pierce WS, Pae WE, et al. Heterotopic prosthetic ventricles as a bridge to cardiac transplantation. A multicenter study in 29 patients. N Engl J Med. 1988;318:333–40. 5. Catanese KA, Goldstein DJ, Williams DL, Foray AT, Illick CD, Gardocki MT, et al. Outpatient left ventricular assist device support: a destination rather than a bridge. Ann Thorac Surg. 1996;62:646–52.
6. Hrobowski T, Lanfear DE. Ventricular assist devices: is destination therapy a viable alternative in the non-transplant candidate? Curr Heart Fail Rep. 2013;10:101–7. 7. Stevenson LW, Miller LW, Desvigne-Nickens P, Ascheim DD, Parides MK, Renlund DG, et al. Left ventricular assist device as destination for patients undergoing intravenous inotropic therapy: a subset analysis from REMATCH (Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure). Circulation. 2004;110:975–81. 8. Neragi-Miandoab S. A ventricular assist device as a bridge to recovery, decision making, or transplantation in patients with advanced cardiac failure. Surg Today. 2012;42:917–26. 9. Matsumiya G, Saitoh S, Sakata Y, Sawa Y. Myocardial recovery by mechanical unloading with left ventricular assist system. Circ J. 2009;73:1386–92. 10. Morita S. An old ventricular assist device still working for patients with end-stage heart failure in Japan. Circ J. 2011;75: 53–4. 11. Saito S, Matsumiya G, Sakaguchi T, Fujita T, Kuratani T, Ichikawa H, Sawa Y. Fifteen-year experience with Toyobo paracorporeal left ventricular assist system. J Artif Organs. 2009;12: 27–34. 12. Eghtesady P, Almond CS, Tjossem C, Epstein D, Imamura M, Turrentine M, Tweddell J, Jaquiss RD, Canter C. Berlin heart investigators. Post-transplant outcomes of children bridged to transplant with the Berlin Heart EXCOR Pediatric ventricular assist device. Circulation. 2013;128(Suppl 1):S24–31. 13. Cassidy J, Dominguez T, Haynes S, Burch M, Kirk R, Hoskote A, et al. A longer waiting game: bridging children to heart transplant with the Berlin Heart EXCOR device—the United Kingdom experience. J Heart Lung Transplant. 2013;32:1101–6. 14. McCarthy PM, Portner PM, Tobler HG, Starnes VA, Ramasamy N, Oyer PE. Clinical experience with the Novacor ventricular assist system. Bridge to transplantation and the transition to permanent application. J Thorac Cardiovasc Surg. 1991;102: 578–86. 15. McCarthy PM, James KB, Savage RM, Vargo R, Kendall K, Harasaki H, et al. Implantable left ventricular assist device. Approaching an alternative for end-stage heart failure. Implantable LVAD Study Group. Circulation. 1994;90(5 PT 2):II83–6. 16. Nurozler F, Argenziano M, Oz MC, Naka Y. Fungal left ventricular assist device endocarditis. Ann Thorac Surg. 2001;71(2): 614–8. 17. Yoshioka D, Sakaguchi T, Saito S, Miyagawa S, Nishi H, Yoshikawa Y, et al. Initial experience of conversion of Toyobo paracorporeal left ventricular assist device to DuraHeart left ventricular assist device. Circ J. 2012;76:372–6. 18. Morshuis M, El-Banayosy A, Arusoglu L, Koerfer R, Hetzer R, Wieselthaler G, et al. European experience of DuraHeart magnetically levitated centrifugal left ventricular assist system. Eur J Cardiothorac Surg. 2009;35:1020–7. 19. Yamazaki K, Kihara S, Akimoto T, Tagusari O, Kawai A, Umezu M, et al. EVAHEART: an implantable centrifugal blood pump for long-term circulatory support. Jpn J Thorac Cardiovasc Surg. 2002;50:461–5. 20. Sakaguchi T, Matsumiya G, Yoshioka D, Miyagawa S, Nishi H, Yoshikawa Y, et al. DuraHeartTM magnetically levitated left ventricular assist device: Osaka University experience. Circ J. 2013;77:1736–41. 21. Nojiir C, Kijima T, Maekawa J, Horiuchi K, Kido T, Sugiyama T, et al. Terumo implantable left ventricular assist system: results of long-term animal study. ASAIO J. 2000;46:117–22. 22. Nishinaka T, Schima H, Roethy W, Rajek A, Nojiri C, Wolner E, et al. The DuraHeart VAD, a magnetically levitated centrifugal pump: the University of Vienna bridge-to-transplant experience. Circ J. 2006;70:1421–5.
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temporary right ventricular assist using a centrifugal pump in patients with severe biventricular failure. J Heart Lung Transplant. 2012;31:858–64. Craig ML. Management of right ventricular failure in the era of ventricular assist device therapy. Curr Heart Fail Rep. 2011;8: 65–71. Krabatsch T, Potapov E, Stepanenko A, Schweiger M, Kukucka M, Huebler M, et al. Biventricular circulatory support with two miniaturized implantable assist devices. Circulation. 2011;124(11 Suppl):S179–86. Strueber M, Meyer AL, Malehsa D, Haverich A. Successful use of the HeartWare HVAD rotary blood pump for biventricular support. J Thorac Cardiovasc Surg. 2010;140:936–7. Loforte A, Montalto A, Della Monica PL, Contento C, Musumeci F. Biventricular support with the HeartWare implantable continuous flow pump: an additional contribution. J Heart Lung Transplant. 2010;29:1443–4. Ueno T, Fukushima N, Sakaguchi T, Ide H, Ozawa H, Saito S, et al. First pediatric heart transplantation from a pediatric donor heart in Japan. Circ J. 2012;76:752–4. Miera O, Potapov EV, Redlin M, Stepanenko A, Berger F, Hetzer R, et al. First experiences with the HeartWare ventricular assist system in children. Ann Thorac Surg. 2011;91:1256–60.
REVIEW ARTICLE
Current status of third-generation implantable left ventricular assist devices in Japan, Duraheart and HeartWare Yoshiki Sawa
Received: 1 January 2014 / Accepted: 12 May 2014 Ó Springer Japan 2014
Abstract Recently, left ventricular assist devices (LVADs) have become a viable therapeutic approach as a bridge to cardiac transplantation, as well as destination therapy or as part of the bridge to recovery. In Japan, paracorporeal pneumatic devices are the only choice for such therapy, as implantable LVADs are not yet generally available due to device lag, which represents a serious problem in this field. Clinical trials of four different continuous-flow pumps, both axial and centrifugal flow types, were completed at about the same time, and two of those devices, DuraHeart and EVAHEART, have already been approved for use in Japan. Thus, reports of advanced treatment for severe heart failure with these devices are expected. The DuraHeart (Terumo Heart, Ann Arbor, MI, USA) and another device named the HeartWare (HeartWare Inc, Miami Lakes, FL, USA) are so-called thirdgeneration devices, as they have achieved miniaturization and improvements in performance from the use of magnetic levitation. Based on our experiences from both clinical research and experimental use, we herein discuss the DuraHeart and HeartWare devices, with a focus on the clinical outcomes and management strategies. Because of the long waiting period for heart transplantation in Japan, these two devices are considered to have important roles in the near future for the treatment of severe heart failure, and a comprehensive strategy for LVAD therapy including such third-generation implantable devices is expected.
Y. Sawa (&) Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2, Yamada-Oka, Osaka, Suita 565-0871, Japan e-mail: [email protected]
Keywords Left ventricular assist device Mechanical circulatory support Bridge to transplantation
Introduction The initial development of ventricular assist devices (VADs) began in the 1970s as a permanent treatment option for end-stage heart failure [1, 2]. However, from the mid 1980s, the focus of VAD development shifted to left ventricular support without heart resection, and left ventricular assist devices (LVADs) have since become a viable therapeutic approach as a bridge to cardiac transplantation (BTT) [3, 4]. LVADs provide effective BTT therapy for patients with end-stage heart failure, and are increasingly used for destination therapy (DT) [5–7]. Recently, reports of patients weaned from LVAD use due to recovery of cardiac function have also been increasing, and the concept of bridge to recovery (BTR) using an LVAD has become popular [8, 9]. First-generation LVADs provide pulsatile flow by employing a paracorporeal pulsatile pump device, which drains blood from the left atrium or left ventricle and sends it to the ascending aorta. In Japan, the Nipro LVAD (Nipro, Osaka, Japan) is the only available paracorporeal pneumatic device [10, 11]. Currently, this device is still used for biventricular support or pediatric patients weighing up to 20 kg after the introduction of an implantable device [12, 13]. In such cases, an implantable pulsatile pump is placed into a pocket created in the abdominal cavity and is connected by a driveline cable with a diameter of about 1 cm that passes outside the body. The benefit of this type of device is a high blood flow rate and a small controller, making it possible for patients to be mobile. The Nocavacor
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ventricular assist device (WorldHeart, Canada) [14] and Heart Mate I [15] are other types of implantable pulsatile flow pumps. These can reproduce the physiological hemodynamic status, although they have not shown favorable results due to the lack of miniaturization, the complexity of the device system and the requirement of a thick cable [16]. Thus, continuous-flow LVADs were developed to reduce the size of the pump and cable, and their less complex design was aimed to provide greater long-term mechanical reliability, leading to an improved usefulness in DT [7]. Until very recently, implantable LVADs have not been available in Japan due to device lag [17], which represents a serious problem in this field. Clinical trials of four types of continuous-flow pumps, both axial and centrifugal flow types, were completed at about the same time, and two of those devices, the DuraHeart (Terumo Heart, Ann Arbor, MI, USA) [18] and EVAHEART (SunMedical, Nagano, Japan) [19], have already been approved for use in Japan. Thus, reports of advanced treatment for severe heart failure with these devices are expected. The DuraHeart and another device named the HeartWare (HVAD; HeartWare Inc., Miami Lakes, FL, USA) are so-called third-generation devices, as they have achieved miniaturization and improvements in performance from the use of magnetic levitation. Based on our experiences from both clinical research [20] and experimental use, we herein discuss the DuraHeart and HVAD devices, with a focus on the clinical outcomes and management strategies.
DuraHeart The DuraHeart is the first LVAD to use magnetic levitation for the centrifugal pump, which allows for rotation of the impeller, without contact anywhere on the inner wall of the blood chamber (third-generation pump). In 1994, the development of a magnetic levitation centrifugal pump system was begun as a joint project by Kyoto University, NTN Corporation and Terumo. They achieved long-term support of 864 days in chronic animal experiments using the prototype [21], and confirmed its long-term durability and anti-thrombogenic characteristics. Thereafter, clinical development of the DuraHeart started in 1999, followed by clinical trials in Europe for use in BTT. The pump was approved and obtained the CE mark in Europe in January 2004. In addition, clinical BTT trials were started in February 2007 in the United States [22], and a clinical trial of six cases was started in Japan in October 2008 [20, 23]. The DuraHeart was finally approved in Japan, along with the EVAHEART, in December 2010, and approval for reimbursement from the national health insurance program
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Fig. 1 The blood pump of the DuraHeart (upper) device and the structure of the blood pump (lower)
started in April 2011, which signaled the dawn of a new era of treatment for severe heart failure in Japan. There are two types of third-generation continuous-flow pumps, the magnetic levitation type and magnetic bearing with dynamic pressure type. The DuraHeart (Fig. 1) is a magnetic levitation type centrifugal pump. By levitating the impeller by electromagnetic force to rotate it in the blood flood, the risk of thrombus formation and friction from the bearing are eliminated. The impeller is rotated by a magnetic coupling placed between a permanent magnet incorporated into the motor outside the blood chamber and a passive magnet incorporated into the ring of the motor, while the impeller remains fixed in the center of the blood chamber. A distance of 250 lm from the wall of the blood chamber is set for sufficient blood washout, which results in no mechanical friction in the blood chamber. Therefore, durability, anti-thrombogenic characteristics and low levels of hemolysis are expected with long-term use. If the magnetic levitation system becomes broken, the impeller can continue to rotate from the dynamic pressure generated by the pump housing as a safety back-up. This system is called hydrodynamic bearing driven by hydrodynamic
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Fig. 2 The DuraHeart. a Blood pump, b monitor and c controller and battery
Fig. 3 The intraoperative procedures during the implantation of a DuraHeart device. a Pledgetted sutures were placed on the apex of the left ventricle. b The myocardium was resected, and the cuff was
attached to the apex. c The DuraHeart pump was attached to the cuff and put into the pocket
power. Because of its low noise level, the pump flow rate can be most accurately determined by the amount of hematocrit and the rotational speed of the motor. The pump volume is 180 mL, while the device weight is 540 g, the diameter is 73 mm and the height is 46.2 mm. The rotation rate is variable from 1,200 to 2,400 rpm, with a stroke volume up to 10 L/min being possible. The normal rotational speed setting is 1,600–2,000 rpm, and the flow rate for adults is 4–6 L/min. The pump is made of titanium, with heparin coating applied to blood contact surfaces. The outside kit is composed of two batteries and a controller, and its total weight is 2,250 g. The inflow cannula has an inner diameter of 12 mm and an outer diameter of 14 mm, with three different lengths available depending on patient size (Fig. 2). The outflow graft is a Gelweave graft coated with gelatin, with inner and outer diameters of 12 and 14 mm, respectively. Pre-clotting is not needed with the DuraHeart.
pocket, and a percutaneous cable is initially pulled out from a small skin incision made in the right upper quadrant, then the cable is again pulled out from the left middle abdomen below the navel. This procedure is done to reduce the risk of infection from the cable, which extends to the pump, by increasing the subcutaneous portion. After establishing cardiopulmonary bypass and partial clamping of the ascending aorta, the outflow is anastomosed to the ascending aorta. Next, the apex of the left ventricle is cut out with a coring knife, and the cuff is sewn to the apex using 12 pairs of pledgetted sutures (Fig. 3a), followed by the insertion of the inflow cannula (Fig. 3b, c). The inner diameter of the cuff and the diameter of the outflow graft of the DuraHeart and Nipro LVAD are the same size, providing advantages when exchanging these devices [13].
Surgical technique The implantation technique used at Osaka University has been described in a previous report [20]. After a median sternotomy, a pump pocket is created in the preperitoneal fat layer in the upper left abdomen, and the diaphragm is dissected toward the apex. The device is placed in the
Device management The protocol at Osaka University states that the rpm of the DuraHeart should be set to provide adequate cardiac output and achieve normal left ventricular decompression [17]. We optimize the rpm using both hemodynamic and echocardiographic methods at the time of LVAD implantation, as well as before the patient is discharged from the hospital, and whenever clinical events, such as new symptoms or suction events, warrant further adjustment.
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For postoperative anticoagulation, warfarin is administered to maintain an international normalized ratio (INR) of 2.0–2.5, together with 100 mg of aspirin daily, once the patient is able to take oral medication. In addition, the intravenous administration of heparin is started 12 h after surgery to achieve an activated prothrombin time of 50–70 s unless significant bleeding has occurred [20]. Clinical experience We initially performed two DuraHeart implantations as part of a clinical research project at Osaka University in August 2008, and we had treated a total of 25 cases by November 2011 (Table 1). The mean age of our patients at the time of surgery was 40 ± 10 years (range 17–56 years), and there were 17 males and 8 females. The mean length of the operation for all patients was 404 ± 138 min, and the Table 1 Our cases implanted with the DuraHeart device
DCM dilated cardiomyopathy, dHCM dilated phase hypertrophic cardiomyopathy, CM cardiomyopathy, LVAD left ventricular assist device, RVAD right ventricular assist device, BiVAD biventricular assist device, HTx heart transplantation
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cardiopulmonary bypass time was 132 ± 65 min. The mean length of the operation for the five patients who initially underwent isolated DuraHeart implantation was 330 ± 98 min (205–492 min), and their mean cardiopulmonary bypass time was 137 ± 72 min (67–269 min). There were no cases of 30-day or inhospital mortality. The average duration of support was 615 ± 239 days (254–1,028 days). Two patients with fulminant myocarditis underwent conversion of the LVAD from a Nipro LVAD to a DuraHeart and JARVIK 2000 (Jarvik Heart, Inc, New York, NY, USA), which was implanted as a RVAD. [24]. One of those died on postoperative day 539 due to sepsis, while the other survived and eventually underwent heart transplantation. At present, seven patients have undergone heart transplantation, while all others are still alive and waiting for heart transplantation except for the BiVAD
Pt
Age
Sex
Diagnosis
Operation(s)
Outcome
Support duration (days)
1
45
Male
dHCM
LVAD
HTx
1,012
2
49
Male
ICM
LVAD
HTx
785
3
30
Male
dHCM
LVAD
Ongoing (Home)
4
26
Male
DCM
LVAD
Ongoing (Home)
982
5
35
Female
Myocarditis CM
BiVAD (DuraHeart LVAD ? Jarvik RVAD)
HTx
968
6
30
Female
Myocarditis CM
Death (sepsis)
539
7
34
Female
DCM
BiVAD (DuraHeart LVAD ? Jarvik RVAD) LVAD
HTx
872
8
46
Male
DCM
LVAD
Ongoing
832
9
53
Male
DCM
LVAD
Ongoing (Home)
825
10
28
Male
dHCM
LVAD
HTx
511
11
16
Male
dHCM
LVAD
HTx
574
12
17
Male
DCM
LVAD
Ongoing (Home)
748
13
25
Male
DCM
LVAD
Ongoing (Home)
730
14
35
Female
DCM
LVAD
HTx
443
15
21
Female
dHCM
LVAD
Ongoing (Home)
517
16
31
Male
ICM
LVAD
Ongoing (Home)
502
17
49
Male
ICM
LVAD
Ongoing (Home)
491
18
36
Male
LVAD
Ongoing
254
19
32
Female
Chronic rejection after HTx DCM
LVAD
Ongoing (Home)
460
20
40
Female
ARVC
LVAD
Ongoing (Home)
442
21
24
Male
dHCM
BiVAD (DuraHeart LVAD ? NIPRO RVAD)
Ongoing
419
22
37
Female
DCM
LVAD
Ongoing (Home)
408
23
43
Male
Becker secondary CM
LVAD
Ongoing (Home)
384
24
56
Male
DCM
LVAD
Ongoing (Home)
356
25
31
Male
DCM
LVAD
Ongoing (Home)
308
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patient described above. All but three patients were discharged from the hospital to home, one of whom had received a DuraHeart due to chronic rejection after transplantation, one with a Nipro RVAD and one whose household was in a remote area. We experienced nine cases of exchange from an extracorporeal Nipro LVAD to the DuraHeart. Six patients required a RVAD due to right heart dysfunction, three of whom were able to be weaned from that device and three of whom required BiVAD. We also encountered three cases in pressure mode due to partial disconnection of the cable, two of whom underwent a device exchange procedure and one of whom has been waiting in dynamic pressure mode for 267 days for heart transplantation as of the writing of this manuscript. Six cases develop LVAD-related infections, four of whom had an omentum flap, one of whom had a free latissimus dorsi flap and one of whom had a free thigh muscle flap. The infection was well controlled in all cases. Four patients had cerebrovascular events (two cases each of cerebral hemorrhage and cerebral infarction). Although DuraHeart implantation generally improved the quality of life of our patients, device infection or failure, right heart failure and cerebrovascular accidents are still considered to be potential problems. The System Interagency Registry for Mechanically Assisted Circulatory Support administered through INTERMACS to monitor the performance and usage of VADs has been introduced in the United States [25], while in Japan, the Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS) was started in 2012. In the near future, the long-term results of patients with an implantable ventricular assist device in Japan will be available through the J-MACS.
HeartWare (HVAD) The HVAD is a third-generation type of implantable VAD that can generate a high flow rate of up to 10 L/min. Due to the small (50 mL) pump body, the creation of a pump pocket is not required. The diameter of the drive line is thin, at 4.2 mm, and the weight of the pump itself is light at 160 g, while the outflow graft is only 10 mm. Together with one controller and two batteries, this compact device weighs 1.1 kg. The impellor is levitated by a magnetic hydrodynamic suspended system, and operates at 1,800–4,000 rpm [26] (Figs. 4, 5). The HVAD has received the CE mark based on good early results reported in Europe. In the United States, a large clinical study of the HVAD was recently completed, with feasibility reported, which was followed by approval by the FDA, while a clinical trial for destination therapy (Endurance trial) is
presently in progress. We conducted the first nine cases of HVAD implantation surgery in Japan as part of a clinical research study. The following is an overview of the perioperative management and surgical technique used for the HVAD cases. Surgical technique The following implantation technique is used at Osaka University: After a usual median sternotomy, cardiopulmonary bypass is established in the usual manner with the ascending aorta and bicaval cannulation. Creating a pump pocket is unnecessary for HVAD implantation. Basically, the operation is performed on a beating heart, and we begin with an apical procedure. First, the apex is lifted with a surgical towel, and the appropriate position of the inflow cuff is determined. We identify the location in a straight line in the direction of the mitral valve using transesophageal echocardiography. It is preferable to mark the appropriate position to place the cuff on the apex. We also mark the insertion point of the needle, the coring portion and the outer diameter of the cuff. Then, 12 sutures with large felt are placed evenly around the apex (Fig. 6a). We have found that it is better to simultaneously sew the sutures to the cuff and heart muscle. It is important to firmly secure the sutures to the myocardium in order to avoid bleeding, because it would be difficult to deal with bleeding from the left side of the apex. In addition, care should be taken to adjust the position of the fixed screw towards the surgeon’s side. We then attach a fibrin glue sheet (TacosealÒ) around the cuff to prevent further bleeding after appropriately tying the sutures. Next, with the patient in a head down position, the muscle of the apex is punched out using a coring device under ventricular rapid pacing (Fig. 6b). We examine the inside of the left ventricle to check for the presence of thrombi, and the trabecular portion is carefully removed as much as possible. After securing a sufficient lumen, the HVAD is quickly connected while preventing air contamination as much as possible (Fig. 6c). The position and direction of the HVAD, driveline and outflow graft are then adjusted, followed by fixing the device with screws. If the position is incorrect, it is easy to re-adjust by loosening the screws, which is also a great advantage in cases requiring replacement. After returning the position of the apex, the rapid pacing is stopped. As the next step, the outflow graft is directed to the ascending aorta so as to pass around the outside of the right atrium and along the acute margin, while adjusting the length by putting volume in the heart. An end-to-side anastomosis to the ascending aorta is performed under partial clamping of the ascending aorta using a 4–0 Prolene continuous suture, which is easy to use due to its small size
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(10 mm). A de-airing needle is inserted slightly on the head side of the anastomosis after declamping the ascending aorta. After performing the outflow graft anastomosis, the driveline is pulled to outside of the body using a dedicated device, which can be connected to the driveline from both sides.
Finally, the HVAD is started at 1,800 rpm while checking the de-airing using transesophageal echocardiography, and the rotational speed is gradually increased. It is often necessary to place an 18-G needle in the outflow graft to remove air in cases. with insufficient de-airing. Weaning from cardiopulmonary bypass is performed in the same manner as with other VADs using an appropriate mix of nitric oxide and inotropes, while paying attention for right ventricular failure. In most cases, the rotational speed of the HVAD at that time ranges from 2,400 to 2,600 rpm, and the flow should be adequate to ensure 4 L/min. Finally, the chest is closed in the usual manner. During HVAD implantation, the creation of a pump pocket is unnecessary, and the procedure is simple after determining the appropriate position of the cuff. As a result, it is possible to reduce both the cardiopulmonary bypass time and the total length of the operation time. Because of its compact size, we have experienced no problems with inserting the device into relatively small Japanese patients. Device management
Fig. 4 The blood pump of the HeartWare device (upper) and the structure of the blood pump (lower)
To manage an HVAD, a viscosity value in accordance with the appropriate hematocrit value at the time of setting the pump flow is entered, and it is necessary to change the number frequently in order to obtain the correct flow. The recommended rotational speed for this device is 2,400–3,200 rpm, and it is important to ensure that the flow remains above 2 L/min, and it is also better when the cardiac index is [2 L/min/m2. Since the pump flow is dependent on the afterload and preload, it is important to maintain an appropriate CVP and mean blood pressure, which should be kept at 90 mmHg or less. We usually check the flow, power consumption and flow pulsatility on the monitor. It is advisable to keep the power consumption within a range of 3–7 W. The flow pulsatility value is the difference between the maximum and minimum values of the flow waveform, and it is advisable to keep it at 2–4 L/min. A high flow pulsatility value may
Fig. 5 The HeartWare (HVAD). a Blood pump, b monitor and c controller and battery
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Fig. 6 The intraoperative procedures during the implantation of a HeartWare device. a Twelve pledgetted sutures were placed on the apex of the left ventricle. b The myocardium was resected using a coring device. c The HVAD pump was attached to the cuff
indicate adverse flow through the pump, while a low flow pulsatility may indicate a sucking problem. In addition, the HVAD is equipped with a Lavare cycle, a specific system mode. The purpose of this mode is to prevent thrombus formation by alternating the rotational speed of the pump, by 200 rpm lower for 2 s and 200 rpm higher for one second every 60 s. This should be activated after the patient’s condition becomes stable. For anticoagulation, the protocol of Osaka University Graduate School of Medicine calls for starting intravenous heparin from postoperative day 1. The activated partial thromboplastin time is then adjusted to a range of 40–50, then 50–60 after the amount of drainage is decreased. We start oral aspirin and warfarin once oral intake is possible. After the INR reaches 2.5–3.0, the intravenous heparin is stopped [27]. The general management is the same as with other VADs. We think that the incidence of driveline trouble will be lower due to the small diameter. Nevertheless, it is important to avoid cardiac tamponade or bleeding, and to appropriately treat right heart failure and control arrhythmia. The administration of appropriate antibiotics is also important. It is advisable to analyze all obtained data, and perform periodic systematic checks of the history of the flow and alarms, in order to ensure that any problems are identified as soon as possible. Clinical experience (Table 2) We have treated nine patients [six males, three females; mean 33.5 ± 7.8 years old; New York Heart Association (NYHA) class III or IV] with an HVAD as BTT. All device-related costs were supported by a Grant-in-Aid for scientific research from the Ministry of Health, Labor, and Welfare of Japan. Five had dilated cardiomyopathy, three had secondary cardiomyopathy and one had dilated phase hypertrophic cardiomyopathy. All pumps were placed in an intra-pericardial manner, and a pump pocket was not
required in any of the cases. The mean length of the operation for all patients was 269 ± 77 min, and the cardiopulmonary bypass time was 121 ± 40 min. The mean length of the operation for the five patients who initially underwent isolated HVAD implantation was 236 ± 39 min (194–294 min), and their mean cardiopulmonary bypass time was 112 ± 39 min (70–184 min). One patient 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. The mean support duration was 245 ± 162 days (50–535 days), and the mean pump blood flow at 1 month postoperatively was 4.8 ± 0.8 L/min. There was no mortality after 30 days, although one patient died during support due to cerebral hemorrhage. Presently, the others are waiting for heart transplantation without problems, except one patient who suffered from an active infection. There has been no pump mechanical failure in any case.
Future perspectives of the DuraHeart and HVAD in Japan Conversion from a Nipro VAD to the DuraHeart device Due to the so-called device lag problem in Japan, implantable VADs have not been available until very recently, and the Nipro LVAD, a paracorporeal pneumatic device, had been the only choice for most patients. As described in previous reports, long-term use of this LVAD can cause serious problems [11]. Considering the long waiting time for patients who have already undergone implantation with a Nipro LVAD, we believe that conversion to an implantable continuous-flow device will provide a safer bridge to transplantation and promises higher quality of life. We have now converted eight patients (four males and four females) from a Nipro paracorporeal LVAD to a DuraHeart device [13]. In those
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Surg Today Table 2 Our cases implanted with the HeartWare device
DCM dilated cardiomyopathy, dHCM dilated phase hypertrophic cardiomyopathy, CM cardiomyopathy, LVAD left ventricular assist device, RVAD right ventricular assist device, BiVAD biventricular assist device, HTx heart transplantation
Pt
Age
Sex
Diagnosis
Operation
Outcome
Support duration (days)
1
36
Male
DCM
LVAD
Ongoing (Home)
533
2
26
Male
Secondary CM
LVAD
Ongoing (Home)
458
3
29
Male
DCM
LVAD
Ongoing (Home)
401
4
40
Male
dHCM
LVAD ? temporary RVAD
Ongoing
370
5
47
Female
DCM
LVAD
Death (cerebral bleeding)
6
27
Male
Doxorubicininduced CM
LVAD
HTx
191
7
34
Female
Doxorubicininduced CM
LVAD
Ongoing (Home)
319
8
46
Male
DCM
LVAD
Ongoing (Home)
120
9
53
Male
DCM
LVAD
Ongoing
50
10
13
Female
dHCM
BiVAD (HeartWare ? HeartWare)
Ongoing
235
cases, the apical cuff of the Nipro was not exchanged because the size was the same as that of the DuraHeart. All conversion operations were performed safely, although three patients who had an infection in the Nipro LVAD cannulation site prior to conversion suffered later pocket infections, and one died because of sepsis. One of these patients underwent heart transplantation, and seven are currently awaiting heart transplantation at home. As noted above, in cases of conversion from a Nipro VAD to DuraHeart device, the apical cuff of the former can be used with the DuraHeart inflow conduit, so it is not necessary to replace the apical cuff, which allows for a shorter operation time and reduces the risk of bleeding. This is especially beneficial in cases of pure LVAD conversion. Even a superficial infection of the cannula exit site is considered to be a significant risk for the development of a refractory pocket infection after conversion, which can lead to fatal complications. Based on our experience, we now consider this procedure to be contraindicated in patients with any signs of infection at the Nipro LVAD cannula exit site. However, most of our conversion cases were safely performed, even in patients with infections. Considering that implantable LVADs provide superior long-term survival and quality of life, conversion is a reasonable decision for Nipro LVAD users who have no infection. Right heart support and support for children Because of the compact size of the HVAD, it can be used for various purposes. For example, it is suitable for the general Japanese population, whose body size is relatively smaller than that of Western populations. Furthermore, there are two possible future indications; right heart support and support for pediatric cases.
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In patients receiving LVAD support, up to 30 % of those with end-stage heart failure experience biventricular failure that requires biventricular support [21, 28–30]. In such cases, a biventricular assist device, which employs a bulky extracorporeal or implantable displacement pump, is required. However, we believe that the use of an implantable continuous-flow device provides safer BTT and promises a higher quality of life. Soon after the market launch of miniaturized LVADs, reports were published about attempts to use these devices for biventricular support [22, 31–33]. Krasbach et al. [31] reported 17 patients, two of whom underwent HVAD implantation for biventricular support. They concluded that two HeartWare HVADs can be used to form an implantable biventricular support system after a few important modifications of the implantation procedure for adjusting the right heart circulation. On the other hand, this small pump also has potential for use in children. Although a recent law in Japan now makes it possible for children to undergo heart transplantation, there are few options for those with terminal heart failure due to the shortage of donor hearts and the unavailability of VADs [24, 33, 34]. The implantable VAD systems suitable for adult patients are too large for use in pediatric patients, thus, paracorporeal systems are routinely utilized. Miera et al. [35] reported the cases of seven children between 6 and 16 years old who received implantation of an HVAD. All patients had multi-organ failure under inotropic support, and six were successfully bridged to cardiac transplantation. Not only were the outcomes good, but the morbidity rate during circulatory support was also low. During a total of more than 480 days of support, none of the patients suffered from an infection or thromboembolism. They concluded that the HeartWare assist system can
Surg Today
be successfully used as a bridge to transplantation in children and adolescents with end-stage heart failure. At our institution, we treated a 13-year-old female with HVAD implantation as part of a clinical research study on severe heart failure in children. Initially, she underwent LVAD implantation, which resulted in the need for temporary right heart support with a centrifugal pump. However, the right-side heart function was not yet recovered, and weaning from the RVAD was thought to be difficult even after unloading the RV volume by use of a temporary centrifugal pump for 3 weeks. We decided to convert to an implantable device for the right heart, which was successfully performed. She is now on the waiting list for heart transplantation and is living at home.
Conclusion With no mechanical friction in the pump chamber as a result of the use of a magnetic levitation system in the DuraHeart, and a magnetic hydrodynamic suspended system in the HVAD, the third-generation implantable VADs are expected to provide long-term durability, with antithrombogenic characteristics and low hemolysis. In light of the long waiting period for heart transplantation in Japan, these devices will play important roles in the treatment of patients with severe heart failure. Furthermore, each has advantageous features making them applicable for specific situations. We anticipate the development of a comprehensive VAD therapy strategy that includes these implantable VADs in the near future.
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