Current status of extracorporeal ventricular assist devices in Japan

J Artif Organs DOI 10.1007/s10047-014-0779-8

REVIEW

Artificial Heart (Clinical)

Current status of extracorporeal ventricular assist devices in Japan Takashi Nishimura

Received: 6 May 2014 / Accepted: 4 June 2014 Ó The Japanese Society for Artificial Organs 2014

Abstract Extracorporeal VADs are less expensive, their prices reimbursable by the health insurance being about one-sixth of those of implantable VADs in Japan. However, a disadvantage is that, in Japan, their use is restricted to hospitals, necessitating prolonged hospitalization, reducing the patients’ quality of life. According to the Japanese registry for Mechanically Assisted Circulatory Support, the survival rate does not differ significantly between patients with extracorporeal and implantable VADs. As in Europe and North America, extracorporeal VADs in Japan are commonly used as Bridge to Decision or Bridge to Recovery. Extracorporeal VADs are switched to implantable VADs as a Bridge-to-Bridge strategy after stabilization or when cardiac function recovery fails. They are also used as right ventricular assist devices (RVADs) in patients with right heart failure. A special characteristic of extracorporeal VADs in Japan is their frequent use as a Bridge to Candidacy. In Japan, indications for implantable VADs are restricted to patients registered for heart transplantation. Therefore, in patients who cannot be registered for transplantation because of transient renal dysfunction, etc., due to heart failure, extracorporeal VADs are used first, and then replaced by implantable VADs after transplant registry is done. Here, we describe the current status of extracorporeal VADs in Japan, focusing on the environmental backgrounds, along with a review of the relevant literature.

T. Nishimura (&) Department of Cardiac Surgery, Tokyo Metropolitan Geriatric Hospital, 35-2, Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan e-mail: [email protected]

Keywords Extracorporeal ventricular assist device VAD type VAD indication Field of research: artificial heart (Basic) Artificial heart (Clinical)

Introduction Since 2011, when 2 reliable continuous flow-type implantable ventricular assist devices (VADs) began to be included in the medical reimbursement system, treatment of severe heart failure in Japan has changed dramatically. Implantable VADs began to be used in patients with severe heart failure who otherwise needed repeated hospitalization; therefore, these patients could receive home treatment and be eventually reintegrated into society. This had a great impact on the society as a whole, including cardiovascular internists. Some people anticipated that the conventional extracorporeal VADs would fade away from use when implantable VADs associated with such high therapeutic efficacy became available in the market. However, as of March 12, 2014, according to a report of the Japanese registry for Mechanically Assisted Circulatory Support (JMACS), among 287 patients with VADs who were registered from 26 institutions, implantable VADs were used in 216 patients, whereas extracorporeal VADs were used in 71 patients, indicating that extracorporeal VADs were used in about one-fourth of all patients even after implantable VADs became available in the market [1]. Therefore, there are still questions that need to be answered: what is required for extracorporeal VADs and in which direction should these devices continue to develop? Here, we discuss the current status of extracorporeal VADs, focusing on their roles in Japan.

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Types and characteristic features of extracorporeal VADs (Table 1) ZEON VAD (The Tokyo University ventricular assist system) Use of VADs in Japan began with the ZEON VAD, an extracorporeal VAD, in 1980 [2]. A clinical trial of ZEON VAD was carried out in 61 patients from 21 institutions between 1985 and 1989. ZEON VAD was approved for manufacture and distribution in 1990, and began to be covered by the health insurance in 1994. This device, manufactured by ZEON Co., Ltd, was a pneumatically driven sac-type VAD [3]. According to the registry of the Japanese Association for Clinical ventricular assist systems, this device was used in 160 patients until its sale was discontinued in 2005 [4]. NIPRO-VAD (National Cardiovascular Center/Toyobo ventricular assist system) NIPRO-VAD was first implanted in 1982 [5], and has been still used most commonly as an extracorporeal VAD in Japan. According to Takano et al. [6] a clinical trial of NIPRO-VAD was begun in 1985, covering 92 patients from 32 institutions. As of September 2012, NIPRO-VAD was being used in 902 patients [4]. The NIPRO-VAD is a Table 1 Profiles of extracorporeal ventricular assist devices

Manufacturing company

pneumatically driven diaphragm-type VAD made of antithrombogenic polyurethane (Toyobo TM3 and TM5 [7]). The blood pump is divided into an air chamber and a blood chamber by the diaphragm. The entry and exit of the blood chamber have built-in mechanical valves (Medtronic Hall valve: Medronic Inc., Minneapolis, MN, USA) that allow the blood to flow in only one direction, preventing regurgitation [8]. The blood pump has a volume of 70 mL, and can pump 50–60 mL per beat during normal operation [6]. Although 1-month use was the condition of approval for production and distribution, Kashiwa et al. [9] reported keeping this device in operation for 1,264 consecutive days without pump replacement. Thus, this system is applicable for prolonged use, although caution is necessary, because breakage of the diaphragm has been reported [9]. Clinical results vary among different indications, and the reported 1-year survival rate of patients on this device is 46–82 % [10–12]. Analysis by J-MACS revealed a favorable 1-year survival rate of 84 % for this system, which was not significantly different from the corresponding survival rate obtained with implantable VADs [13]. Abiomed BVS5000/AB5000 Abiomed BVS5000 is used for short-term assist in gravity drainage of the left atrium, extending for about several weeks. The blood pump consists of two blood chambers Clinical experience in Japan

Current situation in Japan

Approval in other country

Pulsatile pump ZEON VAD

ZEON

160 cases

Discontinued

No approval

NIPRO-VAD

NIPRO

More than 1,000 cases

Approved as VAD

No approval

BVS5000

Abiomed

More than 170 cases

Discontinued

FDA and CE mark approval as VAD

AB5000

Abiomed

6 cases (as clinical trial)

Waiting approval


PVAD

Thoratec

No report

No plan for clinical trial


EXCOR

Berlin Heart

4 cases (as clinical trial)

Waiting approval


Continuous flow pump

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CentriMag

Thoratec

No report



Rotaflow

Maquet

A report of 2 months support

Approved as short-term support

FDA and CE mark approval as short-term support

MERA

Senko

A report of 5 weeks support

Approved as short-term support

No approval

TandemHeart

CardiacAssist

No report


FDA and CE mark approval as short-term support

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lined up vertically. The blood is drained from the patient into the atrial chamber passively by gravitation, sent to the ventricular chamber, and then transmitted to the aorta from the ventricular chamber contracted pneumatically. Because the body of the pump is fixed to the bed rail, the patient has to be confined to bed. The major characteristic feature of this system is that it allows biventricular assist; both the right and left ventricles can be supported by one console [14]. According to the registry of the Japanese Association for Clinical ventricular assist systems, by September 2012, BVS5000 had been used in 174 patients in Japan for shortterm use, with a mean duration of use of 8 days. Among these cases, biventricular assist was attempted in 32 cases. Following short-term use, the weaning rate was 44 %, and the survival rate was 29 % [4]. Morgan et al. [14] reported that the weaning rate was 40 % with a mean duration of assist of 4.9 days, and that replacement with a long-term assist device or change to heart transplantation was possible in 20 % of patients. A recent report indicates that there is no significant difference in the survival rate between BVS5000 and CentriMag, a device currently in common use [15]. Abiomed. Inc. developed AB5000 as a successor to BVS5000. AB5000 is used widely in the clinical setting in the US after it was approved by the FDA in 2003 [16, 17]. In this system, the same drive console as that of BVS5000 can be used. Because blood drainage is performed from the left atrium or the left ventricular apex, short and long blood drainage tubes of 32Fr, 36Fr, and 42Fr are set up. The blood pump is a polyurethane sac-type pump providing a stroke volume of 95 mL. A polyurethane tricuspid valve is placed in the outflow and inflow orifices of the internal structure. The stroke flow is 3–6 L/min, autoconfigured except for the negative drive pressure. This system can be used as a Biventricular VAD (BiVAD) with a single console. This system allows the use of a portable console, which makes it easy for the patient to move by him or herself [18]. The reported clinical results with this system are favorable. According to Anderson et al., who used AB5000 in 100 patients with cardiogenic shock caused by acute myocardial infarction, the survival rate was higher than 40 % [19]. Some clinical studies have also been carried out in Japan, and early initiation of insurance reimbursement is desired. Thoratec PVAD Thoratec Corporation in the US is selling PVAD as an extracorporeal VAD. PVAD is a pneumatic extracorporeal VAD that allows patients to be discharged to home care using the small-size console, TLC.II [20]. This device can also be used as a BiVAD. PVADs are equipped with a pump that is free from mechanical malfunction and in

heavy use in the clinical setting [21]. There is no report of clinical usage of PVAD in Japan. BerlinHeart Excor Excor, a type of VAD manufactured by BerlinHeart, Inc., is widely use in European and other countries. This system is a pneumatically driven extracorporeal VAD that can provide assist in patients ranging in age from neonates to adult. Six sizes of the blood pump are available, ranging in size from 10 to 80 °C, and cannulas corresponding to the respective sizes are available. (Excor for adult patients has three sizes of blood pumps with two types of valves, mechanical valve and polyurethane valve. Excor pediatric has five sizes of blood pumps with polyurethane valve.) The results of ventricular assist by this device in children are favorable. According to Hetzer et al. [22] the percentage of patients who achieved weaning or transplantation was 69 % in 49 patients who underwent implantation in 94 patients treated with EXCOR. In addition, in a prospective comparison with ECMO in children with severe heart failure revealed that the assist period and the survival rate were both significantly better for EXCOR, regardless of the body surface area [23]. A clinical trial of this system has been completed in Japan, and is currently expected to be approved for production and distribution. Extracorporeal centrifugal pump In recent years, centrifugal pumps have also been used as extracorporeal VADs. In the US, since Centrimag (Thoratec Corporation) was approved by the FDA as an extracorporeal VAD, centrifugal pumps have become mainstream in the treatment of cardiogenic shock using a VAD [24]. This system uses a magnetically levitated centrifugal pump as the blood pump, and allows intermediate-term assist ranging from about 1–3 months [25, 26]. Studies from the aspect of cost have been carried out, and it is apparent that this system is, pricewise, a reasonable VAD for short-term use, triggering its wide use [27]. According to Takayama et al. [28] walk rehabilitation was feasible while the patient was using this system. Therefore, longer term use of this system may be facilitated in the future. In Japan, this system is not clinically available at this moment. Rotaflow is an extracorporeal centrifugal pump marketed by Maquet Corporation that is available in Japan as well as other countries [29, 30]. However, this pump is approved only as short-term use in Japan. This pump uses the monopivot bearing mechanism, and has good abrasion resistance. Therefore, this system is expected to be applicable for intermediate-term use. The system has been reported to serve as a left ventricular assist device (LVAD)

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for 15 weeks [31]. The system has also been reported to be used as a temporary right ventricular assist device (RVAD) in patients with right heart failure who were wearing an implantable LVAD [32, 33], indicating its applicability for a wide spectrum of indications. The MERA monopivot centrifugal pump has recently come to be commonly used in Japan. This pump also approved as short-term use in Japan, and all of the longterm support cases are used as ‘‘off-label’’ device. Inoue et al. [34] used this system as an RVAD simultaneously with an LVAD in patients with right and left heart failure for 5 weeks, and reported that weaning was achieved after restoration of the right cardiac function. According to them, there were no mechanical problems or adverse events such as hemolysis or thromboembolism. Therefore, use of this system may become more common in the future. Although not approved in Japan, the TandemHeart System manufactured by CardiacAssist Inc. is an extracorporeal centrifugal pump system that provides percutaneous left ventricular assist. The blood drainage tube is inserted via the femoral vein to allow its tip to enter the left atrium through the atrial septum. In comparison to percutaneous cardiopulmonary assist devices (blood drainage from the right atrium and blood sending from the femoral artery), this system allows decompression of the left side, helping in restoration of the left cardiac function. Because this device causes a decrease in the pulmonary venous pressure, pulmonary damage is minimal. According to Idelchik et al. [35] a bridge to transplantation or long-term device assist devices was achieved in 14 of 18 patients in whom this system was used as a bridge to long-term assist, and serious complications were fewer than in patients who received percutaneous cardiopulmonary assist. However, Chamogeorgakis et al. [36] observed no difference in the survival rate between 11 patients with TandemHeart and 61 patients with PCPS used for cardiogenic shock, and concluded that the two systems were similar in efficacy.

Differences between extracorporeal and implantable VADs Extracorporeal VADs and implantable VADs provide similar results in terms of systemic circulation assist and cardiac unloading effect when used as LVADs. Cardiac assist is provided by assisted blood drainage from the left ventricle (or left atrium) and blood sending to the aorta. Because the assist effect is proportional to the assisted blood flow, whether the pump is outside or inside the body does not have any influence on the effect. Because the blood pump of an extracorporeal VAD is placed outside the body, there is the risk of accidental removal and bending of the inflow or outflow cannula due

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to the pulling force exerted on the blood pump or for other reasons. Therefore, more careful management is required. Namely, the activities of patients wearing the VADs are limited, basically as the patients have to be admitted to the hospital. Biefer et al. [37] reported that accidental removal of the blood pump occurred in 1 patient among 12 patients wearing Excor, an extracorporeal VAD, who were under home care (a total of 2,890 days). Slaughter et al. [20] performed home care of 13 patients wearing the VADs using a TLC-II portable driver (Thoratec Corporation), and reported no case of accidental removal of the blood pump, despite other events such as gastrointestinal bleeding. There were two reports from Japan of out-of-hospital actions permitted temporarily [38, 39]. In both reports, the temporary out-of-hospital actions were restricted to patients who had therapeutically necessary reasons and who strongly requested permission after being given a full explanation. In extracorporeal VADs, the heart and large vessels need to be connected via thick inflow and outflow cannulae, which is associated with the risk of infection at the site of tube insertion in the skin. Kawata et al. [40] reported that infection occurring at the sites extended along the inflow and outflow cannulae, thereby resulting in mediastinitis; thus, they sent an alert on this issue. Infection at the site of insertion of the drive line or infection extending to the pump pocket also occurred in cases of implantable VADs [41]. However, drive lines, which are restricted to electrically sending signals or energy, are likely to be thinner and more flexible than the inflow or outflow cannula, and furthermore, they are not associated with transmission of beats of the blood pump, allowing better rest to the injured part. Based on the above, infection is considered less likely to occur with implantable VADs. Conversely, in comparison with patients with extracorporeal VADs in whom it is relatively easy to achieve rest in the hospital, there is a view that it is more difficult to keep the wound site stable in patients with implantable VADs in whom the levels of activity are higher. A report from J-MACS, the VAD registry of Japan, which was based on a comparison of the data between 133 patients with implantable VADs and 40 patients with extracorporeal VADs, there was no significant difference in the incidence rate of major infections between the two groups [1]. Although the number of subjects included in this analysis was low, the incidence rate of infection in the patients with an implantable VAD was almost the same as that in the 593 patients registered with INTERMACS [42]. The incidence rate of infection obtained in these groups was also similar to that in patients with extracorporeal VADs who included a larger proportion of cardiogenic shock patients and had obviously worse preoperative profiles. This finding is extremely meaningful even though the sample size was limited.

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The major advantage of extracorporeal VADs is the lower cost of production. Because no parts for implantation are required, and because the durability assurance can be shorter, the manufacturing cost can be greatly reduced. When the reimbursement prices for devices that are frequently used in Japan are compared, extracorporeal VADs are priced at 3,130,000 yen per unit, whereas the unit price of an implantable VAD is about sixfold higher, i.e., 18,100,000 yen. As far as short-term assist is concerned, extracorporeal VADs are overwhelmingly advantageous as compared to implantable VADs, especially from the viewpoint of the cost-effectiveness. However, some patients require ultra-long-term assist [9, 43], and in such patients, implantable VADs are often more advantageous, considering the cost required for pump replacement. Another advantage of extracorporeal VADs is the absence of the need to implant the blood pump in the body. No preparation of a pump pocket is required, making the assist procedure less invasive in nature. In addition, extracorporeal VADs can also be used in children or undersized patients [22, 23, 44]. However, recent technologies make implantable devices smaller and smaller, and lower limitation of implantable body size also getting smaller. So, this merit has been decreasing in significance recently with the increasingly frequent use of Jarvik2000 and HVADs, for which no preparation of a pump pocket is required. But, still extracorporeal VADs have advantage for the implantation to small children. Thus, extracorporeal VADs have various advantages and disadvantages in comparison to implantable VADs, but there are no substantial differences between these two types of VADs from the viewpoint of vital prognosis. According to a report of J-MACS, the survival rates of 133 patients with implantable VADs and 50 with extracorporeal VADs were 94 and 89 %, respectively, at 180 days, and 90 and 84 %, respectively, at 360 days, the differences between the two groups not being statistically significant [1].

chronic heart failure to obtain a decrease in the volume overload and pressure overload for recovery of the cardiac function; once the cardiac function recovers, weaning from the VAD is attempted [45]. Ever since the report by Mu¨ller et al. [46] about patients with VADs in whom the cardiac function recovered and weaning from VADs could be achieved, a number of BTR cases have been reported [47]. Nishimura et al. [48, 49] used drug therapy with carvedilol, etc., and cardiac resynchronization therapy in patients with VADs, and reported successful weaning from the VADs after recovery of the cardiac function. Adjunctive treatment for BTR is an important issue for future studies. However, it is difficult to determine preoperatively whether or not the cardiac function would be restored. Matsumiya et al. examined 11 patients who underwent long-term LVAD therapy and found that recovery of cardiac function and weaning from the VAD were achieved only in patients with a low degree of myocardial fibrosis preoperatively. Based on this finding, they concluded that preoperative determination of the degree of myocardial fibrosis might serve as an index for consideration of treatment aimed at BTR [50]. Imamura et al. [51] studied 60 patients with dilated cardiomyopathy with LVADs, and pointed out that adequate drug therapy after the placement of an LVAD might lead to recovery of cardiac function in patients given adequate bblocker therapy. Thus, the use of extracorporeal VADs seems to be indicated for patients who are preoperatively judged as showing a high likelihood of successful weaning from a VAD after short-term assist. However, for patients who show no recovery of cardiac function after assist with an extracorporeal VAD and various additional treatments for heart failure, prolonged assist would be necessary, and the extracorporeal VAD would need to be replaced with an implantable VAD that would allow a high QOL during VAD use and provision of home care [52] (Bridge to Bridge: BTB).

Indications for extracorporeal VADs

Some patients with severe acute heart failure or cardiogenic shock may develop kidney failure, liver failure, pulmonary edema, disseminated intravascular coagulation, etc., thereby leading to the development of multi-organ failure. Although the condition may vary according to the grade of organ damage, it is difficult to predict whether or not the use of a VAD might improve the circulation sufficiently to restore the organ functions. Prolonged consciousness disorder due to cerebral ischemia or cerebral infarction associated with shock may also occur, interfering with the evaluation of the reversibility of the condition within a short period of time. In such cases, the use of implantable VADs targeted at long-term assist is unlikely

Cases where extracorporeal VADs are chosen for shortterm assist Assist aimed at recovery of spontaneous cardiac function (Bridge to Recovery: BTR) Extracorporeal VADs are used as temporary assist until recovery of cardiac function in patients with cardiogenic shock due to fulminant myocarditis or acute myocardial infarction. In a broad sense, VADs are used for patients with transient acute heart failure or acute aggravation of

Assist for patients with multi-organ failure or cerebral complications (Bridge to Decision: BTD)

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to yield favorable results [53]. An extracorporeal VAD should be used first for the purpose of saving the patient’s life, and then monitoring should be carried out for recovery of organ functions after improving organ perfusion. In addition, reversibility of cerebral function should be evaluated to determine whether or not the treatment should be continued [54]. After these procedures, weaning from the VAD should be attempted following recovery of the cardiac function. If there are indications for implantable VAD therapy, the extracorporeal VAD can be replaced with an implantable VAD, targeted at BTB [26, 52].

failure, and reported that there was no significant difference in the in-hospital mortality rate between these patients and those without right heart failure. Weaning should be attempted after recovery of the right heart function. If the right heart function does not recover, change to another system that allows longer term assist is required. Considering the study of implantable right and left VADs reported by Saito et al. [59] the treatment strategies would vary according to the future development of devices and the status of insurance reimbursement. Assist in children and undersized patients

Assist with an extracorporeal VAD in cases where use of an implantable VAD is not possible Biventricular VAD: BiVAD At present, there are no approved RVADs available for long-term use. Therefore, extracorporeal VADs need to be used for left ventricular failure patients with concomitant right heart failure requiring mechanical assist. In patients with acute heart failure, symptoms of left heart failure may predominate, and the presence of biventricular failure may be overlooked. In addition, some patients in poor general condition may require high cardiac outputs during the convalescent phase. In such patients, right heart failure may become obvious only after surgery, when the right cardiac function cannot keep pace with the output of the left heart assisted by an LVAD. Although it is difficult to predict this condition, Shiga et al. [55] reported that the requirement for right ventricular assist can be predicted by risk scores calculated based on the preoperative central venous pressure/pulmonary capillary wedge pressure ratio, body surface area, left ventricular diastolic diameter, B-type natriuretic peptide, etc. Conventional methods of right heart assist include high-dose catecholamine therapy or combined with percutaneous cardiopulmonary assist, none of these methods has yielded adequate LVAD flow volumes or good prognoses. In contrast, combined use of temporary extracorporeal right ventricular assist using a centrifugal pump has been reported to provide adequate assist flow volumes in the acute phase and thereafter, being effective for maintenance of the general condition [56]. Loforte et al. compared 46 patients in whom CentriMag was used as a temporary RVAD and 31 patients in whom Thoratec P-VAD, etc., was used as a long-term RVAD, and reported the absence of any significant difference in the survival rate between the two groups; they suggested that temporary RVADs were advantageous in that they allowed management of the LVAD as a single unit in the chronic phase [57]. In a study of 139 patients wearing HeartMateII, Lazer et al. [58] used temporary right ventricular assist using an extracorporeal VAD in 34 patients with right heart

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At present, implantable VADs covered by the health insurance in Japan are indicated only for patients with a body surface area of C1.2 m2: in smaller patients, extracorporeal VADs need to be used. In particular, in patients with a small anteroposterior diameter of the thorax, flexion of the arterial blood vessels for blood transmission or compression of other organs by the blood pump may occur, necessitating caution. Long-term use of the NIPRO-VAD, which is an extracorporeal VAD, in children weighing 15 kg has been reported. This system can be used even in patients with a thin thorax [44]. Komagamine et al. [60] reported that the goal of bridge to heart transplantation was achieved in 4 of 5 children. On the other hand, development of implantable VADs is progressing, and it is likely that Infant Jarvik and other devices will become available for use in children in the future. Use of extracorporeal VADs in cases where implantable VADs are off-label under the current system of health care in Japan Assist in cases where registration for heart transplantation is under consideration (Bridge to Candidacy: BTC) In cases requiring LVAD implantation, it is possible that the applicability of transplantation cannot be determined immediately. In patients with severe heart failure in whom the hemodynamics is critically or near critically deteriorated, failure of other organs, including kidney or liver failure is often a grave concern [61, 62]. While it is difficult to know in advance whether such organ failure can be reversed by the use of an LVAD [63], in many patients, organ damage improves after implantation of an LVAD [64]. Thus, implantation of LVAD is carried out as BTC while judgment about the applicability of transplantation needs to be suspended for the time being and can be carried out only when the patient becomes eligible for transplantation in the future. In the US, implantation as BTC accounts for more than 40 % of cases of LVAD implantation [65]. Thus, although use of LVAD as BTC is

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standard practice globally, in Japan, use of implantable VADs as BTC is currently difficult, because the indications of implantable VADs are restricted to patients who are waiting for heart transplantation. In Japan, registration on the waiting list for heart transplantation is necessary prior to implantation of an LVAD. This registration procedure includes various tests and documentary examinations that require long hours of preparation. In some patients in whom the circulatory maintenance fails due to acute aggravations during this preparation process, extracorporeal VADs are used, and change to an implantable VAD is attempted after the indications are fulfilled. Assist in patients who are not suitable candidates for heart transplantation (Destination Therapy: DT) Patients in whom extracorporeal VADs are used for the purpose of restoring spontaneous cardiac function are not necessarily suitable candidates for heart transplantation, e.g., elderly patients aged 65 years or older and patients with kidney failure. The role of extracorporeal VADs in such patients is significant when spontaneous cardiac function can be restored and good long-term prognosis can be achieved. However, when spontaneous cardiac function cannot be restored and patients cannot be weaned from VAD, it is necessary to continue VAD therapy for an indefinite period. In many patients in Europe and North America, VAD therapy is not aimed at the ultimate goal of heart transplantation and is used as Destination Therapy (DT). According to Kirklin et al. among 6,633 patients who underwent VAD implantation until 2012 who were registered with INTERMACS, the treatment strategy at the time of implantation of the device was DT in 1,834 cases (27.6 %). In addition, among 896 patients who underwent implantation during the 6-month period between January and June 2012, the corresponding number of patients was 395 (44.0 %), indicating an increase of the percentage [66]. When implantable VADs are used, DT under home care provides a high QOL comparable to transplantation therapy [67]. However, in the case of extracorporeal VADs, hospital care is the only option in Japan, and the patients need continued hospitalization. In Japan, initiation of DT therapy is the most important goal of using implantable VADs in patients who are not suitable candidates for heart transplantation. The use of extracorporeal VADs in out-ofhospital environments is also an important treatment option for such patients in the future.

Conclusion It is expected that implantable VADs will soon begin to be covered by the health insurance, and that the lives of a

large number of patients will be saved. There is a view that extracorporeal VADs are a thing of the past, and that implantable VADs are here to stay. However, with the extremely wide spectrum of presentation of patients with severe heart failure, the role of extracorporeal VADs still remains significant. The use of appropriate devices at the appropriate times is the key to achievement of the best outcomes. Further refinement of extracorporeal VADs and improvement of the use environments, including out-ofhospital use, are desirable in the future. Conflict of interest The authors declare that they have no conflicts of interest to declare.

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