The Asia region consists of 48 countries with a population of 3.8 billion and extends from Saudi Arabia and Turkey in the west to the most eastern part of Russia. The Asia-Pacific region includes East Asia, South Asia, Southeast Asia, and Oceania. It extends from Pakistan in the west to Japan, Australia, and New Zealand in the east.1 Accurate data from Asia on heart transplantation is lacking as not all centers report their data to the International Society for Heart and Lung Transplantation (ISHLT) registry. According to the Global Observatory on Donation and Transplantation, <0.4 heart transplants per million population are performed yearly compared with more than 7.5 per million in the USA.2 Availability of durable continuous-flow left ventricular assist device (LVAD) technology has made mechanical circulatory support (MCS) an attractive alternative for the treatment of advanced heart failure (HF), permitting bridge to transplant therapy or as long-term therapy.3 MCS is emerging as a viable alternative to transplantation in Asia, but limitations in embracing this concept exist, including discrepant practices in reimbursement of costly MCS therapy across the region.
The Asia-Pacific community has conducted biannual educational gatherings in Singapore, supported by ISHLT, since 2015 to advance understanding in this modality of therapy. This editorial is based on the third biannual meeting endorsed by ISHLT and held in Singapore on November 1, 2019 to November 2, 2019 and includes a distillation of the current state of MCS, their principal outcomes, and region-specific challenges by selected countries of origin. This is not meant to be an exhaustive review of the status but to provide a lens into the growing MCS activity in this unique region. The Japanese registry for mechanical cardiac support data is not included in this report as this data is available in the report by Nakatani et al.4
MCS in Australia
Current status. MCS support started soon after heart transplantation in Australia in 1994. Since then, the program is funded with a specific indication of bridge to transplantation. With ongoing donor shortages, MCS is accepted as integral to a successful heart transplant program, funded by individual state governments. At present, approximately 30% to 40% of transplants are supported with mechanical devices.
Destination therapy with a durable mechanical device is approved by the Therapeutic Goods Administration but is not funded; hence, this occurs infrequently. As the number of transplants has increased over the last 5 years with increased donor rates and the introduction of donation after circulatory death in one center (St Vincent's, Sydney, New South Wales, Australia), the number of LVAD implants has not increased over the last 3 to 4 years.5
Budgetary restraint has limited the introduction of newer short-term circulatory devices, with most centers relying on extracorporeal membrane oxygenation (ECMO) for systemic circulatory support in cardiogenic shock. Short-term extracorporeal support may also be used to bridge to transplantation. As with many jurisdictions, patient referrals remain late, with marked deconditioning in decompensated patients.
Unique challenges. Specific challenges apparent across Australasia are the small number of MCS/transplant units compared with the geographic distances. Many patients live more than 500 miles from an implanting center. Patients are usually returned to the implanting center for major medical events, despite the distance. Adelaide, in South Australia, is the only non-implanting city with dedicated MCS cardiovascular and nurse coordinator services, supported by Melbourne and Sydney. Patient isolation is managed through education and maintenance of close contact with the implanting team.
Most units submitted data to the ISHLT Mechanically Assisted Circulatory Support centralized registry until the current recruitment pause.6 After LVAD implantation, survival rates remain strong, with a 1-year survival rate of approximately 80%. Current efforts to increase the implantation rate include dedicated funding applications for alternate indications such as destination therapy and information and education events. Efforts to increase earlier referral are ongoing, and the mnemonic I-NEED-HELP was developed to highlight patients at the need for advanced HF team review.7
MCS in New Zealand
Current status. The Green Lane cardiothoracic surgical unit at Auckland City Hospital is the referral center for cardiothoracic transplants, ECMO, and mechanical support and is a public funded health care system in New Zealand. The program is funded to implant up to 4 LVADs per year, but additional devices can be selectively funded. There is no funding for destination therapy.
The LVAD program started with the Ventrassist Trial in 2005, initially mentored by the Alfred Group from Melbourne, Australia, with an ongoing collaboration. Between 2005 and 2008, 6 LVADs were performed. The HeartWare HVAD (Medtronic, Minneapolis, MN) became the preferred device in 2010. The Excor Berlin Heart (n = 3) has been used as a bridge to transplant but is excluded from this analysis of only dischargeable implanted LVADs. During the coronavirus disease 2019 pandemic, 4 LVADs, including a biventricular pump system, were implanted.
Unique challenges. Most patients are housed within the critical care units in preparation for the implant and after surgery, which creates a shortage of bed availability. The appropriate referral is a challenge to the program, contributed to by remoteness, education, and social structure of our society in New Zealand. For these reasons, the program volumes are small with scattered activity, and most patients are implanted only when they are in the highest severity of illness. A task force to mitigate some of the challenges has been established.
MCS in China
Current status. A number of companies in China are involved in the development and commercialization of implantable ventricular assist devices (VADs). A Chongqing-based joint venture with Sun Medical Co., Japan, has received product registration from the National Medical Products Administration, China, for market entry of the EvaHeart I since September of 2019. The CH-VAD (CH Biomedical Inc, Suzhou, China), a fully magnetically suspended LVAD system, has been introduced with an in vitro study that shows shear-induced hemolysis and platelet activation acceptable relative to 2 other LVADs that are not fully magnetically levitated.8 The first implantation of CH-VAD in a man was performed on June 26, 2017 at Fu Wai Hospital, Beijing, China, and the recipient has crossed 3 years’ survival. A clinical trial in China commenced in March 2019, and 25 implantations have been performed.
Unique challenges. A major challenge in commercialization and application of LVADs in China lies in the lack of infrastructure and requires painstaking collaborative efforts from multiple stakeholders to build such a program. Reimbursement is yet another challenge and unavailable currently. Another challenge encountered in conducting the clinical trial is that the sponsor must bear the overall expenses associated with the device, medical care incurred in the trial, and the associated lifetime thereafter.
MCS in Hong Kong
Current status. The first implantable LVAD surgery in Hong Kong was performed in 2010. Since then, 95 patients have received LVAD as a bridge to heart transplant or as destination therapy. Lately, the number of LVAD implantations has superseded the annual number of heart transplants. This has resulted in a growing list of patients awaiting heart transplantation, with 50% of heart transplant recipients supported by a LVAD. In Hong Kong, the heart transplant program and the implantable VAD program are managed by cardiothoracic surgeons at Queen Mary Hospital and HF cardiologists at Grantham Hospital. The survival rates after implantable LVAD in Hong Kong at 1 year, 2 years, and 5 years are 84%, 81%, and 69%, respectively. Stroke and right HF remain the 2 most commonly occurring complications after LVAD. Almost 10% of patients with LVAD require temporary right VAD support peri-operatively.
Unique challenges. Only LVAD bridge to transplants are approved for reimbursement by the Hong Kong healthcare system. For urgent cases, approval for the bridge to transplant can usually be obtained within a day. However, there is still no reimbursement scheme available in Hong Kong for LVAD in end-stage, non-transplantable patients.
MCS in Taiwan, Vietnam, Philippines, and Brunei
In Taiwan, although heart transplantation is relatively mature, most such recipients were bridged by ECMO instead of LVADs because reimbursement for LVAD was not available until the end of 2019. In Vietnam, the first LVAD surgery was performed in 2013. Owing to lack of reimbursement, the number of implants remains small. The Philippines started its LVAD program with HeartMate II in 2017 with 3 LVADs performed. Because this procedure is cost prohibitive, referrals are not made in a timely manner and most patients present with advanced HF with end organ dysfunction. Brunei is a tiny Southeast Asian nation on the island of Borneo. Brunei does not have a transplant program. Six LVADs were implanted between 2014 and 2016 when reimbursement was available; however, the program is inactive at present.
MCS in India
Current status. The modern era of continuous-flow VADS (LVADS) started in 2012 when the first HeartMate II (Abbott, Chicago, IL) was implanted in a 58-year-old man on inotropic therapy with renal failure. He remained well for 6 years before developing a driveline infection and moderate aortic incompetence and died of a stroke. The first HeartWare HVAD (Medtronic) surgery was performed in India in February 2013. This coincided with the start of a modern transplant program in the state of Tamil Nadu and later in other states. The average wait time for a transplant is 3 months and, because of the high cost of durable LVADs, short-term mechanical support is the primary bridge strategy. There is no national registry for LVADs. In local series, the early outcomes of LVAD therapy are inferior to transplants over the first 1 year at 72%, and the 5-year survival has been significantly less than that for a transplant in our series, at around 50%. The involvement of the cardiologists in transplants and LVADs has been minimal, and referrals are often delayed until the patient is very sick and in a very poor condition for good outcomes.
Unique challenges. Driveline infections are common with longer survival, and the hot and humid weather for most of the year adds to the challenge of maintaining a clean exit site. Strokes are an important cause of morbidity and mortality, with an incidence of 16% within 2 years of implant. Managing strokes on LVADs is difficult as interventional neurologic facilities are available only in major metropolitan areas. Pump thrombosis is treated only by thrombolysis as pump exchange is not a viable option financially. Hypertension is common and controlling it is a challenge. Patients return to the community in a vast country with a lack of cardiologists trained in LVADs. Family members are trained to measure blood pressure with a Doppler probe, and this is often unreliable. Patients manage their international normalized ratio with a point of care device, but the results are often different from those obtained from a regular laboratory. Efforts are underway to get insurance coverage for LVAD therapy.
MCS in South Korea
Current status. Since the introduction of the commercially available LVAD HeartMate II (Abbott) in 2012, about 30 LVAD (HeartMate II and HeartWare (Medtronic, Framingham, MA) operations have been performed in South Korea until December 2018. From October 2018, reimbursement under the national health insurance was introduced to cover LVAD operations. Since then, more than 100 LVAD operations have been performed. The Korean national insurance system requires institutional approval, which needs heart transplantation experience of more than 3 over the last 24 months. Either a bridge to transplant or destination therapy indication are reimbursable. The early mortality is about 5%, and the longest survival is 8 years in a patient with a HeartMate II. Short-term MCS is widely used as a bridge to transplantation, and most patients wait only a few weeks for heart transplantation. Although centers and patients have previously avoided the use of implantable LVADs as a bridge to transplantation because of the high cost and relatively short waiting times (unlike Japan or North America), there is greater acceptance recently because of a worsening donor availability and better insurance coverage.
Unique challenges. Awareness of HF is still low among patients and physicians, leading to long referral times. HeartMate 3, Impella (Abiomed Inc., Danvers, MA), and Centrimag are not yet approved by the Korean Food and Drug Administration and remain under review.
MCS in Malaysia
Current status. The National Heart Institute is the only center that provides MCS and thoracic transplant services in Malaysia. The program was established in 2005 with the funding awarded by the Ministry of Health. Early on, short-term extracorporeal devices were used, but in 2010, the durable continuous-flow LVADs HeartMate II and HeartWare HVAD were implanted. The HeartMate 3 was introduced in 2016 and, until now, a total of 30 LVADs have been implanted. The longest patient on LVAD support is 8 years and 10 months.
Unique challenges. The main challenges are the lack of reimbursement and organ donation. Currently, our patients are self-funding or supported by donations, limiting the number of implants. A fresh proposal has been submitted to the government for funding.
MCS in Singapore
Current status. The Singapore MCS program was initiated in 2001 and durable implantable continuous-flow LVADs were introduced in 2009. Through September 2019, 104 LVADs have been implanted (60 HeartMate II, 24 HeartWare, and 20 HeartMate 3). Bridge to transplant indication is most common in 75 LVADs, and 29 LVADs are long-term therapy. The mean duration of support is 2.9 years, with the longest support of 10.4 years and a 5-year actuarial survival of 83.3%.
Unique challenges. All transplanted patients recently have been bridged using LVADs, which results in longer surgical times, peri-operative bleeding, donor graft dysfunction, and vasoplegia. As our patents remain on long-term LVAD support, driveline infection remains a challenging problem. Reimbursement of up to 80% of costs is provided by government funding.
MCS in Saudi Arabia
Current status. MCS was initiated at King Faisal Specialist Hospital & Research Centre, Saudi Arabia, 20 years ago. During the past few years, 2 other centers have joined to implant durable MCS devices as destination therapy. That led to a total of 45 durable LVADs per year. Besides, King Faisal Specialist Hospital & Research Centre has remained the highest volume center for MCS with an average of 70 ECMO, 30 non-durable VADs, and 22 durable VADs per year. In addition, it remains the main heart transplant center in the Middle East, reaching 35 transplants per year with 89% 1-year survival. Two distinct outcome eras have existed. The first era, 2000 to 2012, was associated with dismal LVAD survival of 23% attributed to a combination of device limitations, patient compliance, patient acceptance to therapy, and lack of a structured heart team. In the second era of 2013 to 2019, with deployment of a multidisciplinary heart team, survival improved to 70% at 1-year. The HeartMate 3 LVAD is associated with an improved survival rate at 1 year of 75% compared with 67% using other LVAD platforms, and morbidity similar to that reported in the clinical trials.9
Unique challenges. The major barrier is the lack of awareness of the benefits of LVADs, fear of device management at home, and sub-optimal compliance in concert with poor lifestyle related habits such as smoking.
In summary, the Asia-Pacific region is represented by MCS programs in variable stages of maturity with the principle challenges that tie each other together through the vine of a need for awareness of advanced HF therapy. Consistent themes appear to be late referrals, cost and reimbursement challenges, and unavailability of structured multidisciplinary team support. Advocacy and educational efforts that seek to focus and overcome these key deficiencies will be necessary to advance the availability and outcomes of MCS in the Asia-Pacific region.
Disclosure statement
Dr. Sivathasan reports personal fees and non-financial support from Abbot South East Asia and non-financial support from Transmedic Singapore Private Limited. Dr. Hayward reports grants, personal fees, and non-financial support from Medtronic, personal fees from Abbott, and personal fees from Novartis. Dr. Jansz reports grants and personal fees from Medtronic. Dr. Chen is an employee of CH Biomedical, Inc. Dr. Mehra reports receiving travel support and consulting fees, paid to Brigham and Women's Hospital, from Abbott; fees for serving on a steering committee from Medtronic and Janssen (Johnson & Johnson); fees for serving on a data and safety monitoring board from Mesoblast; consulting fees from Baim Institute of Clinical Research, Portola, Bayer, and Triple Gene; and fees for serving as a scientific board member from Leviticus, NuPulseCV, and FineHeart. Dr. Mehra is also editor of the Journal of Heart and Lung Transplantation, but this editorial does not represent the official stance of the Journal or the society that it represents. The other authors have no conflicts of interest to disclose.
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