*9.2.1 Enforcement case*

The first heart transplantation based on the Organ Transplant Law was performed in February 1999 [3], and 3 cases were performed in the same year [4]. Since then, the number of heart transplants has increased from around 5 to around 10 per year,

*Heart Transplantation and Mechanical Circulatory Support in Japan – Past, Current and Future… DOI: http://dx.doi.org/10.5772/intechopen.113730*

#### **Figure 3.**

*Pediatric heart transplantation performed in Japan by year (up to December 31, 2021) (by recipient age).*

and the amended Organ Transplant Act was enacted in July 2010, resulting in a marked increase in organ donations from brain-deceased patients [9], and 84 heart transplants in 2019. Of these, 17 children were performed, but the number decreased to 59 due to the impact of the new coronavirus infection (**Figure 2**). By December 31, 2021, 625 heart transplants had been performed, including 446 males (71%) and 179 females (29%), with ages ranging from 1 to 70 years (average 39.1). there were. <10 years: 26 cases, 10-19 years: 48 cases, 20-29 years: 88 cases, 30-39 years: 118 cases, 40-49 years: 160 cases, 50-59 years: 133 cases, 60-69 years Age: 51 cases, age 70 or older: 1 case. Currently, patients under 65 years of age are registered for heart transplantation, but due to the long waiting period, there were 4 patients aged 65 years or older (the oldest was 70 years old) who were transplanted.

#### *9.2.2 Medical condition during waiting heart transplantation*

Most of the heart transplant cases in Japan are BTT cases, and initially, the Nipro VAD was mainly used. After introducing implantable non-pulsatile VAD in 2011, non-pulsatile flow implantable VADs that can be treated at home, such as HeartMate 3, HVAD, EVAHEART, and Jarvik 2000, are mainly used. Therefore, of the 625 cases at the time of heart transplantation, only 3 were children with status 2, 35 were on inotropic agents, and 587 (94%) were BTT cases (including 46 children). BTT cases now account for 71% (444 cases). On the other hand, the number of pediatric cases transplanted from EXCOR Pediatric gradually increased to 6 cases in 2019 and 3 cases in 2021. The survival rate after installation of a non-pulsatile flow implantable VAD is high (3-year survival rate of 87%), and the number of waiting patients is increasing year by year. Of the 56 patients who underwent heart transplantation in 2015, 18 had been supported with a VAD for 4 to <5 years, 21 for 5 to <6 years, and 8 for 6 years or longer prior to heart transplantation (**Figure 4**).

## *9.2.3 Cardioplegia and transplant surgery*

Modified Collins solution, St. Thomas solution, Bredshneider solution, UW solution, and Celsior solution have been used as cardioplegic solutions, but since 2006, Celsior solution has been used at all facilities other than Kyushu University. Lower-Shamway method, bicaval method, modified-bicaval method, etc. are used as surgical methods. The modified-bicaval method, which was developed in Japan [12], has been used, including in pediatric cases, except where the method is being used.

#### **Figure 4.**

*Heart transplantation in patients supported with left ventricular assist device (LVAD) performed in Japan by year (up to December 31, 2021) (by support year of LVAD).*

### *9.2.4 Immunosuppressive regimen*

For induction therapy (including children), anti-CD3 antibody (monoclonal anti-CD3 antibody: OKT3), anti-lymphocyte globulin (ALG), and basiliximab have been used. Although 230 of 625 cases (37%) have been treated with basiliximab, insurance coverage as induction therapy for renal dysfunction cases and pediatric cases described later is awaited.

Initial immunosuppressive therapy was a triple therapy using a calcineurin inhibitor (CNI), cyclosporin (CyA) or tacrolimus (Tac), an antimetabolite [azathioprine or mycophenolate mofetil (MMF)], and a steroid in all patients. Currently, triple therapy with Tac, MMF, and steroids is the mainstream [507 out of 625 patients (81%)]. Everolimus has not been used from the early stage and has been used instead

#### **Figure 5.**

*Cumulative survival rate of heart transplant recipients (up to December 31, 2021). ISHLT, International Society for Heart and Lung Transplantation.*

*DOI: http://dx.doi.org/10.5772/intechopen.113730 Heart Transplantation and Mechanical Circulatory Support in Japan – Past, Current and Future…*

of MMF for post-transplantation coronary artery lesions, renal dysfunction, malignant tumors, and MMF-intolerant patients.
