Sarcopenia in Patients with End-Stage Cardiac Failure Requiring Ventricular Assist Device or Heart Transplantation

Sarcopenia has been defined as the age-related reduced skeletal muscle mass, strength, and physical capacity and is frequently associated with serious complications in patients with heart failure (HF). However, when HF progressed to end-stage HF requiring advanced therapies, such as heart transplantation (HTx) and implantation of left ventricular assist device (LVAD), an even higher prevalence of sarcopenia has been reported in younger patients with end-stage HF than elderly patients with less advanced HF. Many literatures have reported that sarcopenia is greatly associated with high rates of morbidity and mortality after HTx and LVAD implantation. Therefore, therapeutic interventions to prevent and reverse sarcopenia, such as cardiac rehabilitation and nutrition supplementation, are important in patients with end-stage HF prior to HTx and LVAD implantation. Although moderate or severe sarcopenia is a contraindication for HTx, the patients who can recover from sarcopenia after LVAD implantation would be considered eligible for HTx. Then, therapeutic options to reverse sarcopenia in patients supported with LVAD are also important to improve patient prognosis after LVAD implantation. In this review, the impacts of sarcopenia on prognosis after LVAD implantation and HTx and vice versa were summarized and therapeutic interventions to reverse sarcopenia before and after LVAD implantation are discussed

Donor Assessment and Management for Heart Transplantation

For many years, heart transplantation has been an established procedure for patients with end-stage heart failure using the so-called “Standard Criteria” for an optimal heart donor. However, annually listed patients for heart transplantation greatly increased worldwide, and the use of extended criteria donor hearts has been utilized as many as possible in many countries. In this chapter, firstly, pathophysiology of brain death is explained. Secondly, donor assessment and issues of extended criteria donors are introduced. Then, donor management to maximize the heart graft availability, and the Japanese donor assessment and evaluation system and its outcome are reviewed

Novel Diagnostic and Therapeutic Approach to Antibody-Mediated Rejections in Heart Transplantation

Despite the improvement of immunosuppressive therapy in heart transplantation (HTx), antibody-mediated rejection (AMR) is still a great obstacle to prolong cardiac graft survival. Anti-donor-specific antibodies (DSAs), especially anti-donor human leukocyte antigen (HLA) antibody, lead to heart graft failure resulting in hemodynamic consequence and often in the recipient death. To prevent hyperacute rejection, prospective complement-dependent cytotoxicity test has been performed in every cardiac donor in Japan. But in other solid organ transplantations, flow cytometry crossmatch has been recently recommended to crossmatch to select the recipient in Japan as well as the world. However, flow cytometry is too sensitive to select the recipient, because not all DSAs determined by flow cytometry are cytotoxic to the cardiac graft. On the first complement classical pathway, alloantibodies bind to HLA antigens on cells of the graft and then recruit C1q, which is essential to make membrane attack complex and kill the cell. We review a role of the novel monitoring method of complement pathway regarding C1q in occurrence of AMR and its diagnostic and therapeutic significance in managing AMR in HTx

Challenge of Xenotransplantation in Pediatric Heart Transplantation

Although surgical techniques have progressively improved in the field of congenital heart disease (CHD), even such as hypoplastic left heart syndrome, pediatric heart transplantation is the most effective surgical option for complex CHD and cardiomyopathy with severe heart failure. However, even now, donor heart availability has been poor in children. Although technologies for ventricular assist device (VAD) have been progressing even in children, VAD cannot grow as the pediatric recipient grows. Therefore, pediatric cardiac xenotransplantation has a great possibility to save and grow children with end-stage heart failure. In this chapter, I would like to introduce the first pediatric baboon-to-human heart transplantation and its basic animal experiments done by Bailey’s group and the following attempts for pediatric cardiac orthotopic xenotransplantation (rhesus monkey-to-baboon and pig-to-primate combination)

Huge right ventricle–right coronary artery fistula compromising right ventricular function in a patient with pulmonary atresia and intact ventricular septum: A case report

AbstractJ Thorac Cardiovasc Surg 2001;122:1030-

Genetic variants in antioxidant pathway: Risk factors for hepatotoxicity in tuberculosis patients

Tuberculosis (TB) treatment can cause serious sequelae including adverse effects such as anti-TB drug-induced hepatotoxicity (ATDH). We performed a candidate gene-based association study between single nucleotide polymorphisms (SNPs) in 10 genes in the antioxidant pathway and ATDH susceptibility. The subjects comprised 100 Japanese patients with pulmonary TB who received a treatment regimen including isoniazid and rifampicin. Out of them, 18 patients had ATDH. Thirty-four tag SNPs in 10 genes were analyzed by PCR-restriction fragment length polymorphism or PCR-direct DNA sequencing. The frequencies of alleles and genotypes between patients with and without ATDH were compared in three different genetic models. Statistical analyses revealed that a C/C genotype at rs11080344 in NOS2A, a C/C genotype at rs2070401 in BACH1, and a G/A or A/A genotype at rs4720833 in MAFK independently conferred ATDH susceptibility. Remarkably, the association of the latter two tag SNPs with ATDH susceptibility was highly statistically significant (P = 0.0006) with an odds ratio of 9.730. This study is the first report to demonstrate that NOS2A, BACH1, and MAFK appear to be genetic determinants of ATDH in Japanese patients with TB. Furthermore, a combination of BACH1 and MAFK polymorphisms may be useful as new biomarkers to identify high-risk Japanese TB patients for ATDH

Heart Transplantation and Mechanical Circulatory Support in Japan; Past, Current and Future Aspects

The first heart transplantation (HTx) done by Dr. Wada in 1968 misled the general public not to allow to do brain-dead organ transplantation in Japan. It took almost 30 years to issue the Organ Transplantation Act to allow us to perform HTx in Japan. However, this Act required living written consent for brain death and organ donation. Therefore, children younger than 15 years could not donate their organs under brain-dead condition. After 6 years of struggle to revise this Act, the revised Act was issued in 2010 and brain-dead organ donation as well as HTx increased then. But the number in a year has been still extremely less than other developed countries in Japan. Then, we established a special donor management and assessment system to maximize donor organ availability as well as to improve post-transplant outcomes. During these periods, many types of mechanical circulatory supporting (MCS) have been introduced in Japan. Moreover, there have been many developments in immunosuppressive regimens and monitoring to improve outcomes after LVAD implantation and HTx. The chapter will summarize the past, current status, and future aspects of HTx as well as MCS in Japan

Marginal DonorsCurrent and Future Status /

IX, 282 p. 58 illus., 22 illus. in color.online r