How should cardiac xenotransplantation be initiated in Japan?

The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.

Successful surgical resection and reconstruction for a huge primary cardiac lymphoma filling the right heart.

Primary cardiac lymphoma (PCL) is rare, with a frequency of 1.0%-1.6% among cardiac malignant tumors. Chemotherapy is often selected as a first-line treatment for PCL. However, when the tumor causes heart failure or life-threatening hemodynamic collapse, antecedent urgent surgery is required. We herein report a successful case of complete tumor resection and reconstruction of the right atrium and right ventricle using a bovine pericardial patch combined with tricuspid valve replacement in a patient with a huge PCL filling the right heart that manifested as tricuspid valve stenosis and subsequent heart failure.

Diagnosis of Type IV Endoleak After Endovascular Aneurysm Repair Using Visualization With Novel Software.

A Type IV endoleak is a very rare complication following endovascular aneurysm repair (EVAR) and differential diagnosis can be difficult. Reported here is a case that showed the development of a Type IV endoleak after an EVAR procedure, for which a novel software was useful to differentiate that from Type I based on visual confirmation. The 89-year-old man was diagnosed with a large abdominal aortic aneurysm, sized 70 mm, as shown by computed tomography (CT). EVAR was performed in a routine fashion using an Endurant II stent graft. Postoperative CT revealed a massive endoleak around the neck that was difficult to differentiate between Types I and IV. The use of the novel software Viewtify (SCIEMENT, Inc., Tokyo, Japan) to visualize the endoleak with surrounding tissues as real-time three-dimensional computer graphics (3DCG) resulted in confirmation that the endoleak was not from the proximal end but rather the stent graft body. CT findings obtained one week later showed that the endoleak had diminished and no additional procedures were needed. Following a diagnosis of endoleak after EVAR, images viewed with Viewtify helped to confirm the appropriate diagnosis. This novel software was found useful to clarify the position and mechanism of a Type IV endoleak.

Heart transplantation using a donor heart with repaired tetralogy of Fallot: a case report.

Background: Heart transplantation is the gold standard therapy for end-stage heart failure; however, it is limited by a shortage of available donors. In recent years, heart transplantations have been performed using marginal donor hearts with valvular and/or congenital cardiac abnormalities. Case summary: A 60-year-old woman with acromegalic cardiomyopathy underwent left ventricular assist device implantation and aortic valve (AV) closure 4 years prior. After 2 months, repeat AV closure and omental flap transposition were performed. During the outpatient follow-up, the patient developed recurrent severe AV regurgitation and bacteraemia-induced subarachnoid haemorrhage. She underwent urgent heart transplantation using a marginal donor heart with preserved cardiac function, mild pulmonary valve stenosis, and regurgitation after pulmonary valve-sparing tetralogy of Fallot (TOF) repair. An anatomical anastomosis was possible. She had no signs of infection, heart failure, arrhythmia, or immune rejection 15 months after the heart transplantation. Discussion: In this case, the donor heart with repaired TOF did not require pulmonary valve replacement and was anatomically intact. Donor hearts with repaired TOF that are expected to have long-term durability in terms of cardiac function may be used for successful heart transplantations. The repair of marginal donor hearts creates an opportunity to increase the number of viable donors.

Surgical Treatment for Giant Multiple Coronary Artery Aneurysms Caused by an IgG4-Related Disease.

Coronary artery aneurysms (CAAs) due to an immunoglobulin G4 (IgG4)-related disease (IgG4-RD) are relatively rare, and there is no consensus on the choice of treatment method. In the present study, we report the results of the surgical treatment for multiple giant CAAs caused by IgG4-RD. A 71-year-old man was diagnosed with severe aortic regurgitation and CAAs. A blood test showed high IgG4 levels, and computed tomography revealed four giant coronary artery aneurysms: two in the right coronary artery (RCA) (proximal RCA and posterior descending artery (PDA)), one in the left anterior descending (LAD), and one in the diagonal branch (Dx). We planned aortic valve replacement, coronary aneurysm resection, and coronary artery bypass grafting (CABG). After finishing aortic valve replacement, the CAAs in proximal RCA, LAD, and Dx were resected. The proximal and distal tracts of the aneurysm were closed with a pericardial bovine patch and ligation. However, since the distal PDA was too calcified to be anastomosed, and the PDA aneurysm was smaller than the others, it was decided to leave the PDA aneurysm. The anastomoses of SVG-RCA and Dx, as well as the left internal thoracic artery to LAD, were performed. Histopathological examination of the aneurysm wall showed a high IgG4-positive cell/IgG-positive cell ratio, and a diagnosis of IgG4-RD was made. In the treatment of CAAs due to IgG4-RD, it is essential to select a procedure that takes into account the size, location, and nature of the aneurysm, and comorbidities. To ensure resection of the aneurysm and blockade of blood flow, closure of the inflow and outflow tracts with a pericardial bovine patch and CABG are effective.

Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports.

Introduction: With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies. Study design: The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response. Results: In the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation. Conclusions: Our case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.

Efficacy of central extracorporeal life support for patients with fulminant myocarditis and cardiogenic shock.

OBJECTIVES: Fulminant myocarditis with cardiogenic shock requires extracorporeal life support (ECLS) and has poor outcomes. To improve outcomes, we have converted patients with severely impaired cardiac and multiorgan function from peripheral to central ECLS. In this study, we reviewed these patients' clinical outcomes and investigated associated factors. METHODS: We retrospectively studied 70 consecutive patients with fulminant myocarditis under peripheral support from 2006 to 2020. Forty-eight patients underwent surgical conversion to central support, and the remaining patients continued peripheral support. The end point was survival and ventricular assist device-free survival. RESULTS: More severe pulmonary congestion and multiorgan failure were present in patients with central than peripheral support. Weaning from ECLS was achieved in 95% and 62% of patients with peripheral and central support, respectively. Five-year survival was not significantly different between patients with central and peripheral support (71.2% vs 87.5%, respectively; P = 0.15). However, the ventricular assist device-free survival rate was significantly higher in patients with central than peripheral support (82.2% vs 52.0%, respectively; P = 0.017). A peak creatine kinase-MB level of >180 IU/l, rhythm disturbance and aortic valve closure were detrimental to functional recovery in patients with central support. CONCLUSIONS: Conversion to central ECLS is feasible and safe in patients with fulminant myocarditis. Patients with severe myocardial injury as shown by a high creatine kinase-MB level, rhythm disturbance and aortic valve closure should be converted to a durable left ventricular assist device.

Durable ventricular assist device implantation for systemic right ventricle: a case series.

BACKGROUND: A systemic right ventricle (RV) after atrial switch in transposition of the great arteries (TGA) or congenitally corrected TGA (ccTGA) often results in advanced heart failure in adulthood. CASE SUMMARY: Four patients with INTERMACS Class III underwent durable ventricular assist device (VAD) implantation for a systemic RV. Two patients were diagnosed with ccTGA and underwent tricuspid valve replacement, and two were diagnosed with TGA in childhood and underwent Mustard repair. The two patients with ccTGA received an EVAHEART (Sun Medical, Nagano, Japan) and HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) at the age of 56 years and 34 years, respectively. Of the patients with TGA, one received a Heartmate II at age 40 years, and one received a HeartMate 3 at age 40 years. All patients were weaned from cardiopulmonary bypass without subpulmonic VAD support and transferred to the intensive care unit with optimum VAD support. No in-hospital deaths, cerebrovascular accidents, or other major complications occurred. The post-VAD right heart catheter study showed a remarkable reduction in pulmonary capillary wedge pressure in all patients. DISCUSSION: The indications for and surgical technique of durable VAD implantation for a systemic RV after atrial switch of TGA or ccTGA have not been fully established. A durable VAD, including the HeartMate 3, was successfully implanted in four such patients in this study. Pre-operative three-dimensional computed tomography images and intraoperative transoesophageal echocardiography guidance helped to determine the positions of the inflow and pump.

Minimally invasive mitral valve repair via right mini-thoracotomy in patient with myelodysplastic syndrome.

BACKGROUND: Cardiac surgery for myelodysplastic syndrome (MDS) patients is challenging because anemia and neutropenia develop as a result of the syndrome, leading to infection and bleeding tendency during surgery. We report the case of minimally invasive mitral valve repair via a right mini-thoracotomy and perioperative use of granulocyte colony-stimulating factor (G-CSF) in a patient with MDS. CASE PRESENTATION: A 77-year-old man with myelodysplastic syndrome (MDS) was referred for surgical treatment for mitral valve regurgitation and underwent a minimally invasive mitral valve repair via a right mini-thoracotomy (MICS mitral procedure). On admission, laboratory results showed a leukocyte count of 1500/µL and neutrophils at 190/µL. Prior to surgery, a subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) was given, based on a diagnosis of MDS by a hematologist. The MICS-mitral procedure using artificial chordae and an annular ring prosthesis was completed without requiring re-exploration for bleeding. Postoperatively, a G-CSF injection was administered and transfusion was required. There was no infection complication and the postoperative course was uneventful. CONCLUSION: A MICS-mitral procedure may be an effective option for MR patients with MDS who require a mitral valve repair to avoid postoperative infection and reduce the incidence of perioperative transfusion.