[Surgical Replacement of Descending Aorta for Adult Aortic Coarctation by Using Three-dimensional Computer Graphics Reconstruction].

Aortic coarctation is diagnosed in approximately 5% of adult patients with congenital heart disease and is commonly diagnosed through the close examination of hypertension. Various surgical strategies for adult coarctation have been recently reported. Generally, aortic replacement may require blood transfusion in case of injury of the well-developed collateral vessels. Therefore, in order to secure an operative safety, we preoperatively used a medical image viewer to identify the abnormal vessels by three-dimensional computer graphics (3DCG) reconstruction. A 34-year-old male patient was referred to our hospital with hypertension and low ankle-brachial pressure index( ABI). Chest computed tomography( CT) scan showed aortic coarctation and development of abnormal collateral vessels. Descending aorta was replaced via a left third-fourth intercostal thoracotomy under partial extracorporeal circulation. As the image viewer depicted, anatomical abnormality of the collateral vessels was identified precisely, and surgically treated without any injury. The patient was discharged 10 days postoperatively without transfusion and with a normalized ABI.

Impact of prolonged cardiopulmonary resuscitation on outcomes in heart transplantation with higher risk donor heart.

OBJECTIVES: To evaluate the influence of prolonged cardiopulmonary resuscitation (CPR) on outcomes in heart transplantation with higher risk donor hearts (HRDHs). METHODS: Patients transplanted in our hospital between May 2006 and December 2019 were divided into 2 groups, HRDH recipients and non HRDH recipients. HRDH was defined as meeting at least one of the following criteria: (1) donor left ventricular ejection fraction ≤ 50%, (2) donor-recipient predicted heart mass ratio < 0.8 or > 1.2, (3) donor age ≥ 55 years, (4) ischemic time > 4 h and (5) catecholamine index > 20. Recipients of HRDHs were divided into 3 groups according to the time of CPR (Group1: non-CPR, Group 2: less than 30 min-CPR, and Group 3: longer than 30 min CPR). RESULTS: A total of 125 recipients were enrolled in this study, composing of HRDH recipients (n = 97, 78%) and non HRDH recipients (n = 28, 22%). Overall survival and the rate of freedom from cardiac events at 10 years after heart transplantation were comparable between two groups. Of 97 HRDH recipients, 54 (56%) without CPR, 22 (23%) with CPR < 30 min, and 21 (22%) with CPR ≥ 30 min were identified. One-year survival rates were not significantly different among three groups. The 1-year rate of freedom from cardiac events was not also statistically different, excluding the patients with coronary artery disease found in early postoperative period, which was thought to be donor-transmitted disease. Multivariate logistics regression for cardiac events identified that the CPR duration was not a risk factor even in HRDH-recipients. CONCLUSION: The CPR duration did not affect the outcomes after heart transplantation in HRDH recipients.

Modified Ravitch procedure for pectus excavatum in Marfan syndrome with annuloaortic ectasia.

OBJECTIVES: This case series aimed to determine the feasibility of simultaneous modified Ravitch and David procedures for Marfan syndrome patients with pectus excavatum and annuloaortic ectasia. METHODS: Between March 2014 and December 2019, 7 consecutive patients underwent simultaneous surgery of modified Ravitch and David procedures for pectus excavatum and annuloaortic ectasia. The completion of cardiac surgery and sternal closure were followed by the modified Ravitch procedure. The bilateral fourth to seventh costal cartilages were resected, the sternal body partially wedge resected and the sternum raised anteriorly with re-suture. An oblique incision was performed on bilateral third costal cartilages, and they were fixed on top of each other, with the medial end superior and the lateral end inferior. The sternum was raised anteriorly, bypassing the fourth to seventh rib ends through the back of the sternum with threads. The feasibility and safety of the procedure were assessed through a retrospective review of the patients' clinical charts. RESULTS: The total sample had a median age of 28 years and comprised 5 males and 2 females. There was a significant difference in the preoperative and postoperative median Haller index, which were 6.8 and 3.9, respectively. All patients were discharged without serious complications, and there was no significant recurrence of pectus excavatum at 35-92 months postoperatively. CONCLUSIONS: The results of our case series suggest the feasibility of one-stage surgery for pectus excavatum combined with cardiac surgery using the modified Ravitch procedure. Future efforts should be tailored for more uneventful postoperative clinical courses.

[Aortic Root Replacement with Homograft].

Infectious endocarditis is a severe infectious disease in cardiovascular surgery fields. Appropriate antibiotics administration is the principle of treatment, while surgical intervention is required when there is intensive tissue destruction, refractory infection, or high risk of embolism. Usually, surgical risks of infectious endocarditis are rather high as preoperative general condition is often poor. Homografts, which have excellent anti-infective properties, become one of the graft options for infectious endocarditis. Fortunately, we are able to use homografs without so much obstacles thanks to the presence of a tissue bank in our hospital. We will report our strategy and clinical courses of aortic root replacement using homograft for infective endocarditis.

The Myocardial Accumulation of Aggregated Desmin Protein in a Case of Desminopathy with a de novo DES p.R406W Mutation.

Desminopathy is a cardiac and skeletal myopathy caused by disease-causing variants in the desmin (DES) gene and represents a subgroup of myofibrillar myopathies, where cytoplasmic desmin-postive immunoreactivity is the pathological hallmark. We herein report a 28-year-old Japanese man who was initially diagnosed with sporadic hypertrophic cardiomyopathy with atrioventricular block at 9 years old and developed weakness in the soft palate and extremities. The myocardial tissue dissected during implantation of the ventricular-assisted device showed a dilated phase of hypertrophic cardiomyopathy and intracellular accumulation of proteinase K-resistant desmin aggregates. Genetic testing confirmed a de novo mutation of DES, which has already been linked to desminopathy. As the molecular diagnosis of desminopathy is challenging, particularly if patients show predominantly cardiac signs and a routine skeletal muscle biopsy is unavailable, these characteristic pathological findings of endomyocardial proteinase K-resistant desmin aggregates might aid in clinical practice.

Prophylactic negative pressure wound therapy is not effective for preventing driveline infection following left ventricular assist device implantation.

BACKGROUND: Driveline infection (DLI) following left ventricular assist device (LVAD) implantation remains an unresolved problem. Negative pressure wound therapy (NPWT) promotes wound healing by applying negative pressure on the surface of the wound. Recently, the prophylactic application of NPWT to closed surgical incisions has decreased surgical site infections in various postsurgical settings. Therefore, we evaluated the efficacy and safety of prophylactic NPWT for preventing DLI in patients with LVAD implantation. METHODS: Prophylactic NPWT was provided to 50 patients who received continuous-flow LVADs as bridge-to-transplant therapy at our institution between May 2018 and October 2020 (NPWT group). The negative pressure dressing was applied immediately after surgery and retained on the driveline exit site for 7 days with a continuous application of -125 mm Hg negative pressure. The primary outcome was DLI within 1 year of LVAD implantation. We compared the rate of DLI incidence in the NPWT group with that in the historical control cohort (50 patients) treated with the standard dressing (SD) who received LVAD implantation between July 2015 and April 2018 (SD group). RESULTS: No severe complications were associated with the NPWT. During the follow-up period, DLI was diagnosed in 16 participants (32%) in the NPWT group and 21 participants (42%) in the SD group. The rates of DLI incidence and freedom from DLI did not differ between groups (p = 0.30 and p = 0.63). CONCLUSIONS: Prophylactic NPWT at the driveline exit site was safe following LVAD implantation. However, it did not significantly reduce the risk of DLI.

Impact of pathogenic FBN1 variant types on the development of severe scoliosis in patients with Marfan syndrome.

BACKGROUND: Among the several musculoskeletal manifestations in patients with Marfan syndrome, spinal deformity causes pain and respiratory impairment and is a great hindrance to patients' daily activities. The present study elucidates the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome. METHODS: We retrospectively evaluated 278 patients with pathogenic or likely pathogenic FBN1 variants. The patients were divided into those with (n=57) or without (n=221) severe scoliosis. Severe scoliosis was defined as (1) patients undergoing surgery before 50 years of age or (2) patients with a Cobb angle exceeding 50° before 50 years of age. The variants were classified as protein-truncating variants (PTVs), which included variants creating premature termination codons and inframe exon-skipping, or non-PTVs, based on their location and predicted amino acid alterations, and the effect of the FBN1 genotype on the development of severe scoliosis was examined. The impact of location of FBN1 variants on the development of severe scoliosis was also investigated. RESULTS: Univariate and multivariate analyses revealed that female sex, PTVs of FBN1 and variants in the neonatal region (exons 25-33) were all independent significant predictive factors for the development of severe scoliosis. Furthermore, these factors were identified as predictors of progression of existing scoliosis into severe state. CONCLUSIONS: We elucidated the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome. Patients harbouring pathogenic FBN1 variants with these genetic risk factors should be monitored carefully for scoliosis progression.

[Aortic Root Pseudoaneurysm].

Aortic root pseudoaneurysm is often derived from suture sites after aortic root replacement on the basis of connective tissue disease, aortitis, or prosthetic valve endocarditis. Preoperative computed tomography (CT) and echocardiography are useful not only for diagnosing a pseudoaneurysm but also for planning to repair it. Redo aortic root replacement is necessary to repair it in most cases. When a giant pseudoaneurysm is close to a sternal posterior wall, resternotomy may be challenging. In such a case, precedent cardiopulmonary bypass with left ventricular apical vent under mild-moderate hypothermia is useful to control bleeding during resternotomy. Regarding graft selection, cryopreserved homograft is effective for repairing pseudoaneurysm in an active infectious phase, but modified Bentall procedure may be still considerable to expect long-term durability if infection is well controlled by preoperative sufficient antibiotic treatment and intraoperative debridement. In the author's institute, 45 patients with aortic root pseudoaneurysm underwent surgical repair since 2011. Thirty cases (67%) was infectious. Thirty-six patients( 80%) underwent aortic root replacement, including homograft in 14 patients and modified Bentall procedure in 22 patients. All the patients survived at discharge, and 1-year and 5-year survival were 96.8% and 74.9%, respectively. Preoperative infectious status and graft selection did not significantly affect remote-phase survival.

Aortic valve replacement of a quadricuspid aortic valve with right coronary artery ostium adjacent to one of the commissures.

BACKGROUND: Quadricuspid aortic valve is a rare congenital heart disease that may be associated with a different anatomical relationship between the coronary artery ostium and the commissure. CASE PRESENTATION: Herein, we report a case of a 59-year-old woman who underwent aortic valve replacement for a quadricuspid aortic valve with severe aortic regurgitation. Intraoperatively, the aortic valve had four cusps of almost equal size and the right coronary artery arose adjacent to the commissure between the right coronary cusp and one of the two non-coronary cusps. The annular stitches were placed in a non-everting mattress fashion with pledgets on the ventricular side, and stitches near the right coronary ostium were transitioned to the subannular ventricular myocardium to maintain the distance from the ostium. A one-step smaller-sized prosthesis was selected to avoid an oversized prosthetic valve potentially compressing the right coronary ostium. CONCLUSIONS: When performing aortic valve replacement for a quadricuspid aortic valve, careful observation of the coronary location and means to avoid coronary ostium obstruction are essential.

Perigraft seroma after total aortic arch replacement using Triplex graft.

A 42-year-old gentleman underwent total aortic arch replacement with Triplex graft (Terumo corporation, Tokyo, Japan) for acute type A dissection. Sixteen months later, a computed tomography revealed a rapidly enlarging low-density area around the graft, with no contrast enhancement. The area was compressing the mediastinal structures, such as the superior vena cava and right pulmonary artery. Suspecting lymphorrhea or perigraft seroma (PGS), surgical drainage was performed. Although fluid accumulation around the graft was cloudy and yellowish, Gram stain was negative. A fatty preparation was administered from the nasogastric tube, demonstrating no leakage of chyle. Intraoperative lymphangiography with indocyanine green also showed no lymphatic leak. Therefore, PGS was suspected. Fibrin glue was applied to the graft and the surgery was completed. PGS drainage after arch replacement, especially with Triplex graft, is extremely rare. We discuss the strategies of diagnosis and treatment for this uncommon complication after aortic surgery.

Association between left ventricular ejection fraction and mortality after Bentall procedure.

Root infection or dissection involving coronary artery frequently necessitates an emergent Bentall procedure, with low left ventricular ejection fraction (LVEF). In contrast, concerning an elective Bentall for aneurysm, surgeons should balance the risk and benefit of surgery, especially in low LVEF cases. We investigated the association between preoperative LVEF and outcomes after Bentall. We analyzed 98 patients undergoing Bentall between April 2000 and March 2020. The patients were stratified into three groups: (a) 65 with LVEF ≥ 60%, (b) 21 with LVEF 45 to < 60%, and (c) 12 with LVEF < 45%. Baseline characteristics, survivals, and major adverse cardiovascular events (MACE) were compared. To assess potential non-linear relationship between LVEF and mortality, cubic spline analysis was conducted. Median age was similar (a vs b vs c, 52 vs 50 vs 44). In all groups, elective root aneurysm was 50-60%, indicating the rest were complicated and sick. Operative mortality was the highest in group c (4.6% vs 9.5% vs 16.7%, p = 0.294). Survival and MACE-free rate were the worst in group c, though their 10-year survival was 40%. LVEF was an independent risk for mortality, and cubic spline analysis showed potential non-linear association between LVEF and mortality. Although LVEF is an independent predictor of mortality after Bentall, long-term survival was occasionally achieved in low LVEF cases. While surgeons should carefully balance the risk of low LVEF and the benefit of surgery in elective cases, we should perform a non-elective procedure as needed, even if LVEF is low.

A Novel Knitted Polytetrafluoroethylene Patch for Cardiovascular Surgery.

Polytetrafluoroethylene (PTFE) is widely used in cardiovascular surgeries; however, postoperative complications such as thrombosis, calcification, and neointimal hyperplasia are yet to be resolved in patients. We developed two types of novel knitted PTFE patches and evaluated them using a swine model. Both patches were composed of knitted PTFE impregnated with micro-PTFE particles, and one of them was pressed after PTFE impregnation. Twenty micromini pigs were used in this study. After left lateral thoracotomy, the new patches (n = 8 for each type of patch) were implanted into the descending aorta and left atrium for the high- and low-pressure models, respectively. Clinically used expanded PTFE (ePTFE) patches were used as the control material (n = 4). The patches were explanted and histopathologically examined at 4, 12, and 24 weeks after implantation. A tensile test was also applied to the high-pressure model at 12 and 24 weeks. As a result, there was no significant difference noted in the tensile test, intimal hyperplasia thickness, or endothelialization among the three patches. In contrast, the degree of macrophage infiltration into the patches and the degree of macrophage, lymphocyte, and granulocyte infiltration outside the patches were lower in the new patches than in the control ePTFE. The degree of cellular infiltration outside new patches decreased over time. There were no significant differences between the two new patch types in these results. In conclusion, our novel knitted PTFE patch showed noninferiority in durability and intensity and less inflammatory responses than a clinically used ePTFE patch.

Suppression of Tumor Growth in a Rabbit Hepatic Cancer Model by Boron Neutron Capture Therapy With Liposomal Boron Delivery Systems.

BACKGROUND/AIM: Tumor cell destruction by boron neutron capture therapy (BNCT) is attributed to the nuclear reaction between 10B and thermal neutrons. The accumulation of 10B atoms in tumor cells without affecting adjacent healthy cells is crucial for effective BNCT. We previously reported that several types of liposomal boron delivery systems (BDS) delivered effective numbers of boron atoms to cancer tissues, and showed tumor-growth suppression after thermal neutron irradiation. In the present study, we examined the effects of BNCT after intra-arterial infusion of 10B-borono-dodecaborate (10BSH) by liposomal BDS in rabbit hepatic cancer models. MATERIALS AND METHODS: We prepared 10BSH-entrapped transferrin-conjugated polyethylene glycol liposomes constructed with distearoyl-boron lipid (TF-PEG-DSBL), and performed thermal neutron irradiation at the Kyoto University Institute for Integrated Radiation and Nuclear Science after intra-arterial infusion into rabbit VX-2 hepatic tumors. RESULTS: Concentrations of 10B in VX-2 tumors on delivery with TF-PEG-DSBL liposomes reached 25 ppm on day 3 after the injection. Tumor growth was suppressed by thermal neutron irradiation after intra-arterial injection of this 10BSH-containing liposomal BDS, without damage to normal cells. CONCLUSION: The present results demonstrate the applicability of 10B-containing TF-PEG-DSBL liposomes as a novel intra-arterial boron carrier in BNCT for cancer.

Intrabronchial migration of hemostatic agent through a bronchial fistula after lung transplantation: a case report.

BACKGROUND: A bronchial fistula is a relatively rare and potentially fatal complication after lung transplantation. Thoracic surgeons and pulmonologists often face challenges when selecting treatment options. We herein report an exceptional case of intrabronchial migration of a nonabsorbable hemostatic agent, which had been placed around the pulmonary artery at the time of lung transplantation, through a bronchial fistula. CASE PRESENTATION: A 61-year-old man developed respiratory distress 1 year after left single-lung transplantation for idiopathic interstitial pneumonia. Bronchoscopic examination revealed an apparent foreign body protruding from the mediastinum into the distal site of the bronchial anastomosis. The foreign body was easily removed bronchoscopically and appeared to be a hemostatic agent that had been placed during the previous lung transplantation. The patient developed a similar clinical episode and finally developed hemoptysis. Computed tomography revealed a foreign body located between the bronchus and pulmonary artery, partially protruding into the bronchial lumen. Given the possibility of a bronchopulmonary arterial fistula, surgical treatment was performed. The foreign body was located between the bronchus and left pulmonary artery and was easily removed. Multiple bronchial fistulas were found, and all were closed with direct sutures. Bypass grafting of the left pulmonary artery was then performed, initially with a homograft but eventually with an extended polytetrafluoroethylene graft. The patient was finally discharged 5 months after the surgery. CONCLUSION: We experienced an extremely rare case of intrabronchial migration of hemostatic agents used during the previous lung transplantation through a bronchial fistula, which were successfully managed by direct bronchial closure and bypass grafting of the left pulmonary artery.

Single-dose toxicity study by intra-arterial injection of 10BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma.

We developed a mixing medical device by attaching Shirasu porous glass Millipore membrane to prepare water-in-oil-in-water (WOW) emulsion in a shorter time to be applied as 10B-entrapped WOW emulsion for hepatocellular carcinoma (HCC) treatment. Single-dose toxicity studies by intra-arterial injection of 10BSH-entrapped WOW were performed in rabbits and pig, and no side effects were observed. We hope to proceed to the preclinical and clinical studies for further evaluation of 10B compound as multidisciplinary treatments for HCC.

Comparison of two point of care whole blood coagulation analysis devices and conventional coagulation tests as a predicting tool of perioperative bleeding in adult cardiac surgery-a pilot prospective observational study in Japan.

BACKGROUND: It is widely accepted that Point-of Care Test (PoCT) devices are useful in the detection of coagulopathies in situations of massive bleeding such as major cardiac surgery. These devices contribute to the reduction of blood transfusion. However, their implementation remains limited in Japan because of their cost and lack of health insurance support. STUDY DESIGN AND METHODS: Conventional coagulation tests and thromboelastography (TEG)/Sonoclot values were measured in 50 consecutive cardiac surgery cases. Clinical background information such as operative procedures was obtained from electronic medical records, and the theoretical perioperative total blood loss was calculated by measuring the hemoglobin content and total red blood cell transfusion volume. The correlation between perioperative total blood loss and the measured laboratory values or clinical parameters was evaluated by a multivariate linear regression analysis. The risk factors of the total amount of platelet transfusion and postoperative drain bleeding volume were similarly evaluated. RESULTS: No significant association between the estimated perioperative total blood loss (eTBL) and the laboratory measurements including conventional coagulation tests, TEG and Sonoclot was observed. On the other hand, postoperative drain bleeding volume was significantly associated with postoperative Sonoclot CR (p = 0.039) as well as preoperative use of oral anticoagulants and cell saver treated blood volume. Platelet transfusion amount was significantly associated with post-CBP PF and time to peak value of Sonoclot (p = 0.014 and 0.001, respectively). CONCLUSION: Sonoclot measurements may be useful to estimate the risks of postoperative bleeding and platelet transfusion in cardiac surgeries in Japan.

Long-term support by left ventricular assist device for arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by right ventricular enlargement, right heart failure (HF), and ventricular arrhythmias which lead to sudden death especially in young adults. Current recommendations for management of patients with ARVC are antiarrhythmic medications, catheter ablation, and implantable cardioverter defibrillator therapy to prevent sudden cardiac death. However, despite these treatments, few patients suffer from recurrent ventricular arrhythmias or HF unresponsive to conventional management. Heart transplantation (HTx) is a preferred treatment for these cases, but because of a persistent donor heart shortage in Japan, ventricular assist device (VAD) support has become an important option for a management of the end-stage ARVC. Previous articles reported 4 cases of a successful management by left ventricular assist device (LVAD), but the longest interval of LVAD support was only 333 days. We present 3 cases of ARVC patients who were successfully managed by LVAD implantation for more than a year. These 3 cases are unconventional examples of ARVC patients, considering the nature of the disease. The novelty of these cases should be taken in the context of the extremely long waiting period for HTx in Japan.

Lanthanum carbonate, a phosphate binder, inhibits calcification of implanted aortic allografts in a rat model.

OBJECTIVES: Calcification is one of the major postoperative problems after aortic allograft implantation. We hypothesized that phosphate binders, lanthanum carbonate and calcium carbonate inhibit calcification of implanted aortic allografts and verified this hypothesis using a rat model. METHODS: Aortas were harvested from 4-week-old Brown Norway rats and implanted into the subdermal space of 4-week-old Lewis rats. Twenty-seven recipient Lewis rats were divided into Group N, Group L, and Group C (9 rats per group), which were fed a normal diet, a normal diet containing 3% lanthanum carbonate, and a normal diet containing 3% calcium carbonate, respectively. Implanted aortic allografts were explanted 2 weeks later. Calcification of aortic allografts was evaluated using von Kossa staining and calcium content assay. Calcification score was defined in von Kossa staining as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Serum calcium and phosphorus levels at euthanasia were measured. RESULTS: Calcification scores were 2.6, 1.2, and 0.8, and calcium content was 48.9, 15.8, and 8.9 mg/dry·g, in Groups N, L, and C, respectively. Calcification was significantly reduced in Groups L and C. Serum calcium level was 11.5, 12.2, and 13.5 mg/dl, and serum phosphorus level was 15.4, 12.5, and 11.7 mg/dl, in Groups N, L, and C, respectively. Serum calcium level in Group C was significantly higher than in the other two groups. CONCLUSIONS: Lanthanum carbonate and calcium carbonate significantly reduced calcification of implanted aortic allografts in young rats. Although calcium carbonate induced hypercalcemia, lanthanum carbonate has significant potential to inhibit calcification of implanted aortic allografts.

[Aortic Root Replacement with Cryopreserved Allograft Aortic Valve].

Aortic root replacement with a cryopreserved allograft aortic valve is effective for active infectious endocarditis and prosthetic valve endocarditis, especially with a perivalvular abscess, since an allograft seems to be resistant to infection by maintaining viable cells under the process of programmed freezing. From December 1998 to March 2017, aortic root replacement with allograft aortic valves were performed in 38 patients in the University of Tokyo. The in-hospital mortality was 18%, the 5-year survival rate was 68%, and the 5-year freedom rate of reoperation was 75%. Although the clinical outcome was improved as institutional experiences increased recently, pseudoaneurysm during the long-term follow-up period needs special attention. The health-insurance system was applied to this allograft treatment in April 2016 by the Ministry of Health, Labour and Welfare. There are still some hurdles for obtaining institutional certification and financial resources, and enough number of donor allografts, so as to use them more commonly.